Asia Pacific Academy of Science Pte. Ltd.
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GATA3/MiR-199a-3p Suppresses Glycometabolism in Breast Cancer by Inhibiting PFKFB3 Expression
No full textBackground: Dysregulation of glycometabolism is considered an important marker for cancer, and the glycolytic components may be targets for cancer therapy. Hence, we aimed to explore the mechanism by which miR-199a-3p influences breast cancer (BC) glycolysis. Methods: Cell glucose and phosphofructokinase (PFK) levels in miR-199a-3p over-expressing BC cells were determined using the PFK assay kit. Glucose consumption and adenosine-triphosphate (ATP) levels were measured in miR-199a-3p over-expressing BC cells with a Glucose assay kit and ATP detection kit. The expressions of miR-199a-3p, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and GATA binding protein 3 (GATA3) were measured using qPCR in GATA3 over-expressing or knockdown BC cell lines. The expressions of glucose transporter type 5 (GLUT5), lactate dehydrogenase A (LDHA), pyruvate kinase M2 (PKM2) and PFKFB3 were examined using western blotting in two miR-199a-3p over-expressing BC cell lines. Chromatin immunoprecipitation quantitative PCR (ChIP-qPCR) was used to confirm that GATA3 bound to the specific region of the miR-199a-3p promoter in BC cells. Results: Our results showed that miR-199a-3p suppressed PFKFB3 mRNA and protein expression in BC cells (p < 0.05). Mechanistically, luciferase assays demonstrated that miR-199a-3p reduced PFKFB3 by targeting the PFKFB3 3′ untranslated region (3′-UTR) directly. Furthermore, a recovery assay indicated that PFKFB3 overexpression reversed the suppressing effects of miR-199a-3p on aerobic glycolysis (AG) (p < 0.05). More importantly, miR-199a-3p was modulated by the GATA3 transcription element by binding to the promoter. Conclusions: The GATA3/miR-199a-3p axis might be involved in BC cell glycometabolism through regulating PFKFB3 expression, which may provide a good prognosis for breast cancer
Combination of Apatinib and Salidroside Inhibits the Progression of Non-Small Cell Lung Cancer through MAPK/ERK/VEGF Signaling Axis
No full textBackground: Lung cancer is the leading cause of cancer-related deaths, where non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. The potential of apatinib, a small-molecule anti-angiogenic drug, and salidroside, the Chinese herbal extract, as anti-tumor agents has been recognized. Therefore, this study aims to investigate the synergistic effects of apatinib and salidroside on NSCLC and provide insights into this combination to evaluate their combined potential in treating NSCLC. Methods: 3-(4,5-dimethylthiazol)-2,5-diphenyl-tetrazolium bromide (MTT) assay was employed to determine the inhibitory effects of different concentrations of apatinib, salidroside and their combination on NSCLC cell proliferation. The levels of reactive oxygen species (ROS) in NSCLC cells were assessed in treated cells. Furthermore, flow cytometry, wound healing assay, and tube formation assay were used to determine the apoptosis rate, migration ability, and angiogenesis of cells, respectively. Additionally, western blot analysis was utilized to evaluate the levels of apoptosis-related proteins and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK)/vascular endothelial growth factor (VEGF) axis-related proteins. Results: Compared to using either apatinib or salidroside for treatment alone, apatinib in combination with salidroside (Sal) significantly inhibited NSCLC cell proliferation, migration, and tube formation (p < 0.01). Meanwhile, this combination ((apatinib) Apa+Sal) induced ROS production and promoted apoptosis by up-regulating Bcl-2 associated X (Bax) expression and down-regulating B cell lymphoma-2 (Bcl-2) expression (p < 0.01). Western blot analysis revealed a substantial increase in the phosphor (p)-p38 expression, and decreased p-ERK, VEGF, and VEGF receptor (VEGFR) levels in the combined treated group compared to the single treatment group (p < 0.05). Combined treatment coupled with MAPK/ERK inhibitor (SB203580) or activator (anisomycin) significantly enhanced or decreased the inhibitory effect of apatinib and salidroside on human umbilical vein endothelial cells (HUVEC) tube formation, respectively. Conclusion: Apatinib in combination with salidroside exerts a synergistic anticancer effect in NSCLC by down-regulating the MAPK/ERK/VEGF signaling axis, which suggests the potential of this combined therapy in treating NSCLC
FABP6 is a New Diagnostic and Prognostic Marker for Bladder Cancer
