An organ-on-a-chip (OOAC) is a kind of 3D invitro system, that simulates the dynamics, behavior, mechanics, and physiological reactions of entire organs or portions of organ systems in order to create replica of organ (artificial). Technically a microfluidic cell culture chip (multichannel), initially developed to replace previous animal models, nowadays is being widely used in biomedical science and technology. Developed primarily to enable and assist in the creation of models (i.e., human) with functional responses at the primary level, i.e., organ/tissue level, doing away with the requirement for animal models and greatly accelerating newer drug discovery observations for individualized healthcare. OOAC approaches possess higher potential in contrast to traditional cell culture methods for proper estimation of adverse effects, toxicological profile, functional impairments, pharmacokinetic properties, and drug efficacy. Therefore, the normal working of physiological phenomena, tissue, organ, or barrier can be simulated as well as association between various systems. Moreover, this approach further allows the study of pathophysiological and physiological processes. In this chapter, we shall be discussing organ-on-a-chip (OOAC) viz liver OOAC, lung OOAC, kidney OOAC, heart OOAC, brain OOAC, and skin OOAC, their designs, properties, and their applicability in health-related fields.
Autoimmune disorders have a substantial impact on the overall well-being of individuals and present complex genetic foundations that create difficulties in both diagnosis and treatment. The use of conventional diagnostic techniques and treatment options faces certain limitations, emphasizing the necessity for novel approaches. Omics and multiomics technologies, which include genomics, transcriptomics, proteomics, and metabolomics methods, have emerged as encouraging means to tackle these challenges innovatively. This abstract presents a summary of the main themes discussed in the comprehensive review. It begins by highlighting the impact of autoimmune diseases on human health and emphasizes the need for advanced diagnostic and treatment approaches. The role of genetics, particularly HLA genes and susceptibility loci, is explored, along with linkage studies and genome-wide association studies. The current practices for diagnosis and management are examined, underscoring their limitations and emphasizing the importance of personalized care. Furthermore, this abstract introduces omics technology as well as multiomics integration in precision medicine for autoimmune diseases. The abstract further explores the use of multiomics technologies in early diagnosis, highlighting their effectiveness in identifying disease biomarkers and molecular signatures through successful studies. Challenges and limitations related to data integration, standardization, and ethical considerations are recognized in multiomics research. The future directions of technology advancement, data analysis techniques, and integrating multiomics with clinical data are examined to provide insights into the possibilities of incorporating multiomics into routine clinical practice.
Tuberculosis (TB) is an airborne bacterial disease that mainly affects the lungs and is a major public health threat. Among the various global diseases, TB occupies the 10th position for causes of death. The process that leads from TB infection to disease is quite intricate, involving a series of didactic conditions because it progresses by or without apparent signs and symptoms. TB is a poverty-related disease that primarily affects people who are vulnerable in developing countries. The development of multidrug-resistant bacterial strains is a key concern in most countries' TB control efforts. In the search for novel antiTB medications, multiomics approaches are indispensable tools. Omics methods enable a target-based investigation to find new drug targets in druggable pathways and, secondly, to identify the lead compound's mode of action. As omics methods are unbiased and unsupervised, they are quite useful for revealing drug action, determining new insights about the activity of compounds, and finding new avenues. This chapter attempts to summarize the application of omics approaches in the early identification of new treatments for TB.
Global demand for herbal medicines is growing, yet there are not many large-scale manufacturers of therapeutic plants and their derivatives right now. Novel bioactive chemicals that satisfy human pharmacological potentials are naturally found in medicinal plants. There have been numerous advancements in the understanding of crucial genes, metabolites, and enzymes that are involved in the manufacturing and control of active chemicals have been made because of the multiomics study on medicinal plants that have been sparked by the quick development of modern technology. The phytochemical components and possible health advantages of many medicinal plants have not been well investigated. To assist in the development of enhanced and novel medicinal plant resources as well as the discovery of innovative medicinal compounds, the need for research related to using multiomics technology must be highlighted, to solve fundamental and applied issues in medicinal plants. Here, we provide a summary of recent advances in the study of the molecular complexity of medicinal plants, including using genomics to compare species' variations and evolutionary histories, using transcriptomics, proteomics, and metabolomics to look at the dynamic changes of molecular compounds, and exploring potential sources for the discovery of new natural remedies. Understanding the variety and makeup of bioactive substances chemically as well as the conceptual underpinnings of medicinal plants' environmental adaptability is made possible by these multiomics investigations. This is a result of both their wide diversity and widespread distribution, as well as the effects of their long growing times and many environmental conditions on the bioactive phytochemicals they contain in medicinal plants.
