Obesity is associated with lower levels of negative emotions in polycystic ovary syndrome in clinical and animal studies.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic disorders in women of reproductive age. It is frequently comorbid with obesity and negative emotions. Currently, there are few reports on the relationship between obesity and negative emotions in patients with PCOS. Here we performed both basic and clinical studies to study the relationship between obesity and negative emotions in PCOS. METHODS: We performed a cross-sectional study including 608 patients with PCOS and 184 healthy participants to assess the mental health status of people with different body mass indices (BMI). Self-rated anxiety, depression, and perceived stress scales were used for subjective mood evaluations. Rat PCOS models fed 45 and 60% high-fat diets were used to confirm the results of the clinical study. Elevated plus maze and open field tests were used to assess anxiety- and depression-like behaviors in rats. RESULTS: We observed overweight/obesity, increased depression, anxiety, and perceived stress in women with PCOS, and found that anxiety and depression were negatively correlated with BMI in patients with severe obesity and PCOS. Similar results were confirmed in the animal study; the elevated plus maze test and open field test demonstrated that only 60% of high fat diet-induced obesity partly reversed anxiety- and depression-like behaviors in PCOS rats. A high-fat diet also modulated rat hypothalamic and hippocampal luteinizing hormone and testosterone levels. CONCLUSION: These results reveal a potential relationship between obesity and negative emotions in PCOS and prompt further investigation. The interactions between various symptoms of PCOS may be targeted to improve the overall well-being of patients.

Obesity was negatively correlated with negative emotions in patients with PCOS.Obesity may affect the downregulation of LH and testosterone and participate in the regulation of emotions.Increased BMI may be beneficial for patients with PCOS in terms of the psychological aspects.

Optimizing the Conditions of Pretreatment and Enzymatic Hydrolysis of Sugarcane Bagasse for Bioethanol Production.

The agricultural waste sugarcane bagasse (SCB) is a kind of plentiful biomass resource. In this study, different pretreatment methods (NaOH, H2SO4, and sodium percarbonate/glycerol) were utilized and compared. Among the three pretreatment methods, NaOH pretreatment was the most optimal method. Response surface methodology (RSM) was utilized to optimize NaOH pretreatment conditions. After optimization by RSM, the solid yield and lignin removal were 54.60 and 82.30% under the treatment of 1% NaOH, a time of 60 min, and a solid-to-liquid ratio of 1:15, respectively. Then, the enzymolysis conditions of cellulase for NaOH-treated SCB were optimized by RSM. Under the optimal enzymatic hydrolysis conditions (an enzyme dose of 18 FPU/g, a time of 64 h, and a solid-to-liquid ratio of 1:30), the actual yield of reducing sugar in the enzyme-treated hydrolysate was 443.52 mg/g SCB with a cellulose conversion rate of 85.33%. A bacterium, namely, Bacillus sp. EtOH, which produced ethanol and Baijiu aroma substances, was isolated from the high-temperature Daqu of Danquan Baijiu in our previous study. At last, when the strain EtOH was cultured for 36 h in a fermentation medium (reducing sugar from cellulase-treated SCB hydrolysate, yeast extract, and peptone), ethanol concentration reached 2.769 g/L (0.353%, v/v). The sugar-to-ethanol and SCB-to-ethanol yields were 13.85 and 11.81% in this study, respectively. In brief, after NaOH pretreatment, 1 g of original SCB produced 0.5460 g of NaOH-treated SCB. Then, after the enzymatic hydrolysis, reducing sugar yield (443.52 mg/g SCB) was obtained. Our study provided a suitable method for bioethanol production from SCB, which achieved efficient resource utilization of agricultural waste SCB.

Effect of Gubenyiliu formula II and its disassembled prescriptions on cell autophagy in breast cancer through PI3K/AKT/mTOR pathway.

The aim of this study is to reveal the mechanism of Gubenyiliu II (GYII) inhibiting autophagy in breast cancer and the effect of its disassembled prescriptions, Quxie (QX) and Fuzheng (FZ), which cause autophagy difference on tumor growth. After a breast cancer in situ tumor model was established, mice were randomly distributed into different groups: model, GYII, QX, FZ and tamoxifen groups, and treated correspondingly. Then, the tumor volumes and weights were monitored. Immunohistochemistry detected the contents of microtubule-associated protein light chain 3 (LC3), phosphorylated phosphatidylinositol 3-kinase (p-PI3K), phosphorylated protein kinase B (p-AKT) and phosphorylated mammalian target of rapamycin (p-mTOR) in tumor tissues. Furthermore, 4T1 cells were administrated with the 20% contained serum. Cell proliferation, migration and invasion were measured using cell counting kit-8 and transwell assays. Electron microscopy and flow cytometry detected autophagy and apoptosis. The content of LC3 was measured by immunofluorescence. Western blot detected the protein levels of LC3, Beclin1, p-PI3K/PI3K, p-AKT/AKT and p-mTOR/mTOR in tumor tissues and 4T1 cells. GYII, QX and FZ treatment significantly reduced the tumor volumes and weights in breast cancer tumor-bearing mice. The cell proliferation, migration and invasion were restrained, and cell apoptosis and autophagy were promoted in GYII, QX and FZ groups. Moreover, GYII, QX and FZ increased the expression of LC3 in 4T1 cells and tumor tissues and decreased the phosphorylation levels of PI3K, AKT and mTOR in tumor tissues. The protein levels of LC3 and Beclin1 were upregulated, and p-PI3K/PI3K, p-AKT/AKT and p-mTOR/mTOR were downregulated in tumor tissues and 4T1 cells of treatment groups. Our study confirmed that GYII could treat breast cancer by restraining the PI3K/AKT/mTOR signaling pathway-mediated autophagy. While QX focuses on inhibiting tumor growth, FZ acts on inhibiting tumor metastasis.

