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Background The Enoyl-CoA hydratase/isomerase family plays a crucial role in the metabolism of tumors, being crucial for maintaining the energy balance and biosynthetic needs of cancer cells. However, the enzymes within this family that are pivotal in gastric cancer (GC) remain unclear. Methods We employed bioinformatics techniques to identify key Enoyl-CoA hydratase/isomerase in GC. The expression of ECHDC2 and its clinical significance were validated through tissue microarray analysis. The role of ECHDC2 in GC was further assessed using colony formation assays, CCK8 assay, EDU assay, Glucose and lactic acid assay, and subcutaneous tumor experiments in nude mice. The mechanism of action of ECHDC2 was validated through Western blotting, Co-immunoprecipitation, and immunofluorescence experiments. Results Our analysis of multiple datasets indicates that low expression of ECHDC2 in GC is significantly associated with poor prognosis. Overexpression of ECHDC2 notably inhibits aerobic glycolysis and proliferation of GC cells both in vivo and in vitro. Further experiments revealed that overexpression of ECHDC2 suppresses the P38 MAPK pathway by inhibiting the protein level of MCCC2, thereby restraining glycolysis and proliferation in GC cells. Ultimately, it was discovered that ECHDC2 promotes the ubiquitination and subsequent degradation of MCCC2 protein by binding with NEDD4. Conclusions These findings underscore the pivotal role of the ECHDC2 in regulating aerobic glycolysis and proliferation in GC cells, suggesting ECHDC2 as a potential therapeutic target in GC.

β-Elemene, derived from (Wenyujin), is clinically recognized for inducing apoptosis, inhibiting cell cycle progression, and reversing chemotherapy resistance in various cancers. However, its effects on radioresistant gastric cancer (GC) remain unclear. In this study, radioresistant GC cell lines (MKN45/IR and AGS/IR) were established via multiple low-dose radiations. The impact of β-elemene on radiosensitivity was assessed using CCK-8 and clonogenic assays, with ferroptosis markers such as ROS, MDA, and Fe levels measured. Additionally, the influence of β-elemene on GPX4 and its interaction with OTUB1 was examined through qRT-PCR, Western blot, immunofluorescence, co-immunoprecipitation, and in vivo studies. Our findings indicate that β-elemene reverses radioresistance in GC cells and significantly inhibits cell growth when combined with radiotherapy. β-Elemene treatment elevated ROS, MDA, and Fe levels, enhancing ferroptosis, which was confirmed by Ferrostatin-1 and Deferoxamine inhibition studies. Mechanistic analysis revealed that β-elemene disrupts the OTUB1-GPX4 interaction, leading to increased GPX4 ubiquitination and degradation, thus promoting ferroptosis. studies further demonstrated that β-elemene combined with radiotherapy significantly suppressed tumor growth compared to radiotherapy alone. These results suggest that β-elemene effectively modulates radioresistance in GC by targeting the GPX4 pathway and inducing ferroptosis. This highlights its potential as a therapeutic adjunct in radiotherapy for resistant GC cases.

Background Cancer-induced pre-metastatic niches (PMNs) play a decisive role in promoting metastasis by facilitating angiogenesis in distant sites. Evidence accumulates suggesting that microRNAs (miRNAs) exert significant influence on angiogenesis during PMN formation, yet their specific roles and regulatory mechanisms in gastric cancer (GC) remain underexplored. Methods miR-605-3p was identified through miRNA-seq and validated by qRT-PCR. Its correlation with the clinicopathological characteristics and prognosis was analyzed in GC. Functional assays were performed to examine angiogenesis both in vitro and in vivo. The related molecular mechanisms were elucidated using RNA-seq, immunofluorescence, transmission electron microscopy, nanoparticle tracking analysis, enzyme-linked immunosorbent assay, luciferase reporter assays and bioinformatics analysis. Results miR-605-3p was screened as a candidate miRNA that may regulate angiogenesis in GC. Low expression of miR-605-3p is associated with shorter overall survival and disease-free survival in GC. miR-605-3p-mediated GC-secreted exosomes regulate angiogenesis by regulating exosomal nitric oxide synthase 3 (NOS3) derived from GC cells. Mechanistically, miR-605-3p reduced the secretion of exosomes by inhibiting vesicle-associated membrane protein 3 (VAMP3) expression and affects the transport of multivesicular bodies to the GC cell membrane. At the same time, miR-605-3p reduces NOS3 levels in exosomes by inhibiting the expression of intracellular NOS3. Upon uptake of GC cell-derived exosomal NOS3, human umbilical vein endothelial cells exhibited increased nitric oxide levels, which induced angiogenesis, established liver PMN and ultimately promoted the occurrence of liver metastasis. Furthermore, a high level of plasma exosomal NOS3 was clinically associated with metastasis in GC patients. Conclusions miR-605-3p may play a pivotal role in regulating VAMP3-mediated secretion of exosomal NOS3, thereby affecting the formation of GC PMN and thus inhibiting GC metastasis.

