Tag: Biotech

Molecular signaling in cancer stem cells of tongue squamous cell carcinoma: Therapeutic implications and challenges

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Head and neck squamous cell carcinoma is the seventh most common cancer worldwide with high mortality rates. Amongst oral cavity cancers, tongue carcinoma is a very common and aggressive oral cavity carcinoma. Despite the implementation of a multimodality treatment regime including surgical intervention, chemo-radiation as well as targeted therapy, tongue carcinoma shows a poor overall 5-year survival pattern, which is attributed to therapy resistance and recurrence of the disease. The presence of a rare population, i.e., cancer stem cells (CSCs) within the tumor, are involved in therapy resistance, recurrence, and distant metastasis that results in poor survival patterns. Therapeutic agents targeting CSCs have been in clinical trials, although they are unable to reach into therapy stage which is due to their failure in trials. A more detailed understanding of the CSCs is essential for identifying efficient targets. Molecular signaling pathways, which are differentially regulated in the CSCs, are one of the promising targets to manipulate the CSCs that would provide an improved outcome. In this review, we summarize the current understanding of molecular signaling associated with the maintenance and regulation of CSCs in tongue squamous cell carcinoma in order to emphasize the need of the hour to get a deeper understanding to unravel novel targets.

Core Tip: Tongue squamous cell carcinoma is one of the most common and aggressive oral cavity carcinomas, particularly among the Indian population. Despite various treatment strategies employed, the survival rates of the patients remain poor. A rare population i.e., cancer stem cells (CSCs), plays an important role in resistance, recurrence as well as metastasis which are factors responsible for the poor survival outcome. In this review, we discuss the recent findings regarding cell signaling pathways and markers associated with the CSCs and the need to gain a deeper understanding on the properties of the CSCs.

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World Journal of Stem Cells

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May 26, 2023
Advancements in adipose-derived stem cell therapy for skin fibrosis

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Pathological scarring and scleroderma, which are the most common conditions of skin fibrosis, pathologically manifest as fibroblast proliferation and extracellular matrix (ECM) hyperplasia. Fibroblast proliferation and ECM hyperplasia lead to fibrotic tissue remodeling, causing an exaggerated and prolonged wound-healing response. The pathogenesis of these diseases has not been fully clarified and is unfortunately accompanied by exceptionally high medical needs and poor treatment effects. Currently, a promising and relatively low-cost treatment has emerged-adipose-derived stem cell (ASC) therapy as a branch of stem cell therapy, including ASCs and their derivatives-purified ASC, stromal vascular fraction, ASC-conditioned medium, ASC exosomes, etc., which are rich in sources and easy to obtain. ASCs have been widely used in therapeutic settings for patients, primarily for the defection of soft tissues, such as breast enhancement and facial contouring. In the field of skin regeneration, ASC therapy has become a hot research topic because it is beneficial for reversing skin fibrosis. The ability of ASCs to control profibrotic factors as well as anti-inflammatory and immunomodulatory actions will be discussed in this review, as well as their new applications in the treatment of skin fibrosis. Although the long-term effect of ASC therapy is still unclear, ASCs have emerged as one of the most promising systemic antifibrotic therapies under development.

Core Tip: Pathological scarring and scleroderma are the most common conditions of skin fibrosis with high medical needs and poor therapeutic effects. Adipose-derived stem cell (ASC) therapy has emerged as a promising treatment for skin fibrosis. Here, we discuss the possible mechanism of skin fibrosis as well as the latest research about the mechanism of ASC therapy and its application in treating these conditions. ASC therapy provides a brand-new insight into the treatment of skin fibrosis.

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World Journal of Stem Cells

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May 26, 2023
Stromal cell-derived factor-1α regulates chondrogenic differentiation via activation of the Wnt/β-catenin pathway in mesenchymal stem cells

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BACKGROUND

Mesenchymal stem cells (MSCs) have been applied to treat degenerative articular diseases, and stromal cell-derived factor-1α (SDF-1α) may enhance their therapeutic efficacy. However, the regulatory effects of SDF-1α on cartilage differentiation remain largely unknown. Identifying the specific regulatory effects of SDF-1α on MSCs will provide a useful target for the treatment of degenerative articular diseases.

AIM

To explore the role and mechanism of SDF-1α in cartilage differentiation of MSCs and primary chondrocytes.

METHODS

The expression level of C-X-C chemokine receptor 4 (CXCR4) in MSCs was assessed by immunofluorescence. MSCs treated with SDF-1α were stained for alkaline phosphatase (ALP) and with Alcian blue to observe differentiation. Western blot analysis was used to examine the expression of SRY-box transcription factor 9, aggrecan, collagen II, runt-related transcription factor 2, collagen X, and matrix metalloproteinase (MMP)13 in untreated MSCs, of aggrecan, collagen II, collagen X, and MMP13 in SDF-1α-treated primary chondrocytes, of glycogen synthase kinase 3β (GSK3β) p-GSK3β and β-catenin expression in SDF-1α-treated MSCs, and of aggrecan, collagen X, and MMP13 in SDF-1α-treated MSCs in the presence or absence of ICG-001 (SDF-1α inhibitor).

RESULTS

Immunofluorescence showed CXCR4 expression in the membranes of MSCs. ALP stain was intensified in MSCs treated with SDF-1α for 14 d. The SDF-1α treatment promoted expression of collagen X and MMP13 during cartilage differentiation, whereas it had no effect on the expression of collagen II or aggrecan nor on the formation of cartilage matrix in MSCs. Further, those SDF-1α-mediated effects on MSCs were validated in primary chondrocytes. SDF-1α promoted the expression of p-GSK3β and β-catenin in MSCs. And, finally, inhibition of this pathway by ICG-001 (5 µmol/L) neutralized the SDF-1α-mediated up-regulation of collagen X and MMP13 expression in MSCs.

CONCLUSION

SDF-1α may promote hypertrophic cartilage differentiation in MSCs by activating the Wnt/β-catenin pathway. These findings provide further evidence for the use of MSCs and SDF-1α in the treatment of cartilage degeneration and osteoarthritis.

Core Tip: In this study, we investigated the effect of stromal cell-derived factor-1α (SDF-1α) on the differentiation of bone marrow mesenchymal stem cells (MSCs) and primary chondrocytes in vitro. We demonstrated that SDF-1α promotes the chondrogenic differentiation of MSCs, and similar results were observed in primary chondrocytes. In addition, SDF-1α also activates the Wnt/β-catenin pathway to regulate chondrocyte hypertrophy and maturation in MSCs.

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World Journal of Stem Cells

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May 26, 2023
Delineating the glioblastoma stemness by genes involved in cytoskeletal rearrangements and metabolic alterations

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Colorectal cancer (CRC) remains the third most prevalent cancer disease and involves a multi-step process in which intestinal cells acquire malignant characteristics. It is well established that the appearance of distal metastasis in CRC patients is the cause of a poor prognosis and treatment failure. Nevertheless, in the last decades, CRC aggressiveness and progression have been attributed to a specific cell population called CRC stem cells (CCSC) with features like tumor initiation capacity, self-renewal capacity, and acquired multidrug resistance. Emerging data highlight the concept of this cell subtype as a plastic entity that has a dynamic status and can be originated from different types of cells through genetic and epigenetic changes. These alterations are modulated by complex and dynamic crosstalk with environmental factors by paracrine signaling. It is known that in the tumor niche, different cell types, structures, and biomolecules coexist and interact with cancer cells favoring cancer growth and development. Together, these components constitute the tumor microenvironment (TME). Most recently, researchers have also deepened the influence of the complex variety of microorganisms that inhabit the intestinal mucosa, collectively known as gut microbiota, on CRC. Both TME and microorganisms participate in inflammatory processes that can drive the initiation and evolution of CRC. Since in the last decade, crucial advances have been made concerning to the synergistic interaction among the TME and gut microorganisms that condition the identity of CCSC, the data exposed in this review could provide valuable insights into the biology of CRC and the development of new targeted therapies.

