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Objective An epidemic of obesity is prevalent in the world. Recent evidences have linked obesity to male infertility , but the underlying mechanisms remain to be elucidated. Although spermatozoa dysfunction is the most cause of infertility and defective mitochondrial function plays a key role in impairing the sperm quality , there was little study on the role of mitochondria within spermatozoa in obese male infertility. Methods In this study, the semen parameters in Chinese obesity (BMI ≥ 28 kg/m2, n = 51) and normal (BMI of 18.5 to 23.9 kg/m2, n = 42) volunteers were investigated. Moreover, the oxidative stress injury was explored in human spermatozoa by examining the activity of intracellular SOD and MDA in sperm and LDH release from sperm. The activity test of mitochondrial respiratory chain complexes and the mitochondrial membrane potential were also performed. Results We found that obesity had a negative influence on the quality of semen. Furthermore, oxidative stress was detected in sperm from obese males. Oxidative stress-related mitochondrial dysfunction was also observed in the spermatozoa of obese males. Conclusions In total, these results indicated that oxidative stress-related mitochondrial dysfunction might be a reason for obesity-induced infertility, which provided the insights into the pathophysiological mechanism behind obesity-induced infertility in obese human males.

Introduction: Kidney cancer is among the 10 most common cancers in both men and women. As we know, obesity and overweight is one of the confirmed risk factors. However, several studies found that overweight or obese patients with kidney cancer had a better prognosis than normal weight patients, as known as the “obesity paradox”. Therefore, in this study, we aimed to conduct a systematic meta- analysis of peer- reviewed literature to investigate the association between obesity or overweight and kidney cancer outcomes.Methods and analysis: Our review will assess case-control or cohort studies on prognosis of kidney cancer patients who are classified as obese, overweight or normal weight before 1 August 2020. Databases to be searched include PubMed/MEDLINE, Scopus, Web of Science and Embase. Two authors will independently conduct eligible studies selection process, perform data extraction and appraise the quality of included studies. Original case-control or cohort studies published in English will be considered for inclusion. The outcomes of interest will be progression-free survival, cancer- specific survival and overall survival. Meta-analyses will be performed to calculate pooled estimates. Ethics and dissemination: Our study will be based on published data, and thus there is no requirement for ethics approval. The results will be shared through publication in a peer- reviewed journal and presentations at academic conferences. PROSPERO registration number: CRD42021223347

Protein homeostasis serves as an important step in regulating diverse cellular processes underlying the function and development of the nervous system. In particular, the ubiquitination proteasome system (UPS), a universal pathway mediating protein degradation, contributes to the development of numerous synaptic structures, including theDrosophilaolfactory-associative learning center mushroom body (MB), thereby affecting associated function. Here, we describe the function of a newly characterizedDrosophilaF-box protein CG5003, an adaptor for the RING-domain type E3 ligase (SCF complex), in MB development. Lacking CG5003 ubiquitously causes MB γ axon pruning defects and selectiveCG5003expression in pan-neurons leads to both γ axon and α/β lobe abnormalities. Interestingly, change inCG5003expression in MB neurons does not cause any abnormalities in axons, suggesting that CG5003 functions in cells extrinsic to MB to regulate its development. Mass spectrum analysis indicates that silencingCG5003expression in all neurons affects expression levels of proteins in the cell and structural morphogenesis, transcription regulator activity, and catalytic activity. Our findings reinforce the importance of UPS and identify a new factor in regulating neuronal development as exemplified by the synaptic structure MB.

Objective With the discovery of thermogenic adipocytes in humans, it has been hypothesized that enhancing adaptive thermogenesis may improve obesity. Although many studies have found that ginseng can improve obesity, the beneficial effects of ginsenoside Rd on obesity and its mechanisms have not been studied. Methods High-fat diet-induced obese mice were used as the study subjects, with intraperitoneal injection of Rd daily at a dose of 15 mg/kg. Body weight and energy metabolism were observed. The effects of Rd on glucose tolerance, insulin sensitivity, and cold tolerance were tested. The expression of genes associated with thermogenesis was analyzed. Finally, the mechanisms by which Rd regulates adaptive thermogenesis were studied. Results Rd ameliorated obesity and insulin resistance. Rd increased cold tolerance through enhancing thermogenic gene expression in brown adipose tissue and increased the browning of white adipose tissue induced by cold stress. Rd increased intracellular cyclic adenosine monophosphate (cAMP) content. Decreasing intracellular cAMP levels by an inhibitor of adenylyl cyclase SQ22536 abolished the promoting effects of Rd on the expression of thermogenic genes. Conclusions Rd improves obesity and insulin resistance. The upregulation of thermogenesis by Rd is dependent on the cAMP/protein kinase A signaling pathway.

