Repetitive transcranial magnetic stimulation promotes neurological functional recovery in rats with traumatic brain injury by upregulating synaptic plasticity-related proteins.

Studies have shown that repetitive transcranial magnetic stimulation (rTMS) can enhance synaptic plasticity and improve neurological dysfunction. However, the mechanism through which rTMS can improve moderate traumatic brain injury remains poorly understood. In this study, we established rat models of moderate traumatic brain injury using Feeney's weight-dropping method and treated them using rTMS. To help determine the mechanism of action, we measured levels of several important brain activity-related proteins and their mRNA. On the injured side of the brain, we found that rTMS increased the protein levels and mRNA expression of brain-derived neurotrophic factor, tropomyosin receptor kinase B, N-methyl-D-aspartic acid receptor 1, and phosphorylated cAMP response element binding protein, which are closely associated with the occurrence of long-term potentiation. rTMS also partially reversed the loss of synaptophysin after injury and promoted the remodeling of synaptic ultrastructure. These findings suggest that upregulation of synaptic plasticity-related protein expression is the mechanism through which rTMS promotes neurological function recovery after moderate traumatic brain injury.

Correlation between monocyte to high-density lipoprotein cholesterol ratio and insulin resistance in male patients with type 2 diabetes mellitus combined with metabolic-related fatty liver disease / 中国热带医学

@#Abstract: Objective　To explore the correlation between monocyte to high-density lipoprotein cholesterol ratio (MHR) and insulin resistance (IR) in male patients with type 2 diabetes mellitus (T2DM) combined with metabolic-related fatty liver disease (MAFLD). Methods A total of 454 male patients with T2DM combined with MAFLD in National Metabolic Management Center (MMC) of the Affiliated Hospital of Jiangsu University from May 2018 to July 2020 were enrolled. The general clinical data of subjects were collected, blood routine and biochemical indexes were tested, homeostasis model insulin resistance index (HOMA-IR) was calculated, visceral fat area (VFA) and subcutaneous fat area (SFA) were measured. Accordingtothe MHR quartile, patients were divided into group Q1 (MHR≤0.38), group Q2 (0.38<MHR≤0.48), group Q3 (0.48<MHR≤0.64) and group Q4 (MHR>0.64) to compare the differences in measured indicators above. In addition, patients were divided into two groups according to HOMA-IR, HOMA-IR<2.5 and HOMA-IR≥2.5, and the differences in MHR were compared. Results The patients were divided into four groups according to MHR:group Q1 (n=115), group Q2 (n=110), group Q3 (n=120) and group Q4 (n=109). Fasting insulin (FINS) were respectively 6.17(4.20,9.76), 7.73(4.94,10.66), 8.92(5.32,11.33) and 9.13(5.25,12.27) mU/L, 2-hour postprandial insulin were 22.75(12.87,39.59), 27.55(16.44,39.77), 30.98(17.46,43.11) and 31.28(18.54,45.92) U/L. HOMA-IR were 3.12(1.63,4.25), 3.72(2.26,4.66), 3.87(2.48,5.44) and 3.95(2.42,5.31). Neutrophil (Neu) were 3.10(2.60,3.70), 3.20(2.50,3.93), 3.60(2.80,4.28), 4.20(3.30,5.00)×109/L. Subcutaneous fat area (SFA) were (181.27±53.60), (192.64±62.41), (199.53±61.40) and (203.69±71.51) cm2. They all increased gradually. However, the levels of high-density lipoprotein cholesterol (HDL-c) [1.18(1.06,1.35), 1.02(0.86,1.17), 0.96(0.80,1.03) and 0.80(0.69,0.92) mmol/L] and low-density lipoprotein cholesterol (LDL-c) [(3.00±0.79), (2.76±0.83), (2.67±0.85) and (2.59±0.92) mmol/L] decreased gradually. Pearson's or Spearman's correlation analysis showed that MHR was positively correlated with FINS, 2-hour postprandial insulin (2hINS), HOMA-IR, VFA and SFA (r=0.190, 0.153, 0.184, 0.114, 0.127, P<0.05). The coronary heart disease history, systolic blood pressure,diastolic blood pressure,fasting plasmaglucose (FPG), FINS, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood uric acid (Ur), body mass index (BMI), VFA, SFA and MHR of patients in group HOMA-IR≥2.5 were higher than group HOMA-IR<2.5 (P<0.05). Conclusion　MHR is positively correlated with IR in male patients with T2DM combined with MAFLD, and as MHR increases, the degree of IR is higher.

