Fatty Acid Oxidation Mediated by Malonyl-CoA Decarboxylase Represses Renal Cell Carcinoma Progression.

Fatty acid metabolism reprogramming is a prominent feature of clear cell renal cell carcinoma (ccRCC). Increased lipid storage supports ccRCC progression, highlighting the importance of understanding the molecular mechanisms driving altered fatty acid synthesis in tumors. Here, we identified that malonyl-CoA decarboxylase (MLYCD), a key regulator of fatty acid anabolism, was downregulated in ccRCC, and low expression correlated with poor prognosis in patients. Restoring MLYCD expression in ccRCC cells decreased the content of malonyl CoA, which blocked de novo fatty acid synthesis and promoted fatty acid translocation into mitochondria for oxidation. Inhibition of lipid droplet accumulation induced by MLYCD-mediated fatty acid oxidation disrupted endoplasmic reticulum and mitochondrial homeostasis, increased reactive oxygen species levels, and induced ferroptosis. Moreover, overexpressing MLYCD reduced tumor growth and reversed resistance to sunitinib in vitro and in vivo. Mechanistically, HIF2α inhibited MLYCD translation by upregulating expression of eIF4G3 microexons. Together, this study demonstrates that fatty acid catabolism mediated by MLYCD disrupts lipid homeostasis to repress ccRCC progression. Activating MLYCD-mediated fatty acid metabolism could be a promising therapeutic strategy for treating ccRCC. SIGNIFICANCE: MLYCD deficiency facilitates fatty acid synthesis and lipid droplet accumulation to drive progression of renal cell carcinoma, indicating inducing MYLCD as a potential approach to reprogram fatty acid metabolism in kidney cancer.

miRNA-633 and KAI1 as Potential Biomarkers of Malignant Melanoma with Gastric Cancer.

OBJECTIVE: Malignant melanoma with gastric cancer is one of the most malignant tumors. However, there have been no reports on the effects of KAI1 and miRNA-633 on the survival and prognosis of patients with malignant melanoma with gastric cancer. METHODS: Fifty patients with malignant melanoma and gastric cancer were collected from October 2017 to December 2019. The clinical parameters included clinical information, such as sex, age, tumor size, and tumor staging. RT-qPCR was used to detect the expression of KAI1 and miRNA- 633. The role of KAI1 and miRNA-633 on the overall survival of melanoma was explored by the Pearson chi-square test, Spearman-rho correlation test, Univariate and multivariate cox regression analyses, and Kaplan-Meier method. Furthermore, the bioinformatic analysis was used to verify the role of KAI1 and miRNA-633 on malignant melanoma with gastric cancer. RESULTS: The expression of KAI1 and miRNA-633 was significantly related with the tumor size and staging of tumor (p<0.05) based on the Pearson chi-square test. Spearman's correlation coefficient displayed that KAI1 was significantly correlated with the miRNA-633 (ρ=-0.439, p=0.001). The result of multivariate cox proportional regression analysis showed that KAI1 (HR =0.109, 95% CI: 0.031-0.375, p< 0.001), and miRNA-633 (HR = 13.315, 95% CI: 3.844-46.119, p<0.001) were significantly associated with overall survival. CONCLUSION: The low expression level of KAI1 and high expression of miRNA-633 are significantly correlated with the poor overall survival prognosis of malignant melanoma with gastric cancer, to provide a basis for KAI1 and miRNA-633 to become novel molecular targets for malignant melanoma with gastric cancer.

Gastric mucosal precancerous lesions in Helicobacter pylori-infected pediatric patients in central China: A single-center, retrospective investigation.

