Retrolaminar Demyelination of Structurally Intact Axons in Nonhuman Primate Experimental Glaucoma.

Purpose: To determine if structurally intact, retrolaminar optic nerve (RON) axons are demyelinated in nonhuman primate (NHP) experimental glaucoma (EG). Methods: Unilateral EG NHPs (n = 3) were perfusion fixed, EG and control eyes were enucleated, and foveal Bruch's membrane opening (FoBMO) 30° sectoral axon counts were estimated. Optic nerve heads were trephined; serial vibratome sections (VSs) were imaged and colocalized to a fundus photograph establishing their FoBMO location. The peripheral neural canal region within n = 5 EG versus control eye VS comparisons was targeted for scanning block-face electron microscopic reconstruction (SBEMR) using micro-computed tomographic reconstructions (µCTRs) of each VS. Posterior laminar beams within each µCTR were segmented, allowing a best-fit posterior laminar surface (PLS) to be colocalized into its respective SBEMR. Within each SBEMR, up to 300 axons were randomly traced until they ended (nonintact) or left the block (intact). For each intact axon, myelin onset was identified and myelin onset distance (MOD) was measured relative to the PLS. For each EG versus control SBEMR comparison, survival analyses compared EG and control MOD. Results: MOD calculations were successful in three EG and five control eye SBEMRs. Within each SBEMR comparison, EG versus control eye axon loss was -32.9%, -8.3%, and -15.2% (respectively), and MOD was increased in the EG versus control SBEMR (P < 0.0001 for each EG versus control SBEMR comparison). When data from all three EG eye SBEMRs were compared to all five control eye SBEMRs, MOD was increased within the EG eyes. Conclusions: Structurally intact, RON axons are demyelinated in NHP early to moderate EG. Studies to determine their functional status are indicated.

Modulation of gut-microbiota through probiotics and dietary interventions to improve host health.

Dietary patterns play an important role in regards to the modulation and control of the gut microbiome composition and function. The interaction between diet and microbiota plays an important role in order to maintain intestinal homeostasis, which ultimately affect the host's health. Diet directly impacts the microbes that inhabit the gastrointestinal tract (GIT), which then contributes to the production of secondary metabolites, such as short-chain fatty acids, neurotransmitters, and antimicrobial peptides. Dietary consumption with genetically modified probiotics can be the best vaccine delivery vector and protect cells from various illnesses. A holistic approach to disease prevention, treatment, and management takes these intrinsically linked diet-microbes, microbe-microbe interactions, and microbe-host interactions into account. Dietary components, such as fiber can modulate beneficial gut microbiota, and they have resulting ameliorative effects against metabolic disorders. Medical interventions, such as antibiotic drugs can conversely have detrimental effects on gut microbiota by disputing the balance between Bacteroides and firmicute, which contribute to continuing disease states. We summarize the known effects of various dietary components, such as fibers, carbohydrates, fatty acids, vitamins, minerals, proteins, phenolic acids, and antibiotics on the composition of the gut microbiota in this article in addition to the beneficial effect of genetically modified probiotics and consequentially their role in regards to shaping human health. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Etiology of lung carcinoma and treatment through medicinal plants, marine plants and green synthesized nanoparticles: A comprehensive review.

