Heat shock protein 90 (HSP90) functions as a well-known onco-protein to regulate protein conformation, stability and degradation. Pyruvate kinase M2 (PKM2), a critical regulator of the metabolism, growth and metastasis of cancer cells, has been confirmed to be overexpressed in various human cancer including hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying the oncogenic functions of HSP90 and PKM2 overexpression in HCC remain unknown. The expression of HSP90 and PKM2 in HCC specimens and cells were detected by immunoblotting and immunostaining. The interaction between HSP90 and PKM2 was confirmed by tandem affinity purification, co-immunoprecipitation and Glutathione S transferase (GST)-pulldown assay. In this study, we found that HSP90 could bind to PKM2 and subsequently increased PKM2 abundance in HCC cells. Immunohistochemistry (IHC) staining showed that HSP90 level was positively correlated with PKM2 level in HCC tissues. Mechanistically, HSP90 was found to increase the phosphorylation of PKM2 at Thr-328. Protein kinase glycogen synthase kinase-3β (GSK-3β) formed a protein complex with HSP90 and PKM2, and directly mediated Thr-328 phosphorylation of PKM2 induced by HSP90. Thr-328 phosphorylation was critical for maintaining PKM2 stability and its biological functions in regulating glycolysis, mitochondria respiration, proliferation and apoptosis. Functionally, we found that HSP90 promoted the glycolysis and proliferation and inhibited apoptosis of HCC cells in a PKM2 dependent manner. In vivo experiments disclosed that PKM2 was required for the promoting effects of HSP90 on the growth of HCC cells in mice. Furthermore, we demonstrated that positive expression of HSP90 and PKM2 was correlated with poor clinicopathological features including high alpha fetoprotein (AFP) level, large tumor size, portal vein tumor thrombus (PVTT) and advanced tumor-node-metastasis (TNM) stage. Furthermore, we demonstrated that positive expression of HSP90 and PKM2, and a combination of these proteins could strongly predict the poor prognosis of HCC patients. We suggest that HSP90 potentiates the glycolysis and proliferation, reduces the apoptosis and thus enhances the growth of HCC cells through PKM2.

Helicobacter pylori (H pylori) is known as one of the most common infectious pathogens, with high infection and recurrence rates worldwide. The prevalence of H pylori is up to 90% in developing countries, while the annual recurrence rate is much higher than that in developed countries. Recurrence can occur either by recrudescence or reinfection. Compared with reinfection, the time window for recrudescence is generally shorter, followed by the recurrence of H pylori–associated diseases in the short‐term. Many factors are involved in the H pylori reinfection, such as the prevalence of H pylori infection, living conditions and economic development, health conditions and so forth. Previous studies focused less on H pylori recrudescence. Therefore, the influencing factors for H pylori recrudescence needed further exploration. This study reviewed the recrudescence of H pylori infection and its influencing factors.

MicroRNA (miR)-145-5p has been reported to function as a suppressor of cancer and plays an important role in cancer invasiveness. Epithelial–mesenchymal transition (EMT) is an important process in cancer invasion and migration. However, the involvement of miR-145-5p in EMT in human gastric cancer (GC) remains unclear. In this study, we aimed to investigate the molecular mechanisms by which miR-145-5p regulates EMT in GC invasiveness. We used quantitative real-time polymerase chain reaction to investigate the miR-145-5p expression level in GC and matched normal tissues. The effects of miR-145-5p on GC cell invasion and migration abilities were evaluated using Transwell models. The relationships among miR-145-5p and zinc-finger E-box binding homeobox 2 (ZEB2), E-cadherin, and N-cadherin were analyzed by quantitative real-time polymerase chain reaction and Western blot analyses. miR-145-5p levels in primary GC tissues obtained from 60 patients were significantly downregulated, compared to those in paired normal tissues. Lauren classification, depth of tumor invasion, lymph node metastasis, lymphatic invasion, and tumor–node–metastasis stage were associated with miR-145-5p expression. miR-145-5p inhibits the expression of the candidate target gene ZEB2 to delay the invasion and migration of GC cells. ZEB2 acts as transcriptional repressor of E-cadherin, while miR-145-5p is known to suppress N-cadherin directly to regulate EMT. Therefore, we concluded that miR-145-5p may target N-cadherin and ZEB2 directly to influence EMT.

