Search

A method for high-throughput cloning and analysis of short hairpin RNAs (shRNAs) is described. Using this approach, 464 shRNAs against 116 different genes were screened for knockdown efficacy, enabling rapid [...]

RPM2 is a Saccharomyces cerevisiae nuclear gene that encodes the protein subunit of mitochondrial RNase P and has an unknown function essential for fermentative growth. Cells lacking mitochondrial RNase P cannot respire and accumulate lesions in their mitochondrial DNA. The effects of a new RPM2 allele, rpm2-100, reveal a novel function of RPM2 in mitochondrial biogenesis. Cells with rpm2-100 as their only source of Rpm2p have correctly processed mitochondrial tRNAs but are still respiratory deficient. Mitochondrial mRNA and rRNA levels are reduced in rpm2-100 cells compared to wild type. The general reduction in mRNA is not reflected in a similar reduction in mitochondrial protein synthesis. Incorporation of labeled precursors into mitochondrially encoded Atp6, Atp8, Atp9, and Cytb protein was enhanced in the mutant relative to wild type, while incorporation into Cox1p, Cox2p, Cox3p, and Var1p was reduced. Pulse-chase analysis of mitochondrial translation revealed decreased rates of translation of COX1, COX2, and COX3 mRNAs. This decrease leads to low steady-state levels of Cox1p, Cox2p, and Cox3p, loss of visible spectra of [aa.sub.3] cytochromes, and low cytochrome c oxidase activity in mutant mitochondria. Thus, RPM2 has a previously unrecognized role in mitochondrial biogenesis, in addition to its role as a subunit of mitochondrial RNase P. Moreover, there is a synthetic lethal interaction between the disruption of this novel respiratory function and the loss of wild-type mtDNA. This synthetic interaction explains why a complete deletion of RPM2 is lethal.

Objective: To explore the efficacy of integrating Traditional Chinese Medicine (TCM) and anti-retroviral therapy (ART), a customized combination of different classes of medications which was also called cock-tail treatment, on the immunological nonresponse (INR) in people living with human immunodeficiency virus (HIV) (PLWH)., Methods: Relevant literature in databases such as China National Knowledge Infrastructure Database (CNKI), Wanfang Digital Journal, Chinese Medical Journal Database (CMJD), Chinese Biomedical Literature Database (CBM), PubMed, Cochrane, and Embase was reviewed by two independent investigators. Data were extracted from the studies according to the eligible criteria and analyzed using Review Manager 5.3., Results: Nine randomized controlled trials (RCTs) with 1078 patients were analyzed. Our analyses showed that CD4 T cell counts in the treatment group improved compared with that in the control group [mean difference (MD) = 13.51, 95% confidence interval (CI): 7.42-19.60, P < 0.0001]. There was no significant difference between the treated and control groups after 3 months (MD = 25.31, 95% CI: ?2.78 to 53.41, P = 0.08). However, after 6 and 12 months, the response of the treatment group was superior to the control group (MD = 27.45, 95% CI: 7.09-47.81, P = 0.008 and MD = 27.34, 95% CI: 6.31-48.37, P = 0.01, respectively). The clinical efficacy of the treatment group was also higher than that of the control group (RR = 1.75, 95% CI: 1.16-2.65, P = 0.007). However, CD45RO and CD45RA T cell counts did not differ significantly between the two groups (MD = 12.37, 95% CI: ?6.71 to 31.45, P = 0.20 and MD = 5.67, 95% CI: ?3.00 to14.35, P = 0.20, respectively)., Conclusion: The combined treatment strategy of integrated TCM and Western Medicine promotes long-term reconstitution of the immune system and thus, is beneficial and has potential use for improving INR in PLWH. However, large-scale RCTs are required to provide evidence for optimal intervention strategies.