Lung cancer, a leading global cause of mortality, poses a significant public health challenge primarily linked to tobacco use. While tobacco contributes to over 90% of cases, factors like dietary choices and radiation exposure also play a role. Despite potential benefits from early detection, cancer patients face hurdles, including drug resistance, chemotherapy side effects, high treatment costs, and limited healthcare access. Traditional medicinal plant knowledge has recently unveiled diverse cancer chemopreventive agents from terrestrial and marine sources. These phytochemicals regulate intricate molecular processes, influencing the immune system, apoptosis, cell cycle, proliferation, carcinogen elimination, and antioxidant levels. In pursuing cutting-edge strategies to combat the diverse forms of cancer, technological advancements have spurred innovative approaches. Researchers have focused on the green synthesis of metallic nanoparticles using plant metabolites. This method offers distinct advantages over conventional physical and chemical synthesis techniques, such as cost-effectiveness, biocompatibility, and energy efficiency. Metallic nanoparticles, through various pathways such as the generation of reactive oxygen species, modulation of enzyme activity, DNA fragmentation, disruption of signaling pathways, perturbation of cell membranes, and interference with mitochondrial function resulting in DNA damage, cell cycle arrest, and apoptosis, exhibit significant potential for preventive applications. Thus, the amalgamation of phytocompounds and metallic nanoparticles holds promise as a novel approach to lung cancer therapy. However, further refinements and advancements are necessary to enhance the environmentally friendly process of metallic nanoparticle synthesis.

A systematic review on multipotent carcinogenic agent, N-nitrosodiethylamine (NDEA), its major risk assessment, and precautions.

The International Agency for Research on Cancer has classified N-nitrosodiethylamine (NDEA) as a possible carcinogen and mutagenic substances, placing it in category 2A of compounds that are probably harmful to humans. It is found in nature and tobacco smoke, along with its precursors, and is also synthesized endogenously in the human body. The oral or parenteral administration of a minimal quantity of NDEA results in severe liver and kidney organ damage. The NDEA required bioactivation by CYP450 enzyme to form DNA adduct in the alkylation mechanism. Thus, this bioactivation directs oxidative stress and injury to cells due to the higher formation of reactive oxygen species and alters antioxidant system in tissues, whereas free radical scavengers guard the membranes from NDEA-directed injury in many enzymes. This might be one of the reasons in the etiology of cancer that is not limited to a certain target organ but can affect various organs and organ systems. Although there are various possible approaches for the treatment of NDEA-induced cancer, their therapeutic outcomes are still very dismal. However, several precautions were considered to be taken during handling or working with NDEA, as it considered being the best way to lower down the occurrence of NDEA-directed cancers. The present review was designed to enlighten the general guidelines for working with NDEA, possible mechanism, to alter the antioxidant line to cause malignancy in different parts of animal body along with its protective agents. Thus, revelation to constant, unpredictable stress situations even in common life may remarkably augment the toxic potential through the rise in the oxidative stress and damage of DNA.

Positive and negative aspects of bacteriophages and their immense role in the food chain.

Bacteriophages infect and replicate inside a bacterial host as well as serve as natural bio-control agents. Phages were once viewed as nuisances that caused fermentation failures with cheese-making and other industrial processes, which lead to economic losses, but phages are now increasingly being observed as being promising antimicrobials that can fight against spoilage and pathogenic bacteria. Pathogen-free meals that fulfil industry requirements without synthetic additives are always in demand in the food sector. This study introduces the readers to the history, sources, and biology of bacteriophages, which include their host ranges, absorption mechanisms, lytic profiles, lysogenic profiles, and the influence of external factors on the growth of phages. Phages and their derivatives have emerged as antimicrobial agents, biodetectors, and biofilm controllers, which have been comprehensively discussed in addition to their potential applications in the food and gastrointestinal tract, and they are a feasible and safe option for preventing, treating, and/or eradicating contaminants in various foods and food processing environments. Furthermore, phages and phage-derived lytic proteins can be considered potential antimicrobials in the traditional farm-to-fork context, which include phage-based mixtures and commercially available phage products. This paper concludes with some potential safety concerns that need to be addressed to enable bacteriophage use efficiently.

Removal of emergent pollutants: A review on recent updates and future perspectives on polysaccharide-based composites vis-à-vis traditional adsorbents.

