Therapeutic Potential of Quercetin as an Antioxidant for Bone-Muscle-Tendon Regeneration and Aging.

Quercetin (QC), a naturally occurring bioflavonoid found in various fruits and vegetables, possesses many potential health benefits, primarily attributed to its robust antioxidant properties. The generation of oxidative stress in bone cells is a key modulator of their physiological behavior. Moreover, oxidative stress status influences the pathophysiology of mineralized tissues. Increasing scientific evidence demonstrates that manipulating the redox balance in bone cells might be an effective technique for developing bone disease therapies. The QC antioxidant abilities in skeletal muscle significantly enhance muscle regeneration and reduce muscle atrophy. In addition, QC has been shown to have protective effects against oxidative stress, inflammation, apoptosis, and matrix degradation in tendons, helping to maintain the structural integrity and functionality of tendons. Thus, the antioxidant properties of QC might be crucial for addressing age-related musculoskeletal disorders like osteoporosis, sarcopenia, and tendon-related inflammatory conditions. Understanding how QC influences redox signaling pathways involved in musculoskeletal disorders, including their effect on bone, muscle, and tendon differentiation, might provide insights into the diverse advantages of QC in promoting tissue regeneration and preventing cellular damage. Therefore, this study reviewed the intricate relationship among oxidative stress, inflammation, and tissue repair, affected by the antioxidative abilities of QC, in age-related musculoskeletal tissues to improve the overall health of bones, muscles, and tendons of the skeletal system. Also, reviewing the ongoing clinical trials of QC for musculoskeletal systems is encouraging. Given the positive effect of QC on musculoskeletal health, further scientific investigations and controlled human intervention studies are necessary to explore the therapeutic potential to its optimum strength.

Gene expression profiling and the isocitrate dehydrogenase mutational landscape of temozolomide­resistant glioblastoma.

Glioblastoma multiforme (GBM) is an aggressive brain cancer that occurs more frequently than other brain tumors. The present study aimed to reveal a novel mechanism of temozolomide resistance in GBM using bioinformatics and wet lab analyses, including meta-Z analysis, Kaplan-Meier survival analysis, protein-protein interaction (PPI) network establishment, cluster analysis of co-expressed gene networks, and hierarchical clustering of upregulated and downregulated genes. Next-generation sequencing and quantitative PCR analyses revealed downregulated [tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 1 (TIE1), calcium voltage-gated channel auxiliary subunit α2Δ1 (CACNA2D1), calpain 6 (CAPN6) and a disintegrin and metalloproteinase with thrombospondin motifs 6 (ADAMTS6)] and upregulated [serum amyloid (SA)A1, SAA2, growth differentiation factor 15 (GDF15) and ubiquitin specific peptidase 26 (USP26)] genes. Different statistical models were developed for these genes using the Z-score for P-value conversion, and Kaplan-Meier plots were constructed using several patient cohorts with brain tumors. The highest number of nodes was observed in the PPI network was for ADAMTS6 and TIE1. The PPI network model for all genes contained 35 nodes and 241 edges. Immunohistochemical staining was performed using isocitrate dehydrogenase (IDH)-wild-type or IDH-mutant GBM samples from patients and a significant upregulation of TIE1 (P<0.001) and CAPN6 (P<0.05) protein expression was demonstrated in IDH-mutant GBM in comparison with IDH-wild-type GBM. Structural analysis revealed an IDH-mutant model demonstrating the mutant residues (R132, R140 and R172). The findings of the present study will help the future development of novel biomarkers and therapeutics for brain tumors.

Reverse Zoonotic Transmission of SARS-CoV-2 and Monkeypox Virus: A Comprehensive Review.

Reverse zoonosis reveals the process of transmission of a pathogen through the human-animal interface and the spillback of the zoonotic pathogen. In this article, we methodically demonstrate various aspects of reverse zoonosis, with a comprehensive discussion of SARS-CoV-2 and MPXV reverse zoonosis. First, different components of reverse zoonosis, such as humans, different pathogens, and numerous animals (poultry, livestock, pets, wild animals, and zoo animals), have been demonstrated. Second, it explains the present status of reverse zoonosis with different pathogens during previous occurrences of various outbreaks, epidemics, and pandemics. Here, we present 25 examples from literature. Third, using several examples, we comprehensively illustrate the present status of the reverse zoonosis of SARS-CoV-2 and MPXV. Here, we have provided 17 examples of SARS-CoV-2 reverse zoonosis and two examples of MPXV reverse zoonosis. Fourth, we have described two significant aspects of reverse zoonosis: understanding the fundamental aspects of spillback and awareness. These two aspects are required to prevent reverse zoonosis from the current infection with two significant viruses. Finally, the One Health approach was discussed vividly, where we urge scientists from different areas to work collaboratively to solve the issue of reverse zoonosis.

