Carnosol suppresses cardiomyocyte hypertrophy via promoting the activation of AMPK pathway.

Pathological cardiac hypertrophy is associated with adverse cardiovascular events and can gradually lead to heart failure, arrhythmia, and even sudden death. However, the current development of treatment strategies has been unsatisfactory. Therefore, it is of great significance to find new and effective drugs for the treatment of myocardial hypertrophy. We found that carnosol can inhibit myocardial hypertrophy induced by PE stimulation, and the effect is very significant at 5 µM. Moreover, we demonstrated that 50 mg/kg of carnosol protect against cardiac hypertrophy and fibrosis induced by TAC surgery in mice. Mechanically, we proved that the inhibitory effect of carnosol on cardiac hypertrophy depends on its regulation on the phosphorylation activation of AMPK. In conclusion, our study suggested that carnosol may be a novel drug component for the treatment of pathological cardiac hypertrophy.

RING finger protein 5 protects against acute myocardial infarction by inhibiting ASK1.

BACKGROUND: Myocardial infarction (MI) is a major disease with high morbidity and mortality worldwide. However, existing treatments are far from satisfactory, making the exploration of potent molecular targets more imperative. The E3 ubiquitin ligase RING finger protein 5 (RNF5) has been previously reported to be involved in several diseases by regulating ubiquitination-mediated protein degradation. Nevertheless, few reports have focused on its function in cardiovascular diseases, including MI. METHODS: In this study, we established RNF5 knockout mice through precise CRISPR-mediated genome editing and utilized left anterior descending coronary artery ligation in 9-11-week-old male C57BL/6 mice. Subsequently, serum biochemical analysis and histopathological examination of heart tissues were performed. Furthermore, we engineered adenoviruses for modulating RNF5 expression and subjected neonatal rat cardiomyocytes to oxygen-glucose deprivation (OGD) to mimic ischemic conditions, demonstrating the impact of RNF5 manipulation on cellular viability. Gene and protein expression analysis provided insights into the molecular mechanisms. Statistical methods were rigorously employed to assess the significance of experimental findings. RESULTS: We found RNF5 was downregulated in infarcted heart tissue of mice and NRCMs subjected to OGD treatment. RNF5 knockout in mice resulted in exacerbated heart dysfunction, more severe inflammatory responses, and increased apoptosis after MI surgery. In vitro, RNF5 knockdown exacerbated the OGD-induced decline in cell activity, increased apoptosis, while RNF5 overexpression had the opposite effect. Mechanistically, it was proven that the kinase cascade initiated by apoptosis signal-regulating kinase 1 (ASK1) activation was closely regulated by RNF5 and mediated RNF5's protective function during MI. CONCLUSIONS: We demonstrated the protective effect of RNF5 on myocardial infarction and its function was dependent on inhibiting the activation of ASK1, which adds a new regulatory component to the myocardial infarction associated network and promises to enable new therapeutic strategy.

Six-Transmembrane Epithelial Antigen of Prostate 3 Promotes Hepatic Insulin Resistance and Steatosis.

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by excessive deposition of fatty acids in the liver. Further deterioration leads to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma, creating a heavy burden on human health and the social economy. Currently, there are no effective and specific drugs for the treatment of NAFLD. Therefore, it is important to further investigate the pathogenesis of NAFLD and explore effective therapeutic targets for the prevention and treatment of the disease. Six-transmembrane epithelial antigen of prostate 3 (STEAP3), a STEAP family protein, is a metalloreductase. Studies have shown that it can participate in the regulation of liver ischemia-reperfusion injury, hepatocellular carcinoma, myocardial hypertrophy, and other diseases. In this study, we found that the expression of STEAP3 is upregulated in NAFLD. Deletion of STEAP3 inhibits the development of NAFLD in vivo and in vitro, whereas its overexpression promotes palmitic acid/oleic acid stimulation-induced lipid deposition in hepatocytes. Mechanistically, it interacts with transforming growth factor beta-activated kinase 1 (TAK1) to regulate the progression of NAFLD by promoting TAK1 phosphorylation and activating the TAK1-c-Jun N-terminal kinase/p38 signaling pathway. Taken together, our results provide further insight into the involvement of STEAP3 in liver pathology.

Identification of angiogenesis-related subtypes and risk models for predicting the prognosis of gastric cancer patients.

