E3 ubiquitin ligase DTX2 fosters ferroptosis resistance via suppressing NCOA4-mediated ferritinophagy in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) remains the foremost contributor to cancer-related fatalities globally, with limited effective therapeutic modalities. Recent research has shed light on the role of ferroptosis in various types of cancers, offering a potential avenue for improving cancer therapy. Herein, we identified E3 ubiquitin ligase deltex 2 (DTX2) as a potential therapeutic target candidate implicated in promoting NSCLC cell growth by inhibiting ferroptosis. Our investigation revealed a significant upregulation of DTX2 in NSCLC cells and tissues, which was correlated with poor prognosis. Downregulation of DTX2 suppressed NSCLC cell growth both in vitro and in vivo, while its overexpression accelerated cell proliferation. Moreover, knockdown of DTX2 promoted ferroptosis in NSCLC cells, which was mitigated by DTX2 overexpression. Mechanistically, we uncovered that DTX2 binds to nuclear receptor coactivator 4 (NCOA4), facilitating its ubiquitination and degradation via the K48 chain, which subsequently dampens NCOA4-driven ferritinophagy and ferroptosis in NSCLC cells. Notably, DTX2 knockdown promotes cisplatin-induced ferroptosis and overcomes drug resistance of NSCLC cells. These findings underscore the critical role of DTX2 in regulating ferroptosis and NCOA4-mediated ferritinophagy, suggesting its potential as a novel therapeutic target for NSCLC.

Development and validation of a machine-learning model for preoperative risk of gastric gastrointestinal stromal tumors.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) have malignant potential, and treatment varies according to risk. However, no specific protocols exist to preoperatively assess the malignant potential of gastric stromal tumors (gGISTs). This study aimed to use machine learning (ML) to develop and validate clinically relevant preoperative models to predict the malignant potential of gGISTs. METHODS: We screened patients diagnosed with gGISTs at the Affiliated Hospital of North Sichuan Medical College. We employed the Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression to identify risk factors. Subsequently, an ensemble of ML models was deployed to determine the optimal classifier. Additionally, we harnessed SHapley Additive exPlanations (SHAP) for tailored risk profiling. RESULTS: We enrolled 318 patients with gGISTs. Utilizing LASSO regression and multifactorial logistic regression, we analyzed the training dataset, revealing that the presence of endoscopic ultrasound (EUS) high-risk features, tumor border clarity, tumor diameter, and monocyte-to-lymphocyte ratio (MLR) were significant predictors of high malignancy risk in gGIST. As determined by our ML approach, the logistic classification model demonstrated optimal performance, with an area under the receiver operating characteristic curve of 0.919 and 0.925 for the training and test sets, respectively. Furthermore, decision curve analysis substantiated the clinical relevance of the model. CONCLUSION: High-risk EUS features, ill-defined tumor margins, larger tumor diameters, and elevated MLR independently predicted heightened malignant potential in gGIST. We developed logistic regression models based on these factors, which were further interpreted using the SHAP methodology. This analytical approach facilitated personalized therapeutic decision-making for diverse patient populations.

F13B regulates angiogenesis and tumor progression in hepatocellular carcinoma via the HIF-1α/VEGF pathway.

Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor with a poor prognosis. This research aimed to investigate the role of F13B in HCC and its underlying mechanisms. Through comprehensive bioinformatics analysis of the GSE120123 and The Cancer Genome Atlas (TCGA)-Liver hepatocellular carcinoma (LIHC) datasets, we identified 220 overlapping prognosis-related genes. Eight key genes, including the previously unreported CCDC170 and F13B in HCC, were identified through Least Absolute Shrinkage and Selection Operator (LASSO)-Cox regression analysis. F13B emerged as a significant prognostic factor in HCC, warranting further investigation in subsequent analyses. In vitro experiments showed that F13B expression was notably reduced in HCC cell lines and tissues, particularly in Huh-7 and SMMC-7721 cells. Overexpression of F13B inhibited cell invasion, migration, and proliferation, while its knockdown produced the opposite effect. A lactate dehydrogenase (LDH) activity assay in human umbilical vein endothelial cells (HUVECs) demonstrated that F13B overexpression reduced vascular endothelial growth factor (VEGF)-induced cytotoxicity, whereas knockdown increased it. Further analysis revealed that F13B negatively regulates VEGFA expression, affecting HUVEC proliferation. In HUVECs, F13B overexpression reversed VEGF-induced upregulation of key angiogenesis markers, including phospho-VEGF receptor 2 (p-VEGFR2), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), as well as AKT/mTOR signaling proteins, phospho-Akt (p-AKT), and phospho-mTOR (p-mTOR). Additionally, F13B negatively regulated VEGFA and hypoxia-inducible factor 1 A (HIF1A) under hypoxic conditions, counteracting the hypoxia-induced increase in cell viability. These findings suggest that F13B regulates angiogenesis through the HIF-1α/VEGF pathway and plays a crucial role in HCC progression. Our results highlight the potential of F13B as a therapeutic target in HCC, providing novel insights into the molecular mechanisms of HCC and its prognostic significance.

Development of a High-Sensitivity Acoustic Sensor Based on Grating Interferometer Combined with Glass Diaphragm.

In this study, based on the principle of grating interferometer-based acoustic sensors, design guidelines for the grating interferometric module were obtained and analyzed considering various factors in order to obtain high sensitivity, and a glass-based grating interference component and its acoustic sensor device were developed. The key parameters of the grating interference structure were extracted, and their effects on the acoustic response sensitivity were quantified for multiple mechanisms. For the development of the acoustic sensor, the grating-on-convex-platform structure and the micromachining processes of the glass-based components were designed and developed. The developed acoustic sensor samples achieved high sensitivity. In particular, the sample suitable for low-frequency application obtained a sensitivity of 0.776 V/Pa @ 1 kHz, and the spectrum of its sensitivity was flat from 50 Hz to 8 Hz with a deviation less than 1.5 dB and a sensitivity of 0.408 V/Pa @ 20 Hz.

Extracorporeal shock wave therapy (ESWT) favors healing of diabetic foot ulcers: A systematic review and meta-analysis.

AIMS: To investigate the efficacy and safety of extracorporeal shockwave therapy(ESWT) for diabetic foot ulcers(DFUs). METHODS: Search in PubMed, EMBASE, the Cochrane Controlled Register of Trials (CENTAL), and Web of Science for randomized controlled trials (RCTs) published before August 8, 2023. All identified studies were screened following the selection criteria. Finally, we employed the STATA 14.0 software for conducting a meta-analysis to evaluate the efficacy and safety of ESWT. RESULTS: A total of ten RCTs with moderate methodological quality were included for data analysis. The findings showed that ESWT was significantly associated with significantly complete healed ulcers (risk ratio [RR]: 1.57, 95 % confidence interval [CI]:1.26 to 1.95) and lower rate of unchanged ulcers (RR: 0.25, 95 %CI: 0.14 to 0.42) compared to controls. Subgroup analysis further revealed that ESWT was better than both hyperbaric oxygen therapy (HOT) and the standard of care (SOC). Moreover, ESWT also significantly improved the average transcutaneous partial oxygen pressure (TcPO2) (mean difference[MD]: 1.71, 95 %CI: 1.22 to 2.19, p < 0.001). However, the rate of ≥ 50 % improved ulcers and treatment-emergent adverse events (TEAEs) were not significantly different between the ESWT and controls. CONCLUSIONS: ESWT has shown promising efficacy and a favorable safety profile in the treatment of DFUs.

Analysis of tissue-substrate adhesion by hyperspectral surface plasmon resonance microscopy.

