Follicle stimulating hormone controls granulosa cell glutamine synthesis to regulate ovulation.

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility. Inadequate understanding of the ovulation drivers hinders PCOS intervention. Herein, we report that follicle stimulating hormone (FSH) controls follicular fluid (FF) glutamine levels to determine ovulation. Murine ovulation starts from FF-exposing granulosa cell (GC) apoptosis. FF glutamine, which decreases in pre-ovulation porcine FF, elevates in PCOS patients FF. High-glutamine chow to elevate FF glutamine inhibits mouse GC apoptosis and induces hormonal, metabolic, and morphologic PCOS traits. Mechanistically, follicle-development-driving FSH promotes GC glutamine synthesis to elevate FF glutamine, which maintain follicle wall integrity by inhibiting GC apoptosis through inactivating ASK1-JNK apoptotic pathway. FSH and glutamine inhibit the rapture of cultured murine follicles. Glutamine removal or ASK1-JNK pathway activation with metformin or AT-101 reversed PCOS traits in PCOS models that are induced with either glutamine or EsR1-KO. These suggest that glutamine, FSH, and ASK1-JNK pathway are targetable to alleviate PCOS.

Validity of total polar compound and its three components in monitoring the evolution of epoxy fatty acids in frying oil: Fast food restaurant conditions.

This study evaluated the validity of total polar compounds (TPC) and its three components in monitoring the evolution of epoxy fatty acids in frying oil under fast food restaurant conditions. The content of epoxy fatty acids can be predicted using the TPC rather than oxidized triglyceride monomer. When TPC content reached 24 g/100 g, 25 g/100 g, and 27 g/100 g, the epoxy fatty acid content in oil was found to be 1.47-3.63 mg/g, 1.58-4.06 mg/g, and 1.83-5.08 mg/g, respectively. More epoxy fatty acids were generated in high oleic sunflower oil than in canola and cottonseed oil during frying. At current discarding points of TPC 24-27 g/100 g, its epoxy fatty acid content was 3.63-5.08 mg/g, which was lower than the limit of 7 mg/g recommended by Max Rubner-Institut in Germany. Our results indicate that the risk of epoxy fatty acids can be monitored using the current TPC index.

2,3,7,8-Tetrachlorodibenzo-p-dioxin induces liver lipid metabolism disorder via the ROS/AMPK/CD36 signaling pathway.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is widely considered as the most toxic and common carcinogen in the world. Exposure to TCDD causes liver lipid metabolism disorder and steatosis. However, the molecular mechanism of TCDD-induced liver lipid accumulation is not completely clear. Here, we found that a 5 µg/kg TCDD exposure for 3 weeks induced hepatocyte lipid deposition, increased CD36 expression, and promoted AMP-activated protein kinase (AMPK) ɑ phosphorylation in the liver of C57BL/6J mice. Furthermore, sulfo-N-succinimidyl oleate, a CD36 inhibiter, blunted TCDD-induced lipid deposition in Huh7 cells, confirming the critical role of CD36 in TCDD-induced hepatic steatosis. In terms of molecular mechanisms, we found that TCDD exposure increased reactive oxygen species (ROS) levels in Huh7 cells, which activated AMPK. Moreover, the activated AMPK upregulated CD36 expression. Therefore, we can see that the increase in CD36 expression induced by TCDD was regulated by ROS/AMPK/CD36 signaling pathway. Our results help to clarify the molecular mechanism of TCDD-induced hepatic steatosis.

Investigation of oxidized triglyceride monomer (oxTGM) produced in deteriorated soybean oil at frying temperatures: A kinetic study.

This work evaluated the feasibility of total polar compound (TPC) and its five components to monitor the deterioration of soybean oil at frying temperatures, and traditional indicators were used as a reference. The preliminary correlation analysis showed that polar compounds accumulated earlier than classical oxidation products like the peroxide value (PV). Equations for two types of characteristic kinetic time, the induction time (turning point of sigmoid curve) and intersection time (intersection point of two tangent lines representing the initiation and propagation reaction), were also derived. Their mathematical difference and relationship were then evaluated. Based on the kinetic analysis, the overall cumulative process of oxidation products of triglycerides (oxTGM) was found to be 2.35%-12.35% earlier than that of fatty acids (PV). Our results supported the index of oxTGM in TPC to be a better indicator to monitor the deterioration of heated edible oil.

The effects of nutritional support team intervention on postoperative immune function, nutritional statuses, inflammatory responses, clinical outcomes of elderly patients with gastric cancer.

