Exploring the impact of ITGB2 on glioma progression and treatment: Insights from non-apoptotic cell death and immunotherapy.

In the realm of glioma treatment, our groundbreaking research has uncovered the pivotal role of Integrin Beta 2 (ITGB2) in non-apoptotic cell death and its profound implications for immunotherapy efficacy. Gliomas, known for their aggressive and infiltrative nature, demand innovative therapeutic strategies for improved patient outcomes. Our study bridges a critical gap by examining the interplay between non-apoptotic cell death and immunotherapy response in gliomas. Through comprehensive analysis of ten diverse glioma datasets, we developed a unique death enrichment score and identified ITGB2 as a significant risk marker. This study demonstrates that ITGB2 can predict immune activity, mutation characteristics, and drug response in glioma patients. We reveal that ITGB2 not only mediates glioma proliferation and migration but also crucially influences immunotherapy responses by modulating the interaction between gliomas and macrophages by single-cell sequencing analysis (iTalk and ICELLNET). Employing a variety of molecular and cellular methodologies, including in vitro models, our findings highlight ITGB2 as a potent marker in glioma biology, particularly impacting macrophage migration and polarization. We present compelling evidence of ITGB2's dual role in regulating tumor cell behavior and shaping the immune landscape, thereby influencing therapeutic outcomes. The study underlines the potential of ITGB2-targeted strategies in enhancing the efficacy of immunotherapy and opens new avenues for personalized treatment approaches in glioma management. In conclusion, this research marks a significant stride in understanding glioma pathology and therapy, positioning ITGB2 as a key biomarker and a promising target in the quest for effective glioma treatments.

IGFBP2 from a novel copper metabolism-associated biomarker promoted glioma progression and response to immunotherapy.

Introduction: Copper metabolism encompasses all cellular metabolic processes involving copper ions and plays a significant role in the pathogenesis of diseases, including cancer. Furthermore, copper is intricately involved in various processes related to nucleotide metabolism. However, a comprehensive analysis of copper metabolism in gliomas remains lacking despite its importance. Methods: To address this gap, glioma patients were stratified based on the expression levels of copper metabolism-related genes. By utilizing machine learning techniques, a novel copper metabolism-associated biomarker was developed. The potential of this biomarker in prognosis, mutation analysis, and predicting immunotherapy response efficiency in gliomas was systematically investigated. Results: Notably, IGFBP2, identified as a glioma tumor promoter, was found to promote disease progression and influence immunotherapy response. Additionally, glioma-derived IGFBP2 was observed to enhance microglial migration. High IGFBP2 expression in GBM cells facilitated macrophage interactions through the EGFR, CD63, ITGB1, and CD44 signaling pathways. Discussion: Overall, the copper metabolism-associated biomarker shows promising potential to enhance the clinical management of gliomas, offering valuable insights into disease prognosis and treatment strategies.

GPX8 regulates pan-apoptosis in gliomas to promote microglial migration and mediate immunotherapy responses.

Introduction: Gliomas have emerged as the predominant brain tumor type in recent decades, yet the exploration of non-apoptotic cell death regulated by the pan-optosome complex, known as pan-apoptosis, remains largely unexplored in this context. This study aims to illuminate the molecular properties of pan-apoptosis-related genes in glioma patients, classifying them and developing a signature using machine learning techniques. Methods: The prognostic significance, mutation features, immunological characteristics, and pharmaceutical prediction performance of this signature were comprehensively investigated. Furthermore, GPX8, a gene of interest, was extensively examined for its prognostic value, immunological characteristics, medication prediction performance, and immunotherapy prediction potential. Results: Experimental techniques such as CCK-8, Transwell, and EdU investigations revealed that GPX8 acts as a tumor accelerator in gliomas. At the single-cell RNA sequencing level, GPX8 appeared to facilitate cell contact between tumor cells and macrophages, potentially enhancing microglial migration. Conclusions: The incorporation of pan-apoptosis-related features shows promising potential for clinical applications in predicting tumor progression and advancing immunotherapeutic strategies. However, further in vitro and in vivo investigations are necessary to validate the tumorigenic and immunogenic processes associated with GPX8 in gliomas.

Targeting MYH9 represses USP14-mediated NAP1L1 deubiquitination and cell proliferation in glioma.