There is a growing incidence in the presence of emergent pollutants like the pesticides and pharmaceuticals in water bodies. The matter of environmental concern is their synthetic and persistent nature which has resulted in induced toxicity/damaging effect to the vital functioning of the different organs in the aquatic community. Traditional adsorbents have exhibited limitations like low stability and minimum reuse ability. Composites of such adsorbents with polysaccharides have demonstrated distinct features like improved surface area, porosity, adsorptivity; improved reusability and structural integrity; improved mechanical strength, thermal stability when applied for the removal of the emergent pollutants. The biocompatibility and biodegradability of such fabricated composites is established; thereby making the water treatment process cost effective, sustainable and environmentally friendly. The present review has dealt with an in-depth, up-dated literature compilation of traditional as well as polysaccharide based composite adsorbents and addressed their performance evaluation for the removal of pharmaceuticals and pesticides from wastewater. A comparative study has revealed the merits of polysaccharide based composites and discussions have been made with a focus on future research directions in the related area.

Microscopic characterization, TLC fingerprinting and optimization of total lipid content from Euphorbia neriifolia (L.) using response surface methodology.

Euphorbia neriifolia (EN) is a medicinal plant used to treat a variety of ailments in traditional systems. Despite numerous studies on pharmacological activities, no information was available on the microscopic study of this plant. This is the first study that has been attempted to fill this need by performing the light and field emission scanning electron microscopy (FESEM) of leaf, stem, and latex. The powder microscopy of several organs (leaves, stem, and bark) and exudate (latex) of EN was carried out using safranine, fast green, phloroglucinol, and other standard solutions at different magnifications. The chemical fingerprinting of petroleum ether extract was accomplished by using thin layer chromatography. The optimization of total lipid content from the EN leaf under ultrasound-assisted extraction (UAE) and soxhlet extraction (SE) procedure was determined using response surface methodology (RSM). The studied factors that affect the lipid content were: solvent ratio, extraction temperature, and extraction time. Several notable characteristics observed in the leaf of EN are amphistomatic leaves with anticlinical cell walls, anomocytic stomata, spongy mesophyll cells, elongated palisade cells, angular collenchyma, and U-shaped vascular bundle. The plano-convex midrib is covered by polygonal to oval-shaped cuticles and contains anomocytic stomata. The circular petiole has no trichomes and contains laticifers, crystals, and idioblasts. The circular stem was observed with trichomes, hypodermis, collenchyma, parenchymatous cells, central pith, pentagonal stellar region, cambium, and 2-4 times more xylem that of phloem. All of the powdered plant parts and exudate under study contained trichomes, xylem vessels, wood fibers, cork cells, starch grains, calcium oxalate crystals, idioblasts, lignified cork, tannin content, stone cells, and oil globules. The blackish-green colored petroleum ether extract with semi-solid consistency showed the greatest percent (%) yield of 4% in the latex of EN. The thin layer chromatography (TLC) examination of petroleum ether extract of EN leaf produced a maximum 6 spots with Rf values of 0.16, 0.58, 0.62, 0.73, and 0.96 in the mobile phase of petroleum ether-acetone (8:2). In terms of optimization, the dark green colored UAE extract with semi-sticky consistency showed highest % yield of 4.5% whereas the yellowish green colored SE extract of sticky consistency showed the highest % yield of 4.9%. The findings showed that there were not many differences in the total lipid content between UAE (0.16%) and SE (0.11%). However, the best optimum condition for lipid content extraction analysis was obtained as follows: solvent ratio (PE:HE) 50:50, extraction temperature 50°C, extraction time 45 min for UAE, and solvent ratio (PE:HE) 60:40, extraction temperature 45°C, and extraction time of 24 h for SE. Hence, this study signifies the various noteworthy microscopic features along with the presence of different phytocompounds through TLC and best optimized condition for the extraction of lipids from different parts of EN. As no previous study has been reported, the outcomes obtained from the current study prove to be beneficial in the identification of species, quality control, and detection of any adulteration from the laboratory and commercial samples of EN. RESEARCH HIGHLIGHTS: The percent yield was found to be maximum in latex extract (4%). The leaf pet ether extract was separated into 6 bands with different Rf values. The extracted compounds from Euphorbia neriifolia leaves were categorized into non-polar heat tolerant. The highest total lipid yield (0.1119) was obtained at solvent ratios 60:40 of PE:HE (petroleum ether: petroleum hexane).

