Chinese Herbal Medicine for the Treatment of Adult Viral Myocarditis: An Overview of Systematic Reviews and Meta-analyses of Randomized Controlled Trials.

PURPOSE: Viral myocarditis (VMC) is a life-threatening disease that can affect all ages and genders, with middle-aged adults being particularly susceptible. Numerous systematic reviews have been conducted to investigate the efficacy and safety of Chinese herbal medicine (CHM) in treating adult viral myocarditis (AVM). The objective of this study was to conduct a comprehensive overview of systematic reviews and meta-analyses of randomized controlled trials (RCTs) regarding the efficacy and safety of CHM for AVM. METHODS: A comprehensive systematic search was conducted across 8 electronic databases from their inception to June 23, 2022, augmented by manual searches of the gray literature. Systematic reviews were independently selected and data extracted in accordance with predetermined criteria by 2 reviewers. Included systematic reviews were assessed for methodologic and reporting quality using Assessing the Methodological Quality of Systematic Reviews 2 and Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The quality of evidence relating to outcome measures was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation tool. Recalculation of effect sizes and subsequent determination of 95% CIs were conducted with either a fixed-effects or random-effects model. FINDINGS: The current overview of systematic reviews included a total of 6 systematic reviews, which reported on 67 RCTs with a participant pool of 5611 individuals. The findings of our study indicate that the combination of CHM and Western medications had positive effects on the effective rate, cure rate, ECG recovery, atrial premature contraction/premature ventricular contraction, left ventricular ejection fraction, myocardial enzymes, and improvement of clinical symptoms for AVM. The adverse drug reactions in the combination therapy group were generally less than or lighter than that in the Western medication group (relative risk = 0.79; 95% CI, 0.44-1.40; P > 0.05, I2 = 0). IMPLICATIONS: Our research results provide evidence that combining CHM with Western medicine could offer potential benefits for patients with AVM. However, the number of studies included in our review is limited and the methodologic quality of these studies is modest. Therefore, there are potential uncertainties regarding the conclusion that CHM with Western medication may benefit patients with AVM. We call for more large-scale, high-quality studies with standardized designs to further verify and support our findings. This would promote a better understanding of the efficacy and safety profile of CHM and provide reliable reference evidence for clinical practice and policy making. Moreover, future research should explore optimal drug combinations, examine therapeutic doses and durations of CHM combination therapy, and evaluate its long-term efficacy and safety.

Solution and rheological properties of cationic cellulose/gemini surfactant: Effect of the alkyl chain and spacer length.

In this paper, three sulfonate-containing gemini surfactants, sodium 1,1'-(4,4'-methylenebis(4,1-phenylene))bis(1-oxooctane-2-sulfonate) (C8-M1-C8), sodium 1,1'-(4,4'-(ethane-1,2-diyl)bis(4,1-phenylene))bis(1-oxooctane-2-sulfonate) (C8-M2-C8), sodium 1,1'-(4,4'-methylenebis(4,1-phenylene))-bis(1-oxododecane-2-sulfonate) (C12-M2-C12), were synthesized and characterized with FT-IR, 1H NMR and MS. Furthermore, interaction between a cationic cellulose-based polyelectrolyte, PQ-10, and gemini surfactants were investigated by surface tension, turbidity, flow and low-amplitude oscillation rheology analysis. For comparing, the interaction of their corresponding monomeric counterpart sodium dodecyl sulfate (SDS), sodium 1-octanesulfate (SOS) was also studied. Results showed that the concentration value at T1, defined as critical surface complex concentration, for the PQ-10/surfactant was in order of PQ-10/C8-M2-C8> PQ-10/C8-M1-C8 > PQ-10/C12-M2-C12. Precipitation appeared at low concentration for Gemini surfactants than their monomeric counterparts, and for the gemini surfactants with shorter spacer or longer hydrocarbon chain. The increase/decrease of the crossover frequency (ωc) (the relaxation time, τc) for PQ-10/C12-M2-C12 indicated the formation/collapse of network structures, while PQ-10/SDS showed no obvious change.

Mixed-ligand copper(ii) Schiff base complexes: the role of the co-ligand in DNA binding, DNA cleavage, protein binding and cytotoxicity.