Expression analysis and mapping of Viral-Host Protein interactions of Poxviridae suggests a lead candidate molecule targeting Mpox.

BACKGROUND: Monkeypox (Mpox) is an important human pathogen without etiological treatment. A viral-host interactome study may advance our understanding of molecular pathogenesis and lead to the discovery of suitable therapeutic targets. METHODS: GEO Expression datasets characterizing mRNA profile changes in different host responses to poxviruses were analyzed for shared pathway identification, and then, the Protein-protein interaction (PPI) maps were built. The viral gene expression datasets of Monkeypox virus (MPXV) and Vaccinia virus (VACV) were used to identify the significant viral genes and further investigated for their binding to the library of targeting molecules. RESULTS: Infection with MPXV interferes with various cellular pathways, including interleukin and MAPK signaling. While most host differentially expressed genes (DEGs) are predominantly downregulated upon infection, marked enrichments in histone modifiers and immune-related genes were observed. PPI analysis revealed a set of novel virus-specific protein interactions for the genes in the above functional clusters. The viral DEGs exhibited variable expression patterns in three studied cell types: primary human monocytes, primary human fibroblast, and HeLa, resulting in 118 commonly deregulated proteins. Poxvirus proteins C6R derived protein K7 and K7R of MPXV and VACV were prioritized as targets for potential therapeutic interventions based on their histone-regulating and immunosuppressive properties. In the computational docking and Molecular Dynamics (MD) experiments, these proteins were shown to bind the candidate small molecule S3I-201, which was further prioritized for lead development. RESULTS: MPXV circumvents cellular antiviral defenses by engaging histone modification and immune evasion strategies. C6R-derived protein K7 binding candidate molecule S3I-201 is a priority promising candidate for treating Mpox.

FLip mutations (L455F + F456L) in newly emerging VOI, JN.1: Its antibody and immune escape.

During the COVID-19 pandemic, one of the biggest challenges was the continuous evolution of SARS-CoV-2 through various mutations. This has resulted in the emergence of several variants and subvariants. The escape mutations are reported as significant mutations in several variants and subvariants responsible for immune, antibody, and nAb escape. It has been reported that FLip mutations (L455F and F456L) in the spike RBD are responsible for immune evasion and antibody escape. Recently, WHO has included a new SARS-CoV-2 VOI, JN.1 lineage, a descendent of BA.2.86. The variant is reported from more than 41 countries, including France, the USA, Canada, the UK, Singapore, Sweden, and India. It contains FLip mutations in the spike protein in RBD (L455F and F456L). The risk assessment of the variant by WHO shows it has increased transmission, immune escape, and antibody escape due to the mutations. The article illustrated that FLip mutations in RBD (L455F and F456L) are responsible for augmented transmission and immune and antibody escape.

SARS-CoV-2 Omicron Spike shows strong binding affinity and favourable interaction landscape with the TLR4/MD2 compared to other variants.

Emergences of SARS-CoV-2 variants have made the pandemic more critical. Toll-like receptor 4 (TLR4) recognizes the molecular patterns of pathogens and activates the production of proinflammatory cytokines to restrain the infection. We have identified a molecular basis of interaction between the Spike and TLR4 of SARS-CoV-2 and its present and past VOCs (variant- of concern) through in silico analysis. The interaction of wild type Spike with TLR4 showed 15 number hydrogen bonds formation. Similarly, the Alpha variants' Spike with the TLR4 has illustrated that 14 hydrogen bonds participated in the interaction. However, the Delta Spike and TLR4 interaction interface showed that 17 hydrogen bonds were formed during the interaction. Furthermore, Omicron S-glycoprotein and TLR4 interaction interface was depicted (interaction score: -170.3), and 16 hydrogen bonds were found to have been formed in the interaction. Omicron S-glycoprotein shows stronger binding affinity with the TLR4 than wild type, Alpha, and Delta variants. Similarly, the Alpha Spike shows higher binding affinity with TLR4 than the wild type and Delta variant. Now, it is an open question of the molecular basis of the interaction of Spike and TLR4 and the activated downstream signaling events of TLR4 for SARS-CoV-2 and its variants.

