Acute or subchronic clozapine treatment does not ameliorate prepulse inhibition (PPI) deficits in CPB-K mice with low levels of hippocampal NMDA receptor density

Introduction The hypo-glutamatergic hypothesis of schizophrenia is based on clinical similarities between schizophrenia and phencyclidine (PCP)-induced psychosis in mentally healthy humans. Sensorimotor gating, as measured by prepulse inhibition (PPI) of the acoustic startle response (ASR), is impaired in schizophrenic patients. In animals, noncompetitive N-methyl-d-aspartate (NMDA) antagonists such as PCP disrupt PPI in a way that resembles the defect seen in schizophrenia. In a previous study with inbred mouse strains, low PPI levels have been demonstrated in CPB-K mice possessing low levels of hippocampal NMDA receptor densities. The present study was performed to test whether the low magnitude of PPI in CPB-K mice can be reversed by the atypical antipsychotic drug clozapine (CLZ). Results Before any treatment, CPB-K mice displayed a significant (p < 0.001) lower level in PPI and a significant (p < 0.001) higher ASR when compared to BALB/cJ mice known to have high hippocampal NMDA receptor densities. Acute and subchronic effects of a 2-week treatment with CLZ at daily doses of 5 and 10 mg/kg intraperitoneally, respectively, did not reveal any significant alteration of PPI levels in CPB-K mice. Nevertheless, the examination of motor behavior during nonstimulus trials provided a positive control for the drug’s effectiveness. Conclusion In summary, (1) this study confirmed our working hypothesis: Lower levels of hippocampal glutamatergic receptor densities correspond to lower sensorimotor gating in CPB-K mice, and (2) acute or subchronic treatment with CLZ did not elevate low PPI levels in CPB-K mice. Thus, further experiments will concentrate on other antipsychotic drugs to prove the predictive validity of this animal model.     

人牙源性iPSCs分化心肌细胞促进急性心肌梗死小鼠心肌修复的研究

目的 探讨人牙源性诱导性多能干细胞（iPSCs）分化心肌细胞对急性心肌梗死（AMI）小鼠心功能的影响。方法 采用仙台病毒诱导、单克隆挑选和无饲养层体系将人牙根尖乳头干细胞（SCAP）重编程为iPSCs,心肌分化培养基定向诱导。9只BALB/C雄性小鼠按照随机数字表法分为正常组（不干预）、AMI组（AMI造模）和实验组（...     

Discovery of novel 1,3,5-triazines as potent antibacterial agent against urinary tract infection-causing clinical isolates of Escherichia coli via inhibition of DNA Gyrase

A novel series of 1,3,5-triazine-phenylthiazole-pyrazole derivatives were synthesized and subsequently tested for Escherichia coli DNA Gyrase inhibitory activity where they showed excellent inhibitory activity. The top-three ranked DNA gyrase inhibitor ( 4e , 4g and 4h ) were further subjected to antibacterial and anti-biofilm activity against clinical isolates of resistant E. coli strains obtained from Urinary Tract Infection (UTI) patients (CREC81, CREC106, CREC163). Compound 4h was identified as most potent antibacterial agent in the above study. The compound 4h was further evaluated in murine model of E. coli UTI in BALB/c mice infected by transurethral injection of CREC106 strain. Results of the study suggest that compound 4h reduces bacterial load of CREC106 in the treated mice and found approximately equipotent to Novobiocin as standard.     

