A series of isoindoline derivatives were designed, synthesized, and evaluated for their double inhibitory activities. All of them were new compounds, and their structures were confirmed by 1H NMR and HR-MS. Preliminary in vitro pharmacological tests showed that all compounds exhibited 5-HT or NE reuptake inhibition activity. Among the tested compounds, compound I-3 exhibited potent inhibitory activity against 5-HT and NE reuptake in vitro, and exhibited potent antidepressant activity in vivo. These compounds designed can be further optimized for finding more potent 5-HT/NE dual reuptake inhibitors and antidepressant candidates as well.
Antidepressive Agents ; chemical synthesis ; chemistry ; Biological Transport ; Drug Design ; Isoindoles ; chemical synthesis ; chemistry ; Serotonin Uptake Inhibitors ; chemical synthesis ; chemistry ; Structure-Activity Relationship

Male infertility is one of the serious problems currently affecting human reproduction and health.Healthy gut microbi-ota is involved in the development of the immune system and protection against pathogen invasion,and it maintain normal metabolism and improve reproductive potential by secreting a variety of substances.The imbalance of gut microbiota can promote the local and sys-temic immune inflammatory response,induce chronic metabolic diseases,affect the synthesis of sex hormones,cause abnormal sper-matogenesis,maturation or activation,and it is closely related to the decline of male fertility.By exploring the correlation between gut microbiota and male infertility,this paper aims to provide new clues and directions for the clinical diagnosis and treatment of male in-fertility.

OBJECTIVETo study the antifertility and anti-inflammatory effects of compound Kucen gel in vivo.

METHODSAs antifertility experiment, we randomly divided 60 female SD rats into six groups of equal number: normal saline, blank gel, low-, medium- and high-dose compound Kucen gel (0.05, 0.10 and 0.15 g/g), and positive control (4% nonoxynol gel) to receive intravaginal administration of 200 microl of respective agent, followed by copulation with male rats in a 1:1 ratio. At 12 days after successful mating, the female rats were dissected for calculation of the embryos and the rate of contraception. As an anti-inflammatory trial, we established a mouse model of inflammation by applying xylene to the pinna, and equally randomized 60 Kunming mice to six groups as in the former experiment. We determined the degrees and average rates of swelling inhibition in the left ear.

RESULTSHigh-dose compound Kucen gel achieved a fertility-inhibition rate of 100% in the female rats, the number of embryos significantly lower than in the normal saline group (0.00 +/- 0.00 vs 11.00 +/- 2. 00, P < 0.05), but with no statistically insignificant difference from that of the positive control (0.00 +/- 0.00, P > 0.05). High-dose compound Kucen gel also markedly suppressed swelling in the left ear of the mice, with an inhibition rate of 52.3%, the average swelling degree significantly lower than in the normal saline group (10.17 +/- 2.56 vs 21.32 +/- 3.17, P < 0.01), but not remarkably different from that of the positive control (8.53 +/- 1.89, P > 0.05).

CONCLUSIONCompound Kucen gel, with its strong antifertility and anti-inflammatory effects, deserves further study and clinical application.

Animals ; Anti-Inflammatory Agents ; pharmacology ; Contraceptive Agents ; pharmacology ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Female ; Gels ; Inflammation ; Male ; Mice ; Mice, Inbred Strains ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo observe the spermicidal effect of alcohol extracts from different ratios of Sophora flavescens Ait/Chinese Bulbul in vitro.

METHODSSemen samples aseptically obtained by masturbation and prepared by density gradient centrifugation from 15 healthy men were incubated in the alcohol extracts from 9 different ratios of Sophora flavescens Ait/Chinese Bulbul for 20 seconds, 2 minutes and 4 minutes. Then the motility and movement parameters of the sperm were detected by computer-assisted semen analysis, and the minimal effective concentrations of the instant spermicidal effect of the extracts were determined.

RESULTSAt the ratio of 3:1, the extract at 0.5 mg/ml significantly inhibited the sperm motility and other sperm movement parameters VCL, VSL, VAP, ALH, WOB and MAD, as compared with the control group. The minimal effective concentration of the instant spermicidal effect of the extracts was 3.5 mg/ml at 3:1.

