Effects of forages on the microbiota of crossed sheep on cold Plateau.

Diet is an important component to influence microbiota, there are less data available about the microbiome of Suffolk cross with Tibetan (SCT) animals with different fodders. The current study was conducted for comparing the fungi microbiota in SCT sheep fed with different forages. Sequencing of ileum samples from sheep groups of AH (alfalfa and oat grass), BH (mixture of grass and concentrated feeds), CH (concentrated feed I), DH (concentrated feed II) and EH (concentrated feed III) achieved 3,171,271 raw and 2,719,649 filtered sequences. Concentrated feeds changed fungi microbiota in SCT sheep with three phyla and 47 genera significantly different among the groups. Genera include positive genus of Scytalidium and negative fungi of Sarocladium, Kazachstania, Gibberella, Scytalidium, Candida, Wickerhamomyces. The findings of our study will contribute to efficient feeding of SCT sheep at cold plateau areas.

Molecular mechanism of miR-203a targeting Runx2 to regulate thiram induced-chondrocyte development.

Thiram is a kind of organic compound, which is commonly used for sterilization, insecticidal and deodorization in daily life. Its toxicology has been broadly studied. Recently, more and more microRNAs have been shown to participate in the regulation of cartilage development. However, the potential mechanism by which microRNA regulates chondrocyte growth is still unclear. Our experiments have demonstrated that thiram can hamper chondrocytes development and cause a significant increase in miR-203a content in vitro and in vivo trials. miR-203a mimic significantly decrease in mRNA and protein expression of Wnt4, Runx2, COL2A1, ß-catenin and ALP, and significantly enhance the mRNA and protein levels of GSK-3ß. It has been observed that overexpression of miR-203a hindered chondrocytes development. In addition, Runx2 was confirmed to be a direct target of miR-203a by dual luciferase report gene assay. Transfection of si-Runx2 into chondrocytes reveals that significant downregulation of genes is associated with cartilage development. Overall, these results suggest that overexpression of miR-203a inhibits the expression of Runx2. These findings are conducive to elucidate the mechanism of chondrocytes dysplasia induced by thiram and provide new research ideas for the toxicology of thiram.

Inorganic carbon is overlooked in global soil carbon research: A bibliometric analysis.

Soils are a major player in the global carbon (C) cycle and climate change by functioning as a sink or a source of atmospheric carbon dioxide (CO2). The largest terrestrial C reservoir in soils comprises two main pools: organic (SOC) and inorganic C (SIC), each having distinct fates and functions but with a large disparity in global research attention. This study quantified global soil C research trends and the proportional focus on SOC and SIC pools based on a bibliometric analysis and raise the importance of SIC pools fully underrepresented in research, applications, and modeling. Studies on soil C pools started in 1905 and has produced over 47,000 publications (>1.7 million citations). Although the global C stocks down to 2 m depth are nearly the same for SOC and SIC, the research has dominantly examined SOC (>96 % of publications and citations) with a minimal share on SIC (<4%). Approximately 40 % of the soil C research was related to climate change. Despite poor coverage and publications, the climate change-related research impact (citations per document) of SIC studies was higher than that of SOC. Mineral associated organic carbon, machine learning, soil health, and biochar were the recent top trend topics for SOC research (2020-2023), whereas digital soil mapping, soil properties, soil acidification, and calcite were recent top trend topics for SIC. SOC research was contributed by 151 countries compared to 88 for SIC. As assessed by publications, soil C research was mainly concentrated in a few countries, with only 9 countries accounting for 70 % of the research. China and the USA were the major producers (45 %), collaborators (37 %), and funders of soil C research. SIC is a long-lived soil C pool with a turnover rate (leaching and recrystallization) of more than 1000 years in natural ecosystems, but intensive agricultural practices have accelerated SIC losses, making SIC an important player in global C cycle and climate change. The lack of attention and investment towards SIC research could jeopardize the ongoing efforts to mitigate climate change impacts to meet the 1.5-2.0 °C targets under the Paris Climate Agreement of 2015. This bibliographic study calls to expand the research focus on SIC and including SIC fluxes in C budgets and models, without which the representation of the global C cycle is incomplete.

Inflammation targeted nanomedicines: Patents and applications in cancer therapy.