Targeting Induced Local Lesions in Genomes (TILLING): advances and opportunities for fast tracking crop breeding.

The intensification of food production via conventional crop breeding alone is inadequate to cater for global hunger. The development of precise and expeditious high throughput reverse genetics approaches has hugely benefited modern plant breeding programs. Targeting Induced Local Lesions in Genomes (TILLING) is one such reverse genetics approach which employs chemical/physical mutagenesis to create new genetic sources and identifies superior/novel alleles. Owing to technical limitations and sectional applicability of the original TILLING protocol, it has been timely modified. Successions include: EcoTILLING, Double stranded EcoTILLING (DEcoTILLING), Self-EcoTILLING, Individualized TILLING (iTILLING), Deletion-TILLING (De-TILLING), PolyTILLING, and VeggieTILLING. This has widened its application to a variety of crops and needs. They can characterize mutations in coding as well as non-coding regions and can overcome complexities associated with the large genomes. Combining next generation sequencing tools with the existing TILLING protocols has enabled screening of huge germplasm collections and mutant populations for the target genes. In silico TILLING platforms have transformed TILLING into an exciting breeding approach. The present review outlines these multifarious TILLING modifications for precise mutation detection and their application in advance breeding programmes together with relevant case studies. Appropriate use of these protocols will open up new avenues for crop improvement in the twenty first century.

Oxidative stress, free radicals and antioxidants: potential crosstalk in the pathophysiology of human diseases.

Introduction: Free radicals are reactive oxygen species that constantly circulate through the body and occur as a side effect of many reactions that take place in the human body. Under normal conditions, they are removed from the body by antioxidant processes. If these natural mechanisms are disrupted, radicals accumulate in excess and contribute to the development of many diseases. Methodology: Relevant recent information on oxidative stress, free radicals, reactive oxidative species, and natural and synthetic antioxidants was collected by researching electronic databases such as PubMed / Medline, Web of Science, and Science Direct. Results: According to the analysed studies, this comprehensive review provided a recent update on oxidative stress, free radicals and antioxidants and their impact on the pathophysiology of human diseases. Discussion: To counteract the condition of oxidative stress, synthetic antioxidants must be provided from external sources to supplement the antioxidant defense mechanism internally. Because of their therapeutic potential and natural origin, medicinal plants have been reported as the main source of natural antioxidants phytocompounds. Some non-enzymatic phytocompounds such as flavonoids, polyphenols, and glutathione, along with some vitamins have been reported to possess strong antioxidant activities in vivo and in vitro studies. Thus, the present review describes, in brief, the overview of oxidative stress-directed cellular damage and the unction of dietary antioxidants in the management of different diseases. The therapeutic limitations in correlating the antioxidant activity of foods to human health were also discussed.

Role of Fungi in Imparting General Disease Suppressiveness in Soil from Organic Field.

Soil microbial communities are key players responsible for imparting suppressive potential to the soil against soil-borne phytopathogens. Fungi have an immense potential to inhibit soil-borne phytopathogens, but the fungal counterpart has been less explored in this context. We assessed the composition of fungal communities in soil under long-term organic and conventional farming practice, and control soil. The disease-suppressive potential of organic field was already established. A comparative analysis of the disease suppressiveness contributed by the fungal component of soil from conventional and organic farms was assessed using dual culture assays. The quantification of biocontrol markers and total fungi was done; the characterization of fungal community was carried out using ITS-based amplicon sequencing. Soil from organic field exhibited higher disease-suppressive potential than that from conventional farming, against the pathogens selected for the study. Higher levels of hydrolytic enzymes such as chitinase and cellulase, and siderophore production were observed in soil from the organic field compared to the conventional field. Differences in community composition were observed under conventional and organic farming, with soil from organic field exhibiting specific enrichment of key biocontrol fungal genera. The fungal alpha diversity was lower in soil from the organic field compared to the conventional field. Our results highlight the role of fungi in contributing to general disease-suppressive ability of the soil against phytopathogens. The identification of fungal taxa specifically associated with organic farming can aid in understanding the mechanism of disease suppression under such a practice, and can be exploited to induce general disease suppressiveness in otherwise conducive soil.