Core Tip: Colorectal cancer (CRC) represents one of the most prevalent tumors worldwide. The tumor microenvironment (TME) through its proinflammatory role, among others, actively participates in CRC progression and the disturbance of gut microbiota (dysbiosis) can influence this inflammatory process. CRC stem cells (CCSC) are a tumor cell subpopulation that drives CRC initiation, progression and treatment failure. The features and behavior of CCSC are modulated by several factors including TME and gut microbiota. Here, we will give an overview of the synergistic interaction among TME and intestinal microorganisms that condition the CRC environment and shape CCSC characteristics allowing CRC evolution.

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World Journal of Stem Cells

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May 26, 2023
Single-cell RNA sequencing in cornea research: Insights into limbal stem cells and their niche regulation

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The corneal epithelium is composed of stratified squamous epithelial cells on the outer surface of the eye, which acts as a protective barrier and is critical for clear and stable vision. Its continuous renewal or wound healing depends on the proliferation and differentiation of limbal stem cells (LSCs), a cell population that resides at the limbus in a highly regulated niche. Dysfunction of LSCs or their niche can cause limbal stem cell deficiency, a disease that is manifested by failed epithelial wound healing or even blindness. Nevertheless, compared to stem cells in other tissues, little is known about the LSCs and their niche. With the advent of single-cell RNA sequencing, our understanding of LSC characteristics and their microenvironment has grown considerably. In this review, we summarized the current findings from single-cell studies in the field of cornea research and focused on important advancements driven by this technology, including the heterogeneity of the LSC population, novel LSC markers and regulation of the LSC niche, which will provide a reference for clinical issues such as corneal epithelial wound healing, ocular surface reconstruction and interventions for related diseases.

Core Tip: Limbal stem cells (LSCs), a cell population that resides at the limbus in a highly regulated niche. With the advent of single-cell RNA sequencing, our understanding of LSC characteristics and their microenvironment has grown considerably. This review focuses on the current research on single cell sequencing in LSCs. We highlight the heterogeneity, novel specific markers and niche regulation of LSCs.

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World Journal of Stem Cells

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May 26, 2023
Stimulating factors for regulation of osteogenic and chondrogenic differentiation of mesenchymal stem cells

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Mesenchymal stem cells (MSCs), distributed in many tissues in the human body, are multipotent cells capable of differentiating in specific directions. It is usually considered that the differentiation process of MSCs depends on specialized external stimulating factors, including cell signaling pathways, cytokines, and other physical stimuli. Recent findings have revealed other underrated roles in the differentiation process of MSCs, such as material morphology and exosomes. Although relevant achievements have substantially advanced the applicability of MSCs, some of these regulatory mechanisms still need to be better understood. Moreover, limitations such as long-term survival in vivo hinder the clinical application of MSCs therapy. This review article summarizes current knowledge regarding the differentiation patterns of MSCs under specific stimulating factors.

Core Tip: Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating in specific directions. The differentiation process of MSCs depends on diverse specialized external stimulating factors. The results from recent studies have revealed other underrated roles in the differentiation process of MSCs. However, several questions remain to be solved prior to stable and effective clinical treatment. Our review explores the differentiation patterns of MSCs and summarizes the relevant research according to stimulus types. Finally, future prospects are discussed with regard to their clinical applications.

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World Journal of Stem Cells

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May 26, 2023
Different priming strategies improve distinct therapeutic capabilities of mesenchymal stromal/stem cells: Potential implications for their clinical use

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Mesenchymal stromal/stem cells (MSCs) have shown significant therapeutic potential, and have therefore been extensively investigated in preclinical studies of regenerative medicine. However, while MSCs have been shown to be safe as a cellular treatment, they have usually been therapeutically ineffective in human diseases. In fact, in many clinical trials it has been shown that MSCs have moderate or poor efficacy. This inefficacy appears to be ascribable primarily to the heterogeneity of MSCs. Recently, specific priming strategies have been used to improve the therapeutic properties of MSCs. In this review, we explore the literature on the principal priming approaches used to enhance the preclinical inefficacy of MSCs. We found that different priming strategies have been used to direct the therapeutic effects of MSCs toward specific pathological processes. Particularly, while hypoxic priming can be used primarily for the treatment of acute diseases, inflammatory cytokines can be used mainly to prime MSCs in order to treat chronic immune-related disorders. The shift in approach from regeneration to inflammation implies, in MSCs, a shift in the production of functional factors that stimulate regenerative or anti-inflammatory pathways. The opportunity to fine-tune the therapeutic properties of MSCs through different priming strategies could conceivably pave the way for optimizing their therapeutic potential.

Core Tip: Mesenchymal stromal/stem cells (MSCs) have demonstrated promising therapeutic results in the field of regenerative medicine. However, due to their heterogeneity, the application of MSCs in clinical trials has shown moderate or poor efficacy. Here, we review data on the principal priming approaches for enhancing the therapeutic potential of MSCs. We found that different priming strategies can modify MSC properties and, in this case some therapeutic effects on different disease models can be obtained in relation to dose and/or combination of the priming factors used. The production of priming type-specific functional factors in MSCs could pave the way toward implementing new MSC-based therapies.

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World Journal of Stem Cells

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May 26, 2023
Cell transplantation therapies for spinal cord injury focusing on bone marrow mesenchymal stem cells: Advances and challenges

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Spinal cord injury (SCI) is a devastating condition with complex pathological mechanisms that lead to sensory, motor, and autonomic dysfunction below the site of injury. To date, no effective therapy is available for the treatment of SCI. Recently, bone marrow-derived mesenchymal stem cells (BMMSCs) have been considered to be the most promising source for cellular therapies following SCI. The objective of the present review is to summarize the most recent insights into the cellular and molecular mechanism using BMMSC therapy to treat SCI. In this work, we review the specific mechanism of BMMSCs in SCI repair mainly from the following aspects: Neuroprotection, axon sprouting and/or regeneration, myelin regeneration, inhibitory microenvironments, glial scar formation, immunomodulation, and angiogenesis. Additionally, we summarize the latest evidence on the application of BMMSCs in clinical trials and further discuss the challenges and future directions for stem cell therapy in SCI models.

Core Tip: In this work, we review the specific mechanism of bone marrow-derived mesenchymal stem cell (BMMSC) in spinal cord injury (SCI) repair mainly from the following aspects: Neuroprotection, neuronal circuit, axon sprouting and or regeneration, myelin regeneration, inhibitory microenvironment, glial scar formation, immunomodulation, and angiogenesis. Additionally, we also summarize the latest evidence on application of BMMSC in clinical trials and further discuss the challenges and future directions for stem cell therapy in SCI models.