Evident role of inflammation in cancer development and progression prompted the application of anti-inflammatory medications as a therapeutic strategy. The major bottleneck for the anti-inflammatory drugs is targeted delivery to the cancerous cell. Nanotechnology has provided safe and effective way for targeted cancer therapy. However, the complex and heterogeneous traits of cancer, incomplete information on fate and behavior of nanomedicines in human body, and lack of large-scale commercial production have slowed down the pace of nanomedicines development. To shift the paradigm from conventional cancer therapeutics to anti-inflammatory nano-therapeutics, thorough understanding of the strategies, progress, success, challenges and future perspectives are needed. The present review highlights all these aspects in addition to innovations patented on them. In fact, patent plays a vital role in protection of innovations, and further translation of lab-scale outcomes into bedside medications. Thus, the review introspects and recognizes the glitches in successful clinical translation of anti-inflammatory nanomedicines.

Effects of Cryptosporidium parvum infection on intestinal fungal microbiota in yaks (Bos grunniens).

During the last decade, researchers had started to focus on the relationship between intestinal parasitic infection and variation of intestinal microflora. Cryptosporidium is a widely known opportunistic and zoonotic pathogen. Several studies have shown that Cryptosporidium infection has impact to alter the gut microflora. However, there are only few studies referring to the fungal microflora changes in response to Cryptosporidium infection in highland ruminants. Therefore, the present study was performed for exploring the alternations of intestinal fungal microbiota in yaks after exposure to Cryptosporidium infection. In present study, Amplicon sequencing of ITS regions was used to study the variations of fungal microflora in yaks. After filtering the raw data, over 45 000 and 62 000 clean data were obtained in uninfected and infected yaks, respectively. By using alpha diversity analysis, it was found that there is no significant difference in the richness and evenness when positive samples were compared with negative ones, whereas intestinal fungal communities in different taxa in yaks were changed. The results of present study depicted that 2-phyla and 21-genera in the infected animals had significantly (P < 0.05) changed. These genera were Septoria, Coniothyrium, Cleistothelebolus, Bensingtonia, Cystobasidium, Filobasidium, Coprotus, Carex, Blumeria, Coprinellus, Leucosporidium, Phialophora, Isolepis, Ascobolus, Thecaphora, Mortierella, Urocystis, Symmetrospora and Lasiobolus. In addition, we found variations in 28 enzymes suggesting that the function of microbiota was also affected. It is concluded that there are drastic changes in the fungal microflora and microbiota functions after exposure to Cryptosporidium infection in yak. Our results help to focus on the prompt way for the development of new therapies to control Cryptosporidiosis.

Leg disorders in broiler chickens: a review of current knowledge.

Ensuring improved leg health is an important prerequisite for broilers to achieve optimal production performance and welfare status. Broiler leg disease is characterized by leg muscle weakness, leg bone deformation, joint cysts, arthritis, femoral head necrosis, and other symptoms that result in lameness or paralysis. These conditions significantly affect movement, feeding and broiler growth performance. Nowadays, the high incidence of leg abnormalities in broiler chickens has become an important issue that hampers the development of broiler farming. Therefore, it is imperative to prevent leg diseases and improve the health of broiler legs. This review mainly discusses the current prevalence of broiler leg diseases and describes the risk factors, diagnosis, and prevention of leg diseases to provide a scientific basis for addressing broiler leg health problems.

Baicalin inhibits apoptosis and enhances chondrocyte proliferation in thiram-induced tibial dyschondroplasia in chickens by regulating Bcl-2/Caspase-9 and Sox-9/Collagen-II expressions.