Proteomics analysis of tumor exosomes reveals vital pathways of Jinfukang inhibiting circulating tumor cells metastasis in lung cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Jinfukang has long been used for the clinical treatment of lung cancer. Previous studies have shown that Jinfukang can induce the apoptosis of circulating tumor cells by intervening ROS-mediated DNA damage pathway. However, whether Jinfukang can inhibit the metastasis of circulating tumor cells and its mechanism are still unclear. AIM OF THE STUDY: To further investigate the mechanism of Jinfukang in anti-metastasis of lung cancer from the perspective of intervention of tumor exosomes. MATERIALS AND METHODS: The invadopodia formation was determined with immunofluorescence. Invasion and migration were detected using the Transwell assay. Ultracentrifugation was used to isolate exosomes. Exosomes were characterized by electron microscopy, nanoparticle tracking analysis and immunoblotting, and the protein profile was evaluated by proteomic analysis. The molecular functions, biological processes and signaling pathway enrichment analysis were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Key differentially expressed proteins were verified by Western blot. RESULTS: Jinfukang can inhibit the expression of MMP14, cortactin, Tks5 and the formation of invadopodia of CTC-TJH-01 cells. Furthermore, Jinfukang can significantly inhibit the invasion and migration of CTC-TJH-01 cells. The diameter of exosomes extracted from the CTC-TJH-01 cells treated by Jinfukang was 30-100 nm, and the exosomal markers CD63, CD81 and TSG101 were expressed. We identified 680 deferentially expressed proteins. Gene oncology analysis indicated that exosomes were mostly derived from plasma membrane and mainly involved in protein localization and intracellular signaling. The ingenuity pathway analysis showed that the EGF pathway was significantly inhibited, whereas the GP6 signaling pathway was significantly activated. We also confirmed that Jinfukang inhibited the expression of EGF pathway-related proteins in CTC-TJH-01 cells. Besides, when EGF was used to activate EGF signaling pathway, the inhibition of Jinfukang on CTC cell metastasis was reversed. CONCLUSION: Jinfukang inhibits the metastasis of CTC-TJH-01 cells through the EGF pathway.

TOB1-AS1 suppresses non-small cell lung cancer cell migration and invasion through a ceRNA network.

Non-small cell lung cancer (NSCLC) is the leading cause of lung cancer-associated mortality. Recent studies revealed that long non-coding (lnc)RNAs have crucial roles in human cancers. The present study was the first, to the best of our knowledge, to indicate that the lncRNA transducer of ERBB2, 1-antisense 1 (TOB1-AS1) acts as a tumor suppressor in NSCLC. Knockdown of TOB1-AS1 significantly induced NSCLC cell migration, invasion and proliferation. It was also demonstrated that the higher expression of TOB1-AS1 in NSCLC samples was associated with longer overall survival time. Furthermore, a TOB1-AS1-mediated competing endogenous RNA network in NSCLC was constructed, including Homo sapiens (hsa)-microRNA (miR)-27a-3p, hsa-miR-23a-3p, hsa-miR-23b-3p, hsa-miR-27b-3p, hsa-miR-23c, dynein cytoplasmic 2 light intermediate chain 1, E4F transcription factor 1, TSPY-like 4, component of oligomeric Golgi complex 7, inositol hexakisphosphate kinase 2 and deltex E3 ubiquitin ligase 3. Of note, dysregulation of targets of TOB1-AS1 was associated with the prognosis of NSCLC patients. The present study suggested that TOB1-AS1 may serve as a novel biomarker for NSCLC.

Exome sequencing identifies MVK mutations in disseminated superficial actinic porokeratosis.

