Senolytic therapeutics: An emerging treatment modality for osteoarthritis.

Osteoarthritis (OA), a chronic joint disease affecting millions of people aged over 65 years, is the main musculoskeletal cause of diminished joint mobility in the elderly. It is characterized by lingering pain and increasing deterioration of articular cartilage. Aging and accumulation of senescent cells (SCs) in the joints are frequently associated with OA. Apoptosis resistance; irreversible cell cycle arrest; increased p16INK4a expression, secretion of senescence-associated secretory phenotype factors, senescence-associated ß-galactosidase levels, secretion of extracellular vesicles, and levels of reactive oxygen and reactive nitrogen species; and mitochondrial dysregulation are some common changes in cellular senescence in joint tissues. Development of OA correlates with an increase in the density of SCs in joint tissues. Senescence-associated secretory phenotype has been linked to OA and cartilage breakdown. Senolytics and therapeutic pharmaceuticals are being focused upon for OA management. SCs can be selectively eliminated or killed by senolytics to halt the pathogenesis and progression of OA. Comprehensive understanding of how aging affects joint dysfunction will benefit OA patients. Here, we discuss age-related mechanisms associated with OA pathogenesis and senolytics as an emerging modality in the management of age-related SCs and pathogenesis of OA in preclinical and clinical studies.

Inhibitory effects of Acanthopanax sessiliflorus Harms extract on the etiology of rheumatoid arthritis in a collagen-induced arthritis mouse model.

BACKGROUND: The biological function of Acanthopanax sessiliflorus Harm (ASH) has been investigated on various diseases; however, the effects of ASH on arthritis have not been investigated so far. This study investigates the effects of ASH on rheumatoid arthritis (RA). METHODS: Supercritical carbon dioxide (CO2) was used for ASH extract preparation, and its primary components, pimaric and kaurenoic acids, were identified using gas chromatography-mass spectrometer (GC-MS). Collagenase-induced arthritis (CIA) was used as the RA model, and primary cultures of articular chondrocytes were used to examine the inhibitory effects of ASH extract on arthritis in three synovial joints: ankle, sole, and knee. RESULTS: Pimaric and kaurenoic acids attenuated pro-inflammatory cytokine-mediated increase in the catabolic factors and retrieved pro-inflammatory cytokine-mediated decrease in related anabolic factors in vitro; however, they did not affect pro-inflammatory cytokine (IL-1ß, TNF-α, and IL-6)-mediated cytotoxicity. ASH effectively inhibited cartilage degradation in the knee, ankle, and toe in the CIA model and decreased pannus development in the knee. Immunohistochemistry demonstrated that ASH mostly inhibited the IL-6-mediated matrix metalloproteinase. Gene Ontology and pathway studies bridge major gaps in the literature and provide insights into the pathophysiology and in-depth mechanisms of RA-like joint degeneration. CONCLUSIONS: To the best of our knowledge, this is the first study to conduct extensive research on the efficacy of ASH extract in inhibiting the pathogenesis of RA. However, additional animal models and clinical studies are required to validate this hypothesis.

A trinuclear Zn (II) schiff base dicyanamide complex attenuates bacterial biofilm formation by ROS generation and membrane damage and exhibits anticancer activity.

A trinuclear Zn (II) complex, [(ZnL{N(CN)2})2Zn], termed complex 1 has been synthesized by the reaction of an aqueous solution of sodium dicyanamide to the methanolic solution of Zn (CH3COO)2, 2H2O and corresponding Schiff base (H2L) which is derived from 1:2 condensation of 1, 4 butane diamine with 3-ethoxy salicylaldehyde. Complex 1 is characterized by elemental analysis, IR, UV and Single X-ray diffraction study. Drug resistance is a growing global public health concern that has prompted researchers to look into advanced alternative treatment modalities. In this context, complex 1 has shown promising antibacterial and antibiofilm efficacy against gram-positive Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus strains. Complex 1 attenuated Staphylococcal biofilm formation by reducing several virulence factors including the formation of extracellular polysaccharide matrix, slime, haemolysin, staphyloxanthin, auto-aggregation, cell surface hydrophobicity, and motility. Notably, complex 1 mechanistically potentiated Reactive Oxygen Species (ROS) generation within the bacterial cells, leading to the damage of bacterial cell membrane followed by DNA leakage and thereby impeding the growth of Staphylococcus aureus. Furthermore, complex 1 significantly exhibited anticancer activity by reducing the growth of prostate adenocarcinoma cells. It obstructed the migration of cancer cells by potentiating apoptosis and arresting the cell cycle at the G2/M phase. In summary, complex 1 could act as a potent candidate for the generation of novel antibacterial, antibiofilm as well as anticancer treatment regimens for the management of drug-resistant biofilm-mediated Staphylococcus aureus infection and lethal prostate malignancy.

