ABSTRACT
Purpose@#The soluble form programmed death-ligand 1 (sPDL1) has immunosuppressive properties and is being studied as a candidate biomarker for immuno-oncology drug development. We measured the serum sPDL1 at pre-and post-chemotherapy and evaluated its prognostic implication and dynamics during chemotherapy in advanced gastric cancer (GC). @*Materials and Methods@#We prospectively enrolled 68 GC patients who were candidates for palliative standard first-line chemotherapy, and serially collected blood at baseline and after one cycle of chemotherapy, at the best response and after disease progression. sPDL1 was measured using an enzyme-linked immunosorbent assay. Response to chemotherapy, overall survival (OS), progressionfree survival (PFS) and other prognostic factors including neutrophil-lymphocyte ratio (NLR) were obtained. The cut-off value of sPDL1 levels for survival analysis was found using C-statistics. @*Results@#The median baseline sPDL1 was 0.8 ng/mL (range, 0.06 to 6.06 ng/mL). The median OS and PFS were 14.9 months and 8.0 months, respectively. sPDL1 and NLR showed a weak positive correlation (Spearman’s rho=0.301, p=0.013). Patients with low levels of sPDL1 at diagnosis (< 1.92 ng/mL) showed a better OS and PFS than patients with a high sPDL1. The baseline sPDL1 before treatment was higher in the progressive disease group than in the stable disease and partial response groups. Patients whose sPDL1 increased after the first cycle of chemotherapy showed worse PFS and OS. Following disease progression, sPDL1 increased compared with the baseline. @*Conclusion@#sPDL1 at prechemotherapy confers a prognostic value for PFS and OS in GC patients under palliative first-line chemotherapy. Dynamics of sPDL1 during chemotherapy correlates with disease progression.
ABSTRACT
Purpose@#Currently, the DNA damage response (DDR) pathway represents a key target for new cancer drug development. Advanced biliary tract cancer (BTC) has a poor prognosis because of the lack of efficacious treatment options. Although DNA repair pathway alterations have been reported in many patients with BTC, little is known regarding the effects of DDR-targeted agents against BTC. @*Materials and Methods@#In this study, nine BTC cell lines were exposed to the WEE1 inhibitor (AZD1775). In vitro, MTT assay, colony-forming assay, cell cycle analysis, phospho-histone H3 staining assay, Transwell migration assay, and western blot were performed. Then, to enhance the antitumor effect of AZD1775, the combination treatment of WEE1 inhibitor and ataxia telangiectasia mutated and Rad3 related (ATR) inhibitor (AZD6738) was conducted using MTT assay and comet assay. Finally, HuCCT-1 and SNU2670 xenograft models were established to confirm the anti-tumor effect of AZD1775 alone. Furthermore, the combination treatment was also evaluated in SNU2670 xenograft models. @*Results@#AZD1775 blocked the phosphorylation of CDC2 and CDC25C in all cell lines, but significantly increased apoptosis and S phase arrest in sensitive cells. However, increased p-ATR and phosphorylated ataxia telangiectasia mutated levels were observed in less sensitive cells. In addition, in vitro and in vivo data illustrated that AZD1775 combined with AZD6738 exerted more potent anti-tumor effects than either drug alone. Although WEE1 inhibition has promising anti-tumor effects in some BTC cells, the addition of ATR inhibitors could enhance its efficacy. @*Conclusion@#Taken together, this study supports further clinical development of DDR-targeted strategies as monotherapy or combination regimens for BTC.
ABSTRACT
Purpose@#Pancreatic cancer (PC) is one of the most lethal cancers worldwide, but there are currently no effective treatments. The DNA damage response (DDR) is under investigation for the development of novel anti-cancer drugs. Since DNA repair pathway alterations have been found frequently in PC, the purpose of this study was to test the DDR-targeting strategy in PC using WEE1 and ATM inhibitors. @*Materials and Methods@#We performed in vitro experiments using a total of ten human PC cell lines to evaluate antitumor effect of AZD1775 (WEE1 inhibitor) alone or combination with AZD0156 (ATM inhibitor). We established Capan-1–mouse model for in vivo experiments to confirm our findings. @*Results@#In our research, we found that WEE1 inhibitor (AZD1775) as single agent showed anti-tumor effects in PC cells, however, targeting WEE1 upregulated p-ATM level. Here, we observed that co-targeting of WEE1 and ATM acted synergistically to reduce cell proliferation and migration, and to induce DNA damage in vitro. Notably, inhibition of WEE1 or WEE1/ATM downregulated programmed cell death ligand 1 expression by blocking glycogen synthase kinase-3β serine 9 phosphorylation and decrease of CMTM6 expression. In Capan-1 mouse xenograft model, AZD1775 plus AZD0156 (ATM inhibitor) treatment reduced tumor growth and downregulated tumor expression of programmed cell death ligand 1, CMTM6, CD163, and CXCR2, all of which contribute to tumor immune evasion. @*Conclusion@#Dual blockade of WEE1 and ATM might be a potential therapeutic strategy for PC. Taken toget
ABSTRACT
