H2A.Z is involved in premature aging and DSB repair initiation in muscle fibers.

Histone variants are key epigenetic players, but their functional and physiological roles remain poorly understood. Here, we show that depletion of the histone variant H2A.Z in mouse skeletal muscle causes oxidative stress, oxidation of proteins, accumulation of DNA damages, and both neuromuscular junction and mitochondria lesions that consequently lead to premature muscle aging and reduced life span. Investigation of the molecular mechanisms involved shows that H2A.Z is required to initiate DNA double strand break repair by recruiting Ku80 at DNA lesions. This is achieved via specific interactions of Ku80 vWA domain with H2A.Z. Taken as a whole, our data reveal that H2A.Z containing nucleosomes act as a molecular platform to bring together the proteins required to initiate and process DNA double strand break repair.

Pancreatic regenerative potential of manuka honey evidenced through pancreatic histology and levels of transcription factors in diabetic rat model.

Background: Diabetes mellitus is a commonly occurring metabolic disorder accompanied by high morbidity and alarming mortality. Besides various available therapies, induction of pancreatic regeneration has emerged as a promising strategy for alleviating the damaging effect of diabetes. Honey, a potent antioxidative and anti-inflammatory agent, has been reported in the literature archive to exhibit favourable results in the regeneration process of several organ systems. Design: The current research work was intended to explore the potential role of manuka honey in pancreatic regeneration in alloxan-induced diabetic rats by accessing the pancreatic histology and levels of relevant transcription factors, including MAFA, PDX-1, INS-1, INS-2, NEUROG3, NKX6-1, and NEUROD. An equal number of rats were allocated to all four experimental groups: normal, negative control, positive control, and treatment group. Diabetes was induced in all groups except normal through a single intraperitoneal dose of alloxan monohydrate. No subsequent treatment was given to the negative control group, while the positive control and treatment groups were supplemented with metformin (150 mg/kg/day) and manuka honey (3 g/kg/day), respectively. Results: Statistical comparison of glucose and insulin levels, oxidative stress indicators, changes in the architecture of pancreatic islets, and expression levels of regeneration-associated transcription factors advocated the potential role of manuka honey in ameliorating the alloxan-induced hyperglycaemia, hyperinsulinemia, oxidative stress, and necrotic changes in islets along with significant upregulation of relevant transcription factors. Conclusion: This suggests to us the auspicious role of antioxidants in honey in pancreatic regeneration and advocates the favourable role of manuka honey in combating diabetes mellitus.

Human targeted phenobarbital presents a poor substrate of gut microbiome deciphering new drug targets beyond pharmacokinetic curbs.

BACKGROUND: The gut microbiome, a new organ of the body, can potentially alter the pharmacokinetics of orally administered drugs through microbial enzymes. However, absorption of orally administered non-antibiotic drugs by the gut microbiome, during drug-microbiome interaction, is barely addressed. Structural homology studies confirm similar membrane transport proteins in gut epithelial cells and the gut microbiome of the host that may compete for drug substrates with the host itself for its absorbance. Therefore, it is hypothesized that orally administered human targeted phenobarbital may interact and/or be uptake by the gut microbiome during its transit through the small intestine. METHODS: In the current in vivo study, thirty-six male Wistar albino rats were divided into six groups including one control and 5 treatment groups, each having an equal number of rats (n = 6). Phenobarbital was administered orally (single dose of 15 mg/kg bw) to treatment groups. Animals were subsequently sacrificed to harvest microbial mass pallets residing in the small intestine after 2, 3, 4, 5, and 6 h of phenobarbital administration. Phenobarbital absorbance by the microbiome in the microbial lysate was estimated through RP-HPLC-UV at a wavelength of 207 nm. RESULTS: Maximum phenobarbital absorbance (149.0 ± 5.93 µg) and drug absorbance per milligram of microbial mass (1.19 ± 0.05 µg) were found significantly higher at 4 h of post-administration in comparison to other groups. Percent dose recovery of phenobarbital was 5.73 ± 0.19% at 4 h while the maximum intestinal transit time was 5 h till the drug was absorbed by the microbes. Such results pronounce the idea of the existence of structural homology between membrane transporters of the gut microbiome and intestinal enterocytes of the host that may competitively absorb orally administered phenobarbital during transit in the small intestine. The docking studies revealed that the phenobarbital is a poor substrate for the gut microbiome. CONCLUSION: Gut microbiome may competitively absorb the non-antibiotics such as phenobarbital as novel substrates due to the presence of structurally homologous transporting proteins as in enterocytes. This phenomenon suggests the microbiome as a potential candidate that can significantly alter the pharmacokinetics of drugs.

