Effectiveness of Chinese herbal medicine in treating liver fibrosis: a systematic review and meta-analysis of randomized controlled trials

Background

The studies on the effectiveness of Chinese herbal medicines (CHM) in treating liver fibrosis (LF) were not consistent. This study aims to systematically review the effectiveness of CHM on treating LF patients.

Methods

Databases including MEDLINE, AMED, EMBASE, The Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, TCMOnline, Chinese Biomedical Literature Database, and Chinese Medical Current Contents were searched up to March 2011. Randomized controlled trials (RCTs) involving LF patients receiving CHM, Western medicine, combined CHM and Western medicine compared with placebo, Western medicine or no intervention were included. LF markers including serum hyaluronic acid (HA), laminin (LN), procollagen type III (PC-III), type IV collagen (IV-C), matrix metalloproteinase (MMP), and tissue inhibitors of metalloproteinase (TIMP) were measured as primary outcomes. Liver biochemistry, including alanine aminotransferase (ALT) and aspartarte aminotransferase (AST), and improvement of related clinical symptoms were measured as secondary outcomes. Risk of bias of allocation sequence, allocation concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases were assessed.

Results

Twenty-three RCTs with 2123 participants were analyzed in subgroups of types of comparison and study quality. Fifteen studies were graded as good quality. CHM alone and combined with Western medicine showed significant improvements in HA, LN, PC-III and IV-C compared with Western medicine alone. However, there were no significant differences observed between CHM and placebo treatments.

Conclusion

The current inconclusive results in determining the effectiveness of CHM treatment on LF, due to the poor methodological quality and high heterogeneity of the studies, suggests that large RCTs using standardized Chinese medicine syndrome diagnosis and CHM formulae with longer follow-up are required for further evaluation.     

The reversal of cisplatin-induced nephrotoxicity by selenium nanoparticles functionalized with 11-mercapto-1-undecanol by inhibition of ROS-mediated apoptosis

Although cisplatin is still one of the most effective chemotherapy agents for human cancers, its clinical use is limited by serious side effects, especially nephrotoxicity. Oxidative stress is an important mediator of cisplatin-induced nephrotoxicity. In the present study, a simple method for functionalization of selenium nanoparticles by self-assembly of 11-mercapto-1-undecanol (Se@MUN) to achieve enhanced antioxidant activity and antagonis against cisplatin-induced nephrotoxicity has been demonstrated. The chemical structure of the nanoparticles was characterized by various microscopic and spectroscopic methods. The results revealed that the spherical nanoparticles were capped with MUN on the surface through formation of Se-S bond. The in vitro protective effects of Se@MUN on HK-2 proximal tubular cells against cisplatin-induced nephrotoxicity and the underlying mechanisms were also investigated. Se@MUN exhibited free radical scavenging activity and higher cellular uptake in human normal cells by comparing with SeNPs. Se@MUN significantly attenuated cisplatin-induced reduction in cell viability, appearance of Sub-G1 peak, nuclear condensation and DNA fragmentation in HK-2 cells. Activation of caspase-3 in cells exposed to cisplatin was also effectively blocked by Se@MUN. Moreover, Se@MUN significantly prevented the cisplatin-induced overproduction of intracellular ROS. Our findings suggest that Se@MUN is a promising selenium species with potential application in prevention of cisplatin-induced renal injury.     

Partial protection against enterovirus 71 (EV71) infection in a mouse model immunized with recombinant Newcastle disease virus capsids displaying the EV71 VP1 fragment

Enterovirus 71 (EV71) infection may cause severe neurological complications, particularly in young children. Despite the risks, there are still no commercially available EV71 vaccines. Hence, a candidate vaccine construct, containing recombinant Newcastle disease virus capsids that display an EV71 VP1 fragment (NPt-VP1(1-100) ) protein, was evaluated in a mouse model of EV71 infection. Previously, it was shown that this protein construct provoked a strong immune response in vaccinated adult rabbits. That study, however, did not address the issue of its effectiveness against EV71 infection in young animals. In the present study, EV71 viral challenge in vaccinated newborn mice resulted in more than 40% increase in survival rate. Significantly, half of the surviving mice fully recovered from their paralysis. Histological analysis of all of the surviving mice revealed a complete clearance of EV71 viral antigens from their brains and spinal cords. In hind limb muscles, the amounts of the antigens detected correlated with the degrees of tissue damage and paralysis. Findings from this study provide evidence that immunization with the NPt-VP1(1-100) immunogen in a newborn mouse model confers partial protection against EV71 infection, and also highlights the importance of NPt-VP1(1-100) as a possible candidate vaccine for protection against EV71 infections.     

Dengue virus PrM/M proteins fail to show pH-dependent ion channel activity in Xenopus oocytes

The transmembrane domains (TMDs) of dengue virus type-1 M protein (DENV-1M) were reported to form cation-selective channels in artificial lipid bilayers. We further explored this observation using the two-electrode voltage clamp (TEVC) method on the Xenopus laevis oocytes expressing DENV PrM and M proteins. Using myc epitope tagged M proteins, M was first shown to adopt its predicted native topology in mammalian cells when expressed on its own. The recombinant proteins were then successfully expressed on the surface of Xenopus oocytes. Using influenza A M2 (Inf A/M2) protein as a control, we measured the conductance of oocytes expressing DENV proteins under hyperpolarized or low-pH conditions. Inf A/M2 showed pH-dependent, amantadine-sensitive channel activity that was consistent with previously published reports. However, no activity was detected for DENV proteins. We conclude that DENV PrM and M proteins do not show pH-activated ion channel activity.     

