Association of Atrazine-Induced Overexpression of Aldo-Keto-Reductase 1C2 (AKR1C2) with Hypoandrogenism and Infertility: An Experimental Study in Male Wistar Rat.

Atrazine (ATZ, C8H14ClN5) is a widely used synthetic herbicide that contaminates drinking water. It is a known endocrine disruptor that disrupts various molecular pathways involved in hormone signaling, and DNA damage, and can cause reproductive disorders, including decreased fertility, and abnormal development of reproductive organs, as revealed in animal model studies. However, the effect of ATZ on steroidogenesis in the male reproductive system, especially reduction of ketosteroids to hydroxysteroids, remains unclear. This study investigated the toxicity of ATZ on the male reproductive system in the Wistar rat model, with an emphasis on its adverse effect on aldo-ketoreductase family 1 member C2 (AKR1C2). Male Wistar rats were administered ATZ for 56 days (duration of one spermatogenic cycle) through oral route, at 20, 40 and 60 mg/kg body weight (bw) doses. The results indicate that ATZ exposure affects the body weight, impairs sperm production, and decrease FSH, LH, and testosterone levels. Additionally, the down-regulation of key steroidogenic enzymes by ATZ disrupted the synthesis of testosterone, leading to decreased levels of this essential male hormone. On the other hand, the expression of AKR1C2 (mRNA and protein) in the testis was upregulated. The findings suggest that AKR1C2 plays a role in androgen metabolism. Furthermore, its overexpression may lead to alteration in the expression of genes in the connected pathway, causing an increase in the breakdown or inactivation of androgens, which would result in lower androgen levels and, thereby, lead to hypoandrogenism, as the combined effects of down-regulation of steroidogenic genes and up-regulation of AKR1C2. These findings reveal direct implication of disrupted AKR1C2 in male reproductive health and highlight the need for further research on the impact of environmental toxins on human fertility, ultimately providing for better patient care.

Association of Bacterial Communities with Psychedelic Mushroom and Soil as Revealed in 16S rRNA Gene Sequencing.

Microbial communities' resident in the mushroom fruiting body and the soil around it play critical roles in the growth and propagation of the mushroom. Among the microbial communities associated with psychedelic mushrooms and the rhizosphere soil, bacterial communities are considered vital since their presence greatly influences the health of the mushrooms. The present study aimed at finding the microbiota present in the psychedelic mushroom Psilocybe cubensis and the soil the mushroom inhabits. The study was conducted at two different locations in Kodaikanal, Tamil Nadu, India. The composition and structure of microbial communities in the mushroom fruiting body and the soil were deciphered. The genomes of the microbial communities were directly assessed. High-throughput amplicon sequencing revealed distinct microbial diversity in the mushroom and the related soil. The interaction of environmental and anthropogenic factors appeared to have a significant impact on the mushroom and soil microbiome. The most abundant bacterial genera were Ochrobactrum, Stenotrophomonas, Achromobacter, and Brevundimonas. Thus, the study advances the knowledge of the composition of the microbiome and microbial ecology of a psychedelic mushroom, and paves the way for in-depth investigation of the influence of microbiota on the mushroom, with special emphasis on the impact of bacterial communities on mushroom growth. Further studies are required for a deeper understanding of the microbial communities that influence the growth of P. cubensis mushroom.

Salivary luteinizing hormone: An open window to detect oestrous period in buffalo.

Silent oestrus is an unsurmountable problem in the management of buffalo reproduction. In addressing this issue, we have earlier reported variation in the levels of urinary luteinizing hormone (LH) through the different phases of oestrous cycle with an extended window during the mid-oestrous phase. Based on this report, the present study is designed to assess the salivary LH levels in buffalo during the different phases of oestrous cycle. Bovine LH ELISA kit was used to determine the level of salivary LH. We observed a notable variation in salivary LH levels during the different phases of oestrous cycle. The maximum LH level, 39.07 mIU/ml, observed during oestrus, which was significantly (p < .05) higher than other consecutive phases. Altogether, the results showed a significant (p < .05) fold variation during oestrus compared with other phases. Therefore, the study convincingly shows that salivary LH has the potential of application in development of a modality for non-invasive oestrous detection in buffalo.

Synthesis of Biocompatible Cellulose-Coated Nanoceria with pH-Dependent Antioxidant Property.

