Qili Qiangxin (QLQX) capsule as a multi-functional traditional Chinese medicine in treating chronic heart failure (CHF): A review of ingredients, molecular, cellular, and pharmacological mechanisms.

Chronic heart failure (CHF) is a key part of cardiovascular continuum. Under the guidance of the theory of vessel-collateral doctrine, the present study proposes therapeutic benefits of Qili Qiangxin (QLQX) capsules, an innovative Chinese medicine, on chronic heart failure. The studies show that multiple targets of the drug on CHF, including enhancing myocardial systole, promoting urine excretion, inhibiting excessive activation of the neuroendocrine system, preventing ventricular remodeling by inhibiting inflammatory response, myocardial fibrosis, apoptosis and autophagy, enhancing myocardial energy metabolism, promoting angiogenesis, and improving endothelial function. Investigation on the effects and mechanism of the drug is beneficial to the treatment of chronic heart failure (CHF) through multiple targets and/or signaling pathways. Meanwhile, it provides new insights to further understand other refractory diseases in the cardiovascular continuum, and it also has an important theoretical and practical significance in enhancing prevention and therapeutic effect of traditional Chinese medicine for these diseases.

Effects of gut microbiota on omega-3-mediated ovary and metabolic benefits in polycystic ovary syndrome mice.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder that frequently exhibits low-grade inflammation, pro-oxidant activity, and gut dysbiosis. PCOS has become one of the leading causes of female infertility worldwide. Recently, omega-3 polyunsaturated fatty acids (PUFAs) have been proven to benefit metabolic disorders in PCOS patients. However, its roles in the regulation of metabolic and endocrinal balances in PCOS pathophysiology are not clear. In the present study, we aimed to explore how omega-3 PUFAs alleviate ovarian dysfunction and insulin resistance in mice with dehydroepiandrosterone (DHEA)-induced PCOS by modulating the gut microbiota. METHODS: We induced PCOS in female mice by injecting them with DHEA and then treated them with omega-3 PUFAs. 16S ribosomal DNA (rDNA) amplicon sequencing, fecal microbiota transplantation (FMT) and antibiotic treatment were used to evaluate the role of microbiota in the regulation of ovarian functions and insulin resistance (IR) by omega-3 PUFAs. To further investigate the mechanism of gut microbiota on omega-3-mediated ovarian and metabolic protective effects, inflammatory and oxidative stress markers in ovaries and thermogenic markers in subcutaneous and brown adipose tissues were investigated. RESULTS: We found that oral supplementation with omega-3 PUFAs ameliorates the PCOS phenotype. 16S rDNA analysis revealed that omega-3 PUFA treatment increased the abundance of beneficial bacteria in the gut, thereby alleviating DHEA-induced gut dysbiosis. Antibiotic treatment and FMT experiments further demonstrated that the mechanisms underlying omega-3 benefits likely involve direct effects on the ovary to inhibit inflammatory cytokines such as IL-1ß, TNF-α and IL-18. In addition, the gut microbiota played a key role in the improvement of adipose tissue morphology and function by decreasing multilocular cells and thermogenic markers such as Ucp1, Pgc1a, Cited and Cox8b within the subcutaneous adipose tissues. CONCLUSION: These findings indicate that omega-3 PUFAs ameliorate androgen-induced gut microbiota dysbiosis. The gut microbiota plays a key role in the regulation of omega-3-mediated IR protective effects in polycystic ovary syndrome mice. Moreover, omega-3 PUFA-regulated improvements in the ovarian dysfunction associated with PCOS likely involve direct effects on the ovary to inhibit inflammation. Our findings suggest that omega-3 supplementation may be a promising therapeutic approach for the treatment of PCOS by modulating gut microbiota and alleviating ovarian dysfunction and insulin resistance.