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World Journal of Stem Cells

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May 26, 2023
Chemical ‘supercharger’ solves molecular membrane mystery

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More than 60% of market drugs aimed at fighting disease target molecular proteins in the cell membranes – but techological limitations have previously limited researchers’ ability to observe these proteins in their natural environment.

Now, scientists in the lab of Yale School of Medicine’s Kallol Gupta, PhD, have identified a class of chemicals, called “superchargers,” that gently destabilize the cell membrane while leaving cell proteins intact. The team was able to show how cell membranes regulate the speed of neurotransmitter release, a key step in central nervous system signaling.

Traditional methods of isolating proteins from the membrane environment with mass spectrometry have damaged the proteins and their ability to bind with other molecules – including those with potentially therapeutic value. This breakthrough technology will allow scientists to screen future therapeutics precisely and directly at the point where proteins encounter new drugs.

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Yale University School of Medicine

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May 24, 2023
A New Strategy to Break Through Bacterial Barriers in Chronic Treatment-Resistant Wounds

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Newswise — CHAPEL HILL, N.C. – Chronic wounds are open sores or injured tissue that fail to heal properly. These types of wounds are notoriously challenging to treat because of bacterial infections like Staphylococcus aureus, or S. aureus. Additionally, bacterial infections that are highly resistant to antibiotics, such as methicillin-resistant S. aureus (MRSA), are one of the main causes of life-threatening infections in hospital patients.

To defend itself from our immune system and other threats, S. aureus can band together, creating a slick, slimy forcefield – or biofilm – around itself. The biofilm barrier is so thick that neither immune cells nor antibiotics can penetrate through and neutralize the harmful bacteria.

Researchers at the UNC School of Medicine and the UNC-NC State Joint Department of Biomedical Engineering have developed a new method that combines palmitoleic acid, gentamicin, and non-invasive ultrasound to help improve drug delivery in chronic wounds that have been infected with S. aureus.

Using their new strategy, researchers were able to reduce the challenging MRSA infection in the wounds of diabetic mice by 94%. They were able to completely sterilize the wounds in several of the mice, and the rest had significantly reduced bacterial burden. Their results were published in Cell Chemical Biology.

“When bacteria are not completely cleared from chronic wounds, it puts the patient at high risk for the infection recurring or of developing a secondary infection,” said senior author Sarah Rowe-Conlon, PhD, a research associate professor in the Department of Microbiology and Immunology. “This therapeutic strategy has the potential to improve outcomes and reduce relapse of chronic wound infections in patients. We are excited about the potential of translating this to the clinic, and that’s what we’re exploring right now.”

Biofilms act as a physical barrier to many classes of antibiotics. Virginie Papadopoulou, PhD, a research assistant professor in the UNC-NCSU Joint Department of Biomedical Engineering, was curious to know if non-invasive cavitation-enhanced ultrasound could create enough agitation to form open spaces in the biofilm to facilitate drug-delivery.

Liquid droplets which can be activated by ultrasound, called phase change contrast agent (PCCA), are applied topically to the wound. An ultrasound transducer is focused on the wound and turned on, causing the liquid inside the droplets to expand and turn into microscopic gas-filled microbubbles, when then move rapidly.

The oscillation of these microbubbles agitates the biofilm, both mechanically disrupting it as well as increasing fluid flow. Ultimately, the combination of the biofilm disruption and the increased permeation of the drugs through the biofilm allowed the drugs to come in and kill the bacterial biofilm with very high efficiency.

“Microbubbles and phase change contrast agents act as local amplifiers of ultrasound energy, allowing us to precisely target wounds and areas of the body to achieve therapeutic outcomes not possible with standard ultrasound,” said Dayton, the William R. Kenan Jr. Distinguished Professor and Department Chair of the UNC-NCSU Joint Department of Biomedical Engineering. “We hope to be able to use similar technologies to locally delivery chemotherapeutics to stubborn tumors or drive new genetic material into damaged cells as well.”

When the bacterial cells are trapped inside the biofilm, they are left with little access to nutrients and oxygen. To conserve their resources and energy, they transition into a dormant or sleepy state. The bacteria, which are known as persister cells in this state, are extremely resistant to antibiotics.

Researchers chose gentamicin, a topical antibiotic typically ineffective against S. aureus due to widespread antibiotic resistance and poor activity against persister cells. The researchers also introduced a novel antibiotic adjuvant, palmitoleic acid, to their models.

Palmitoleic acid, an unsaturated fatty acid, is a natural product of the human body that has strong antibacterial properties. The fatty acid embeds itself into the membrane of bacterial cells, and the authors discovered that it facilitates the antibiotic’s successful entry into S. aureus cells and is able to kill persister cells and reverse antibiotic resistance.

Overall, the team is enthusiastic about the new topical, non-invasive approach because it may give scientists and doctors more tools to combat antibiotic resistance and to lessen the serious adverse effects of taking oral antibiotics.

“Systemic antibiotics, such as oral or IV, work very well, but there’s often a large risk associated with them such as toxicity, wiping out gut microflora and C. difficile infection,” said Rowe-Conlon. “Using this system, we are able to make topical drugs work and they can be applied to the site of infection at very high concentrations, without the risks associated with systemic delivery.”

About UNC School of Medicine

The UNC School of Medicine (SOM) is the state’s largest medical school, graduating more than 180 new physicians each year. It is consistently ranked among the top medical schools in the US, including 5^th overall for primary care by US News & World Report, and 6^th for research among public universities. More than half of the school’s 1,700 faculty members served as principal investigators on active research awards in 2021. Two UNC SOM faculty members have earned Nobel Prize awards.

About the Joint Department of Biomedical Engineering

The Joint Department is ranked in the top 10 biomedical engineering programs in the US by the Blue Ridge Institute for Medical Research, top 20 biomedical engineering programs worldwide by the Shanghai Academic Ranking of World Universities, and is a top 5 institution for total bachelor’s degrees awarded in biomedical engineering (ASEE).

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University of North Carolina School of Medicine

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May 22, 2023
Artificial Intelligence Catalyzes Gene Activation Research and Uncovers Rare DNA Sequences

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BYLINE: Mario Aguilera

Newswise — Artificial intelligence has exploded across our news feeds, with ChatGPT and related AI technologies becoming the focus of broad public scrutiny. Beyond popular chatbots, biologists are finding ways to leverage AI to probe the core functions of our genes.

Previously, University of California San Diego researchers who investigate DNA sequences that switch genes on used artificial intelligence to identify an enigmatic puzzle piece tied to gene activation, a fundamental process involved in growth, development and disease. Using machine learning, a type of artificial intelligence, School of Biological Sciences Professor James T. Kadonaga and his colleagues discovered the downstream core promoter region (DPR), a “gateway” DNA activation code that’s involved in the operation of up to a third of our genes.

Building from this discovery, Kadonaga and researchers Long Vo ngoc and Torrey E. Rhyne have now used machine learning to identify “synthetic extreme” DNA sequences with specifically designed functions in gene activation. Publishing in the journal Genes & Development, the researchers tested millions of different DNA sequences through machine learning (AI) by comparing the DPR gene activation element in humans versus fruit flies (Drosophila). By using AI, they were able to find rare, custom-tailored DPR sequences that are active in humans but not fruit flies and vice versa. More generally, this approach could now be used to identify synthetic DNA sequences with activities that could be useful in biotechnology and medicine.

