Characteristic gut microbiota and metabolic changes in patients with pulmonary tuberculosis

Intestinal flora provides an important contribution to the development of pulmonary tuberculosis (PTB). We performed a cross-sectional study in 52 healthy controls (HCs) and 83 patients with untreated active PTB to assess the differences in their microbiomic and metabolic profiles in faeces via V3-V4 16S rRNA gene sequencing and gas chromatography–mass spectrometry. Patients with PTB had considerable reductions in phylogenetic alpha diversity and the production of short-chain fatty acids, dysbiosis of the intestinal flora and alterations in the faecal metabolomics composition compared with HCs. Significant alterations in faecal metabolites were associated with changes in the relative abundance of specific genera. Our study describes the imbalance of the gut microbiota and altered faecal metabolomics profiles in patients with PTB; the results indicate that the gut microbiota and faecal metabolomic profiles can be used as potential preventive and therapeutic targets for PTB.     

ICAM-1 promotes cancer progression by regulating SRC activity as an adapter protein in colorectal cancer

Colorectal cancer (CRC) has a 5-year survival rate of <10%, as it can metastasize to the lungs and liver. Anticancer drugs and targeted therapies used to treat metastatic colorectal cancer have insufficient therapeutic efficacy and are associated with complications. Therefore, research to develop new targeted therapeutics is necessary. Here, we present a novel discovery that intracellular adhesion molecule-1 (ICAM-1) is a potential therapeutic target to enhance therapeutic effectiveness for CRC. ICAM-1 is an important regulator of cell–cell interactions and recent studies have shown that it promotes malignancy in several carcinomas. However, little is known about its effect on CRC. Therefore, we conducted a study to define the mechanism by which ICAM-1 acts. ICAM-1 is phosphorylated by tyrosine-protein kinase Met (c-MET), and phosphorylated ICAM-1 can interact with SRC to increase SRC activity. Consequently, ICAM-1 may further accelerate SRC signaling, promoting the malignant potential of cancer. In addition, treatment with antibodies targeting ICAM-1 showed excellent therapeutic effects in reducing metastasis and angiogenesis. These findings suggest for the first time that ICAM-1 is an important adapter protein capable of mediating the c-MET-SRC signaling axis. Therefore, ICAM-1 can be used as a novel therapeutic target and a metastatic marker for CRC.Subject terms: Metastasis, Oncogenes     

ATG7-enhanced impaired autophagy exacerbates acute pancreatitis by promoting regulated necrosis via the miR-30b-5p/CAMKII pathway

The present study was performed to explore whether and how impaired autophagy could modulate calcium/calmodulin-dependent protein kinase II (CAMKII)-regulated necrosis in the pathogenesis of acute pancreatitis (AP). Wistar rats and AR42J cells were used for AP modeling. When indicated, genetic regulation of CAMKII or ATG7 was performed prior to AP induction. AP-related necrotic injury was positively regulated by the incubation level of CAMKII. ATG7 positively modulated the level of CAMKII and necrosis following AP induction, indicating that there might be a connection between impaired autophagy and CAMKII-regulated necrosis in the pathogenesis of AP. microRNA (miR)-30b-5p was predicted and then verified as the upstream regulator of CAMKII mRNA in our setting of AP. Given that the level of miR-30b-5p was negatively correlated with the incubation levels of ATG7 after AP induction, a rescue experiment was performed and indicated that the miR-30b-5p mimic compromised ATG7 overexpression-induced upregulation of CAMKII-regulated necrosis after AP induction. In conclusion, our results indicate that ATG7-enhanced impaired autophagy exacerbates AP by promoting regulated necrosis via the miR-30b-5p/CAMKII pathway.Subject terms: Cytokines, Acute inflammation     

亚热带河口养殖塘沉积物有机碳矿化及其影响因子

亚热带河口的养殖塘是温室气体二氧化碳(CO2)的重要排放源,但其沉积物有机碳矿化动力学特征目前尚未厘清.以我国东南沿海亚热带闽江、木兰溪以及九龙江河口区的6个凡纳滨对虾(Penaeus vannamei)养殖塘为研究对象,对沉积物取样,并进行为期60 d的室内厌氧培养,对养殖塘沉积物CO2累积产量曲线利用一阶动力学模型...     

The Effect of Lactobacillus plantarum Extracellular Vesicles from Korean Women in Their 20s on Skin Aging

Extracellular vesicles, which are highly conserved in most cells, contain biologically active substances. The vesicles and substances interact with cells and impact physiological mechanisms. The skin is the most external organ and is in direct contact with the external environment. Photoaging and skin damage are caused by extrinsic factors. The formation of wrinkles is a major indicator of skin aging and is caused by a decrease in collagen and hyaluronic acid. MMP-1 expression is also increased. Due to accruing damage, skin aging reduces the ability of the skin barrier, thereby lowering the skin’s ability to contain water and increasing the amount of water loss. L. plantarum suppresses various harmful bacteria by secreting an antimicrobial substance. L. plantarum is also found in the skin, and research on the interactions between the bacteria and the skin is in progress. Although several studies have investigated L. plantarum, there are only a limited number of studies on extracellular vesicles (EV) derived from L. plantarum, especially in relation to skin aging. Herein, we isolated EVs that were secreted from L. plantarum of women in their 20s (LpEVs). We then investigated the effect of LpEVs on skin aging in CCD986sk. We showed that LpEVs modulated the mRNA expression of ECM related genes in vitro. Furthermore, LpEVs suppressed wrinkle formation and pigmentation in clinical trials. These results demonstrated that LpEVs have a great effect on skin aging by regulating ECM related genes. In addition, our study offers important evidence on the depigmentation effect of LpEVs.     