Antipyretic Medicinal Plants, Phytocompounds, and Green Nanoparticles: An Updated Review.

Pyrexia itself is not a terminal condition. Basically, it occurs with mild to serious diseases affecting alarge population of the world. Other than a high body temperature, pyrexia is accompanied by several sickness behaviors, changes in physiological and metabolic characteristics of the body system, and alterations in the immune responses. Various allopathic drugs are available to treat pyrexia by targeting the symptom or the pathogen itself. Drug-resistance has made control and treatment of vectors more difficult. However, many marginal people are obligated to utilize locally available medicinal plants for the treatment of various diseases due to limited access to synthetic drugs. Developments in the field of nanotechnology and phytochemical research towards the discovery of new antimicrobial agents have also drawn the interest of researchers towards the synthesis of green nanoparticles from plant extracts due to their several benefits over the other methods. Thus, the present report discusses the use of ethnomedicinal plants, phytocompounds, and the application of green nanoparticles synthesized from plant extracts to treat pyrexia.

Satellite hyperspectral imaging technology as a potential rapid pollution assessment tool for urban landfill sites: case study of Ghazipur and Okhla landfill sites in Delhi, India.

Hyperspectral imaging technology has been used for biochemical analysis of Earth's surface exploiting the spectral reflectance signatures of various materials. The new-generation Italian PRISMA (PRecursore IperSpettrale dellaMissione Applicativa) hyperspectral satellite launched by the Italian space agency (ASI) provides a unique opportunity to map various materials through spectral signature analysis for recourse management and sustainable development. In this study PRISMA hyperspectral satellite imagery-based multiple spectral indices were generated for rapid pollution assessment at Ghazipur and Okhla landfill sites in Delhi, India. It was found that the combined risk score for Okhla landfill site was higher than the Ghazipur landfill site. Various manmade materials identified, exploiting the hyperspectral imagery and spectral signature libraries, indicated presence of highly saline water, plastic (black, ABS, pipe, netting, etc.), asphalt tar, black tar paper, kerogen BK-Cornell, black paint and graphite, chalcocite minerals, etc. in large quantities in both the landfill sites. The methodology provides a rapid pollution assessment tool for municipal landfill sites.

Optic Nerve Head Myelin-Related Protein, GFAP, and Iba1 Alterations in Non-Human Primates With Early to Moderate Experimental Glaucoma.

Purpose: The purpose of this study was to test if optic nerve head (ONH) myelin basic protein (MBP), 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), glial fibrillary acidic protein (GFAP), and ionized calcium binding adaptor molecule 1 (Iba1) proteins are altered in non-human primate (NHP) early/moderate experimental glaucoma (EG). Methods: Following paraformaldehyde perfusion, control and EG eye ONH tissues from four NHPs were paraffin embedded and serially (5 µm) vertically sectioned. Anti-MBP, CNPase, GFAP, Iba1, and nuclear dye-stained sections were imaged using sub-saturating light intensities. Whole-section images were segmented creating anatomically consistent laminar (L) and retrolaminar (RL) regions/sub-regions. EG versus control eye intensity/pixel-cluster density data within L and two RL regions (RL1 [1-250 µm]/RL2 [251-500 µm] from L) were compared using random effects models within the statistical program "R." Results: EG eye retinal nerve fiber loss ranged from 0% to 20%. EG eyes' MBP and CNPase intensity were decreased within the RL1 (MBP = 31.4%, P < 0.001; CNPase =62.3%, P < 0.001) and RL2 (MBP = 19.6%, P < 0.001; CNPase = 56.1%, P = 0.0004) regions. EG eye GFAP intensity was decreased in the L (41.6%, P < 0.001) and RL regions (26.7% for RL1, and 28.4% for RL2, both P < 0.001). Iba1+ and NucBlue pixel-cluster density were increased in the laminar (28.2%, P = 0.03 and 16.6%, P = 0.008) and both RL regions (RL1 = 37.3%, P = 0.01 and 23.7%, P = 0.0002; RL2 = 53.7%, P = 0.002 and 33.2%, P < 0.001). Conclusions: Retrolaminar myelin disruption occurs early in NHP EG and may be accompanied by laminar and retrolaminar decreases in astrocyte process labeling and increases in microglial/ macrophage density. The mechanistic and therapeutic implications of these findings warrant further study.

