α‐ketoglutarate delays age‐related fertility decline in mammals

The fecundity reduction with aging is referred as the reproductive aging which comes earlier than that of chronological aging. Since humans have postponed their childbearing age, to prolong the reproductive age becomes urgent agenda for reproductive biologists. In the current study, we examined the potential associations of α‐ketoglutarate (α‐KG) and reproductive aging in mammals including mice, swine, and humans. There is a clear tendency of reduced α‐KG level with aging in the follicle fluids of human. To explore the mechanisms, mice were selected as the convenient animal model. It is observed that a long term of α‐KG administration preserves the ovarian function, the quality and quantity of oocytes as well as the telomere maintaining system in mice. α‐KG suppresses ATP synthase and alterations of the energy metabolism trigger the nutritional sensors to down‐regulate mTOR pathway. These events not only benefit the general aging process but also maintain ovarian function and delay the reproductive decline. Considering the safety of the α‐KG as a naturally occurring molecule in energy metabolism, its utility in reproduction of large mammals including humans deserves further investigation.     

Comparative mineral and hormonal analyses of wild type and TLS somaclonal variant derived from oil palm (Elaeis guineensis Jacq. var. tenera) tissue culture

Comparative mineral and hormonal analyses were made on tissue culture derived truncated leaf syndrome and wild type oil palm seedlings. Mineral analysis confirmed that Boron, Zinc and chlorophyll levels were significantly lower in truncated leaf syndrome leaves than those of wild type. Hormonal analysis also revealed various cytokinin derivatives such as trans-zeatin, trans-zeatin riboside, trans-zeatin O-glucoside and trans-zeatin riboside 5??mono phosphate were significantly higher in truncated leaf syndrome leaves compared to wild type leaves. Brassinolide level was also significantly higher in truncated leaf syndrome leaves than those of the wild type. These observations suggest that the truncated leaf syndrome abnormality could be associated to high cytokinin and brassinosteroid production which affects the uptake of Boron and Zinc.     

Monthly variations in drug-induced gastric ulcers in rats

Clinical evidence suggests that there may be some relationship between the occurrence of peptic ulcers and the season of the year. As little experimental work has been carried out on this subject, three drugs commonly used to induce experimental ulcers in rats (acetylsalicylic acid, 300 mg/kg; phenylbutazone, 200 mg/kg; reserpine, 10 mg/kg) were tested every month for one year under standardised experimental conditions (T_a, RH, LD 12:12). In rats given phenylbutazone the maximum area of ulceration was found in October and December, and in rats given acetylsalicylic acid in February and March. In rats given reserpine, there were no significant monthly variations. An influence of climatic factors on ulcer induction cannot be completely excluded. Endogenous conditions might also account for the monthly differences in ulceration.     

Alleviation of Liver Dysfunction,Oxidative Stress,and Inflammation Underlines the Protective Effects of Polysaccharides from Cordyceps cicadae on High Sugar/High Fat Diet-Induced Metabolic Syndrome in Rats

This study investigated the protective effects of two polysaccharides (CPA-1 and CPB-2) from Cordyceps cicadae against high fructose/high fat diet (HF/HFD) induced obesity and metabolic disorders in rats. Rats were either fed with normal diet or HF/HFD and treated with CPA-1 and CPB-2 (100 and 300 mg/kg) for 11 weeks. Administration of CPA-1 and CPB-2 significantly and dose dependently reduced body and liver weight, insulin and glucose tolerance, serum insulin and glucose levels. Furthermore, serum and hepatic lipid profiles, liver function enzymes and proinflammatory cytokines (TNF-α, IL-1β and IL-6) were markedly reduced. Additionally, CPA-1 and CPB-2 treatment alleviated hepatic oxidative stress by reducing lipid peroxidation level (MDA) and upregulating glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) activities as well as ameliorated histological alterations through the reduction of hepatic lipid accumulation. These results suggested that the polysaccharides from C. cicadae showed protective effects against HF/HFD induced metabolic disturbances and may be considered as a dietary supplement for treating obesity.     