Cynanbungeigenin C and D, a pair of novel epimers from Cynanchum bungei, suppress hedgehog pathway-dependent medulloblastoma by blocking signaling at the level of Gli.

Uncontrolled excessive activation of Hedgehog (Hh) signaling pathway is linked to a number of human malignant tumorigenesis. To obtain valuable Hh pathway inhibitors from natural product, in present study, a pair of novel epimers, Cynanbungeigenin C (CBC) and D (CBD) from the plant Cynanchum bungei Decne were chemically characterized by multiple spectroscopic data and chemical derivatization, and evaluated for their inhibition on Hh pathway. Mechanistically, CBC and CBD block Hh pathway signaling not through targeting Smo and Sufu, but at the level of Gli. In addition, both eipmers significantly suppress Hh pathway-dependent Ptch+/-; p53-/- medulloblastoma in vitro and in vivo. Furthermore, both CBC and CBD inhibited two Smo mutants induced Hh pathway activation, which suggested that they are potential compounds for the treatment of medulloblastoma with primary or acquired resistance to current Smo inhibitors. These results highlight the potential of CBC and CBD as effective lead compounds in the treatment of medulloblastoma and other Hh-dependent malignancy.

The Loss of a Sugar Chain at C(3) Position Enhances Stemucronatoside K-Induced Apoptosis, Cell Cycle Arrest, and Hedgehog Pathway Inhibition in HT-29 Cells.

Stemucronatoside K (SMK) and its aglycone stephanthraniline A (STA) are the most representative of a series of novel C21 steriodal compounds that we have previously isolated from Asclepiadaceae plants. The objectives of this study were to investigate the antitumor activity of SMK and STA, and clarify the effect of the sugar chain at the C(3) position. Our results showed that both SMK and STA decreased the growth of HT-29 cells in a dose- and time-dependent manner. Meanwhile, STA showed much stronger inhibitory effect than SMK. Treatment of HT-29 cells with STA increased the apoptotic cell numbers and the protein expression of cleaved caspase 3 and cleaved-PARP. G1 phase cell cycle arrest and decreased expression of cyclin D1 and cyclin-dependent kinases 4 were also observed after STA treatment. Furthermore, STA reduced the mRNA levels of four Hedgehog pathway components (GLI1, GLI2, GLI3, and PTCH1) and suppressed Shh-induced Hedgehog pathway activation in a concentration-dependent manner. These results indicated that SMK and STA could inhibit the growth of HT-29 cells by inducing apoptosis, cell cycle arrest, and hedgehog pathway inhibition. The loss of sugar chain at C(3) position could enhance SMK's activity. This study is beneficial to understand the use of natural C21 steroids as antitumor lead compounds.

Stephanthraniline A suppressed CD4(+) T cell-mediated immunological hepatitis through impairing PKCθ function.

Stephanthraniline A (STA), a C21 steroid isolated from Stephanotis mucronata (Blanco) Merr., was previously shown to inhibit T cells activation and proliferation in vitro and in vivo. The purpose of this study was to further evaluate the in vivo immunosuppressive activity of STA and to elucidate its potential mechanisms. The results showed that pretreatment with STA significantly attenuated concanavalin A (Con A)-induced hepatitis and reduced CD4(+) T cells activation and aggregation in hepatic tissue in mice. STA directly suppressed the activation and proliferation of Con A-induced CD4(+) T cells, and inhibited NFAT, NFκB and MAPK signaling cascades in activated CD4(+) T cells in vitro. Moreover, it was proved that STA inhibited T cells activation and proliferation through proximal T cell-receptor (TCR) signaling- and Ca(2+) signaling-independent way. The molecular docking studies predicted that STA could tight bind to PKCθ via five hydrogen. The further findings indicated STA directly inhibited PKCθ kinase activity, and its phosphorylation in activated CD4(+) T cells in vitro. Collectively, the present study indicated that STA could protect against CD4(+) T cell-mediated immunological hepatitis in mice through PKCθ and its downstream NFAT, NFκB and MAPK signaling cascades. These results highlight the potential of STA as an effective leading compound for use in the treatment of CD4(+) T cell-mediated inflammatory and autoimmune diseases.