Background The effectiveness of laparoscopic total gastrectomy with D2 lymphadenectomy (LTGD2) remains controversial. This meta-analysis compares surgical and survival outcomes of LTGD2 and open total gastrectomy with D2 lymphadenectomy (OTGD2) for gastric cancer. Methods Controlled studies comparing LTGD2 and OTGD2 published before November 2021 were retrieved via database searches. We compared intraoperative outcomes, pathological data, postoperative outcomes, 5-year disease-free survival (DFS), and overall survival (OS). Results 17 studies were included, containing 4742 patients. Compared with OTGD2, the LTGD2 group had less blood loss (mean difference [MD] = − 122.48; 95% CI: − 187.60, − 57.37; P = 0.0002), fewer analgesic medication (MD = -2.48; 95% CI: − 2.69, − 2.27; P < 0.00001), earlier first flatus (MD = − 1.03; 95% CI: − 1.80, − 0.26; P = 0.009), earlier initial food intake (MD = − 0.89; 95% CI: − 1.09, − 0.68; P < 0.00001) and shorter hospital stay (MD = − 3.24; 95% CI: − 3.75, − 2.73; P < 0.00001). The LTGD2 group had lower postoperative total complication ratio (OR = 0.76; 95% CI: 0.62, 0.92; P = 0.006), incision (OR = 0.50; 95% CI:0.31, 0.79; P = 0.003) and pulmonary (OR = 0.57; 95% CI: 0.34, 0.96; P = 0.03) complication rates, but similar rates of other complications and mortality. Total number of dissected lymph nodes were similar, but the number of No. 10 dissected nodes was less with LTGD2 (MD = − 0.31; 95% CI: − 0.46, − 0.16; P < 0.0001). There was no difference in 5-year OS (P = 0.19) and DFS (P = 0.34) between LTGD2 and OTGD2 groups. Conclusions LTGD2 produces small trauma, fast postoperative recovery and small length of hospital stays than OTGD2, and had similar long-term clinical efficacy as OTGD2. However, these results still need further high-quality prospective randomized controlled trials confirmation.

Objective The aim of this study was to measure the extracellular matrix protein Spondin-2 (SPON2) in hepatocellular carcinoma (HCC) tissues and to determine its potential value as a prognostic indicator by assessing its correlation with clinicopathological variables and survival. Methods SPON2 mRNA expression was assessed in 20 matched pairs of HCC and non-cancerous liver tissues by quantitative reverse transcription-polymerase chain reaction analysis. SPON2 protein expression was determined in 107 matched pairs of HCC and normal liver tissue by immunohistochemical staining of tissue microarrays. Results Analysis of patient tissues and Oncomine datasets showed that SPON2 mRNA and SPON2 protein expression were both significantly upregulated in HCC tissues, compared with non-cancerous liver tissue; moreover, both correlated significantly with tumor size. Kaplan-Meier analysis revealed that HCC patients who showed high levels of cytoplasmic SPON2 protein had poorer survival following curative resection, compared with HCC patients who exhibited low protein expression levels. Multivariate Cox regression analysis showed that tumor thrombus and SPON2 protein expression both independently correlated with reduced survival in HCC patients. Conclusion Upregulated expression of SPON2 protein in tumor tissue could be an effective prognostic indicator for patients with HCC.

Background Lymphatic metastasis in gastric cancer (GC) profoundly influences its prognosis, but the precise mechanism remains elusive. In this study, we identified the long noncoding RNA MIR181A2HG as being upregulated in GC and associated with LNs metastasis and prognosis. Methods The expression of MIR181A2HG in GC was identified through bioinformatics screening analysis and qRT‐PCR validation. Both in vitro and in vivo functional studies revealed that MIR181A2HG facilitates lymphangiogenesis and lymphatic metastasis. Techniques such as immunofluorescence, immunohistochemistry, qRT‐PCR, ELISA, CHIP, RNA‐pulldown, luciferase reporter assay, and Co‐IP were employed to investigate the mechanism of MIR181A2HG in LNs metastasis of GC. Results MIR181A2HG overexpressed in GC signifies an unfavorable prognosis and drives M2 polarization of TAMs enhancing lymphangiogenesis. Mechanistically, MIR181A2HG/miR‐5680 axis as a novel ceRNA regulatory axis to upregulate versican (VCAN). On one hand, VCAN interacts with CD44 receptors on the surface of TAMs through paracrine secretion, promoting M2 macrophage polarization and subsequently enhancing the secretion of VEGF‐C, ultimately facilitating lymphangiogenesis. On the other hand, VCAN binds to CD44 receptors on the surface of GC cells through autocrine secretion, activating the Hippo pathway and upregulating SP1, thereby promoting the transcription of MIR181A2HG and establishing a feedback loop driving lymphatic metastasis. Conclusion This study highlights the pivotal role of MIR181A2HG in GC progression and LNs metastasis. MIR181A2HG‐based targeted therapy would represent a novel strategy for GC.

