Immobilization stress exacerbates arsenic-induced reprotoxic effects in adult rats.

Objective: The central objective of this study was to investigate the cumulative effects restraint stress and sodium arsenite on reproductive health in male rats. Methods: Healthy male Wistar rats were allocated into 4 groups (n = 8). Animals in group 1 served as controls and did not subjected to any stress. Rats in groups 2, 3, and 4 were subjected to either restraint stress (5 h/day) or maintained on arsenic (25 ppm) via drinking water or both for 65 days. After completion of the experimental period, all the rats were analyzed for selected reproductive endpoints. Results: Restraint stress or sodium arsenite treatment increased serum corticosterone levels, reduced testicular daily sperm count, epididymal sperm viability, motility, membrane integrity, and decreased testicular steroidogenic enzymes such as 3ß- and 17ß-hydroxysteroid dehydrogenases associated with reduced serum testosterone levels, deteriorated testicular architecture, and reduced activity levels of testicular superoxide dismutase and catalase accompanied by elevated lipid peroxidation levels. In rats subjected to restraint stress and sodium arsenite, a significant decrease in selected sperm qualitative and quantitative parameters, serum testosterone levels were observed as compared with rats subjected to sodium arsenite alone. A significant increase in the levels of lipid peroxidation with a concomitant decrease in the activities of antioxidant enzymes was observed in the testis of rats subjected to both restraint stress and sodium arsenite treatment as compared with sodium arsenite alone intoxicated rats. Surprisingly, serum corticosterone levels were significantly elevated in rats following both stressors as compared with arsenic alone treated rats. Analysis of atomic absorption spectroscopy revealed that the accumulation of arsenic in the testis of arsenic-treated and arsenic plus immobilization stress groups was significant as compared with controls. Conclusions: Based on the findings, it can be concluded that deterioration of male reproductive health could be accelerated in arsenic intoxicated rats following restraint stress.

Recovery of Prenatal Baicalein Exposure Perturbed Reproduction by Postnatal Exposure of Testosterone in Male Mice.

Baicalein (BC), a flavonoid, which lacks the qualities of reproductive health and shows adverse effects, is tested in this study. Inseminated mice were injected with 30, 60, and 90 mg BC/Kg body weight on gestation days 11, 13, 15, and 17. The F1 BC-exposed males of each dosage were divided into six groups. First three groups (n = 6 from each BC dosage) were used for assessment of reproductive performance, the others (n = 4 from each BC dosage) were administered with testosterone 4.16 mg/kg body weight on postnatal days 21, 31, and 41. The reproductive health of adult F1 males at the age of 55 and 60 was tested. Prenatal BC exposure showed reduced fertility after cohabitation with control females. The BC exposure significantly reduced the body weight, tissue indices, and sperm parameters (motility, count, viability, and daily sperm count) and altered the sperm membrane in a hypoosmotic swelling test. A downward trend was observed in testicular steroidogenic marker enzymes (3ß- and 17ß-steroid dehydrogenases) and serum testosterone, whereas increase in serum titers of FSH and LH along with altered the testicular histology. Conversely, testosterone (4.16 mg/kg body weight) partially recovered reduced male reproductive health by BC. BC impaired male reproductive health due to low levels of testosterone is reverted by external testosterone is evidenced in this study.

One-pot synthesis of thiazolo[3,2-a]pyrimidine derivatives, their cytotoxic evaluation and molecular docking studies.