// Ling Qi 1,* , Lijuan Ding 2,* , Shuran Wang 3 , Yue Zhong 3 , Donghai Zhao 3 , Ling Gao 2 , Weiyao Wang 1 , Peng Lv 1 , Ye Xu 1 and Shudong Wang 4 1 Basic Medical College, Jilin Medical University, Jilin, China 2 Department of Radiation Oncology, First Hospital of Jilin University, Changchun, China 3 Department of Science and Technology, Jilin Medical University, Jilin, China 4 Center of Cardiovascular Diseases, First Hospital of Jilin University, Changchun, China * These authors have contributed equally to this work Correspondence to: Ye Xu, email: // Shudong Wang, email: // Keywords : chemotherapy, radiotherapy, glioma, network meta-analysis, temozolomide Received : April 05, 2016 Accepted : July 10, 2016 Published : July 21, 2016 Abstract Different chemotherapy drugs are generally introduced in clinical practices combining with therapy for glioma treatment. However, these chemotherapy drugs have rarely been compared with each other and the optimum drug still remains to be proved. In this research, medical databases were consulted, PubMed, Embase and Cochrane Library included. As primary outcomes, hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS) with their corresponding 95% credential intervals ( CrI ) were reported. A network meta-analysis was conducted; the surface under the cumulative ranking curve (SUCRA) was utilized for treatment rank and a cluster analysis based on SUCRA values was performed. This research includes 14 trials with 3,681 subjects and eight interventions. In terms of network meta-analysis, placebo was proved to be inferior to the combination of temozolomide (TMZ), nimustine (ACNU) and cisplatin (CDDP). Also, bevacizumab (BEV) in conjunction with TMZ were significantly more effective than placebo with an HR of 0.40. The estimated probabilities from SUCRA verified the above outcomes, confirming that the combination of TMZ, ACNU and CDDP exhibited the highest ranking probability of 0.889 with respect to OS, while BEV in combination with TMZ - with a probability of 0.772 - ranked the first place with respect to PFS. According to the results of this network meta-analysis, the combination of (1) TMZ, ACNU and CDDP; (2) BEV in combination with TMZ and (3) cilengitide in combination with TMZ, are considered as the preferable choices of chemotherapy drugs for glioma treatment.

To investigate the association between pathological myopia (PM) and immunological/inflammatory markers and to identify the possible risk factors for the formation of myopic choroidal neovascularization (mCNV).One hundred fourteen unrelated subjects were recruited: 63 PM patients (PM group) with spherical equivalent of at least -8.00 diopters (range, -8.00 to -25.00) and axial length exceeding 26.5 mm, accompanied by characteristic pathologic changes, and 51 emmetropic age- and sex-matched individuals (control group) with spherical equivalent within ±1.0 diopter in both eyes. In the PM group, patients were assigned to two subgroups, mCNV group and no CNV group, according to the results of fluorescein angiography. Serum high-sensitivity C-reactive protein (hs-CRP) and complement profile (C3, C4, and CH50) were assayed. Statistical analysis was performed between the two groups. Binary logistic regression analysis was used to analyze the relative risk factors that were associated with the development of mCNV in the PM group patients.The range of axial length was 26.50 to 37.08 mm in the PM group and 22.32 to 24.56 mm in the control group. There were 24 patients in the mCNV group and 39 patients in the no CNV group. The PM group patients had significantly higher serum hs-CRP (p = 0.033), C3 (p = 0.004), and CH50 (p0.001) compared with the control group patients. There were no significant differences between the two groups for C4 level (p = 0.071). Binary logistic regression analysis, which included hs-CRP, C3, C4, CH50, age, and sex as covariates, showed that C3 (p = 0.03) and age (p = 0.01) were risk factors for mCNV, whereas serum hs-CRP, C4, CH50, and sex were not statistically significant predictors of mCNV in the PM group patients (p0.05).Our data support the hypothesis that immunological/inflammatory markers, namely hs-CRP, C3, and CH50 may play an important role in the development of PM, and that C3 level may be a predictive risk factor for mCNV formation.