Myosin heavy chain 9 (MYH9) plays an important role in a number of diseases. Nevertheless, the function of MYH9 in glioma is unclear. The present research aimed to investigate the role of MYH9 in glioma and determine whether MYH9 is involved in the temozolomide chemoresistance of glioma cells. Our results showed that MYH9 increased the proliferation and temozolomide resistance of glioma cells. The mechanistic experiments showed that the binding of MYH9 to NAP1L1, a potential promoter of tumor proliferation, inhibited the ubiquitination and degradation of NAP1L1 by recruiting USP14. Upregulation of NAP1L1 increased its binding with c-Myc and activated c-Myc, which induced the expression of CCND1/CDK4, promoting glioma cell temozolomide resistance and proliferation. Additionally, we found that MYH9 upregulation was strongly related to patient survival and is therefore a negative factor for patients with glioma. Altogether, our results show that MYH9 plays a role in glioma progression by regulating NAP1L1 deubiquitination. Thus, targeting MYH9 is a potential therapeutic strategy for the clinical treatment of glioma in the future.

Production of polyhydroxyalkanoate by mixed cultivation of Brevundimonas diminuta R79 and Pseudomonas balearica R90.

The microflora in the activated sludge of propylene oxide saponification wastewater is characterized by a clear succession after enrichment and domestication, and the specifically enriched strains can significantly increase the yield of polyhydroxyalkanoate. In this study, Pseudomonas balearica R90 and Brevundimonas diminuta R79, which are dominant strain after domestication, were selected as models to examine the interactive mechanisms associated with the synthesis of polyhydroxyalkanoate by co-cultured strains. RNA-Seq analysis revealed the up-regulated expression of the acs and phaA genes of strains R79 and R90 in the co-culture group, which enhanced their utilization of acetic acid and synthesis of poly-ß-hydroxybutyrate. Cell dry weight and the yield of poly-ß-hydroxybutyrate in the co-culture group were accordingly considerably higher than those in the respective pure culture groups. In addition, two-component system, quorum-sensing, flagellar synthesis-related, and chemotaxis-related genes were enriched in strain R90, thereby indicating that compared with the R79 strain, R90 can adapt more rapidly to a domesticated environment. Expression of the acs gene was higher in R79 than in R90, and consequently, strain R79 could more efficiently assimilate acetate in the domesticated environment, and thus predominated in the culture population at the end of the fermentation period.

Clinical efficacy and safety of robot assisted surgery for choledochal cysts excisions: a systematic review and meta-analysis.

BACKGROUND: This study aimed to evaluate the safety and therapeutic effect of Robot-assisted surgery (RAS) for choledochal cysts (CCs) excisions. RESEARCH DESIGN AND METHODS: PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, WanFang, VIP, and CBM were searched from database inception to 1 May 2022. The Newcastle-Ottawa scale (NOS) was used to conduct quality assessments, and RevMan (Version 5.4) was used to perform the meta-analysis. RESULTS: In all, 9 studies, involving 623 patients, were analyzed. RAS compared with LAS was associated with less intraoperative blood loss, shorter time to start solid diets, shorter postoperative hospital stay, and lower complications. There was no significant difference in operative time between the two groups, but the total costs were higher in RAS. Our subgroup analysis showed that RAS had significant advantages over LAS in the child group: minor bleeding, shorter length of hospital stay, and fewer postoperative complications. CONCLUSIONS: The available evidence indicates that the RAS system has the advantages of less intraoperative blood loss, minor tissue damage, quick recovery, and sound healing in treating choledochal cyst, which proves that the RAS is safely feasible. Especially in children, RAS tends to be a better choice.

Centromeric protein K (CENPK) promotes gastric cancer proliferation and migration via interacting with XRCC5.

BACKGROUND: CENPK is a novel oncogene which is aberrantly expression in some malignant tumors. However, the role and mechanisms of CENPK in gastric cancer have not been explored. METHODS: In this study, we use RT-PCR and IHC to study CENPK expression in gastric cancer cells and tissues. In addition, we constructed the two kinds of CENPK siRNA lentivirus to knock down CENPK. Then, we use High content living cell imaging System, Cell Counting Kit-8, colony formation, wound healing and Transwell assays to demonstrate the function of CENPK on gastric cancer cells AGS and MKN45. Meanwhile, we use flow cytometry assay to study CENPK function on gastric cancer cell apoptosis and cell cycle arrest. Subcutaneous tumorigenesis in nude mice was also performed to confirm CENPK function on gastric cancer. Finally, we use Co-IP, LC-MS and function rescue assay to study the downstream interaction molecular of CENPK. RESULTS: We demonstrated that CENPK expression were up-regulated in GC cell lines. Poor differentiation and III-IV stage had more percentages of high CENPK expression. Knocking down CENPK could significantly suppress GC cells proliferation, migration and invasion, and induce GC cells apoptosis and G1/S phase transition arrest. Subcutaneous tumorigenesis confirmed the tumor-promoting effects of CENPK in vivo. Remarkably, we found for the first time that XRCC5 might be interacted with CENPK through Co-IP, LC-MS and rescue study. CONCLUSION: CENPK promotes GC cell proliferation and migration via interacting with XRCC5 and may be a novel prognostic factor or therapeutic target for CENPK.

