MicroRNA-181a Functions as an Oncogene in Gastric Cancer by Targeting Caprin-1

MicroRNA-181a (miRNA-181a) is a multifaceted miRNA implicated in various cellular processes, particularly in cell fate determination and cellular invasion. It is frequently expressed aberrantly in human tumors and shows opposing functions in different types of cancers. In this study, we found that miRNA-181a is overexpressed in Gastric cancer (GC) tissues. Clinical and pathological analyses revealed that the expression of miRNA-181a is correlated with tumor size, lymph node metastasis, distant metastasis, and TNM stage. Kaplan-Meier analysis indicated that overexpression of miRNA-181a is associated with poor overall survival of patients with GC. Moreover, miRNA-181a is overexpressed in GC cells, and downregulation of miRNA-181a induced cell apoptosis and suppressed the proliferation, invasion, and metastasis of GC cells both in vitro and in vivo. Target prediction and luciferase reporter assay showed that caprin-1 was a direct target of miRNA-181a. Downregulation of caprin-1 expression resulted in a converse change with miRNA-181a in GC. Spearman’s correlation test confirmed that the expression of miRNA-181a expression was inversely correlated with that of caprin-1 in GC cells. Furthermore, the expression of caprin-1 increased after downregulation of miRNA-181a in the GC cells. Caprin-1 siRNA can rescue the oncogenic effect of miRNA-181a on GC cell proliferation, apoptosis, migration, and invasion. These findings suggest that miRNA-181a directly inhibits caprin-1 and promotes GC development. miRNA-181a could be a target for anticancer drug development

Efficacy and pregnancy outcomes of focused ultrasound for cervical high-grade squamous intraepithelial lesions

AbstractObjective To investigate the efficacy and adverse effects of focused ultrasound (FU) in the treatment of high-grade squamous intraepithelial lesions (HSIL) and follow up on pregnancy outcomes in patients.Methods This retrospective study recruited 57 patients aged 20–40 years with cervical HSIL combined with HR-HPV infection who received FU treatment between September 2019 and April 2022. Clinical data of the patients were obtained from hospital records. HSIL cure rate and cumulative HR-HPV clearance rate were assessed after treatment. Patients were followed up on fertility and pregnancy outcomes after treatment by telephone interviews until April 1, 2023.Results During a 6-month follow-up, the HSIL cure rate was 73.7%, and a statistical difference between CIN2 and CIN3 (75.6% vs. 66.7%, p = 0.713) was not present. HSIL -recurrence was not observed during the follow-up period, and the median follow-up duration was 12 months. The cumulative HR-HPV clearance rates at the 6- and 12-month follow-ups were 56.1% and 75.4%, respectively. The median clearance time of HR-HPV was 6 (95% confidence interval, 5.46–6.54) months. The clearance rate was higher in HPV16/18 than in non-HPV16/18 (86.7% vs. 62.9%, p = 0.038). After treatment, the successful pregnancy rate in patients with fertility intentions and spontaneous abortion rate were 73.9% and 5.9%, respectively. Preterm birth, preterm premature rupture of membranes, or low-birth-weight infants were not observed.Conclusion FU treatment can regress HSIL and accelerate HR-HPV clearance in young women of childbearing age with cervical HSIL associated with HR-HPV infection, and has no significant adverse effects on pregnancy outcomes

Identification of serous ovarian tumors based on polarization imaging and correlation analysis with clinicopathological features

Ovarian cancer is one of the most aggressive and heterogeneous female tumors in the world, and serous ovarian cancer (SOC) is of particular concern for being the leading cause of ovarian cancer death. Due to its clinical and biological complexities, ovarian cancer is still considered one of the most difficult tumors to diagnose and manage. In this study, three datasets were assembled, including 30 cases of serous cystadenoma (SCA), 30 cases of serous borderline tumor (SBT), and 45 cases of serous adenocarcinoma (SAC). Mueller matrix microscopy is used to obtain the polarimetry basis parameters (PBPs) of each case, combined with a machine learning (ML) model to derive the polarimetry feature parameters (PFPs) for distinguishing serous ovarian tumor (SOT). The correlation between the mean values of PBPs and the clinicopathological features of serous ovarian cancer was analyzed. The accuracies of PFPs obtained from three types of SOT for identifying dichotomous groups (SCA versus SAC, SCA versus SBT, and SBT versus SAC) were 0.91, 0.92, and 0.8, respectively. The accuracy of PFP for identifying triadic groups (SCA versus SBT versus SAC) was 0.75. Correlation analysis between PBPs and the clinicopathological features of SOC was performed. There were correlations between some PBPs ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], rqcross, [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text]) and clinicopathological features, including the International Federation of Gynecology and Obstetrics (FIGO) stage, pathological grading, preoperative ascites, malignant ascites, and peritoneal implantation. The research showed that PFPs extracted from polarization images have potential applications in quantitatively differentiating the SOTs. These polarimetry basis parameters related to the clinicopathological features of SOC can be used as prognostic factors

CHE and 5-HD reversed the inhibition of SPC on intestinal apoptosis induced by intestinal IRI in rats.