The preparation of histology slides is a critical step in histopathology, and poor-quality histology slides with weak adhesion of tissue sections to the substrate often affect diagnostic accuracy and sometimes lead to diagnostic failure due to tissue section detachment. This issue has been of concern and some methods have been proposed to enhance tissue-substrate adhesion. Unfortunately, quantitative analysis of the adhesion between tissue sections and glass slides is still challenging. In this work, the adhesion of mouse brain tissue sections on gold-coated glass slides was analyzed using a laboratory-fabricated hyperspectral surface plasmon resonance microscopy (HSPRM) system that enabled single-pixel spectral SPR sensing and provided two-dimensional (2D) distribution of resonance wavelengths (RWs). The existence of the nanoscale water gap between the tissue section and the substrate was verified by fitting the RW measured in each pixel using the five-layer Fresnel reflection model. In addition, a 2D image of the tissue-substrate adhesion distance (AD) was obtained from the measured 2D distribution of RWs. The results showed that tissue-substrate AD was 20-35 nm in deionized water and 4-24 nm in saline solution. The HSPRM system used in this work has a wide wavelength range of 400-1000 nm and can perform highly sensitive and label-free detection over a large dynamic detection range with high spectral and spatial resolutions, showing significant potential applications in stain-free tissue imaging, quantitative analysis of tissue-substrate adhesion, accurate identification of tumor cells, and rapid histopathological diagnosis.

Symptom clusters and network analysis of patients with intermediate and advanced liver cancer treated with targeted immunotherapy.

BACKGROUND: This study aims to identify symptom clusters in patients with intermediate and advanced liver cancer receiving targeted immunotherapy, focusing on core and bridge symptoms to establish a foundation for precise symptom management. METHODS: This study used a cross-sectional survey and utilized convenience sampling from May 2023 to January 2024 at a third-class hospital in Shanghai, China. The severity of symptoms in liver cancer patients during treatment was evaluated using the Memorial Symptom Assessment Scale. Network analysis was employed to depict the interrelation of symptom clusters and identify core and bridge symptoms. RESULTS: The symptoms were classified by severity into five clusters: oral, gastrointestinal, fatigue-related, body image, and pain-sleep. Within the symptom network, the core symptoms were pain, "I don't look like myself," and nausea, while the critical bridge symptoms included pain, itching, and feeling bloated. The strongest connections were observed between nausea and vomiting, followed by taste changes and dry mouth, as well as weight loss and "I don't look like myself." CONCLUSION: In patients receiving targeted immunotherapy for intermediate and advanced liver cancer, multiple symptoms can emerge simultaneously, forming interconnected clusters. By identifying and intervening in core and bridge symptoms, personalized management strategies can be developed to relieve other symptoms and disrupt connections between symptom clusters, thereby enhancing symptom management efficacy. This study has significant clinical and research implications, offering new insights to improve patients' quality of life and treatment outcomes.

Effect of bile duct resection on the prognosis of patients with hepatocellular carcinoma combined with extrahepatic bile duct tumor thrombus.

BACKGROUND: Surgical therapy is the most optimal treatment for hepatocellular carcinoma (HCC) combined with bile duct tumor thrombus (BDTT) patients. However, whether to perform bile duct resection (BDR) is still controversial. The purpose of this multicenter research is to compare the effect of BDR on the prognosis of extrahepatic BDTT patients. METHODS: We collected the data of 111 HCC patients combined with extrahepatic BDTT who underwent radical hepatectomy from June 1, 2004 to December 31, 2021. Those patients had either received hepatectomy with extrahepatic bile duct resection (BDR group) or hepatectomy without bile duct resection (NBDR group). Inverse probability of treatment weighting (IPTW) was used to reduce the potential bias between two groups and balance the influence of confounding factors in baseline data. Then compare the prognosis between the two groups of patients. Cox regression model was used for univariate and multivariate analysis to further determine the independent risk factors that influence the prognosis of HCC-BDTT patients. RESULTS: There were 38 patients in the BDR group and 73 patients in the NBDR group. Before and after IPTW, there were no statistical significance in OS, RFS and intraoperative median blood loss between the two groups (all P > 0.05). Before IPTW, the median postoperative hospital stay in the NBDR group was shorter (P = 0.046) and the grade of postoperative complications was lower than BDR group (P = 0.014). After IPTW, there was no difference in postoperative hospital stay between the two groups (P > 0.05). The complication grade in the NBDR group was still lower than that in the BDR group (P = 0.046). The univariate analysis showed that TNM stage and portal vein tumor thrombus (PVTT) were significantly correlated with OS (both P < 0.05). Preoperative AFP level, TNM stage and prognostic nutritional index (PNI) were significantly correlated with postoperative RFS (all P < 0.05). Multivariate analysis showed that tumor TNM stage was an independent risk factor for the OS rate (P = 0.014). TNM stage, PNI and AFP were independent predictors of RFS after radical hepatectomy (all P < 0.05). CONCLUSIONS: For HCC-BDTT patients, hepatocellular carcinoma resection combined with choledochotomy to remove the tumor thrombus may benefit more.