No full textPurpose: Recent studies have shown that fatty acid-binding protein 6 (FABP6) is not only a risk factor for digestive tract tumors, but also a diagnostic marker for digestive tract tumors. This study aimed to extend our understanding by investigating the potential significance of FABP6 in urinary tract tumors, particularly its role in the bladder cancer progression. We aimed to assess whether FABP6 influences bladder cancer progression through immune cell interactions. Methods: Utilizing data from the cancer genome atlas (TCGA) database, the association between FABP6 expression level and clinical data of bladder cancer was analyzed. This investigation aimed to determine the feasibility of FABP6 as a marker gene for the diagnosis and prognosis of bladder cancer. Additionally, the correlation between FABP6 and immune cells in bladder cancer was analyzed. Results: FABP6 was highly expressed in bladder cancer (p < 0.05). The overall survival (OS), progression-free interval (PFI) and disease-specific survival (DSS) in the high FABP6 expression group were higher than those in the low FABP6 expression group (all p < 0.05). The expression of FABP6 was negatively correlated with the infiltration of Th2 cells, macrophages, and Th1 cells (all p < 0.05). Conversely, the expression level of FABP6 was positively correlated with the infiltration of NK CD56bright cells (all p < 0.05). Conclusion: FABP6 emerges as a promising prognostic marker for bladder cancer. FABP6 may have an impact on the disease progression of bladder cancer by interacting with different types of immune cells in bladder cancer
Progress of Perioperative Oxidative Stress in Children
No full textOxidative stress occurs when the accumulation of oxidants exceeds the bodys antioxidant defenses. Reactive oxygen species (ROS) are the primary oxidants and their generation is influenced by various factors including disease states, surgical procedures, and anesthetics. Studies have shown that various perioperative complications are attributed to ROS, especially in immature organs and systems. The pediatric oxidative stress profile is distinct from that seen in adults. We conducted a search for publicly available studies on perioperative oxidative stress, including both reviews and original research articles, animal studies, and clinical trials. In this review, we provide an overview of the factors that influence oxidative stress, the impact of perioperative oxidative stress on the body, and the biomarkers and measurement methods for oxidative stress. We also summarize current knowledge of oxidative stress in children during the perioperative period. Emphasis was placed on various factors during the perioperative period that affect oxidative stress in children including specific surgical procedures, anesthetic agents and their use, fluid therapy, mechanical ventilation, and oxygen inhalation. This review also provides several insights into oxidative stress in children during the perioperative period. Current evidence indicates that the greater the surgical trauma, the stronger the oxidative stress response, and this is due to ischemia-reperfusion injury which is particularly evident in pediatric cardiac surgery. Regional anesthesia is helpful in reducing systemic oxidative stress levels compared to general anesthesia. Intravenous anesthetics have an inhibitory effect on the build-up of oxidative stress when compared to inhaled anesthetics. Further, compared with unrestrictive fluid therapy, restrictive fluid therapy, during the perioperative period, can enhance the bodys antioxidant capacity. In addition, we found that mechanical ventilation also increases oxidative stress. Therefore, to minimize perioperative oxidative stress, children undergoing surgery should, whenever possible, be treated with minimally invasive techniques such as laparoscopy and arthroscopy. Children undergoing general anesthesia should be given intravenous anesthetics if possible. A restrictive fluid therapy strategy should be adopted, and mechanical ventilation should be avoided. Finally, during perioperative treatment, exogenous antioxidants could be included
Integrating Silybin and Sirtuin Related Pathways in Steatosis-Related Liver Diseases
No full textSilybin represents the most bioactive compound of Silymarin, a flavonoid derived from Silybum marianum species. As a medicinal plant extract, Silybin possesses protective and regenerative action with respect to hepatic parenchyma. Due to its anti-oxidant, anti-inflammatory and anti-fibrotic effects, Silybin has been proposed as an extremely attractive molecule in the prevention and treatment of different hepatic diseases related to steatosis, such as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). However, the full comprehension of the molecular mechanisms by which Silybin acts as hepato-protector is still far from being complete. Silybin-mediated properties usually involve modulation of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor family (PPARs) pathways, which can affect NAD+-dependent protein lysine deacetylase Sirtuin (SIRT) family members either directly or indirectly. Starting from a detailed overview of its liver-related features, as well as the underlying molecular mechanisms, this review aimed at collecting evidence that correlates Silybin-mediated outcomes with SIRT pathways. With particular reference to SIRT1 and SIRT2, a theoretical map is designed in an effort to highlight shared molecular interactions. Finally, future perspectives concerning the integration of Silybin and Sirtuin pathways in fatty liver diseases are discussed, along with the major limits for its current therapeutic usage