Effects of n-3 PUFA supplementation on oocyte in vitro maturation in mice with polycystic ovary syndrome.

n-3 PUFAs are classic antioxidant that can be used to treat follicular dysplasia and hyperinsulinemia caused by excessive oxidative stress in PCOS women. To investigate the effect of n-3 PUFA supplementation on the oocyte quality of polycystic ovary syndrome (PCOS) mice during in vitro maturation, a PCOS mouse model was established by dehydroepiandrosterone (DHEA). The GV oocytes of the control and PCOS groups were collected and cultured in vitro with or without n-3 PUFAs. After 14 h, the oocytes were collected. Our data demonstrated that the oocyte maturation rate of PCOS mice significantly increased after the addition of 50 µM n-3 PUFAs. The results of immunofluorescence showed that the abnormal rates of spindles and chromosomes in the PCOS + n-3 PUFA group were lower than those in the PCOS group. The mRNA expression of an antioxidant-related gene (Sirt1) and DNA damage repair genes (Brca1/Msh2) was found to be significantly rescued after n-3 treatment. Additionally, the results of living cell staining showed that the addition of n-3 PUFAs could reduce the levels of reactive oxygen species and mitochondrial superoxide in PCOS oocytes. In conclusion, the addition of 50 µM n-3 PUFAs during the in vitro maturation of PCOS mouse oocytes can improve the maturation rate by reducing the level of oxidative stress and the rate of spindle/chromosome abnormalities, providing valuable support during the IVM process.

Bioactive peptides from scorpion venoms: therapeutic scaffolds and pharmacological tools.

Evolution and natural selection have endowed animal venoms, including scorpion venoms, with a wide range of pharmacological properties. Consequently, scorpions, their venoms, and/or their body parts have been used since time immemorial in traditional medicines, especially in Africa and Asia. With respect to their pharmacological potential, bioactive peptides from scorpion venoms have become an important source of scientific research. With the rapid increase in the characterization of various components from scorpion venoms, a large number of peptides are identified with an aim of combating a myriad of emerging global health problems. Moreover, some scorpion venom-derived peptides have been established as potential scaffolds helpful for drug development. In this review, we summarize the promising scorpion venoms-derived peptides as drug candidates. Accordingly, we highlight the data and knowledge needed for continuous characterization and development of additional natural peptides from scorpion venoms, as potential drugs that can treat related diseases.

Atorvastatin remodels lipid distribution between liver and adipose tissues through blocking lipoprotein efflux in fish.

The regulation of cholesterol metabolism in fish is still unclear. Statins play important roles in promoting cholesterol metabolism development in mammals. However, studies on the role of statins in cholesterol metabolism in fish are currently limited. The present study evaluated the effects of statins on cholesterol metabolism in fish. Nile tilapia (Oreochromis niloticus) were fed on control diets supplemented with three atorvastatin levels (0, 12, and 24 mg/kg diet, ATV0, ATV12, and ATV24, respectively) for 4 wk. Intriguingly, the results showed that both atorvastatin treatments increased hepatic cholesterol and triglyceride contents mainly through inhibiting bile acid synthesis and efflux, and compensatorily enhancing cholesterol synthesis in fish liver (P < 0.05). Moreover, atorvastatin treatment significantly inhibited hepatic very-low-density lipoprotein (VLDL) assembly and thus decreased serum VLDL content (P < 0.05). However, fish treated with atorvastatin significantly reduced cholesterol and triglycerides contents in adipose tissue (P < 0.05). Further molecular analysis showed that atorvastatin treatment promoted cholesterol synthesis and lipogenesis pathways, but inhibited lipid catabolism and low-density lipoprotein (LDL) uptake in the adipose tissue of fish (P < 0.05). In general, atorvastatin induced the remodeling of lipid distribution between liver and adipose tissues through blocking VLDL efflux from the liver to adipose tissue of fish. Our results provide a novel regulatory pattern of cholesterol metabolism response caused by atorvastatin in fish, which is distinct from mammals: cholesterol inhibition by atorvastatin activates hepatic cholesterol synthesis and inhibits its efflux to maintain cholesterol homeostasis, consequently reduces cholesterol storage in fish adipose tissue.

Jinlida Granules Reduce Obesity in db/db Mice by Activating Beige Adipocytes.