“In the future, this strategy could be used to identify synthetic extreme DNA sequences with practical and useful applications. Instead of comparing humans (condition X) versus fruit flies (condition Y) we could test the ability of drug A (condition X) but not drug B (condition Y) to activate a gene,” said Kadonaga, a distinguished professor in the Department of Molecular Biology. “This method could also be used to find custom-tailored DNA sequences that activate a gene in tissue 1 (condition X) but not in tissue 2 (condition Y). There are countless practical applications of this AI-based approach. The synthetic extreme DNA sequences might be very rare, perhaps one-in-a-million—if they exist they could be found by using AI.”

Machine learning is a branch of AI in which computer systems continually improve and learn based on data and experience. In the new research, Kadonaga, Vo ngoc (a former UC San Diego postdoctoral researcher now at Velia Therapeutics) and Rhyne (a staff research associate) used a method known as support vector regression to “train” machine learning models with 200,000 established DNA sequences based on data from real-world laboratory experiments. These were the targets presented as examples for the machine learning system. They then “fed” 50 million test DNA sequences into the machine learning systems for humans and fruit flies and asked them to compare the sequences and identify unique sequences within the two enormous data sets.

While the machine learning systems showed that human and fruit fly sequences largely overlapped, the researchers focused on the core question of whether the AI models could identify rare instances where gene activation is highly active in humans but not in fruit flies. The answer was a resounding “yes.” The machine learning models succeeded in identifying human-specific (and fruit fly-specific) DNA sequences. Importantly, the AI-predicted functions of the extreme sequences were verified in Kadonaga’s laboratory by using conventional (wet lab) testing methods.

“Before embarking on this work, we didn’t know if the AI models were ‘intelligent’ enough to predict the activities of 50 million sequences, particularly outlier ‘extreme’ sequences with unusual activities. So, it’s very impressive and quite remarkable that the AI models could predict the activities of the rare one-in-a-million extreme sequences,” said Kadonaga, who added that it would be essentially impossible to conduct the comparable 100 million wet lab experiments that the machine learning technology analyzed since each wet lab experiment would take nearly three weeks to complete.

The rare sequences identified by the machine learning system serve as a successful demonstration and set the stage for other uses of machine learning and other AI technologies in biology.

“In everyday life, people are finding new applications for AI tools such as ChatGPT. Here, we’ve demonstrated the use of AI for the design of customized DNA elements in gene activation. This method should have practical applications in biotechnology and biomedical research,” said Kadonaga. “More broadly, biologists are probably at the very beginning of tapping into the power of AI technology.”

Funding from the National Institutes of Health (R35 GM118060) supported the research.

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University of California San Diego

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May 19, 2023
Urine use for sustainable food systems in sub-Saharan cities

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Newswise — Installing urine collection systems in sub-Saharan city regions would make those conurbations more sustainable. This was demonstrated by a study by four researchers from CIRAD, IRD, Boubakar Bâ University of Tillaberi (Niger) and Joseph Ki-Zerbo University, Ouagadougou (Burkina Faso), published on 3 May 2023 in the journal Regional Environmental Change. For their study, the researchers analysed nitrogen flows in waste in two sub-Saharan cities: Maradi (Niger) and Ouagadougou. The study was a first, and showed that urine was the main source of nitrogen losses. Collecting that urine could provide valuable fertilizer suitable for local agricultural use, and thus serve to make city region food systems more sustainable.

Current urban development trajectories in sub-Saharan Africa are not sustainable. Fast-growing cities constitute nutrient sinks relying on nutrient-poor hinterlands. Those sinks, and the degradation and draining of nutrients in hinterlands, have significant environmental and health impacts. This runs counter to The UN Sustainable Development Goal 11, which aims to “make cities and human settlements inclusive, safe, resilient and sustainable”.

To give the authorities a cross-sectoral view of a city’s nutrient sink status, the researchers identified and analysed a range of waste flows. Their approach distinguished four nested spatial levels: the urban area; the potential territorial recycling system; the country and the international level. Based on that analysis, the researchers focused on the origin and fate of those nutrient-containing waste flows. The method was applied to nitrogen in Maradi and Ouagadougou, to determine whether and to what extent those city regions could progress towards sustainable urban food systems. The fact of focusing on the nitrogen in waste rather than on waste flows themselves enabled a systemic understanding useful to the local authorities.

The study showed that Maradi was a nitrogen sink, albeit at the heart of a still relatively sustainable urban food system. However, it could well evolve towards a situation similar to that of Ouagadougou: a large nitrogen sink with no significant city-hinterland recycling. Although of contrasting size, currently around 400 000 and 2 800 000 inhabitants respectively, these two cities evolve in highly similar biophysical, climatic, agricultural and socioeconomic settings. Their respective results may thus be considered an approximate illustration of a development trajectory.

The study provided the first overview of waste-contained nitrogen flows in sub-Saharan cities. Existing reports so far provided only partial, sectoral assessments, focusing either on waste management, on sanitation, or on agriculture, while this study showed that nitrogen losses through sanitation and waste management largely exceeded other waste-contained nitrogen flows in these cities. Urine is therefore the main source of nitrogen loss. Urine collection initiatives to enable its use as a fertilizer would make urban systems more independent and resilient. This would improve regional food provision and reduce sanitation-induced urban water pollution, making urban systems more sustainable. The researchers consider that addressing the potential for urine recycling would be a worthwhile follow-up to this study.

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Institut de Recherche pour le Developpement (IRD)

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May 12, 2023
The Association of Biomolecular Resource Facilities 2023 Annual Meeting, May 7-10, Boston

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Newswise — May 5, 2023 (Lexington, KY) – The Association of Biomolecular Resource Facilities (ABRF) 2023 Annual Meeting will be held May 7-10 at the Sheraton Boston Hotel. This year’s meeting focuses on Driving Collaborative Science, and features dozens of sessions on timely topics on the latest technology and strategies for shared research resources. With close to 1000 attendees from more than 200 leading academic research institutions and commercial manufacturers attending, the ABRF 2023 Annual Meeting will be the largest event for shared research resources, or Core, facilities.

Among the notable sessions at the 2023 ABRF Annual Meeting are:

ABRF Award for Outstanding Contributions to Biomolecular Technologies – presented to Dr. Chris Enke and Richard Yost for the development of the triple quadrupole mass spectrometer and the tremendous impact triple quads have made for a wide range of biomedical research applications.

ABRF Diversity Equity and Inclusion Award – presented to Dr. Tshaka Cunningham with Polaris Genomics and Future Kings, a regional nonprofit which serves boys and girls of color from economically challenged communities through a unique, year-long afterschool educational program that guides young men and women in grades 6-12 from underserved communities to explore exciting career opportunities in science, technology, engineering, and mathematics (STEM). Their targeted focus is on cybersecurity, computer game design, biomedical sciences, and engineering.

Keynote speakers: Beth Cimini, Ph.D., Senior Group Leader, Broad Institute will present Making More from Your Microscopy: Advances in High-Content Image Analysis

Ed Boyden, Ph.D., HHMI and MIT, will close the meeting with an engaging presentation on Optical Tools for Analyzing and Controlling Biological Systems.

