[GPCR48 promotes invasion and metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma cells].

Objective: To observe the G protein-coupled receptor 48 (GPCR48) expression in hepatocellular carcinoma (HCC) cell lines with different metastatic potential and its characteristics effect on the invasion and metastasis of Huh7 hepatoma cells via epithelial-mesenchymal transition (EMT). Methods: Western blot was used to detect the protein expression level of GPCR48 in HCC cells with different metastatic potential. The lentivirus vector expressing GPCR48 gene was constructed. GPCR48 was overexpressed in Huh7 hepatoma cells. The GPCR48 overexpression level was detected by real-time PCR and Western blot. Transwell invasion and migration assay was used to detect the Huh7 hepatoma cells invasion and migration ability in the Control, Mock and GPCR48 overexpression group. Real-time PCR and Western blot were used to detect Huh7 hepatoma cells mRNA and protein expression levels of the EMT related markers (E-cadherin, N-cadherin, vimentin, and γ catenin) in the Control, Mock and GPCR48 overexpression groups, respectively. Analysis of variance was used to compare the differences between data sets. Results: GPCR48 protein expression level in metastatic HCC cell lines was significantly higher than non-metastatic HCC cell lines (P < 0.05). The lentivirus vector expressing the GPCR48 gene had effectively transfected the Huh7 hepatoma cells and stably expressed the GPCR48mRNA and protein. Compared with the Mock and the Control group, Huh7 hepatoma cells invasion and migration ability in the GPCR48 overexpression group was significantly enhanced (F≥5.54, P < 0.05), and the mRNA and protein expression levels of epithelial phenotypic markers E-cadherin and γ-catenin were decreased (P < 0.05). The mRNA and protein expression levels of the mesenchymal phenotypic markers N-cadherin and Vimentin were increased (P < 0.05), indicating that EMT changes occurred in Huh7 hepatoma cells had overexpressed GPCR48. Conclusion: GPCR48 expression level is positively correlated with the metastatic potential of HCC cells. GPCR48 overexpression can down-regulate the expression of epithelial phenotypic markers and up-regulate the expression of mesenchymal phenotypic markers, and induce EMT changes in HCC cells, thus promoting HCC cells invasion and migration.

Fibrogrowth factor-2 protects against acute lung injury by activating the PI3K/Akt signaling pathway.

Acute lung injury (ALI)/Acute respiratory distress syndrome (ARDS) is a very dangerous disease. The purpose of this study was to investigate the effects of fibrogrowth factor-2 (FGF-2) on lipopolysaccharide (LPS)-induced lung injury and its mechanisms. C57/BL6 mice were used in the study and LPS was used to construct the ALI/ARDS model. In addition, human normal lung epithelial cell line BEAS-2B was cultured to investigate the effect of FGF-2 on the lung and its mechanism of action in vitro. FGF-2 significantly reduced wet/dry weight ratio of mice, the number of cells and inflammatory factors in BALF, and MPO activity in lung tissue. In addition, FGF-2 also reduced the level of oxidative stress in mouse lung tissue. In vitro, FGF-2 effectively reduced LPS-induced inflammatory and apoptotic levels of BEAS-2B cells and increased the activity of the PI3K/Akt signaling pathway. However, LY294002, an inhibitor of the PI3K/Akt signaling pathway, alleviated the protective effect of FGF-2 on lung tissue. Therefore, FGF-2 attenuated inflammation, oxidative stress and apoptosis in alveolar epithelial cells by activating the PI3K/Akt signaling pathway.

Association of thymosin ß4 expression with clinicopathological parameters and clinical outcomes of bladder cancer patients.

The clinical significance of thymosin ß4 (Tß4) expression in bladder transitional cell carcinoma (BTCC) remains unclear. The present study assessed the relationship between the expression of Tß4 protein and the clinicopathological features, as well as the prognosis of bladder cancer patients. Tß4 protein expression in 24 normal bladder and 138 primary BTCC tissue specimens was detected by immunohistochemistry, and the association of this expression with BTCC clinicopathological features and recurrence as well as patient survival was analyzed. Tß4 expression was significantly stronger in BTCC patients than in normal volunteers. The expression of Tß4 was significantly associated with differentiation capability, tumor stage and lymph node metastasis (P = 0.025, 0.043, and 0.039, respectively). Moreover, Tß4 expression was positively correlated with integrin-linked kinase (ILK) and ß-catenin expression (P = 0.042, 0.031, respectively) and inversely correlated with E-cadherin expression (P = 0.022). In the present cohort of bladder cancer patients, Tß4 expression was found to be a predictor of poor survival (P < 0.05); however, high Tß4 expression exhibited unfavorable prognostic value for recurrence. These data suggested that Tß4 is correlated with the pathogenesis of BTCC. In addition, the patients with higher Tß4 expression had a shorter survival.