Fiber-optic bionic microphone based compact sound source localization system with extended directional range.

Traditional sound source localization (SSL) systems based on electret condenser microphone arrays are bulky because their localization accuracy depends on the size of the array. Inspired by the hearing mechanism of the parasitic fly Ormia ochracea, the localization accuracy of miniature bionic SSL devices breaks through the limitations of device size, but their ability to localize low-frequency sound sources over a wide angular range remains a challenge. In this work, a compact low-frequency SSL system with an extended directional range was prepared using two bionic micro-electro-mechanical system diaphragm based fiber-optic microphones, which form a non-coplanar array with a size of Φ44 mm × 13 mm. An algorithm for quantifying the azimuthal angle of a sound source is established for the prepared SSL system. Simulation and experimental results show that the prepared SSL system is capable of determining the propagation direction of acoustic signals with a frequency of less than 1 kHz in the azimuthal range from -90° to 90°, with a linear response in the range from -70° to 70°, and an angular measurement accuracy of the system within the range of ±7°.

Acrolein exposure affects ovarian function by interfering with glycolysis and mitochondrial energy metabolism in mouse.

Acrolein is a widespread contaminant found in both diet and environment, entering the human body through food, alcohol, smoking, and exposure to fuel combustion fumes. While prior studies have highlighted acrolein's harmful impact on oocyte quality and early embryonic development in vitro, the specific mechanisms by which acrolein affects the female reproductive system in vivo remain poorly understood. This study first confirmed that in vitro acrolein exposure disrupts spindle morphology and chromosome alignment during the mid-MI stage of oocyte development, thus hindering oocyte maturation. Besides, exposure to acrolein not only stunts growth in mice but also impairs ovarian development, decreases the ovarian coefficient, disrupts follicular development, and increases the count of atretic follicles in vivo. Additional research has shown that acrolein exposure reduces the activity of key enzymes in glycolysis, pyruvate metabolism, and the tricarboxylic acid cycle within the ovaries. It also suppresses mitochondrial complex expression and disturbs the balance between mitochondrial fission and fusion, as confirmed by metabolomic analyses. Moreover, acrolein exposure in vivo induced granulosa cell apoptosis and reduced oocyte number. In summary, acrolein exposure impairs glucose metabolism and induces mitochondrial dysfunction in the ovaries.

Combined healthy lifestyles and risk of depressive symptoms: A baseline survey in China.

BACKGROUND: Little evidence exists about whether a combination of healthy lifestyle factors is associated with a lower risk of depressive symptoms among Chinese population. We aimed to investigate the association between combined healthy lifestyle factors and risk of depressive symptoms. METHODS: We conducted a baseline survey from July 2021 to December 2023, including 53,642 Chinese adults from general population. A healthy lifestyle score was constructed based on six lifestyle factors (physical activity, smoking status, alcohol consumption, diet, sleep duration, and body mass index). Logistic regression models were used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) adjusted for confounding variables. RESULTS: Each additional healthy lifestyle score was associated with a 20 % lower risk of having depressive symptoms (OR (95 % CI): 0.80 (0.78-0.81)). Compared with individuals with ≤2 healthy lifestyle factors, individuals with all the six healthy lifestyle factors had a 58 % reduced risk of having depressive symptoms (0.42 (0.37-0.47)). After stratification by gender, education and urbanization, the significant inverse association with healthy lifestyle score was stronger in women, individuals with high education, and urban residents. Besides, the significant negative association between healthy lifestyle score and depressive symptoms remained for different severity of depressive symptoms. LIMITATIONS: Given the cross-sectional nature of data, we cannot make causal inferences. CONCLUSIONS: Our study indicated that adherence to healthy lifestyle factors was associated with a reduced risk of having depressive symptoms among Chinese adults. The observed associations were modified by gender, education and urbanization. These findings warrant further verification in interventional studies.

