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Leukaemia inhibitory factor (LIF) plays an indispensible role in embryo implantation. Aberrant LIF production is linked to implantation failure. LIF regulates multiple processes prior to and during implantation such as uterine transformation into a receptive state, decidualization, blastocyst growth and development, embryo-endometrial interaction, trophoblast invasion, and immune modulation. Due to its critical role, LIF has been a target for a nonhormonal contraception. In this review, we summarize up-to-date information on the role of LIF in implantation and its role in contraception.

Vitamin D deficiency is a common health problem worldwide. Despite its known skeletal effects, studies have begun to explore its extra-skeletal effects, that is, in preventing metabolic diseases such as obesity, hyperlipidemia, and diabetes mellitus. The mechanisms by which vitamin D deficiency led to these unfavorable metabolic consequences have been explored. Current evidence indicates that the deficiency of vitamin D could impair the pancreatic β-cell functions, thus compromising its insulin secretion. Besides, vitamin D deficiency could also exacerbate inflammation, oxidative stress, and apoptosis in the pancreas and many organs, which leads to insulin resistance. Together, these will contribute to impairment in glucose homeostasis. This review summarizes the reported metabolic effects of vitamin D, in order to identify its potential use to prevent and overcome metabolic diseases.

It was hypothesized that endometrial tight junction morphology and expression of tight junction proteins i.e., claudin-4 and occludin in the uterus, are affected by testosterone. Therefore, the effects of testosterone on these parameters in the uterus during receptivity period were investigated. Ovariectomized adult female rats were given testosterone (1 mg/kg/day) alone or in combination with flutamide or finasteride between days 6 to 8 of sex-steroid replacement treatment, which was considered the period of uterine receptivity. Ultramorphology of tight junctions was visualized by transmission electron microscopy while distribution and expression of claudin-4 and occludin were examined by immunofluorescence and real-time polymerase chain reaction respectively. Administration of testosterone caused loss of tight junction complexity and down-regulated expression of claudin-4 and occludin in the uterus. Decreased endometrial tight junction complexity and expression of claudin-4 and occludin in the uterus during receptivity period by testosterone may interfere with embryo attachment and subsequent implantation.

The objective of our study was to evaluate the time-dependent humoral immunity kinetics among multi-ethnic population of medical students and healthcare professionals across Malaysia following two doses of Comirnaty, Vaxzevria, and CoronaVac vaccines. Prospective observational cohort research was carried out from September 2021-March 2023. 242 vaccine recipients have completed the follow-up. After second vaccination dosage, peripheral blood was drawn every four weeks from week 0–24. Anti-S IgG and percentage of neutralization were measured from each individual plasma sample. Recipients of Comirnaty and Vaxzevria vaccine, exhibited adequate anti-S IgG and neutralizing antibody till week 24. In compared to Comirnaty/Vaxzevria vaccine group, CoronaVac group showed significant decrease of antibody as early as week 12. The Comirnaty vaccine peaked anti-S IgG production at week 4, while the Vaxzevria and CoronaVac vaccines peaked at week 2. The Comirnaty vaccine (91.3%) showed strong Ig-RBD neutralizing antibody response even after week 24, which led to the slowest rate of antibody waning when compared to CoronaVac (13%), which never achieves high Ig-RBD neutralizing antibody. The percentage of inhibition of Ig-RBD binding on ACE 2 receptor and anti-S IgG seroconversion were significantly higher in the Comirnaty vaccine. The antibody response of Comirnaty was lower in recipients with higher BMIs than in those with normal or low BMIs. Higher BMI, however, was associated with more robust humoral immune responses to Vaxzevria vaccine. Following immunisation, the Chinese and Indian populations might exhibit a stronger humoral immune response than the Malay population.

Testosterone could have adverse effect on fertility. In this study, we hypothesized that this hormone could reduce the number of embryo implantations via affecting the normal endometrium ultrastructure and expression of endometrial proteins involved in implantation. Therefore, the aims were to identify these adverse testosterone effects. Methods: Intact pregnant rats were given 250 or 500 µg/kg/day testosterone for three days, beginning from day 1 of pregnancy. Rats were euthanized either at day 4 to analyze the ultra-structural changes in the endometrium and expression and distribution of MECA-79 protein, or at day 6 to determine the number of implantation sites. Results: Administration of 500 µg/kg/day testosterone suppresses endometrial pinopodes development and down-regulates expression and distribution of MECA-79 protein in the uterus. In addition, the number of implantation sites were markedly decreased. Conclusions: Changes in endometrial ultrastructure and expression of implantation protein in the endometrium in early pregnancy period could be the reason for failure of embryo implantation under testosterone influence.