Regulatory role of miRNAs in the human immune and inflammatory response during the infection of SARS-CoV-2 and other respiratory viruses: A comprehensive review.

miRNAs are single-stranded ncRNAs that act as regulators of different human body processes. Several miRNAs have been noted to control the human immune and inflammatory response during severe acute respiratory infection syndrome (SARS-CoV-2) infection. Similarly, many miRNAs were upregulated and downregulated during different respiratory virus infections. Here, an attempt has been made to capture the regulatory role of miRNAs in the human immune and inflammatory response during the infection of SARS-CoV-2 and other respiratory viruses. Firstly, the role of miRNAs has been depicted in the human immune and inflammatory response during the infection of SARS-CoV-2. In this direction, several significant points have been discussed about SARS-CoV-2 infection, such as the role of miRNAs in human innate immune response; miRNAs and its regulation of granulocytes; the role of miRNAs in macrophage activation and polarisation; miRNAs and neutrophil extracellular trap formation; miRNA-related inflammatory response; and miRNAs association in adaptive immunity. Secondly, the miRNAs landscape has been depicted during human respiratory virus infections such as human coronavirus, respiratory syncytial virus, influenza virus, rhinovirus, and human metapneumovirus. The article will provide more understanding of the miRNA-controlled mechanism of the immune and inflammatory response during COVID-19, which will help more therapeutics discoveries to fight against the future pandemic.

Current landscape of long COVID clinical trials.

Long COVID was reported as a multi-systemic condition after the infection of SARS-CoV-2, and more than 65 million people are suffering from this disease. It has been noted that around 10% of severe SARS-CoV-2 infected individuals are suffering from the enduring effects of long COVID. The symptoms of long COVID have also been noted in several mild or asymptomatic SARS-CoV-2 infected individuals. While limited reports on clinical trials investigating new therapeutics for long COVID exist, there is an abundance of scattered information available regarding these trials. This review explores the extensive literature search, and complete clinical trial database search to map the current status of long COVID clinical trials worldwide. The study listed about 110 long COVID clinical trials. In addition to conducting extensive long COVID clinical trials, we have comprehensively presented an overview of the condition, its symptoms, notable manifestations, associated clinical trials, the unique challenges it poses, and our recommendations for addressing long COVID.

Blueprint of differentially expressed genes reveals the dynamic gene expression landscape and the gender biases in long COVID.

BACKGROUND: Long COVID has appeared as a significant global health issue and is an extra burden to the healthcare system. It affects a considerable number of people throughout the globe. However, substantial research gaps have been noted in understanding the mechanism and genomic landscape during the long COVID infection. A study has aimed to identify the differentially expressed genes (DEGs) in long COVID patients to fill the gap. METHODS: We used the RNA-seq GEO dataset acquired through the GPL20301 Illumina HiSeq 4000 platform. The dataset contains 36 human samples derived from PBMC (Peripheral blood mononuclear cells). Thirty-six human samples contain 13 non-long COVID individuals' samples and 23 long COVID individuals' samples, considered the first direction analysis. Here, we performed two-direction analyses. In the second direction analysis, we divided the dataset gender-wise into four groups: the non-long COVID male group, the long COVID male group, the non-long COVID female group, and the long COVID female group. RESULTS: In the first analysis, we found no gene expression. In the second analysis, we identified 250 DEGs. During the DEG profile analysis of the non-long COVID male group and the long COVID male group, we found three upregulated genes: IGHG2, IGHG4, and MIR8071-2. Similarly, the analysis of the non-long COVID female group and the long COVID female group reveals eight top-ranking genes. It also indicates the gender biases of differentially expressed genes among long COVID individuals. We found several DEGs involved in PPI and co-expression network formation. Similarly, cluster enrichment and gene list enrichment analysis were performed, suggesting several genes are involved in different biological pathways or processes. CONCLUSIONS: This study will help better understand the gene expression landscape in long COVID. However, it might help the discovery and development of therapeutics for long COVID.