High-Sucrose Diet Accelerates Arthritis Progression in a Collagen-Induced Rheumatoid Arthritis Model.

SCOPE: High dietary sugar and sweeteners are suspected to cause the development of rheumatoid arthritis (RA) symptoms through the induction of proinflammatory cytokine release. However, the mechanisms by which increased dietary sugar affects RA etiology are not yet fully understood. The study uses a mouse model of collagen-induced RA (CIA) to investigate the relationship between excessive sugar consumption and RA risk. METHODS AND RESULTS: RA-associated pathological features are assessed in the nonimmunized (NI) control group, the CIA-positive control group, and the CIA + high-sucrose diet (CIA+HS, 63% calories from sucrose) group. Compared with the CIA group, the CIA+HS group shows a greater increase in paw thickness and clinical scores, as well as, a higher degree of pannus formation and inflammation in the knee, ankle, and sole tissues. Moreover, the infiltration of immune cells is increased in the CIA+HS group. Although the expression of hepatic lipogenic genes, is not altered, that of toll-like receptor (TLR4) and IL-1ß is considerably elevated in the CIA+HS group. CONCLUSIONS: These findings suggest that excessive sucrose consumption causes hepatic fibrosis and inflammation, contributing to the pathophysiology of RA.

A mononuclear N,N,N,O donor schiff base Cu(II) complex inhibits bacterial biofilm formation and promotes apoptosis and cell cycle arrest in prostate cancer cells.

In this work, we report a distorted square pyramidal mononuclear copper(II) complex [Cu(L)(NCS)] (1) which was obtained by the reaction of the aqueous solution of ammonium thiocyanate to a methanolic solution of copper nitrate trihydrate and corresponding Schiff-base ligands. Schiff bases, HL (C12H19N3O) act as a tetradentate Schiff base, derived from 1:1 condensation of o-hydroxyacetophenone and diethylenetriamine. The synthesized complex has been successfully characterized based on elemental analysis and Infrared (IR) spectroscopy. The structure of complex 1 was confirmed by single-crystal X-ray diffraction study. In our study, we investigated synthesis, structural characterization, antimicrobial, anti-biofilm, and anti-cancer activity, and plausible mechanism of action of a novel mononuclear copper(II) schiff base complex. Increasing microbial resistance to several commercially available or traditional antimicrobial compounds has become a major global health concern at present time. The mononuclear copper(II) complex exhibited potential antibacterial activity against two strains of the gram-negative pathogen Pseudomonas aeruginosa. The copper compound dependent damage of bacterial cell membrane and inhibition of bacterial biofilm formation were also identified. Moreover, complex 1 inhibited prostate cancer cell growth, and migration by inducing apoptosis and arresting the cell cycle at the G2/M phase. Based on the results, we are suggesting our novel mononuclear copper(II) compound as a potential candidate for the development of new antibacterial and anti-cancer drugs.

Metal-Based Nanoparticles and Their Relevant Consequences on Cytotoxicity Cascade and Induced Oxidative Stress.