Exploring the Significance of SOAT1/ACAT1 in Cancer Pathogenesis
No full textSterol O-acyltransferase 1 (SOAT1), also known as Acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT1), belongs to the membrane-bound O-acyltransferase enzyme family and plays a crucial role in maintaining intracellular cholesterol homeostasis. Numerous studies have documented the association between aberrant SOAT1 expression and various aspects of cancer biology, including cell proliferation, apoptosis, invasion, and metastasis. In this comprehensive review, we outline the multifaceted role of SOAT1 in tumor initiation, progression, and therapeutic responses. Furthermore, we elucidate its potential as a prognostic marker and highlight its clinical relevance as a promising therapeutic target for malignancies
Carvedilol Combined with Endoscopy vs. Endoscopy for Prevention of Esophagogastric Varices Rebleeding in Cirrhotic Patients with Different Severity of Esophagogastric Varices
Get PDFPurpose: This study aimed to assess the efficacy of endoscopic treatment alone compared to the combination of carvedilol with endoscopic treatment in preventing rebleeding of esophagogastric varices of varying severity in patients with hepatic cirrhosis. Methods: The study included 867 patients with hepatic cirrhosis and esophagogastric varices, who were admitted to Nanjing Drum Tower Hospital between July 2018 and December 2022. A 180-day follow-up period was implemented to evaluate the association between the combined use of carvedilol and endoscopy and clinical outcomes, focusing on esophagogastric variceal rebleeding and all-cause mortality. Propensity score matching (PSM) was performed on initially enrolled patients meeting the inclusion criteria (n = 232), resulting in the selection of 105 patients each in the endoscopy group and the combined carvedilol and endoscopy group. Subgroup analyses based on the severity of esophagogastric varices were conducted to compare the efficacy of the two treatment modalities. Results: After PSM, the endoscopy group and the combined carvedilol and endoscopy group exhibited a significant difference in rebleeding rates (29.52% vs. 14.29%, p = 0.006) and no significant difference in all-cause mortality (6.67% vs. 1.90%, p = 0.085). Multivariate Cox regression analysis revealed that the severity of esophagogastric varices was an independent risk factor influencing rebleeding (χ2 = 3.993, p = 0.046, hazard ratios (HR) = 2.85, 95% confidence intervals (CI): 1.02–7.95), while carvedilol emerged as an independent protective factor against rebleeding (χ2 = 6.222, p = 0.013, HR = 0.46, 95% CI: 0.25–0.85). Subgroup analysis based on the severity of esophagogastric varices showed that among patients with severe esophagogastric varices, the endoscopy group and the combined carvedilol and endoscopy group exhibited significant differences in rebleeding rates (34.12% vs. 16.25%, p = 0.009) and no significant differences in all-cause mortality (7.06% vs. 1.25%, p = 0.063). Among patients with non-severe esophagogastric varices, the endoscopy group and the combined carvedilol and endoscopy group showed no significant differences in rebleeding rates (10.00% vs. 8.00%, p = 0.684) and all-cause mortality (5.00% vs. 4.00%, p = 0.860). Conclusion: Combining carvedilol with endoscopy is more effective than endoscopy alone in preventing rebleeding from esophagogastric varices, though it does not impact patient survival. In patients with non-severe esophagogastric varices, the incorporation of carvedilol alongside endoscopy does not yield significant benefits in rebleeding or survival compared to endoscopy alone. Conversely, for patients with severe esophagogastric varices, the combined use of carvedilol and endoscopy demonstrates greater efficacy in preventing rebleeding than endoscopy alone, yet it does not influence all-cause mortality. Clinical Trial Registration: Chinese Clinical Trial Registry: ChiCTR-IPR-17012836
Efficient transfer attacks via enhancing perturbation robustness