Genome-wide association studies of seedling quantitative trait loci against salt tolerance in wheat.

Salinity is one of the significant factors in decreasing wheat yield and quality. To counter this, it is necessary to develop salt-tolerant wheat varieties through conventional and advanced molecular techniques. The current study identified quantitative trait loci in response to salt stress among worldwide landraces and improved varieties of wheat at the seedling stage. A total of 125 landraces and wheat varieties were subjected to salt treatment (50, 100, and 150 mM) with control. Morphological seedling traits, i.e., shoot length, root length, and fresh and dry shoot and root weights for salinity tolerance were observed to assess salt tolerance and genetic analysis using SNP data through DArT-seq. The results showed that, at the seedling stage, 150 mM NaCl treatment decreased shoot length, root length, and fresh and dry weights of the shoot and root. The root length and dry root weight were the most affected traits at the seedling stage. Effective 4417 SNPs encompassing all the chromosomes of the wheat genome with marker density, i.e., 37%, fall in genome B, genome D (32%), and genome A (31%). Five loci were found on four chromosomes 6B, 6D, 7A, and 7D, showing strong associations with the root length, fresh shoot weight, fresh root weight, and dry root weight at the p < 0.03 significance level. The positive correlation was found among all morphological traits under study.

Potential Therapeutic Benefits of Honey in Neurological Disorders: The Role of Polyphenols.

Honey is the principal premier product of beekeeping familiar to Homo for centuries. In every geological era and culture, evidence can be traced to the potential usefulness of honey in several ailments. With the advent of recent scientific approaches, honey has been proclaimed as a potent complementary and alternative medicine for the management and treatment of several maladies including various neurological disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis, etc. In the literature archive, oxidative stress and the deprivation of antioxidants are believed to be the paramount cause of many of these neuropathies. Since different types of honey are abundant with certain antioxidants, primarily in the form of diverse polyphenols, honey is undoubtedly a strong pharmaceutic candidate against multiple neurological diseases. In this review, we have indexed and comprehended the involved mechanisms of various constituent polyphenols including different phenolic acids, flavonoids, and other phytochemicals that manifest multiple antioxidant effects in various neurological disorders. All these mechanistic interpretations of the nutritious components of honey explain and justify the potential recommendation of sweet nectar in ameliorating the burden of neurological disorders that have significantly increased across the world in the last few decades.

The Competitive Absorption by the Gut Microbiome Suggests the First-Order Absorption Kinetics of Caffeine.

In the literature archive, the intestinal microbiome is now considered as a discrete organ system. Despite living symbiotically with the human body, the gut microbiome is represented as potential drug targets because of its ability to modify the pharmacokinetics of orally administered drugs. Structural biology analysis indicates the existence of homology between transport proteins of microbial cells and membranes of enterocytes. It is speculated that structural similarity in the protein transporters may provoke an unwanted phenomenon of drug uptake by the gut microbiome present in the small intestine of the host. Considering this hypothesis, we analyzed the absorbance of orally administered caffeine by the gut microbiota in in vivo albino rat model through the RP-HPLC-UV approach. Microbiome absorbed the caffeine maximally at 2 hours and minimally at 5 hours post-drug administration following first-order absorption kinetics in a nonlinear way. Drug absorbance of microbial pellet and percent dose recovery was found significantly higher (P ≤ .05) at 2 hours post-administration as compared to all other groups. As speculated, our findings advocated the phenomenon that the gut microbiome influences the absorption of caffeine molecules. Members of the gut microbiome exhibited grouped behavior following first-order absorption kinetics in a nonlinear pattern.

Biodiversity of Gut Microbiota: Impact of Various Host and Environmental Factors.

Human bodies encompass very important symbiotic and mutualistic relationships with tiny creatures known as microbiota. Trillions of these tiny creatures including protozoa, viruses, bacteria, and fungi are present in and on our bodies. They play important roles in various physiological mechanisms of our bodies. In return, our bodies provide them with the habitat and food necessary for their survival. In this review, we comprehend the gut microbial species present in various regions of the gut. We can get benefits from microbiota only if they are present in appropriate concentrations, as if their concentration is altered, it will lead to dysbiosis of microbiota which further contributes to various health ailments. The composition, diversity, and functionality of gut microbiota do not remain static throughout life as they keep on changing over time. In this review, we also reviewed the various biotic and abiotic factors influencing the quantity and quality of these microbiota. These factors serve a significant role in shaping the gut microbiota population.