Along with these key sessions, the ABRF Annual Meeting will include dozens of workshops on current developments in specific technology areas, including Genomics, Imaging, Mass Spectrometry, Flow Cytometry, and Proteomics, as well as best practices for Core Facilities Management and Leadership. Attendees will also engage with over 70 biotechnology manufacturers and systems developers to view the latest advances in research instrumentation and tools to support their ground-breaking work. Visit the meeting web site for the latest information or contact ABRF to learn more.

About the Association of Biomolecular Resource Facilities

The Association of Biomolecular Resource Facilities is a unique membership association comprising over 2000 members working within or in the support of resource and research biotechnology laboratories. Our members represent over 400 laboratories and administrative offices in government, academia, research, industry and commercial settings. ABRF promotes education and career advancement for scientists, core administrators, and staff through conferences, a quarterly journal, publication of research group studies and conference scholarships. The society also sponsors multi-center research studies designed to help members incorporate new biotechnologies into their laboratories.

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Federation of American Societies for Experimental Biology (FASEB)

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May 5, 2023
Quantum-Enhanced Microscope Doubles Resolution

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Newswise — Using a “spooky” phenomenon of quantum physics, Caltech researchers have discovered a way to double the resolution of light microscopes.

In a paper appearing in the journal Nature Communications, a team led by Lihong Wang, Bren Professor of Medical Engineering and Electrical Engineering, shows the achievement of a leap forward in microscopy through what is known as quantum entanglement. Quantum entanglement is a phenomenon in which two particles are linked such that the state of one particle is tied to the state of the other particle regardless of whether the particles are anywhere near each other. Albert Einstein famously referred to quantum entanglement as “spooky action at a distance” because it could not be explained by his relativity theory.

According to quantum theory, any type of particle can be entangled. In the case of Wang’s new microscopy technique, dubbed quantum microscopy by coincidence (QMC), the entangled particles are photons. Collectively, two entangled photons are known as a biphoton, and, importantly for Wang’s microscopy, they behave in some ways as a single particle that has double the momentum of a single photon.

Since quantum mechanics says that all particles are also waves, and that the wavelength of a wave is inversely related to the momentum of the particle, particles with larger momenta have smaller wavelengths. So, because a biphoton has double the momentum of a photon, its wavelength is half that of the individual photons.

This is key to how QMC works. A microscope can only image the features of an object whose minimum size is half the wavelength of light used by the microscope. Reducing the wavelength of that light means the microscope can see even smaller things, which results in increased resolution.

Quantum entanglement is not the only way to reduce the wavelength of light being used in a microscope. Green light has a shorter wavelength than red light, for example, and purple light has a shorter wavelength than green light. But due to another quirk of quantum physics, light with shorter wavelengths carries more energy. So, once you get down to light with a wavelength small enough to image tiny things, the light carries so much energy that it will damage the items being imaged, especially living things such as cells. This is why ultraviolet (UV) light, which has a very short wavelength, gives you a sunburn.

QMC gets around this limit by using biphotons that carry the lower energy of longer-wavelength photons while having the shorter wavelength of higher-energy photons.

“Cells don’t like UV light,” Wang says. “But if we can use 400-nanometer light to image the cell and achieve the effect of 200-nm light, which is UV, the cells will be happy, and we’re getting the resolution of UV.”

To achieve that, Wang’s team built an optical apparatus that shines laser light into a special kind of crystal that converts some of the photons passing through it into biphotons. Even using this special crystal, the conversion is very rare and occurs in about one in a million photons. Using a series of mirrors, lenses, and prisms, each biphoton—which actually consists of two discrete photons—is split up and shuttled along two paths, so that one of the paired photons passes through the object being imaged and the other does not. The photon passing through the object is called the signal photon, and the one that does not is called the idler photon. These photons then continue along through more optics until they reach a detector connected to a computer that builds an image of the cell based on the information carried by the signal photon. Amazingly, the paired photons remain entangled as a biphoton behaving at half the wavelength despite the presence of the object and their separate pathways.

Wang’s lab was not the first to work on this kind of biphoton imaging, but it was the first to create a viable system using the concept. “We developed what we believe a rigorous theory as well as a faster and more accurate entanglement-measurement method. We reached microscopic resolution and imaged cells.”

While there is no theoretical limit to the number of photons that can be entangled with each other, each additional photon would further increase the momentum of the resulting multiphoton while further decreasing its wavelength.

Wang says future research could enable entanglement of even more photons, although he notes that each extra photon further reduces the probability of a successful entanglement, which, as mentioned above, is already as low as a one-in-a-million chance.

The paper describing the work, “Quantum Microscopy of Cells at the Heisenberg Limit,” appears in the April 28 issue of Nature Communications. Co-authors are Zhe Heand Yide Zhang, both postdoctoral scholar research associates in medical engineering; medical engineering graduate student Xin Tong (MS ’21); and Lei Li (PhD ’19), formerly a medical engineering postdoctoral scholar and now an assistant professor of electrical and computer engineering at Rice University.

Funding for the research was provided by the Chan Zuckerberg Initiative and the National Institutes of Health.

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California Institute of Technology

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May 2, 2023
Mushrooms communicate with electricity after rain

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Newswise — Certain fungi play a critical role in the ecological sustenance of forest trees. Ectomycorrhizal fungi are one such example. Commonly found on pine, oak, and birch trees, ectomycorrhizal fungi form a sheath around the outside of tree roots, and their mycelial body develops into vast underground networks that absorb vital nutrients from the soil and transfer it to the trees.

Scientists have been studying the possibility of electrical signal transfer between mushrooms and across trees via the mycelial networks. It is thought that fungi generate electrical signals in response to external stimuli and use these signals to communicate with each other, coordinating growth and other behavior. It has even been hypothesized that these signals can be used to help transfer nutrients to plants and trees.

Still, current scientific evidence remains sparse. Moreover, many studies have been limited to the laboratory, failing to recreate what happens in the wild.

Now, a group of researchers has recently headed to the forest floor to examine small, tan-colored ectomycorrhizal mushrooms known as Laccaria bicolor. Attaching electrodes to six mushrooms in a cluster, the researchers discovered that the electrical signals increased after rainfall.

“In the beginning, the mushrooms exhibited less electrical potential, and we boiled this down to the lack of precipitation,” says Yu Fukasawa from Tohoku University, who lead the project along with Takayuki Takehi and Daisuke Akai from the National Institute of Technology, Nagaoka College, and Masayuki Ushio from the Hakubi Center, Kyoto University (presently at the Hong Kong University of Science and Technology). “However, the electrical potential began to fluctuate after raining, sometimes going over 100 mV.”

The researcher correlated this fluctuation with precipitation and temperature, and causality analysis revealed that the post-rain electric potential showed signal transport among mushrooms. This transport was particularly strong between spatially close mushrooms and demonstrated directionality.

“Our results confirm the need for further studies on fungal electrical potentials under a true ecological context,” adds Fukasawa.

Details of their research were reported in the journal Fungal Ecology on March 14, 2023.

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Tohoku University

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April 28, 2023
Digital Health Initiative Research Could Lead to More Reliable Health Apps
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BYLINE: Doug M Dollemore

Newswise — Seven University of Utah Health projects have received seed grants that could promote the development and use of more scientifically based digital health applications in daily health care.