Association of ankylosing spondylitis with cardiovascular disease: a bidirectional two-sample mendelian randomization study.

Backgrounds: Current observational investigations hint at a potential linkage between ankylosing spondylitis and cardiovascular wellness. However, the nature of this causality remains to be elucidated. Consequently, this study is designed to evaluate the causal interconnection between ankylosing spondylitis and cardiovascular-related conditions utilizing a bidirectional two-sample Mendelian Randomization (MR) methodology. Methods: In this study, we conducted Mendelian randomization (MR) analyses using genome-wide association study (GWAS) data. The fixed-effects inverse variance weighted (IVW) model was used as the primary analysis method, and MR-Egger regression and the weighted median method were employed as supplementary approaches. Horizontal pleiotropy and heterogeneity were evaluated using various statistical tests, including MR-PRESSO global test, MR-Egger intercept, and Cochran's Q test. Results: The MR result demonstrated an increased risk of heart failure in individuals with ankylosing spondylitis (OR: 1.0132, 95% CI = 1.0043-1.0221, p = 0.003). The MR analysis results did not demonstrate a causal relationship between ankylosing spondylitis and other cardiovascular diseases, such as atrial fibrillation, coronary artery disease, ischemic stroke, myocardial infarction, and valvular heart disease (all p > 0.05). No evidence of reverse causality was found between ankylosing spondylitis and mentioned cardiovascular diseases in reverse MR analyses. Sensitivity analysis verified the reliability of the results. Conclusion: Our MR study indicates a relationship between ankylosing spondylitis and an increased risk of heart failure. Further research is needed to confirm these findings and elucidate the underlying mechanisms involved.

Effects of dietary selenium deficiency and supplementation on liver in grazing sheep: insights from transcriptomic and metabolomic analysis.

Background: Mineral elements play a crucial role in supporting the life activities and physiological functions of animals. However, numerous studies have revealed that in some geographical areas and certain grazing situations, grazing livestock frequently suffers from mineral element deficiencies due to the loss of mineral elements from grassland forages, such as selenium (Se). To shed fresh light on this issue, this study aims to investigate the impact of dietary Se deficiency and supplementation on the liver of grazing sheep in these challenging conditions. Method: This study involved 28 grazing Mongolian Wu Ranke sheep with an average body weight of about 32.20 ± 0.37 kg, which were divided into the Se treatment group and the control group. The Se treatment group was fed with the low-Se diet for 60 days and then continued to be fed with the high-Se diet for 41 days. The liver concentration of minerals, transcriptomic analysis, and untargeted metabolomic analysis were conducted to assess the impact of Se deficiency and supplementation on the liver of grazing sheep. Results: Dietary Se deficiency and supplementation significantly reduced and elevated liver concentration of Se, respectively (p < 0.05). Gene functional enrichment analysis suggested that dietary Se deficiency might impair protein synthesis efficiency, while Se supplementation was found to enhance liver protein synthesis in grazing sheep. AGAP1, ERN1, MAL2, NFIC, and RERG were identified as critical genes through the weighted gene correlation network analysis, the quantitative real-time polymerase chain reaction, and the receiver operating characteristic curve validation that could potentially serve as biomarkers. Metabolomics analysis revealed that dietary Se deficiency significantly reduced the abundance of metabolites such as 5-hydroxytryptamine, while dietary Se supplementation significantly elevated the abundance of metabolites such as 5-hydroxytryptophan (p < 0.05). Conclusion: Integrative analysis of the transcriptome and metabolome revealed that dietary Se deficiency led to reduced hepatic antioxidant and anti-inflammatory capacity, whereas Se supplementation increased the hepatic antioxidant and anti-inflammatory capacity in grazing Wu Ranke sheep. These findings provide new insights into the effects of dietary Se deficiency and supplementation on the liver of grazing sheep, potentially leading to improved overall health and well-being of grazing livestock.