Emerging nanoscience allows us to take advantage of the improved evolutionary components and apply today's advanced characterization and fabrication techniques to solve environmental and biological problems. Despite the promise that nanotechnology will improve our lives, the potential risks of technology remain largely uncertain. The lack of information on bio-impacts and the absence of consistent standards are the limitations of using metal-based nanoparticles (mNPs) for existing applications. To analyze the role played by the mNPs physicochemical characteristics and tactics to protect live beings, the field of nanotoxicology nowadays is focused on collecting and analyzing data from in vitro and in vivo investigations. The degree of reactive oxygen species (ROS) and oxidative stress caused by material nanoparticles (NPs) depends on many factors, such as size, shape, chemical composition, etc. These characteristics enable NPs to enter cells and interact with biological macromolecules and cell organelles, resulting in oxidative damage, an inflammatory response, the development of mitochondrial dysfunction, damage to genetic material, or cytotoxic effects. This report explored the mechanisms and cellular signaling cascades of mNPs-induced oxidative stress and the relevant health consequences.

Draft genome of clinical isolate Salmonella enterica Typhimurium ms204 from Odisha, India, reveals multi drug resistance and decreased virulent gene expression.

Salmonellosis, a food-borne illnesses caused by enteropathogenic bacterium Salmonella spp., is a continuous concern in both developed and developing countries. This study was carried out to perform an in-depth examination of an MDR Salmonella strain isolated from gastroenteritis patients in Odisha, India, in order to understand the genomic architecture, distribution of pathogenic island regions, and virulence factor diversity. Fecal samples were obtained from individuals with acute gastroenteritis and further subjected to panel of biochemical tests. The IlluminaHiSeq X sequencer system was used to generate whole-genome sequencing. The draft genome was submitted to gene prediction and annotation using RAST annotation system. Pathogenicity Island database and bioinformatics pipeline were used to find Salmonella pathogenicity islands (SPI) from the built scaffold. The gene expression in SPI1 and SPI2 encoded regions was investigated using qRT-PCR. The taxonomic position of Salmonella enterica subsp. enterica serovar Typhimurium was validated by serotype analysis and 16S rRNA based phylogenetic analysis. The de-novo genome assembly showed total length of 5,034,110 bp and produced 37 contigs. There are nine prophage areas, comprising of 12 regions and scaffold 8 contained a single plasmid, IncFIB. The isolate contains six known SPI genes content which was shown to be largely conserved from SPI1 to SPI2. We identified the sit ABCD cluster regulatory cascade and acquired antibiotic resistance genes in S. enterica Typhimurium ms204. Further research may aid in the correct diagnosis and monitoring of MDR Salmonella strains with a variety of physiological activities.

Inhibitory effects of Ganoderma lucidum spore oil on rheumatoid arthritis in a collagen-induced arthritis mouse model.

Holistic healthcare practitioners have now started to focus on specific traditional medicinal mushrooms to treat rheumatoid arthritis (RA). Ganoderma lucidum (GL) is one of the oldest mushrooms that have been used in ancient Chinese medicine to treat inflammatory ailments, including autoimmune diseases such as RA. Spores from this mushroom have specific effects on immunomodulation, aging, and cancer. However, the effect of G. lucidum spores (GLS) on arthritis remains unclear. Therefore, we investigated the effects of GLS oil in a collagen-induced rheumatoid arthritis (CIA) model. Metabolomics analysis revealed that GLS oil contains ten acids, of which oleic acid (52.12%) and linoleic acid (16.77%) predominated. The GLS oil-treated CIA mice had a significantly lower clinical score (p = 0.0384) for RA than the control CIA mice. Moreover, GLS oil reduced CIA-induced cartilage degeneration and synovial membrane inflammation in the knee. The GLS oil group showed significantly reduced knee eosinophilia (p = 0.0056). Immunostaining of neutrophils revealed that neutrophils infiltrated the CIA group; however, infiltrated neutrophils were significantly reduced in the GLS oil group in both the knees (p = 0.0006) and ankles (p = 0.0023). GLS oil treatment substantially suppressed LPS- or TNF-α-induced IL-6 mRNA expression in primary cultured chondrocytes. IL-6 immunohistochemistry results showed that the protein levels of IL-6 were attenuated in the GLS oil group compared to the CIA group. These findings suggest that GLS oil may be useful for the development of RA drugs. Further clinical research is required to identify significant improvements.

The Innovative Informatics Approaches of High-Throughput Technologies in Livestock: Spearheading the Sustainability and Resiliency of Agrigenomics Research.