Ultrasonic bone curette in thoracic spinal decompression: a comprehensive systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to compare the efficacy and safety of ultrasonic bone curette (UBC) and conventional surgical instruments in thoracic laminectomy decompression (TLD) for the treatment of thoracic spinal stenosis (TSS) by meta-analysis. MATERIALS AND METHODS: Two authors independently searched Medline via PubMed, Embase, Cochrane Library, Web of Science, Wanfang Database, and China National Knowledge Infrastructure for the period from the establishment of the database until January 2023 to identify the studies on the safety and efficacy of UBC vs. conventional instruments for TSS. Data extraction and quality assessment were performed by two researchers independently. We used RevMan 5.4 software (Review Manager Web, The Cochrane Collaboration, Copenhagen, Denmark) to analyze the data. RESULTS: Eight retrospective studies were included in the present work. This meta-analysis revealed that no significant differences in the preoperative JOA scores, the JOA scores at the last follow-up, the improvement rate of JOA scores, and the incidence of cerebrospinal fluid leakage/dura injury were detected between the two groups (p>0.05). However, there were significant differences in the operative time and intraoperative blood loss during single-level TLD [operative time: MD=-1.47, 95% CI (-1.86, -1.09), p<0.001; intraoperative blood loss: MD=-46.62, 95% CI (-53.83, -39.40), p<0.001], total operative time [MD=-56.88, 95% CI (-69.66, -44.10), p<0.001], total intraoperative blood loss [MD=-143.52, 95% CI (-212.49, -74.54), p<0.001], the incidence of neurological deterioration/nerve root injury [RR= 0.29, 95% CI (0.09, 0.91), p=0.03] between the groups. CONCLUSIONS: The application of UBC in TLD to treat TSS is safe and effective. UBC can significantly shorten operation time and reduce intraoperative blood loss compared to traditional surgical instruments. Moreover, it has the advantage of reducing perioperative nerve injury.

Intradiscal steroid injection for the treatment of chronic non-specific low back pain in patients with Modic type 1 change.

OBJECTIVE: The aim of this study was to evaluate and aggregate the evidence from the published studies to determine the effectiveness of intradiscal steroid injection (ISI) in patients with symptomatic Modic type I change (MCI). MATERIALS AND METHODS: A systematic literature search was independently performed by two authors. The electronic database, including PubMed, Embase, the Cochrane Library, and Web of Science, were searched with the given search terms but without language restriction. The studies that met the inclusion criteria were included. The relevant data were extracted, and two authors independently assessed the quality of the included studies. We performed the present study using the STATA software package. RESULTS: The present work included seven studies with 434 patients with chronic low back pain (CLBP). The risk of bias in the included randomized controlled trials (RCTs) was rated from low to unclear, and all the included observational studies were rated as high quality. The result of the meta-analysis revealed that there were significant differences in pain intensity [standardized mean difference (SMD): 3.09, 95% confidence interval (CI): 1.60-4.58; p<0.01] and self-assessed improvement/satisfaction [odds ratio (OR): 11.41, 95% CI: 3.39-38.41; p=0.05] after ISI compared to before treatment. However, no significant differences in the proportion of patients with full or part-time employment (OR: 1.03, 95% CI: 0.55-1.91; p>0.05), receiving additional care for CLBP (OR: 0.78, 95% CI: 0.36-1.71; p>0.05), and serious adverse events (OR: 1.09, 95% CI: 0.58 to 2.05; p>0.05) were detected between the groups. CONCLUSIONS: Among CLBP patients with MCI, the use of ISI was significantly associated with a reduction in pain intensity in the short term.

Genome-wide scanning for CHD1L gene in papillary thyroid carcinoma complicated with type 2 diabetes mellitus.