ObjectiveRenal fibrosis is the basic pathological process of chronic kidney disease. To explore the protective effect of sildenafil (Sil) on renal fibrosis in mice, and provide experimental evidence for the clinical application of sildenafil in the treatment of renal fibrosis.Methods90 Kunming mice were randomly divided into three groups. Sham operation group (n=30), the mice only had ureteral separation, no ligation and ureteral clipping, which was subcutaneously injected with 0.9% NaCl solution in dose of 1 mL/(10 g·d); UUO model group (n=30), the UUO model was prepared by separating and ligating ureters in mice, and those were given subcutaneous injection with 0.9% NaCl solution in 1 mL/(10 g·d); UUO+Sil medicated group (n=30), mice were subcutaneously injected with sildena in 12 mg/(kg·d) at the same time every day for 14 days from the 1st day of UUO model. On the 3rd, 7th and 14th day, 10 mice whoes blood from eyeball was collected to determine serum creatinine and urea nitrogen were randomly selected from each group. HE and Masson staining were performed on the left kidney tissue to observe the pathological changes of the kidney tissue. The levels of Akt and GSK-3β protein and its phosphorylation in renal tissue were determined by western blot.ResultsAfter 3 days in UUO model, the contents of serum creatinine (63.10±2.90mol/L ) and urea nitrogen (12.87±0.40mmol/L) in the UUO group were significantly higher than those in the sham group [(26.00±3.70) mol/L, (8.07±0.60) mmol/L] (P<0.05). The contents of serum creatinine and urea nitrogen [(64.39±2.50) mol/L, (13.59±0.30) mmol/L] on the 7th day were higher than those in the sham group [(29.18±3.50) mol/L, (9.14±0.50) mmol/L] (P<0.05). The contents of serum creatinine and urea nitrogen [(64.39±2.50) mol/L, (15.03±0.50) mmol/L] on the 14th day were also significantly higher than those in the sham group [(29.74±2.50) mol/L, (9.90±0.20) mmol/L] (P<0.05). Compared with UUO group, the creatinine of mice on the 3rd, 7th and 14th day in the medicated group was lower (P<0.05). Compared with UUO group , urea nitrogen on the 3rd, 7th and 14th day in the medicated group was decreased (P<0.05). Compared with the sham operation group, the expression levels of p-AKT /Akt and p-GSK-3β/GSK-3β in the UUO group were significantly decreased (P<0.05), while the protein expression levels of p-AKT /Akt and p-GSK-3β/GSK-3β in the medicated group were significantly increased compared with the UUO group (P<0.05). On the 7th day in UUO model, there were many changes included atrophic renal tubular epithelial cells, dilated lumen, widened interstitium and more infiltrated inflammatory cells. On the 14th day in UUO, the above changes were more obvious, interstitial fibroblast hyperplasia and interstitial fibrosis, and the above pathological changes were reduced in the medicated group compared with the UUO model group. The collagen fibers in the UUO model group increased gradually with time. On the 14th day in UUO, the collagen fibers in the interstitium increased significantly, the tubular epithelium was damaged, and the red staining cells became lighter. These findings were less severe in the medicated group than in the UUO model group.ConclusionSildenafil can alleviate renal damage caused by renal fibrosis. Sildenafil inhibited renal fibrosis in UUO model, and its mechanism may be related to up-regulation of Akt/GSK3β pathway.
ABSTRACT
ObjectiveRenal fibrosis is the basic pathological process of chronic kidney disease. To explore the protective effect of sildenafil (Sil) on renal fibrosis in mice, and provide experimental evidence for the clinical application of sildenafil in the treatment of renal fibrosis.Methods90 Kunming mice were randomly divided into three groups. Sham operation group (n=30), the mice only had ureteral separation, no ligation and ureteral clipping, which was subcutaneously injected with 0.9% NaCl solution in dose of 1 mL/(10 g·d); UUO model group (n=30), the UUO model was prepared by separating and ligating ureters in mice, and those were given subcutaneous injection with 0.9% NaCl solution in 1 mL/(10 g·d); UUO+Sil medicated group (n=30), mice were subcutaneously injected with sildena in 12 mg/(kg·d) at the same time every day for 14 days from the 1st day of UUO model. On the 3rd, 7th and 14th day, 10 mice whoes blood from eyeball was collected to determine serum creatinine and urea nitrogen were randomly selected from each group. HE and Masson staining were performed on the left kidney tissue to observe the pathological changes of the kidney tissue. The levels of Akt and GSK-3β protein and its phosphorylation in renal tissue were determined by western blot.ResultsAfter 3 days in UUO model, the contents of serum creatinine (63.10±2.90mol/L ) and urea nitrogen (12.87±0.40mmol/L) in the UUO group were significantly higher than those in the sham group [(26.00±3.70) mol/L, (8.07±0.60) mmol/L] (P<0.05). The contents of serum creatinine and urea nitrogen [(64.39±2.50) mol/L, (13.59±0.30) mmol/L] on the 7th day were higher than those in the sham group [(29.18±3.50) mol/L, (9.14±0.50) mmol/L] (P<0.05). The contents of serum creatinine and urea nitrogen [(64.39±2.50) mol/L, (15.03±0.50) mmol/L] on the 14th day were also significantly higher than those in the sham group [(29.74±2.50) mol/L, (9.90±0.20) mmol/L] (P<0.05). Compared with UUO group, the creatinine of mice on the 3rd, 7th and 14th day in the