For more than a decade, next-generation sequencing (NGS) has been emerging as the mainstay of agrigenomics research. High-throughput technologies have made it feasible to facilitate research at the scale and cost required for using this data in livestock research. Scale frameworks of sequencing for agricultural and livestock improvement, management, and conservation are partly attributable to innovative informatics methodologies and advancements in sequencing practices. Genome-wide sequence-based investigations are often conducted worldwide, and several databases have been created to discover the connections between worldwide scientific accomplishments. Such studies are beginning to provide revolutionary insights into a new era of genomic prediction and selection capabilities of various domesticated livestock species. In this concise review, we provide selected examples of the current state of sequencing methods, many of which are already being used in animal genomic studies, and summarize the state of the positive attributes of genome-based research for cattle (Bos taurus), sheep (Ovis aries), pigs (Sus scrofa domesticus), horses (Equus caballus), chickens (Gallus gallus domesticus), and ducks (Anas platyrhyncos). This review also emphasizes the advantageous features of sequencing technologies in monitoring and detecting infectious zoonotic diseases. In the coming years, the continued advancement of sequencing technologies in livestock agrigenomics will significantly influence the sustained momentum toward regulatory approaches that encourage innovation to ensure continued access to a safe, abundant, and affordable food supplies for future generations.

Marine Antimicrobial Peptides-Based Strategies for Tackling Bacterial Biofilm and Biofouling Challenges.

An assemblage nexus of microorganisms enclosed in a composite extracellular polymeric matrix is called as a biofilm. The main factor causing biological fouling, or biofouling, is biofilms. Biofilm-mediated biofouling is a significant detrimental issue in several industries, including the maritime environment, industrial facilities, water treatment facilities, and medical implants. Conventional antibacterial remedies cannot wholly eradicate bacterial species owing to the structural rigidity of biofilm and the eventual growth of antibiotic-resistant microorganisms. Consequently, several approaches to disrupt the biofilm have been investigated to address this particular phenomenon. Antimicrobial peptides (AMPs) have emerged as a promising contender in this category, offering several advantages over traditional solutions, including broad-spectrum action and lack of antibiotic resistance. Because biofouling significantly impacts the marine industry, AMPs derived from marine sources may be suitable natural inhibitors of bacterial proliferation. In this article, we discuss the range of physicochemical and structural diversity and the model of action seen in marine AMPs. This makes them an appealing strategy to mitigate biofilm and biofilm-mediated biofouling. This review also systematically summarizes recent research on marine AMPs from vertebrates and invertebrates and their industrial significance, shedding light on developing even better anti-biofouling materials shortly.

High-throughput sequencing technologies in the detection of livestock pathogens, diagnosis, and zoonotic surveillance.

Increasing globalization, agricultural intensification, urbanization, and climatic changes have resulted in a significant recent increase in emerging infectious zoonotic diseases. Zoonotic diseases are becoming more common, so innovative, effective, and integrative research is required to better understand their transmission, ecological implications, and dynamics at wildlife-human interfaces. High-throughput sequencing (HTS) methodologies have enormous potential for unraveling these contingencies and improving our understanding, but they are only now beginning to be realized in livestock research. This study investigates the current state of use of sequencing technologies in the detection of livestock pathogens such as bovine, dogs (Canis lupus familiaris), sheep (Ovis aries), pigs (Sus scrofa), horses (Equus caballus), chicken (Gallus gallus domesticus), and ducks (Anatidae) as well as how it can improve the monitoring and detection of zoonotic infections. We also described several high-throughput sequencing approaches for improved detection of known, unknown, and emerging infectious agents, resulting in better infectious disease diagnosis, as well as surveillance of zoonotic infectious diseases. In the coming years, the continued advancement of sequencing technologies will improve livestock research and hasten the development of various new genomic and technological studies on farm animals.

Innate Immune Response Analysis in Meniscus Xenotransplantation Using Normal and Triple Knockout Jeju Native Pigs.