BACKGROUND: To explore the effects of nutrition support team (NST) intervention on elderly patients with gastric cancer (GC). METHODS: The elderly GC patients (tumor stage I/II/III), admitted to our department from January 2015 to September 2021, were retrospectively analyzed and divided into NST group and traditional nutrition (TN) group according to nutritional management methods. The immune, inflammatory, nutrition-related indices, postoperative recovery and long-term prognosis of two groups were analyzed. RESULTS: A total of 258 elderly GC patients were included (NST group, n = 125; TN group, n = 133). After propensity score matching (PSM) in ratio of 1:1, 73 pairs of patients were matched. There were statistically significant differences in CD3 and CD4 level postoperative one month and IgG level postoperative one week between NST group and TN group (P < 0.05). There was no significant differences in serum CRP and IL-6 levels preoperative one day, postoperative one week and one month between two groups (P > 0.05). There were significant differences in body mass index (BMI) between the two groups postoperative one month (P < 0.05). The rate of infectious complications in TN group was significantly higher than that in NST group (P < 0.05). There was no statistically significant differences in 3-year relapse-free survival (RFS) or 3-year overall survival (OS) between NST group and TN group (P > 0.05). CONCLUSIONS: Compared with TN management, NST intervention might be benefit to the immune function recovery and nutritional status, but there was no evidence that NST could improve the prognosis of elderly GC patients.

Methylene-bridge tryptophan fatty acylation regulates PI3K-AKT signaling and glucose uptake.

Protein fatty acylation regulates numerous cell signaling pathways. Polyunsaturated fatty acids (PUFAs) exert a plethora of physiological effects, including cell signaling regulation, with underlying mechanisms to be fully understood. Herein, we report that docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) regulate PI3K-AKT signaling by modifying PDK1 and AKT2. DHA-administered mice exhibit altered phosphorylation of proteins in signaling pathways. Methylene bridge-containing DHA/EPA acylate δ1 carbon of tryptophan 448/543 in PDK1 and tryptophan 414 in AKT2 via free radical pathway, recruit both the proteins to the cytoplasmic membrane, and activate PI3K signaling and glucose uptake in a tryptophan acylation-dependent but insulin-independent manner in cultured cells and in mice. DHA/EPA deplete cytosolic PDK1 and AKT2 and induce insulin resistance. Akt2 knockout in mice abrogates DHA/EPA-induced PI3K-AKT signaling. Our results identify PUFA's methylene bridge tryptophan acylation, a protein fatty acylation that regulates cell signaling and may underlie multifaceted effects of methylene-bridge-containing PUFAs.

The factors related to failure of Enhanced Recovery after Surgery (ERAS) in colon cancer surgery.

PURPOSE: Enhanced Recovery after Surgery has been proven effective for patients with gastrointestinal cancer. But radical enhanced recovery could also lead to adverse clinical outcomes. Compared with reports on the estimation of successful implementation of enhanced recovery, studies on risk factors of enhanced recovery failure are still lacking. METHODS: A retrospective analysis was carried out on 102 patients in ERAS who underwent elective colon cancer surgery. This study included 102 patients with colon cancer between 2015 and 2019, defining enhanced recovery failure as postoperative length of stay over 10 days, stay in ICU over 24 h after surgery, reoperation, death, or unplanned readmission within 30 days after surgery. Univariate and multivariate analyses were performed to explore potential risk factors of failure. RESULTS: Aged ≥ 75, open operation, number of drainage tube over 1, re-urethral catheterization, and Clavien-Dindo grade over 2 were associated with ERAS failure, according to univariate analysis. Multivariate analysis showed that age ≥ 75 [OR 7.231; P = 0.009]; open operation (OR 3.599; P = 0.021); and number of drainage tube over 1 (OR 3.202; P = 0.020) were independent risk factors for ERAS failure. CONCLUSIONS: We found age ≥ 75, open operation, and number of drainage tube over 1 are independent risk factors associated with ERAS failure after colon cancer surgery.

Resveratrol Inhibits Human Visceral Preadipocyte Proliferation and Differentiation in vitro.

Visceral obesity is a high-risk factor for diabetes and metabolic syndrome. Resveratrol, a natural polyphenolic compound, has been reported to inhibit preadipocyte differentiation. However, the effect of resveratrol on human visceral preadipocyte (HPA-v) differentiation remains largely unknown. LIM domain only 3 (LMO3) promotes human preadipocyte differentiation by enhancing peroxisome proliferator-activated receptor γ (PPARγ) transcriptional activity, which is the master regulator of adipogenesis. The purpose of our study was to determine the effect of resveratrol (0-50 µM) on HPA-v proliferation and differentiation, and the role of LMO3 in resveratrol-mediated regulation of HPA-v differentiation. Resveratrol inhibited HPA-v proliferation and differentiation in a dose-dependent manner, and significantly decreased the mRNA expression levels of PPARG, CCAAT/enhancer-binding protein α (CEBPA), fatty acid-binding protein 4 (FABP4), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) (p < 0.05) at 10, 20, and 50 µM. The mRNA and protein levels of LMO3 were significantly reduced by ≥20 µM resveratrol (p < 0.05), and overexpression of LMO3 partially attenuated resveratrol-induced reduction of HPA-v differentiation by enhancing the PPARG transcriptional activity. Together, our study suggested that resveratrol reduced HPA-v proliferation and differentiation, as well as LMO3, which was partially responsible for the reduction of resveratrol-mediated adipocyte differentiation.

