Research progress of natural products interfering with cell signaling pathway in liver fibrosis.

Liver cirrhosis and hepatocellular carcinoma are the late stage of liver fibrosis. How to early use drugs to intervene in liver fibrosis is a prerequisite for the reversal of liver fibrosis. This paper mainly introduces a cell signaling transduction pathway in liver fibrosis and the intervention of natural products in order to provide theoretical basis for the treatment of liver fibrosis.

Genomic Evolution and Variation of SARS-CoV-2 in the Early Phase of COVID-19 Pandemic in Guangdong Province, China.

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) with unknown origin spread rapidly to 222 countries, areas or territories. To investigate the genomic evolution and variation in the early phase of COVID-19 pandemic in Guangdong, 60 specimens of SARS-CoV-2 were used to perform whole genome sequencing, and genomics, amino acid variation and Spike protein structure modeling analyses. Phylogenetic analysis suggested that the early variation in the SARS-CoV-2 genome was still intra-species, with no evolution to other coronaviruses. There were one to seven nucleotide variations (SNVs) in each genome and all SNVs were distributed in various fragments of the genome. The Spike protein bound with human receptor, an amino acid salt bridge and a potential furin cleavage site were found in the SARS-CoV-2 using molecular modeling. Our study clarified the characteristics of SARS-CoV-2 genomic evolution, variation and Spike protein structure in the early phase of local cases in Guangdong, which provided reference for generating prevention and control strategies and tracing the source of new outbreaks.

Mycotoxin zearalenone induces AIF- and ROS-mediated cell death through p53- and MAPK-dependent signaling pathways in RAW264.7 macrophages.

Zearalenone (ZEN) is commonly found in many food commodities and is known to cause reproductive disorders and genotoxic effects. However, the mode of ZEN-induced cell death of macrophages and the mechanisms by which ZEN causes cytotoxicity remain unclear. The present study shows that ZEN treatment reduces viability of RAW264.7 cells in a dose-dependent manner. ZEN causes predominantly necrotic and late apoptotic cell death. ZEN treatment also results in the loss of mitochondrial membrane potential (MMP), mitochondrial changes in Bcl-2 and Bax proteins, and cytoplasmic release of cytochrome c and apoptosis-inducing factor (AIF). Pre-treatment of the cells with either z-VAD-fmk or z-IETD-fmk does not attenuate ZEN-mediated cell death, whereas catalase suppresses the ZEN-induced decrease in viability in RAW264.7 cells. Treating the cells with c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), or p53 inhibitor prevented ZEN-mediated changes, such as MMP loss, cellular reactive oxygen species (ROS) increase, and cell death. JNK or p38 MAPK inhibitor inhibited mitochondrial alterations of Bcl-2 and Bax proteins with attendant decreases in cellular ROS levels. Knockdown of AIF via siRNA transfection also diminished ZEN-induced cell death. Further, adenosine triphosphate was markedly depleted in the ZEN-exposed cells. Collectively, these results suggest that ZEN induces cytotoxicity in RAW264.7 cells via AIF- and ROS-mediated signaling, in which the activations of p53 and JNK/p38 play a key role.

[In vitro activities of Odorrana grahami antimicrobial peptides from skin against 5 pathogenic bacteria].

OBJECTIVE: To evaluate the efficiency of 4 Odorrana grahami antimicrobial peptides from skin against 5 pathogenic bacteria, include 2 wild strains and 7 resistant strains. METHODS: Broth microdilution antimicrobial susceptibility test was used for bacteria that growed aerobically. RESULTS: The 4 Odorrana grahami antimicrobial peptides were basically in vitro efficient agents for inhibition against to methicillin-resistant coagulase negative Staphylococcus (MRSCN, 85460), wild Staphylococcus aureus (24157), penicillin-resistant Streptococcus pneumoniae (PRSP, 84688 and 91452), class I beta-lactamase Enterobacter cloacae (AmpC, 85439 and 93543), wild Escherichia coli (84492), extended-spectrum beta-lactamases Escherichia coli (ESBL, 84492), inhabitor-resistant TEM beta-lactamase Escherichia coli (IRT, 85580). CONCLUSION: The 4 Odorrana grahami antimicrobial peptides from skin have broad spectrum antimicrobial activity; especially have in vitro activity to resistant strains. So it is hopeful to be developed as the antimicrobial agent as well as the disinfectant and the antiseptic.