Class-Incremental Learning: A Survey.

Deep models, e.g., CNNs and Vision Transformers, have achieved impressive achievements in many vision tasks in the closed world. However, novel classes emerge from time to time in our ever-changing world, requiring a learning system to acquire new knowledge continually. Class-Incremental Learning (CIL) enables the learner to incorporate the knowledge of new classes incrementally and build a universal classifier among all seen classes. Correspondingly, when directly training the model with new class instances, a fatal problem occurs - the model tends to catastrophically forget the characteristics of former ones, and its performance drastically degrades. There have been numerous efforts to tackle catastrophic forgetting in the machine learning community. In this paper, we survey comprehensively recent advances in class-incremental learning and summarize these methods from several aspects. We also provide a rigorous and unified evaluation of 17 methods in benchmark image classification tasks to find out the characteristics of different algorithms empirically. Furthermore, we notice that the current comparison protocol ignores the influence of memory budget in model storage, which may result in unfair comparison and biased results. Hence, we advocate fair comparison by aligning the memory budget in evaluation, as well as several memory-agnostic performance measures. The source code is available at https://github.com/zhoudw-zdw/CIL_Survey/.

Scutellarin alleviates microglia-mediated neuroinflammation and apoptosis after ischemic stroke through the PI3K/AKT/GSK3ß signaling pathway.

Microglia are resident immune cells in the central nervous system that are rapidly activated to mediate neuroinflammation and apoptosis, thereby aggravating brain tissue damage after ischemic stroke (IS). Although scutellarin has a specific therapeutic effect on IS, the potential target mechanism of its treatment has not been fully elucidated. In this study, we explored the potential mechanism of scutellarin in treating IS using network pharmacology. Lipopolysaccharide (LPS) was used to induce an in vitro BV-2 microglial cell model, while middle cerebral artery occlusion (MCAO) was used to induce an in vivo animal model. Our findings indicated that scutellarin promoted the recovery of cerebral blood flow in MCAO rats at 3 days, significantly different from that in the MCAO group. Western blotting and immunofluorescence revealed that scutellarin treatment of BV-2 microglial cells resulted in a significant reduction in the protein expression levels and incidence of cells immunopositive for p-NF-κB, TNF-α, IL-1ß, Bax, and C-caspase-3. In contrast, the expression levels of p-PI3K, p-AKT, p-GSK3ß, and Bcl-2 were further increased, significantly different from those in the LPS group. The PI3K inhibitor LY294002 had similar effects to scutellarin by inhibiting neuroinflammation and apoptosis in activated microglia. The results of the PI3K/AKT/GSK3ß signaling pathway and NF-κB pathway in vivo in MCAO models induced microglia at 3 days were consistent with those obtained from in vitro cells. These findings indicate that scutellarin plays a neuroprotective role by reducing microglial neuroinflammation and apoptosis mediated by the activated PI3K/AKT/GSK3ß/NF-κB signaling pathway.

A novel selenium analog of HDACi-based twin drug induces apoptosis and cell cycle arrest via CDC25A to improve prostate cancer therapy.

