Chronic stress affects tyrosine phosphorylated protein expression and secretion of male rat epididymis

Chronic stress (CS) is shown to decrease the semen quality with changed expression of tyrosine phosphorylated (TyrPho) proteins in testicular and seminal tissues. However, the alterations of such proteins and fluid contents in the epididymis, producing sperm maturation factors, have never been reported. Sixteen adult rats were randomly divided into 2 groups (n = 8). The control animals were not subjected to stressors whereas CS rats were immobilised within restraint cage (4 hr/day) before cold forced-water swimming (15 min/day) for 60 days. Corticosterone, testosterone, blood glucose level (BGL), malondialdehyde (MDA) and biochemical components in epididymal fluid were assayed. Expressions of heat shock protein 70 (HSP-70), androgen receptor (AR) and TyrPho protein were investigated in epididymal tissue and fluid. Significantly, CS increased the corticosterone and BGL but decreased testosterone and epididymal substance levels. MDA level in tail epididymal fluid and HSP-70 expression in both regions of epididymal tissues and fluids, except in head epididymal fluid of CS were increased. Epididymal tissues showed the decrease of AR expression. Presence and changes of many TyrPho proteins were observed in CS. In conclusion, CS could affect functional proteins particularly TyrPho in epididymis, resulted in low semen quality.     

A population-based assessment of blood lead levels in relation to inflammation

Background

Some experimental and observational research suggests that inflammation may be an important mediator of lead toxicity. However, lead-induced inflammation has not been well-studied in non-occupationally exposed populations.

Methods

Using data for 9,145 individuals ≥40 years of age from the National Health and Nutrition Examination Survey 1999-2004, we assessed the association between blood lead levels (BLLs) and C-reactive protein (CRP), fibrinogen, and white blood cell (WBC) count via ordinal logistic regression. We also examined the interaction between BLL and gender in relation to the inflammatory markers.

Results

No evidence for an association between lead exposure and inflammatory markers was observed with odds ratios around or below the null. Although men but not women appeared to be at increased risk of lead-induced inflammation, no consistent dose-response patterns were observed across BLL quintiles.

Conclusion

Inflammation does not appear to be an important mediator of lead toxicity.     

Multi-dimensional analysis identifies an immune signature predicting response to decitabine treatment in elderly patients with AML

Decitabine is a DNA-hypomethylating agent that has been widely applied for the treatment of acute myeloid leukaemia (AML) patients who are elderly or unfit for intensive therapy. Although effective, the complete response rate to decitabine is only around 30% and the overall survival remains poor. Emerging data support that regulation of DNA methylation is critical to control immune cell development, differentiation and activation. We hypothesize that defining how decitabine influences the immune responses in AML will facilitate the development of novel immune-based leukaemia therapeutics. Here, we performed phenotypic and functional immune analysis on clinical samples from AML patients receiving decitabine treatment and demonstrated a significant impact of decitabine on the immune system. T-cell expression of inhibitory molecules was upregulated and the ability of CD8 T cells to produce cytokines was decreased upon decitabine treatment. Importantly, in an unbiased comprehensive analysis, we identified a unique immune signature containing a cluster of key immune markers that clearly separate patients who achieved complete remission after decitabine from those who failed to do so. Therefore, this immune signature has a strong predictive value for clinical response. Collectively, our study suggests that immune-based analyses may predict clinical response to decitabine and provide a therapeutic strategy to improve the treatment of AML.     

Seed extract of Thai Mucuna pruriens reduced male reproductive damage in rats induced by chronic stress

ContextThai Mucuna pruriens (L.) DC. var. pruriens (Fabaceae) (TMP) is known to enrich reproduction but preventive effects on stress related adverse reproductive parameters are not documented.ObjectiveThis study investigates the protective property of TMP seed extract on reproductive damage under chronic stress (CS).Materials and methodsMale Sprague-Dawley rats were divided into four groups. The control and CS groups received distilled water, whereas the pre-treated rats received the aqueous TMP seed extract at doses of 150 and 300 mg/kg BW for 20 days before co-treatments with CS induction (immobilization and forced swimming) for 81 days. Serum was used to determine the cortisol and testosterone levels. Histology of testis and epididymis was observed with localization of androgen receptor (AR). Sperm parameters and the expression of steroidogenic acute regulatory (StAR), cytochrome P450 family 11 subfamily a member 1 (CYP11A1), AR, HSP70, caspases (3 and 9) and tyrosine phosphorylation (TyrPho) proteins were investigated.ResultsTMP extract improved cortisol level (0.84 ± 0.02 µg/dL) and protected against the damage of reproductive tissues and sperm parameters (count [49.78 ± 3.74 million sperm/mL], viability [90.01 ± 1.17%] and precocious acrosome reaction [1.38 ± 0.48%]). Expression of testicular StAR, CYP11A1, AR and HSP70 proteins was improved. Caspase expression was decreased in treated rats. TMP increased AR expression in CS sperm. Moreover, TyrPho protein expression was corrected after TMP administration.ConclusionsTMP seed protected against adverse reproductive parameters in CS via improvements of functionally testicular markers and reductions of apoptotic proteins. It is possible to develop the TMP beans as an alternative medicine in treating of male subfertility caused by CS.     

Room-Temperature Lewis Acid Organocatalysts for Bulk Ring-Opening Polymerization of Bis-Lithium N-Heterocyclic Carbenes Complexes Activated on ε-Caprolactone: Synthetic,Experimental, and Density Functional Theory of Mechanistic Studies

This work investigates the high catalytic activity of bi-functional lithium N-heterocyclic carbene (bisLiNHCs) complexes in bulk ring-opening polymerization (ROP) of ε-caprolactone (ε-CL) monomer at room temperature. The study employs a bulk ROP technique using tetramethylene-tethered bis[N-(N′-alkyl/arylimidazolium)] bishexafluorophosphate (bis[Bim][PF₆]), benzyl alcohol (BnOH), and n-butyl lithium (nBuLi) in molar ratios of 1:2:4. The results show that 1,4-bisLiNHC ( 3a ) has the highest catalytic capability, producing the highest molecular weight of PCL with acceptable dispersity in only 93 s (59 361 g mol⁻¹, Đ = 1.8). However, longer and aromatic linker chains ( 3b - 3g ) are found to be less effective due to the increased steric effect for complex formation with the monomer, leading to longer reaction times and lower molecular weight PCL with wider dispersity. Additionally, the study conducts a mechanistic analysis using the DFT method with B3LYP (6-31G(d,p)) as the basis set. The most plausible mechanism proposed involves continuous and coordinated insertion with low energy barriers.