Proximal Gastrectomy Versus Total Gastrectomy for Siewert II/III Adenocarcinoma of the Gastroesophageal Junction: a Systematic Review and Meta-analysis.

BACKGROUND: The incidence of adenocarcinoma of the esophagogastric junction (AEG) has rapidly increased in recent years. Popular surgical approaches for AEG are proximal gastrectomy (PG) and total gastrectomy (TG), but it is controversial as to which approach is superior. Therefore, we conducted a systematic review and meta-analysis to evaluate the short- and long-term clinical outcomes of PG and TG for AEG. METHODS: PubMed, Embase, Web of Science, and Cochrane Library were searched from inception to 1 June 2021. The Newcastle-Ottawa scale was used to conduct quality assessments, and RevMan (Version 5.4) was used to perform the meta-analysis. RESULTS: In all, 1,734 patients with Siewert II/III AEG in 12 studies were included in the meta-analysis. PG was associated with less number of harvested lymph nodes (WMD = - 9.00, 95% CI - 12.61 to - 5.39, P < 0.00001), smaller tumor size (WMD = - 1.02, 95% CI - 1.71 to - 0.33, P = 0.004), shorter hospital length of stay (WMD = - 3.99, 95% CI - 7.27 to - 0.71, P = 0.02), and better long-term nutritional status compared with TG. Overall complications, other complications, and overall survival were not significantly different between the two groups. Moreover, subgroup analysis revealed that the occurrence of anastomotic strictures and reflux esophagitis was associated with the use of novel gastrointestinal tract (GI) anastomoses (double-tract reconstruction, jejunal interposition, and semi-embedded valve anastomosis) after PG. CONCLUSIONS: Based on the available evidence, we recommend that surgeons accept PG combined with multiple novel anastomoses as an optimal surgical approach in patients diagnosed with resectable Siewert type II/III AEG.

Metabolic engineering for biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) from glucose and propionic acid in recombinant Escherichia coli.

In this study, novel polyhydroxyalkanoate (PHA)-associated genes (phaCp and phaABp) cloned from Propylenella binzhouense L72T were expressed in Escherichiacoli cells for PHA production, and the recombinant strains were used to analyze PHA yields with various substrates. The highest poly (3-hydroxybutyrate-co-3-hydroxy-valerate) (PHBV) yield (1.06 g/L) and cell dry weight (3.31 g/L) in E. coli DH5α/ΔptsG-CpABp were achieved by using glucose and propionicacid as substrates. Structural verification of PHBV produced by E. coli DH5α/ΔptsG-CpABp was performed to evaluate the characteristics of the polymers using Fourier transform infrared spectroscopy and nuclear magnetic resonance analysis. In addition, the X-ray diffraction results showed improved crystallinity of PHBV, and thermogravimetric analysis showed good thermal stability of 298 °C. The above findings indicated that the expression of phaCp and phaABp genes resulted in improved PHBV synthesis activity, and the polymer had better performance at higher processing temperatures.

Biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) in metabolically recombinant Escherichia coli.

In this study, a phaCR gene encoding PHA synthase was identified in Rhodoligotrophos defluvii which was adjacent to ß-ketothiolase encoded by phaAR gene and acetoacetyl-CoA reductase encoded by phaBR gene. Amino acid comparison of PhaCR showed the highest homology of 65.98% with PhaC of R. appendicifer, while its homology with typical class I PHA synthase in Cupriavidus necator was only 42.54%. PHA synthesis genes were then transformed into E. coli harboring phaCABR and phaCRABC which were cultured with 15 g/L glucose respectively, and 20.46 wt% and 16.95 wt% of CDW for poly(3-hydroxybutyrate) (PHB) were accumulated respectively. To further explore the effect of substrate specificity for PHA production, the ptsG gene was then deleted and 15 g/L glucose and 1.5 g/L propionate were co-employed as carbon sources, which enabled the synthesis of poly(3HB-co-3HV) copolymer. As a result, poly(3HB-co-3HV) was accumulated up to 24.74 wt% of CDW, and the highest content of 3-hydroxyvalerate (3HV) was 10.86 mol%. The Td5 was 260 °C, which implied that it possessed good thermal stability, and the Mw of GPC in recombinant strains were between 22 and 26 × 104 g/mol, and the highest PDI was 3.771. The structure of poly (3HB-co-3HV) copolymer was determined through 1H NMR analysis.

Robotic surgeries for patients with colorectal cancer who have undergone abdominal procedures: Protocol for meta-analysis.