CONCLUSIONThe alcohol extracts from Sophora flavescens Ait and Chinese Bulbul at the ratio of 3:1 have the best spermicidal effect in vitro.

Adult ; Humans ; Male ; Plant Extracts ; pharmacology ; Pulsatilla ; Semen Analysis ; Sophora ; Sperm Motility ; drug effects ; Spermatocidal Agents ; pharmacology ; Spermatozoa ; drug effects ; Young Adult

Objective To investigate the expression of vasoactive intestinal peptide (VIP)in gastric adenocarcinoma,and to evaluate the correlation of VIP level with clinical pathologic parameters. Methods The level of VIP in sera from gastric adenocarcinoma patients and healthy people was investigated by ELISA. Moreover,the differential gene expression between gastric adenocarcinoma,gastric dysplasia,and the corresponding normal gastric mucosa were determined by RT-PCR. Western Blot was also used to measure the expression of VIP in the gastric odenouarcinoma and the normal gastric mucosa. Results The serum level of VIP was (5.794±0.014) ng/ ml in normal control and was (14.437±0.825) ng/ml in gastric adenocareinoma patients,showing significant difference (P<0.05). Meanwhile,the V/B of gastric adenocarcinoma tissues was greater than that of gastric dysplasia and the corresponding normal gastric mucosa (P < 0.01 ),the values of V/B were 1.5261±0.3028,0.9334±0.2872,and 0.9051±0.2794,respectively. The values of V/B between normal gastric mncesa and gastric dysplasia were not different significantly (P0.05).There were significantly negative correlation between the VIP mRNA expression of the differentiation degree of tumor( P < 0.05). The VIP mRNA expression was higher in gastric adenocarcinoma with lymph node metastasis than that without lymph node matsstsis (P<0.05).The VIP protein expression of the gastric adenouarcinoma tissues was greater than that of normal control. Conclusion This findings provide a direct evidence to support the possibility that VIP play a cofactor role in the pathogenesis of gastric adenccareinoma.

OBJECTIVETo investigate the early changes of some immunological function of T-cell in chromate workers.

METHODSA total of 115 workers exposed to different levels of soluble chromate were enrolled in exposed group; while 90 non-exposure workers who lived far away from the chromate plant were enrolled as control. The air concentration of soluble chromate was determined by atomic absorption spectrometry. CD3(+), CD3(+)CD4(+), CD3(+)CD8(+) and CD4(+)/CD8(+) of T-cell were determined by flow cytometry analysis.

RESULTSThe individual air chromate concentration in the exposed group was (27.51 +/- 33.25) microg/m(3), and the control group was (0.16 +/- 0.15) microg/m(3). The significant difference between the two groups was observed (z = 8.045, P < 0.01). The levels of the lymphocyte subsets (CD3(+), CD3(+)CD4(+), CD3(+)CD8(+) and CD4(+)/CD8(+)) in exposed group were (30.08 +/- 17.75)%, (1.04 +/- 1.73)%, (11.94 +/- 9.78)%, 0.10 +/- 0.14. While, those of control group were (63.00 +/- 13.57)%, (30.51 +/- 5.16)%, (14.82 +/- 4.59)%, 2.17 +/- 0.53, higher than that of the exposed group (z values were 4.484, 5.227, 1.976, -5.218, respectively, P < 0.05).

CONCLUSIONOn the basis of individual air monitoring, the cellular immune function affected by soluble chromate is mainly based on T lymphocyte inhibition. The indicators CD3(+)CD4(+) mentioned above may be considered as efficient biomarkers in further research.

Adult ; CD4-CD8 Ratio ; Case-Control Studies ; Chromates ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Occupational Exposure ; T-Cell Antigen Receptor Specificity ; drug effects ; immunology ; T-Lymphocytes ; drug effects ; immunology

BACKGROUNDNontraumatic osteonecrosis of the femoral head (NONFH) is a debilitating disease that represents a significant financial burden for both individuals and healthcare systems. Despite its significance, however, its prevalence in the Chinese general population remains unknown. This study aimed to investigate the prevalence of NONFH and its associated risk factors in the Chinese population.