We evaluated factors associated with mortality in patients with moderate/severe generalized tetanus. This retrospective study included patients with moderate/severe generalized tetanus admitted to the Affiliated Hospital of Nantong University (China) between January 2005 and January 2017. Clinical data were extracted from medical records. Patients were divided into two groups based on outcome (survival or death). Factors associated with mortality were analyzed using univariate and multivariate logistic regression. Seventy-five patients were included (57.3% male; age, 57.9 ± 18.4 years; APACHE II score, 10.6 ± 3.4; severe tetanus, 49.3%; mortality, 25.3%). Multivariate analysis identified severe tetanus (odds ratio [OR], 30.364; 95% confidence interval [CI], 2.459–374.896) and APACHE II score (OR, 1.536; 95%CI, 1.051–2.243) as positively associated with mortality, whereas high-calorie nutrition (OR, 0.027; 95%CI, 0.002–0.359) and dexmedetomidine use (OR, 0.035; 95%CI, 0.003–0.467) were negatively associated with mortality (all P < 0.05). Tetanus severity and APACHE II score were associated with mortality in patients with generalized tetanus, whereas high-calorie nutrition and dexmedetomidine use reduced the odds of death. High-calorie nutrition and dexmedetomidine administration may improve prognosis in adult patients with moderate/severe generalized tetanus.

Background This study aimed to investigate whether the detection of methylation in the promoter of the Ras association domain family 10 gene (RASSF10) in the serum of patients with gastric cancer (GC) by methylation-specific PCR (MSP) can be used as a diagnostic and prognostic indicator of GC. Methods We used MSP to examine RASSF10 methylation levels in the serum and/or tumor samples from 100 GC patients, 50 patients with chronic atrophic gastritis (CAG), and 45 healthy controls (HC). We also analyzed clinicopathological and follow-up data. Results Our results showed that the rate of serum RASFF10 promoter methylation among patients with GC (49/100) was higher than in those with CAG (1/50) or HC (0/45). Moreover, the RASSF10 methylation status was consistent between serum and tumor tissues. GC patients with serum RASSF10 promoter methylation had significantly shorter overall survival and disease-free survival times than GC patients without serum RASSF10 promoter methylation. Multivariable Cox regression analysis showed that serum RASSF10 promoter methylation and lymph node metastasis both correlated with reduced survival in GC patients. Conclusions Detection of the serum RASSF10 methylation status by MSP is feasible as a diagnostic and prognostic indicator of GC.

Spondin 2 (SPON2), a member of the Mindin F‐Spondin family, identifies pathogens, activates congenital immunity and promotes the growth and adhesion of neurons as well as binding to their receptors, but its role in promoting or inhibiting tumour metastasis is controversial. Here, we investigated its expression levels and mechanism of action in gastric cancer (GC). Western blotting and GC tissue arrays were used to determine the expression levels of SPON2. ELISAs were performed to measure the serum levels of SPON2 in patients with GC. Two GC cell lines expressing low levels of SPON2 were used to analyse the effects of regulating SPON2 expression on proliferation, migration, invasion, the cell cycle and apoptosis. The results revealed that SPON2 was highly expressed in GC tissues from patients with relapse or metastasis. The levels of SPON2 in sera of patients with GC were significantly higher compared with those of healthy individuals and patients with atrophic gastritis. Knockdown of SPON2 expression significantly inhibited the proliferation, migration and invasion of GC cells in vitro and in vivo. Down‐regulation of SPON2 arrested the cell cycle in G1/S, accelerated apoptosis through the mitochondrial pathway and inhibited the epithelial‐mesenchymal transition by blocking activation of the ERK1/2 pathway. In summary, this study suggests that SPON2 acts as an oncogene in the development of GC and may serve as a marker for the diagnosing GC as well as a new therapeutic target for GC.

BackgroundThe SCY1-like (SCYL) family has been reported to be closely related to cancer metastasis, but it has not been reported in gastric cancer (GC), and its specific mechanism is not clear.MethodsWe utilized databases like Deepmap, TCGA, and GEO to identify SCYL1's role in GC. Clinical samples were analyzed for SCYL1 expression and its correlation with patient prognosis. In vitro and in vivo experiments were conducted to assess SCYL1's function in GC cell migration, invasion, and autophagy.ResultsSCYL1 showed an increased expression in GC tissues, which correlated with a negative prognosis. In vitro experiments demonstrated that SCYL1 promotes GC cell migration and invasion and inhibits autophagy. GSEA indicated an inverse relationship between SCYL1 and autophagy, while a direct relationship was observed with the mTORC1 signaling pathway. Knockdown of SCYL1 enhanced autophagy, while activation of mTORC1 reversed this effect.ConclusionsSCYL1 is a significant contributor to GC progression, promoting metastasis by activating the mTORC1 signaling pathway and inhibiting autophagy. These findings suggest SCYL1 as a potential therapeutic target for GC treatment.