In human history, crippling viral pandemics have occurred many times and recently Coronavirus-19 (COVID-19) disease caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 in Wuhan, China. The present study aims to use various computational approaches to study the mutational status, mutational frequency in viral genome, phylogenetics, genetic epidemiology, spatiotemporal and mutational dynamics of variants of interest (VOIs), and variants of concern (VOCs). The findings of Coronapp revealed several mutations with the highest number of mutations in OQ118414.1 and OQ118474.1 (SARS-CoV-2/USA) variants. In the present study, the most frequently found events per type, nucleotides, and protein were C>T transition, A18163G, and 3′-UTR 28271 respectively. In the present study, taxonomy-built Cov2Tree evaluated the full diversity of viral genome sequences and displayed 6,652,546 sequence trees of SARS-CoV-2. The findings obtained from ViralVar revealed variations in the dynamics of the SARS-CoV-2 variants. The linear distributions of the Omicron variant were similar across the regions making up most of COVID-19 infections followed by the Delta variant. In the present study, the D614G mutation located in the viral spike protein was the topmost mutated residue demonstrating that this variation facilitates viral transmission. Our study also found a higher concentration of mutations in N protein (average odds ratio = 4.477, q-value = 0), NS8 (average odds ratio = 3.53, q-value = 0) and in the spike protein (average odds ratio = 1.61, q-value = 0) respectively. In the present work, the genetic epidemiology of all the reported SARS-CoV-2 variants was determined via Nextstrain. Thus, computational approaches could offer significant insights into the SARS-CoV-2 and henceforth could facilitate early detection, variant surveillance, and therapeutic interventions. These findings could be very helpful in planning and evaluating the effectiveness of regionally-based actions implemented to stop the spread of SARS-CoV-2.
In women of reproductive age, polycystic ovarian syndrome (PCOS) is the most widespread endocrine, mental, reproductive, and metabolic disorder that can cause a variety of clinical symptoms. Menstrual disruption and androgen excess are two symptoms of PCOS that affect women in a variety of ways that have a significant impact on quality of life. The etiology of PCOS syndrome is not well understood since it is regarded as a complex condition and a systemic syndrome in first-degree relatives. A multitude of morbidities, including ovarian and endometrial cancer, obesity, diabetes, insulin resistance, cardiovascular disease, and infertility, could develop over time as a result. In addition to affecting different metabolic processes, numerous linked medical conditions are included with PCOS. Since there are various routes and proteins involved in complex pathophysiology, only one genetic diagnostic test is possible and is unable to provide an unequivocal diagnosis. Clarification of the numerous genetic players, and cellular, and metabolic mechanisms that underlie PCOS may expand our understanding of its pathogenesis. With applications in screening, diagnosis, characterization, and monitoring, biomarkers provide exciting and effective techniques to understand the full scope of PCOS. The pathophysiological relationship between biomarkers and how they relate to PCOS disease must be understood. To show the connection between PCOS disease and cutting-edge technology, this chapter relies on the endeavor to find a wide variety of candidates as potential biomarkers based on omics technologies. The discussed biomarkers may be useful in the future for predicting clinical outcomes, managing disease risk, and directing medicines. As a result, the current review's goal is to summarize more research on innovative developments in the potential application of biomarkers for PCOS conditions.
The central nervous system (CNS) is widely recognized as the only organ system without lymphatic capillaries to promote the removal of interstitial metabolic by-products. Thus, the newly identified glymphatic system which provides a pseudolymphatic activity in the nervous system has been focus of latest research in neurosciences. Also, findings reported that, sleep stimulates the elimination actions of glymphatic system and is linked to normal brain homeostatis. The CNS is cleared of potentially hazardous compounds via the glymphatic system, particularly during sleep. Any age-related alterations in brain functioning and pathophysiology of various neurodegenerative illnesses indicates the disturbance of the brain's glymphatic system. In this context, β-amyloid as well as tau leaves the CNS through the glymphatic system, it's functioning and CSF discharge markedly altered in elderly brains as per many findings. Thus, glymphatic failure may have a potential mechanism which may be therapeutically targetable in several neurodegenerative and age-associated cognitive diseases. Therefore, there is an urge to focus for more research into the connection among glymphatic system and several potential brain related diseases. Here, in our current review paper, we reviewed current research on the glymphatic system's involvement in a number of prevalent neurodegenerative and neuropsychiatric diseases and, we also discussed several therapeutic approaches, diet and life style modifications which might be used to acquire a more thorough performance and purpose of the glymphatic system to decipher novel prospects for clinical applicability for the management of these diseases.