METHODSA nationally representative survey of 30,030 respondents was undertaken from June 2012 to August 2013. All participants underwent a questionnaire investigation, physical examination of hip, and bilateral hip joint X-ray and/or magnetic resonance imaging examination. Blood samples were taken after overnight fasting to test serum total cholesterol, triglyceride, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels. We then used multivariate logistic regression analysis to investigate the associations between various metabolic, demographic, and lifestyle-related variables and NONFH.

RESULTSNONFH was diagnosed in 218 subjects (0.725%) and the estimated NONFH cases were 8.12 million among Chinese people aged 15 years and over. The prevalence of NONFH was significantly higher in males than in females (1.02% vs. 0.51%, χ2 = 24.997, P < 0.001). Among NONFH patients, North residents were subjected to higher prevalence of NONFH than that of South residents (0.85% vs. 0.61%, χ 2 = 5.847, P = 0.016). Our multivariate regression analysis showed that high blood levels of triglycerides, total cholesterol, LDL-cholesterol, and non-HDL-cholesterol, male, urban residence, family history of osteonecrosis of the femoral head, heavy smoking, alcohol abuse and glucocorticoid intake, overweight, and obesity were all significantly associated with an increased risk of NONFH.

CONCLUSIONSOur findings highlight that NONFH is a significant public health challenge in China and underscore the need for policy measures on the national level. Furthermore, NONFH shares a number of risk factors with atherosclerosis.

Adult ; Age Distribution ; Aged ; Asian Continental Ancestry Group ; China ; epidemiology ; Female ; Femur Head Necrosis ; epidemiology ; Humans ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Young Adult

[ Abstract] Objective To explore the role pathway and pattern of the Kruppel-like factor 4 (KLF4) and its mRNA interaction with microRNA (miRNAs) and circular RNA (circRNAs) at 0 hour and the 120 th hour in the rat liver regeneration. Methods The rat 2 / 3 hepatectomy (partial hepatectomy, PH) model was prepared as described by Higgins, the hepatocytes were isolated according to the method of Smedsrod et al, the expression changes of mRNA, miRNA and circRNA together named as competing endogenous RNA (ceRNA) were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3. 2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at the 0 hour and the 120th hour PH, the ratio value of KLF4 mRNA showed 1. 00±0. 16 and 3. 14±0. 27, miR-881-3p displays 18. 30±1. 44 and 0. 47±0. 02, circRNA_20298 indicated 0. 32±0. 10 and 4. 24±0. 22, circRNA_14826 showed 0. 42±0. 13 and 0. 61±0. 08. At the same time, the four kinds of cell apoptosis-related genes adrenoceptor beta 2 (ADRB2), dimethylarginine dimethylaminohydrolase 2 (DDAH2), annexin A5 (ANXA5), ect, which were promoted in expression by KLF4, were down-regulated at 0 hour after PH, but the cell apoptosis-related genes synuclein gamma (SNCG), glutathione-disulfide reductase (GSR), FYVE, RhoGEF and PH domain containing 4 (FGD4), ect, which were inhibited in expression by KLF4, were up-regulated at 0 hour after PH. On the other hand, the cell apoptosis-related genes ANXA5 and thymosin beta 10 (TMSB10), which are promoted in expression by KLF4, were up-regulated at the 120th hour after PH, but the cell apoptosis-related genes chloride intracellular channel 4 (CLIC4) and ataxin 3 (ATXN3), ect, which were inhibited in expression by KLF4, were down-regulated at the 120th hour after PH. Conclusion The correlation in expression and role of the miRNAs, which are inhibited by circRNAs, KLF4, its mRNA is inhibited by miRNAs, and the cell apoptosis-related genes, which are regulated by KLF4, are helpful for the hepatocyte to be in active state 0 hour after PH and to be in apoptotic state 120-hour after PH.