Assessing the environmental impact of air pollution on crops by monitoring air pollution tolerance index (APTI) and anticipated performance index (API).

Air pollutants adversely affect the physiological, biochemical parameters, and productivity of the crops, but scarce and meager reports are available to know the certain impact of air pollution on crops. The aim of the present study was to assess environmental impact of air pollutants on biochemical parameters of the crops by monitoring two important indicators, i.e., Air Pollution Tolerance Index (APTI) and Anticipated Performance Index (API). These two indicators provide the sensitivity and the tolerance level of the crops towards the air pollutants. Seven different crops were selected in four different locations in the vicinity of a thermal power plant. The results depicted the maximum aerial particulate matter deposition on crop canopy (ADCC) in barley (Hordeum vulgare 2.15 mg/cm2) and wheat (Triticum aestivum 2.21 mg/cm2). The maximum APTI value was found in berseem (Trifolium alexandrinum, 9.45 and 11.44) during the first and second year of study, respectively. Results indicated that all crops were sensitive to air pollution in the selected area, but berseem (Trifolium alexandrinum) was less sensitive in comparison to other crops. API value showed that wheat (Triticum aestivum) and rice (Oryza sativa) were best-suited crops in the selected study area as compared to other crops. It has been found in the study that the API and APTI are two important indicators for the selection of crops in the severe air polluting area.

Clinical Characteristics and Outcomes Among Adults Hospitalized with Laboratory-Confirmed SARS-CoV-2 Infection During Periods of B.1.617.2 (Delta) and B.1.1.529 (Omicron) Variant Predominance - One Hospital, California, July 15-September 23, 2021, and December 21, 2021-January 27, 2022.

In mid-December 2021, the B.1.1.529 (Omicron) variant of SARS-CoV-2, the virus that causes COVID-19, surpassed the B.1.617.2 (Delta) variant as the predominant strain in California.§ Initial reports suggest that the Omicron variant is more transmissible and resistant to vaccine neutralization but causes less severe illness compared with previous variants (1-3). To describe characteristics of patients hospitalized with SARS-CoV-2 infection during periods of Delta and Omicron predominance, clinical characteristics and outcomes were retrospectively abstracted from the electronic health records (EHRs) of adults aged ≥18 years with positive reverse transcription-polymerase chain reaction (RT-PCR) SARS-CoV-2 test results admitted to one academic hospital in Los Angeles, California, during July 15-September 23, 2021 (Delta predominant period, 339 patients) and December 21, 2021-January 27, 2022 (Omicron predominant period, 737 patients). Compared with patients during the period of Delta predominance, a higher proportion of adults admitted during Omicron predominance had received the final dose in a primary COVID-19 vaccination series (were fully vaccinated) (39.6% versus 25.1%), and fewer received COVID-19-directed therapies. Although fewer required intensive care unit (ICU) admission and invasive mechanical ventilation (IMV), and fewer died while hospitalized during Omicron predominance, there were no significant differences in ICU admission or IMV when stratified by vaccination status. Fewer fully vaccinated Omicron-period patients died while hospitalized (3.4%), compared with Delta-period patients (10.6%). Among Omicron-period patients, vaccination was associated with lower likelihood of ICU admission, and among adults aged ≥65 years, lower likelihood of death while hospitalized. Likelihood of ICU admission and death were lowest among adults who had received a booster dose. Among the first 131 Omicron-period hospitalizations, 19.8% of patients were clinically assessed as admitted for non-COVID-19 conditions. Compared with adults considered likely to have been admitted because of COVID-19, these patients were younger (median age = 38 versus 67 years) and more likely to have received at least one dose of a COVID-19 vaccine (84.6% versus 61.0%). Although 20% of SARS-CoV-2-associated hospitalizations during the period of Omicron predominance might be driven by non-COVID-19 conditions, large numbers of hospitalizations place a strain on health systems. Vaccination, including a booster dose for those who are fully vaccinated, remains critical to minimizing risk for severe health outcomes among adults with SARS-CoV-2 infection.