Avian tibial dyschondroplasia (TD) is a skeletal disease affecting fast growing chickens, resulting in non-mineralized avascular cartilage. This metabolic disorder is characterized by lameness and reduced growth performance causing economic losses. The aim of this study was to investigate the protective effects of baicalin against TD caused by thiram exposure. A total of two hundred and forty (n = 240) one day-old broiler chickens were uniformly and randomly allocated into three different groups (n = 80) viz. control, TD, and baicalin groups. All chickens received standard feed, however, to induce TD, the TD and baicalin groups received thiram (tetramethylthiuram disulfide) at a rate of 50 mg/kg feed from days 4-7. The thiram induction in TD and baicalin groups resulted in lameness, high mortality, and enlarged growth-plate, poor production performance, reduction in ALP, GSH-Px, SOD, and T-AOC levels, and increased AST and ALT, and MDA levels. Furthermore, histopathological results showed less vascularization, and mRNA and protein expression levels of Sox-9, Col-II, and Bcl-2 showed significant downward trend, while caspase-9 displayed significant up-regulation in TD-affected chickens. After the TD induction, the baicalin group was orally administered with baicalin at a rate of 200 mg/kg from days 8-18. Baicalin administration increased the vascularization, and chondrocytes with intact nuclei, alleviated lameness, decreased GP size, increased productive capacity, and restored the liver antioxidant enzymes and serum biochemical levels. Furthermore, baicalin significantly up-regulated the gene and protein expressions of Sox-9, Col-II, and Bcl-2, and significantly down-regulated the expression of caspase-9 (p < 0.05). Therefore, the obtained results suggest that baicalin could be a possible choice in thiram toxicity alleviation by regulating apoptosis and chondrocyte proliferation in thiram-induced tibial dyschondroplasia.

The effect of Abrus cantoniensis Hance on liver damage in mice.

The liver is a well-known organ contributing to digestion, hemostasis and detoxification, while liver injury is a world-widely distributed health problem with limited treatment choices. We detected the protective effect of Abrus cantoniensis Hance (ACH) on Carbon tetrachloride-induced (CCl4) liver injury in mice. Fifty ICR (Institute of Cancer Research) animals were grouped into five groups of control (a), CCl4 (d), ACH (25 mg/kg) treated group (c), ACH (50 mg/kg) treated group (b), and ACH (100 mg/kg) treated group (e). Mice in groups d, c, b, and e were given CCl4 every four days, and treated animals received daily ACH supplementation. The results showed that the daily body weights in CCl4-induced animals were slightly lower; however, the weight of ACH-treated mice increased, particularly in the higher dose group. Treatment with CCl4 led to increased liver weight and liver indices in mice, whereas supplementation with ACH reduced both liver weights and liver indices in animals. Histo-pathological analysis indicated that CCl4 led to inflammatory cell infiltration and hepatocellular degeneration, with collagenous fibers proliferation in ICR animals. In contrast, supplementation with ACH prominently decreased inflammatory cells and degeneration of hepatocytes and inhibited collagen fiber hyperplasia. Furthermore, the levels or concentrations of AST (p < 0.0001), ALT (p < 0.0001), MDA (p < 0.0001), IL-1ß (p < 0.01), TNF-α (p < 0.01) and IL-6 (p < 0.01) were significantly higher in CCl4 induced ICR animals in group d. However, mice treated with ACH showed lower levels or concentrations of those indices in dose dependent manner. The levels of GSH-px (p < 0.0001), CAT (p < 0.0001) and SOD (p < 0.0001) were significantly reduced in CCl4 group; however, all these three enzymes exhibited significant (p < 0.05) increase in animals supplemented with ACH in dose dependent manner. The microbiome sequencing generated 1,168,327 filtered reads in the mice samples. A notable difference was observed in the composition of 6 phyla and 37 genera among the five ICR animal groups. Supplementation with ACH increased the abundance of beneficial genera of Coprococcus, Blautia and Clostridium, while concurrently decreased the presence of pathogenic genera of Mycoplasma and Helicobacter. In conclusion, we revealed that Abrus cantoniensis Hance has the potential to relieve liver damage induced by CCl4, through the reduction of inflammation, enhancement of antioxidant capacity, and regulation of intestinal microbiota.

Swertia bimaculata moderated liver damage in mice by regulating intestine microbiota.

Swertia bimaculata (SB) is a medicinal herb in China having an array of therapeutic and biological properties. This study aimed to explore the attenuating effect of SB on carbon tetrachloride (CCl4) induced hepato-toxicity by regulation of gut microbiome in ICR mice. For this purpose, CCl4 was injected intraperitoneally in different mice groups (B, C, D and E) every 4th day for a period of 47 days. Additionally, C, D, and E groups received a daily dose (50 mg/kg, 100 mg/kg, and 200 mg/kg respectively) of Ether extract of SB via gavage for the whole study period. The results of serum biochemistry analysis, ELISA, H&E staining, and sequencing of the gut microbiome, indicated that SB significantly alleviates the CCl4-induced liver damage and hepatocyte degeneration. The serum levels of alanine transaminase, aspartate aminotransferase, malondialdehyde, interleukin 1 beta and tumor necrosis factor-alpha were significantly lower in SB treated groups compared to control while levels of glutathione peroxidase were raised. Also, the sequencing data indicate that supplementation with SB could restore the microbiome and its function in CCl4-induced variations in intestinal microbiome of mice by significantly downregulating the abundances of pathogenic intestinal bacteria species including Bacteroides, Enterococcus, Eubacterium, Bifidobacterium while upregulating the levels of beneficial bacteria like Christensenella in the gut. In conclusion, we revealed that SB depicts a beneficial effect against hepatotoxicity induced by CCl4 in mice through the remission of hepatic inflammation and injury, through regulation of oxidative stress, and by restoring gut microbiota dysbiosis.