Although allogenic meniscus grafting can be immunologically safe, it causes immune rejection due to an imbalanced tissue supply between donor and recipient. Pigs are anatomically and physiologically similar to adult humans and are, therefore, considered to be advantageous xenotransplantation models. However, immune rejection caused by genetic difference damages the donor tissue and can sometimes cause sudden death. Immune rejection is caused by genes; porcine GGTA1, CMAH, and B4GLANT2 are the most common. In this study, we evaluated immune cells infiltrating the pig meniscus transplanted subcutaneously into BALB/c mice bred for three weeks. We compared the biocompatibility of normal Jeju native black pig (JNP) meniscus with that of triple knockout (TKO) JNP meniscus (α-gal epitope, N-glycolylneuraminic acid (Neu5Gc), and Sd (a) epitope knockout using CRISPR-Cas 9). Mast cells, eosinophils, neutrophils, and macrophages were found to have infiltrated the transplant boundary in the sham (without transplantation), normal (normal JNP), and test (TKO JNP) samples after immunohistochemical analysis. When compared to normal and sham groups, TKO was lower. Cytokine levels did not differ significantly between normal and test groups. Because chronic rejection can occur after meniscus transplantation associated with immune cell infiltration, we propose studies with multiple genetic editing to prevent immune rejection.

An Efficacious Transgenic Strategy for Triple Knockout of Xeno-Reactive Antigen Genes GGTA1, CMAH, and B4GALNT2 from Jeju Native Pigs.

Pigs are promising donors of biological materials for xenotransplantation; however, cell surface carbohydrate antigens, including galactose-alpha-1,3-galactose (α-Gal), N-glycolylneuraminic acid (Neu5Gc), and Sd blood group antigens, play a significant role in porcine xenograft rejection. Inactivating swine endogenous genes, including GGTA1, CMAH, and B4GALNT2, decreases the binding ratio of human IgG/IgM in peripheral blood mononuclear cells and erythrocytes and impedes the effectiveness of α-Gal, Neu5Gc, and Sd, thereby successfully preventing hyperacute rejection. Therefore, in this study, an effective transgenic system was developed to target GGTA1, CMAH, and B4GALNT2 using CRISPR-CAS9 and develop triple-knockout pigs. The findings revealed that all three antigens (α-Gal, Neu5Gc, and Sd) were not expressed in the heart, lungs, or liver of the triple-knockout Jeju Native Pigs (JNPs), and poor expression of α-Gal and Neu5G was confirmed in the kidneys. Compared with the kidney, heart, and lung tissues from wild-type JNPs, those from GGTA1/CMAH/ B4GALNT2 knockout-recipient JNPs exhibited reduced human IgM and IgG binding and expression of each immunological rejection component. Hence, reducing the expression of swine xenogeneic antigens identifiable by human immunoglobulins can lessen the immunological rejection against xenotransplantation. The findings support the possibility of employing knockout JNP organs for xenogeneic transplantation to minimize or completely eradicate rejection using multiple gene-editing methods.

Genome analysis and virulence gene expression profile of a multi drug resistant Salmonella enterica serovar Typhimurium ms202.

BACKGROUND: In India, multi-drug resistance in Salmonella enterica serovar Typhimurium poses a significant health threat. Indeed, S. Typhimurium has remained unknown for a large portion of its genome associated with various physiological functions including mechanism of drug resistance and virulence. The whole-genome sequence of a Salmonella strain obtained from feces of a patient with gastroenteritis in Odisha, India, was analyzed for understanding the disease association and underlying virulence mechanisms. RESULTS: The de novo assembly yielded 17 contigs and showed 99.9% similarity to S. enterica sub sp enterica strain LT2 and S. enteric subsp salamae strain DSM 9220. S. Typhimurium ms202 strain constitutes six known Salmonella pathogenicity islands and nine different phages. The comparative interpretation of pathogenic islands displayed the genes contained in SPI-1 and SPI-2 to be highly conserved. We identified sit ABCD cluster regulatory cascade in SPI-1. Multiple antimicrobial resistance genes were identified that directly implies antibiotic-resistant phenotype. Notably, seven unique genes were identified as "acquired antibiotic resistance". These data suggest that virulence in S. enterica Typhimurium ms202 is associated with SPI-1 and SPI-2. Further, we found several virulent genes encoding SPI regions belonging to type III secretion systems (T3SS) of bacteria were significantly upregulated in ms202 compared to control LT2. Moreover, all these genes were significantly downregulated in S. enterica Typhimurium ms202 as compared to control LT2 on adding Mn2+ exogenously. CONCLUSIONS: Our study raises a vital concern about the potential diffusion of a novel multi-drug resistant S. enterica Typhimurium ms202. It justifies this clinical pathogen to demonstrate a higher degree survival due to higher expression of virulent genes and enhanced ability of metallic ion acquisition.