medicated group was lower (P<0.05). Compared with UUO group , urea nitrogen on the 3rd, 7th and 14th day in the medicated group was decreased (P<0.05). Compared with the sham operation group, the expression levels of p-AKT /Akt and p-GSK-3β/GSK-3β in the UUO group were significantly decreased (P<0.05), while the protein expression levels of p-AKT /Akt and p-GSK-3β/GSK-3β in the medicated group were significantly increased compared with the UUO group (P<0.05). On the 7th day in UUO model, there were many changes included atrophic renal tubular epithelial cells, dilated lumen, widened interstitium and more infiltrated inflammatory cells. On the 14th day in UUO, the above changes were more obvious, interstitial fibroblast hyperplasia and interstitial fibrosis, and the above pathological changes were reduced in the medicated group compared with the UUO model group. The collagen fibers in the UUO model group increased gradually with time. On the 14th day in UUO, the collagen fibers in the interstitium increased significantly, the tubular epithelium was damaged, and the red staining cells became lighter. These findings were less severe in the medicated group than in the UUO model group.ConclusionSildenafil can alleviate renal damage caused by renal fibrosis. Sildenafil inhibited renal fibrosis in UUO model, and its mechanism may be related to up-regulation of Akt/GSK3β pathway.
ABSTRACT
PURPOSE: Jab1 is a coactivator of c-Jun that enhances the transcriptional function of c-Jun. Jab1 is frequently overexpressed in various cancers and is associatedwith poor prognosis of cancer patients. Thus, Jab1 could be a potential therapeutic target in cancer. However, the role of Jab1 in biliary tract cancer (BTC) has not been studied. MATERIALS AND METHODS: We performed in vitro and in vivo experiments to evaluate the therapeutic potential ofJab1 inhibition in BTC. RESULTS: Among 8 BTC cell lines, many showed higher Jab1 expression levels. In addition, Jab1 silencing by siRNA increased p27 expression levels. SNU478 and HuCCT-1 cells exhibited profound Jab1 knockdown and increased p27 expression by Jab1-specific siRNA transfection. Jab1 silencing induced anti-proliferative and anti-migratory effects and resulted in G1 cell cycle arrest in SNU478 and HuCCT-1 cells. In addition, Jab1 silencing potentiated the anti-proliferative and anti-migratory effects of cisplatin by increasing DNA damage. Interestingly,Jab1 knockdown increased PTEN protein half-life, resulting in increased PTEN expression. In the HuCCT-1 mouse xenograft model, stable knockdown of Jab1 by shRNA also showed anti-proliferative effects in vivo, with decreased Ki-67 expression and AKT phosphorylation and increased Terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling and p27 expression. CONCLUSION: Jab1 knockdown demonstrated anti-proliferative and anti-migratory effects in BTC cells by increasing DNA damage and stabilizing PTEN, resulting in G1 cell cycle arrest. In addition, Jab1 silencing potentiated the anti-proliferative effects of cisplatin. Our data suggest that Jab1 may be a potential therapeutic target in BTC that is worthy of further investigations.
Subject(s)
Animals , Humans , Mice , Biliary Tract Neoplasms , Biliary Tract , Cell Line , Cisplatin , DNA Damage , G1 Phase Cell Cycle Checkpoints , Half-Life , Heterografts , In Vitro Techniques , Phosphorylation , Prognosis , PTEN Phosphohydrolase , RNA, Small Interfering , TransfectionABSTRACT
PURPOSE: The DNA damage response (DDR) is a multi-complex network of signaling pathways involved in DNA damage repair, cell cycle checkpoints, and apoptosis. In the case of biliary tract cancer (BTC), the strategy of DDR targeting has not been evaluated, even though many patients have DNA repair pathway alterations. The purpose of this study was to test the DDR-targeting strategy in BTC using an ataxia-telangiectasia and Rad3-related (ATR) inhibitor. MATERIALS AND METHODS: A total of nine human BTC cell lines were used for evaluating anti-tumor effect of AZD6738 (ATR inhibitor) alone or combination with cytotoxic chemotherapeutic agents through MTT assay, colony-forming assays, cell cycle analyses, and comet assays. We established SNU478-mouse model for in vivo experiments to confirm our findings. RESULTS: Among nine human BTC cell lines, SNU478 and SNU869 were the most sensitive to AZD6738, and showed low expression of both ataxia-telangiectasia mutated (ATM) and p53. AZD6738 blocked p-Chk1 and p-glycoprotein and increased γH2AX, a marker of DNA damage, in sensitive cells. AZD6738 significantly increased apoptosis, G2/M arrest and p21, and decreased CDC2. Combinations of AZD6738 and cytotoxic chemotherapeutic agents exerted synergistic effects in colony-forming assays, cell cycle analyses, and comet assays. In our mouse models, AZD6738 monotherapy decreased tumor growth and the combination with cisplatin showed more potent effects on growth inhibition, decreased Ki-67, and increased terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling than monotherapy with each drug. CONCLUSION: In BTC, DDR targeting strategy using ATR inhibitor demonstrated promising antitumor activity alone or in combination with cytotoxic chemotherapeutic agents. This supports further clinical development of DDR targeting strategy in BTC.