Recent studies indicate existence of beige adipocytes in adults. Upon activation, beige adipocytes burn energy for thermogenesis and contribute to regulation of energy balance. In this study, we have analyzed whether Jinlida granules (JLD) could activate beige adipocytes. JLD suspended in 0.5% carboxymethyl cellulose (CMC) was gavage fed to db/db mice at a daily dose of 3.8 g/kg. After 10 weeks, body weight, biochemical, and histological analyses were performed. In situ hybridization, immunofluorescence, and western blotting were conducted to test beige adipocyte activation in mice. X9 cells were induced with induction medium and maintenance medium containing 400 µg/mL of JLD. After completion of induction, cells were analyzed by Nile red staining, time polymerase chain reaction (PCR), western blotting, and immunofluorescence to understand the effect of JLD on the activation of beige adipocytes. A molecular docking method was used to preliminarily identify compounds in JLD, which hold the potential activation effect on uncoupling protein 1 (UCP1). JLD treatment significantly improved obesity in db/db mice. Biochemical results showed that JLD reduced blood glucose (GLU), triglyceride (TG), and low-density lipoprotein cholesterol (LDL) levels as well as liver aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in mice. Hematoxylin and eosin staining (H&E) showed that JLD reduced hepatocyte ballooning changes in the liver. Immunofluorescence showed that JLD increased the expression of the thermogenic protein, UCP1, in the beige adipose tissue of mice. JLD also increased the expression of UCP1 and inhibited the expression of miR-27a in X9 cells. Molecular docking results showed that epmedin B, epmedin C, icariin, puerarin, and salvianolic acid B had potential activation effects on UCP1. The results suggest that JLD may activate beige adipocytes by inhibiting miR-27a expression, thereby promoting thermogenesis in beige adipocytes. This study provides a new pharmacological basis for the clinical use of JLD.

Core-Shell-Structured Covalent-Organic Framework as a Nanoagent for Single-Laser-Induced Phototherapy.

Imaging-guided phototherapy, including photothermal therapy and photodynamic therapy, has been emerging as a promising avenue for precision cancer treatment. However, the utilization of a single laser to induce combination phototherapy and multiple-model imaging remains a great challenge. Herein, we report, the first of its kind, a covalent-organic framework (COF)-based magnetic core-shell nanocomposite, Fe3O4@COF-DhaTph, that is used as a multifunctional nanoagent for cancer theranostics under single 660 nm NIR irradiation. Besides significant photothermal and photodynamic effects, it still permits triple-modal magnetic resonance/photoacoustic/near-infrared thermal (IR) imaging due to its unequaled magnetic and optical performance. We believe that the results obtained herein could obviously promote the application of COF-based multifunctional nanomaterials in cancer theranostics.

Electroacupuncture Reduces Oocyte Number and Maintains Vascular Barrier Against Ovarian Hyperstimulation Syndrome by Regulating CD200.

Ovarian hyperstimulation syndrome (OHSS) is a common complication caused by ovulatory stimulation therapy, which manifests as an increase in ovarian volume, an increase in the number of oocytes retrieved, and increased vascular permeability throughout the body and especially in ovarian tissue. In our previous study, we found that electroacupuncture (EA) could prevent the progression of OHSS, by mainly affecting ovary. However, the specific molecules and the mechanism of this process were still unknown. In order to explore the underlying mechanism, OHSS rat model was established and EA treatment was performed, which was followed by proteomic analysis of ovaries. Results showed a significant increase in the expression level of CD200 in the ovaries of OHSS group treated with EA than those of OHSS group. Clinical data showed that the level of CD200 in follicular fluid was negatively correlated with the number of oocytes retrieved and serum E2 level. Further in vitro experiments showed a concentration-dependent role of human chorionic gonadotropin (hCG) in reducing CD200 and CD200R levels, and increasing inflammatory cytokine levels in cultured KGN cells. In human umbilical vein endothelial cells (HUVECs), the vascular barrier function was improved by CM (cultural medium from KGN cell) which treated with CD200Fc (CD200R agonist). Meanwhile, the results of in vivo experiments indicated that EA reduced the number of ovarian corpora lutea, decreased inflammatory response, and improved the vascular barrier function by increasing the expression of CD200 and CD200R in rat ovaries. These findings suggest that EA treatment may reduce oocyte number and maintain vascular barrier against OHSS through ovarian anti-inflammatory response mediated by CD200. Therefore, this study is the first to identify CD200 as a main of EA in the ovary and elucidate the possible mechanism of EA on preventing and treating OHSS, which provide a scientific basis for CD200 as an effector and indicator in EA treatment.

