Unleashed Treasures of Solanaceae: Mechanistic Insights into Phytochemicals with Therapeutic Potential for Combatting Human Diseases.

Plants that possess a diverse range of bioactive compounds are essential for maintaining human health and survival. The diversity of bioactive compounds with distinct therapeutic potential contributes to their role in health systems, in addition to their function as a source of nutrients. Studies on the genetic makeup and composition of bioactive compounds have revealed them to be rich in steroidal alkaloids, saponins, terpenes, flavonoids, and phenolics. The Solanaceae family, having a rich abundance of bioactive compounds with varying degrees of pharmacological activities, holds significant promise in the management of different diseases. Investigation into Solanum species has revealed them to exhibit a wide range of pharmacological properties, including antioxidant, hepatoprotective, cardioprotective, nephroprotective, anti-inflammatory, and anti-ulcerogenic effects. Phytochemical analysis of isolated compounds such as diosgenin, solamargine, solanine, apigenin, and lupeol has shown them to be cytotoxic in different cancer cell lines, including liver cancer (HepG2, Hep3B, SMMC-772), lung cancer (A549, H441, H520), human breast cancer (HBL-100), and prostate cancer (PC3). Since analysis of their phytochemical constituents has shown them to have a notable effect on several signaling pathways, a great deal of attention has been paid to identifying the biological targets and cellular mechanisms involved therein. Considering the promising aspects of bioactive constituents of different Solanum members, the main emphasis was on finding and reporting notable cultivars, their phytochemical contents, and their pharmacological properties. This review offers mechanistic insights into the bioactive ingredients intended to treat different ailments with the least harmful effects for potential applications in the advancement of medical research.

Antioxidant, hepatoprotective & nephroprotective potential of a novel synthetic compound 2', 3'-dihydroxybenzylidene in paracetamol intoxicated rats.

Paracetamol is a commonly used analgesic and antipyretic drug, but at a high dose level, it leads to deleterious side effects. The need to investigate new hepatoprotective drugs is driven by the lack of safety and efficiency of existing medications. A newly synthesized compound 2', 3'-dihydroxybenzylidene (DHB) was evaluated in the present study for its antioxidant, hepatoprotective and nephroprotective potential compared to ascorbic acid in paracetamol intoxicated rats. DHB and ascorbic acid were evaluated against 2, 2-diphenyl-1-picrylhydrazyl (DPPH) for assessment of the antioxidant potential. Male albino rats (n = 20) were categorized into 5 groups with 4 rats each and the test compounds were administered for 14 days consecutively. On day 15th, the rats were anesthetized, and blood was collected through heart puncture for the evaluation of hematological and serological parameters. Subsequently, the rats were dissected for the histopathology of liver and kidney. Alanine Transaminase (ALT), Alkaline Phosphatase (ALP), Serum Bilirubin (SBR), Cholesterol level and Renal Function Tests (RFTs) showed a substantial increase in the paracetamol treated group. Healing in liver and kidney tissues was observed in the DHB treated groups compared to paracetamol intoxicated group. The hemoglobin (HB), mean corpuscular hemoglobin (MCH), RBCs and mean corpuscular hemoglobin concentration (MCHC) were found significantly elevated while the total leukocytes count (TLC), platelets (PLT) and neutrophils significantly decreased in the DHB treated group compared to the paracetamol intoxicated group. It is concluded that DHB possesses antioxidant, hepatoprotective, nephroprotective, and anti-inflammatory potential against paracetamol induced hepatotoxicity and nephrotoxicity in rats.

Study of Amiloride Binding to Human Serum Albumin: Insights from Thermodynamic, Spectroscopic, and Molecular Docking Investigations.