Get PDFWith the rapid development of deep learning technology, artificial intelligence (AI) has found wide applications in diverse domains such as image classification, text processing, and autonomous driving. However, the increasing prevalence of security issues cannot be ignored. Studies have shown that deep neural network models face security risks due to adversarial sample attacks. These attacks involve adding imperceptible perturbations to deceive the model’s classification results, exposing vulnerabilities in deep learning model applications. While transfer attack methods offer practicality in real-world scenarios, their current performance in black-box attacks is limited. In this study, we propose a method that combines an attention mechanism and a frequency domain transformation to enhance the robustness of adversarial perturbations, thereby improving the performance of transfer attacks in black-box attack scenarios of deep learning models. Specifically, we introduce the CBAM-ResNet50 enhancement model based on attention mechanisms into transfer attacks, enhancing the model’s ability to identify important image regions. By adding perturbations to these attention-concentrated regions, adversary perturbation robustness is improved. Furthermore, we introduce a method for randomly transforming image enhancement in the frequency domain, which increases the diversity and robustness of adversarial perturbation by distributing perturbations across edges and textures. Experimental results demonstrate that our proposed method, considering both human perceptibility and computational cost, achieves a maximum black-box transfer attack success rate of 60.05%, surpassing the 49.65% success rate achieved by the NI-FGSM method across three models. The average success rate of the five methods exceeds an improvement of 6 percentage points in black-box attacks
Defining and validating limits of meteorological parameters for high yield of wheat in Punjab, India
Get PDFWheat is a rabi season crop and is highly susceptible to abrupt increases/decreases in weather parameters. So, a study was conducted to compute the critical limits of temperature, relative humidity, and rainfall by analyzing meteorological and crop data (1999–00 to 2018–19) for six locations (Ballowal Saunkhari, Ludhiana, Patiala, Amritsar, Bathinda, and Faridkot) in Punjab. Amongst the 20 years, high, medium, and low yield years for each location were identified, and then meteorological data for crop growth stages, i.e., sowing-emergence (43–47 Standard Meteorological Week (SMW)), vegetative (48–02 SMW), anthesis (03–06 SMW), grain filling (07–11 SMW), and physiological maturity (12–15 SMW), were tabulated. The week-wise deviations of maximum/minimum temperature, maximum/minimum relative humidity, and rainfall from normal data of those 20 years under study were computed to derive their critical limits. Then these stage-wise critical limits were validated using the actual yields achieved during crop years 2019–20, 2020–21, and 2021–22. During a good crop year 2019–20, the upper and lower limits of the ranges accounted for high yields obtained at 03 locations and medium yields at the remaining 03 locations. During the crop year 2020–21, when the medium yield was obtained at all six locations, the major reason was the deviation of temperature above the upper range during the later grain-filling stage. On the other hand, during 2021–22, when low yield was reported at 03 locations and medium yield at remaining 03 locations, in addition to temperature deviations, heavy rainfall during SMW 1 and 2 (late vegetative stage) and hot and dry weather during SMW 10 and 11 (late grain development stage) were the major reasons. Hence it may be concluded that to get higher wheat productivity during vegetative growth, flowering, and grain filling, the maximum/minimum temperature ranges should be 16–22/4–9 ℃, 21–28/7–13 ℃ and 25–32/11–16 ℃, respectively; the maximum/minimum relative humidity ranges should be 85%–99%/39%–77%, 80%–92%/32%–66% and 75%–86%/31%–59%, respectively
Biomagnetic monitoring of the spatial distribution of atmospheric particulate matter in an industrialized city in Japan: Case study at Muroran
Get PDFJapan has 111 active volcanoes, supplying a great amount of magnetically-enhanced fly ashes. Such fly ashes likely mask anthropogenic magnetic signals; therefore, only a few magnetic biomonitoring studies have been reported in active volcanic regions, including Japan. The environmental magnetic results are reported for the materials deposited on Sasa Kurilensis, also known as dwarf bamboo, in the vicinity of the industrialized Muroran city center in Japan. The dust on the ten leaves at 105 sites was wiped off with a commercial wipe sheet, and their rock magnetic properties were analyzed. Room- and low-temperature magnetic analyses indicate that the major magnetic mineral in the dust is partially oxidized magnetite, ranging from single to pseudo single domain size, and the magnetic mineralogy on the leaves’ surface remains consistent throughout the study area. Much higher saturation isothermal remanent magnetization intensities are observed in the city’s eastern parts. The dominant wind directions in Muroran city are northwest, indicating that the steel companies in the city center are the major source of the fine-grained magnetic minerals on the dwarf bamboo leaves. These results indicate that using the leaves of dwarf bamboo for magnetic biomonitoring can be a non-destructive and rapid method to study the spatial distribution of atmospheric particulate matter from local industrial activities, even in active volcanic areas