Four novel mononuclear Schiff base copper(ii) complexes, namely, [Cu(L)(OAc)]·H2O (), [Cu(HL)(C2O4)(EtOH)]·EtOH (), [Cu(L)(Bza)] () and [Cu(L)(Sal)] () (HL = 1-(((2-((2-hydroxypropyl)amino)ethyl)imino)methyl)naphthalene-2-ol), Bza = benzoic acid, Sal = salicylic acid), were synthesized and characterized by X-ray crystallography, elemental analysis and infrared spectroscopy. Single-crystal diffraction analysis revealed that all the complexes were mononuclear molecules, in which the Schiff base ligand exhibited different coordination modes and conformations. The N-HO and O-HO inter- and intramolecular hydrogen bonding interactions linked these molecules into multidimensional networks. Their interactions with calf thymus DNA (CT-DNA) were investigated by UV-visible and fluorescence spectrometry, as well as by viscosity measurements. The magnitude of the Kapp values of the four complexes was 10(5), indicating a moderate intercalative binding mode between the complexes and DNA. Electrophoresis results showed that all these complexes induced double strand breaks of pUC19 plasmid DNA in the presence of H2O2 through an oxidative pathway. In addition, the fluorescence spectrum of human serum albumin (HSA) with the complexes suggested that the quenching mechanism of HSA by the complexes was a static process. Moreover, the antiproliferative activity of the four complexes against HeLa (human cervical carcinoma) and HepG-2 (human liver hepatocellular carcinoma) cells evaluated by colorimetric cell proliferation assay and clonogenic assay revealed that all four complexes had improved cytotoxicity against cancer cells. Inspiringly, complex , with salicylic acid as the auxiliary ligand, displayed a stronger anticancer activity, suggesting that a synergistic effect of the Schiff base complex and the nonsteroidal anti-inflammatory drug may be involved in the cell killing process. The biological features of mixed-ligand copper(ii) Schiff base complexes and how acetic auxiliary ligands manipulate these features are also discussed.

Reduced BMP6 expression by DNA methylation contributes to EMT and drug resistance in breast cancer cells.

Bone morphogenetic protein 6 (BMP6) is an important regulator of cell growth, differentiation and apoptosis in various types of tumor. In breast cancer, it was considered as a tumor suppressor. Our previous study also confirmed that BMP6 was a critical regulator of breast cancer drug resistance. However, little is known about how its expression is regulated and its mechanisms in breast cancer drug resistance. In the present study, we assessed the DNA methylation regulation of BMP6 based on the presence of a large CpG island in the BMP6 gene promoter. Quantitative DNA methylation analyses showed a significantly increased DNA methylation level in the drug-resistant cell line MCF-7/ADR compared to their parental cells MCF-7. Moreover, the drug-resistant cell line MCF-7/ADR showed an EMT phenotype confirmed by morphology and the expression of EMT marker gene. MCF-7 cells transfected with BMP6-specific shRNA vector also showed an EMT phenotype. The MCF-7/ADR cells treated with the recombinant BMP6 proteins reversed their EMT phenotype. These data indicated that hypermethylation modifications contributed to the regulation of BMP6 and induced an EMT phenotype of breast cancer during the acquisition of drug resistance.

[Expression and clinical significance of bone morphogenetic protein 6 in human breast cancer].

OBJECTIVE: To investigate the expression pattern and clinical significance of bone morphogenetic protein 6 (BMP6) in breast tissues. METHODS: The tumor and adjacent noncancerous tissues were harvested from 36 cases of breast cancer, the expression level of BMP6 mRNA of each sample was measured by quantitative RT-PCR. Immunohistochemistry study was used to examine BMP6 protein expression in 80 cases of breast cancer, then the relationship between the expression of BMP6 and relevant clinical and pathological parameters was analyzed. RESULTS: BMP6 mRNA expression in breast cancer was significantly reduced when compared with normal breast tissues (P< 0.01), BMP6 mRNA level in estrogen receptor-positive (ER) breast cancer was distinctly higher than that in ER breast cancer. The expression of BMP6 mRNA was correlated to tumor grade (P < 0.01). The expression level of BMP6 protein in breast cancer was associated to ER and PR status, histological grade and Ki-67 status (P < 0.05), but not correlated to age, tumor size, human epidermal factor receptor 2 (Her2) status and molecular subtypes of breast cancer (P > 0.05). CONCLUSION: The ectopic expression of BMP6 may play an important role in the development and progression of breast cancer.