In the present study, we investigated the potential efficacy of cruciferous vegetable-derived sulforaphane (SFN) in improving homocysteine (HCY)-stressed cells. After human hepatocyte line HHL-5 was preincubated with SFN and subsequently with 10 mmol/L HCY, SFN improved the pathologic changes which are caused by HCY, including cell morphological abnormality, endoplasmic reticulum (ER) swelling, excessive generation of reactive oxygen species (ROS), the increased malondialdehyde (MDA) levels, as well as the increased activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Phase II enzymes, thioredoxin reductase-1 (TrxR-1) andquinone oxidoreductase 1 (NQO1), were involved in the protective effect of SFN against injury by HCY. The ER stress-specific proteins, such as glucose-regulated protein-78 (GRP78) and protein kinase RNA (PKR)-like ER kinase (PERK), were strikingly abolished by SFN. Furthermore, Nrf-2 translocation was enhanced by SFN, which lead to the induction of TrxR-1and NQO1.

Background: Body energy homeostasis is largely regulated by the interactions between appetite-related brain regions and gut hormones. Objective: We hypothesized that the sensitivity of appetite-related brain regions [eg, hypothalamus, insula, thalamus, parahippocampal/ hippocampal cortex, caudate, putamen, amygdala, and orbitofrontal cortex (OFC)] varies for each macronutrient, and the differential sensitivity is associated with gut hormone concentrations in humans. Design: Brain activation responses to ingested fat, glucose, protein, and water in the above-mentioned 8 brain regions of 14 healthy men were investigated by using functional magnetic resonance imaging. Fasting and postprandial plasma glucose, insulin, ghrelin, cholecystokinin (CCK), and glucagon-like peptide 1 (GLP-1) concentrations were measured. The relation of the blood oxygen level–dependent (BOLD) signal with plasma glucose and hormone concentrations was assessed by using Pearson’s correlation analysis. Results: Ingested macronutrients similarly reduced the BOLD signal in the middle insula, thalamus, parahippocampal cortex, caudate, and lateral OFC. Protein ingestion reduced the BOLD signal in the amygdala more effectively than did fat and glucose ingestion. BOLD signal changes were positively correlated with circulating ghrelin concentrations and were negatively correlated with circulating insulin, CCK, and GLP-1 concentrations. The findings indicate variations in the correlation between brain activation and plasma hormone concentrations after ingestion of different macronutrients. Conclusions: The middle insula, thalamus, parahippocampal cortex, caudate, and lateral OFC, but not the amygdala, have sensitivities similar to those of isocaloric and isovolumetric macronutrient solutions. Differential correlations exist between BOLD signal changes in activated brain regions and postprandial changes in plasma concentrations of different gut hormones in response to the ingestion of different macronutrients. This trial was registered at chictr.org as ChiCTR-TRC-12001945. Am J Clin Nutr 2012; 96:275–82.

To investigate the effect of topical pranoprofen 0.1% on the clinical evaluation and conjunctival human leukocyte antigen II (HLA-DR) expression in dry eyes.Sixty patients with dry eyes were randomized to 2 groups. Patients in group 1 received topical pranoprofen 0.1% plus topical sodium hyaluronate 0.1%; and patients in group 2 received sodium hyaluronate without pranoprofen. Ocular surface disease index (OSDI), tearfilig;lm break-up time (TBUT), Schirmer I test, ocular surface staining (OSS), and conjunctival HLA-DR expression were evaluated before treatment and at 15 and 30 days after treatment.On day 15, patients in group 1 had significantly lower OSDI, OSS, and HLA-DR-positive cells compared with patients in group 2 (P0.01), and the TBUT was significantly longer in patients in group 1 than that of patients in group 2 (P0.01). On day 30, the difference between the 2 groups in OSS lost significance; however, there continued to be significant differences in the OSDI, TBUT, and HLA-DR expression between the 2 groups (P0.01). On days 15 and 30, the values in group 1 patients had significant improvement compared with their baseline values in terms of the above-mentioned parameters. The comparisons within group 2 did not reveal any significant differences. There was no significant effect in the Schirmer I test value in eyes of patients in group 1 or group 2 at days 15 or 30 (P0.05).Topical pranoprofen 0.1% has a beneficial effect in reducing the ocular signs and symptoms of dry eyes and decreasing the inflammatory markers of conjunctival epithelial cells.