Helicobacter pylori is an important risk factor for gastric ulcers. However, antibacterial therapies increase the resistance rate and decrease the eradication rate of H. pylori . Inspired by the microaerophilic characteristics of H. pylori , we aimed at effectively establishing an oxygen-enriched environment to eradicate and prevent the recurrence of H. pylori . The effect and the mechanism of an oxygen-enriched environment in eradicating H. pylori and preventing the recurrence were explored in vitro and in vivo .

Endoscopic submucosal dissection (ESD) is the standard therapy for superficial esophageal cancer (SEC) presently. However, postoperative mucosal defects often lead to esophageal stricture. Although steroid application is effective prophylaxis, the efficacy and safety of various steroid administration modes remain unclear. Thus, this study aimed to evaluate the efficacy and safety of different steroid administrations for SEC patients post-ESD. A search for relevant studies was conducted on China National Knowledge Infrastructure, Wanfang Database, PubMed, Embase, and Web of Science up to March 25, 2024. Treatment strategies were categorized into four groups: no prevention as control (CON), steroid injection (SI), oral steroids (OS), and SI combined with OS (SI+OS). Comparative meta-analysis was conducted to assess outcomes, including postoperative esophageal stricture rate and the number of endoscopic balloon dilatation (EBD) sessions required after stricture. A total of 25 studies, involving 1555 patients, were included. The SUCRA rankings were as follows: SI+OS (98.9%) > OS (59.9%) > SI (41.2%) > CON (0.0%) in preventing postoperative esophageal stricture rate, and OS (76.9%) > SI+OS (62.1%) > SI (61.0%) > CON (0.0%) in the number of EBD sessions required. Forest plot results indicated that compared with the non-steroid group, steroid interventions were associated with lower rates of postoperative stricture and fewer EBD sessions. Additionally, SI+OS was superior to SI or OS alone in preventing stricture, with no significant differences observed between different steroid administrations in terms of EBD sessions. The incidence of adverse reactions was less than 10% for all interventions, mostly mild and resolvable upon discontinuation. This study suggests that combined administration appears preferable for preventing esophageal stricture in patients post-ESD, and steroids could enhance stricture prognosis. However, due to the lack of large-sample RCT studies comparing different steroid administrations, more high-quality research is necessary to confirm these findings in the future.

Increasing evidence demonstrates that microRNAs (miRNAs/miRs), a type of non‑coding small RNA, can regulate tumor cell migration, invasion and metastasis, and may therefore serve a major function in the occurrence and development of tumors. The present study investigated the effect of miR‑383 on the proliferation, migration and invasion of colon cancer HT‑29 and LoVo cell lines. The expression of miR‑383 in colon cancer and adjacent non‑tumor tissues was examined by reverse transcription‑quantitative polymerase chain reaction. MiR‑383 upregulation was stimulated by transfection with a miR‑383 mimic. Cell proliferation was measured with MTT and colony formation assays, and cell migration and invasion potential were examined by Transwell chamber assays. A proliferating‑inducing ligand (APRIL), myeloid cell leukemia‑1 and cyclooxygenase‑2 protein expression was analyzed by western blotting. The expression of miR‑383 was decreased in colon cancer tissues compared with adjacent non‑tumor tissues (P<0.05). Transfection with a miR‑383 mimic suppressed proliferation and inhibited cell migration and invasion in HT‑29 and LoVo colon cancer cell lines. Overexpression of miR‑383 in HT‑29 and LoVo cells resulted in the suppression of APRIL protein expression. In conclusion, miR‑383 was downregulated in colon cancer. The upregulation of miR‑383 inhibited proliferation, migration and invasion of colon cancer cells, potentially through the regulation of target gene APRIL.