Disseminated superficial actinic porokeratosis (DSAP) is an autosomal dominantly inherited epidermal keratinization disorder whose etiology remains unclear. We performed exome sequencing in one unaffected and two affected individuals from a DSAP family. The mevalonate kinase gene (MVK) emerged as the only candidate gene located in previously defined linkage regions after filtering against existing SNP databases, eight HapMap exomes and 1000 Genomes Project data and taking into consideration the functional implications of the mutations. Sanger sequencing in 57 individuals with familial DSAP and 25 individuals with sporadic DSAP identified MVK mutations in 33% and 16% of these individuals (cases), respectively. All 14 MVK mutations identified in our study were absent in 676 individuals without DSAP. Our functional studies in cultured primary keratinocytes suggest that MVK has a role in regulating calcium-induced keratinocyte differentiation and could protect keratinocytes from apoptosis induced by type A ultraviolet radiation. Our results should help advance the understanding of DSAP pathogenesis.

[Effects of Xuebijing injection on protein C and tumor necrosis factor-alpha mRNA in rats with sepsis].

OBJECTIVE: To investigate the effects of the integrated traditional Chinese medicine Xuebijing injection on protein C (PC) and tumor necrosis factor-alpha (TNF-alpha) mRNA in rats with sepsis. METHODS: Sepsis was induced in Wistar rats by cecal ligation and puncture (CLP). Ninety-six healthy animals were randomly divided into four groups: normal group, sham-operation group, CLP model group, and Xuebijing-treated group. The two latter groups were divided into 2, 8, 24, 48, and 72-hour subgroups with 8 rats in each subgroup. Platelet count of blood obtained from abdominal aorta was determined and tissue samples from liver and lungs were collected to measure tissue PC and TNF-alpha mRNA expression. RESULTS: PC gene expression levels in lung tissues were significantly lowered (all P<0.01), but they were dramatically raised by Xuebijing injection during 8-72 hours post-CLP (all P<0.01). Compared with normal group, TNF-alpha mRNA levels in liver and lungs were significantly elevated at 2 hours post-CLP (P<0.05 or P<0.01). However, treatment with Xuebijing injection markedly reduced TNF-alpha mRNA both in liver and lungs at 2-24 hours (P<0.05 or P<0.01). In CLP group, blood platelet count was significantly decreased to certain extent at different intervals within 8-72 hours, and it was markedly elevated in the Xuebijing-treated group (P<0.05 or P<0.01). CONCLUSION: The current study suggests that Xuebijing injection could exert preventing effect on the development of severe sepsis by suppressing PC and TNF-alpha mRNA.

[Effects of Xuebijing injection on thrombomodulin and endothelial cell protein C receptor in septic rats].

OBJECTIVE: To investigate effects of the integrated traditional Chinese medicine Xuebijing injection on thrombomodulin (TM) and endothelial cell protein C receptor (EPCR) in septic rats. METHODS: Ninety-six healthy Wistar rats were randomly divided into four groups: control group, sham operation group, cecal ligation and puncture (CLP) model group, and Xuebijing-treated group. Sepsis was reproduced by CLP. The two latter groups were divided into five subgroups of 2, 8, 24, 48 and 72-hour with 8 rats in each subgroup. Tissue samples from liver and lung were collected to determine tissue TM and EPCR mRNA expression. RESULTS: TM and EPCR mRNA expressions were observed in liver and lung in control group and sham operation group, while with no significant differences at 2 hours post-CLP (both P>0.05). TM and EPCR gene expression levels in tissues were significantly increased to certain extent at 8-48 hours (all P<0.01), and were dramatically decreased following Xuebijing injection at 72 hours post-CLP (both P>0.05). Also, treatment with Xuebijing injection markedly decreased TM and EPCR mRNA levels to certain extents at 8 and 24 hours, and markedly increased at 48 and 72 hours compared with those of model group. CONCLUSION: These data suggest that Xuebijing injection could raise TM and EPCR mRNA expression, thereby it might be effective in prevention of development of severe sepsis.