Metastasis and recurrence of bladder cancer are the main reasons for its poor prognosis and high mortality rates. Because of its biological activity and high metabolic accumulation in urine, sulforaphane, a phytochemical exclusively occurring in cruciferous vegetables, has a powerful and specific potential for preventing bladder cancer. In this paper, sulforaphane is shown to significantly suppress a variety of biochemical pathways including the attachment, invasion, migration and chemotaxis motion in malignant transitional bladder cancer T24 cells. Transfection with cyclooxygenase-2 (COX-2) overexpression plasmid largely abolished inhibition of MMP2/9 expression as well as cell invasive capability by sulforaphane. Moreover, sulforaphane inhibited the epithelial-to-mesenchymal transition (EMT) process which underlies tumor cell invasion and migration mediated by E-cadherin induction through reducing transcriptional repressors, such as ZEB1 and Snail. Under conditions of over-expression of COX-2 and/or MMP2/9, sulforaphane was still able to induce E-cadherin or reduce Snail/ZEB1 expression, suggesting that additional pathways might be involved. Further studies indicated that miR-200c played a role in the regulation of E-cadherin via the ZEB1 repressor but not by the Snail repressor. In conclusion, the EMT and two recognized signaling pathways (COX-2/MMP2,9/ ZEB1, Snail and miR-200c/ZEB1) are all targets for sulforaphane. This study indicated that sulforaphane may possess therapeutic potential in preventing recurrence of human bladder cancer.

Gastrointestinal (GI) motility and gut hormones have been considered to be involved in the development and maintenance of obesity. Our aim was to assess the relationships between gastric emptying (GE), GI transit and gut hormones and leptin concentrations in diet-induced obese rat model. Male 6-week-old Sprague–Dawley rats were fed with a high-fat (HF) diet for 8 weeks to generate diet-induced obesity (DIO) and diet resistant (DR) rats. GE, GI transit and plasma ghrelin, cholecystokinin (CCK), PYY and leptin concentrations were determined in DIO, DR and control (CON) rats. The DIO rats had slower GE, higher plasma leptin and CCK concentrations, and lower plasma ghrelin concentration compared with CON and DR rats. GE was correlated with plasma ghrelin ( r = 0.402, P = 0.028), CCK ( r = − 0.518, P = 0.003) and leptin concentration ( r = − 0.514, P = 0.004). The slower GE, which can be considered as an adaptive response aimed at HF diet induced obesity, may be mediated by changes of plasma ghrelin, CCK and leptin concentrations.

Sulforaphane (SFN), mainly derived from cruciferous vegetables, has received much attention for its cancer chemopreventive property. Though there have been a few epidemiological studies supporting its beneficial effect on cardiovascular diseases, much experimental evidence are still required to understand its mechanism. In this study, human vascular endothelial cell, a barrier of blood, was used as an in vitro model to investigate the protective effect of sulforaphane on inflammatory damage induced by lipopolysaccharide (LPS). The results showed that sulforaphane inhibited the expression of COX-2 and iNOS stimulated by lipopolysaccharide in a dose- and time-dependent manner. Moreover, sulforaphane suppressed the phosphorylation of ERK1/2, JNK, and p38 activated by lipopolysaccharide. Pretreatment with SB202190, the specific inhibitor of p38, abolished the expression of COX-2 induced by LPS. Likewise, SP600125, inhibitor of JNK, abrogated iNOS expression stimulated by LPS. Moreover, pretreatment with anisomycin (AM), an activator of p38 and JNK, instead of LPS, the expression of COX-2 and iNOS is still inhibited by sulforaphane. Interestingly, SFN significantly induced HO-1 and TR expression down-regulated by LPS. Taken together, these data indicated that sulforaphane exhibited the protective role against the inflammatory injury in vascular endothelia cells, through inactivating p38 MAPK and JNK, as well as inducing phase 2 enzymes.

Cyclooxygenase-2 (COX-2) overexpression has been associated with the grade, prognosis and recurrence of transitional cell carcinoma (TCC) of the bladder. In this study, sulforaphane, a dietary isothiocyanate, down-regulated COX-2 expression in human bladder transitional cancer T24 cells at both transcriptional- and translational levels. Sulforaphane (5-20 microM) induced nuclear translocation of NF-kappaB and reduced its binding to the COX-2 promoter, a key mechanism for suppressing COX-2 expression by sulforaphane. Moreover, sulforaphane increased expression of p38 and phosphorylated-p38 protein. A specific inhibitor of p38 MAPK, SB202190, was used to further investigate its pivotal role in sulforaphane-mediated down-regulation of COX-2. Exposure of T24 cells to SB202190 1 hour prior to sulforaphane treatment abolished the effect of sulforaphane on COX-2 mRNA down-regulation, but enhanced COX-2 transcription. Furthermore, SB202190 alone induced NF-kappaB translocation to the nucleus, promoted NF-kappaB binding to the COX-2 promoter and resulted in up-regulation of COX-2 expression. Taken together, these data suggest that p38 is essential in sulforaphane-mediated COX-2 suppression and provide new insights into the molecular mechanisms of sulforaphane in the chemoprevention of bladder cancer.