Efficacy and safety of adjuvant curcumin therapy in ulcerative colitis: A systematic review and meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcumin, an active polyphenol extracted from Traditional Chinese medicine Curcuma longa (turmeric), has shown many health-related benefits and pharmacological effects. Adjuvant curcumin therapy for ulcerative colitis has become increasingly popular, but its efficacy and safety of which is still controversial. The purpose of this study is to evaluate the efficacy and safety of adjuvant curcumin therapy in ulcerative colitis. MATERIALS AND METHODS: The Medline, EMBASE, the Cochrane Library, CNKI, VIP, WanFang, and SinoMed databases were searched from inception to June 2021, to identify all randomized controlled clinical trials with adjuvant curcumin therapy in ulcerative colitis. The primary outcomes were clinical and endoscopic remission, and subgroup analyses were also performed. RESULTS: Six randomized trials with a total of 385 participants were included in this study. Qualified trials recommended that adjuvant curcumin therapy for ulcerative colitis was effective in inducing clinical remission (RR = 2.10, 95% CI 1.13 to 3.89), but not in clinical improvement (RR = 1.62, 95% CI 1.00 to 2.61), endoscopic remission (RR = 4.17, 95% CI 0.63 to 27.71) or endoscopic improvement (RR = 4.13, 95% CI 0.20 to 87.07). Included studies showed that appropriate dosage, formation, longer duration, and topical medication may have a greater potential advantage. No severe adverse effects had been reported. CONCLUSIONS: Available evidence suggested that adjuvant curcumin therapy may be effective for clinical remission in ulcerative colitis patients without causing severe adverse effects. The appropriate methods of administration can achieve better curative effect, which requires further study to verify.

Expression and prognosis analysis of JMJD5 in human cancers.

Background: JumonjiC (JmjC) domain-containing protein 5 (JMJD5) plays an important part in cancer metabolism. However, the prognostic value of JMJD5 in most human cancers is unknown yet. We aimed to examine the expression level and prognostic value of JMJD5, immune cell infiltration in cancer patients, and simultaneously to examine the correlations among them. Materials and methods: The mRNA and protein expression of JMJD5 were analyzed through online Tumor Immune Estimation Resource (TIMER) or immunohistochemistry (IHC) of tissue microarray sections (TMAs) in cancer versus normal tissues. The Kaplan-Meier Plotter databases were used to assess the prognostic values. The connection between the expression of JMJD5 and the abundances of six infiltrating immune cells were explored by TIMER in breast cancer (BRCA), liver hepatocellular carcinoma (LIHC), lung squamous cell carcinoma (LUSC), lung adenocarcinoma (LUAD) and stomach adenocarcinoma (STAD). We used the Cox proportional hazards model to investigate the correlations among clinical outcome, the abundance of immune cell infiltration and JMJD5 expression. Results: We found that the JMJD5 expression was obviously lower in BRCA, LIHC and lung cancer (LUC) but higher in STAD than in normal tissues. High expression of JMJD5 had a better prognosis only in BRCA, LIHC and LUC but a worse prognosis in STAD. The expression of JMJD5 has a significant connection with the abundance of six kind of infiltrating immune cells. The expression of JMJD5 plus the number of immune-infiltrating B cells or macrophages may jointly serve as a prognostic marker in the above four cancers. Conclusion: We provided novel evidence of JMJD5 as an essential prognostic biomarker and perspective therapeutic target in BRCA, LUAD, LIHC and STAD.

Prognostic values of GPNMB identified by mining TCGA database and STAD microenvironment.