Subject(s)
Animals , Humans , Mice , Apoptosis , Ataxia Telangiectasia , Biliary Tract Neoplasms , Biliary Tract , Cell Cycle , Cell Cycle Checkpoints , Cell Line , Cisplatin , Comet Assay , DNA Damage , DNA Repair , DNA , ATP Binding Cassette Transporter, Subfamily B, Member 1ABSTRACT
PURPOSE: The soluble programmed death-ligand 1 (sPDL1) has immunosuppressive activity and is a candidate biomarker for immuno-oncology drug development. In this study, we measured sPDL1 at pre- and post-chemotherapy and at disease progression to uncover the dynamics of sPDL1 during treatment in biliary tract cancer (BTC) patients. MATERIALS AND METHODS: From 90 BTC patients (training cohort, 53; validation cohort, 37) who were candidates for palliative first-line chemotherapy, blood was collected at pre- and post-chemotherapy (at the time of best response) and at disease progression. The sPDL1 levels were measured using an enzyme-linked immunosorbent assay. Responses to chemotherapy, overall survival (OS), and other prognostic factors including the neutrophil-lymphocyte ratio (NLR) were analyzed. RESULTS: The OS of all patients was 11.5 months (confidence interval [CI], 9.7 to 16.2). The best response was complete response in seven (7.8%), partial response in 20 (22.2%), stable disease in 52 (57.8%), and disease progression (PD) in 11 patients (12.2%). Patients with high pre-chemotherapy sPDL1 (≥ 1.30 ng/mL) showed worse OS than patients with low prechemotherapy sPDL1 (9.1 months vs. 12.5 months, p=0.003). In multivariate analyses, high pre-chemotherapy sPDL1 (hazard ratio [HR], 1.96; 95% CI, 1.2 to 3.9; p=0.011) and high pre-chemotherapy NLR (HR, 1.82; 95% CI, 1.1 to 3.0; p=0.020) were independent poor prognostic factors for OS. At the time of PD, sPDL1 was increased significantly compared with pre-chemotherapy sPDL1 (1.59 ng/mL vs. 0.72 ng/mL, p=0.003). CONCLUSION: The sPDL1 at pre-chemotherapy confers the prognostic value for OS in BTC patients under palliative chemotherapy. The dynamics of sPDL1 during chemotherapy correlate with disease burden and have prognostic value.
Subject(s)
Humans , Biliary Tract Neoplasms , Biomarkers , Cohort Studies , Disease Progression , Drug Therapy , Enzyme-Linked Immunosorbent Assay , Multivariate Analysis , PrognosisABSTRACT
Lenvatinib is a multitargeted tyrosine kinase inhibitor approved for use in patients with iodine-131–refractory thyroid cancer. The common adverse events of lenvatinib include hypertension, proteinuria, fatigue, and diarrhea. To date, no report on Pneumocystis pneumonia (PCP) in patients receiving lenvatinib has been published. Here, we present a case of severe PCP that led to the death of a 79-year-old woman who was diagnosed with poorly differentiated thyroid cancer and received lenvatinib. The development of PCP should be considered when patients taking lenvatinib show clinical symptoms of pneumonia, and regular chest X-ray follow-up is needed for patients receiving lenvatinib.