BACKGROUND: Helicobacter pylori (H. pylori) infects about 50% of the world population and is the major cause of chronic gastritis, peptic ulcers, and gastric cancer. Chronic H. pylori infection induces gastric mucosal precancerous lesions mostly in adulthood, and it is debatable whether these pathological conditions can occur in childhood and adolescents as well. Since this is a critical issue to determine if intervention should be offered for this population group, we investigated the gastric mucosal precancerous lesions in pediatric patients in an area in central China with a high prevalence of H. pylori and gastric cancer. AIM: To investigate the relationship of H. pylori infection and gastric mucosal precancerous lesions in children and adolescents in central China. METHODS: We screened 4258 ward-admitted children and adolescent patients with upper gastrointestinal symptoms, and finally enrolled 1015 pediatric patients with H. pylori infection and endoscopic and histological data. H. pylori infection status was determined by rapid urease test and histopathological examination. Both clinical and pathological data were collected and analyzed retrospectively. Occurrence of gastric mucosal precancerous lesions, inflammatory activity and degree of inflammatory cell infiltration between H. pylori-positive and -negative groups were compared. RESULTS: Among the 1015 eligible children and adolescents, the overall H. pylori infection rate was 84.14% (854/1015). The infection rate increased with age. The incidence of gastric mucosal precancerous lesions in H. pylori-infected children was 4.33% (37/854), which included atrophic gastritis (17 cases), intestinal metaplasia (11 cases) and dysplasia (9 cases). In H. pylori-negative patients, only 1 atrophic gastritis case [0.62%, (1/161)] was found (P < 0.05). Active inflammation in H. pylori-infected patients was significantly higher than that in non-infected patients, and the H. pylori-infected group showed more severe lymphocyte and neutrophil granulocyte infiltration (P < 0.001). In addition, endoscopy revealed that the most common findings in H. pylori-positive patients were antral nodularity, but in H. pylori-negative patients only superficial gastritis was observed. CONCLUSION: In children and adolescents, gastric mucosal precancerous lesions occurred in 4.33% of H. pylori-infected patients in central China. These cases included atrophic gastritis, intestinal metaplasia, and dysplasia. The data revealed an obvious critical issue requiring future investigation and intervention for this population group.

LncRNA 1700020I14Rik promotes AKR1B10 expression and activates Erk pathway to induce hepatocyte damage in alcoholic hepatitis.

Alcoholic hepatitis (AH), a kind of alcoholic liver disease, shows poor prognosis. Long noncoding RNAs (lncRNAs) exert critical role in liver diseases. Here, we intended to investigate the possible molecular mechanism that 1700020I14Rik-based regulation of microRNA (miR)-137/Aldo-keto reductase family 1 member B10 (AKR1B10) affecting the inflammatory response and hepatocyte damage in AH. AH-related genes and the down-stream regulatory pathway were screnned by bioinformatics. Mouse normal hepatocyte cell line AML12 was selected to construct an ethanol-induced hepatocyte injury model for in vitro mechanistic validation, while we also established an AH mouse model using the ethanol with gradually increased concentration of 2-4% (v/v) for in vivo study. Specific role of 1700020I14Rik/miR-137/AKR1B10 in AML12 cell viability, proliferation and apoptotic capacity as well as inflammation and liver damage in mice were analyzed following ectopic and depletion approaches. We found elevated AKR1B10 and 1700020I14Rik but reduced miR-137 in AH. 1700020I14Rik was able to elevated miR-137-mediated AKR1B10. In vitro cell experiments and in vivo animal experiments validated that 1700020I14Rik reduced ethanol-induced hepatocyte damage and inflammation in AH mice through regulation of miR-137-mediated AKR1B10/Erk axis. The current study underlied that 1700020I14Rik could activate AKR1B10/Erk signaling through inhibition of miR-137, thereby promoting the hepatocyte damage in AH mice.

miR-129-5p Plays an Anticancer Role in Colon Cancer by Targeting RSF1.

This study aimed to investigate the inhibitory effect of miR-129-5p on colon cancer by targeting RSF1. For this purpose, real-time quantitative PCR was used to analyze whether the expression of miR-129-5p in colon cancer and adjacent normal tissues had an impact on the proliferation and apoptosis of cancer cells (CC). We evaluated the role of miR-129-5p by targeting RSF1 in colon cancer tissue in the experimental group. But in the control group, only miR-129-5p was considered as a protective factor. Finally, we retrospectively analyzed data of 56 cases of colon cancer patients admitted to our clinical department between January 2019 and December 2019. Twenty-eight cases were investigated through just miR-129-5p protective factors for cancer (group A). The other 28 cases were studied by miR-129-5p anti-cancer agent and a completed RSF1 carcinoma factors for cancer (group B). We evaluated the comparative analysis of the patient's age and gender, clinical indicators (including for the first time of hospitalization and postoperative hospital stay, three times of anal exhaust), and complications (including chills, vomiting, hypertension, diabetes). The results showed that miR-129-5p had a more substantial effect on the proliferation and apoptosis of CC by targeting RSF1.

