Induced expression of AMOT reverses adriamycin resistance in breast cancer cells.

Adriamycin (ADR) is widely used against breast cancer, but subsequent resistance always occurs. YAP, a downstream protein of angiomotin (AMOT), importantly contributes to ADR resistance, whereas the mechanism is largely unknown. MCF-7 cells and MDA-MB-231 cells were used to establish ADR-resistant cell. Then, mRNA and protein expressions of AMOT and YAP expressions were determined. After AMOT transfection alone or in combination with YAP, the sensitivity of the cells to ADR were evaluated in vitro by examining cell proliferation, apoptosis, and cell cycle, as well as in vivo by examining tumor growth. Additionally, the expressions of proteins in YAP pathway were determined in AMOT-overexpressing cells. In the ADR-resistant cells, the expression of AMOT was decreased while YAP was increased, respectively, and the nucleus localization of YAP was increased at the same time. After AMOT overexpression, these were inhibited, whereas the cell sensitivity to ADR was enhanced. However, the AMOT-induced changes were significantly suppressed by YAP knockdown. The consistent results in vivo showed that AMOT enhanced the inhibition of ADR on tumor growth, and inhibited YAP signaling, evidenced by decreased levels of YAP, CycD1, and p-ERK. Our data revealed that decreased AMOT contributed to ADR resistance in breast cancer cells, which was importantly negatively mediated YAP. These observations provide a potential therapy against breast cancer with ADR resistance.

Causal associations between the gut microbiota and multiple myeloma: a two-sample Mendelian randomization study.

Background: Previous observational studies have indicated a potential association between the gut microbiota and multiple myeloma (MM). However, the relationship between the gut microbiota and MM remains unclear. This study aimed to ascertain the existence of a causal link between the gut microbiota and MM. Methods: To investigate the potential causal relationship between gut microbiota and MM, a two-sample Mendelian randomization (MR) analysis was conducted. Exposure data was obtained from the MiBioGen consortium, which provided genetic variants associated with 211 bacterial traits. MM outcome data was obtained from the FinnGen consortium. The selection of Single nucleotide polymorphisms estimates was performed through meta-analysis using inverse-variance weighting, and sensitivity analyses were conducted using weighted median, MR Egger, Simple mode, and MR-PRESSO. Results: The results of the study demonstrated a significant positive correlation between the genus Eubacterium ruminantium group and the risk of MM (OR 1.71, 95% CI 1.21 to 2.39). Conversely, the genus: Dorea (OR 0.46, 95% CI 0.24 to 0.86), Coprococcus1 (OR 0.47, 95% CI 0.22 to 1.00), RuminococcaceaeUCG014 (OR 0.57, 95% CI 0.33 to 0.99), Eubacterium rectale group (OR 0.37, 95% CI 0.18 to 0.77), and order: Victivallales (OR 0.62, 95% CI 0.41-0.94), class: Lentisphaeria (OR 0.62, 95% CI 0.41 to 0.94), exhibited a negative association with MM. The inverse variance weighting analysis provided additional support for these findings. Conclusion: This study represents an inaugural exploration of MR to investigate the connections between gut microbiota and MM, thereby suggesting potential significance for the prevention and treatment of MM.

Effects of Physicochemical and Biological Treatment on Structure, Functional and Prebiotic Properties of Dietary Fiber from Corn Straw.

Corn straw is one kind of agricultural by-product containing 70-80% insoluble dietary fiber (IDF). In order to develop corn straw dietary fiber, this study was conducted to increase soluble dietary fiber (SDF) yield and improve the structure, functional and prebiotic properties of IDF and SDF from corn straw treated by alkali oxidation treatment, enzymatic hydrolysis, microbial fermentation and the combination of these methods. The results demonstrated that the yield of SDF was significantly increased from 2.64% to 17.15% after corn straw was treated by alkali oxidation treatment + Aspergillus niger fermentation + cellulase hydrolysis, compared with untreated corn straw. The SDF extracted from corn straw treated by alkali oxidation treatment + Aspergillus niger fermentation + cellulase hydrolysis (F-SDF) exhibited a honeycomb structure, low crystallinity (11.97%), good antioxidant capacity and high capacities of water holding, water solubility and cholesterol absorption and promoted short-chain fatty acids production by chicken cecal microbial fermentation in vitro. F-SDF enhanced the antibacterial activity against Escherichia coli and Staphylococcus aureus proliferations of Lactobacillus plantarum when it was used as a substrate for Lactobacillus plantarum fermentation. It could be concluded that the combined treatments could increase SDF yield from corn straw and improve its functional and prebiotic properties.

Exploring the recycled water acceptance based on the technological perspective of UTAUT2: a hybrid analytical approach.