Cancer therapy has moved from single agents to more mechanism-based targeted approaches. In recent years, the combination of HDAC inhibitors and other anticancer chemicals has produced exciting progress in cancer treatment. Herein, we developed a novel prodrug via the ligation of dichloroacetate to selenium-containing potent HDAC inhibitors. The effect and mechanism of this compound in the treatment of prostate cancer were also studied. Methods: The concerned prodrug SeSA-DCA was designed and synthesized under mild conditions. This compound's preclinical studies, including the pharmacokinetics, cell toxicity, and anti-tumor effect on prostate cancer cell lines, were thoroughly investigated, and its possible synergistic mechanism was also explored and discussed. Results: SeSA-DCA showed good stability in physiological conditions and could be rapidly decomposed into DCA and selenium analog of SAHA (SeSAHA) in the tumor microenvironment. CCK-8 experiments identified that SeSA-DCA could effectively inhibit the proliferation of a variety of tumor cell lines, especially in prostate cancer. In further studies, we found that SeSA-DCA could also inhibit the metastasis of prostate cancer cell lines and promote cell apoptosis. At the animal level, oral administration of SeSA-DCA led to significant tumor regression without obvious toxicity. Moreover, as a bimolecular coupling compound, SeSA-DCA exhibited vastly superior efficacy than the mixture with equimolar SeSAHA and DCA both in vitro and in vivo. Our findings provide an important theoretical basis for clinical prostate cancer treatment. Conclusions: Our in vivo and in vitro results showed that SeSA-DCA is a highly effective anti-tumor compound for PCa. It can effectively induce cell cycle arrest and growth suppression and inhibit the migration and metastasis of PCa cell lines compared with monotherapy. SeSA-DCA's ability to decrease the growth of xenografts is a little better than that of docetaxel without any apparent signs of toxicity. Our findings provide an important theoretical basis for clinical prostate cancer treatment.

Cocaine and amphetamine-regulated transcript improves myocardial ischemia-reperfusion injury through PI3K/AKT signalling pathway.

Myocardial ischemia-reperfusion injury (MIRI) is a common clinic scenario that occurs in the context of reperfusion therapy for acute myocardial infarction. It has been shown that cocaine and amphetamine-regulated transcript (CART) can ameliorate cerebral ischemia-reperfusion (I/R) injury, but the effect of CART on MIRI has not been studied yet. Here, we revealed that CART protected the heart during I/R process by inhibiting apoptosis and excessive autophagy, indicating that CART would be a potential drug candidate for the treatment of MIRI. Further analysis showed that CART upregulated the activation of phospho-AKT, leading to downregulation of lactate dehydrogenase (LDH) release, apoptosis, oxidative stress and excessive autophagy after I/R, which was inhibited by PI3K inhibitor, LY294002. Collectively, CART attenuated MIRI through inhibition of cardiomyocytes apoptosis and excessive autophagy, and the protective effect was dependent on PI3K/AKT signalling pathway.

Effect of scutellarin on BV-2 microglial-mediated apoptosis in PC12 cells via JAK2/STAT3 signalling pathway.

Previous studies have shown that scutellarin inhibits the excessive activation of microglia, reduces neuronal apoptosis, and exerts neuroprotective effects. However, whether scutellarin regulates activated microglia-mediated neuronal apoptosis and its mechanisms remains unclear. This study aimed to investigate whether scutellarin can attenuate PC12 cell apoptosis induced by activated microglia via the JAK2/STAT3 signalling pathway. Microglia were cultured in oxygen-glucose deprivation (OGD) medium, which acted as a conditioning medium (CM) to activate PC12 cells, to investigate the expression of apoptosis and JAK2/STAT3 signalling-related proteins. We observed that PC12 cells apoptosis in CM was significantly increased, the expression and fluorescence intensity of the pro-apoptotic protein Bax and apoptosis-related protein cleaved caspase-3 were increased, and expression of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) was decreased. Phosphorylation levels and fluorescence intensity of the JAK2/STAT3 signalling pathway-related proteins JAK2 and STAT3 decreased. After treatment with scutellarin, PC12 cells apoptosis as well as cleaved caspase-3 and Bax protein expression and fluorescence intensity decreased. The expression and fluorescence intensity of Bcl-2, phosphorylated JAK2, and STAT3 increased. AG490, a specific inhibitor of the JAK2/STAT3 signalling pathway, was used. Our findings suggest that AG490 attenuates the effects of scutellarin. Our study revealed that scutellarin inhibited OGD-activated microglia-mediated PC12 cells apoptosis which was regulated via the JAK2/STAT3 signalling pathway.