Optimal Sequence of Irinotecan and Oxaliplatin-Based Regimens in Metastatic Colorectal Cancer: A Population-Based Observational Study

The optimal sequence of irinotecan and oxaliplatin-based regimens for metastatic colorectal cancer remains unclear. We conducted a population-based observational study by retrospectively reviewing records from Taiwan’s National Health Insurance Research Database to explore this issue. Patients aged ≥20 years with metastatic colorectal cancer newly diagnosed between 2004 and 2008 (n = 9490) were enrolled in current study. Among these 9490 patients, 3895 patients (41.04%) did not receive any chemotherapy within the first three months after catastrophic illness registration. Patients who received best supportive care were older and had higher Charlson comorbidity indexes and incidences of comorbidities than those who received irinotecan-based regimens, oxaliplatin-based regimens, and 5-fluorouracil/capecitabine alone. Patients who received irinotecan followed by oxaliplatin-based regimens and those who received the reverse sequence were further stratified into arm A (n = 542) and arm B (n = 1156), respectively. The median first time to next treatment was not significantly different between arm A and arm B (210 days vs. 196 days; p = 0.17). However, the median second time to next treatment was longer in arm A than in arm B (155 days vs. 123 days; p = 0.006), which translated into a better overall survival (487 days vs. 454 days; p = 0.02). The crossover rate was higher in arm A than in arm B (47.84% vs. 41.61%; p<0.001). Multivariate Cox regression analyses showed that overall survival was comparable between the two chemotherapy sequences (p = 0.27). Our study suggested that irinotecan followed by oxaliplatin-based regimens might be a better chemotherapy treatment option for metastatic colorectal cancer than the reverse sequence given the higher crossover rate and potential overall survival benefit.     

Quantification of müllerian inhibiting substance in developing chick gonads by a competitive enzyme-linked immunosorbent assay

An immunoblotting method was used to purify a Müllerian-inhibiting substance (MIS)-specific antiserum. The serum was used to quantify the content of MIS in developing chick gonads by competitive enzyme-linked immunosorbent assay. From embryonic stages to the eleventh week after hatching, male chicken testes have a high content of MIS in the following two stages: (1) from the sixth to the eighth day and from the fourteenth to the twentieth day of incubation, and (2) from the second to the eighth week after hatching. The high content of MIS in the early embryonic stage is closely correlated with the natural pattern of Müllerian duct regression observed in the male embryo. From the sixth to the twelfth day of incubation, the female right ovary contains a higher content of MIS than that of the left ovary. Up to the fourteenth day of incubation, the content of MIS in the left ovary reaches maximum levels and then declines. The combination of MIS from right and left ovaries was found to be highest in the ninth to the fourteenth day of incubation, when the regression of the right Müllerian duct reached its highest peak. However, the question of the inability of MIS to cause regression of the female left Müllerian duct and the caudal part of the right duct is raised and discussed. The hypothesis that prenatal estrogenic hormone (diethylstilbestrol) protects the Müllerian duct has been reevaluated. It was found that estrogen does not reduce the MIS content in prenatally treated gonads.     

The androgen-dependent mouse seminal vesicle secretory protein IV: characterization and complementary deoxyribonucleic acid cloning

Seminal vesicle secretory protein IV of a mouse has been isolated, and the cDNA coding for its mRNA has been cloned and sequenced. The 556-nucleotides encode 16 amino acid signal peptides and 92 residues of mature protein. Considerable homology between mouse and rat SVS IV cDNA was found. In the leader peptide and 3'-noncoding region there is 92% and 85% homology, respectively. The other regional homologies are 86% for the first 12, 68.5% for the last 35, and 40% for the middle 44 amino acids. The expression of mouse SVS IV mRNA is under the control of androgen. Administration of testosterone to castrated mice resulted in induction of the mRNA level to 50% of the mature male in 96 h of hormone treatment. Secretion of the protein after testosterone injection follows a similar pattern.     

Reaction of nucleic acids with cis-diamminedichloroplatinum(II): interstrand cross-links

In the reaction of cis-diamminedichloroplatinum(II) (cis-DDP) with double-helical (dC-dG)4.(dC-dG)4 or (dC-dG)5.(dC-dG)5, intrastrand and interstrand cross-links between two guanine residues are formed. This is shown by gel electrophoresis in denaturing conditions of the reaction products and by high-performance liquid chromatography (HPLC) analysis of the products digested with nuclease P1. In the reaction of cis-DDP and poly(dG-dC).poly(dG-dC), at relatively low levels of platination, it is mainly interstrand cross-links between two guanine residues that are formed. This is shown by HPLC analysis of the nuclease P1 digest and by gel electrophoresis in denaturing and nondenaturing conditions of the platinated polymer after cleavage with the restriction enzyme HhaI. Moreover, the antibodies to platinated poly(dG-dC).poly(dG-dC) cross-react with the interstrand cross-linked (dC-dG)4 or (dC-dG)5 but not with the intrastrand cross-linked (dC-dG)4 or (dC-dG)5. These antibodies cross-react with platinated natural DNA. The amount of interstrand cross-links deduced from radioimmunoassays (0.5% of the total bound platinum) is lower than that (2%) deduced by gel electrophoresis in denaturing conditions of a platinated DNA restriction fragment. By gel electrophoresis, it is also shown that in vitro the isomer trans-DDP is more efficient in forming interstrand cross-links than cis-DDP.