Comprehensive analysis of PSMG3 in pan-cancer and validation of its role in hepatocellular carcinoma.

BACKGROUND: Proteasome assembly chaperone 3 (PSMG3), a subunit of proteasome, has been found to be associated with lung cancer. However, the role of PSMG3 in other cancers has not been elucidated. The objective of this study was to explore the immune role of PSMG3 in pan-cancer and confirm the oncogenic significance in liver hepatocellular carcinoma (LIHC). METHODS: We examined the differential expression of PSMG3 across various cancer types using data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. We investigated the prognostic value of PSMG3 and examined its relationship with tumor mutation burden (TMB), microsatellite instability (MSI), and immune infiltration. The functional enrichment analysis was performed to explore the potential molecular mechanism of PSMG3. To elucidate the biological function of PSMG3, we conducted in vitro experiments using liver cancer cell lines. RESULTS: PSMG3 was highly expressed in most cancers. The high PSMG3 expression value of PSMG3 was closely related to poor prognosis. We observed correlations between PSMG3 and TMB, and MSI immune infiltration. PSMG3 may be involved in metabolic reprogramming, cell cycle, and PPAR pathways. The over-expression of PSMG3 promoted the proliferation, migration, and invasion capabilities of liver cancer cells. CONCLUSION: Our study demonstrated that PSMG3 was a pivotal oncogene in multiple cancers. PSMG3 contributed to the progression and immune infiltration in pan-cancer, especially in LIHC.

Design, synthesis and bioactivity evaluation of 4-hydroxycoumarin derivatives as potential anti-inflammatory agents against acute lung injury and colitis.

Acute lung injury (ALI) and inflammatory bowel disease (IBD) are common inflammatory illnesses that seriously affect people's health. Herein, a series of 4-hydroxylcoumarin (4-HC) derivatives were designed and synthesized. The inhibitory effects of these compounds on LPS-induced interleukin-6 (IL-6) release from J774A.1 cells were then screened via ELISA assay, compound B8 showed 3 times more active than the lead compound 4-HC. The most active compound B8 had the IC50 values of 4.57 µM and 6.51 µM for IL-6 release on mouse cells J774A.1 and human cells THP-1, respectively. Furthermore, we also found that B8 could act on the MAPK pathway. Based on the target prediction results of computer virtual docking, kinase inhibitory assay was carried out, and it revealed that targeting IRAK1 was a key mechanism for B8 to exert anti-inflammatory activity. Moreover, B8 exerted a good therapeutic effect on the dextran sulfate sodium (DSS)-induced colitis model and liposaccharide (LPS)-induced ALI mouse models. The acute toxicity experiments indicated that high-dose B8 caused no adverse reactions in mice, confirming its safety in vivo. Additionally, the preliminary pharmacokinetic (PK) parameters of B8 in SD rats were also examined, revealing a bioavailability (F) of 28.72 %. In conclusion, B8 is a potential candidate of drug for the treatment of ALI and colitis.

Endoscopic extraction of a submucosal esophageal foreign body piercing into the thoracic aorta: A case report.

BACKGROUND: Aorto-esophageal injury is a rare but life-threatening complication of esophageal foreign bodies, which typically requires open surgery. The best way to treat patients with this condition remains unclear. To date, few reports have described an aortic wall directly penetrated by a sharp foreign body. Here, we present a rare case of a fishbone completely embedded in the esophageal muscularis propria and directly piercing the aorta, which was successfully treated by endoscopy and thoracic endovascular aortic repair (TEVAR). CASE SUMMARY: We report the case of a 71-year-old man with a 1-d history of retrosternal pain after eating fish. No abnormal findings were observed by the emergency esophagoscopy. Computed tomography showed a fishbone that had completely pierced through the esophageal mucosa and into the aorta. The patient refused to undergo surgery for personal reasons and was discharged. Five days after the onset of illness, he was readmitted to our hospital. Endoscopy examination showed a nodule with a smooth surface in the middle of the esophagus. Endoscopic ultrasonography confirmed a fishbone under the nodule. After performing TEVAR, we incised the esophageal mucosa under an endoscope and successfully removed the fishbone. The patient has remained in good condition for 1 year. CONCLUSION: Incising the esophageal wall under endoscope and extracting a foreign body after TEVAR may be a feasible option for cases such as ours.

Knocking down Dp71 expression in A549 cells reduces its malignancy in vivo and in vitro.

Dp71 is one of the most ubiquitously expressed isoforms of dystrophin, the pathological genes of DMD. In order to find whether the alteration of Dp71 can affect the phenotypes of cell other than PC12, an A549 cell line with stably transfected Dp71 siRNA plasmids was set up and named A549-Dp71AS cell. It is demonstrated for the first time that the A549-Dp71AS cell line displayed decreased invasion capabilities, reduced migration ability, decreased proliferation rate, and lessened clonogenic formation. Cisplatin-induced apoptosis was also increased in A549-Dp71AS cell line via enhancing the Caspase 3, Caspase 8, and Caspase 9 activities. Knocking down Dp71 expression can significantly inhibit the A549 xenograft tumor growth in nude mice. The A549-Dp71AS cells and xenograft tumor tissues displayed reduced lamin B1, Bcl-2, and MMP2 protein expression, which accounts for the reduced malignancy of A549-Dp71AS cells in vivo and in vitro.