Profiling of phytochemical and antioxidant activity of wild mushrooms: Evidence from the in vitro study and phytoconstituent's binding affinity to the human erythrocyte catalase and human glutathione reductase.

This study was undertaken to evaluate the appearance of phytochemicals and antioxidant activity of seven wild mushrooms of the University of Chittagong campus. Phytochemical screening was performed using standard methods, whereas DPPH radical scavenging assay was used to elucidate the antioxidant effect. Besides, in silico studies were implemented using the targets of human erythrocyte catalase 3-amino-1,2,4-triazole, human glutathione reductase, and selected compounds. Again, the absorption, distribution, metabolism, elimination and toxicity (ADME/T) analysis has been determined by using online tools. Both Ganoderma lucidum (Curtis) Karst. and Ganoderma applanatum (Pers.) Pat. showed a significant (p < .001) increase in the percentage of scavenging activity at 400 µg/ml concentration when compared with ascorbic acid. The methanol extract of G. lucidum, G. applanatum, and Rhodofomes cajanderi (P. Karst.) B. K. Cui, M. L. Han & Y. C. Dai showed strong antioxidant activity with an IC50 value. In addition, molecular docking studies of the previously isolated compounds from three selective mushrooms revealed that the targeted compounds along with positive controls were able to interact strongly (range: -3.498 to -8.655) with the enzymes. The study concludes that the G . lucidum, G. applanatum, and R. cajanderi mushrooms can be a strong source in the management of oxidative stress-induced diseases.

Redox Activity of Flavonoids: Impact on Human Health, Therapeutics, and Chemical Safety.

The cost-effectiveness of presently used therapies is a problem in overall redox-based management, which is posing a significant financial burden on communities across the world. As a result, sophisticated treatment models that provide notions of predictive diagnoses followed by targeted preventive therapies adapted to individual patient profiles are gaining global acclaim as being beneficial to patients, the healthcare sector, and society as a whole. In this context, natural flavonoids were considered due to their multifaceted antioxidant, anti-inflammatory, and anticancer effects as well as their low toxicity and ease of availability. The aim of this review is to focus on the capacity of flavonoids to modulate the responsiveness of various diseases and ailments associated with redox toxicity. The review will also focus on the flavonoids' pathway-based redox activity and the advancement of redox-based therapies as well as flavonoids' antioxidant characteristics and their influence on human health, therapeutics, and chemical safety. Research findings indicated that flavonoids significantly exhibit various redox-based therapeutic responses against several diseases such as inflammatory, neurodegenerative, cardiovascular, and hepatic diseases and various types of cancer by activating the Nrf2/Keap1 transcription system, suppressing the nuclear factor κB (NF-κB)/IκB kinase inflammatory pathway, abrogating the function of the Hsp90/Hsf1 complex, inhibiting the PTEN/PI3K/Akt pathway, and preventing mitochondrial dysfunction. Some flavonoids, especially genistein, apigenin, amentoflavone, baicalein, quercetin, licochalcone A, and biochanin A, play a potential role in redox regulation. Conclusions of this review on the antioxidant aspects of flavonoids highlight the medicinal and folk values of these compounds against oxidative stress and various diseases and ailments. In short, treatment with flavonoids could be a novel therapeutic invention in clinical trials, as we hope.