Gastric cancer (GC) is a leading cause of cancer-related mortality and is characterized by significant heterogeneity, highlighting the need for further studies aimed at personalized treatment strategies. Tumor angiogenesis is critical for tumor development and metastasis, yet its role in molecular subtyping and prognosis prediction remains underexplored. This study aims to identify angiogenesis-related subtypes and develop a prognostic model for GC patients. Using data from The Cancer Genome Atlas (TCGA), we performed consensus cluster analysis on differentially expressed angiogenesis-related genes (ARGs), identifying two patient subtypes with distinct survival outcomes. Differentially expressed genes between the subtypes were analyzed via Cox and LASSO regression, leading to the establishment of a subtype-based prognostic model using a machine learning algorithm. Patients were classified into high- and low-risk groups based on the risk score. Validation was performed using independent datasets (ICGC and GSE15459). We utilized a deconvolution algorithm to investigate the tumor immune microenvironment in different risk groups and conducted analyses on genetic profiling, sensitivity and combination of anti-tumor drug. Our study identified ten prognostic signature genes, enabling the calculation of a risk score to predict prognosis and overall survival. This provides critical data for stratified diagnosis and treatment upon patient admission, monitoring disease progression throughout the entire course, evaluating immunotherapy efficacy, and selecting personalized medications for GC patients.

WDR1 promotes prostate cancer progression through Wnt/ß-catenin signaling.

Prostate cancer (PCa) is the second most common cancer and the fifth leading cause of cancer-related death among men. A comprehensive understanding of PCa progression is crucial for the development of innovative therapeutic strategies for its treatment. While WDR1 (WD-repeat domain 1) serves as a significant cofactor of actin-depolymerizing factor/cofilin, its role in PCa progression remains unknown. In this study, we demonstrated that knockdown of WDR1 in various PCa cells substantially inhibited cell proliferation, migration, and invasion in vitro, as confirmed at both the cellular and molecular levels. Moreover, the overexpression of WDR1 promoted PCa cell proliferation and metastasis in vitro. Mechanistically, we showed that the application of lithium chloride, an activator of the Wnt/ß-Catenin signaling pathway, restored the suppressive effects of WDR1 deficiency on cell proliferation and migration in PCa cells. Our findings suggest that the WDR1-ß-Catenin axis functions as an activator of the malignant phenotype and represents a promising therapeutic target for PCa treatment.

Magnesium Lithospermate B Inhibits Colorectal Cancer Cell Progression Through JAK2-STAT3 Signaling.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide. The discovery of new effective therapeutic drugs is always a priority. Magnesium lithospermate B (MLB), a native polyphenol acid, is the major component of the aqueous extracts from Danshen, a traditional Chinese medicine derived from the dry root and rhizome of Salvia miltiorrhiza. MLB has been reported to have antioxidant, anti-inflammatory, and ion channel-regulating activities in several diseases, including cardiovascular, renal, and neuronal diseases. However, the effect of MLB on cancer progression has not been reported. In this study, a series of cellular and molecular experiments were conducted on two CRC cell lines (HCT116 and SW480) to investigate the effects of. The results demonstrated that MLB exerted inhibitory effects on cell proliferation, migration, and invasion. The administration of 50 mg/kg MLB inhibited tumor growth in HCT116 cells in xenografted models. Importantly, we found that MLB treatment inhibited the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway, and activation of JAK2-STAT3 signaling with interleukin 6 or overexpression STAT3 significantly suppressed the inhibitory effect of MLB. These findings provide evidence that MLB could inhibit CRC cell progression in vitro and might serve as a potential therapeutic drug for the treatment of CRC.

Orientin regulates the proliferation and migration of hepatocellular carcinoma cells.

Orientin is a flavone isolated from medicinal plants used in traditional Chinese medicine (TCM) that suppresses the growth of cancer cells in vitro. The effects of orientin in hepatoma carcinoma cells remain unknown. The aim of this paper is to investigate the effects of orientin on the viability, proliferation, and migration of hepatocellular carcinoma cells in vitro. In this study, we found that orientin could inhibit the proliferation, migration, and the activation of NF-κB signaling pathway in hepatocellular carcinoma cells. An activator of NF-κB signaling pathway, PMA, could abolish the inhibitory effect of orientin on NF-κB signaling pathway and proliferation and migration of Huh7 cells. These findings raise the possibility that orientin can be used in the treatment of hepatocellular carcinoma.

Gastrodin inhibits prostate cancer proliferation by targeting canonical Wnt/ß-catenin signaling pathway.

