Evaluation of phytochemicals from Thymus serpyllum as potential drug candidates to manage oxidative stress in transition dairy cows.

Dairy cows undergo immense stress and experience autoimmune reactions during the transition period, majorly due to the generation of ROS in the body. So, pharmacological approaches are needed to manage oxidative stress in the transition cows. Recently, the use of phytochemicals as feed additives in cows' nutrition has gained interest in managing various disease conditions. In the current study, we have evaluated the potential effects of phytochemicals derived from methanolic extract of Thymus serpyllum against oxidative stress and autoimmunity via inhibition of bovine nuclear factor kappa B (NF-κB). The free radical scavenging activity of Thymus serpyllum seed and leaf extracts was 71.8 and 75.6%, respectively at 100 µg/mL concentration. Similarly, both extracts displayed radicals reducing power and inhibition of lipid-peroxidation maximally at 100 µg/mL. A total of 52 bioactive compounds were identified when the plant extract was characterized by the GC-MS analysis, and five (Thymol, Luteolin 7-o-glucuronide, Rosmarinic acid, Apigenin 6,8-di-c-glucoside, Kaempferol) had binding free energy values of -11.6433, -10.002, -8.2615, -7.1714, -6.4870, respectively, in complexes with bovine NF-κB. Through computational analysis, the screened compounds showed good pharmacokinetic parameters, including non-toxicity, non-carcinogenic, high gastrointestinal absorption and thus can serve as potential drug candidates. MD simulation studies predicted the stability of complexes and the complex of Kaempferol was most stable based on RSMD value and MM/GBSA binding energy. The biochemical assays and computational studies indicated that Thymus serpyllum could be used as a promising feed additive in dairy cows to manage oxidative stress during the transition period.Communicated by Ramaswamy H. Sarma.

Thymus serpyllum Exhibits Anti-Diabetic Potential in Streptozotocin-Induced Diabetes Mellitus Type 2 Mice: A Combined Biochemical and In Vivo Study.

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder that is characterized by hyperglycemia, insulin resistance, and lack of insulin production. It has been previously reported that Thymus serpyllum has therapeutic potential against many diseases. To investigate the antidiabetic action of Thymus serpyllum, this study aimed to analyze its restorative impact in diabetic mice, in which it was administered in diet. Diabetes was induced in BALB/c mice fed with a high-fat diet and two intraperitoneal injections of streptozotocin. With the onset of diabetes, the mice were administered daily with aqueous extract of Thymus serpyllum (500 mg/kg/d and 800 mg/kg/d) for 4 weeks. Body weight and fasting blood glucose levels were measured after every 1 week of the treatment. Subsequently, intraperitoneal glucose tolerance and insulin tolerance tests were conducted. In addition, liver tissue was isolated for assessment in terms of levels of gene expression of the AMPK, IRS1, and GLUT2 gene. Treatment with the aqueous extract of Thymus serpyllum was found to be significantly effective in controlling hyperglycemia and improving glucose and insulin tolerance. Predictable with these impacts, the extract of Thymus serpyllum upregulated the AMPK expression at the mRNA level, as well as upregulating the expression of IRS1 and GLUT2 gene. Histopathological examination of the liver, kidney, and pancreas also revealed the restorative impact in terms of cellular morphology. The results hence demonstrated that oral administration of aqueous extract of Thymus serpyllum can potentially attenuate hyperglycemia in the liver muscle of streptozotocin (STZ)-induced diabetic mice via AMPK and IRS1 upregulation.

Nutrigenomic Interventions to Address Metabolic Stress and Related Disorders in Transition Cows.

For dairy cattle, the period involving a shift from late pregnancy to early lactation termed transition or periparturient is an excruciating phase. Health-related disorders are likely to happen in this time frame. Timely postpartum and metabolic adjustments to this new physical state demands correct management strategies to fulfill the cow's needs for a successful transition to this phase. Among the management strategies, one of the most researched methods for managing transition-related stress is nutritional supplementation. Dietary components directly or indirectly affect the expression of various genes that are believed to be involved in various stress-related responses during this phase. Nutrigenomics, an interdisciplinary approach that combines nutritional science with omics technologies, opens new avenues for studying the genome's complicated interactions with food. This revolutionary technique emphasizes the importance of food-gene interactions on various physiological and metabolic mechanisms. In animal sciences, nutrigenomics aims to promote the welfare of livestock animals and enhance their commercially important qualities through nutritional interventions. To this end, an increasing volume of research shows that nutritional supplementation can be effectively used to manage the metabolic stress dairy cows undergo during the transition period. These nutritional supplements, including polyunsaturated fatty acids, vitamins, dietary amino acids, and phytochemicals, have been shown to modulate energy homeostasis through different pathways, leading to addressing metabolic issues in transition cows.