Background: Diabetes mellitus is a chronic metabolic disorder characterized by elevated plasma glucose levels. It is often defined as a lifestyle disease having severe economic and physiological repercussions on the individual. One of the most prevalent clinical consequences of diabetes is the lagging pace of injury healing leading to chronic wounds, which still to date have limited treatment options. The objective of this research is to look into the wound healing capabilities of gallocatechin (GC) and silver nanoparticles (AgNPs) impregnated patches in diabetic rats. Experimental rats were dressed patches and the wound healing skin region was dissected at the end of the experiment for molecular analysis. The wound healing rate in diabetic rats dressed with CGP2 and CGP3 & silver sulfadiazine (AgS) patches were found to be high. While mRNA and immunofluorescence or immunohistochemistry assays reveal that Wnt3a and β-catenin levels were higher with Gsk-3β and c-fos levels were lower in diabetic rats dressed with in CGP2 and CGP3 as compared with diabetic rats dressed with DC+CGP1. Furthermore, apoptosis markers such as caspase-3, caspase-9, and Bax levels were reduced, whereas anti-apoptosis maker (Bcl-2) and proliferation marker (PCNA) levels were increased in diabetic rats dressed with CGP2 and CGP3 as compared with diabetic rats dressed with DC+CGP1. In conclusion, the results demonstrated that GC-AgNPs-CGP (CGP2 & CGP3) dressing on diabetes wound rats decreased changes in Wnt3a/β-catenin pathways, resulting in lower apoptosis and greater proliferation, so drastically improving diabetic wound healing.

Diabetes mellitus (DM) has been associated with sperm damage. In view of the fact that quercetin possesses antioxidant and anti-inflammatory activities, this compound may help to protect sperm against damage in DM. In this study, effects of quercetin on sperm parameters in DM were investigated. Quercetin (10, 25 and 50 mg/kg/b.w.) was given orally to streptozotocin-nicotinamide induced adult male diabetic rats for 28 days. Following treatment completion, rats were sacrificed and sperm were harvested from the cauda epididymis. Sperm count, motility, viability, hyperosmotic swelling (HOS) tail-coiled sperm and morphology were assessed. Levels of lipid peroxidation (LPO) and anti-oxidative enzymes (SOD, CAT and GPx) in sperm with and without H O incubation were determined by biochemical assays. Expression levels of SOD, CAT and GPx mRNAs in sperm were evaluated by qPCR. Sperm DNA integrity was estimated by flow cytometry while expression levels of the inflammatory markers NF-κβ and TNF-α in sperm were determined by Western blotting. In diabetic rats receiving quercetin, sperm count and motility, viability and HOS tail-coiled sperm increased ( < 0.05) while sperm with abnormal morphology decreased. Moreover, sperm SOD, CAT, GPx activities and their mRNA expression levels increased while sperm LPO, NF-κβ and TNF-α levels decreased. In normal and diabetic rat sperm incubated with H O , a further increase in MDA and further decreases in SOD, CAT and GPx were observed, and these were ameliorated by quercetin treatment. administration of quercetin to diabetic rats helps to ameliorate sperm damage and improves sperm morphology and functions in DM.