Both family-based Helicobacter pylori infection control and management strategy and screen-and-treat strategy are cost-effective for gastric cancer prevention.

BACKGROUND: Helicobacter pylori (H. pylori) infection and its related diseases are substantial public health burden for highly infected areas. Recently, a novel family-based H. pylori infection control and management (FBCM) strategy is introduced for H. pylori infection prevention and control. However, its cost-effectiveness has not been evaluated. We conducted this health economic evaluation to investigate the cost-effectiveness of FBCM, screen-and-treat, and no-screen strategies in Chinese population. MATERIALS AND METHODS: Cost-effectiveness analysis was performed using decision tree and Markov model. Parameters required for the model were from published literatures and public databases, including health state utility, screening characteristics, treatment effectiveness, and medical costs for the three strategies. Outcomes were cost, quality-adjusted life year (QALY), incremental cost-effectiveness ratio (ICER). Uncertainty analysis was performed to verify the robustness of this model. RESULTS: To prevent gastric cancer in a cohort of 1 million asymptomatic Chinese families, FBCM and screen-and-treat strategies prevented 1010 and 1201 new gastric cancer cases, reduced 2809 and 3339 gastric cancer-related death, and saved 956,971 and 1,137,549 QALYs, respectively, when compared with no-screen strategy. Cost-effectiveness analysis showed that FBCM strategy cost $9.18/QALY, and screen-and-treat strategy cost $12.08/QALY for gastric cancer prevention when compared with no-screen strategy. One-way sensitivity analysis revealed that screening from younger age by both strategies are more cost-effective. When compared with FBCM strategy, screen-and-treat strategy saved 5.98% gastric cancer cases and 5.78% of gastric cancer deaths, but costed $9348 to reduce a gastric cancer case. Results are not sensitive to any variables, and probabilistic sensitivity analysis confirmed robustness of the results. CONCLUSIONS: Both FBCM and screen-and-treat strategies are cost-effective for gastric cancer prevention compared with no-screen strategy. Since FBCM is more practical and convenient, it may be an efficient and excellent cost-effective strategy for gastric cancer prevention in H. pylori and gastric cancer prevalent areas.

Rabeprazole plus amoxicillin dual therapy is equally effective to bismuth-containing quadruple therapy for Helicobacter pylori eradication in central China: A single-center, prospective, open-label, randomized-controlled trial.

BACKGROUND: Antibiotic resistance emerges as a major issue for Helicobacter pylori (H. pylori) treatment. High-dose dual therapy has recently shown encouraging results in H. pylori eradication, but it has yet to be validated in this H. pylori highly infected area; it is also not known if this concept can be extended to antibiotics other than amoxicillin, and factors that affect the eradication. We investigate if rabeprazole plus amoxicillin or furazolidone regimens could be a first-line therapy for H. pylori eradication, and factors that affect the curing rate. METHODS: This is a single-center, prospective, open-label, randomized-controlled trial. Naive patients (n=292) were randomly treated with bismuth-containing quadruple therapy (BQT), rabeprazole plus amoxicillin (RADT), or furazolidone (RFDT) groups. RADT and FADT use three times daily regimens. H. pylori diagnosis and eradication were determined and confirmed by 13 C-urea breath test. RESULTS: In per-protocol (PP) analysis, H. pylori eradication rate was 91.2% in BQT group, 89.6% in RADT, and 51.0% in RFDT group. In intention-to-treat (ITT) analysis, infection was eradicated in 86.7% of patients in BQT group, 85.8% in RADT, and 48.1% in RFDT groups, respectively. Noninferiority was confirmed between BQT and RADT groups. The incidence of side effects in BQT group was significantly higher than that in RADT group. Successful eradication was associated with lower body surface area (BSA) and low body mass index (BMI) in BQT group. Smoking and high BSA index reduced H. pylori eradication rate in RADT group. CONCLUSIONS: Rabeprazole-amoxicillin dual therapy is equally effective to the bismuth-containing quadruple therapy for H. pylori eradication with fewer side effects and saves use of one antibiotic per each treatment. Successful eradication is also associated with low BSA and non-smoking condition, which deserves future stratified analysis for refinement and optimization.