白介素-18对肝癌裸鼠皮下移植瘤浸润的CD4+T细胞子集的影响

目的探讨白介素-18(IL-18)影响肝癌裸鼠皮下移植瘤浸润的T细胞子集变化的机制。方法以HepG2细胞在裸鼠皮下接种,形成人肝癌皮下移植瘤的同时,以不同剂量IL-18分为4组治疗,4组分别腹腔注射IL-18 0.75,1.00,1.25,0(模型组)μg(0.1 mL)/只,治疗4周,另设正常对照组。观察肿瘤的生长速度和瘤体大小的变化。4周后处死取肿瘤组织和脾组织,免疫磁珠阴选组织中CD4+T细胞,流式细胞术检测各组肿瘤组织及脾组织中IL-17+/IFN-γ-CD4+T(Th17细胞)、IL-17-/IFN-γ+CD4+T(Th1)和IL-17+/IFN-γ+CD4+T细胞的变化。结果 HepG2细胞株建立了裸鼠肝癌皮下移植瘤模型,IL-18抑制人肝癌皮下移植瘤的形成及转移,治疗时间越长剂量越大,抑制效果越明显;与正常对照组比较,肿瘤组织中Th17和IL-17+/IFN-γ+CD4+T细胞浸润数目增加,Th1细胞降低,与脾组织中一致,与正常对照组比较有显著差异(P<0.05)。给IL-18后,随着剂量的增加,Th1细胞增加,IL-17+/IFN-γ+CD4+T细胞和Th17细胞浸润数目降低,给药组与模型组比较有显著差异(P<0.05或0.01)。结论 IL-17+/IFN-γ+CD4+T细胞数目在裸鼠移植瘤及其脾组织中增加,可能是在肿瘤环境中,促进其向Th17细胞分化;IL-18通过诱导IFN-γ的生成促进Th1细胞的生成,呈正反馈效应抑制肿瘤的增殖和转移。     

山药提取物联合替加氟对结肠癌HT-29细胞株体内外杀伤作用的研究

目的 观察山药提取物联合替加氟对结肠癌 HT-29 细胞的体内外杀伤作用。方法 采用 2×2 析因设计的方法,用含二甲基亚砜的生理盐水（空白对照）、替加氟（36 mg/L）、山药提取物（125 mg/L）、山药提取物（125 mg/L）联合替加氟（36 mg/L）作用于结肠癌 HT-29 细胞后,观察细胞形态的变化,用 MTT 法检测对结肠癌 HT-29 细胞增殖抑制的情况,用流式细胞仪检测肿瘤干细胞（CD133+细胞）表达的情况。建立荷结肠癌 HT-29 细胞裸鼠模型,按上述方法给予治疗,计算抑瘤率。用免疫组化法检测瘤体组织的血管内皮生长因子（VEGF）阳性率。结果 联合治疗组（山药提取物联合替加氟治疗组）对结肠癌 HT-29 增殖的抑制明显高于单独使用山药提取物组及替加氟组,3 个给药组均 高于空白对照组;联合治疗组作用于 HT-29 细胞后,细胞中 CD133+细胞的比例明显低于山药提取物组及替加氟组,3 个给药组均低于空白对照组。3 个给药组治疗结束后,荷瘤鼠的瘤质量及 VEGF 阳性率明显低于空白对照组,联合治疗组低于山药提取物组及替加氟组。结论 山药提取物联合替加氟对结肠癌体内外均有杀伤作用。     

Evaluation of Alum-Naltrexone Adjuvant Activity,on Efficacy of Anti-Leishmania Immunization with Autoclaved Leishmania major (MRHO/IR/75/ER) Antigens in BALB/C Mice

Background

Naltrexone, an opioid receptor antagonist shifts the immune response toward a Th1 profile. In the current study, we evaluated the efficacy of the mixture of NTX and alum, as a new adjuvant, to enhance immune response and induce protection against Leishmania major in a mouse model.

Methods

BALB/c mice were immunized three times either autoclaved L. major promastigotes’ antigens alone or in combination with the adjuvant alum, naltrexone or the alum–naltrexone mixture. Both humoral and cellular immune responses were assessed two weeks after the last immunization and compared with control mice.

Results

The administration of alum- NTX in combination with the parasite antigen, significantly increased production of IFN-γ IFN-γ /IL-5 ratio, lymphocyte proliferation and improved DTH response against L. major. There was no significant difference in survival following challenge among groups.

Conclusion

Immunization with the alum– naltrexone mixture as an adjuvant, in combination with the autoclaved L. major promastigotes antigens, can enhance cellular immunity and shift the immune responses to a Th1 pattern.     