miR-181b-1-3p affects the proliferation and differentiation of chondrocytes in TD broilers through the WIF1/Wnt/ß-catenin pathway.

Thiram is a plant fungicide, its excessive use has exceeded the required environmental standards. It causes tibial dyschondroplasia (TD) in broilers which is a common metabolic disease that affects the growth plate of tibia bone. It has been studied that many microRNAs (miRNAs) are involved in the differentiation of chondrocytes however, their specific roles and mechanisms have not been fully investigated. The selected features of tibial chondrocytes of broilers were studied in this experiment which included the expression of miR-181b-1-3p and the genes related to WIF1/Wnt/ß-catenin pathway in chondrocytes through qRT-PCR, western blot and immunofluorescence. The correlation between miR-181b-1-3p and WIF1 was determined by dual luciferase reporter gene assay whereas, the role of miR-181b-1-3p and WIF1/Wnt/ß-catenin in chondrocyte differentiation was determined by mimics and inhibitor transfection experiments. Results revealed that thiram exposure resulted in decreased expression of miR-181b-1-3p and increased expression of WIF1 in chondrocytes. A negative correlation was also observed between miR-181b-1-3p and WIF1. After overexpression of miR-181b-1-3p, the expression of ACAN, ß-catenin and Col2a1 increased but the expression of GSK-3ß decreased. It was observed that inhibition of WIF1 increased the expression of ALP, ß-catenin, Col2a1 and ACAN but decreased the expression of GSK-3ß. It is concluded that miR-181b-1-3p can reverse the inhibitory effect of thiram on cartilage proliferation and differentiation by inhibiting WIF1 expression and activating Wnt/ß-catenin signaling pathway. This study provides a new molecular target for the early diagnosis and possible treatment of TD in broilers.

A detailed biochemical characterization, toxicological assessment and molecular docking studies of Launaea fragilis: An important medicinal xero-halophyte.

Launaea fragilis (Asso) Pau (Family: Asteraceae) is a wild medicinal plant that has been used in the folklore as a potential treatment for numerous ailments such as skin diseases, diarrhea, infected wounds, inflammation, child fever and hepatic pain. This study explored the chemical constitution, in-vivo toxicity, antimicrobial, antioxidant, and enzyme inhibition potential of ethanolic extract of L. fragilis (EELF). Additionally, in-silico docking studies of predominant compounds were performed against in-vitro tested enzymes. Similarly, in-silico ADMET properties of the compounds were performed to determine their pharmacokinetics, physicochemical properties, and toxicity profiles. The EELF was found rich in TFC (73.45 ± 0.25 mg QE/g) and TPC (109.02 ± 0.23 mg GAE/g). GC-MS profiling of EELF indicated the presence of a total of 47 compounds mainly fatty acids and essential oil. EELF showed no toxicity or growth retardation in chicks up to 300 mg/kg with no effect on the biochemistry and hematology of the chicks. EELF gave promising antioxidant activity through the CUPRAC method with an IC50 value of 13.14 ± 0.18 µg/ml. The highest inhibition activity against tyrosinase followed by acetylcholinesterase and α-Glucosidase was detected. Similarly, the antimicrobial study revealed the extract with good antibacterial and antiviral activity. A good docking score was observed in the in silico computational study of the predominant compounds. The findings revealed L. fragilis as a biocompatible, potent therapeutic alternative and suggest isolation and further in vivo pharmacological studies.

Analysis of Isocitrate dehydrogenase (IDH) mutation in Gliomas: A call for neurosurgeons and pathologists in Pakistan.