TREM2 is thyroid hormone regulated making the TREM2 pathway druggable with ligands for thyroid hormone receptor.

Triggering receptor expressed on myeloid cells-2 (TREM2) is a cell surface receptor on macrophages and microglia that senses and responds to disease-associated signals to regulate the phenotype of these innate immune cells. The TREM2 signaling pathway has been implicated in a variety of diseases ranging from neurodegeneration in the central nervous system to metabolic disease in the periphery. Here, we report that TREM2 is a thyroid hormone-regulated gene and its expression in macrophages and microglia is stimulated by thyroid hormone and synthetic thyroid hormone agonists (thyromimetics). Our findings report the endocrine regulation of TREM2 by thyroid hormone, and provide a unique opportunity to drug the TREM2 signaling pathway with orally active small-molecule therapeutic agents.

Tobacco Smoking and Liver Cancer Risk: Potential Avenues for Carcinogenesis.

Smoking a cigarette generates over 4000 chemicals that have a deleterious impact on each part of the human body. It produces three main severe effects on the liver organ: oncogenic, immunological, and indirect or direct toxic effects. It results in the production of cytotoxic substances, which raises fibrosis and necro-inflammation. Additionally, it also directs the production of pro-inflammatory cytokines tumour necrosis factor alfa (TNF-α) and interleukins (IL-1ß, IL-6) that will be responsible for the chronic liver injury. Furthermore, it gives rise to secondary polycythemia and successively raises the turnover and mass of red cells, which might be a common factor responsible for the development of oxidative stress in the liver due to iron overload. It also produces chemicals that are having oncogenic properties and raises the risk of liver cancer especially in sufferers of chronic hepatitis C. Smoking modulates both humoral and cell-mediated responses by restricting the proliferation of lymphocytes and inducing their apoptosis and ultimately decreasing the surveillance of cancer cells. Moreover, it has been determined that heavy smoking impacts the response of hepatitis C patients to interferon (IFN) therapy through different mechanisms, which can be improved by phlebotomy. Efforts are being made in different nations in decreasing the prevalence of smoking to improve premature death and ill effects of their nation's individuals.

Potential inhibitors of SARS-CoV-2 (COVID 19) proteases PLpro and Mpro/ 3CLpro: molecular docking and simulation studies of three pertinent medicinal plant natural components.

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - coronavirus disease 2019 (COVID-19) has raised a severe global public health issue and creates a pandemic situation. The present work aims to study the molecular -docking and dynamic of three pertinent medicinal plants i.e. Eurycoma harmandiana, Sophora flavescens and Andrographis paniculata phyto-compounds against SARS-COV-2 papain-like protease (PLpro) and main protease (Mpro)/3-chymotrypsin-like protease (3CLpro). The interaction of protein targets and ligands was performed through AutoDock-Vina visualized using PyMOL and BIOVIA-Discovery Studio 2020. Molecular docking with canthin-6-one 9-O-beta-glucopyranoside showed highest binding affinity and less binding energy with both PLpro and Mpro/3CLpro proteases and was subjected to molecular dynamic (MD) simulations for a period of 100ns. Stability of the protein-ligand complexes was evaluated by different analyses. The binding free energy calculated using MM-PBSA and the results showed that the molecule must have stable interactions with the protein binding site. ADMET analysis of the compounds suggested that it is having drug-like properties like high gastrointestinal (GI) absorption, no blood-brain barrier permeability and high lipophilicity. The outcome revealed that canthin-6-one 9-O-beta-glucopyranoside can be used as a potential natural drug against COVID-19 protease.