Current efforts on sustainable green growth in the manufacturing sector to complement "make in India" for making "self-reliant India".

In an effort to become a global manufacturing giant, India has launched an ambitious "Make in India" campaign. In this article, we discussed the initiatives launched by Indian Government to create a sustainable economy, as well as opportunities for national and international start-up organisations to reinforce "Make in India" campaign. For the first time, we present an in-depth discussion of Green India policies and manufacturing sector challenges. The aim is to improve the manufacturing output of India and reduce dependence on foreign imports for which campaigns like "Atmanirbhar Bharat" which translates into "Self-Reliant-Green" India has also been started. Department of Science & Technology play a key role in establishing various programs such as infrastructure development, technological support, and green manufacturing programs all of which help to translate "discovery research" into "commercially viable technologies". It focuses specifically on "Startups", MSME's, young scientists, R&D labs and traditional manufacturing units that have little access to financial support but are an integral part of the Indian manufacturing ambit. The programs are interconnected and designed to function in a way that every support could be provided to the indigenous manufacturing, innovation and implementation of climate-resilient green growth strategies.

Development of a Conserved Chimeric Vaccine for Induction of Strong Immune Response against Staphylococcus aureus Using Immunoinformatics Approaches.

Staphylococcus aureus is one of the most notorious Gram-positive bacteria with a very high mortality rate. The WHO has listed S. aureus as one of the ESKAPE pathogens requiring urgent research and development efforts to fight against it. Yet there is a major layback in the advancement of effective vaccines against this multidrug-resistant pathogen. SdrD and SdrE proteins are attractive immunogen candidates as they are conserved among all the strains and contribute specifically to bacterial adherence to the host cells. Furthermore, these proteins are predicted to be highly antigenic and essential for pathogen survival. Therefore, in this study, using the immunoinformatics approach, a novel vaccine candidate was constructed using highly immunogenic conserved T-cell and B-cell epitopes along with specific linkers, adjuvants, and consequently modeled for docking with human Toll-like receptor 2. Additionally, physicochemical properties, secondary structure, disulphide engineering, and population coverage analysis were also analyzed for the vaccine. The constructed vaccine showed good results of worldwide population coverage and a promising immune response. For evaluation of the stability of the vaccine-TLR-2 docked complex, a molecular dynamics simulation was performed. The constructed vaccine was subjected to in silico immune simulations by C-ImmSim and Immune simulation significantly provided high levels of immunoglobulins, T-helper cells, T-cytotoxic cells, and INF-γ. Lastly, upon cloning, the vaccine protein was reverse transcribed into a DNA sequence and cloned into a pET28a (+) vector to ensure translational potency and microbial expression. The overall results of the study showed that the designed novel chimeric vaccine can simultaneously elicit humoral and cell-mediated immune responses and is a reliable construct for subsequent in vivo and in vitro studies against the pathogen.

Inhibitory Effects of IL-6-Mediated Matrix Metalloproteinase-3 and -13 by Achyranthes japonica Nakai Root in Osteoarthritis and Rheumatoid Arthritis Mice Models.

Achyranthes japonica Nakai root (AJNR) is used to treat osteoarthritis (OA) and rheumatoid arthritis (RA) owing to its anti-inflammatory and antioxidant effects. This study investigated the inhibitory effects of AJNR on arthritis. AJNR was extracted using supercritical carbon dioxide (CO2), and its main compounds, pimaric and kaurenoic acid, were identified. ANJR's inhibitory effects against arthritis were evaluated using primary cultures of articular chondrocytes and two in vivo arthritis models: destabilization of the medial meniscus (DMM) as an OA model, and collagenase-induced arthritis (CIA) as an RA model. AJNR did not affect pro-inflammatory cytokine (IL-1ß, TNF-α, IL-6)-mediated cytotoxicity, but attenuated pro-inflammatory cytokine-mediated increases in catabolic factors, and recovered pro-inflammatory cytokine-mediated decreases in related anabolic factors related to in vitro. The effect of AJNR is particularly specific to IL-6-mediated catabolic or anabolic alteration. In a DMM model, AJNR decreased cartilage erosion, subchondral plate thickness, osteophyte size, and osteophyte maturity. In a CIA model, AJNR effectively inhibited cartilage degeneration and synovium inflammation in either the ankle or knee and reduced pannus formation in both the knee and ankle. Immunohistochemistry analysis revealed that AJNR mainly acted via the inhibitory effects of IL-6-mediated matrix metalloproteinase-3 and -13 in both arthritis models. Therefore, AJNR is a potential therapeutic agent for relieving arthritis symptoms.