Tumours of the central nervous system, though not very common, pose a serious health burden owing to their high mortality rate. Glial tumours are the commonest type of brain tumours in Pakistani population. Diagnosis of gliomas has been greatly revolutionised over the past few years with integration of immunohistochemistry and molecular subtyping in the World Health Organisation's updated 2016 classification of glial tumours. One of the major changes was incorporation of isocitrate dehydrogenase mutation detection that is considerably a significant prognostic and predictive marker. The published data on isocitrate dehydrogenase mutation in the local population is hard to find. The current narrative review was planned to briefly describe the international trends regarding frequency of isocitrate dehydrogenase mutation in gliomas, its predictive and prognostic significance and its impact on accurate diagnosis leading to a targeted therapeutic approach for patients.

Methicillin resistant Staphylococcus aureus: A brief review of virulence and resistance.

Staphylococcus aureus is a common gram-positive human pathogen involved in both community-acquired and nosocomial infections ranging from localised superficial lesions to food poisoning and fatal systemic infections owing to its impressive array of virulence factors responsible for attaching, colonising, invading, and avoiding host immune system. The discovery of antibiotics effectively checked the once deadly infections. However, resistance started soon after their discovery and the first methicillin-resistant strain of staphylococcus aureus was reported in the early 1960s. The most important attribute of methicillin-resistant staphylococcus aureus is its acquisition of mecA gene coding for penicillin-binding protein-2a that blocks inhibitory action on peptidoglycan cross-linking. Methicillin-resistant staphylococcus aureus presents a serious global healthcare concern being responsible for prolonged hospital stays and increased mortality. The precise information of virulence factors and resistant traits of methicillin-resistant staphylococcus aureus and their interplay in a community is key to minimize the intermixing of resistant and susceptible pathogens in the community.

Comparative analysis of fecal microbiota composition diversity in Tibetan piglets suffering from diarrheagenic Escherichia coli (DEC).

This study was ascertained to investigate the adverse effects of pathogenic E. coli on gut microbiota of Tibetan piglets with history of yellow and white dysentery. For this purpose, a total of 18 fecal samples were collected from infected and healthy Tibetan piglets for 16S rRNA gene amplification and sequencing of V3-V4 region. Results showed that Firmicutes, Bacteroidia Fusobacteriota, Proteobacteria and Actinobacteriota were the predominant bacteria in Tibetan piglets at the level of phylum classification. Results on classification at family level showed that Lactobacillus, Bacteroidota, Fusobacteriota and Enterobacteriaceae were the dominant bacteria. Results on classification of bacteria at phylum level compared with normal piglets indicated that Bacteroidota, Actinobacteriota, Euryarchaota and Spirochaetota in fecal microbial community in Tibetan piglets showing yellow dysenteric and diarrhea group were significantly decreased (P ≤ 0.05). Compared with the feces of healthy Tibetan piglets, the abundance of Escherichia-Shigella, Lactobacillus and Enterococcus increased significantly in feces of Tibetan piglets having yellow dysentery and white dysentery. Moreover, results exhibited that the Proteobacteria and Fusobacteriota were significantly increased (P ≤ 0.05) suggesting dominant microbial community. Results revealed that E. coli induced different pathological alterations in intestine including damage to intestinal epithelial cells, infiltration of inflammatory cells, presence of red blood cells in spaces of tissues, hemorrhages and necrosis of intestinal villi in piglets with history of yellow dysentery. This study for the first time reported the composition, characteristics, and differences of the fecal microflora diversity of Tibetan piglets with yellow and white dysentery in Qinghai-Tibet Plateau, which can provide a suitable support for effective control of diarrhoeal disease in these animals.

Effect of paraquat on cytotoxicity involved in oxidative stress and inflammatory reaction: A review of mechanisms and ecological implications.

Paraquat (PQ) is a cheap and an effective herbicide, which is widely being used worldwide to remove weeds in cultivated crop fields. However, it can cause soil and water pollution, and pose serious harm to the environment and organisms. Several countries have started to limit or prohibit the use of PQ because of the increasing number of human deaths. Its toxicity can damage the organisms with a multi-target mechanism, which has not been fully understood yet. That is why it is hard to treat as well. The current research on PQ focuses on its targeted organ, the lungs, in which PQ mostly trigger pulmonary fibrosis. While there is a lack of systematic research, there are few studies published discussing its toxic effects at systematic level. This review summarizes the major damages caused by PQ in different organisms and partial mechanisms by which it causes these damages. For this purpose, we consulted several research articles that studied the toxicity of PQ in various tissues. We also listed some drugs that can be used to alleviate the toxicity of PQ. However, at present, the effectiveness of these drugs is still being explored in animal experiments and the study of their mechanism will also help in understanding the poisoning mechanism of PQ, which will ultimately lead to effective treatment in future.