A Domain-Specific Next-Generation Large Language Model (LLM) or ChatGPT is Required for Biomedical Engineering and Research.

Large language models or ChatGPT have recently gained extensive media coverage. At the same time, the use of ChatGPT has increased deistically. Biomedical researchers, engineers, and clinicians have shown significant interest and started using it due to its diverse applications, especially in the biomedical field. However, it has been found that ChatGPT sometimes provided incorrect or partly correct information. It is unable to give the most recent information. Therefore, we urgently advocate a domain-specific next-generation, ChatBot for biomedical engineering and research, providing error-free, more accurate, and updated information. The domain-specific ChatBot can perform diversified functions in biomedical engineering, such as performing innovation in biomedical engineering, designing a medical device, etc. The domain-specific artificial intelligence enabled device will revolutionize biomedical engineering and research if a biomedical domain-specific ChatBot is produced.

Quantum Computing in the Next-Generation Computational Biology Landscape: From Protein Folding to Molecular Dynamics.

Modern biological science is trying to solve the fundamental complex problems of molecular biology, which include protein folding, drug discovery, simulation of macromolecular structure, genome assembly, and many more. Currently, quantum computing (QC), a rapidly emerging technology exploiting quantum mechanical phenomena, has developed to address current significant physical, chemical, biological issues, and complex questions. The present review discusses quantum computing technology and its status in solving molecular biology problems, especially in the next-generation computational biology scenario. First, the article explained the basic concept of quantum computing, the functioning of quantum systems where information is stored as qubits, and data storage capacity using quantum gates. Second, the review discussed quantum computing components, such as quantum hardware, quantum processors, and quantum annealing. At the same time, article also discussed quantum algorithms, such as the grover search algorithm and discrete and factorization algorithms. Furthermore, the article discussed the different applications of quantum computing to understand the next-generation biological problems, such as simulation and modeling of biological macromolecules, computational biology problems, data analysis in bioinformatics, protein folding, molecular biology problems, modeling of gene regulatory networks, drug discovery and development, mechano-biology, and RNA folding. Finally, the article represented different probable prospects of quantum computing in molecular biology.

Need an AI-Enabled, Next-Generation, Advanced ChatGPT or Large Language Models (LLMs) for Error-Free and Accurate Medical Information.

Recently, the interest in AI-guided ChatGPT has increased day-to-day, and different applications have been explored, including the medical field. The publication number is also increasing. At the same time, people are trying to get medical information from this Chartbot. However, researchers found that ChatGPT also provides partly correct or false information. Therefore, in this article, we urge the researchers to develop an AI-enabled, next-generation, advanced ChatGPT or large language models (LLMs) so that people can get accurate and error-free medical information.

India's Quantum Move: From Budget Allocation, Action and Future Challenges.

Major countries like the USA, European Union, UK, Japan, Canada, Australia, Singapore, and China have taken significant initiatives to develop quantum computation infrastructure. India has also taken several steps to join the quantum computation family. The Indian government has taken several initiatives to build the nation's infrastructure on quantum computation and participate in the global quantum landscape. The Indian government has created a roadmap in this direction. The significant steps are: firstly, noteworthy budget allocation (1.12 billion USD in 2020 and 734 million USD for the National Quantum Mission in 2023); secondly, 21 quantum hubs are being developed throughout the country; thirdly, 4 quantum research parks have been created and finally, Department of Science and Technology (DST) has initiated QuEST (Quantum Enabled Science and Technology) programme during 2017-18. The article also discusses other effective strategies and moves by the Indian government, like different ambitious national missions on quantum science and technology to create the country's ecosystem. In that direction, the article addresses the opportunities and challenges of quantum science and technology for India. However, the Indian government should encourage quantum computation research more for the country's development. Finally, the information provided here depicts an overall view of India's quantum computation landscape.

ChatGPT and large language models in orthopedics: from education and surgery to research.