PURPOSE: Papillary thyroid carcinoma (PTC) represents the most common subtype of thyroid cancer (TC). This study was set out to explore the potential effect of CHD1L on PTC and type 2 diabetes mellitus (T2DM). METHODS: We searched for T2DM susceptibility genes through the GWAS database and obtained T2DM-related differentially expressed gene from the GEO database. The expression and clinical data of TC and normal samples were collated from the TCGA database. Receiver operating characteristic (ROC) curve analysis was subsequently applied to assess the sensitivity and specificity of the CHD1L for the diagnosis of PTC. The MCP-counter package in R language was then utilized to generate immune cell score to evaluate the relationship between CHD1L expression and immune cells. Then, we performed functional enrichment analysis of co-expressed genes and DEGs to determine significantly enriched GO terms and KEGG to predict the potential functions of CHD1L in PTC samples and T2DM adipose tissue. RESULTS: From two genes (ABCB9, CHD1L) were identified to be DEGs (p < 1 * 10-5) that exerted effects on survival (HR > 1, p < 0.05) in PTC and served as T2DM susceptibility genes. The gene expression matrix-based scoring of immunocytes suggested that PTC samples with high and low CHD1L expression presented with significant differences in the tumor microenvironment (TME). The enrichment analysis of CHD1L co-expressed genes and DEGs suggested that CHD1L was involved in multiple pathways to regulate the development of PTC. Among them, Kaposi sarcoma-associated herpesvirus infection, salmonella infection and TNF signaling pathways were highlighted as the three most relevant pathways. GSEA analysis, employed to analyze the genome dataset of PTC samples and T2DM adipose tissue presenting with high and low expression groups of CHD1L, suggests that these differential genes are related to chemokine signaling pathway, leukocyte transendothelial migration and TCELL receptor signaling pathway. CONCLUSION: CHD1L may potentially serve as an early diagnostic biomarker for PTC, and a target of immunotherapy for PTC and T2DM.

Examination of the effect of procalcitonin on human leucocytes and the porcine isolated coronary artery.

BACKGROUND: The aim of this study was to investigate the effects of procalcitonin on the lipopolysaccharide (LPS)-induced changes in human leucocytes and porcine isolated coronary artery. METHODS: Using flow cytometry, changes in forward scatter and intracellular calcium in human neutrophils and monocytes were determined after exposure to procalcitonin, calcitonin gene-related peptide (CGRP), LPS, and the known chemoattractants formylated methionine-leucine-phenylalanine (fMLP) and interleukin-8 (IL-8). In porcine isolated coronary artery, the effects of procalcitonin were evaluated using the contractile function change and the release of TNFalpha. RESULTS: In human neutrophils and monocytes, procalcitonin (100 nM), but not CGRP, increased forward scatter and the expression of surface markers (CD16 and CD14, respectively) in a similar manner to 10 microg ml(-1) LPS. Procalcitonin, but not CGRP, also increased the proportion of cells exhibiting an increase in intracellular calcium ions similar to that produced by fMLP and IL-8. Acute exposure of the coronary artery to procalcitonin produced a small, endothelium-independent relaxation (approximately 15% of constrictor tone), but failed to modify subsequent relaxations to CGRP. After 16 h exposure, procalcitonin (100 nM) increased TNFalpha release from the coronary artery equivalent to 70% of that produced by LPS, but did not modify the inhibitory effect of LPS (100 microg ml(-1)) on contractile responses. CONCLUSIONS: Procalcitonin has a proinflammatory effect on human leucocytes and porcine coronary artery, but it is not capable of modulating LPS-induced changes in vascular responsiveness in vitro.

MiR-4421 regulates the progression of preeclampsia by regulating CYP11B2.