Whole family-based Helicobacter pylori eradication is a superior strategy to single-infected patient treatment approach: A systematic review and meta-analysis.

BACKGROUND: Two critical concerns during Helicobacter pylori (H. pylori) eradication are the successful eradication and recurrence. It is debatable whether whole family-based H. pylori treatment regimen might have any advantage over single-infected patient treatment approach in increasing eradication rate and reducing recurrence rate. We conduct systematic review and meta-analysis to compare the efficacy of these two treatment regimens in order to provide clinical practice a better option for H. pylori eradication. METHODS: Randomized controlled trials evaluating H. pylori eradication and recurrence in whole family-based treatment group (WFTG) versus single-infected patient treatment group (SPTG) were collected from published literature up to July 2020 from common databases. Pooled results were analyzed using either fixed-effect or random-effect model. Results were expressed as the odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of 1751 relevant articles were identified, and 12 studies were eligible for analysis. Among them: (a) Eight articles including 1198 patients were selected to analyze H. pylori eradication rate, pooled result showed that eradication rate of WFTG was higher than that of SPTG (OR=2.93; 95% CI 1.68-5.13). Stratified analysis showed that H. pylori eradication rate in WFTG were higher over SPTG in children subgroup, but had no difference in spouse subgroup. (b) Six studies including 881 patients were analyzed for recurrence rate between the two groups, pooled analysis showed that the overall recurrence rate of WFTG was lower than that of SPTG (OR=0.3; 95% CI 0.19-0.48). Stratified analysis showed that the recurrence rate in WFTG was lower over SPTG at 6, 12, 18, and more than 24 months post-treatment subgroups. CONCLUSION: Whole family-based H. pylori treatment can partially increase eradication rate and reduce recurrence rate over single-infected patient treatment approach, the results provide clinical practice a novel notion for H. pylori eradication and infection prevention.

Type I and type II Helicobacter pylori infection status and their impact on gastrin and pepsinogen level in a gastric cancer prevalent area.

BACKGROUND: Type I Helicobacter pylori (H. pylori) infection causes severe gastric inflammation and is a predisposing factor for gastric carcinogenesis. However, its infection status in stepwise gastric disease progression in this gastric cancer prevalent area has not been evaluated; it is also not known its impact on commonly used epidemiological gastric cancer risk markers such as gastrin-17 (G-17) and pepsinogens (PGs) during clinical practice. AIM: To explore the prevalence of type I and type II H. pylori infection status and their impact on G-17 and PG levels in clinical practice. METHODS: Thirty-five hundred and seventy-two hospital admitted patients with upper gastrointestinal symptoms were examined, and 523 patients were enrolled in this study. H. pylori infection was confirmed by both 13C-urea breath test and serological assay. Patients were divided into non-atrophic gastritis (NAG), non-atrophic gastritis with erosion (NAGE), chronic atrophic gastritis (CAG), peptic ulcers (PU) and gastric cancer (GC) groups. Their serological G-17, PG I and PG II values and PG I/PG II ratio were also measured. RESULTS: A total H. pylori infection rate of 3572 examined patients was 75.9%, the infection rate of 523 enrolled patients was 76.9%, among which type I H. pylori infection accounted for 72.4% (291/402) and type II was 27.6%; 88.4% of GC patients were H. pylori positive, and 84.2% of them were type I infection, only 11.6% of GC patients were H. pylori negative. Infection rates of type I H. pylori in NAG, NAGE, CAG, PU and GC groups were 67.9%, 62.7%, 79.7%, 77.6% and 84.2%, respectively. H. pylori infection resulted in significantly higher G-17 and PG II values and decreased PG I/PG II ratio. Both types of H. pylori induced higher G-17 level, but type I strain infection resulted in an increased PG II level and decreased PG I/PG II ratio in NAG, NAGE and CAG groups over uninfected controls. Overall PG I levels showed no difference among all disease groups and in the presence or absence of H. pylori; in stratified analysis, its level was increased in GC and PU patients in H. pylori and type I H. pylori-positive groups. CONCLUSION: Type I H. pylori infection is the major form of infection in this geographic region, and a very low percentage (11.6%) of GC patients are not infected by H. pylori. Both types of H. pylori induce an increase in G-17 level, while type I H. pylori is the major strain that affects PG I and PG IIs level and PG I/PG II ratio in stepwise chronic gastric disease. The data provide insights into H. pylori infection status and indicate the necessity and urgency for bacteria eradication and disease prevention in clinical practice.