Introduction: The development of advanced sewage technologies empowers the industry to produce high-quality recycled water, which greatly influences human's life and health. Thus, this study investigates the mechanism of individuals' adoption of recycled water from the technology adoption perspective. Methods: Employing the mixed method of structural equation modeling and artificial neural network analysis, we examined a research model developed from the extended Unified Theory of Acceptance and Use of Technology (UTAUT2) framework. To examine the research model, this study employs a leading web-survey company (Sojump) to collect 308 valid samples from the residents in mainland China. Results: The structural equation modeling results verified the associations between the six predictors (performance expectancy, effort expectancy, social influence, facilitating conditions, environmental motivation, and price value), individuals' cognitive and emotional attitudes, and acceptance intention. The artificial neural network analysis validates and complements the structural equation modeling results by unveiling the importance rank of the significant determinants of the acceptance decisions. Discussion: The study provides theoretical implications for recycled water research and useful insights for practitioners and policymakers to reduce the environmental hazards of water scarcity.

Exploring the influence of students' perceptions of face-to-face collaboration on cognitive engagement and learning outcomes in collaborative programming.

Collaborative programming is being increasingly used to overcome the difficulties of the individual programming process. In this study, we investigated the effect of collaborative perception on cognitive engagement and learning outcomes in collaborative programming. We used a quasi-experimental research to determine the differences in cognitive engagement and learning outcomes of three groups with different levels of collaborative perception. The findings highlight several important conclusions. First, there were significant differences in cognitive engagement and learning outcomes across collaborative perception groups. Students with high levels of collaborative perception demonstrate more comprehensive and diverse cognitive engagement, resulting in higher learning outcomes compared to those with lower perception. Second, students in the low collaborative perception group had more Clarification-Elaboration cognitive connections, and students in the high collaborative perception group had stronger Clarification-Positioning and Clarification-Verification cognitive connections. Third, collaborative perception positively moderated the relationship between cognitive engagement and learning outcomes. In particular, three cognitive engagement, Clarification, Elaboration, and Positioning, had a greater impact on performance when moderated by collaborative perceptions. These findings have practical implications for educators and course designers, emphasizing the importance of considering students' collaborative perception when forming groups and promoting effective collaborative programming.

Complete genome sequence of Erwinia amylovora PBI209 isolated from a necrotic flower of Pyrus sinkiangensis in China.

Here, we report the complete genome sequence of Erwinia amylovora PBI209 that causes fire blight isolated from a necrotic flower of Pyrus sinkiangensis in Xinjiang, China. The genome consists of 3,800,955 bp, with 3,403 protein-coding genes and a guanine-cytosine content of 53.61%.

Benzimidazole-based structure optimization to discover novel anti-gastric cancer agents targeting ROS/MAPK pathway.

Given the malignancy of gastric cancer, developing highly effective and low-toxic targeted drugs is essential to prolong patient survival and improve patient outcomes. In this study, we conducted structural optimizations based on the benzimidazole scaffold. Notably, compound 8 f presented the most potent antiproliferative activity in MGC803 cells and induced cell cycle arrest at the G0/G1 phase. Further mechanistic studies demonstrated that compound 8 f caused the apoptosis of MGC803 cells by elevating intracellular reactive oxygen species (ROS) levels and activating the mitogen-activated protein kinase (MAPK) signaling pathway, accompanied by corresponding markers change. In vivo investigations additionally validated the inhibitory effect of compound 8 f on tumor growth in xenograft models bearing MGC803 cells without obvious toxicity. Our studies suggest that compound 8 f holds promise as a potential and safe lead compound for developing anti-gastric cancer agents.

Comparative proteomic analysis of plasma exosomes reveals the functional contribution of N-acetyl-alphaglucosaminidase to Parkinson's disease.

ABSTRACT: Parkinson's disease is the second most common progressive neurodegenerative disorder, and few reliable biomarkers are available to track disease progression. The proteins, DNA, mRNA, and lipids carried by exosomes reflect intracellular changes, and thus can serve as biomarkers for a variety of conditions. In this study, we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson's disease and the potential therapeutic roles of these proteins in Parkinson's disease. Using a tandem mass tag-based quantitative proteomics approach, we characterized the proteomes of plasma exosomes derived from individual patients, identified exosomal protein signatures specific to patients with Parkinson's disease, and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein. N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western blot. The results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson's disease, but also decreased with increasing Hoehn-Yahr stage, suggesting that N-acetyl- alpha-glucosaminidase could be used to rapidly evaluate Parkinson's disease severity. Furthermore, western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with methyl-4-phenylpyridinium (MPP+) and cells overexpressing a-synuclein (α-syn) compared with control cells. Additionally, N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibited α-syn expression in MPP+-treated cells. Taken together, our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson's disease diagnosis, and that N-acetyl-alpha- glucosaminidase may reduce α-syn expression and MPP+-induced neurotoxicity, thus providing a new therapeutic target for Parkinson's disease.