Expression of PD-1, PD-L1 and PD-L2 is associated with differentiation status and histological type of endometrial cancer.

Endometrial cancer (EC) is the most frequent gynecological malignancy and a major cause of morbidity and mortality for women worldwide. Programmed cell death protein 1 (PD-1) and its ligands programmed death ligand 1 (PD-L1) and programmed death ligand 2 (PD-L2) have been well studied in lung cancer, melanoma and renal-cell cancer. However, few studies have been performed in EC. The purpose of the present study was to assess the expression of PD-1, PD-L1 and PD-L2 in 35 human normal endometrial tissue samples and 75 human EC tissue samples using immunohistochemical staining. It was found that 61.3% of ECs were positive for PD-1 staining, which was almost exclusively found in the tumor-infiltrating immune cells. By contrast, PD-1 was not expressed in the tumor cells or normal endometrial tissues. It was also found that 14.3% of normal endometria and 17.3% of EC tissues were positive for PD-L1 expression, while 20.0% of normal endometrium and 37.3% of EC tissues were positive for PD-L2 expression; however, there was no statistically significant difference between the normal endometrium and EC tissues. PD-1 expression in the tumor-infiltrating immune cells was more frequently found in the moderately and poorly-differentiated ECs and non-endometrioid (type II) ECs than in the well-differentiated ECs and endometrioid (type I) ECs. Similarly, PD-L1 and PD-L2 expression in the tumor-infiltrating immune cells was more frequently found in the moderately and poorly-differentiated ECs and type II ECs than in the type I ECs. The present findings indicate a possible better outcome for future treatment with anti-PD-1 or anti-PD-L1 antibody-based therapies against these subgroups of endometrial cancers with frequent expression of the PD-1/PD-L1/PD-L2 axis.

Total synthesis of anticoagulant pentasaccharide fondaparinux.

The anticoagulant pentasaccharide fondaparinux was synthesized using an improved and optimized synthetic strategy including a convergent [3+2] coupling approach, orthogonal protecting groups and various glycosyl donors. The new methods of glycosylation were also used for controlling the stereochemical configuration and improving the yield of the glycosylation. In addition, HPLC and NMR methods to monitor the process of total synthesis of fondaparinux were employed. This work provides a comprehensive elaboration for the synthesis and analysis of fondaparinux based on related literature, as well as abundant information for the synthesis of heparin-like oligosaccharides.

A safe and facile route to imidazole-1-sulfonyl azide as a diazotransfer reagent.

A facile approach to the diazotransfer reagent of imidazole-1-sulfonyl azide was reported. The procedure was well optimized to clarify potential explosion risks. A high production yield as well as small batch variation was achieved even without careful pretreatment of reagents and solvents. HPLC and NMR methods to monitor the process were provided. These features made this protocol suitable for large scale preparation in academia and industry as well.

Facile synthesis of 1,2,3-triazole analogs of SGLT2 inhibitors by 'click chemistry'.

Novel analogs of SGLT2 inhibitors containing the 1,2,3-triazole motif were designed and synthesized for urinary glucose excretion evaluation. The C-glucosides with triazole aglycone can be easily constructed by click chemistry. Most of the synthesized compounds increased urinary glucose excretion and demonstrated inhibition of glucose transport.

[Study on mesh-augmented vaginal reconstructive surgery in treatment of pelvic organ prolapse].

OBJECTIVE: To evaluate clinical outcome and complications of mesh-augmented vaginal reconstructive surgery in treatment of pelvic organ prolapse. METHODS: From Feb 2007 to Jan 2009, mesh-augmented vaginal reconstructive surgery were performed on 66 women with pelvic organ prolapse stage III-IV. Pre and postoperative symptoms, pelvic organ prolapse quantitation (POP-Q) stage and pelvic floor distress inventory-short form 20 (PFDI-20) measurements were studied to assess anatomic and quality-of-life outcome. Operative complications were also analyzed. RESULTS: Totally 65 patients underwent successful surgeries. The rate of follow-up was 97% (63/65) with a median follow-up of 17.2 months. Subjective cure rate and objective cure rate were both 97% (61/63) at 6 and 12 months after surgeries, 51 women completed PFDI-20 measurements and scores were 102 ± 50 before surgery, 16 ± 21 at 6 months and 15 ± 20 at 12 months. It reached statistical difference when scores were compared before and after surgeries (P < 0.05). Among 66 patients, 2 patients underwent organ injuries, 2 had recurrent prolapse, 4 had mesh-related complications and 1 had severe de novo stress urinary incontinence. Six patients underwent second surgery. CONCLUSIONS: Mesh-augmented vaginal reconstructive surgery in treatment of pelvic organ prolapsed brought satisfied clinical outcome. The incidence of mesh-related complications was low and secondary operative interventions were effective.