利用白消安致BALB/c小鼠生殖毒性建立NOA疾病模型

目的利用白消安对BALB/c雄性小鼠生殖毒性,建立不同损伤程度的NOA(non-obstructive azoospermia,NOA)动物模型。方法本研究取6~8周龄性成熟的BALB/c雄性小鼠共45只,随机分为3组:0 mg/kg组、30 mg/kg组、40 mg/kg组,每组15只。每2周观察并记录小鼠体重,睾丸和附睾湿重,睾丸体积,及生精细胞损伤程度。通过HE染色,判断生精细胞受损情况;通过免疫组化技术检测受损生精细胞停滞的减数分裂阶段,该法主要借助生精细胞减数分裂过程中的三个标记蛋白:STRA8(Stimulated by Retinoic Acid 8,STRA8)减数分裂启动标记蛋白,SCP3(Synaptonemal Complex Protein 3,SCP3)减数分裂中标记蛋白,TNP1(Transition Protein 1,TNP1)减数分裂后标记蛋白。结果注射白消安后小鼠存活良好,注射白消安2周时,生精细胞开始损伤,30 mg/kg组轻于40 mg/kg组;4周时,40 mg/kg组呈唯支持细胞样变化;6-10周时,生精功能开始恢复,30 mg/kg组恢复明显快于40 mg/kg组;40 mg/kg组STRA8、SCP3、TNP1表达在注射4周最低,第8周开始恢复到正常水平。结论白消安40 mg/kg组单次注射4周时,可建立为唯支持细胞型NOA生精障碍模型;单词注射4-8周期间,可建立损伤程度不同的NOA生精障碍模型,为睾丸组织体外培养提供稳定的研究组织。     

4-Carvomenthenol ameliorates the murine combined allergic rhinitis and asthma syndrome by inhibiting IL-13 and mucus production via p38MAPK/NF-κB signaling pathway axis

The aim of this study was to analyze the 4-carvomenthenol (carvo) oral treatment on the experimental model of the combined allergic rhinitis and asthma syndrome (CARAS). BALB/c mice were OVA-sensitized on day zero and 7th (50 μg/mL OVA in 10 mg/mL Al (OH)3) and OVA-challenged (5 mg/mL, 20 μL/animal) for three weeks. In the last week, the animals were dally challenged with aerosol of OVA and the carvo treatment (12.5, 25 or 50 mg/kg) occurred one hour before each OVA-challenge. Data were analyzed and p < 0.05 was considered significant. Carvo (12.5–50 mg/kg) decreased significantly the eosinophil migration into the nasal (NALF) and bronchoalveolar (BALF) cavities as well as on the nasal and lung tissues of sick animals. The treatment also decreased mucus production on both tissue sections stained with PAS (periodic acid-Schiff satin). In addition, the histological analyzes demonstrated that sick mice presented hyperplasia and hypertrophy of the lung smooth muscle layer followed by increasing of extracellular matrix and carvo (50 mg/kg) inhibited these asthmatic parameters. We analyzed the allergic rhinitis signals as nasal frictions and sneezing and observed that carvo decreased these two signals as well as serum OVA-specific IgE titer, type 2 cytokine synthesis, mainly IL-13, with increasing of IL-10 production. Decreasing of IL-13 production corroborated with decreasing of mucus production and these effects were dependent on p38MAPK/NF-κB(p65) signaling pathway inhibition. Therefore, these data demonstrated that a monoterpene of essential oils presents anti-allergic property on an experimental model of CARAS suggesting a new drug prototype to treat this allergic syndrome.     

伯氏考克斯体新桥株感染BALB/c小鼠的实验研究

目的:分析伯氏考克斯体新桥株对BALB/c小鼠的感染性.方法:用伯氏考克斯体新桥株腹腔接种感染小鼠,于感染后7,14,21,28 d分别处死小鼠,采用伯氏考克斯体特异的荧光定量PCR检测感染小鼠肝、脾、肺组织样本中伯氏考克斯体含量.采用间接免疫荧光法检测感染小鼠血清特异性抗体水平.结果:感染后28 d内,小鼠肝、脾、肺组织中均检出大量伯氏考克斯体,第7天检出量最高,脾的含量显著高于肝和肺,肝的含量显著高于肺.随着感染时间延长,伯氏考克斯体检出量呈下降趋势,但血清特异性抗体水平则不断升高.结论:伯氏考克斯体新桥株为强毒株,可以引起BALB/c小鼠较长时间的稳定感染;BALB/c小鼠可以用作伯氏考克斯体感染模型.