Pharmaceuticals and Personal Care Products (PPCPs) as emerging pollutants have attracted revelatory recognition from research organizations for two decades due to their consistent presence in wastewater. Such ubiquitous contaminants have received alarming apprehension globally for their persistence and potential peril to the health status of organisms and the natural atmosphere. These looming toxins often exist in low concentrations and have complicated structures, making it challenging for wastewater treatment plants to eliminate them; hence, highly efficient and novel eco-friendly technologies are essential for their elimination. This review discusses the source, occurrence, and fate and is followed by a comprehensive analysis of the adverse effects on aquatic biota as well as human well-being.The toxicity analysis with multiple bioassays has also been summarised in this paper. This review covers the multiple remedial technologies, like phytoremediation, and advanced treatment technologies, viz., membrane filtration, adsorption, the photo-Fenton process, and ozonation, that can be adopted in sewage treatment unit processes. We also reviewed the regulatory aspects and risk mitigation policies that are being implemented and are needed now. Thus, the goal of this paper is to provide insight into the aftermath consequences of PPCPs and offer more research that should be focused on the remedial measures of these emerging pollutants and risk-mitigating strategies.
"This book focuses on basic biochemistry with extensive revision to align with the recommended syllabus to cater to the student needs. Additionally, new tables have been included in multiple chapters to enhance the learning experience. To aid students in connecting the subjects fundamentals with a clinical perspective, the book offers insights into the clinical relevance at various points. By studying this book, students will not only improve their grasp of the subject but also establish a solid foundation for integrating biochemical processes into clinical subjects. Although the main target audience for this book is medical students in the pre-clinical stage, it can also benefit individuals in the para-clinical and clinical phases of medical education. The book delves into the essential aspects of biochemistry, offering comprehensive interpretations and visual aids that relate to both health and disease. Consequently, it will undoubtedly captivate the attention of both medical students and teachers. "
With recent advances in the scientific world, drug design, drug work, and metabolism have been revolutionized. A "one-size-fits-all" model for drug distribution is faulty because there is significant heterogeneity in drug-response characteristics. The goal of pharmacogenomics is to increase therapeutic efficacy and minimize negative effects by examining how human genetic information affects drug response. The field of pharmacogenomics under which comprises of pharmacokinetics (PK) and pharmacodynamics (PD) has been revolutionized by well-established fields such as molecular modeling, computational biology, computational tools, computer-aided drug design (CADD), structure-based drug design (SBDD), ligand-based drug design (LBDD), C2Maps, and traditional Chinese medicine systems pharmacology database and analytic platform (TCMSP). Pharmacogenomic resources, which include Pharmacogenomics Knowledge Base (PharmGKB), Pharmacogene Variation (PharmVar), DrugBank, SCAN and PACdb, Genotype-Cytotoxicity Association, Human Cytochrome P450 database, etc., are the backbone in the development design and metabolism of drugs. With these resources and associated fields, the construction of drugs on one's genome specificity is giving leads all the way. The field of pharmacogenomics is leading from the front for the treatment and eradication of serious illness through the construction of personalized drugs by considering genome specificity. The computational approaches are more commonly used to identify disease-causing variants; however, their impact is quite less on variant drug response. Until now, a few algorithms have been developed to predict the effect of pharmacogenomic variations. Bioinformatics and pharmacogenomics are the two emerging fields that have a positive impact and decrease the risk along with overall cost.