The grants, supported by the Digital Health Initiative (DHI), will focus on projects designed to produce safer and more effective digital tools than are currently available, according to Guilherme Del Fiol, M.D., Ph.D., co-director of DHI and a professor in the Department of Biomedical Informatics at U of U Health.

“There’s been a surge in the use of digital health applications in the past few years, both by patients and their doctors,” Del Fiol says. “But how many of these apps actually work as intended? Most are promoted with little or no rigorous scientific evidence.”

In fact, a 2019 analysis of studies conducted by the 25 top-funded American producers of digital health tools, including wearable biosensors and mobile health apps, found that most of these products did not have a substantial impact on health outcomes, cost, or access to care. Another study of mental health apps concluded that only 14% of the 1,400 apps evaluated were based on real-world experiences, and none mentioned a certification or accreditation process.

“We see these seed grants as a tremendous opportunity to alter that trajectory,” Del Fiol says. “They represent a starting point for taking innovative, reliable, and scientifically tested digital health applications from bench to bedside.”

The seed grant projects will receive up to $50,000 for one year. The researchers will develop, test, and evaluate digital applications that fall within one of the four main areas of interest within the DHI:
- Mobile apps and games for health
- Virtual reality and sensors
- Clinical decision support tools
- Integration with electronic health records (EHR)
If successful, the projects will progress to clinical trials designed to assess their usefulness in a larger context, says Victoria Tiase, Ph.D., R.N., director of strategic development at DHI.

“Clinicians treating patients at the bedside need better efficiency today,” Tiase says. “So, we need to get more practical and effective digital tools in the pipeline. We hope that these seed grants will be a jumping-off point for that effort.”

Recipients of the seven seed grants represent 11 U of U Health disciplines, ranging from anesthesiology to nursing to population health.

Project Titles, Summaries, & Awardees

Health Records and Community Service Integration of the Going Home Toolkit

Andrea Wallace, Ph.D. (Nursing)

Roger Altizer, Ph.D. (Entertainment Arts Engineering, Population Health Sciences)

Kensaku Kawamoto, M.D., Ph.D. (Biomedical Informatics)

Wallace and colleagues will evaluate the effectiveness of a digital resource planner to help patients self-manage their health conditions after they leave the hospital. Called the “Going Home Toolkit”, the planner includes sections on transportation, medication, errands, meals, housework, personal care, billing, and insurance. It is also designed to help patients better communicate their needs to family, friends, and health care providers.

Broadening the Impact of Symptom Care at Home Through EHR Integration and Implementation Science

Elizabeth Sloss, Ph.D., M.B.A., R.N. (Nursing, Huntsman Cancer Institute)

Kathi Mooney, Ph.D., R.N (Nursing)

Justin D. Smith, Ph.D. (Population Health Sciences)

Guilherme Del Fiol, M.D., Ph.D. (Biomedical Informatics)

Kensaku Kawamoto, M.D., Ph.D. (Biomedical Informatics)

Symptom Care at Home, a program that helps cancer patients reduce symptoms that occur during treatment for cancer, asks patients to report daily symptoms in a mobile application or by phone and receive automated coaching or follow-up from a nurse practitioner to manage their symptoms. With this DHI seed grant, the researchers will identify ways that Symptom Care at Home can incorporate patient-reported symptoms into their electronic health records.

Patient Generated Health Data for Geriatrics Patients

Jorie Butler, Ph.D. (Biomedical Informatics)

Butler will collect patient-generated health data, using mobile devices like a Fitbit, from patients aged 65 and older with chronic pain. The participating patients will review and discuss their personal data with the research team to help them understand how these data are useful to patients in managing their own health. This research can be applied to future care of pain and other health conditions.

Expanding the Capability of Intraprocedure Anesthesia Information Display and Pharmacology Forecasting

Ken B. Johnson, M.D., M.S. (Anesthesiology)

Beca Chacin (Anesthesiology Center for Patient Simulation)

Soeren Hoehne (Anesthesiology Center for Patient Simulation)

Cameron Jacobsen, M.S. (Anesthesiology)

Noah Syroid, M.S. (Anesthesiology)

Johnson and colleagues seek to combine an anesthesia forecasting system with electronic health records at U of U Health. With this system, an anesthesia provider will have visual guidance to monitor and predict the levels of sedation, analgesia (pain relief), and muscle relaxation for a patient who is undergoing general anesthesia.

Explainable AI for Equitable Risk Stratification of Atrial Fibrillation and Stroke

Mark Yandell, Ph.D. (Human Genetics, Bioinformatics)

Martin Tristani Firouzi, M.D. (Pediatrics)

Benjamin Steinberg M.D. (Cardiology)

Using artificial intelligence, Yandell and colleagues seek to produce more accurate predictions of individual stroke risk. The computational model will account for socioeconomic disparities seldom considered in previous attempts at predicting strokes. These considerations include housing, transportation, and discrimination, and accessibility to nutritious foods and exercise. These refined predictions will enable doctors to offer patients more personalized stroke prevention advice.

Remote sensing of autonomic function and mobility coupling using wearables to monitor recovery after mild traumatic brain injury.

Peter Fino, Ph.D. (Health and Kinesiology)

Melissa Cortez, D.O. (Neurology)

Leland Dibble, Ph.D., P.T. (Physical Therapy & Athletic Training)

Fino and his colleagues seek to develop a system to assess individuals who have persistent symptoms of mild traumatic brain injury (mTBI), such as concussions. The researchers will monitor activity, heart rate, and other key indicators of mTBI using wearable at-home devices.

By combining data streams from these devices worn at home, the researchers believe they can identify individuals with persistent mTBI symptoms earlier and expedite rehabilitation when they show signs of atypical recovery.

Spanish Language Translation and Preliminary Feasibility of NeuroFlex: A Digital Cognitive Intervention for Late Life Depression

Sarah Morimoto, Psy.D. (Population Health Sciences)

Morimoto will translate and test a video game designed to relieve depression among older Spanish-speaking volunteers. The game, called Neurogrow, allows players to tend a virtual garden, performing tasks including watering, fertilizing, and eliminating pesky bugs.

In previous research, the scientists found that Neurogrow helped relieve depression and improve cognitive function among English-speaking, non-Hispanic older men and women. The researchers hope to find similar results in Spanish-speaking volunteers. If successful, they plan to use Neurogrow more broadly in Latino/Hispanic communities.

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University of Utah Health

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April 28, 2023
Farm waste turned into air-cleaning substance

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Newswise — Air pollution and its high concentration in cities is one of the problems facing society today, due to its harmful effects on the environment, but also on human health. One of the causes of this pollution is the increase in nitrogen oxide emissions, mainly due to the use of fossil fuels.

While the emissions of these gases are being reduced, photocatalysis is proving to be a tool for decontaminating air in cities: materials called semiconductors are created which, when coming into contact with the pollutant, under the effect of ultraviolet light, cause it to degrade, thus reducing its concentration in the air.