An economical, simple and efficient one-pot method has been developed for the synthesis of thiazolo[3,2-a]pyrimidine hydrobromide derivatives. 2,4-diaryl-6,7,8,9-tetrahydro-4H-benzo[4,5]thiazolo[3,2-a]pyrimidine hydrobromides were synthesized by the α-bromination of cyclohexanone with N-Bromosuccinamide (NBS) and followed by cyclization with 3,4-dihydropyrimidine-2(1H)-thiones, respectively, in the presence of p-toluenesulfonic acid (PTSA) in acetonitrile. However when cyclohexanone was replaced by acetyl acetone and alpha-tetralone gave the corresponding 1-(3-methyl-5,7-diaryl-5H-thiazolo[3,2-a]pyrimidin-2-yl)ethan-1-one hydrobromide and 9,11-diaryl-6,11-dihydro-5H-naphtho[1',2':4,5]thiazolo[3,2-a]pyrimidine hydrobromide derivatives, respectively. The significant features of this method are novel, simple, inexpensive experimental procedure, short reaction time, and good yield. The some of the synthesized compounds were evaluated for cytotoxic activity against human lung adenocarcinoma cell line (A549), human breast carcinoma cell line (MCF-7), human cervical cancer cell line (HeLa) and human neuronal carcinoma cell lines (SKNSH). Tested compounds 5(b-e) showed the excellent anticancer activity against various cell lines. Particularly compound 5c with IC50 value of 2.2 ± 0.6 µM against A549 and compound 5e with IC50 value of 5.6 ± 0.4 µM against HeLa showed best cytotoxic effects. Furthermore, Molecular docking study was performed for some of the synthesized compounds 5(b-e) against topoisomerase-II by using Auto dock method. Docking results of the compounds 5c, 5d, and 5e exhibited higher cytotoxic activity than the standard doxorubicin.

α-Lipoic acid inhibits testicular and epididymal oxidative damage and improves fertility efficacy in arsenic-intoxicated rats.

The present study evaluates the protective effect of α-lipoic acid (LA) against arsenic-induced testicular and epididymal oxidative damage in rats. Arsenic caused significant reduction in the reproductive organ weights, serum testosterone levels, testicular daily sperm count, epididymal sperm count, sperm motility, sperm viability, and sperm membrane integrity. Significant reduction in the activity levels of superoxide dismutase, catalase, and glutathione levels with a concomitant increase in the lipid peroxidation and protein carbonyl content in the testis and the cauda epididymis of arsenic-exposed rats. Arsenic intoxication also enhanced the testicular caspase-3 mRNA levels, disorganization of testicular and cauda epididymal architecture as well as increased arsenic content in the testis and the cauda epididymis of rats. Arsenic exposure also deteriorated fertility ability in male rats over controls. Conversely, α-LA negated the testicular and cauda epididymal oxidative stress and restored the male reproductive health in arsenic-exposed rats.

The Origin and Diversity of Cpt1 Genes in Vertebrate Species.

The Carnitine palmitoyltransferase I (Cpt1) gene family plays a crucial role in energy homeostasis since it is required for the occurrence of fatty acid ß-oxidation in the mitochondria. The exact gene repertoire in different vertebrate lineages is variable. Presently, four genes are documented: Cpt1a, also known as Cpt1a1, Cpt1a2; Cpt1b and Cpt1c. The later is considered a mammalian innovation resulting from a gene duplication event in the ancestor of mammals, after the divergence of sauropsids. In contrast, Cpt1a2 has been found exclusively in teleosts. Here, we reassess the overall evolutionary relationships of Cpt1 genes using a combination of approaches, including the survey of the gene repertoire in basal gnathostome lineages. Through molecular phylogenetics and synteny studies, we find that Cpt1c is most likely a rapidly evolving orthologue of Cpt1a2. Thus, Cpt1c is present in other lineages such as cartilaginous fish, reptiles, amphibians and the coelacanth. We show that genome duplications (2R) and variable rates of sequence evolution contribute to the history of Cpt1 genes in vertebrates. Finally, we propose that loss of Cpt1b is the likely cause for the unusual energy metabolism of elasmobranch.

CGMD: An integrated database of cancer genes and markers.

Integrating cancer genes and markers with experimental evidence might provide valuable information for the further investigation of crosstalk between tumor genes and markers in cancer biology. To achieve this objective, we developed a database known as the Cancer Gene Marker Database (CGMD), which integrates data on tumor genes and markers based on experimental evidence. The major goal of CGMD is to provide the following: 1) current systematic treatment approaches and recent advances in different cancer treatments; 2) the aggregation of different genes and markers by their molecular characteristics and pathway associations; and 3) free access to the data compiled by CGMD at http://cgmd.in/. The database consists of 309 genes and 206 markers, as well as a list of 40 different human cancers, with detailed descriptions of all characterized markers. CGMD provides complete cancer annotations and molecular descriptions of cancer genes and markers such as CpG islands, promoters, exons, PDB structures, active sites and domains.