Prostate cancer is an epithelial malignant tumor occurring in the prostate and is the most common malignant tumor in the male genitourinary system. In recent years, the incidence of prostate cancer in China has shown a trend of sudden increase. The search for new and effective drugs to treat prostate cancer is therefore extremely important.The canonical Wnt/ß-catenin signaling pathway has been shown to be involved in the regulation of tumor proliferation, migration and differentiation. Activation of the canonical Wnt/ß-Catenin signaling pathway in the prostate has oncogenic effects. Drugs targeting the canonical Wnt/ß-catenin signaling pathway have great potential in the treatment of prostate cancer. In this study, we found that Gastrodin could significantly inhibit the proliferation of prostate cancer cell line PC3 and DU145. Oral administration Gastrodin could significantly inhibit the tumor growth of PC3 cells subcutaneously injected. Gastrodin has an inhibitory effect on canonical Wnt/ß-Catenin signaling pathway in Prostate cancer, and this inhibitory effect can be abolished by Wnt/ß-Catenin agonist LiCl. These findings raise the possibility that Gastrodin can be used in the treatment of Prostate cancer by targeting canonical Wnt/ß-Catenin signaling pathway.

Applications of improved first Rayleigh-Sommerfeld method to analyze the performance of cylindrical microlenses with different f-numbers.

Based on the previous Letter [Opt. Lett. 29, 2345 (2004)], we significantly extend the applications of the improved first Rayleigh-Sommerfeld method (IRSM1) to analyze the focusing performance of cylindrical micro-lenses for different types of profile (continuous or stepwise), different f-numbers (from f/1.5 to f/0.75), and different polarizations (the TE or TM). A number of performance measures of the cylindrical microlenses, such as the focal spot size, the diffraction efficiency, the real focal position, and the normalized sidelobe power, are studied in detail. We compare numerical results obtained by the IRSM1, by the original first Rayleigh-Sommerfeld method (ORSM1), and by the rigorous boundary element method (BEM). For continuously refractive lenses, the results calculated by the IRSM1 are quite close to those obtained by the BEM; in contrast, the results calculated by the ORSM1 significantly deviate from those obtained from the rigorous BEM. For multilevel diffractive lenses, the IRSM1 also provides much more accurate results than the ORSM1. In addition, compared with the BEM, a notable advantage of the IRSM1 is much lower computer memory and time consumption in computations.

Improved first Rayleigh-sommerfeld method for analysis of cylindrical microlenses with small f-numbers.

An improved first Rayleigh-Sommerfeld method (IRSM1) is proposed and applied to the analysis of cylindrical microlenses with small f-numbers. Numerical results obtained by both the IRSM1 and the original Rayleigh-Sommerfeld method (ORSM1) are compared with those obtained by the rigorous boundary element method (BEM). For both refractive and diffractive lenses, the results obtained by the IRSM1 are close to those obtained by the BEM even for small f-numbers; by contrast, the results by the ORSM1 differ significantly from those obtained by the BEM. Moreover, the IRSM1 uses much less time and computer memory in the computations than the BEM.

Analysis of a cylindrical microlens array with long focal depth by a rigorous boundary-element method and scalar approximations.

We investigated the focal characteristics of open-regional cylindrical microlens arrays with long focal depth by using a rigorous boundary-element method (BEM) and three scalar methods, i.e., a Kirchhoff and two Rayleigh-Sommerfeld diffraction integral forms. Numerical analysis clearly shows that the model cylindrical microlens arrays with different f-numbers can generate focusing beams with both long focal depth and high transverse resolution. The performance of the cylindrical microlens arrays, such as extended focal depth, relative extended focal depth, diffraction efficiency, and focal spot size, is appraised and analyzed. From a comparison of the results obtained by the rigorous BEM and by scalar approximations, we found that the results are quite similar when the f-number equals f/1.6; however, they are quite different for f/0.8. We conclude that the BEM should be adopted to analyze the performance of a microlens array system whose f-number is less than f/1.0.

Analysis of a closed-boundary axilens with long focal depth and high transverse resolution based on rigorous electromagnetic theory.

We find that a microcylindrical axilens with a closed boundary and with an f-number less than 1 still can achieve the properties of long focal depth and high transverse resolution, unlike a microcylindrical axilens with an open boundary, which fails to maintain those properties for low f-numbers. The focusing characteristics of the closed-boundary axilens and the open-boundary axilens are numerically investigated based on the boundary integral method. The numerical results show that the ratio of the extended focal depth of the closed-boundary axilens to the focal depth of the conventional microlens can reach up to 1.26 and 2.12 for the preset focal depths 3 and 5 microm, respectively, even though the f-number is reduced to 1/3.