Two research groups of the University of Cordoba, belonging to the Chemical Institute for Energy and the Environment (IQUEMA),and the Department of Inorganic Chemistry and Chemical Engineering,have been working to produce these materials. The team,formed by the BioPrEn and Inorganic Chemistry groups, has obtained biodegradable materials to fix nanoparticles with photocatalytic activity (in this case, titanium dioxide), augmentingthe power and, therefore,the decontaminating effect.

The advances made by this work consist of “first, the creation of a biodegradable medium based on nanocellulose, obtained from agricultural waste; and, second, the development of a surface modification process of these nanoparticles, which results on their greater dispersion and immobilization,and, therefore, enhanced photocatalytic activity”, explains one of the authors of the article, researcher Eduardo Espinosa.

The progress is twofold: it is possible to create a sustainable material by recovering a form of agricultural waste(thus contributing to the Circular Economy) and the process of fixing photocatalytic nanoparticles to this biodegradable medium is simplified. The benefit is, in fact, exponential, since the result is greater air decontamination due to the porosity and the three-dimensional nature of the material, which means that more photocatalytic particles are exposed to ultraviolet light compared to an opaque material or one in which only one surface is exposed to light.

What is it like? Where is it used?

Those who see this material will recognize a light, solid foam, but with very little density, similar to insulation coverings used in construction,or the popular corn “puffs.” To effect decontamination “it can be used as a porous filter through which the gas stream passes, always exposed to ultraviolet light, and the gas comes out decontaminated,” says Espinosa. Thus, gases released by industry, for example, would come out almost clean of nitrogen oxides.

A further step in this research would be to modify the photocatalytic particle so that it is more sensitive to light from the visible spectrum, without having to resort to ultraviolet sources. In this way the photocatalytic power would be activated by sunlight alone, and this type of technology could be applied to textiles and other types of materials,thereby reducing the concentration of gases only through exposure to the sun.

References:

Carrasco, Sergio & Espinosa Víctor, Eduardo & González, Zoilo & Cruz-Yusta, Manuel & Sánchez, Luis & Rodríguez, Alejandro (2023). Simple Route to Prepare Composite Nanocellulose Aerogels: A Case of Photocatalytic De-NO x Materials Application. ACS Sustainable Chemistry &Engineering. https://doi.org/10.1021/acssuschemeng.2c06170

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University of Cordoba

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April 19, 2023
Capsule Wonder Drug Could Replace Insulin Injections for Diabetics

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Newswise — Scientists in Melbourne have designed a new type of oral capsule that could mean pain-free delivery of insulin and other protein drugs.

Co-lead researcher Professor Charlotte Conn, a biophysical chemist from RMIT University, said protein drugs had proven challenging to deliver orally as the drugs degrade very quickly in the stomach – until now.

“These types of drugs are typically administered with an injection – thousands of diabetics in Australia need insulin injections up to several times a day, which can be unpleasant for the patient and results in high healthcare costs,” said Conn, from RMIT’s School of Science.

She said the new technology could also be used to deliver other protein drugs orally – including a new type of oral antibiotic developed by the RMIT team that can avoid resistance by dangerous superbugs.

“Other protein drugs such as monoclonal antibodies have been developed to treat inflammatory conditions, cancer and other diseases with a projected market value of about $400 billion by 2030,” Conn said.

An international patent application has been filed for RMIT’s technology.

Strong pre-clinical results provide optimism for a new way to deliver insulin

The team has tested the new oral capsule with insulin in a pre-clinical study and the results have been published in the international journal Biomaterials Advances.

“We think the results are really exciting, and we’re doing a suite of pre-clinical testing so we can move to clinical trials as soon as possible,” Conn said.

The research paper assessed the performance of the oral capsules with both fast-acting and slow-acting insulin.

“When controlling the blood-sugar, you need a very fast response if you’re eating a meal. That’s known as fast-acting insulin,” Conn said.

A slow-acting form acts over a much longer timeframe – up to a day or so – to keep the insulin in the body steady. Most diabetics take a combination of both types of insulin.

“We had excellent absorption results for the slow-acting form – about 50% better than injection delivery for the same quantity of insulin,” Conn said.

The capsule achieved good absorption results for fast-acting insulin, but the significant lag in the insulin taking effect compared with injection delivery would likely make it less practical.

“Our results show there is real promise for using these oral capsules for slow-acting insulin, which diabetics could one day take in addition to having fast-acting insulin injections,” Conn said.

“The oral capsules could potentially be designed to allow dosing over specific time periods, similar to injection delivery. We need to investigate this further, develop a way of doing so and undergo rigorous testing as part of future human trials.”

How does the team’s drug capsule work?

Dr Jamie Strachan, the first author on the paper, said the capsule protected the drug inside so that it passed safely through the stomach to the small intestine.

“The capsule has a special coating designed to not breakdown in the low pH environment of the stomach, before the higher pH levels in the small intestine trigger the capsule to dissolve,” said Strachan, from RMIT’s School of Science.

“We package the insulin inside a fatty nanomaterial within the capsule that helps camouflage the insulin so that it can cross the intestinal walls.

“It’s actually similar to how the Pfizer and the Moderna COVID vaccines work where the mRNA in those vaccines is also packaged within fats, helping to keep the drugs active and safe during delivery in the body.”

These vaccines contain mRNA, which is similar to DNA, to safely carry the instructions for making a viral protein within the body, activating our immune system.

A cheaper and more efficient way to deliver protein drugs

Dr Céline Valéry, a pharmaceutical scientist from RMIT and study co-author, said they used the same amount of insulin in the oral capsules and in the injection delivery.

“For many pre-clinical trials the oral formulations by necessity contain much higher levels of insulin to achieve the same response as the injection delivery. This is not a very cost-effective way to deliver protein drugs which tend to be expensive,” said Valéry, from RMIT’s School of Health and Biomedical Sciences.

“It’s a great starting point but we need to do further trials to develop an alternative, pain-free method for the delivery of insulin and other protein drugs.”

‘A promising new oral delivery mode for insulin using lipid-filled enteric-coated capsules,’ is published in Biomaterials Advances (DOI: 10.1016/j.bioadv.2023.213368).

Jamie Strachan, Brendan Dyett, Stanley Chan, Brody McDonald, Ross Vlahos, Céline Valéry and Charlotte Conn are co-authors.

MULTIMEDIA FOR MEDIA USE

Here’s a link to images related to the story: https://cloudstor.aarnet.edu.au/plus/s/4gw6HYR8NokqnAL.

There are photos of the oral capsule, along with a visual explanation from the scientists of what’s in the capsule and how it is prepared.

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RMIT University

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April 19, 2023
Safe Bioink for Artificial Organ Printing

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Newswise — The development of biomaterials for artificial organs and tissues is active due to an increase in accidental injuries and chronic diseases, along with the entry into a super-aged society. 3D bioprinting technology, which uses cells and biomaterials to create three-dimensional artificial tissue structures, has recently gained popularity. However, commonly used hydrogel-based bioinks can cause cytotoxicity due to the chemical crosslinking agent and ultraviolet light that connect the molecular structure of photocuring 3D-printed bioink.

Dr. Song Soo-chang’s research team at the Center for Biomaterials, Korea Institute of Science and Technology (KIST, President Yoon Seok-jin), revealed the first development of poly(organophosphazene) hydrogel-based temperature-sensitive bioink that stably maintained its physical structure only by temperature control without photocuring, induced tissue regeneration, and then biodegraded in the body after a certain period of time.