Investigation of causes of oseltamivir chemoprophylaxis failures during influenza A (H1N1-2009) outbreaks

BackgroundAntiviral post-exposure prophylaxis with oseltamivir has been used as a strategy in mitigating the Influenza A (H1N1-2009) pandemic. There have been few reports of well-documented prophylaxis failures and the reasons for failure.ObjectivesWe report herein a series of 10 cases of prophylaxis failures and explore the reasons behind their prophylaxis failure.Study designIn the early pandemic phase, the military employed oseltamivir post-exposure ring-prophylaxis of affected units. From June 22 to July 30, 2009, cases of laboratory-confirmed prophylaxis failures were identified. Nasopharyngeal swabs were collected and tested by PCR. Samples with sufficient RNA material were sent for whole genome sequencing, and screened for mutations that confer oseltamivir resistance, especially the H275Y mutation.ResultsTen cases of laboratory-confirmed prophylaxis failure were identified, with a mean age of 22.3 years. One case was asymptomatic; the remaining 9 had fever or cough but without severe complications. The mean duration of exposure before starting oseltamivir was 1.9 days (SD 0.9), while the mean duration of oseltamivir consumption before symptom onset was 1.9 days (SD 1.4). None of the samples had the H275Y mutation or other known mutations that confer resistance. From the whole genome sequencing, several mutations at the HA (T220S, E275V, T333A, D239G); PB2 (K660R, L607V, V292I); NS1 (F103S), and NP (W104G) gene segments were detected, but none of them were likely to result in anti-viral resistance.ConclusionsPrimary prophylaxis failures exhibited mild symptoms without complications; all did not have the H275Y mutation and were unlikely to result from other mutations.     

Exploring genotype‐phenotype relationships in the CDKL5 deficiency disorder using an international dataset

Characterized by early‐onset seizures, global developmental delay and severe motor deficits, CDKL5 deficiency disorder is caused by pathogenic variants in the cyclin‐dependent kinase‐like 5 gene. Previous efforts to investigate genotype‐phenotype relationships have been limited due to small numbers of recurrent mutations and small cohort sizes. Using data from the International CDKL5 Disorder Database we examined genotype‐phenotype relationships for 13 recurrent CDKL5 variants and the previously analyzed historic variant groupings. We have applied the CDKL5 Developmental Score (CDS) and an adapted version of the CDKL5 Clinical Severity Assessment (CCSA), to grade the severity of phenotype and developmental outcomes for 285 individuals with CDKL5 variants. Comparisons of adapted CCSA and CDS between recurrent variants and variant groups were performed using multiple linear regression adjusting for age and sex. Individuals with the missense variant, p.Arg178Trp, had the highest mean adapted CCSA and lowest mean developmental scores. Other variants producing severe phenotypes included p.Arg559* and p.Arg178Gln. Variants producing milder phenotypes included p.Arg134*, p.Arg550*, and p.Glu55Argfs*20. There are observed differences in phenotype severity and developmental outcomes for individuals with different CDKL5 variants. However, the historic variant groupings did not seem to reflect differences in phenotype severity or developmental outcomes as clearly as analyzed by individual variants.     

Rapid and simultaneous detection of Mycobacterium tuberculosis complex and Beijing/W genotype in sputum by an optimized DNA extraction protocol and a novel multiplex real-time PCR

Rapid diagnosis and genotyping of Mycobacterium tuberculosis by molecular methods are often limited by the amount and purity of DNA extracted from body fluids. In this study, we evaluated 12 DNA extraction methods and developed a highly sensitive protocol for mycobacterial DNA extraction directly from sputa using surface-coated magnetic particles. We have also developed a novel multiplex real-time PCR for simultaneous identification of M. tuberculosis complex and the Beijing/W genotype (a hypervirulent sublineage of M. tuberculosis) by using multiple fluorogenic probes targeting both the M. tuberculosis IS6110 and the Rv0927c-pstS3 intergenic region. With reference strains and clinical isolates, our real-time PCR accurately identified 20 non-Beijing/W and 20 Beijing/W M. tuberculosis strains from 17 different species of nontuberculosis Mycobacterium (NTM). Further assessment of our DNA extraction protocol and real-time PCR with 335 nonduplicate sputum specimens correctly identified all 74 M. tuberculosis culture-positive specimens. In addition, 15 culture-negative specimens from patients with confirmed tuberculosis were also identified. No cross-reactivity was detected with NTM specimens (n = 31). The detection limit of the assay is 10 M. tuberculosis bacilli, as determined by endpoint dilution analysis. In conclusion, an optimized DNA extraction protocol coupled with a novel multiprobe multiplex real-time PCR for the direct detection of M. tuberculosis, including Beijing/W M. tuberculosis, was found to confer high sensitivity and specificity. The combined procedure has the potential to compensate for the drawbacks of conventional mycobacterial culture in routine clinical laboratory setting, such as the lengthy incubation period and the limitation to viable organisms.     

The myeloid transcription factor KLF2 regulates the host response to polymicrobial infection and endotoxic shock

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Highlights? KLF2 deficiency confers a proinflammatory phenotype to myeloid cells ? Myeloid KLF2 deficiency renders animals resistant to polymicrobial infection ? Myeloid KLF2 deficiency renders animals susceptible to endotoxic shock ? KLF2 negatively regulates the NF-κB-HIF-1α axis in macrophages