Sulpiride Serves, a Substrate for the Gut Microbiome.

In the contemporary research world, the intestinal microbiome is now envisioned as a new body organ. Recently, the gut microbiome represents a new drug target in the gut, since various orthologues of intestinal drug transporters are also found present in the microbiome that lines the small intestine of the host. Owing to this, absorbance of sulpiride by the gut microbiome in an in vivo albino rats model was assessed after the oral administration with a single dose of 20mg/kg b.w. The rats were subsequently sacrificed at 2, 3, 4, 5 and 6 hours post oral administration to collect the gut microbial mass pellet. The drug absorbance by the gut microbiome was determined by pursuing the microbial lysate through RP-HPLC-UV. Total absorbance of sulpiride by the whole gut microbiome and drug absorbance per milligram of microbial pellet were found significantly higher at 4 hours post-administration as compared to all other groups. These results affirm the hypothesis that the structural homology between membrane transporters of the gut microbiome and intestinal epithelium of the host might play an important role in drug absorbance by gut microbes in an in vivo condition.

Efficacy of Euphorbia helioscopia in context to a possible connection between antioxidant and antidiabetic activities: a comparative study of different extracts.

BACKGROUND: Euphorbia helioscopia, conventionally known as sun spurge, has been used as a traditional medicine to treat different diseases owing to its reported antitumor, antiviral and antioxidant activities. METHODS: The current research was formulated to assess the in-vitro antioxidant and antidiabetic ability of Euphorbia helioscopia subsequent to the phytochemical analysis of its various extracts. For this purpose, methanol, ethanol and aqueous extracts were prepared using the whole dried plant. Phytochemical analysis of the extracts was done to evaluate the total flavonoid components (TFC) and total phenolic components (TPC) in the extracts. A total of seven phenolic and three flavonoid contents were documented and quantified using HPLC. Antioxidant values were found by DPPH● assay, FRAP and ABTS assays. The antidiabetic potential of the extracts was evaluated by measuring the inhibition ability of the activity of enzymes α amylase and α glucosidase. RESULTS: After analyzing statistically, the results showed that methanolic extract possesses the highest TFC and TPC values while aqueous extract encompassed the lowest level of these contents. Invitro results showed that methanolic extract of the Euphorbia helioscopia has the maximum antioxidant capability since it showed the highest scavenging ability towards the DPPH● (IC50 value = 0.06 ± 0.02 mg/ml), FRAP (758.9 ± 25.1 µMFe+ 2/g), and ABTS (689 ± 25.94 µMTEq/g) due to the presence of high TPC (24.77 ± 0.35 mgGAEq/g) and TFC (17.95 ± 0.32 mgQEq/g) values. Antidiabetic activity in terms of inhibition potential of α amylase and α glucosidase activity was also observed maximum in methanolic extract having lowest IC50 value (0.4 ± 0.01 mg/ml and 0.45 ± 0.01 mg/ml respectively) and minimum in the aqueous extract (IC50 value = 0.57 ± 0.02 mg/ml and 0.76 ± 0.1 mg/ml respectively). CONCLUSION: The experiment outcomes have shown that Euphorbia helioscopia extracts used in the current study contain antioxidant and antidiabetic activities; however, it is highest in its methanolic extract. The presence of the same trend towards the highest antidiabetic activity of the methanolic extract in terms of maximum inhibiting activity of α amylase and α glucosidase enzymes suggests a close association of TFC and TPC in minimizing diabetes.

Retrospective study of frequency of ABO and Rhesus blood group among population of Safdarabad and Faisalabad cities of Pakistan.

OBJECTIVE: The current study aimed to investigate the ABO and rhesus (Rh) blood group frequency in the people of District Faisalabad and Sheikhupura, Punjab Province, Pakistan. The retrospective study was conducted on more than thirty thousand people including both male and female patients admitted to the Tehsil Headquarter Hospital, Safdarabad and The Best Hospital, Faisalabad. Blood samples were taken from each subject and subsequently ABO and Rh blood groups were evaluated separately. The antigen antibody agglutination slide test for blood grouping (ABO) and Rh were used to assess the blood group frequencies. RESULTS: The frequencies of ABO blood group distribution indicated that blood group B was predominant in the people of Safdarabad followed by O, A and AB respectively. While, among people of Faisalabad, blood group O was predominant followed B, A and AB respectively. Rh negative phenotype was found lesser distributed as compared to the positive Rh phenotype.