OBJECTIVE: Preeclampsia is a serious disease that affects maternal and fetal health in pregnancy. Mechanism of miRNA in preeclampsia has gradually been explored. This study mainly investigated the mechanism of miR-4421 in preeclampsia. PATIENTS AND METHODS: The expression of miR-4421 in 42 preeclampsia tissues and 42 normal pregnancy placentas tissues was detected by qRT-PCR. The relationship between the miR-4421 level and clinicopathological features of preeclampsia was analyzed. After miR-4421 was overexpressed, cell proliferation, cell cycle, and apoptosis were examined. The target gene CYP11B2 of miR-4421 was detected by luciferase reporter assay. The protein expressions were accessed by Western blot. RESULTS: miR-4421 was highly expressed in the placenta of preeclampsia. Clinical data analysis revealed higher systolic blood pressure, diastolic blood pressure, and urinary protein level in preeclampsia patients with high expression of miR-4421 compared with those in low expression group. Birth weight of fetuses was significantly lower than those born from normal pregnant women. After overexpression of miR-4421, trophoblast proliferation was significantly inhibited and cell cycle was significantly blocked. Luciferase reporter assay and Western blot showed that CYP11B2 can be served as a target gene of miR-4421. CONCLUSIONS: MiR-4421 was highly expressed in preeclampsia, which may promote the progression of preeclampsia by down-regulating the expression of CYP11B2.

Breast cancer metastasis suppressor 1 (BRMS1) suppresses prostate cancer progression by inducing apoptosis and regulating invasion.

OBJECTIVE: Breast cancer metastasis suppressor 1 (BRMS1) was originally identified as a metastasis suppressor gene in human breast cancer. MATERIALS AND METHODS: A recent study has established an association between BRMS1 with the clinical stage and different pathology grades of prostate cancer. However, whether BRMS1 plays a role in prostate cancer has not been elucidated. RESULTS: In this study, we found that overexpression of BRMS1 in PC-3 cells induced apoptosis and inhibited invasion; moreover, we found that overexpression BRMS1 was associated with the suppressed expression of EMMPRIN. CONCLUSIONS: Taken together, our results show that BRMS1 may suppress progression and metastasis of prostate cancer through modulating EMMPRIN expression.

Neoplastic transformation dose response of oncogene-transfected rat embryo cells by gamma rays or 6 MeV alpha particles.

We measured a dose-response relationship for induction of neoplastic transformation by 6 MeV alpha particles and 137Cs gamma rays in REC:myc and REC:ras cells, that is, rat embryo cells (REC) transfected with the c-myc or the Ha-ras oncogenes. The 6 MeV alpha particles simulated 222Rn emissions for risk assessment relative to low-LET radiations. The dose of gamma rays was approximately twice that of alpha particles for a neoplastic transformation frequency of 10(-3). The survival of the REC cells containing oncogenes was comparable to that of the commonly used C3H 10T1/2 cells for the same dose, but the former were more refractory to radiation-induced neoplastic transformation. Neoplastic transformation frequency measured in REC cells was 3 times lower than those typically measured in C3H 10T1/2 cells at a gamma-ray dose of 6 Gy, and 5-10 times lower at an alpha-particle dose of 3 Gy.

[Feasibility of the new WHO Trachoma Grading System in China].

The New WHO Trachoma Grading System is found feasible in China by an epidemiological survey of trachoma using the two trachoma grading systems, the new WHO system and the Chinese conventional system, especially for large scale examination and treatment and for epidemiological survey. However, the New System regards the proportion of active trachoma amongst children under 10 years as the index of the scope and severity of the disease in a community, while the authors opine that the trachoma prevalence in teenagers, especially in middle school students, better reflects the situation of trachoma infection in a Chinese community.

[Chemical constituents of roots, rhizomes and stems of Amomum villosum Lour].

Ethyl octacosate, docosyl hexylate, a new compound stigmast-4-ene-1,3-dione, beta-sitosterol and daucosterol were isolated and identified from the roots and rhizomes of Amomum villosum cultivated in Xishuangbanna, Yunnan. Two compounds daucosterol and emodin monoglycoside were isolated and identified from the stems of A. villosum.

Genome-wide scanning for CHD1L gene in papillary thyroid carcinoma complicated with type 2 diabetes mellitus