Subject(s)
Aged , Female , Humans , Diarrhea , Fatigue , Follow-Up Studies , Hypertension , Lung Diseases, Interstitial , Pneumocystis , Pneumonia , Pneumonia, Pneumocystis , Protein-Tyrosine Kinases , Proteinuria , Thorax , Thyroid Gland , Thyroid NeoplasmsABSTRACT
PURPOSE: The neurological molecular mechanisms underlying the voiding dysfunction associated with nonbacterial chronic prostatitis/chronic pelvic pain syndrome remain poorly understood. In this study, we assessed whether prostate inflammation activated bladder afferent neurons, leading to bladder dysfunction, and sought to elucidate the underlying mechanisms. METHODS: Thirty male Sprague-Dawley rats were divided into 3 groups: sham-saline, formalin-injected, and capsaicin-pretreated and formalin-injected. Chemical prostatitis was induced by 0.1 mL of 10% buffered formalin injected into the ventral prostate. Capsaicin was injected subcutaneously to desensitize capsaicin-sensitive nerves. In each group, conscious cystometry was performed, and c-fos expression within the spinal cord was determined immunocytochemically. Double immunofluorescent staining with c-fos and choline acetyltransferase (ChAT) was performed. On the third day after pseudorabies virus (PRV) infection, c-fos and PRV double-staining was performed. RESULTS: Intraprostatic formalin significantly increased the maximal voiding pressure and decreased the intercontraction interval, compared with controls. Pretreatment with capsaicin significantly reversed these effects. More c-fos-positive cells were observed in the sacral parasympathetic nucleus (SPN) and dorsal gray commissure (DCM) in the prostatitis group than in the sham group. c-fos-positive cells decreased in the capsaicin-pretreated group. Preganglionic neurons labeled by c-fos and ChAT were observed in the SPN in rats with prostatitis. Interneurons labeled by c-fos and PRV were identified in the DCM after PRV infection. CONCLUSIONS: Our results suggest that prostate inflammation activates afferent nerve fibers projecting to the lumbosacral spinal cord, producing reflex activation of spinal neurons innervating the bladder and bladder hyperreflexia. This is mediated by capsaicin-sensitive prostate afferent neurons.
Subject(s)
Animals , Humans , Male , Rats , Capsaicin , Choline O-Acetyltransferase , Formaldehyde , Herpesvirus 1, Suid , Inflammation , Interneurons , Models, Animal , Nerve Fibers , Neurons , Neurons, Afferent , Pelvic Pain , Prostate , Prostatitis , Rats, Sprague-Dawley , Reflex , Reflex, Abnormal , Spinal Cord , Urinary BladderABSTRACT
PURPOSE: To evaluate whether mild chemical irritation of the bladder in neonatal rats is associated with persistent vanilloid receptor transient receptor potential vanilloid subfamily 1 (TRPV1) activity in adult rats. METHODS: Female Sprague-Dawley rats were used. Ten-day-old rat pups underwent bladder sensitization via intravesical infusion of 0.2% acetic acid in saline with or without prior bladder desensitization with capsaicin. After 8 weeks, 3 groups of rats (control [group 1], bladder sensitization [group 2], and bladder desensitization [group 3]) underwent cystometry. Inflammation of bladder tissue and the expression of TRPV1 in bladder tissue and dorsal root ganglia (DRG) were also evaluated. RESULTS: The bladder sensitization group showed more frequent voiding contractions. TRPV1 expression in adult bladder tissue was elevated in group 2. TRPV1 mRNA levels in the bladder and DRG were significantly higher in group 2 than in group 1. Moreover, group 2 had significantly more DRG neurons (identified by uptake of the retrograde label Fast Blue) that exhibited TRPV1 immunoreactivity. CONCLUSIONS: We found a significant association between neonatal bladder sensitization and persistent TRPV1 activity in adult rats. This is the first study to focus on the underlying pathogenesis of bladder overactivity from childhood to adulthood. Our findings could lead to the development of new strategies for the treatment and prevention of adult urinary symptoms arising from childhood urinary tract dysfunction.
Subject(s)
Adult , Animals , Female , Humans , Rats , Acetic Acid , Capsaicin , Cystitis, Interstitial , Diagnosis-Related Groups , Ganglia, Spinal , Inflammation , Neurons , Rats, Sprague-Dawley , RNA, Messenger , TRPV Cation Channels , Urinary Bladder , Urinary Tract , Urinary Tract InfectionsABSTRACT
Objective The aim of this study is to explore epidemic characteristics of HIV/AIDS by different route of transmission during 2011—2014 in Huzhou City,then to provide a scientific basis for the prevention and control of HIV. Methods The epidemiological case data of HIV/AIDS from 2011 to 2014 were collected in Huzhou City by China information system for disease control and prevention.Descriptive epidemiological methods were used for analysis.Results A total of 436 cases with HIV/AIDS were reported during 2011—2014 in Huzhou City,and the number of HIV/AIDS reports increased year by year.The main route of transmission include heterosexual contact,which was accounted for 56.65%.MSM transmission was accounted for 38.53%,and injection drug transmission was accounted for 3.90%.Mother to child transmission was 1 case and blood transfusion /blood products transmission were 3 cases,which accounting for 0.92%.The constituent ratio of injecting drug patients,mother to child transmission or blood transfusion /blood products patients presented declining trend (P <0.05).Patients who were infected through heterosexual contact mainly were 30 to <60 years of age (68.83%),junior middle school or below education level (80.97%),married (61.94%).Patients who were infected through MSMmainly were 15 to <45 years of age (76.19%),high school or higher education (47.62%), unmarried (51.19%),household registration of Huzhou City (52.98%).Patients who were infected through injection <br> drug mainly were 30 to <45 years of age (70.59%),primary school or lower education level (82.35%),unmarried (47.06%),household registration of other province (94.12%).Most cases were detected HIV positive through clinical tests,which accounting for 51.15%.Most HIV /AIDS of MSM,heterosexual transmission and inject -drugs were distributed in Wu Xing District,which accounting for 67.26%,51.42% and 64.71%,respectively.51.15% HIV /AIDS were detected by clinical test.Conclusion The reported cases of HIV /AIDS were still mainly transmitted by heterosexual contact in recent years in Huzhou City,and the constituent ratio of MSMtransmission has increased slightly.