The survival rate of stomach adenocarcinoma patients with immune and stromal scores and different clinicopathological features obtained from the TCGA datasets was systematically compared. A list of genes that are correlated with stomach adenocarcinoma microenvironment were extracted using the TCGA database to predict the prognosis and survival. In addition, the differentially expressed genes were extracted by comparing the immune and stromal scores of the groups. The protein-protein interaction network, and functional and pathway enrichment analyses of differentially expressed genes were performed. A total of 8 hub genes were selected from the differentially expressed genes to predict the overall survival and disease-free survival rates. GPNMB was selected from the hub genes based on the survival and prognosis analyses. A nomogram was built by including the potential risk factors based on multivariate Cox analysis. Cell function experiments and xenograft tumors were conducted in vivo to further verify the role of GPNMB in tumor progression. The predicted microRNA, miR-30b-3p, might act as upstream negative regulator and binding to 3' UTR of GPNMB, confirming by fluorescent enzyme reporter gene experiment. In summary, immune-related scores are crucial factors in the malignant progression of stomach adenocarcinoma and GPNMB acts as a potentially useful prognostic factor for stratification and in developing the treatment strategy.

LINC00619 restricts gastric cancer progression by preventing microRNA-224-5p-mediated inhibition of OPCML.

Several long intergenic noncoding RNAs (lincRNAs) have been linked to carcinogenesis; however, little is known about the role of LINC00619 in gastric cancer (GC). LINC00619 was identified among differentially expressed lncRNAs linked to gastric cancer based on microarray analysis and its relationships with miR-224-5p and opioid binding protein/cell adhesion molecule-like gene (OPCML) were investigated. LINC00619, miR-224-5p, and OPCML expression were measured in GC tissues and cells. Ectopic expression and depletion experiments were conducted to assess the effects of LINC00619, miR-224-5p and OPCML on cell proliferation, invasion, migration and apoptosis as well as their effects on the expression of apoptosis- and metastasis-related genes (Bcl-2, Bax, MMP-2 and MMP-9). Tumorigenicity in the nude mice was also examined. Gastric cancer was characterized by downregulation of LINC00619 and OPCML and upregulation of miR-224-5p. Additionally, we found that miR-224-5p could interact with both LINC00619 and OPCML. Upregulation of LINC00619, which binds to miR-224-5p, led to decreased miR-224-5p expression while increasing the expression of OPCML, a target gene of miR-224-5p. Overexpression of LINC00619 or OPCML or downregulation of miR-224-5p suppressed cell proliferation, invasion, migration and tumorigenicity while promoting apoptosis in GC. Our results indicated that LINC00619 functions as a tumor suppressor in GC by impairing miR-224-5p-mediated inhibition of OPCML.

Synthesis of nanobubbles for improved ultrasound tumor-imaging applications.

The present work showed the preparation of highly stable spherical nanobubbles using 3 mg/ml of soy lipid and 1% of Tween 80 as surfactant. The prepared nanobubbles were characterized using TEM and zeta-potential analyzer, which confirmed the formation of spherical nanobubbles with negative surface charge and high structural stability. The MTT cell viability studies confirmed that the fabricated nanobubbles were safe and nontoxic. Furthermore, the ultrasound imaging studies were performed to assess the improved imaging facility of the prepared nanobubbles. The in vitro studies exhibited that both the nanobubbles and SonoVue had a similar image enhancement capability. The in vivo studies revealed that nanobubbles exhibited an enhanced tumor intensity, which was stronger compared to that of Sono Vue. Therefore, the prepared nanobubbles could have potential for effective tumor imaging.

Clinical utilization of serum- or plasma-based miRNAs as early detection biomarkers for pancreatic cancer: A meta-analysis up to now.