Next-Generation Bioinformatics Approaches and Resources for Coronavirus Vaccine Discovery and Development-A Perspective Review.

COVID-19 is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To fight this pandemic, which has caused a massive death toll around the globe, researchers are putting efforts into developing an effective vaccine against the pathogen. As genome sequencing projects for several coronavirus strains have been completed, a detailed investigation of the functions of the proteins and their 3D structures has gained increasing attention. These high throughput data are a valuable resource for accelerating the emerging field of immuno-informatics, which is primarily aimed toward the identification of potential antigenic epitopes in viral proteins that can be targeted for the development of a vaccine construct eliciting a high immune response. Bioinformatics platforms and various computational tools and databases are also essential for the identification of promising vaccine targets making the best use of genomic resources, for further experimental validation. The present review focuses on the various stages of the vaccine development process and the vaccines available for COVID-19. Additionally, recent advances in genomic platforms and publicly available bioinformatics resources in coronavirus vaccine discovery together with related immunoinformatics databases and advances in technology are discussed.

Differential expression patterns of myogenic regulatory factors in the postnatal longissimus dorsi muscle of Jeju Native Pig and Berkshire breeds along with their co-expression with Pax7

BACKGROUND: Myogenic regulatory factors (MRFs) such as MyoD, Myf6 and Myf5 play a vital role in the growth and development of muscles. Jeju Native Pig (JNP) is the top ranker in Korea amongst the indigenous livestock reared for meat purpose. Few studies covering transcript abundance of the MRFs and related to their co-expression with Pax7 in JNP have been conducted. Despite having better quality pork, JNP does not have a comparative growth rate with respect to western breeds. Therefore, the present study was designed with the objective to study the relative transcript levels of MRFs in the postnatal myogenesis of longissimus dorsi muscles in JNP and Berkshire breeds. RESULTS: Relative transcript levels were analyzed by qRT-PCR and blot expression analysis through Western blotting. Immunocytochemistry was performed to analyze their expressions at cellular levels. ToppCluster aided in the analysis of gene ontology of biological processes. The quantitative transcript levels of MyoD and Pax7 were significantly (P < 0.05) higher in Berkshire than in JNP. Myotube formation was observed under the co-expression of MyoD and Pax7. ToppCluster helped in the understanding of the linking of biological processes of the MRFs with the different signaling pathways. MyBPH had significantly (P < 0.05) high transcript levels during the chosen age groups in JNP than Berkshire. CONCLUSIONS: The current study can be helpful in understanding the genetic basis for myogenesis in postnatal stage. Moreover, it can act as stepping stone for the identification of marker genes related to body growth and meat quality in JNP.

Interplay between miRNAs and Mycobacterium tuberculosis: diagnostic and therapeutic implications.

Increasing evidence suggests that mycobacteria change the host miRNA profile to their advantage. The active participation of miRNAs in controlling immune responses in TB has raised the possibility of utilizing miRNA-based therapy itself or canonically with a standard drug regimen for shortening the duration of treatment. The development of delivery systems for optimal delivery of oligonucleotides, including small interfering (si)RNA/miRNAs-based therapeutics has shown potential as a new therapeutic intervention. However, studies related to the exploitation of miRNAs as both biomarkers and as therapeutics in TB are scarce; thus, more in vitro and in vivo studies are required to fully determine the role of miRNAs as potential diagnostic biomarkers and to improve the pharmacological profile of this class of therapeutics.