This study was undertaken to investigate the interaction between the sodium channel blocker amiloride (AML) and human serum albumin (HSA). A combination of multi-spectroscopic techniques and computational methods were employed to identify the AML binding site on HSA and the forces responsible for the formation of the HSA-AML complex. Our findings revealed that AML specifically binds to Sudlow's site II, located in subdomain IIIA of HSA, and that the complex formed is stabilized using van der Waals hydrogen-bonding and hydrophobic interactions. FRET analysis showed that the distance between AML and Trp214 was optimal for efficient quenching. UV-Vis spectroscopy and circular dichroism indicated minor changes in the structure of HSA after AML binding, and molecular dynamics simulations (MDS) conducted over 100 ns provided additional evidence of stable HSA-AML-complex formation. This study enhances understanding of the interaction between AML and HSA and the mechanism responsible.

Pollutants in aquatic system: a frontier perspective of emerging threat and strategies to solve the crisis for safe drinking water.

Water is an indispensable natural resource and is the most vital substance for the existence of life on earth. However, due to anthropogenic activities, it is being polluted at an alarming rate which has led to serious concern about water shortage across the world. Moreover, toxic contaminants released into water bodies from various industrial and domestic activities negatively affect aquatic and terrestrial organisms and cause serious diseases such as cancer, renal problems, gastroenteritis, diarrhea, and nausea in humans. Therefore, water treatments that can eliminate toxins are very crucial. Unfortunately, pollution treatment remains a difficulty when four broad considerations are taken into account: effectiveness, reusability, environmental friendliness, and affordability. In this situation, protecting water from contamination or creating affordable remedial techniques has become a serious issue. Although traditional wastewater treatment technologies have existed since antiquity, they are both expensive and inefficient. Nowadays, advanced sustainable technical approaches are being created to replace traditional wastewater treatment processes. The present study reviews the sources, toxicity, and possible remediation techniques of the water contaminants.

Habitat overlap among native and introduced cold-water fishes in the Himalayas.

Fish invasions threaten native freshwater ecosystems worldwide, yet methods to map biodiversity in data-deficient regions are scarce. Rainbow trout (Oncorhynchus mykiss) and brown trout (Salmo trutta fario) have been introduced to the Himalayan ecoregion where they are sympatric with vulnerable native snow trout Schizothorax plagiostomus and Schizothorax richardsonii. We aim to evaluate potential habitat overlap among snow trout and non-native trout in the Indus and Ganges River basins, Himalayan ecoregion. We transferred maximum entropy (MaxEnt) models developed with spatially continuous freshwater-specific environmental variables to map the distribution of potentially suitable habitats for rainbow and brown trout in the Himalayas. We adopted a similar procedure to map suitable habitats for snow trout species. There were substantial habitat overlaps (up to 96%) among snow trout and non-native trout. Yet, the physiography of receiving basins could play a role minimizing the impacts of each non-native trout on native snow trout. We generate high-resolution classified stream suitability maps as decision support tools to help managers in habitat allocation and policy formation to balance recreational fisheries with conservation of snow trout. Our workflow can be transferred to other basins and species for mapping freshwater biodiversity patterns in species-rich yet data-poor regions of the world.

Elaeagnus umbellata: A miraculous shrub with potent health-promoting benefits from Northwest Himalaya.

Medicinal plants encompassing a series of bioactive compounds have gained significant importance for use in the treatment of different diseases. Of them, Elaeagnus umbellata Thunb. (Deciduous shrub found in dappled shade, and sunny hedge) exhibits high medicinal value, with a widespread distribution across the Pir Panjal region of the Himalayas. Fruits serve as an excellent source of vitamins, minerals, and other essential compounds that exhibits hypolipidemic, hepatoprotective, and nephroprotective effects. The phytochemical fingerprint of berries revealed them to have a high content of polyphenols (with major proportion of anthocyanins), followed by monoterpenes and vitamin C. Extract of fruits help in regulating the digestion and absorption of glucose and reduces inflammation and oxidative stress. The phytosterols upholding anticoagulant activity serve the purpose of causing decrease in angina and the blood cholesterol levels. Phytochemicals such as eugenol, palmitic acid, and methyl palmitate exhibit potent antibacterial activity against broad range of disease-causing agents. Additionally, a high percentage of essential oils attribute it with the property of being effective against heart ailments. The present study highlights the importance of E. umbellata in traditional medicinal practices, and summarizes the knowledge of its bioactive constituents and a snapshot vision of remarkable biological activities like antimicrobial, antidiabetic, antioxidant, etc towards understanding its role in the development of efficient drug regimens for use in the treatment of different diseases. It also underlines the need to explore the plant on nutritional aspects to strengthen the existing knowledge pertaining to health promoting potential of E. umbellata.