Objective: To observe the effect of auricular electroacupuncture (EA) on intracellular Raf/ extracellular signal-regulated kinase (ERK)/ ribosomal S6 kinase (RSK)/ cAMP response element-binding protein (CREB) signal pathway in the hippocampus of depression model rats, so as to explore its anti-depressive mechanism., Methods: A total of 60 male SD rats were randomly divided into control, model, auricular EA, PD98059(ERK inhibitor), DMSO (Dimethylsulfoxide), PD98059+EA groups ( n =10 in each group). The rats in the control group were fed with normal diet without any treatment. The depression model was induced by chronic unpredictable mild stress (CUMS) for consecutive 21 days. EA (20 Hz, 2 mA) was applied to bilateral auricular "Xin"(Heart) and "Shenmen" for 30 min, once daily for 28 days. Rats of the PD98059, DMSO and PD98059+EA groups received intracerebroventricular injection of PD98059(100 µmol/L), DMSO and PD98059 (dissolved by DMSO) solutions (5 µL/d), respectively, once daily for 28 days. Sucrose preference test (sucrose consumption) was conducted at the baseline, before and after the intervention. The expression of hippocampal Raf, phosphorylated (p)-Raf, ERK, p-ERK, RSK, CREB and p-CREB proteins were detected by Western blot after EA intervention., Results: Following modeling, the sucrose consumption volume, and the expression levels of hippocampal Raf, p-Raf, ERK, p-ERK, RSK, CREB, p-CREB proteins were significantly lower in the model group than those in the control group ( P <0.01). Following the treatment, the sucrose consumption and the expression levels of Raf, p-Raf, ERK, p-ERK, RSK, CREB, p-CREB in the auricular EA group and those of p-Raf, ERK and CREB in the PD98059+EA group were obviously increased in comparison with the model group ( P <0.05, P <0.01), the expression level of p-ERK in the PD98059 group was obviously decreased in comparison with the model group ( P <0.05), suggesting an improvement of depression after auricular EA. Compared with auricular EA group, the expression level of p-ERK, p-CREB and RSK in the PD98059+EA group were significantly decreased ( P <0.05)., Conclusion: EA of auricular "Xin" and "Shenmen" is able to improve depression in depression rats, which is probably related to its effect in promoting activities of hippocampal Raf/ERK/RSK/CREB signaling.

In this paper, a detailed analysis was made on relevant literatures about bear bile powder in terms of chemical component, pharmacological effect and clinical efficacy, indicating bear bile powder's significant pharmacological effects and clinical application in treating various diseases. Due to the complex composition, bear bile powder is relatively toxic. Therefore, efforts shall be made to study bear bile powder's pharmacological effects, clinical application, chemical composition and toxic side-effects, with the aim to provide a scientific basis for widespread reasonable clinical application of bear bile powder.

Highly active antiretroviral therapy (HAART) have made great progress in rapid inhibition of HIV, reduce the morbidity and mortality, etc; while it exists many limits, such as viruses rebound after discontinuation of drug, side effects, drug-resistant. With the emergence of these problems, researchers explored therapies by traditional Chinese medicine, so as to achieve target of lower antiviral drug side effect, raising antiviral treatment adherence. Through a large number of clinical tests, we achieved encouraging effects in treating HAART related side effects by Chinese medicine.

This article reviews the research reports of Chinese herbal compound on AIDS immune reconstitution for nearly 20 years, found that Chinese herbal compound has exact clinical efficacy for AIDS immune reconstitution. Therefore, we should give full play to the unique advantages of Chinese herbal compound in improving immunity, thus improving symptoms and improve quality of life, to achieve optimal clinical treatment of AIDS.

Highly active antiretroviral combination therapy significantly reduced the mortality, but in the high-speed copying, high genetic variation and drug selection pressure under the effect of the increasingly serious problem of drug resistance greatly weakened the role of HAART inhibit viral replication and reduce antiviral treatment. This paper reports the latest trends in HIV drug-resistance in order to develop anti-HIV drugs in clinical programs, research and development of new guidance anti-HIV-1 strategy to bring guidance.

Purpose: Inhibitor of apoptosis (IAP) family proteins are suppressors of apoptosis that have been implicated in apoptosis resistance in some cancers. Their expression and relevance to the prognosis of prostate cancer were investigated., Experimental Design: The expression of four members of the IAP family (cellular inhibitor of apoptosis protein 1, cellular inhibitor of apoptosis protein 2, X chromosome-linked IAP, and survivin) was examined by immunohistochemistry and immunoblotting in human prostate cancers and in prostate tissues from transgenic mice expressing SV40 large T antigen under control of a probasin promoter., Results: Tumor-associated elevations in the levels of all four IAP family members were common in prostate cancers of both humans and mice, suggesting concomitant up-regulation of multiple IAP family proteins. Compared with normal prostatic epithelium, increased IAP expression was often evident even in prostatic intraepithelial neoplasia lesions (carcinoma in situ), suggesting that deregulation of IAP expression occurs early in the pathogenesis of prostate cancer. IAP expression did not correlate with Gleason grade or prostate-specific antigen levels., Conclusions: The findings demonstrate that tumor- associated elevations in the expression of several IAP family proteins occur as a frequent and early event in the etiology of prostate cancer.