Dietary supplementation of 25-hydroxycholecalciferol increases tibial mass by suppression bone resorption in meat ducks.

Leg problems often result from the rapid weight gain and poor bone quality in modern ducks, leading to a high risk of fractures and continuous pain. We hypothesized that improving bone quality in combination with delaying weight gain via a low nutrient density (LND) diet probably reverses these skeletal abnormalities. Studies indicated that 25-hydroxycholecalciferol (25-OH-D3), a vitamin D3 metabolite, is effective in treating bone-related disorders. Therefore, Exp. 1 evaluated the effects of 25-OH-D3 on tibial mass of meat ducks. Male meat ducklings were fed a standard nutrient density diet (containing a regular vitamin regimen) without or with 25-OH-D3 at 0.069 mg/kg for 35 d. The results showed that 25-OH-D3 supplementation improved the mineral content, microarchitecture and mechanical properties of tibias, and this companied by a decreased serum bone resorption marker and a concomitant decrement in osteoclast-specific marker genes expression. Subsequently, Exp. 2 was conducted to examine the impacts of 25-OH-D3 incorporating an LND diet on tibial quality of ducks under 2 different vitamin regimens (regular and high). Ducklings were allocated to a 2 × 2 factorial arrangement with 2 kinds of vitamin premixes and without or with 25-OH-D3 at 0.069 mg/kg in LND diets. The high premix had higher levels of all vitamins except biotin than the regular premix. The results demonstrated that high vitamin diets exhibited more significant effects than regular vitamin diets on inhibiting bone turnover and increasing minerals deposition. Tibial mineral content, microarchitecture, and strength of birds under the regular vitamin regimen were increased by 25-OH-D3 supplementation; However, these positive effects were not observed in ducks under the high vitamin regimen. To conclude, 25-OH-D3 supplementation improves tibial mass by suppressing osteoclast-mediated bone resorption in meat ducks, and this positive impact only was observed in regular but not high vitamin regimen when birds fed an LND diet.

Omega-3 polyunsaturated fatty acids alleviate hydrogen sulfide-induced blood-testis barrier disruption in the testes of adult mice.

Hydrogen sulfide (H2S), a gaseous intracellular signal transducer, participates in multiple physiological and pathological conditions, including reproductive conditions, and disrupts spermatogenesis. The blood-testis barrier (BTB) plays a vital role in spermatogenesis. However, the effect of H2S on the BTB and the underlying mechanism remain unclear. Herein, we examined the effect of H2S and omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on the BTB and testicular functions. ICR male mice were randomly divided into the following groups: control, H2S exposure, and H2S exposure with ω-3 PUFAs intervention. The sperm parameters (sperm concentration and sperm motility) declined in the H2S group and improved in the ω-3 intervention group. BTB integrity was severely disrupted by H2S, and the BTB-related gene levels (ZO-1, Occludin, Claudin 11) decreased; ω-3 supplementation could alleviate BTB disruption by upregulating BTB-related genes, and TM4 Sertoli cells had a similar trend in vitro. p38 MAPK phosphorylation was upregulated in the Na2S treatment group and downregulated after ω-3 cotreatment. These findings suggest that H2S can impair the BTB and that ω-3 PUFAs supplementation can attenuate H2S toxicity in the male reproductive system. Our study elucidated the relationship between a gasotransmitter (H2S) and the BTB and identified the potential therapeutic effect of ω-3 PUFAs.

Developmental changes and sex differences in DNA methylation and demethylation in hypothalamic regions of the mouse brain.