Plant Growth Promoting Rhizobacteria in Plant Health: A Perspective Study of the Underground Interaction.

Plants are affected by various environmental stresses such as high or low temperatures, drought, and high salt levels, which can disrupt their normal cellular functioning and impact their growth and productivity. These stressors offer a major constraint to the morphological, physiological, and biochemical parameters; thereby attributing serious complications in the growth of crops such as rice, wheat, and corn. Considering the strategic and intricate association of soil microbiota, known as plant growth-promoting rhizobacteria (PGPR), with the plant roots, PGPR helps plants to adapt and survive under changing environmental conditions and become more resilient to stress. They aid in nutrient acquisition and regulation of water content in the soil and also play a role in regulating osmotic balance and ion homeostasis. Boosting key physiological processes, they contribute significantly to the alleviation of stress and promoting the growth and development of plants. This review examines the use of PGPR in increasing plant tolerance to different stresses, focusing on their impact on water uptake, nutrient acquisition, ion homeostasis, and osmotic balance, as well as their effects on crop yield and food security.

Gut Microbiota and Cardiovascular System: An Intricate Balance of Health and the Diseased State.

Gut microbiota encompasses the resident microflora of the gut. Having an intricate relationship with the host, it plays an important role in regulating physiology and in the maintenance of balance between health and disease. Though dietary habits and the environment play a critical role in shaping the gut, an imbalance (referred to as dysbiosis) serves as a driving factor in the occurrence of different diseases, including cardiovascular disease (CVD). With risk factors of hypertension, diabetes, dyslipidemia, etc., CVD accounts for a large number of deaths among men (32%) and women (35%) worldwide. As gut microbiota is reported to have a direct influence on the risk factors associated with CVDs, this opens up new avenues in exploring the possible role of gut microbiota in regulating the gross physiological aspects along the gut-heart axis. The present study elaborates on different aspects of the gut microbiota and possible interaction with the host towards maintaining a balance between health and the occurrence of CVDs. As the gut microbiota makes regulatory checks for these risk factors, it has a possible role in shaping the gut and, as such, in decreasing the chances of the occurrence of CVDs. With special emphasis on the risk factors for CVDs, this paper includes information on the prominent bacterial species (Firmicutes, Bacteriodetes and others) towards an advance in our understanding of the etiology of CVDs and an exploration of the best possible therapeutic modules for implementation in the treatment of different CVDs along the gut-heart axis.

Myostatin and its Regulation: A Comprehensive Review of Myostatin Inhibiting Strategies.

Myostatin (MSTN) is a well-reported negative regulator of muscle growth and a member of the transforming growth factor (TGF) family. MSTN has important functions in skeletal muscle (SM), and its crucial involvement in several disorders has made it an important therapeutic target. Several strategies based on the use of natural compounds to inhibitory peptides are being used to inhibit the activity of MSTN. This review delivers an overview of the current state of knowledge about SM and myogenesis with particular emphasis on the structural characteristics and regulatory functions of MSTN during myogenesis and its involvements in various muscle related disorders. In addition, we review the diverse approaches used to inhibit the activity of MSTN, especially in silico approaches to the screening of natural compounds and the design of novel short peptides derived from proteins that typically interact with MSTN.