Current hydrogel-based bioinks must go through a photocuring process to enhance the mechanical properties of the 3D scaffold after printing, with a high risk of adverse effects in the human body. In addition, there have been possibility of side effects by transplanting externally cultured cells within bioink to increase the tissue regeneration effect. Accordingly, the research team developed a new bioink material using a temperature-sensitive poly(organophosphazene) hydrogel, which existed in a liquid form at low temperatures and changed to a hard gel at body temperature. This enabled the regeneration of tissues only by temperature control without chemical crosslinking agents or UV irradiation and the manufacture of a three-dimensional scaffold with a physically stable structure, minimizing the possibility of immune adverse effects in the human body.

The developed bioink also had a molecular structure that could interact with growth factors, which were proteins that help in tissue regeneration to preserve growth factors that regulated cell growth, differentiation, and immune responses for a long period of time. The research team was able to maximize the effect of tissue regeneration by creating an environment in which cell differentiation could be autonomously regulated within the 3D scaffold printed with bioink.

The research team fabricated the 3D scaffold by printing it with a 3D bioprinter using bioink containing transforming growth factor beta 1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2), which were required for cell infiltration and bone regeneration, and conducted an experiment by implanting it into a damaged bone in a rat. As a result, cells from the surrounding tissue were migrated into the scaffold, and the defected bone was regenerated to a normal tissue level, and the implanted 3D scaffold slowly biodegraded in the body over 42 days.

Dr. Song Soo-Chang of KIST said, “The research team has transferred technology for the thermo-sensitive polyphosphazene hydrogel to NexGel Biotech Co., Ltd. in June 2022, and the development of products such as bone graft materials and cosmetic fillers is underway.” “As the bioink developed this time has different physical properties, follow-up research to apply it to the regeneration of other tissues besides bone tissue is being conducted, and we expect to finally be able to commercialize bioink tailored to each tissue and organ,” he said.

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KIST was established in 1966 as the first government-funded research institute in Korea. KIST now strives to solve national and social challenges and secure growth engines through leading and innovative research. For more information, please visit KIST’s website at https://eng.kist.re.kr/

This research was conducted through the KIST Major Projects supported by the Ministry of Science and ICT (Minister Lee Jong-ho), and the research results were published as the inside back cover in the latest issue of “Small” (IF: 15.153, top 7.101% in the JCR field), an international academic journal in the field of materials.

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National Research Council of Science and Technology

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April 13, 2023
tRNA biomarkers for cancer diagnosis and prognosis enabled by new method

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Newswise — Ribonucleic acid (RNA) molecules are present in all living cells, with different types of RNA having different jobs. For example, messenger RNA is copied from DNA and carries instructions on how to make a protein. Transfer RNA (tRNA) links the mRNA sequence with its corresponding amino acid, ensuring that proteins are stitched together correctly as instructed by DNA.

Cells naturally modify RNA molecules in order to enhance their stability, structure and function. When this modification process goes wrong, it can have important consequences for human health and disease. In the case of tRNA, incorrect or missing modifications produce faulty or incomplete proteins, with the dysregulation of tRNA modifications being linked to various human diseases, including neurodegenerative diseases, metabolic diseases, and cancer.

tRNAs are “information-rich” molecules with huge potential for the diagnosis and prognosis of diseases, but so far haven’t been exploited for such purpose due to the lack of methods that can capture this information in a quantitative and cost-efficient manner. For example, some types of cancers are difficult to diagnose because their symptoms are non-specific and can be confused with other conditions. At the same time, certain tRNA modification profiles are only known to exist in specific cancer types and can serve as highly-specific biomarkers.

Being able to isolate tRNA molecules from blood samples and quantify their modifications can help diagnose cancers without the use of imaging tests or invasive biopsies. Furthermore, the type of tRNA modifications can change depending on the state of the disease, providing valuable information about the prognosis of the condition.

Current methods for measuring tRNA molecules typically involve techniques such as next-generation sequencing or mass spectrometry, however, these methods have limited use for diagnostic purposes because they are either unable to detect modifications, or they cannot identify at which location of the tRNA they are occurring at.

Researchers at the Centre for Genomic Regulation (CRG) in Barcelona have addressed this challenge by developing a new method that can measure both the abundance and modification of tRNA molecules in a single step. The method is called Nano-tRNAseq and is first described today in the journal Nature Biotechnology.

Nano-tRNAseq is based on nanopore sequencing, a technology that can directly sequence individual RNA molecules by passing them through a small pore. Each of the nucleotides that compose an RNA molecule has a slightly different size and shape, with a corresponding change in the electrical current that occurs as each nucleotide passes through the pore. Computer programs detect changes in the current to identify the sequence of the RNA molecules, including any modifications. As a proof of concept, the researchers used Nano-tRNAseq to accurately measure tRNA abundances and modifications in samples taken from yeast cells exposed to different environmental conditions.

The method has significant advantages over conventional techniques. “For the first time, we can study both tRNA abundance and tRNA modification profiles simultaneously. As a bonus, the method is rapid, cost-effective, high-throughput, and has single-molecule resolution. Previously, we relied on two separate methods that, together, are less informative, and it would take weeks and cost thousands of euros to obtain results. Nano-tRNAseq is a fraction of the cost, and we can have results within a couple of days, and in the near future, within a few hours” says Morghan Lucas, PhD candidate at the Centre for Genomic Regulation and first author of the study.

The rapid data analysis enabled by the method is critical for clinical decision-making. Another advantage is that the nanopore sequencing machines required for the technique are small, lightweight and can be powered by a laptop or portable battery, making them easy to transport to remote locations and enable use in the field or the clinic.

The researchers note there are still some limitations to the new method, such as the inability to predict which tRNA modification is dysregulated in a given sample unless the precise modifications found in that tRNA have been previously identified using other experimental methods. “While tRNA modification profiles of lower eukaryotic species, such as yeast, are well characterized, this is not the case for humans. By using Nano-tRNAseq in parallel with other methods, we can describe the modification profiles of the complete set of human tRNAs and, in the future, use Nano-tRNAseq to identify which changes in tRNAs are associated with a given human disease,” adds Morghan Lucas.

The method was developed by Dr. Eva Novoa’s research group at the Centre for Genomic Regulation (CRG). Dr. Novoa plans on using the technology to further her research efforts funded by the Spanish Association Against Cancer (AECC).

“tRNA molecules can be cleaved into small but stable RNA fragments which circulate in blood plasma. These molecules are typically altered in cancer patients, and are hugely information-rich for diagnostic and prognostic purposes. Nano-tRNAseq is a proof-of-concept technology that paves the way for the development of a simple, cost-effective and highly-precise method that can quantify these molecules in a non-invasive manner. Our aim is to further develop this technology and combine it with artificial intelligence tools to determine the malignancy of a biological sample in less than 3 hours, and at a cost of no more than 50 euros per sample” says Dr. Eva Novoa, senior author of the study and researcher at the Centre for Genomic Regulation.

The study was funded by the Spanish Ministry of Economy, Industry, and Competitiveness and a European Research Council Starting Grant. Collaborators include the Institute for Research in Biomedicine (IRB) in Barcelona and the CNRS-Université de Lorraine in Nancy, France. 

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Center for Genomic Regulation

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April 6, 2023