DNA methylation is dynamically modulated during postnatal brain development, and plays a key role in neuronal lineage commitment. This epigenetic mark has also recently been implicated in the development of neural sex differences, many of which are found in the hypothalamus. The level of DNA methylation depends on a balance between the placement of methyl marks by DNA methyltransferases (Dnmts) and their removal, which is catalyzed by ten-eleven translocation (Tet) methylcytosine dioxygenases. Here, we examined developmental changes and sex differences in the expression of Tet and Dnmt enzymes from birth to adulthood in two hypothalamic regions (the preoptic area and ventromedial nucleus) and the hippocampus of mice. We found highest expression of all Tet enzymes (Tet1, Tet2, Tet3) and Dnmts (Dnmt1, Dnmt3a, Dnmt3b) in newborns, despite the fact that global methylation and hydroxymethylation were at their lowest levels at birth. Expression of the Dnmt co-activator, Dnmt3l, followed a pattern opposite to that of the canonical Dnmts (i.e., was very low in newborns and increased with age). Tet enzyme activity was much higher at birth than at weaning in both the hypothalamus and hippocampus, mirroring developmental changes in gene expression. Sex differences in Tet enzyme expression were seen in all brain regions examined during the first week of life, whereas Dnmt expression was more balanced between the sexes. Neonatal testosterone treatment of females only partially masculinized enzyme expression. Thus, Tet expression and activity are elevated during neonatal brain development, and may play important roles in sexual differentiation of the brain.

[Repairing effect of wheat-grain moxibustion on thin-type endometrium in rats].

OBJECTIVE: To observe the repairing effects of estrogen and wheat-grain moxibustion on thin-type endometrium in rats and to explore its possible mechanism. METHODS: Forty healthy SPF-grade adult female SD rats were randomly divided into a normal group, a model group, an estrogen group and a moxibustion group according to random number table method, 10 rats in each group. The model of thin-type endometrium was established during estrous period in all the groups except for the normal group. No intervention was given in the normal group. The intragastric administration of 2 mL of 0.9% sodium chloride solution was applied the next day after modeling in the model group. The intragastric administration of 2 mL of estradiol was given the next day after modeling in the estrogen group. The wheat-grain moxibustion was given at "Guanyuan" (CV 4) and "Shenshu" (BL 23) the next day after modeling in the moxibustion group, 7 moxa cones for each acupoint. The treatment in 3 groups was given once a day. After three estrous cycles, the samples were collected during estrous period; the thickness and morphology of endometrium were observed by HE staining; the expressions of vimentin, keratin and vascular endothelial growth factor (VEGF) in endometrium tissue were detected by immunohistochemistry; the expressions of HOXA10 and LIF in endometrium tissue were detected by Western blot. RESULTS: The endometrial thickness in the model group was significantly thinner than that in the normal group (P<0.01); compared with the model group, the endometrial thickness in the estrogen group and the moxibustion group were increased significantly (P<0.05, P<0.01); the endometrial thickness in the moxibustion group was insignificantly higher than that in the estrogen group (P>0.05). The expressions of keratin, vimentin and VEGF in endometrium in the model group were significantly lower than those in the normal group (P<0.01); compared with the model group, the expressions of keratin, vimentin and VEGF in endometrium in the estrogen group and the moxibustion group were significantly increased (P<0.01). The expressions of keratin, vimentin and VEGF in the moxibustion group were insignificantly higher than those in the estrogen group (P>0.05). The expressions of HOXA10 and LIF in endometrium in the model group were significantly lower than those in the normal group (P<0.01); compared with the model group, the expressions of HOXA10 and LIF in endometrium in the estrogen group and moxibustion group were significantly increased (P<0.05). CONCLUSION: The wheat-grain moxibustion could up-regulate the expressions of keratin, vimentin and VEGF in endometrium to improve the endometrial thickness; in addition, it could increase the levels of factors related to endometrial receptivity including HOXA10, LIF, which improves endometrial receptivity and play a repair role.

[Effect on sperm quality of asthenospermia and oligospermia treated with grain-moxibustion combined with medicine therapy].