Genomic and Computational Analysis of Novel SNPs in TNP1 Gene Promoter Region of Bos indicus Breeding Bulls.

Transition nuclear proteins (TNPs), the principal proteins identified in the condensing spermatids chromatin, have been found to play a key role in histone displacement and chromatin condensation during mammalian spermatogenesis. One such gene belonging to the TNP family called TNP1 gene is abundantly expressed in the regulation of spermatogenesis, and its sequence is remarkably well conserved among mammals. Genomic analysis, by sequencing and computational approach, was used to identify the novel polymorphisms and to evaluate the molecular regulation of TNP1 gene expression in Sahiwal cattle breeding bulls. DNA samples were sequenced to identify novel single nucleotide polymorphisms (SNPs) in the TNP1 gene. Modern computational tools were used to predict putative transcription factor binding in the TNP1 promoter and CpG islands in the TNP1 promoter region. In the TNP1 gene, four SNPs, three TATA boxes, and one CAAT box were identified. One CAAT box was discovered at 89 bp upstream of start site ATG. The computational analyses indicated that the polymorphisms inside the promoter sequence results in an added HNF-1 transcription factor binding site. In contrast, the other variations may remove the naturally occurring SRF transcription factor binding site. The CpG islands in the TNP1 promoter region were predicted to be absent by the MethPrimer program before and after SNP site mutations. These findings pave the way for more research into the TNP1 gene's promoter activity and the links between these SNPs and reproductive attributes in the Sahiwal breeding bulls.

Role of Peroxisome Proliferator-Activated Receptors (PPARs) in Energy Homeostasis of Dairy Animals: Exploiting Their Modulation through Nutrigenomic Interventions.

Peroxisome proliferator-activated receptors (PPARs) are the nuclear receptors that could mediate the nutrient-dependent transcriptional activation and regulate metabolic networks through energy homeostasis. However, these receptors cannot work properly under metabolic stress. PPARs and their subtypes can be modulated by nutrigenomic interventions, particularly under stress conditions to restore cellular homeostasis. Many nutrients such as polyunsaturated fatty acids, vitamins, dietary amino acids and phytochemicals have shown their ability for potential activation or inhibition of PPARs. Thus, through different mechanisms, all these nutrients can modulate PPARs and are ultimately helpful to prevent various metabolic disorders, particularly in transition dairy cows. This review aims to provide insights into the crucial role of PPARs in energy metabolism and their potential modulation through nutrigenomic interventions to improve energy homeostasis in dairy animals.

Carboxylic group riched graphene oxide based disposable electrochemical immunosensor for cancer biomarker detection.

In this work, we have developed for the first time a carboxylic group riched graphene oxide based disposable electrochemical immunosensor for cancer biomarker detection using methylene blue (MB). The developed immunosensor is highly sensitive for detection of biomarker Mucin1 (MUC1) in human serum samples. Development of this disposable electrochemical immunosensor was premeditated by applying specific monoclonal antibodies against MUC1. In this method, we explored highly conductive surface of carboxylic group (-COOH-) rich graphene oxide (GO) on screen-printed carbon electrodes (SPCE). This modified GO-COOH-SPCE was employed for the detection of MUC1 protein based on the reaction with methylene blue (MB) redox probe using differential pulse voltammetry (DPV) technique. Developed immunosensor exhibited good detection range for MUC1 with excellent linearity (0.1 U/mL- 2 U/mL), with a limit of detection of 0.04 U/mL. Upon potential application of developed biosensor, good recoveries were recorded in the range of 96-96.67% with % R.S.D 4.2. Analytical performance of the developed immunosensor assures the applicability in clinical diagnostic applications.