Triptonide acts as a novel antiprostate cancer agent mainly through inhibition of mTOR signaling pathway.

BACKGROUND: The increasing incidence of prostate cancer (PCa) indicates an urgent need for the development of new effective drugs in PCa therapy. Triptonide has been reported to have a strong inhibition activity in cancers through screening of Chinese herbal medicine. This study aims to investigate the effects of triptonide on anti-PCa activity and its mechanisms. METHODS: Three human advanced PCa cell lines PC3, DU145, and LNCap, and a human normal prostate epithelial cell line RWPE were treated with a range (0, 1.25, 2.5, 5, 10, 20, 40, 80, 160, and 320 nM) of triptonide concentrations for 72 hours respectively. Then, cell viability was assessed by cell counting kit-8. PCa cells were treated with different doses (0-20 nM) of triptonide for 72 hours. Cell cycle and apoptosis were assessed by flow cytometry assays. Nude mice bearing human PCa xenografts were intraperitoneally injected daily with either triptonide (10 mg/kg/d) or phosphate-buffered saline as a control for 35 days. RNA-sequencing (RNA-seq) was performed by an Illumina Hiseq Sequencing platform and confirmed by a real-time polymerase chain reaction. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and ingenuity pathway analysis were used to analyze RNA-seq results. RESULTS: Triptonide effectively inhibits the proliferation of human PCa cells PC3, DU145, and LNCap in vitro with their IC50 values as 11.961, 10.259, and 12.012 nM, respectively. Triptonide (10 mg/kg) potently inhibits the growth of PCa cell xenografts in vivo at an inhibition rate of over 97.95%. Treatment with triptonide (5 nM) significantly promotes cell apoptosis and retaining cell-cycle arrest in the G2/M phase. RNA-seq data revealed that total of 936 genes were upregulated or downregulated in triptonide treated. Moreover, the phosphorylation of mechanistic target of rapamycin (mTOR) and the downstream protein p70S6K were both inhibited, most obviously in PCa cells. CONCLUSIONS: Our findings suggest that triptonide can efficaciously suppress PCa growth in vitro and in vivo via inhibiting the phosphorylation of mTOR and the activities of related downstream signaling pathways.

SIRT1 downregulation mediated Manganese-induced neuronal apoptosis through activation of FOXO3a-Bim/PUMA axis.

Manganese (Mn) is an essential trace element. Excessive exposure to Mn may lead to neuronal death and neurodegenerative disorders. Accumulating evidence has shown that silent mating type information regulation 2 homolog 1 (SIRT1) plays a vital role in brain damage. However, whether aberrant SIRT1 levels contribute to Mn-induced neurotoxicity remains unknown. In this study, we report the important role of SIRT1 downregulation during Mn-induced neuronal apoptosis. Mn was found to downregulate SIRT1 protein levels in the rat pheochromocytoma (PC12) cells and mouse brain tissues. Mn enhanced SIRT1 protein degradation and downregulated its gene expression. Furthermore, Mn induced cell apoptosis in a dose-dependent manner both in vitro and in vivo, and resulted in an increase in forkhead box O (FOXO) 3a expression and acetylation. SIRT1 activation by resveratrol clearly attenuated Mn-triggered apoptosis and FOXO3a activation. Mn markedly increased the expression of Bcl-2 interacting mediator of cell death (Bim) and p53-up-regulated modulator of apoptosis (PUMA), whereas downregulation of FOXO3a significantly inhibited their upregulation and subsequent apoptosis. In summary, we determined that Mn downregulated SIRT1 by multiple mechanisms, thus led to apoptosis via activation of the FOXO3a-Bim/PUMA axis in PC12 cells. These findings on the impact of Mn on SIRT1 may lead to an improved understanding of Mn-induced neurotoxicity and provide a molecular target to antagonise Mn-associated neuronal damage.

miR-17-5p Regulates Differential Expression of NCOA3 in Pig Intramuscular and Subcutaneous Adipose Tissue.