Mini-Review on SARS-CoV-2 Infection and Neurological Manifestations: A Perspective.

The coronavirus, also known as SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus-19), with its rapid rate of transmission, has progressed with a great impact on respiratory function and mortality worldwide. The nasal cavity is the promising gateway of SARS-CoV-2 to reach the brain via systemic circulatory distribution. Recent reports have revealed that the loss of involuntary process of breathing control into the brainstem that results in death is a signal of neurological involvement. Early neurological symptoms, like loss of smell, convulsions, and ataxia, are the clues of the involvement of the central nervous system that makes the entry of SARS-CoV-2 further fatal and life-threatening, requiring artificial respiration and emergency admission in hospitals. Studies performed on patients infected with SARS-CoV-2 has revealed three-stage involvement of the Central Nervous System (CNS) in the progression of SARS-CoV-2 infection: Direct involvement of CNS with headache, ataxia, dizziness, altered or impaired consciousness, acute stroke or seizures as major symptoms, peripheral involvement with impaired taste, smell, vision, and altered nociception, and skeletal muscle impairment that includes skeletal muscle disorders leading to acute paralysis in a particular area of the body. In the previous era, most studied and researched viruses were beta coronavirus and mouse hepatitis virus, which were studied for acute and chronic encephalitis and Multiple Sclerosis (MS). Although the early symptoms of SARS-CoV are respiratory pathogenesis, the differential diagnosis should always be considered for neurological perspective to stop the mortalities.

Myxobacteria as a Source of New Bioactive Compounds: A Perspective Study.

Myxobacteria are unicellular, Gram-negative, soil-dwelling, gliding bacteria that belong to class δ-proteobacteria and order Myxococcales. They grow and proliferate by transverse fission under normal conditions, but form fruiting bodies which contain myxospores during unfavorable conditions. In view of the escalating problem of antibiotic resistance among disease-causing pathogens, it becomes mandatory to search for new antibiotics effective against such pathogens from natural sources. Among the different approaches, Myxobacteria, having a rich armor of secondary metabolites, preferably derivatives of polyketide synthases (PKSs) along with non-ribosomal peptide synthases (NRPSs) and their hybrids, are currently being explored as producers of new antibiotics. The Myxobacterial species are functionally characterized to assess their ability to produce antibacterial, antifungal, anticancer, antimalarial, immunosuppressive, cytotoxic and antioxidative bioactive compounds. In our study, we have found their compounds to be effective against a wide range of pathogens associated with the concurrence of different infectious diseases.

Molecular Perspective of Nanoparticle Mediated Therapeutic Targeting in Breast Cancer: An Odyssey of Endoplasmic Reticulum Unfolded Protein Response (UPRER) and Beyond.

Breast cancer (BC) is the second most frequent cause of death among women. Representing a complex and heterogeneous type of cancer, its occurrence is attributed by both genetic (gene mutations, e.g., BRCA1, BRCA2) and non-genetic (race, ethnicity, etc.) risk factors. The effectiveness of available treatment regimens (small molecules, cytotoxic agents, and inhibitors) decreased due to their poor penetration across biological barriers, limited targeting, and rapid body clearance along with their effect on normal resident cells of bone marrow, gastrointestinal tract, and hair follicles. This significantly reduced their clinical outcomes, which led to an unprecedented increase in the number of cases worldwide. Nanomedicine, a nano-formulation of therapeutics, emerged as a versatile delivering module for employment in achieving the effective and target specific delivery of pharmaceutical payloads. Adoption of nanotechnological approaches in delivering therapeutic molecules to target cells ensures not only reduced immune response and toxicity, but increases the stability of therapeutic entities in the systemic circulation that averts their degradation and as such increased extravasations and accumulation via enhanced permeation and the retention (EPR) effect in target tissues. Additionally, nanoparticle (NP)-induced ER stress, which enhances apoptosis and autophagy, has been utilized as a combative strategy in the treatment of cancerous cells. As nanoparticles-based avenues have been capitalized to achieve better efficacy of the new genera of therapeutics with enhanced specificity and safety, the present study is aimed at providing the fundamentals of BC, nanotechnological modules (organic, inorganic, and hybrid) employed in delivering different therapeutic molecules, and mechanistic insights of nano-ER stress induced apoptosis and autophagy with a perspective of exploring this avenue for use in the nano-toxicological studies. Furthermore, the current scenario of USA FDA approved nano-formulations and the future perspective of nanotechnological based interventions to overcome the existing challenges are also discussed.