Background: Parkinson's disease (PD) is the second most complex neurodegenerative disorder associated with the loss of dopaminergic neurons and has an unknown etiology. Several pathogenic mechanisms including inflammation, oxidative stress, protein dysfunction, apoptosis, mitochondrial dysfunction, abnormal alpha-synuclein, and autophagy are associated with this dis-order. The current existing medications show limited efficacy and adverse health effects. Hence, in such a scenario, phytocom-pounds can provide an alternate way of effective treatment by repurposing these natural molecules using computational based approaches. Methods: In this study, we explored various plant bioactives as possible inhibitors against the Parkin gene using in silico ap-proaches. In the present study, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of the bioactives were determined via predicting small-molecule pharmacokinetic properties (pkCSM). Moreover, the evaluation of molecular docking, dynamics, binding pockets, and protein-protein interactions of the protein was determined via AutoDock Vina, WEBnm@, Computed Atlas of Surface Topography of Proteins (CASTp), and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Results: The findings obtained from molecular docking analysis revealed that Cytochalasin E was the most effective bioactive compound that showed the highest binding affinity of -8.6 kcal/mol when docked against the selected protein. In this study, all the bioactives followed Lipinski's rule of five except Sitoindoside IX. The CASTp tool identified the binding pockets in the protein with the top binding site having an accessible surface (AS) area of 250.39 angstrom 2 and an accessible surface (AS) volume of 203.03 angstrom 3 respectively. STRING tool determined the protein-protein interactions by visualizing protein structure. Conclusion: The findings obtained from this study suggest that Cytochalasin E could be repurposed as a potential inhibitor tar-geting Parkin and these outcomes may prove significant in the process of drug designing. However, further in vitro and in vivo studies are required to validate these results.
In glucose metabolism, the pentose phosphate pathway (PPP) is the major metabolic pathway that plays a crucial role in cancer growth and metastasis. Although it has been pointed out that blockade of the PPP is a promising approach against cancer, in the clinical setting, effective anti-PPP agents are still not available. Dysfunction of the G6PD enzyme in this pathway leads to cancer development as this enzyme possesses oncogenic activity. In the present study, an attempt was made to identify bioactive compounds that can be developed as potential G6PD inhibitors. In the present study, 11 natural compounds and a controlled drug were taken. The physicochemical and toxicity properties of the compounds were determined via ADMET and ProTox-II analysis. In the present study, the findings of docking studies revealed that staurosporine was the most effective compound with the highest binding energy of −9.2 kcal/mol when docked against G6PD. Homology modeling revealed that 97.56% of the residues were occupied in the Ramachandran-favored region. The modeled protein gave a quality Z-score of −10.13 by ProSA tool. iMODS server provided significant insights into the mobility, stability and flexibility of the G6PD protein that described the collective functional protein motion. In the present study, the physical and functional interactions between proteins were determined by STRING. CASTp server determined the topological and geometric properties of the G6PD protein. The findings of the present study revealed that staurosporine could be developed as a potential G6PD inhibitor; however, further in vivo and in vitro studies are needed for further validation of these results.
Background: Sphingosine kinase 1 (SphK1) isa crucial oncogenic lipid kinase responsible for regulating the sphingolipid balance. It plays a key role in apoptosis, cell growth, proliferation, inflammation, migration, signal transduction, metabolism, and cancer progression. Overexpression of SphK1 is observed in cancer, making it a potential target for cancer treatment and other diseases. Our study aimed to identify novel fungal bioactives with possible anti-SphK1 activity using in-silico approaches.Methods: The bioactives' absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties were determined, and molecular docking was conducted with the target protein. Protein-protein interactions, gene enrichment analysis, and comprehensive topological properties of selected protein were also assessed. Furthermore, we evaluated the molecular dynamics simulation (MDs) of the top-docked protein-ligand complex.Results: All the compounds selected for the present study met the criteria for drug-like characteristics and adhered to Lipinski's rule of five (RO5). The Molecular binding results showed that Cytochalasin H was the most significant molecule, displaying a binding affinity of -11.1 kcal/mol. The search tool for the retrieval of interacting genes/proteins (STRING) database provided insights into the protein-protein network interactions. This study's enrichment analysis indicated that the differentially expressed genes were significantly enriched in sphingolipid metabolism, followed closely by the vascular endothelial growth factor (VEGF) signaling pathway. Computed atlas of surface topography of proteins (CASTp) analysis revealed the topographic properties of SphK1 protein, with the top pocket having an area accessible surface (AS) of 7119.22 angstrom 2 and volume accessible surface (AS) of 7762.45 angstrom 3. The MDs analysis showed increased root mean square deviation (RMSD) and radius of gyration (Rg) values, indicating significant conformational alterations during the simulation period.Conclusions: This study suggests that cytochalasin H may be repurposed as a potential SphK1 inhibitor. These findings could be