Arsenic and antimony co-induced nephrotoxicity via autophagy and pyroptosis through ROS-mediated pathway in vivo and in vitro.

Arsenic (As) and antimony (Sb) are commonly accumulated environmental pollutants that often coexist in nature and cause serious widespread biological toxicity. To investigate the nephrotoxicity induced by As and Sb in detail, we explored the mechanism by which As and Sb cotreatment induced autophagy and pyroptosis in vivo and in vitro. In this study, mice were treated with 4 mg/kg arsenic trioxide (ATO) or/and 15 mg/kg antimony trichloride (SbCl3) by intragastric intubation for 60 days. TCMK-1 cells were treated with ATO (12.5 µM), SbCl3 (25 µM) or a combination of As and Sb for 24 h. The results of the in vivo experiment demonstrated that As or/and Sb exposure could induce histopathological changes in the kidneys, and increase the levels of biochemical indicators of nephrotoxicity. In addition, As and Sb can co-induce oxidative stress, which further activate autophagy and pyroptosis. In an in vitro experiment, As and/or Sb coexposure increased ROS generation and decreased MMP. Moreover, the results of related molecular experiments further confirmed that As and Sb coactivated autophagy and pyroptosis. In conclusion, our results indicated that As and Sb co-exposure could cause autophagy and pyroptosis via the ROS pathway, and these two metals might have a synergistic effect on nephrotoxicity.

Long-term exposure to the fluoride blocks the development of chondrocytes in the ducks: The molecular mechanism of fluoride regulating autophagy and apoptosis.

Long-term exposure to excessive fluoride causes chronic damage in the body tissues and could lead to skeletal and dental fluorosis. Cartilage damage caused by excessive fluoride intake has gained wide attention, but how fluoride accumulation blocks the development of chondrocytes is still unclear. Here, we report a negative correlation between the length and growth plate width after NaF treatments via apoptosis and autophagy, with shrinkage of cells, nuclear retraction, dissolution of chondrocytes. Whereas, fluoride exposure had no significant effect on the number and distribution of the osteoclasts which were well aligned. More importantly, fluoride exposure induced apoptosis of tibial bone through CytC/Bcl-2/P53 pathways via targeting Caspase3, Caspase9, Bak1, and Bax expressions. Meanwhile, the Beclin1, mTOR, Pakin, Pink, and p62 were elevated in NaF treatment group, which indicated that long-term excessive fluoride triggered the autophagy in the tibial bone and produced the chondrocyte injury. Altogether, fluoride exposure induced the chondrocyte injury by regulating the autophagy and apoptosis in the tibial bone of ducks, which demonstrates that fluoride exposure is a risk factor for cartilage development. These findings revealed the essential role of CytC/Bcl-2/P53 pathways in long-term exposure to fluoride pollution and block the development of chondrocytes in ducks, and CytC/Bcl-2/P53 can be targeted to prevent fluoride induced chondrocyte injury.

Exposure to Fluoride induces apoptosis in liver of ducks by regulating Cyt-C/Caspase 3/9 signaling pathway.

Fluorine being a well-known and essential element for normal physiological functions of tissues of different organisms is frequently used for growth and development of body. The mechanisms of adverse and injurious impacts of fluoride are not clear and still are under debate. Therefore, this study was executed to ascertain the potential mechanisms of sodium fluoride in liver tissues of ducks. For this purpose, a total of 14 ducks were randomly divided and kept in two groups including control group and sodium fluoride treated group. The ducks in control group were fed with normal diet while the ducks in other group were exposed to sodium fluoride (750 mg/kg) for 28 days. The results showed that exposure to sodium fluoride induced deleterious effects in different liver tissues of ducks. The results indicated that mRNA levels of Cas-3, Cas-9, p53, Apaf-1, Bax and Cyt-c were increased in treated ducks with significantly higher mRNA level of Cas-9 and lower levels of the mRNA level of Bcl-2 as compared to untreated control group (P < 0.01). The results showed that protein expression levels of Bax and p53 were increased while protein expression level of Bcl-2 was reduced in treated ducks. No difference was observed in protein expression level of Cas-3 between treated and untreated ducks. The results of this study suggest that sodium fluoride damages the normal structure of liver and induces abnormal process of apoptosis in hepatocyte, which provide a new idea for elucidating the mechanisms of sodium fluoride induced hepatotoxicity in ducks.