BACKGROUND: Pancreatic cancer (PC) is a lethal disease, however current screening methods unable to achieve early diagnosis. Blood-based microRNAs (miRNAs) are promising molecular biomarkers for detecting PC. This meta-analysis summaries studies identifying serum- or plasma-based miRNAs dysregulated in PC patients compared to non-PC cases to evaluate their diagnostic accuracy for characterizing PC. METHODS: A systematically reviews and meta-analysis of published studies was conducted to compare the serum or plasma miRNAs expressions between PC patients and non-PC cases. Summary estimates for sensitivity, specificity, along with other measures of accuracy of miRNAs in the diagnosis of PC were pooled using the random-effects model. I and Q tests were used to assess the heterogeneity of included studies. The Spearman test was used to analyze the threshold effect. RESULTS: Twenty-seven eligible studies were identified after electronic search and literature selection. For single miRNA dysregulation, 32 miRNAs were found to be upregulated in PC patients, and 5 miRNAs were downregulated. Four studies identified a 2-miRNA panel, and 10 studies identified a panel consisting of 3 or more miRNAs which were used to detect PC patients. Additionally, 8 studies combined miRNA panels and carbohydrate antigen 19-9 (CA 19-9) to diagnose PC. The pooled sensitivities for these 4 groups were 0.77 to 0.85, and specificities were 0.70 to 0.87. The highest area under the curve (AUC), 0.9308, was identified using 2 miRNA panels with sensitivity and specificity of 0.79 (0.74-0.83) and 0.85 (0.81-0.89), respectively. There was great heterogeneity of these 4 miRNA groups. Results of Spearman test revealed that there existed a threshold effect on single miRNA group (r=-0.437, P=.001), and none of the other groups (P all>.05). CONCLUSIONS: Serum- or plasma-based miRNAs are capable of distinguishing PC from non-PC with relatively high sensitivity and specificity. In future, miRNAs may be used as promising diagnostic biomarkers for detection of PC.

Diagnostic value of contrast-enhanced ultrasound in hepatocellular carcinoma: a meta-analysis with evidence from 1998 to 2016.

BACKGROUND: This meta-analysis is aimed at determining the diagnostic value of hepatocellular carcinoma (HCC) with contrast-enhanced ultrasound (CEUS). MATERIALS AND METHODS: A comprehensive literature search of Pubmed, Web of Science, and the Cochrane Library was performed to identify published studies. The methodological quality of the included studies was evaluated. Data from eligible studies were used to estimate the pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive and negative likelihood ratio (LR) and summary receiver operating characteristic (SROC) curve. Meta-Disc and STATA softwares were utilized for all statistical analyses. RESULTS: Fifty-three eligible studies (publication years ranged from 1998 to 2016) were selected according to inclusion criteria. The meta-analysis showed that the pooled sensitivity and specificity of CEUS to detect HCC were 0.85 (95% CI: 0.84-0.86) and 0.91 (95% CI: 0.90-0.92), respectively. The pooled positive and negative LRs were 6.28 (95% CI: 4.49-8.77) and 0.16 (95% CI: 0.12-0.22), respectively. The pooled DOR was 55.01 (95% CI: 35.25-83.47). The area under the SCOR curve was 0.9432. Meta-regression and funnel plot indicated that sample size, type of contrast agents and publication bias might be the major sources of heterogeneity. CONCLUSIONS: CEUS is a valuable diagnostic tool for identifying HCC in clinic with highly sensitive and specific.

Comparing the long-term efficacy of standard and combined minimally invasive procedures for unresectable HCC: a mixed treatment comparison.

A small proportion of hepatocellular carcinoma (HCC) patients are suitable for surgical resections and various minimally invasive procedures have been introduced as alternatives to surgical resections. However, the relative efficacy of minimally invasive procedures remains to be studied in the current literature. Several popular minimally invasive procedures (monotherapy or combined therapies) were selected for comparison and their relative long-term efficacy were determined by using the statistics of hazard ratio (HR) which evaluates the survival status of HCC patients in one, two, three and four years, respectively. Evidence were obtained from the current literature and synthesized by using the approach of conventional pairwise meta-analysis and network meta-analysis (NMA). Moreover, selected minimally invasive procedures were ranked according to their surface under the cumulative ranking curve (SUCRA) which was produced by NMA in conjunction with the Markov Chain Monte Carlo (MCMC) sampling method. HCC patients treated by combined minimally invasive procedures, particularly transcatheter arterial chemoembolization (TACE) + high intensity focused ultrasound (HIFU), TACE + radiofrequency ablation (RFA), TACE + radiotherapy (RT) and TACE + Sorafenib (SOR) exhibited a significant decrease in the HR compared to those with standard TACE (HR < 1). The combined minimally invasive procedure of TACE + HIFU appears to be the most preferable therapy. PEI seems to be less favorable than other minimally invasive procedures. Combined minimally invasive procedures may be more preferable than standard minimally invasive procedures. Percutaneous ethanol injection (PEI) may not provide adequate efficacy compared to other minimally invasive procedures for unresectable HCC patients.