Fat distribution affects economic value in pork production. Intramuscular adipose tissue (IMAT) improves meat quality, whereas subcutaneous adipose tissue (SCAT) is usually regarded as waste. In the present study, we analyzed IMAT/SCAT (I/S) ratios in each pig. Individuals selected from a population of 1200 Suhuai pigs were divided into two cohorts; those with high I/S ratios and those with low I/S ratios, and correlations between nuclear Receptor Co-activator 3 (NCOA3), a critical gene involved in regulating fat accumulation, and fat distribution were investigated. The ratio of IMAT NCOA3 to SCAT NCOA3 expression levels (NCOA3I/NCOA3S) was higher in the high I/S group compared with the low I/S group. The NCOA3 expression level in fat tissue was positively correlated with fat deposition. miR-17-5p was identified as a putative regulator of NCOA3 based on bioinformatics prediction analysis followed by gene expression analysis. The miR-17-5pI/miR-17-5pS ratio was negatively correlated with the NCOA3I/NCOA3S ratio. The predicted relationship between miR-17-5p and NCOA3 was further verified by dual luciferase activity assays, qPCR, and western blots. Overexpression of miR-17-5p in intramuscular preadipocytes inhibited NCOA3 expression and reduced preadipocyte differentiation. FABP4 and PPARG expression were also significantly decreased, as was triglyceride content. Meanwhile, knockdown of miR-17-5p significantly increased NCOA3 expression and promoted intramuscular preadipocyte differentiation. Based on these results, we propose that differential expression of NCOA3 in pig intramuscular and subcutaneous adipose tissue is regulated by miR-17-5p.

Synthesis, characterization and evaluation cytotoxic activity of silver nanoparticles synthesized by Chinese herbal Cornus officinalis via environment friendly approach.

Cornus officinalis has been widely used as a precious herb and as the tonic food to improve kidney function in China. Its fruits have been used in many traditional Chinese medicine prescriptions to treat kidney diseases, diabetes, cancer and shock. In this study, a new eco-friendly approach for green synthesis of silver nanoparticles (AgNPs) by using the fruits of Cornus officinalis aqueous extract as a reducing and stabilizing agent. The so-synthesized AgNPs showed quasi-spherical in shape with uniform dispersal and an average mean size of 11.7nm. Water soluble biomolecules such as flavonoids and/or anthocyanins from the extract played important roles in the nanoparticles formation. The AgNPs displayed distinctive cytotoxicity activities against human prostate cancer (PC-3) and human liver cancer (HepG2) cell lines. The results provided a low cost, nontoxic and eco-friendly approach for synthesizing metal nanoparticles to explore alternative anticancer agents on the way fighting against cancer in future.

Association between early bacterial carriage and otitis media in Aboriginal and non-Aboriginal children in a semi-arid area of Western Australia: a cohort study.

BACKGROUND: Streptococcus pneumoniae (Pnc), nontypeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) are the most important bacterial pathogens associated with otitis media (OM). Previous studies have suggested that early upper respiratory tract (URT) bacterial carriage may increase risk of subsequent OM. We investigated associations between early onset of URT bacterial carriage and subsequent diagnosis of OM in Aboriginal and non-Aboriginal children living in the Kalgoorlie-Boulder region located in a semi-arid zone of Western Australia. METHODS: Aboriginal and non-Aboriginal children who had nasopharyngeal aspirates collected at age 1- < 3 months and at least one clinical examination for OM by an ear, nose and throat specialist before age 2 years were included in this analysis. Tympanometry to detect middle ear effusion was also performed at 2- to 6-monthly scheduled field visits from age 3 months. Multivariate regression models were used to investigate the relationship between early carriage and subsequent diagnosis of OM controlling for environmental factors. RESULTS: Carriage rates of Pnc, NTHi and Mcat at age 1- < 3 months were 45%, 29% and 48%, respectively, in 66 Aboriginal children and 14%, 5% and 18% in 146 non-Aboriginal children. OM was diagnosed at least once in 71% of Aboriginal children and 43% of non-Aboriginal children. After controlling for age, sex, presence of other bacteria and environmental factors, early nasopharyngeal carriage of NTHi increased the risk of subsequent OM (odds ratio = 3.70, 95% CI 1.22-11.23) in Aboriginal children, while Mcat increased the risk of OM in non-Aboriginal children (odds ratio = 2.63, 95% CI 1.32-5.23). Early carriage of Pnc was not associated with increased risk of OM. CONCLUSION: Early NTHi carriage in Aboriginal children and Mcat in non-Aboriginal children is associated with increased risk of OM independent of environmental factors. In addition to addressing environmental risk factors for carriage such as overcrowding and exposure to environmental tobacco smoke, early administration of pneumococcal-Haemophilus influenzae D protein conjugate vaccine to reduce bacterial carriage in infants, may be beneficial for Aboriginal children; such an approach is currently being evaluated in Australia.