Molecular mechanism of Ganoderma against gastric cancer based on network pharmacology and experimental test / 中国中药杂志

This study aims to explore the molecular mechanism of Ganoderma against gastric cancer based on network pharmacology, molecular docking, and cell experiment. The active components and targets of Ganoderma were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and gastric cancer-related targets from GeneCards and Online Mendelian Inheritance in Man(OMIM). The protein-protein interaction(PPI) network of the common targets was constructed with STRING, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the common genes based on Bioconductor and R language. The medicinal-disease-component-target network and medicinal-disease-component-target-pathway network were established by Cytoscape. Molecular docking was performed between β-sitosterol(the key component in Ganoderma) and the top 15 targets in the PPI network. Cell experiment was performed to verify the findings. A total of 14 active components and 28 targets of Ganoderma were retrieved, and the medicinal and the disease shared 25 targets, including caspase-3(CASP3), caspase-8(CASP8), caspase-9(CASP9), and B-cell lymphoma-2(BCL2). The common targets involved 72 signaling pathways and apoptosis and p53 signaling pathway may play a crucial role in the effect of Ganoderma against gastric cancer. β-sitosterol had strong binding activity to the top 15 targets in the PPI network. The in vitro cell experiment demonstrated that β-sitosterol inhibited gastric cancer AGS cell proliferation by inducing cell apoptosis and cell cycle arrest in the S phase, which might be related to the regulation of the p53 pathway. This study shows the multi-component, multi-target, and multi-pathway characteristics of Ganoderma against gastric cancer, which lays a scientific basis for further research on the molecular mechanism.

Mutation analysis of a Chinese family with autosomal dominant Emery-Dreifuss muscular dystrophy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the clinical, pathological and genetic characteristics in a family with autosomal dominant Emery-Dreifuss muscular dystrophy (AD-EDMD).</p><p><b>METHODS</b>Clinical data and skeletal muscle specimens were collected from two patients (the proband and her daughter) for pathological analysis. DNA samples of the proband and her family members (7 persons from 3 generations) were obtained for PCR amplification and direct DNA sequencing of the lamin A/C (LMNA) gene. Haplotype analysis was performed after the identification of mutation.</p><p><b>RESULTS</b>The proband had typical clinical manifestation of EDMD: joint contracture, progressive muscle weakness and atrophy and cardiac conduction dysfunction. Muscular pathology revealed myopathic changes combined with slight neuropathic changes. A heterozygous missense mutation 1583 (C to G)(T528R) was identified in exon 9 of the LMNA gene in the two patients, but not in other family members. Haplotype analysis indicated that the proband and her daughter shared the same causative haplotype.</p><p><b>CONCLUSION</b>This is the first report of the phenotype and genotype of AD-EDMD in Chinese.</p>

Analysis of clinical and molecular pathology in 8 patients of Chinese dysferlinopathy / 中华神经科杂志

Objective To investigate the clinical and molecular pathological features of dysferlinopathy in China.Methods Four patients with limb-girdle muscular dystrophy2B(LGMD2B)and 4 patients with Miyoshi-type distal muscular dystrophy(MMD)were clinically analyzed, their skeletal muscle were biopsied and immunohistochemical stained.Four cases of each Duchenne-Aran muscular atrophy and myotis were served as controls.Results The clinical situation of dysferlinopathy was characterized by progressive muscle weakness and atrophy, consistent with progressive muscular dystrophy.Histochemical staining revealed muscle fibers degenerating, regenerating and necrosis in a varying degree.Connective tissue was seen proliferated and inflammatory cells infiltrated in the majority of cases.Immunohistochemical staining with anti-dysferlin monoclonal antibody identified the deficiency of dysferlin on the sarcolemma and in the sarcoplasm of 8 cases with dysferlinopathy.Conclusions(1)The clinical and pathological characters of dysferlinopathy are consistent with progressive muscular dystrophy;(2)Anti-dysferlin monoclonal antibody immunohistochemical staining is a reliable method to diagnose dysferlinopathy, which is worth of wide application in clinic.