Correlation Between CASC8, SMAD7 Polymorphisms and the Susceptibility to Colorectal Cancer: An Updated Meta-Analysis Based on GWAS Results.

Genome-wide association studies (GWASs) and a number of case-control studies have suggested that several single nucleotide polymorphisms (SNPs), rs7837328, rs7014346, rs6983267, rs10505477 on CASC8 gene and rs4939827, rs4464148, rs12953717 on SMAD7 gene are significantly correlated with the susceptibility to colorectal cancer (CRC). For the sake of clarifying the association, a meta-analysis was conducted and population heterogeneity was considered in the study.A total of 34 articles including 90 studies (168,471 cases and 163,223 controls) that evaluated the relationship between the CASC8, SMAD7 genes and the risk of CRC under the allelic model were reviewed. Also subgroup analysis was performed by ethnicity (Caucasian, Asian, and African) and all of the analyses were implemented in R 3.2.1 software.Pooled data from the meta-analysis revealed that the A allele of rs7837328, the A allele of rs7014346, the G allele of rs6983267, the A allele of rs10505477, the T allele of rs4939827, the T of rs4464148, and the T of rs12953717 were significantly associated with an increased risk of CRC under the allelic model. Additionally, subgroup analyses of 6 SNPs by ethnicity (rs4464148 excepted) witnessed that the A allele of rs7837328, the G allele of rs6983267, and the T of rs12953717 were notably associated with an increased risk of CRC among Caucasian and Asian. Furthermore, the A allele of rs7014346, the A allele of rs10505477, and the T allele of rs4939827 were significantly related with an elevated risk of CRC only among Caucasian.Our study suggested that for CASC8 gene, SNP of rs7837328 and rs6983267 are risk factors for CRC among both Caucasian and Asian whereas rs7014346 and rs10505477 are risky gene polymorphisms only among Caucasian. For SMAD7 gene, rs4939827 and rs4464148 are risk factors for CRC among Caucasian whereas rs12953717 could elevate the susceptibility to CRC in both Caucasian and Asian.

TSPAN8 promotes gastric cancer growth and metastasis via ERK MAPK pathway.

AIMS: This study was designed to investigate the effects of Tetraspanin 8 (TSPAN8) overexpression and TSPAN8 suppression on gastric cancer cell proliferation and invasion. Furthermore, whether extracellular-signal regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway was involved in TSPAN8's function on gastric cancer cells was examined. METHODS: The expression of TSPAN8 in human gastric cancer tissues and gastric cancer cell lines was detected using real-time PCR and western blot analysis. TSPAN8-pcDNA3.1 plasmid or TSPAN8 siRNA was transfected into the gastric cancer cell lines to overexpress or suppress TSPAN8. Cells were treated with U0126 to inhibit ERK MAPK pathway. Cell proliferation and invasion were assessed by MTT and transwell-matrigel assay. RESULTS: TSPAN8 was overexpressed in human gastric cancer tissues and gastric cancer cell lines compared with the normal. TSPAN8 overexpression promoted cell proliferation and invasion, while TSPAN8 suppression inhibited cell proliferation and invasion. TSPAN8 could activate the ERK MAPK pathway in gastric cancer cells, and MEK-ERK inhibition reversed the effects of TSPAN8 overexpression on cell proliferation and invasion. CONCLUSION: This study firstly demonstrated that TSPAN8 promotes gastric cancer cell growth and metastasis at least partially through the activation of ERK MAPK pathway. These findings provided a novel molecular basis for the understanding and treatment of gastric cancer.