Recent developments in nanomedicine have validated nanoceria as an antioxidant of therapeutic potential. However, its clinical application is far too limited in view of its poor stability in vivo and the use of hazardous solvents during its synthesis. There is a pertinent need for development of improved strategies for nanoceria to work better, especially by complexation with a matrix to improve upon its antioxidant property without toxicity. In the present study, cellulose has been used as a matrix of nanobiocomposite in which nanoceria are embedded, adopting solution plasma process (SPP). This resulted in cellulose-nanoceria(C/nanoceria) biocomposite by plasma reactions for 15 min using cellulose powder and Ce(NO3)2. Three-dimensional scaffold of the C/nanoceria biocomposite was prepared by lyophilization. The biocomposite was characterized adopting UV-vis spectroscopy, FTIR, FESEM equipped with EDS, and HRTEM analysis. The cubical nanoceria, in the size range 3.2-32 nm, were successfully internalized in the cellulose nanomatrix without agglomeration and exhibited excellent antioxidant property in pH-dependent manner. The nanobiocomposite is not cytotoxic to HeLa cell at a concentration as high as >1 mg.mL-1 as revealed in the cytotoxicity assay. Thus, we describe for the first time synthesis of C/nanoceria, in a manner that is green and sustainable, which has potential in external clinical applications as an effective antioxidative green material for scavenging reactive oxygen species.

Antioxidant and Cholinesterase Inhibitory Activities of Ethyl Acetate Extract of Terminalia chebula: Cell-free In vitro and In silico Studies.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder clinically characterized by memory loss and impaired cognitive function. Cholinergic enzyme deficiency and oxidative stress are the two major factors implicated in the pathogenesis of AD. The symptomatic treatment, as of now, is the use of cholinesterase inhibitors toward cholinergic "downturn." Therefore, there is a search for compounds that will be useful in focused therapies. There has been suggestion that Terminalia chebula fruit would be a potential source. OBJECTIVE: To assess the anticholinesterase and antioxidant activities of T. chebula fruit which is widely practiced in the Ayurvedic medicines for memory enhancement. MATERIALS AND METHODS: Ethyl acetate extract of T. chebula fruit (TCEA) was subjected to phytochemical investigation of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities and cell-free antioxidant activity. TCEA was further subjected to gas chromatography-mass spectrum (GC-MS) analysis. The bioactive compounds were analyzed for molecular docking with AChE and BuChE proteins. RESULTS: TCEA exhibited potent AChE and BuChE inhibitory activities comparable to the standard drug donepezil. In vitro cell-free antioxidant assays demonstrated that TCEA possesses excellent free radical scavenging activity, reducing power, and potent metal-chelating activity. Total polyphenolic content of TCEA was 596.75 ± 0.35 µg gallic acid equivalents/mg of extract, which correlates with the antioxidant activity of TCEA. Molecular docking of compounds expounded in GC-MS analysis for AChE and BuChE enzyme activities revealed that methyl N-(N-benzyloxycarbonyl-beta-l-aspartyl)-beta-d-glucosaminide as the most potent compound with good predicted activities. CONCLUSION: Overall, the results revealed that the bioactive molecule methyl N-(N-benzyloxycarbonyl-beta-l-aspartyl)-beta-d-glucosaminide present in TCEA is a potential depressant for the treatment of AD and related neurodegenerative disorders. SUMMARY: The present study was carried out to assess the neuroprotective effect of Terminalia chebula fruit and its phytoconstituent. Phytochemical analysis of fruit ethyl acetate extract of T. chebula (TCEA) showed the presence of alkaloid, cardiac glycoside, and tannin. TCEA showed potent acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities when compared to standard drug donepezil. Results of in vitro antioxidant assays revealed excellent free radical scavenging activity, reducing power, and potent metal-chelating activity. Gas chromatography-mass spectrum analysis illustrated the presence of 22 active compounds, among which methyl N-(N-benzyloxycarbonyl-beta-l-aspartyl)-beta-d-glucosaminide exhibited potent AChE and BuChE inhibition analyzed through in silico studies. Abbreviations used: AD: Alzheimer's disease; TCEA: Ethyl acetate extract of Terminalia chebula; GC-MS: Gas chromatography-mass spectrum; ROS: Reactive oxygen species; RNS: Reactive nitrogen species; AChE: Acetylcholinesterase; BuChE: Butyrylcholinesterase; NFT: Neurofibrillary tangles; Aµ: µ-amyloid; NSAIDS: Nonsteroidal anti-inflammatory drugs; FDA: Food and Drug Administration; RT: Room temperature; HCl: Hydrochloric acid; ATCI: Acetylthiocholine iodide; BTCI: Butyrylthiocholine iodide; BHT: Butylated hydroxytoluene; DPPH: 2,2-diphenyl-1-picrylhydrazyl; TCA: Trichloroacetic acid; GAE: Gallic acid equivalent; NICT: National Institute of Information and Communications Technology; 3D: Three-dimensional; PDB: Protein data bank; OPLS: Optimized potentials for liquid simulations; XP: Extra precision; SD: Standard deviation; ANOVA: Analysis of variance; EDTA: Ethylenediaminetetraacetic acid.