Activation of LXRß inhibits proliferation, promotes apoptosis, and increases chemosensitivity of gastric cancer cells by upregulating the expression of ATF4.

Recently, great advances have been achieved in both surgery and chemotherapy for the treatment of gastric cancer, but there is still poor prognosis for this disease. The aim of this study is to investigate the role of liver X receptor ß (LXRß) in chemosensitivity of gastric cancer SGC7901 cells. From 171 patients with gastric cancer, the gastric cancer and paracancerous tissues were selected to measure the expression of LXRß and ATF4. Gastric cancer cell lines were cultured and screened to figure out the proliferation and apoptosis of gastric cancer SGC7901 cells with the treatment of LXRß agonist (GW3965), ATF4 short hairpin RNA (shRNA), and chemotherapy drug paclitaxel. The expression of apoptosis-related gene cleaved caspase-3 was detected by Western blot analysis. First, we found that the expressions of LXRß and ATF4 in gastric cancer tissues and cells were significantly lower than those in their paracancerous tissues and gastric mucosal epithelial cells. In addition, activation of LXRß and paclitaxel treatment suppressed proliferation of SGC7901 cells, and the expression of ATF4 was upregulated in a concentration-dependent manner. Furthermore, shRNA significantly inhibited the expression of ATF4 and blocked the chemosensitivity of SGC7901 cells to LXRß activation. Our study demonstrates that the expression of LXRß was low in gastric cancer. In addition, activation of LXRß may inhibit the proliferation of gastric cancer cells, promote apoptosis, and increase chemosensitivity by upregulating the expression of ATF4.

Comprehensive comparison of therapeutic efficacy of radiofrequency target disc decompression and nucleoplasty for lumbar disc herniation: a five year follow-up.

PURPOSE: To compare the therapeutic efficacy of radiofrequency target disc decompression(TDD) and nucleoplasty for lumbar disc herniation. METHODS: Two hundred sixty patients with lumbar disc herniation were divided into two groups: target disc decompression group (group T, n = 147) and nucleoplasty group (group N, n = 113). Visual analogue scale (VAS) and functional rating index (FRI) were measured at one, three, six, 12, 24, and 60 months after the surgery. Hospitalization time, operation time, complications, and recurrence/invalid were compared between the two groups. RESULTS: Compared with the pre-operation, the VAS and FRI in both groups were significantly decreased in post-operation(P < 0.01). The VAS and FRI in group T have no significant difference compared to those in group N. The hospitalization and operation time of group T were significantly longer than those in group N. There was no significant difference of the occurrence of complications and disease recurrence/invalid during the follow-up between the two groups. Logstic regression analysis showed that operation time was an independent factor in the prognosis. Operation time affects the treatment effect. Shorter operation time leads to better therapeutic efficacy, and longer operation time leads to poor therapeutic efficacy. CONCLUSIONS: Both TDD and nucleoplasty can reduce pain in patients with lumbar disc herniation and improve quality of life. Group N had shorter hospitalization and operation time than group T.