OBJECTIVE: To observe the clinical effect of grain-moxibustion combined with medicine therapy for asthenospermia and oligospermia. METHODS: A tatal of 60 patients were randomized into an observation group (30 cases) and a control group (30 cases) according to 1︰1 ratio. In the control group, vitamin E capsules were taken orally one capsule each time, twice a day, and Wuzi Yanzong pills 6 g each time, three times a day for a total of 3 months. In the observation group, grain-moxibustion was applied at Guanyuan (CV 4)，Shenshu (BL 23) and Zusanli (ST 36) based on the control group, once a week for 3 months, with a total of 12 times. The sperm concentration and sperm progressive motility were measured by automatic sperm quality analysis system in the two groups, and the clinical effects were compared. Sperm DNA fragmentation index (DFI) in the observation group was measured by sperm nucleus chromosome structure assay (SCSA). RESULTS: ①The sperm concentrations and sperm progressive motilities after 1-month, 2-month and 3-month of treatment were increased compared with those before treatment in the two groups (P<0.01), and they were increased with time. In the two groups, 2-month and 1-month of treatment, 3-month and 2-month of treatment were compared, the sperm concentrations and sperm progressive motilities were significantly increased (P<0.01). The sperm concentrations after 1-month, 2-month and 3-month of treatment in the observation group were higher than those in the control group (P<0.01), the sperm progressive motility after 3-month of treatment in the observation group was higher than that in the control group (P<0.05). ②After 3-month of treatment，the DFI in the observation group was significantly reduced compared with that before treatment (P<0.01). ③The total effective rate in the observation group after 3-month of treatment was 86.7% (26/30), which was superior to 63.3% (19/30) in the control group (P<0.05). CONCLUSION: Grain-moxibustion combined with medicine therapy can improve sperm concentration and sperm progressive motility, enhance the integrity of sperm DNA.

The effects of acupuncture on pregnancy outcomes of in vitro fertilization: a systematic review and meta-analysis.

BACKGROUND: The effects of acupuncture on in vitro fertilization (IVF) outcomes remain controversial. And the variation in participant, interventions, outcomes studied, and trial design may relate to the efficacy of adjuvant acupuncture. METHODS: We searched digital databases for relevant studies, including Embase, PubMed, Cochrane Library and some Chinese databases up to December 2018, for randomized controlled trials (RCTs) evaluating the effects of acupuncture on women undergoing IVF. We included studies with intervention groups using needling, and control groups consisting of no acupuncture or sham (placebo) acupuncture. Primary outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR). Meta-regression and subgroup analysis were conducted on the basis of eight pre-specified covariates to investigate the variances of the effects of adjuvant acupuncture on pregnancy rates and the sources of heterogeneity. RESULTS: Twenty-seven studies with 6116 participants were included. The pooled clinical pregnancy rate (CPR) from all of acupuncture groups was significantly greater than that of control groups (RR 1.21, 95% CI: 1.07-1.38), whereas the pooled live birth rate (LBR) was not. Meta-regression subgroup analysis showed a more significant benefit of acupuncture for repeated IVF cycle proportion (number of women with a history of prior unsuccessful IVF attempt divided by number of women included in each trial) ≥ 50% group (CPR: RR 1.60, 95% CI: 1.28-2.00; LBR: RR 1.42, 95% CI: 1.05-1.92), and this covariate explained most of the heterogeneity (CPR and LBR: adjusted R2 = 100 and 87.90%). Similar results were found between CPR and number of acupuncture treatments (CPR: p = 0.002, adjusted R2 = 51.90%), but not LBR. CONCLUSIONS: Our analysis finds a benefit of acupuncture for IVF outcomes in women with a history of unsuccessful IVF attempt, and number of acupuncture treatments is a potential influential factor. Given the poor reporting and methodological flaws of existing studies, studies with larger scales and better methodologies are needed to verify these findings.

Chinese medicine Jinlida granules improve high-fat-diet induced metabolic disorders via activation of brown adipose tissue in mice.

AIMS: Activation of brown adipose tissue (BAT) thermogenesis could contribute to energy expenditure, which is critical for the treatment of obesity and type 2 diabetes mellitus (T2DM). In the present study, we aimed to systematically investigate whether traditional Chinese medication Jinlida (JLD) granules could improve metabolic disorders and activate BAT thermogenesis in C57BL/6 J mice fed with a high-fat diet (HFD). METHODS: In the present study, JLD (3.8 g/kg) in 0.5% of carboxymethyl cellulose (CMC) solution was administrated daily by oral gavage to HFD-induced mice for 15 weeks. The body weight, biochemical analysis, histology analysis, intraperitoneal glucose and insulin tolerance (OGTT and ITT) tests were measured to explore metabolic disorders. Cold tolerance test, real-time PCR (qRT-PCR), immunohistochemistry, and western blot were performed to evaluate BAT function. RESULTS: As results, JLD treatment significantly ameliorated HFD-induced obesity and fat mass gain, maintained glucose and lipid homeostasis, and improved hepatic steatosis and inflammation. More importantly, we observed that JLD markedly activated BAT thermogenesis in HFD-induced obese mice. Moreover, our data confirmed that JLD promoted mitochondrial biogenesis and fatty acid oxidation metabolism in BAT. CONCLUSIONS: These data suggested that JLD could improve metabolic disorders in associated with activation of BAT thermogenesis via enhancement of mitochondrial biogenesis and fatty acid oxidation metabolism, thus providing a new pharmacological evidence for the clinical usage of JLD in T2DM treatment.