Cluster of differentiation 147 (CD147) expression is linked with thiram induced chondrocyte's apoptosis via Bcl-2/Bax/Caspase-3 signalling in tibial growth plate under chlorogenic acid repercussion.

Tibial dyschondroplasia (TD) is a metabolic disease of young poultry that affects bone andcartilage's growth. It mostly occurs in broilers due to thiram toxicity in the feed. In this disease, tibial cartilage is not yet ripe for ossification, but it also results in lameness, death, and moral convictions of commercial poultry due to numerous apoptotic changes on cell level. These changes serve a cardinal role in this situation. Many potential problems indicate that chlorogenic acid (CGA) performs an extensive role in controlling apoptosis's perception. However, the actual role of CGA in TD affected chondrocytes in-vitro is still unidentified. The current study investigates the imperceptible insight of CGA on chondrocyte's apoptosis via B-cell lymphoma 2 (Bcl-2), Bcl-2 associated x-protein (Bax), and Caspase-3 with CD147 signalling. The expression of these markers was investigated by Immunofluorescence, western blot analysis, and reverse transcription-quantitative polymerase chain (RT-qPCR). Chondrocytes from the growth plate of tibia were isolated, cultured, and processed. A sub-lethal thiram (2.5 µg/mL) was used to induce cytotoxicity and then treated with an optimum dose (40 µg/ mL) of CGA. According to the results, thiram distorted chondrocyte cells with enhanced apoptotic rate. But, in case of CGA, high expression of CD147 enhanced cell viability of chondrocytes, accompanied by downregulation of Bax/Caspase-3 signalling with the upregulation of Bcl-2. The first possibility has ruled out in the present study by the observation that the cells apoptosis marker, Caspase-3 showed a significant change in CD147 overexpressing cells. Conversely, immunodepletion of CD147 with enhanced cleavage of Caspase-3, indicating the activation of apoptosis in chondrocytes cells. Therefore, these findings suggest a novel insight about CD147 in thiram induced TD about the regulation of Bcl-2/Bax/Caspase-3 apoptosis-signalling axis.

Multi-Targeted Molecular Docking, Pharmacokinetics, and Drug-Likeness Evaluation of Okra-Derived Ligand Abscisic Acid Targeting Signaling Proteins Involved in the Development of Diabetes.

Diabetes mellitus is a global threat affecting millions of people of different age groups. In recent years, the development of naturally derived anti-diabetic agents has gained popularity. Okra is a common vegetable containing important bioactive components such as abscisic acid (ABA). ABA, a phytohormone, has been shown to elicit potent anti-diabetic effects in mouse models. Keeping its anti-diabetic potential in mind, in silico study was performed to explore its role in inhibiting proteins relevant to diabetes mellitus- 11ß-hydroxysteroid dehydrogenase (11ß-HSD1), aldose reductase, glucokinase, glutamine-fructose-6-phosphate amidotransferase (GFAT), peroxisome proliferator-activated receptor-gamma (PPAR-gamma), and Sirtuin family of NAD(+)-dependent protein deacetylases 6 (SIRT6). A comparative study of the ABA-protein docked complex with already known inhibitors of these proteins relevant to diabetes was compared to explore the inhibitory potential. Calculation of molecular binding energy (ΔG), inhibition constant (pKi), and prediction of pharmacokinetics and pharmacodynamics properties were performed. The molecular docking investigation of ABA with 11-HSD1, GFAT, PPAR-gamma, and SIRT6 revealed considerably low binding energy (ΔG from -8.1 to -7.3 Kcal/mol) and predicted inhibition constant (pKi from 6.01 to 5.21 µM). The ADMET study revealed that ABA is a promising drug candidate without any hazardous effect following all current drug-likeness guidelines such as Lipinski, Ghose, Veber, Egan, and Muegge.