ChatGPT has quickly popularized since its release in November 2022. Currently, large language models (LLMs) and ChatGPT have been applied in various domains of medical science, including in cardiology, nephrology, orthopedics, ophthalmology, gastroenterology, and radiology. Researchers are exploring the potential of LLMs and ChatGPT for clinicians and surgeons in every domain. This study discusses how ChatGPT can help orthopedic clinicians and surgeons perform various medical tasks. LLMs and ChatGPT can help the patient community by providing suggestions and diagnostic guidelines. In this study, the use of LLMs and ChatGPT to enhance and expand the field of orthopedics, including orthopedic education, surgery, and research, is explored. Present LLMs have several shortcomings, which are discussed herein. However, next-generation and future domain-specific LLMs are expected to be more potent and transform patients' quality of life.

A next-generation dynamic programming language Julia: Its features and applications in biological science.

BACKGROUND: The advent of Julia as a sophisticated and dynamic programming language in 2012 represented a significant milestone in computational programming, mathematical analysis, and statistical modeling. Having reached its stable release in version 1.9.0 on May 7, 2023, Julia has developed into a powerful and versatile instrument. Despite its potential and widespread adoption across various scientific and technical domains, there exists a noticeable knowledge gap in comprehending its utilization within biological sciences. THE AIM OF REVIEW: This comprehensive review aims to address this particular knowledge gap and offer a thorough examination of Julia's fundamental characteristics and its applications in biology. KEY SCIENTIFIC CONCEPTS OF THE REVIEW: The review focuses on a research gap in the biological science. The review aims to equip researchers with knowledge and tools to utilize Julia's capabilities in biological science effectively and to demonstrate the gap. It paves the way for innovative solutions and discoveries in this rapidly evolving field. It encompasses an analysis of Julia's characteristics, packages, and performance compared to the other programming languages in this field. The initial part of this review discusses the key features of Julia, such as its dynamic and interactive nature, fast processing speed, ease of expression manipulation, user-friendly syntax, code readability, strong support for multiple dispatch, and advanced type system. It also explores Julia's capabilities in data analysis, visualization, machine learning, and algorithms, making it suitable for scientific applications. The next section emphasizes the importance of using Julia in biological research, highlighting its seamless integration with biological studies for data analysis, and computational biology. It also compares Julia with other programming languages commonly used in biological research through benchmarking and performance analysis. Additionally, it provides insights into future directions and potential challenges in Julia's applications in biology.

Overview of Chatbots with special emphasis on artificial intelligence-enabled ChatGPT in medical science.

The release of ChatGPT has initiated new thinking about AI-based Chatbot and its application and has drawn huge public attention worldwide. Researchers and doctors have started thinking about the promise and application of AI-related large language models in medicine during the past few months. Here, the comprehensive review highlighted the overview of Chatbot and ChatGPT and their current role in medicine. Firstly, the general idea of Chatbots, their evolution, architecture, and medical use are discussed. Secondly, ChatGPT is discussed with special emphasis of its application in medicine, architecture and training methods, medical diagnosis and treatment, research ethical issues, and a comparison of ChatGPT with other NLP models are illustrated. The article also discussed the limitations and prospects of ChatGPT. In the future, these large language models and ChatGPT will have immense promise in healthcare. However, more research is needed in this direction.

Current Status of Microneedle Array Technology for Therapeutic Delivery: From Bench to Clinic.

In recent years, microneedle (MN) patches have emerged as an alternative technology for transdermal delivery of various drugs, therapeutics proteins, and vaccines. Therefore, there is an urgent need to understand the status of MN-based therapeutics. The article aims to illustrate the current status of microneedle array technology for therapeutic delivery through a comprehensive review. However, the PubMed search was performed to understand the MN's therapeutics delivery status. At the same time, the search shows the number no of publications on MN is increasing (63). The search was performed with the keywords "Coated microneedle," "Hollow microneedle," "Dissolvable microneedle," and "Hydrogel microneedle," which also shows increasing trend. Similarly, the article highlighted the application of different microneedle arrays for treating different diseases. The article also illustrated the current status of different phases of MN-based therapeutics clinical trials. It discusses the delivery of different therapeutic molecules, such as drug molecule delivery, using microneedle array technology. The approach mainly discusses the delivery of different therapeutic molecules. The leading pharmaceutical companies that produce the microneedle array for therapeutic purposes have also been discussed. Finally, we discussed the limitations and future prospects of this technology.