ABSTRACT
Objective To learn the infection status of sexually transmitted diseases (STDs)and acquired immunodeficiency syndrome (AIDS)among female sex workers (FSWs)in Huzhou,and to learn the awareness rate of knowledge of AIDS, and to provide scientific evidence for the development of prevention and control measures.Methods According to the national AIDS surveillance standards,a questionnaire survey was conducted among FSWs and blood samples were collected to detect the antibodies to human immunodeficiency virus (HIV),syphilis and hepatitis C virus.Results A total of 800 FSWs,with an average age (25. 5 ±5. 0 years old)were investigated,and the awareness rate of AIDS related knowledge was 92. 0%.The positive rate of syphilis antibody was 2. 9%and the positive rate of hepatitis C antibody was 0. 2%.HIV antibody was tested negative.The persistent condom use rate among commercial sex workers was 57. 6% in the recent month.The awareness rate of AIDs related knowledge among FSWs with senior middle school education and above was 3. 51 times of those with primary school education and below.Conclusion The prevalence of syphilis and hepatitis C infection among FSWs were high in Huzhou.It is necessary to strengthen the health education among FSWs to improve the awareness of the knowledge,especially for those with low level education.And it is necessary to improve the accessibility of AIDs prevention service to reduce the spread of HIV.
ABSTRACT
Chemical constituents of Inula japonica were isolated and purified by repeated column chromatographies, over silica gel, and Toyopearl HW-40, and preparative HPLC. On the basis of spectral data analysis, including NMR and MS data, the structures of the isolates were elucidated and their anti-inflammatory activities were assayed. Fifteen compounds were isolated from the ethyl acetate extract of I. japonica, and their structures were elucidated as dihydrosyringenin (1), (3S, 5R, 6S, 7E)-5,6-epoxy-3-hydroxy-7-megastigmen-9-one (2), (6R, 7E) -9-hydroxy-4,7-megastigmadien-3-one (3), arnidiol (4), taraxasterol acetate (5), 8,9,10-trihydroxythymol (6), taxifolin (7), luteolin (8), napetin (9), eupatin (10), spinacetin (11), quercetin (12), p-hydroxycinnamic acid (13), caffeic acid (14), and caffeoyl acetate (15). Compounds 1, 2, 7, 13 and 15 were isolated from the genus Inula for the first time, and compounds 3, 4, 9-11 and 14 were isolated from this plant for the first time. The anti-inflammatory activity result showed that compounds 3, 6-12 and 14 exhibited inhibition effect against leukotriene C4 (LTC4) synthesis and degranulation definitely in c-Kit Ligand (KL) induced mast cells, and compound 8 and 12 also had the suppression effect against lipopolysacharide(LPS) induced nitric oxide (NO) activity in RAW264.7 macrophages. It is firstly reported that compounds 7 and 9-11 possessed potent inhibition activities against LTC4 generation and degranulation in mast cells.
Subject(s)
Animals , Mice , Anti-Inflammatory Agents , Chemistry , Pharmacology , Cell Line , Inula , Chemistry , Macrophages , Mast Cells , Mice, Inbred BALB C , Plant Extracts , Chemistry , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the intervention effect of aqueous fractions from Boschniakia rossica (BRAF) on hepatic oxidative stress in mice with liver injury induced by carbon tetrachloride (CCl4).</p><p><b>METHOD</b>The experimental mice were randomly assigned into the normal control group, the model group, the silymarin (positive control) group, as well as high and low dose BRAF groups. Mice were treated intragastrically with silymarin or BRAF once every day for 7 days. At the end of the experiment, CCl4 was injected intraperitoneally into the mice to establish the acute liver injury model. The pathological changes was detected with hematoxylin and eosin (HE) staining, and the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), superoxide dismutase (SOD) , catalase (CAT), glutathione peroxidase (GPx), Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, and the contents of reduced glutathione (GSH) and malondialdehyde (MDA) were detected by the colorimetric method.</p><p><b>RESULT</b>BRAF significantly reduced ALT, AST and ALP activities in serum, alleviated hepatic injury induced by CCl4, increased SOD, CAT, GPx and GSH levels in liver, and SOD, Na + -K + -ATPase and Ca2+ -Mg2 + -ATPase activities in liver mitochondria, and decreased the MDA content in liver and liver mitochondria.</p><p><b>CONCLUSION</b>BRAF reduces hepatic oxidative stress in mice with acute liver injury induced by CCl4, thereby showing the protective effect on mice with acute liver injury induced by CCl4.</p>
Subject(s)
Animals , Male , Mice , Carbon Tetrachloride , Toxicity , Chemical and Drug Induced Liver Injury , Metabolism , Pathology , Drugs, Chinese Herbal , Chemistry , Pharmacology , Liver , Metabolism , Pathology , Mitochondria , Metabolism , Orobanchaceae , Chemistry , Oxidative Stress , Solubility , Water , ChemistryABSTRACT