Bufalin Induces Apoptosis and Improves the Sensitivity of Human Glioma Stem-Like Cells to Temozolamide.

Glioma is the most common malignant tumor of the central nervous system, and it is characterized by high relapse and fatality rates and poor prognosis. Bufalin is one of the main ingredients of Chan-su, a traditional Chinese medicine (TCM) extracted from toad venom. Previous studies revealed that bufalin exerted inhibitory effects on a variety of tumor cells. To demonstrate the inhibitory effect of bufalin on glioma cells and glioma stem-like cells (GSCs) and discuss the underlying mechanism, the proliferation of glioma cells was detected by MTT and colony formation assays following treatment with bufalin. In addition, we investigated whether bufalin inhibits or kills GSCs using flow cytometry, Western blotting, and reverse transcription polymerase chain reaction analysis (RT-PCR). Finally, we investigated whether bufalin could improve the therapeutic effect of temozolomide (TMZ) and discussed the underlying mechanism. Taken together, our data demonstrated that bufalin inhibits glioma cell growth and proliferation, inhibits GSC proliferation, and kills GSCs. Bufalin was found to induce the apoptosis of GSCs by upregulating the expression of the apoptotic proteins cleaved caspase 3 and poly(ADP-ribose) polymerase (PARP) and by downregulating the expression of human telomerase reverse transcriptase, which is a marker of telomerase activity. Bufalin also improved the inhibitory effect of TMZ on GSCs by activating the mitochondrial apoptotic pathway. These results suggest that bufalin damages GSCs, induces apoptosis, and enhances the sensitivity of GSCs to TMZ.

Effects of saturated palmitic acid and omega-3 polyunsaturated fatty acids on Sertoli cell apoptosis.

Obesity is believed to negatively affect male semen quality and is accompanied by dysregulation of free fatty acid (FFA) metabolism in plasma. However, the implication of dysregulated FFA on semen quality and the involvement of Sertoli cells remain unclear. In the present study, we report obesity decreased Sertoli cell viability through dysregulated FFAs. We observed an increased rate of apoptosis in Sertoli cells, accompanied with elevated FFA levels, in the testes of obese mice that were provided a high-fat diet (HFD). Moreover, the levels of reactive oxygen species were elevated. Furthermore, we demonstrated by in vitro assays that saturated palmitic acid (PA), which is the most common saturated FFA in plasma, led to decreased cell viability of TM4 Sertoli cells in a time- and dose-dependent manner. A similar finding was noted in primary mouse Sertoli cells. In contrast to saturated FFA, omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) protected Sertoli cells from PA-induced lipotoxicity at the physiologically relevant levels. These results indicated that the lipotoxicity of saturated fatty acids might be the cause of obesity-induced Sertoli cell apoptosis, which leads to decreased semen quality. In addition, ω-3 PUFAs could be classified as protective FFAs. ABBREVIATIONS: FFA: free fatty acid; HFD: high-fat diet; SD: standard diet; PA: palmitic acid; PUFA: polyunsaturated fatty acid; AI: apoptotic index; MTT: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide; ROS: reactive oxygen species; HE: Hematoxylin and eosin; WT1: Wilm Tumor 1; NAFLD: non- alcoholic fatty liver disease; DCFH-DA: 2', 7' dichlorofluorescin diacetate; 36B4: acidic ribosomal phosphoprotein P0; SD: standard deviation; EPA: eicosapentaenoic acid; PI: propidium iodide; DHA: docosahexenoic acid.

Effects of electroacupuncture on luteal regression and steroidogenesis in ovarian hyperstimulation syndrome model rat.