Complete genome-wide screening and subtractive genomic approach revealed new virulence factors, potential drug targets against bio-war pathogen Brucella melitensis 16M.

Brucella melitensis 16M is a Gram-negative coccobacillus that infects both animals and humans. It causes a disease known as brucellosis, which is characterized by acute febrile illness in humans and causes abortions in livestock. To prevent and control brucellosis, identification of putative drug targets is crucial. The present study aimed to identify drug targets in B. melitensis 16M by using a subtractive genomic approach. We used available database repositories (Database of Essential Genes, Kyoto Encyclopedia of Genes and Genomes Automatic Annotation Server, and Kyoto Encyclopedia of Genes and Genomes) to identify putative genes that are nonhomologous to humans and essential for pathogen B. melitensis 16M. The results revealed that among 3 Mb genome size of pathogen, 53 putative characterized and 13 uncharacterized hypothetical genes were identified; further, from Basic Local Alignment Search Tool protein analysis, one hypothetical protein showed a close resemblance (50%) to Silicibacter pomeroyi DUF1285 family protein (2RE3). A further homology model of the target was constructed using MODELLER 9.12 and optimized through variable target function method by molecular dynamics optimization with simulating annealing. The stereochemical quality of the restrained model was evaluated by PROCHECK, VERIFY-3D, ERRAT, and WHATIF servers. Furthermore, structure-based virtual screening was carried out against the predicted active site of the respective protein using the glycerol structural analogs from the PubChem database. We identified five best inhibitors with strong affinities, stable interactions, and also with reliable drug-like properties. Hence, these leads might be used as the most effective inhibitors of modeled protein. The outcome of the present work of virtual screening of putative gene targets might facilitate design of potential drugs for better treatment against brucellosis.

Prenatal di-n-butyl phthalate exposure alters reproductive functions at adulthood in male rats.

This study was aimed to investigate the reproductive health in adult male rats exposed to di-n-butyl phthalate (DBP) during embryonic development. Pregnant rats were injected with DBP and F1 male rats were weaned and on postnatal day 100, used for mating with normal cycling females to assess reproductive performance. After completion of cohabitation period, rats were analyzed for other reproductive end points. Transplacental exposure to DBP significantly decreased fertility in adult male rats. Prenatal exposure to DBP significantly decreased sperm density, number of motile sperms, viable sperms, and hypoosmotic swelling tail coiled sperms with an increase in morphological abnormalities in sperms. Testicular steroidogenic enzyme activity levels and serum testosterone levels were significantly decreased in rats exposed to DBP during embryonic development. In conclusion, transplacental exposure to DBP impairs male reproductive performance by decreasing steroidogenesis and spermatogenesis.

Progesterone administration induces preimplantation embryonic loss in mice.

OBJECTIVE: To evaluate the effect of progesterone during early pregnancy on pregnancy maintenance in mice. DESIGN: Experimental study or laboratory investigation. SETTING: An established molecular reproduction laboratory, Department of Biotechnology, S.V. University. ANIMAL(S): Healthy virgin female Swiss albino mice of 8 weeks of age. INTERVENTION(S): After confirmation of the heat period, adult female mice were mated with mature healthy males to achieve pregnancy. Inseminated females received intraperitoneal injections of progesterone at doses of 0, 1, 3.5, 7, 15, 25, or 50 mg/kg body weight on the first, third, and seventh day of pregnancy. MAIN OUTCOME MEASURE(S): Preimplantation embryonic loss. RESULT(S): Pregnancy failure was evidenced by reduction in the number of embryos in females injected with 7 (25.12 %), 15 (38.44 %), 25 (100%), and 50 (100%) mg progesterone/kg body weight. In females with a successful pregnancy, the numbers of corpora lutea and postimplantation loss per dam were comparable across all groups. No increase in the incidence of malformed fetuses was found in any progesterone-treated groups. CONCLUSION(S): Administration of supranormal levels of progesterone during early pregnancy caused a reduction in the number of implantations and an increase in preimplantation loss in mice.