Chlamydia Trachomatis Infection: Their potential implication in the Etiology of Cervical Cancer.

Pathogenic bacterial strains can alter the normal function of cells and induce different levels of inflammatory responses that are connected to the development of different diseases, such as tuberculosis, diarrhea, cancer etc. Chlamydia trachomatis (C. trachomatis) is an intracellular obligate gram-negative bacterium which has been connected with the cervical cancer etiology. Nevertheless, establishment of causality and the underlying mechanisms of carcinogenesis of cervical cancer associated with C. trachomatis remain unclear. Studies reveal the existence of C. trachomatis in cervical cancer patients. The DNA repair pathways including mismatch repair, nucleotide excision, and base excision are vital in the abatement of accumulated mutations that can direct to the process of carcinogenesis. C. trachomatis recruits DDR proteins away from sites of DNA damage and, in this way, impedes the DDR. Therefore, by disturbing host cell-cycle control, chromatin and DDR repair, C. trachomatis makes a situation favorable for malignant transformation. Inflammation originated due to infection directs over production of reactive oxygen species (ROS) and consequent oxidative DNA damage. This review may aid our current understanding of the etiology of cervical cancer in C. trachomatis-infected patients.

Single-Cell Transcriptomics: Current Methods and Challenges in Data Acquisition and Analysis.

Rapid cost drops and advancements in next-generation sequencing have made profiling of cells at individual level a conventional practice in scientific laboratories worldwide. Single-cell transcriptomics [single-cell RNA sequencing (SC-RNA-seq)] has an immense potential of uncovering the novel basis of human life. The well-known heterogeneity of cells at the individual level can be better studied by single-cell transcriptomics. Proper downstream analysis of this data will provide new insights into the scientific communities. However, due to low starting materials, the SC-RNA-seq data face various computational challenges: normalization, differential gene expression analysis, dimensionality reduction, etc. Additionally, new methods like 10× Chromium can profile millions of cells in parallel, which creates a considerable amount of data. Thus, single-cell data handling is another big challenge. This paper reviews the single-cell sequencing methods, library preparation, and data generation. We highlight some of the main computational challenges that require to be addressed by introducing new bioinformatics algorithms and tools for analysis. We also show single-cell transcriptomics data as a big data problem.

Expedition into Exosome Biology: A Perspective of Progress from Discovery to Therapeutic Development.

Exosomes are membrane-enclosed distinct cellular entities of endocytic origin that shuttle proteins and RNA molecules intercellularly for communication purposes. Their surface is embossed by a huge variety of proteins, some of which are used as diagnostic markers. Exosomes are being explored for potential drug delivery, although their therapeutic utilities are impeded by gaps in knowledge regarding their formation and function under physiological condition and by lack of methods capable of shedding light on intraluminal vesicle release at the target site. Nonetheless, exosomes offer a promising means of developing systems that enable the specific delivery of therapeutics in diseases like cancer. This review summarizes information on donor cell types, cargoes, cargo loading, routes of administration, and the engineering of exosomal surfaces for specific peptides that increase target specificity and as such, therapeutic delivery.

IgLON5 Regulates the Adhesion and Differentiation of Myoblasts.