PURPOSE: Bladder outlet obstruction (BOO) causes storage and voiding dysfunction in the lower urinary tract. We investigated the expression of transient receptor potential cation channel subfamily M member 8 (TRPM8) to evaluate the relationship between TRPM8 expression and overactive bladder (OAB) in a rat model of BOO. METHODS: Fifty female Sprague-Dawley rats were divided into 4 groups; normal (n=10), normal-menthol (n=10), BOO (n=15), BOO-menthol (n=15). After 3 weeks, cystometry was performed by infusing physiological saline and menthol (3 mM) into the bladder at a slow infusion rate. The histological changes and expression of TRPM8 in the bladder were investigated by Masson's trichrome staining, immunofluorescence and reverse transcription-polymerase chain reaction. RESULTS: Cystometry showed that the intercontraction interval (ICI; 428.2+/-23.4 vs. 880.4+/-51.2, P<0.001), micturition pressure (MP; 25.7+/-1.01 vs. 71.80+/-3.01, P<0.001), and threshold pressure (2.9+/-0.25 vs. 9.2+/-1.58, P<0.01) were significantly increased in BOO rats. The bladder wall was significantly dilated compared with the control. Detrusor muscle hypertrophy and a thick mucosa layer were observed in BOO bladder. After menthol treatment, ICIs were decreased and MPs were increased in the menthol treatment groups. TRPM8-positive cells and mRNA were predominantly increased in the bladder and dorsal root ganglia of all groups compared with the normal group. CONCLUSIONS: Increased bladder wall thickness and proportion of collagen probably affect voiding dysfunction. Furthermore, an increase of TRPM8 expression in BOO may induce entry of Ca2+ from the extracellular space or stores. The increase of Ca2+ probably causes contraction of smooth muscle in BOO. However, OAB symptoms were not observed after menthol treatment although the expression of TRPM8 was abundant in the bladder epithelium after menthol treatment. Although OAB in BOO models may be caused by complex pathways, regulation of TRPM8 presents possibilities for OAB treatment.
Subject(s)
Animals , Female , Humans , Rats , Cold Temperature , Collagen , Contracts , Epithelium , Extracellular Space , Fluorescent Antibody Technique , Ganglia, Spinal , Hypertrophy , Menthol , Mucous Membrane , Muscle, Smooth , Muscles , Rats, Sprague-Dawley , RNA, Messenger , Urinary Bladder , Urinary Bladder Neck Obstruction , Urinary Bladder, Overactive , Urinary Tract , UrinationABSTRACT
<p><b>OBJECTIVE</b>To understand the situations of pesticide poisoning in Huzhou and take preventive strategy and measures against the pesticide poisoning.</p><p><b>METHODS</b>Case reports between 2006 and 2009 in the data base of reporting system for occupational diseases were computed by Excel for windows and statistical significance by SPSS12.0.</p><p><b>RESULTS</b>A total of 2298 patients were reported from 2006 to 2009. Among them, the incidence of occupational poisoning accounted for 25.59% (588 cases), including 4 fatalities (fatality rate, 0.68%). Male patients (458 cases, 77.89%) were more than female ones (130 cases, 22.11%) in occupational pesticides poisoning. Summer and autumn were the most seasons in occupational pesticides poisoning occurring. The incidence of non-occupational pesticides poisoning accounted for 74.41% (1710, cases), including 112 fatalities (fatality rate, 6.55%). Female patients (952 cases, 55.67%) were more than male ones (758 cases, 44.33%) in non-occupational pesticides poisoning. 15 - 55 years were the highest incidences among non-occupational pesticides poisoning patients. Insecticides especially organophosphorus insecticides such as methamidophos, parathion, and omethoate comprised a higher proportion, accounting for 79.98% of the pesticides poisoning.</p><p><b>CONCLUSION</b>The incidence and the fatality rate of occupational pesticide poisoning were reduced in the city. However, more attention should be paid to non-occupational pesticides poisoning. To decrease the numbers of pesticide poisoning and the risks of death, the relevant departments should take preventive strategy and measures against the pesticide poisoning.</p>
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Humans , Infant , Middle Aged , Young Adult , Age Distribution , Agricultural Workers' Diseases , Epidemiology , China , Epidemiology , Incidence , Occupational Exposure , Pesticides , PoisoningABSTRACT
BACKGROUND: The flowers of Inula japonica (Inulae Flos) have long been used in traditional medicine for the treatment of inflammatory diseases. In the present study, we investigated the anti-inflammatory properties of Inulae Flos Extract (IFE). METHODS: The anti-inflammatory effects of IFE against nitric oxide (NO), PGE2, TNF-alpha, and IL-6 release, as well as NF-kappa B and MAP kinase activation were evaluated in RAW 264.7 cells. RESULTS: IFE inhibited the production of NO and the expression of inducible nitric oxide synthase (iNOS) in LPS-stimulated RAW264.7 cells. In addition, IFE reduced the release of pro-inflammatory cytokines, such as TNF-alpha and IL-6. Furthermore, IFE inhibited the NF-kappa B activation induced by LPS, which was associated with the abrogation of I kappa B-alpha degradation and subsequent decreases in nuclear p65 and p50 levels. Moreover, the phosphorylation of ERK, JNK, and p38 MAP kinases in LPS-stimulated RAW 264.7 cells was suppressed by IFE in a dose-dependent manner. CONCLUSION: These results suggest that the anti-inflammation activities of IFE might be attributed to the inhibition of NO, iNOS and cytokine expression through the down-regulation of NF-kappa B activation via suppression of I kappa B alpha and MAP kinase phosphorylation in macrophages.