Type 2 diabetes mellitus is characterized by both resistance to the action of insulin and defects in insulin secretion. Bird’s nest, which is derived from the saliva of swiftlets are well known to possess multiple health benefits dating back to Imperial China. However, it’s effect on diabetes mellitus and influence on the actions of insulin action remains to be investigated. In the present study, the effect of standardized aqueous extract of hydrolyzed edible bird nest (HBN) on metabolic characteristics and insulin signaling pathway in pancreas, liver and skeletal muscle of db/db , a type 2 diabetic mice model was investigated. Male db/db diabetic and its euglycemic control, C57BL/6J mice were administered HBN (75 and 150 mg/kg) or glibenclamide (1 mg/kg) orally for 28 days. Metabolic parameters were evaluated by measuring fasting blood glucose, serum insulin and oral glucose tolerance test (OGTT). Insulin signaling and activation of inflammatory pathways in liver, adipose, pancreas and muscle tissue were evaluated by Western blotting and immunohistochemistry. Pro-inflammatory cytokines were measured in the serum at the end of the treatment. The results showed that db/db mice treated with HBN significantly reversed the elevated fasting blood glucose, serum insulin, serum pro-inflammatory cytokines levels and the impaired OGTT without affecting the body weight of the mice in all groups. Furthermore, HBN treatment significantly ameliorated pathological changes and increased the protein expression of insulin, and glucose transporters in the pancreatic islets (GLUT-2), liver and skeletal muscle (GLUT-4). Likewise, the Western blots analysis denotes improved insulin signaling and antioxidant enzyme, decreased reactive oxygen species producing enzymes and inflammatory molecules in the liver and adipose tissues of HBN treated diabetic mice. These results suggest that HBN improves β-cell function and insulin signaling by attenuation of oxidative stress mediated chronic inflammation in the type 2 diabetic mice.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of liver disease. Orthosiphon aristatus (Blume) Miq, a traditional plant in South Asia, has previously been shown to attenuate obesity and hyperglycaemic conditions. Eight weeks of feeding C57BL/6 mice with the standardized O. aristatus extract (400 mg/kg) inhibited the progression of NAFLD. Liver enzymes including alanine aminotransferase and aspartate transaminase were significantly reduced in treated mice by 74.2% ± 7.69 and 52.8% ± 7.83, respectively. Furthermore, the treated mice showed a reduction in serum levels of glucose (50% ± 5.71), insulin (70.2% ± 12.09), total cholesterol (27.5% ± 15.93), triglycerides (63.2% ± 16.5), low-density lipoprotein (62.5% ± 4.93) and atherogenic risk index relative to the negative control. Histologically, O. aristatus reversed hepatic fat accumulation and reduced NAFLD severity. Notably, our results showed the antioxidant activity of O. aristatus via increased superoxide dismutase activity and a reduction of hepatic malondialdehyde levels. In addition, the levels of serum pro-inflammatory mediators (IL-6 and TNFα) decreased, indicating anti-inflammatory activity. The aqueous, hydroethanolic and ethanolic fractions of O. aristatus extract significantly reduced intracellular fat accumulation in HepG2 cells that were treated with palmitic–oleic acid. Together, these findings suggest that antioxidant activities are the primary mechanism of action of O. aristatus underlying the anti-NAFLD effects.

Honey has several pharmacological effects, including anti-diabetic activity. However, the effectiveness of bitter gourd honey (BGH) in the treatment of diabetes mellitus (DM) is unknown. The aim of this study was to determine the antioxidant, anti-inflammatory, and anti-apoptotic properties of BGH on the kidney and liver of a streptozotocin-induced diabetes rat model. Methods: A single dose (nicotinamide 110 mg/kg, streptozotocin (STZ) 55 mg/kg, intraperitoneal (i.p.)) was used to induce DM in male rats. For 28 days, normal or diabetic rats were administered 1 g/kg/day and 2 g/kg/day of BGH orally. After the treatment, blood, liver, and kidney samples were collected and analysed for biochemical, histological, and molecular parameters. In addition, liquid chromatography–mass spectrometry (LC-MS) was used to identify the major bioactive components in BGH. Results: The administration of BGH to diabetic rats resulted in significant reductions in alanine transaminase (ALT),aspartate aminotransferase (AST), creatinine, and urea levels. Diabetic rats treated with BGH showed lesser pathophysiological alterations in the liver and kidney as compared to non-treated control rats. BGH-treated diabetic rats exhibited reduced levels of oxidative stress (MDA levels), inflammatory (MYD88, NFKB, p-NFKB, IKKβ), and apoptotic (caspase-3) markers, as well as higher levels of antioxidant enzymes (SOD, CAT, and GPx) in the liver and kidney. BGH contains many bioactive compounds that may have antioxidative stress, anti-inflammatory, and anti-apoptotic effects. Conclusion: BGH protected the liver and kidney in diabetic rats by reducing oxidative stress, inflammation, and apoptosis-induced damage. As a result, BGH can be used as a potential therapy to ameliorate diabetic complications.