BACKGROUND: Although the safety and the advantages of laparoscopic and robotic colorectal surgeries have been confirmed, the use of both modalities in patients with previous abdominal surgeries (PAS) history remains uncertain. Herein, we perform a meta-analysis to investigate the impact of PAS on perioperative recovery outcomes from laparoscopic and robotic colorectal surgeries. METHODS: We will search PUBMED, the Cochrane Library, the Chinese Biomedical database (CBM), WanFang data, China National Knowledge Infrastructure (CNKI) up to January 2018. Studies will be screened by title, abstract, and full text independently and in duplicate. Studies that report the impact of PAS on perioperative recovery outcomes from laparoscopic and robotic colorectal surgeries will be eligible for inclusion. Outcome variables will be assessed included combined resection, conversion, operation time, blood loss, number of retrieved lymph nodes, days to soft diet intake, length of hospital stay, and postoperative complications. Assessment of risk of bias and data synthesis will be performed using STATA SE 12.0. Heterogeneity among studies will be assessed using the I statistic. RESULTS: Randomized controlled trials, prospective cohort studies, and propensity-matched comparative studies will be used for the quantitative synthesis of the meta-analysis to evaluate the impact of PAS on perioperative recovery outcomes from laparoscopic and robotic colorectal surgeries. CONCLUSIONS: We aim to draw an objective conclusion of the comparisons in aspects of perioperative outcomes and provide physicians level I evidences for clinical decision makings.

Four differentially methylated gene pairs to predict the prognosis for early stage hepatocellular carcinoma patients.

Hepatocellular carcinoma (HCC) was the second most common malignant tumor with a poor prognostic condition. We aimed to identify novel methylation signatures to predict HCC patients at their early stages. Differentially expressed methylated genes between HCC patients and normal liver tissues retrieved from TCGA were screened out by SAM. Genes highly related to patients' survival were figured out by COX. The signatures that could identify relapse HCC patients were identified by the forwarding search algorithm. Besides, functional enrichment analysis was performed on the methylation genes in the signature. A total of 5,392 CPG sites that differentially methylated expressed were found out and 4,294 differentially expressed genes were obtained. A total of 197 genes among were associated with RFS of HCC patients at both stage I and stage II. Signature composed of 21 pairs was obtained to predict the prognostic situation by C-index forward search method. The function of these genes was figured out by functional enrichment analysis. To summary, the signature composed of 21 gene pairs that can predict the prognostic situation of HCC patients at both stage I and stage II, provided a reference standard for the adjuvant therapy of HCC patients after surgery.

Inhibition of c-Myc by let-7b mimic reverses mutidrug resistance in gastric cancer cells.

Chemotherapy is one of the few effective choices for patients with advanced or recurrent gastric cancer (GC). However, the development of mutidrug resistance (MDR) to cancer chemotherapy is a major obstacle to the effective treatment of advanced GC. Additionally, the mechanism of MDR remains to be determined. In the present study, we tested IC50 of cisplatin (DDP), vincristine (VCR) and 5-fluorouracil (5-FU) in SGC7901, SGC7901/DDP and SGC7901/VCR gastric cancer cells using an MTT assay. The expression of let-7b and c-Myc in these cells was detected by qPCR and western blot analysis. The relationship between let-7b and c-Myc was explored using a luciferase reporter assay. Transfection of let-7b mimic or inhibitor was used to confirm the effect of let-7b on drug sensitivity in chemotherapy via the regulation of c-Myc expression. We found that the expression of let-7b was lower in chemotherapy-resistant SGC7901/DDP and SGC7901/VCR gastric cancer cells than that in chemotherapy-sensitive SGC7901 cells. By contrast, the expression of c-Myc was higher in SGC7901/DDP and SGC7901/VCR cells than that in SGC7901 cells. Furthermore, we confirmed that let-7b suppresses c-Myc gene expression at the mRNA and protein levels in a sequence-specific manner, while transfection of let-7b mimic increases drug sensitivity in chemotherapy-resistant SGC7901/DDP and SGC7901/VCR cells by targeting downregulation of c-Myc. In SGC7901 drug-sensitive cells, however, the sensitivity of chemotherapy was significantly decreased following let-7b inhibitor transfection. The present study results demonstrated that let-7b increases drug sensitivity in chemotherapy­resistant SGC7901/DDP and SGC7901/VCR gastric cancer cells by targeting the downregulation of c-Myc and that, let-7b mimic reverses MDR by promoting cancer stem cell differentiation controlled by double-negative autoregulatory loops (Lin28/let-7 and Myc/let-7) and a double-positive autoregulatory loop (Lin28/Lin28B/Myc) existing in GC cells, which remains to be confirmed.