AIMS: Electroacupuncture (EA) is an effective and safe therapeutic method widely used for treating clinical diseases. Previously, we found that EA could decrease serum hormones and reduce ovarian size in ovarian hyperstimulation syndrome (OHSS) rat model. Nevertheless, the mechanisms that contribute to these improvements remain unclear. MATERIALS AND METHODS: HE staining was used to count the number of corpora lutea (CL) and follicles. Immunohistochemical and ELISA were applied to examine luteal functional and structural regression. Immunoprecipitation was used for analyzing the interaction between NPY (neuropeptide Y) and COX-2; western blotting and qRT-PCR were used to evaluate the expressions of steroidogenic enzymes and PKA/CREB pathway. KEY FINDINGS: EA treatment significantly reduced the ovarian weight and the number of CL, also decreased ovarian and serum levels of PGE2 and COX-2 expression; increased ovarian PGF2α levels and PGF2α/PGE2 ratio; decreased PCNA expression and distribution; and increased cyclin regulatory inhibitor p27 expression to have further effect on the luteal formation, and promote luteal functional and structural regression. Moreover, expression of COX-2 in ovaries was possessed interactivity increased expression of NPY. Furthermore, EA treatment lowered the serum hormone levels, inhibited PKA/CREB pathway and decreased the expressions of steroidogenic enzymes. Hence, interaction with COX-2, NPY may affect the levels of PGF2α and PGE2 as well as impact the proliferation of granulosa cells in ovaries, thus further reducing the luteal formation, and promoting luteal structural and functional regression, as well as the ovarian steroidogenesis following EA treatment. SIGNIFICANCE: EA treatment could be an option for preventing OHSS in ART.

Effect of Ningmitai capsule plus sertraline on patients with premature ejaculation and enlarged seminal vesicles: A randomized clinical trial.

OBJECTIVE: To investigate the effects of Ningmitai capsule combined with sertraline on patients with premature ejaculation (PE) and an increased anterior-posterior diameter (APD) of the seminal vesicles (SVs). METHODS: Sixty men with acquired PE were enrolled and randomly divided into two groups. The combined group was treated with Ningmitai capsule and sertraline, while the control group was treated with sertraline alone. Main outcomes were measured using the premature ejaculation diagnostic tool (PEDT), APD of SVs, and Clinical Global Impression of Change questionnaire and compared before and after 3 months of treatment. RESULTS: Comparing after treatment with before treatment outcomes within each group, the PEDT score was significantly reduced in the combined group (12.1 ¡À 2.5 vs 8.6 ¡À 3.2, P < 0.001, respectively) and control group (12.9 ¡À 2.6 vs 10.3 ¡À 1.6, P < 0.001, respectively). Furthermore, the PEDT score after treatment was significantly lower in the combined compared with control group (8.6 ¡À 3.2 vs 10.3 ¡À 1.6, P = 0.011, respectively). The APD of SVs in the combined group was significantly decreased after treatment [(10.8 ¡À 2.4) vs (12.9 ¡À 2.2) mm, P = 0.001], while the APD of SVs in the control group was equivalent before and after treatment. The treatment response rate was not significantly higher in the combined compared with control group. CONCLUSION: These results indicated that the effect of Ningmitai capsule combined with sertraline was better than that of sertraline alone for the treatment of PE patients exhibiting an increased APD of SVs. The therapeutic effect found for the combined treatment may be due to antibacterial and anti-inflammatory activity reported for Ningmitai capsule, and may suggest that seminal vesiculitis is a potential pathophysiological factor in acquired PE.

[Discussion on the impact of acupuncture for the pregnancy of in vitro fertilization-embryo transfer].

The impact of acupuncture for the pregnancy of in vitro fertilization-embryo transfer (IVF-ET) is discussed in the paper. Nowadays there are various conclusions about the impact of acupuncture for IVF-ET, and it may result from the differences in research designs. The effect is closely related to the demographic and clinical characteristics of subjects, such as age, the diagnosis of barrenness, blood flow index of uterine spiral arteries, the cycle of IVF, etc. Besides, the efficacy is influenced by treatment based on syndrome differentiation or not, the frequency and course of acupuncture in both the treating group and the control group, etc. If more reasonable design is achieved in the further study based on them, more reliable evidence will be provided for the effect and mechanism of the pregnancy of IVF-EF by acupuncture.