Molecular Characterization of Two Genes Encoding Novel Ca2+-Independent Phospholipase A2s from the Silkworm,Bombyx mori

Eicosanoids are crucial downstream signals in the insect immune responses. Phospholipase A2 (PLA2) catalyzes phospholipids, the initial step in eicosanoid biosynthesis. In mammals, the biological roles of Ca²⁺-independent Phospholipase A2 (iPLA2) have been extensively studied; however, only a few studies have attempted to explore iPLA2 functions in insects. In this study, we identified two iPLA2 genes (designated as BmiPLA2A and BmiPLA2B) in the silkworm, Bombyx mori. BmiPLA2A had a 2427 base pair (bp) open reading frame (ORF) that coded for a protein with 808 amino acids. In contrast, BmiPLA2B had a 1731 bp ORF that coded for a protein with 576 amino acids. Domain analysis revealed that BmiPLA2A had six ankyrin repeat domains, but BmiPLA2B lacks these domains. BmiPLA2A and BmiPLA2B were transcribed widely in various tissues and developmental stages with different expression patterns. The administration of 20-hydroxyecdysone increased their expression levels in the epidermis and hemocytes. Furthermore, challenged with virus, fungus, Gram-negative bacteria, and Gram-positive bacteria induced the expression of BmiPLA2A and BmiPLA2B with variable degrees along with different time points. Our findings imply that BmiPLA2A and BmiPLA2B may have important biological roles in the development and innate immunity of B. mori.     

Stimulatory Effects of Extracellular Vesicles Derived from Leuconostoc holzapfelii That Exists in Human Scalp on Hair Growth in Human Follicle Dermal Papilla Cells

Human hair follicle dermal papilla cells (HFDPCs) located in hair follicles (HFs) play a pivotal role in hair follicle morphogenesis, hair cycling, and hair growth. Over the past few decades, probiotic bacteria (PB) have been reported to have beneficial effects such as improved skin health, anti-obesity, and immuno-modulation for conditions including atopic dermatitis and inflammatory bowel disease (IBD). PB can secrete 50~150 nm sized extracellular vesicles (EVs) containing microbial DNA, miRNA, proteins, lipids, and cell wall components. These EVs can regulate communication between bacteria or between bacteria and their host. Although numerous biological effects of PB-EVs have been reported, the physiological roles of Leuconostoc holzapfelii (hs-Lh), which is isolated from human scalp tissue, and the extracellular vesicles derived from them (hs-LhEVs) are largely unknown. Herein, we investigated the effects of hs-LhEVs on hair growth in HFDPCs. We show that hs-LhEVs increase cell proliferation, migration, and regulate the cell cycle. Furthermore, hs-LhEVs were found to modulate the mRNA expression of hair-growth-related genes in vitro. These data demonstrate that hs-LhEVs can reduce apoptosis by modulating the cell cycle and promote hair growth by regulation via the Wnt/β-catenin signal transduction pathway.     

Hepatitis C Virus Nonstructural 5A Protein Interacts with Telomere Length Regulation Protein: Implications for Telomere Shortening in Patients Infected with HCV

Hepatitis C virus (HCV) is a major cause of chronic liver disease and is highly dependent on cellular proteins for viral propagation. Using protein microarray analysis, we identified 90 cellular proteins as HCV nonstructural 5A (NS5A) interacting partners, and selected telomere length regulation protein (TEN1) for further study. TEN1 forms a heterotrimeric complex with CTC and STN1, which is essential for telomere protection and maintenance. Telomere length decreases in patients with active HCV, chronic liver disease, and hepatocellular carcinoma. However, the molecular mechanism of telomere length shortening in HCV-associated disease is largely unknown. In the present study, protein interactions between NS5A and TEN1 were confirmed by immunoprecipitation assays. Silencing of TEN1 reduced both viral RNA and protein expression levels of HCV, while ectopic expression of the siRNA-resistant TEN1 recovered the viral protein level, suggesting that TEN1 was specifically required for HCV propagation. Importantly, we found that TEN1 is re-localized from the nucleus to the cytoplasm in HCV-infected cells. These data suggest that HCV exploits TEN1 to promote viral propagation and that telomere protection is compromised in HCV-infected cells. Overall, our findings provide mechanistic insight into the telomere shortening in HCV-infected cells.