Taurine deficiency as a driver of aging.

Aging is associated with changes in circulating levels of various molecules, some of which remain undefined. We find that concentrations of circulating taurine decline with aging in mice, monkeys, and humans. A reversal of this decline through taurine supplementation increased the health span (the period of healthy living) and life span in mice and health span in monkeys. Mechanistically, taurine reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, and attenuated inflammaging. In humans, lower taurine concentrations correlated with several age-related diseases and taurine concentrations increased after acute endurance exercise. Thus, taurine deficiency may be a driver of aging because its reversal increases health span in worms, rodents, and primates and life span in worms and rodents. Clinical trials in humans seem warranted to test whether taurine deficiency might drive aging in humans.

Vascular Endothelial Growth Factor Single Nucleotide Polymorphism +405 G/C (rs2010963) is associated with Levels, Infection Severity, and Amputation among South Indian Diabetic Foot Ulcer Patients.

Background: The regulation of vascular endothelial growth factor (VEGF) by genetic factors in T2DM and DFU still requires thorough investigation. Hence, the present study aimed to investigate the association of VEGF +405 G/C in DFU subjects and correlate it with its circulatory levels, infection severity, and amputation rate. Materials and Methods: This study registered a total of 754 participants of which group I: healthy controls (n = 297), group II: T2DM subjects (n = 242), and group III: DFU subjects (n = 215). Genotyping and levels of rs2010963 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and ELISA, respectively. Results: Results of the current study showed a clear decline in circulatory VEGF-A levels in DFU subjects. VEGF-A was decreased in DFU subjects with the mutant "CC" genotype. The mutant "CC" of VEGF +405G/C was also found to be more susceptible to ulcer grade (III and IV) and major amputations. Conclusion: VEGF +405G/C SNP is associated with levels, infection severity, and amputation amongst South Indian DFU patients.

Green synthesized Se nanoparticle-mediated alleviation of salt stress in field mustard, TS-36 variety.

During this decade, selenium nanoparticles have been found to play a crucial role in helping plants endure several stress conditions, which thereby helps enhance the production of crops in such harsh environments. Globally, high salinity is considered a long-term stress in the crop fields which affects the growth and production of many crops, including mustard-one of the most important oil crops. Here, the activities of spherical-shaped selenium nanoparticles with an average particle size of 55.81 nm, synthesized and functionalized by phytochemicals of fresh grape aqueous extract, were evaluated in the salinity stress (200 mM NaCl) tolerance of mustard plants grown hydroponically in modified Hoagland's solution. These bioactive nanoparticles (30 mg L-1) have exhibited significant activity in alleviating the salt stress complications in mustard, enhancing the activities of antioxidant enzymes (SOD 41.20 %, CAT 64.10 %, APX 63.06 %, and POX 70.43 %), phenolic content (98.88 %), flavonoid content (86.90 %), and free radical scavenging activity (61.89 %). The seed germination percentage, root and shoot length, fresh and dry weight per plant, water content percentage, chlorophyll content, carbohydrate content, and protein content were significantly improved by 39.66 %, 75 %, 60.64 %, 41.2 %, 22.11 %, 1.02 %, 81.92 %, 24.65 % and 79.14 % respectively by the nano selenium application during NaCl stress compared to the control group growing under salt stress without nanoparticles. Gas chromatography-mass spectrometry chromatogram analysis inferred the interaction between the nano-selenium and mustard plants under salt stress. Besides, the in-silico analysis revealed the active molecular interactions between selenium and 20 different proteins of mustard, including glutathione peroxidase, an important antioxidant enzyme.

Sertoli cell specific knockdown of RAR-related orphan receptor (ROR) alpha at puberty reduces sperm count in rats.

Globally, there is an alarming decline in sperm count. Very often hormonal supplementation fails to restore normal sperm count. Sertoli cells (Sc) present within seminiferous tubules provide appropriate niche and factors required for the differentiation of germ cells (Gc) into mature sperm (spermatogenesis). Functionally compromised Sc may be one of the reasons for failure of hormones to facilitate normal spermatogenesis. Although role of secretory proteins and signaling molecules of Sc has been studied well, role of transcription factors regulating sperm count has not been addressed appropriately. Retinoic acid receptor-related orphan receptor (ROR)-alpha is one of such transcription factors reported in testis but its role in testicular function is not yet known. In a separate study, we found abundant ROR-alpha binding sites on promoter regions of several genes upregulated in pubertal rat Sc as compared to infant Sc. Immunostaining studies also revealed presence of ROR alpha in nucleus of pubertal Sc. We generated a transgenic knockdown rat model expressing shRNA targeted to ROR-alpha under Sc specific promoter, which is transcriptionally active only at and after puberty. ROR-alpha knockdown animals were found to have abnormal association of Sc and Gc, including Gc sloughing and restricted release of sperm. The knockdown animals displayed compromised spermatogenesis leading to significant reduction in sperm count. This is the first report describing the Sc specific role of ROR-alpha in maintaining quantitatively normal sperm output. Identification of various such molecules can generate avenues to limit or reverse an alarmingly declining sperm count witnessed globally in men.

An integrated transcriptomics-guided genome-wide promoter analysis and next-generation proteomics approach to mine factor(s) regulating cellular differentiation.

Differential next-generation-omics approaches aid in the visualization of biological processes and pave the way for divulging important events and/or interactions leading to a functional output at cellular or systems level. To this end, we undertook an integrated Nextgen transcriptomics and proteomics approach to divulge differential gene expression of infant and pubertal rat Sertoli cells (Sc).Unlike, pubertal Sc, infant Sc are immature and fail to support spermatogenesis. We found exclusive association of 14 and 19 transcription factor binding sites to infantile and pubertal states of Sc, respectively, using differential transcriptomics-guided genome-wide computational analysis of relevant promoters employing 220 Positional Weight Matrices from the TRANSFAC database. Proteomic SWATH-MS analysis provided extensive quantification of nuclear and cytoplasmic protein fractions revealing 1,670 proteins differentially located between the nucleus and cytoplasm of infant Sc and 890 proteins differentially located within those of pubertal Sc. Based on our multi-omics approach, the transcription factor YY1 was identified as one of the lead candidates regulating differentiation of Sc.YY1 was found to have abundant binding sites on promoters of genes upregulated during puberty. To determine its significance, we generated transgenic rats with Sc specific knockdown of YY1 that led to compromised spermatogenesis.