Subject(s)
Cytokines , Dinoprostone , Down-Regulation , Flowers , I-kappa B Proteins , Interleukin-6 , Inula , Macrophages , Medicine, Traditional , NF-kappa B , Nitric Oxide , Nitric Oxide Synthase Type II , Phosphorylation , Phosphotransferases , Tumor Necrosis Factor-alphaABSTRACT
PURPOSE: Exposure of male reproductive organs to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) has been reported to cause developmental changes. In this study, we evaluated the effects of in utero TCDD exposure on male reproductive development. MATERIALS AND METHODS: Pregnant C57BL/6 mice were administered a single intraperitoneal injection of TCDD (1microgram/kg) on gestation day (GD) 15. The offspring were examined in the immature stage on postnatal day (PND) 30 and in the mature stage on PND 60. The testes were examined for histological changes, androgen receptor (AR), proliferating cell nuclear antigen (PCNA) and apoptosis following the measurement of morphological changes. RESULTS: Anogenital distance (AGD) and testis weights were reduced by TCDD exposure both on PND 30 and PND 60 while body weights and length of male offspring were not affected by TCDD. The regular sperm developmental stage was impaired with TCDD treatment on PND 30. However, no difference was found between the control group and TCDD groups on PND 60. Simultaneously, the expression of AR was also reduced on PND 30, while it was increased on PND 60 compared with the control group. The expression of PCNA was decreased whereas apoptosis was not affected by TCDD both on PND 30 and PND 60. CONCLUSION: These results suggest that in utero exposure to TCDD influences the development of testes by inhibiting the expression of AR and PCNA. Moreover, the adverse effects of TCDD on male offspring reduced over time.
Subject(s)
Animals , Female , Male , Mice , Pregnancy , Apoptosis/drug effects , Cell Proliferation , Embryonic Development/drug effects , Environmental Pollutants/toxicity , Maternal Exposure , Mice, Inbred C57BL , Organ Size/drug effects , Receptors, Androgen/metabolism , Testis/drug effects , Polychlorinated Dibenzodioxins/toxicityABSTRACT
PURPOSE: c-fos expression in spinal neurons that are activated by lower urinary tract stimulation are not organ specific. In this experiment, we demonstrated changes of c-fos expression in bladder-specific preganglionic neurons (PGNs) and interneurons using pseudorabies virus (PRV). MATERIALS AND METHODS: Forty Sprague-Dawley rats were used. We identified the neuronal pathway associated with the bladder by injecting PRV into the detrusor. An immunohistochemical method was used to stain Fos-protein encoded by the c-fos gene. Immunofluorescent staining for PRV was performed to evaluate changes in bladder-specific spinal neurons. RESULTS: Immunofluorescent staining with choline acetyltransferase (ChAT) revealed that the sacral parasympathetic nucleus (SPN) regions contained 9.8 PGNs/ section. In rats with chronic spinal cord injury by intravesical saline instillation, 82.4+/-10.3% of PGNs in SPN exhibited Fos-immunoreactive (IR). Two and a half days after PRV infection, PRV-IR PGNs were observed at 5.4 PGNs/ section, and 2.7+/-1.6% of them exhibited Fos-IR. Unlike ChAT-IR PGNs, PRV-IR PGNs are bladder-specific neurons and PRV-IR and Fos-IR cells found in the back of PRV-IR PGNs are bladder- specific interneurons. Three days after PRV infection, we observed many PRV-IR and Fos-IR cells in the dorsal commissure. These neurons are interneurons distributed in the bladder. CONCLUSION: We confirmed that in chronic spinal cord injury, the patterns of c-fos expression in bladder-specific spinal neurons were similar to those in voiding-reflex related spinal neurons, which had already been demonstrated earlier. We believe that our methodology can be applied to study interactions between voiding and other organs as well, such as the urethra and prostate.