Purpose Papillary thyroid carcinoma (PTC) represents the most common subtype of thyroid cancer (TC). This study was set out to explore the potential effect of CHD1L on PTC and type 2 diabetes mellitus (T2DM). Methods We searched for T2DM susceptibility genes through the GWAS database and obtained T2DM-related differentially expressed gene from the GEO database. The expression and clinical data of TC and normal samples were collated from the TCGA database. Receiver operating characteristic (ROC) curve analysis was subsequently applied to assess the sensitivity and specificity of the CHD1L for the diagnosis of PTC. The MCP-counter package in R language was then utilized to generate immune cell score to evaluate the relationship between CHD1L expression and immune cells. Then, we performed functional enrichment analysis of co-expressed genes and DEGs to determine significantly enriched GO terms and KEGG to predict the potential functions of CHD1L in PTC samples and T2DM adipose tissue. Results From two genes (ABCB9, CHD1L) were identified to be DEGs (p < 1 * 10−5) that exerted effects on survival (HR > 1, p < 0.05) in PTC and served as T2DM susceptibility genes. The gene expression matrix-based scoring of immunocytes suggested that PTC samples with high and low CHD1L expression presented with significant differences in the tumor microenvironment (TME). The enrichment analysis of CHD1L co-expressed genes and DEGs suggested that CHD1L was involved in multiple pathways to regulate the development of PTC. Among them, Kaposi sarcoma-associated herpesvirus infection, salmonella infection and TNF signaling pathways were highlighted as the three most relevant pathways. GSEA analysis, employed to analyze the genome dataset of PTC samples and T2DM adipose tissue presenting with high and low expression groups of CHD1L, suggests that these differential genes are related to chemokine signaling pathway, leukocyte transendothelial migration and TCELL receptor signaling pathway (AU)

DeltaNp73alpha regulates MDR1 expression by inhibiting p53 function.

The p73 protein is a transcription factor and member of the p53 protein family that expresses as a complex variety of isoforms. DeltaNp73alpha is an N-terminally truncated isoform of p73. We found that DeltaNp73 protein is upregulated in human gastric carcinoma suggesting that DeltaNp73 may play an oncogenic role in these tumors. Although it has been shown that DeltaNp73alpha inhibits apoptosis and counteracts the effect of chemotherapeutic drugs, the underlying mechanism by which this p73 isoform contributes to chemotherapeutic drug response remains to be explored. We found that DeltaNp73alpha upregulates MDR1 mRNA and p-glycoprotein (p-gp), which is involved in chemotherapeutic drug transport. This p-gp upregulation was accompanied by increased p-gp functional activity in gastric cancer cells. Our data suggest that upregulation of MDR1 by DeltaNp73alpha is mediated by interaction with p53 at the MDR1 promoter.

Evidence that a prostanoid produced by cyclo-oxygenase-2 enhances contractile responses of the porcine isolated coronary artery following exposure to lipopolysaccharide.

BACKGROUND: Prolonged incubation of porcine isolated coronary artery (PCA) to lipopolysaccharide (LPS) causes a moderate reduction in vessel constrictive responsiveness. This has been attributed mainly to the induction of nitric oxide synthase (NOS). We aimed to investigate the role of induction of cyclo-oxygenase (COX) and expression of endothelin receptor 1-A (ET1(A)) in modulating the vascular responses of PCA in vitro. METHODS: Segments of PCA were exposed to 100 microg ml(-1) LPS overnight. L-Arginine 0.4 mM was included in the medium in some preparations to examine the influence of intracellular nitric oxide, and the influence of extracellular donor sodium nitroprusside (SNP) was also examined in separate experiments. After overnight incubation, the contractile function of the artery was evaluated by the isometric tension recording test. The non-selective NOS inhibitor (L-NAME), non-selective COX inhibitor (indomethacin), COX-1 inhibitor (FR 122047), COX-2 inhibitor (NS 398), and ET1(A) receptor antagonist (FR 139317) were added into the organ bath 30 min before eliciting contractile responses to KCl or U46619 separately or in combinations. Vascular relaxations to 10 nM Substance P (SP) were also assessed. RESULTS: L-Arginine did not potentiate the effects of LPS. SNP caused a quantitatively larger reduction in the responsiveness to KCl and U46619 compared with 100 microg ml(-1) LPS. Post exposure to a combination of indomethacin and FR 139317, indomethacin or NS 398 alone enhanced the inhibitory effects of LPS, but FR 122047 or FR 139317 alone failed to modify the responses to LPS. L-NAME fully reversed the changes induced by LPS combined with indomethacin and NS398. In terms of the relaxation by SP, LPS failed to change the magnitude; none of the agents used affected the response except L-NAME which abolished it. CONCLUSION: NOS and COX-2 are both activated by overnight exposure to LPS in vascular smooth muscle from PCA in vitro. The prostanoid produced by COX-2 functionally antagonizes the effects of induction of NOS.