IgLON5 is a cell adhesion protein belonging to the immunoglobulin superfamily and has important cellular functions. The objective of this study was to determine the role played by IgLON5 during myogenesis. We found IgLON5 expression progressively increased in C2C12 myoblasts during transition from the adhesion to differentiation stage. IgLON5 knockdown (IgLON5kd) cells exhibited reduced cell adhesion, myotube formation, and maturation and reduced expressions of different types of genes, including those coding for extracellular matrix (ECM) components (COL1a1, FMOD, DPT, THBS1), cell membrane proteins (ITM2a, CDH15), and cytoskeletal protein (WASP). Furthermore, decreased IgLON5 expression in FMODkd, DPTkd, COL1a1kd, and ITM2akd cells suggested that IgLON5 and these genes mutually control gene expression during myogenesis. IgLON5 immunoneutralization resulted in significant reduction in the protein level of myogenic markers (MYOD, MYOG, MYL2). IgLON5 expression was higher in the CTX-treated gastrocnemius mice muscles (day 7), which confirmed increase expression of IgLON5 during muscle. Collectively, these results suggest IgLON5 plays an important role in myogenesis, muscle regeneration, and that proteins in ECM and myoblast membranes form an interactive network that establishes an essential microenvironment that ensures muscle stem cell survival.

Mechanistic insights of CRISPR/Cas-mediated genome editing towards enhancing abiotic stress tolerance in plants.

Abiotic stresses such as temperature (high/low), drought, salinity, and others make the environment hostile to plants. Abiotic stressors adversely affect plant growth and development; and thereby makes a direct impact on overall plant productivity. Plants confront stress by developing an internal defense system orchestrated by compatible solutes, reactive oxygen species scavengers and phytohormones. However, routine exposure to unpredictable environmental stressors makes it essential to equip plants with a system that contributes to sustainable agricultural productivity, besides imparting multi-stress tolerance. The sustainable approach against abiotic stress is accomplished through breeding of tolerant cultivars. Though eco-friendly, tedious screening and crossing protocol limits its usage to overcome stress and in attaining the goal of global food security. Advancement on the technological front has enabled adoption of genomic engineering approaches to perform site-specific modification in the plant genome for improving adaptability, increasing the yield and in attributing resilience against different stressors. Of the different genome editing approaches, CRISPR/Cas has revolutionized biological research with wider applicability to crop plants. CRISPR/Cas emerged as a versatile tool in editing genomes for desired traits in highly accurate and precise manner. The present study summarizes advancement of the CRISPR/Cas genome editing tool in its adoption to manipulate plant genomes for novel traits towards developing high-yielding and climate-resilient crop varieties.

Coronavirus Disease -2019 (COVID-19) in 2020: A Perspective Study of a Global Pandemic.

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is responsible for the coronavirus disease- 2019 (COVID-19) pandemic, which was first reported from Wuhan, China, in late 2019. This infection spread to thousands of people globally within a short span of time with a progressive trend to mortality of citizens. Posing a potential public health threat, SARS-CoV-2 progressed from animal-to-human to human-tohuman transmission with symptoms ranging from little or no illness to persons being severely ill and many deaths, confirming two criteria for declaring COVID-19 a pandemic. The disease shows a progressive trend in symptomology, ranging from mild to severe pneumoniae to respiratory and multi-visceral failure that often leads to the death of patients with comorbidity within a short span of time. Intensive research efforts on different aspects of this human pathogen are underway across the globe for elucidating viral transmission routes and the mechanisms employed to overcome host defense responses. Due to the massive infective potential, studies are being carried out to develop effective diagnostics and therapeutic interventions, including re-purposing antivirals and other potential inhibitors. Herein, we describe the taxonomic classification of 'SARS-CoV-2', the structural organization of its genome, its infectivity, transmission, and receptor interaction; and we summarize risk assessment and approaches used for prevention of the infection. Finally, we discuss important aspects of the development of diagnostic tools and therapeutic countermeasures that have the potential to help in controlling the COVID-19 pandemic.