OBJECTIVE: To determine the methylation profile of the selected CTAs in our colorectal cancer patients.
METHODS: A total of 54 pairs of colorectal cancer samples were subjected to DNA methylation profiling using the Infinium Human Methylation 450K bead chip.
RESULTS: We found that most of the CTAs were hypomethylated, and CCNA1 and TMEM108 genes were among the few CTAs that were hypermethylated.
CONCLUSION: Overall, our brief report has managed to show the overall methylation profile in over the 200 CTAs in colorectal cancer and this could be used for further refining any immunotherapy targets.
Aim: The objective of this research was to investigate the acute effects of tributyltin chloride (TBTCl) on gonads in the adult stage of Artemia salina by use normal histology and immunohistochemistry (IHC) (Caspase 3 and HSP70) to see specific apoptosis markers.
Methods: After exposure of A. salina to different concentrations of TBTCl (25, 50, 100, 200, and 300 ng.l-1), 50 adult A. salina (25 male and 25 female) were selected randomly from each concentration to histologically study the gonads. The gonad tissue was sectioned (5 μm) and some slides were stained with hematoxylin and eosin and others were stained with IHC avidin-biotin complex, and were examined under a light microscope.
Results: The results showed significant differences (p < 0.05) in histological lesions between different concentrations of TBTCl. The histological lesions in the testis and ovary section were undifferentiated cells, degenerating yolk globules, and follicle cells enveloping the oocyte which was then compared with control tissue, and these effects were found to be increased in females more than in males with the highest concentration of TBTCl. Immunohistochemistry (IHC) showed that positive immunostaining was observed in the testis and ovary as brownish deposits to Caspase 3 and HSP70 antibody after exposure to TBTCl, while the testis and ovary section in control tissue had no immunoreactivity to Caspase 3 and HSP70 antibody; these effects were profoundly increased with the highest concentration of TBTCl in females more than in males. Finally, the histological lesions and IHC (Caspase 3 and HSP70) revealed that the apoptosis and immune system stress of A. salina gonad tissue damage in females were more sensitive to TBTCl toxicity as compared to white males.
Conclusion: In general, the present study aimed to observe the effects TBTCl on A. salina gonads by using histological sections and IHC (Caspase 3 and HSP70), which were evaluated for the first time and have been proven to possess an important function in apoptosis marker and immune system stress in Artemia. Finally, the specific mechanisms through which TBTCl affects A. salina Caspase 3 and HSP70 expression need further investigation.
OBJECTIVE: To examine the effects of metformin on parameters involved in testicular lactate production, transport/utilisation, and sexual behaviour in diabetic state.
METHODS: Male Sprague-Dawley rats were assigned into normal control (NC), diabetic control (DC), and metformin-treated diabetic group (n = 6/group). Metformin (300 mg/kg b.w./day) was administrated orally for 4 weeks.
RESULTS: Intra-testicular glucose and lactate levels, and lactate dehydrogenase (LDH) activity increased, while the mRNA transcript levels of genes responsible for testicular glucose and lactate transport/utilisation (glucose transporter 3, monocarboxylate transporter 4 (MCT4), MCT2, and LDH type C) decreased in DC group. Furthermore, penile nitric oxide increased, while cyclic guanosine monophosphate decreased, with impaired sexual behaviour in DC group. Treatment with metformin improved these parameters.
CONCLUSIONS: Metformin increases testicular lactate transport/utilisation and improves sexual behaviour in diabetic state.
OBJECTIVES: The present study investigated the protective effect of Malaysian propolis on diabetes-induced subfertility/infertility. Additionally, its combined beneficial effects with metformin were investigated.
MATERIALS AND METHODS: Forty adult male Sprague Dawley rats were randomly assigned into five groups, namely normal control, diabetic control, diabetic + Malaysian propolis (300 mg/k.g. b.w.), diabetic + metformin (300 mg/kg b.w.) and diabetic + Malaysian propolis + metformin. Diabetes was induced using a single intraperitoneal injection of streptozotocin (60 mg/kg b.w.) and treatment lasted for 4 weeks. During the 4th week, mating behavioural experiments were performed using sexually receptive female rats. Thereafter, fertility parameters were assessed in the female rats.
RESULTS: Malaysian propolis increased serum and intratesticular free testosterone levels, up-regulated the mRNA levels of AR and luteinizing hormone receptor, up-regulated the mRNA and protein levels of StAR, CYP11A1, CYP17A1, 3β-HSD and 17β-HSD in the testes of diabetic rats. Furthermore, Malaysian propolis up-regulated testicular MCT2, MCT4 and lactate dehydrogenase type C mRNA levels, in addition to improving sperm parameters (count, motility, viability and normal morphology) and decreasing sperm nDNA fragmentation in diabetic rats. Malaysian propolis improved mating behaviour by increasing penile guanosine monophosphate levels. Malaysian propolis also improved fertility outcome as seen with decreases in pre- and post-implantation losses, increases in gravid uterine weight, litter size per dam and foetal weight. Malaysian propolis's effects were comparable to metformin. However, their combination yielded better results relative to the monotherapeutic interventions.
CONCLUSION: Malaysian propolis improves fertility potential in diabetic state by targeting steroidogenesis, testicular lactate metabolism, spermatogenesis and mating behaviour, with better effects when co-administered with metformin. Therefore, Malaysian propolis shows a promising complementary effect with metformin in mitigating Diabetes mellitus-induced subfertility/infertility.