<p>(A) Representative immunohistochemical images of cleaved caspase-3 in the intestinal mucosa (×400), caspase-3 positive cells are stained dark brown under light microscopy shown by the arrows; (B) Representative western blots of cleaved caspase-3 and Bcl-2; (C) The quantitative analysis of Bcl-2 and caspase-3. Data are expressed as the mean ± SD, n = 9. Results were compared using one-way ANOVA with Bonferroni’s posttest. * <i>P < 0</i>.<i>05</i>, ** <i>P < 0</i>.<i>01</i>, *** <i>P < 0</i>.<i>001</i> vs. the Sham; ^###<i>P < 0</i>.<i>001</i> vs. IRI; ^$<i>P < 0</i>.<i>05</i>, ^$$<i>P < 0</i>.<i>01</i>, ^$$$<i>P < 0</i>.<i>001</i> vs. SPC. 5-HD = 5-Hydroxydecanoic; CHE = Chelerythrine; IRI = ischemia-reperfusion injury; SPC = sevoflurane preconditioning.</p

Both SPC and IPC inhibited the increase in IRI-induced TUNEL positive cells in the intestine of rats.

<p>(A) Representative images of TUNEL fluorescent staining in the intestinal mucosa (×200) (scan bar = 100 μm). Green staining indicates TUNEL-positive cells, blue staining indicates nuclear. (B) Quantification of TUNEL positive cells in the intestinal mucosal. Data are expressed as the mean ± SD, n = 9. Results were compared using one-way ANOVA with Bonferroni’s posttest. *** <i>P < 0</i>.<i>001</i> vs. Sham, ^&&&<i>P</i> < 0.001 vs. SPC-Sham. ^▲▲▲<i>P</i> < 0.001 vs. IPC-Sham, ^###<i>P < 0</i>.<i>001</i> vs. IRI. IPC = ischemic preconditioning; IRI = ischemia-reperfusion injury; SPC = sevoflurane preconditioning.</p

ZLN005 improves the protective effect of mitochondrial function on alveolar epithelial cell aging by upregulating PGC-1α.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal pulmonary interstitial disease that usually occurs in the elderly. The senescence of alveolar epithelial cells (AECs) is an important mechanism of IPF. The AECs of patients with IPF have lower expression of peroxisome proliferator-activated receptor-γ coactivator-1 alpha (PGC-1α), which has been shown to play an important role in maintaining mitochondrial morphology and energy metabolism. This study sought to explore the mechanism by which ZLN005 improves mitochondrial function by upregulating PGC-1α to protect AECs from aging. METHODS: Western blot was used to detect the expression of PGC-1α, mitochondrial synthesis protein nuclear respiratory factor-1 (NRF-1), and p21WAF1 in the lung tissue of the IPF patients and the mice with bleomycin (BLM)-induced pulmonary fibrosis. A549 cells and mice AEC2 cells were treated with hydrogen peroxide (H2O2) to construct cell senescence models. Cell senescence was detected by senescence-associated beta-galactosidase staining. The mitochondrial respiratory function was measured, including the adenosine triphosphate (ATP) generation, reactive oxygen species (ROS) level, changes in cell membrane potential, and energy metabolism. Using lentivirus as a vector and using gene editing technology to over express (upPGC-1α) and knockdown PGC-1α (shPGC-1α) in the A549 cells. The PGC-1α agonist ZLN005 was used to pretreat the A549 and shPGC-1α A549 cells, and cell aging and mitochondrial respiratory function were observed. RESULTS: The Western blot and immunofluorescence assays showed that the expression of PGC-1α and NRF-1 was decreased in the lung tissues of the IPF patients and BLM-induced mice pulmonary fibrosis model, while the expression of p21WAF1 was increased. The results of the immunofluorescence and mitochondrial function experiments also indicated that the expression of PGC-1α and mitochondrial synthesis protein NRF-1 were decreased in the senescent cells. Further, the mitochondrial morphology was abnormal and the mitochondrial function was impaired. PGC-1α was involved in the AEC senescence by regulating mitochondrial morphology and function. Treatment with the agonist of PGC-1α (i.e., ZLN005) blocked the H2O2-induced cell senescence by enhancing the expression of PGC-1α. CONCLUSIONS: These results provide preliminary insights into the potential clinical application of ZLN005 as a novel therapeutic agent for the treatment of IPF

Planar {Ni₆} Cluster-Containing Polyoxometalate-based Inorganic–Organic Hybrid Compound and Its Extended Structure

Two {Ni₆} cluster-containing inorganic–organic hybrid compounds have been successfully synthesized in the presence of organic amine under hydrothermal conditions, and they were characterized by powder and single-crystal X-ray diffraction, elemental analysis, thermogravimetric analysis, and IR spectroscopy. Structural analysis indicates that [Ni_0.5(H₂O)₃]­[{Ni₆(μ₃-OH)₃­en­(H₂O)₁₀}­(H₂P₂W₁₅O₅₆)]·10H₂O (<b>1</b>, en = ethylenediamine) is a triangular inorganic {Ni₆} cluster substituted polyoxotungstate with only one en to stabilize the {Ni₆} cluster. However, [Ni­(dap)₂]­{[Ni_1.5(dap)_1.5­(H₂O)₃]­[Ni₆(μ₃-OH)₃­(dap)₂(en)­(H₂O) ​{O₂C­(CH₂)₂CO₂}_0.5­(CH₃COO)­(P₂W₁₅O₅₆)]}·​15H₂O (<b>2</b>, dap = 1,2-diaminopropane) is a three-dimensional inorganic–organic hybrid compound linked by succinic acid. The magnetic properties of both compounds were studied. In addition, the adsorption properties of compound <b>2</b> have also been investigated