Downregulation of BMP6 enhances cell proliferation and chemoresistance via activation of the ERK signaling pathway in breast cancer.

Previous studies indicate that bone morphogenetic protein (BMP) 6 is involved in breast cancer development and progression. However, the mechanism underlying the role of BMP6 in breast cancer cell proliferation, differentiation and chemoresistance remains unknown. In this study, we confirmed that BMP6 expression was downregulated in breast cancer tissues compared with the adjacent normal breast tissues. We further demonstrated that the downregulation of BMP6 was correlated with the estrogen receptor (ER) and progesterone receptor (PR) status, tumor grade and enhanced proliferation (Ki67 proliferation index). In vitro functional experiments showed that the suppression of BMP6 expression by a specific small hairpin (sh)RNA vector led to increased proliferation in the MCF7 breast cancer cell line. Furthermore, knockdown of BMP6 in MCF7 cells enhanced the chemoresistance to doxorubicin by upregulation of mdr-1/P-gp expression and activation of the ERK signaling pathway. Taken together, our data suggest that BMP6 plays a critical role in breast cancer cell aberrant proliferation and chemoresistance and may serve as a novel diagnostic biomarker or therapeutic target for breast cancer.

Altered microRNA expression in skeletal muscle results from high-fat diet-induced insulin resistance in mice.

Skeletal muscle insulin resistance induced by a high-fat diet has been implicated in the development of type 2 diabetes. However, the precise molecular mechanisms involved are only partially understood. Recently, studies have shown that microRNAs play an important role in insulin resistance in various tissues. In this study, microRNA expression profiles of skeletal muscle of mice fed a high-fat or normal diet were analyzed using microarrays and the results were confirmed by real-time reverse-transcription polymerase chain reaction. Gene Ontology (GO) and pathway mapping tools were employed to analyze systemically the biological processes and signaling pathways affected by the differential expression of microRNAs. In this study, we show that 30 microRNAs are differentially expressed between 2 groups of mice. Compared to the mice fed a normal diet, there were 8 microRNAs up-regulated and 22 microRNAs down-regulated in the high-fat diet-fed mice. Furthermore, we confirm that the MAPK signaling pathway highlighted in this study is involved in skeletal muscle insulin resistance. These results indicate that skeletal muscle insulin resistance induced by a high-fat diet is associated with a group of microRNAs. GO and pathway mapping are a valid and effective approach for analyzing the function of microRNAs and the results could be a guideline for further investigation.

Decreased expression of repulsive guidance molecule member A by DNA methylation in colorectal cancer is related to tumor progression.

Previous studies have shown decreased expression of repulsive guidance molecule member A (RGMa) in colorectal cancer. However, the relationship between the expression levels and promoter DNA methylation status of RGMa and the clinical characteristics of colorectal cancer has not been previously reported. Here, we investigated the expression of RGMa by immunohistochemistry, real-time PCR and western blotting and analyzed the methylation status of the RGMa promoter using Sequenom's MassARRAY platform in colorectal cancer tissues and adjacent normal colorectal tissues. The results showed that RGMa expression was decreased in cancer tissues compared with adjacent normal tissues (p<0.01). Furthermore, a tendency for decreased expression in tumor tissues was observed from Dukes' stage A to stage D (p<0.01). In addition, significantly higher levels of hypermethylation in promoter regions of RGMa were observed in colorectal cancer tissues, compared with those in adjacent normal colorectal tissues (p<0.01). Moreover, the methylation levels of RGMa in tumor tissues were significantly increased in Dukes' stage C and D compared with Dukes' stage A and B (p<0.01). Our results indicate that RGMa expression and promoter methylation status are closely related to colorectal cancer genesis and progression. Determination of the expression level and methylation frequency of RGMa in colorectal cancer tissues may have benefit for early diagnosis and for evaluating patient prognosis.