Identification of hub glycolysis-related genes in acute myocardial infarction and their correlation with immune infiltration using bioinformatics analysis.

PURPOSE: Glycolysis and immune metabolism play important roles in acute myocardial infarction (AMI). Therefore, this study aimed to identify and experimentally validate the glycolysis-related hub genes in AMI as diagnostic biomarkers, and further explore the association between hub genes and immune infiltration. METHODS: Differentially expressed genes (DEGs) from AMI peripheral blood mononuclear cells (PBMCs) were analyzed using R software. Glycolysis-related DEGs (GRDEGs) were identified and analyzed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) for functional enrichment. A protein-protein interaction network was constructed using the STRING database and visualized using Cytoscape software. Immune infiltration analysis between patients with AMI and stable coronary artery disease (SCAD) controls was performed using CIBERSORT, and correlation analysis between GRDEGs and immune cell infiltration was performed. We also plotted nomograms and receiver operating characteristic (ROC) curves to assess the predictive accuracy of GRDEGs for AMI occurrence. Finally, key genes were experimentally validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting using PBMCs. RESULTS: A total of 132 GRDEGs and 56 GRDEGs were identified on the first day and 4-6 days after AMI, respectively. Enrichment analysis indicated that these GRDEGs were mainly clustered in the glycolysis/gluconeogenesis and metabolic pathways. Five hub genes (HK2, PFKL, PKM, G6PD, and ALDOA) were selected using the cytoHubba plugin. The link between immune cells and hub genes indicated that HK2, PFKL, PKM, and ALDOA were significantly positively correlated with monocytes and neutrophils, whereas G6PD was significantly positively correlated with neutrophils. The calibration curve, decision curve analysis, and ROC curves indicated that the five hub GRDEGs exhibited high predictive value for AMI. Furthermore, the five hub GRDEGs were validated by RT-qPCR and western blotting. CONCLUSION: We concluded that HK2, PFKL, PKM, G6PD, and ALDOA are hub GRDEGs in AMI and play important roles in AMI progression. This study provides a novel potential immunotherapeutic method for the treatment of AMI.

Histone deacetylase complexes: Structure, regulation and function.

Histone deacetylases (HDACs) are key epigenetic regulators, and transcriptional complexes with deacetylase function are among the epigenetic corepressor complexes in the nucleus that target the epigenome. HDAC-bearing corepressor complexes such as the Sin3 complex, NuRD complex, CoREST complex, and SMRT/NCoR complex are common in biological systems. These complexes activate the otherwise inactive HDACs in a solitary state. HDAC complexes play vital roles in the regulation of key biological processes such as transcription, replication, and DNA repair. Moreover, deregulated HDAC complex function is implicated in human diseases including cancer. Therapeutic strategies targeting HDAC complexes are being sought actively. Thus, illustration of the nature and composition of HDAC complexes is vital to understanding the molecular basis of their functions under physiologic and pathologic conditions, and for designing targeted therapies. This review presents key aspects of large multiprotein HDAC-bearing complexes including their structure, function, regulatory mechanisms, implication in disease development, and role in therapeutics.

Mechanisms and translational applications of regeneration in limbs: From renewable animals to humans.

BACKGROUND: The regenerative capacity of organisms declines throughout evolution, and mammals lack the ability to regenerate limbs after injury. Past approaches to achieving successful restoration through pharmacological intervention, tissue engineering, and cell therapies have faced significant challenges. OBJECTIVES: This review aims to provide an overview of the current understanding of the mechanisms behind animal limb regeneration and the successful translation of these mechanisms for human tissue regeneration. RESULTS: Particular attention was paid to the Mexican axolotl (Ambystoma mexicanum), the only adult tetrapod capable of limb regeneration. We will explore fundamental questions surrounding limb regeneration, such as how amputation initiates regeneration, how the limb knows when to stop and which parts to regenerate, and how these findings can apply to mammalian systems. CONCLUSIONS: Given the urgent need for regenerative therapies to treat conditions like diabetic foot ulcers and trauma survivors, this review provides valuable insights and ideas for researchers, clinicians, and biomedical engineers seeking to facilitate the regeneration process or elicit full regeneration from partial regeneration events.

Syntaxin5 is essential for survival by ensuring midgut epithelial homeostsis and regulating feeding in Locusta migratoria.

Syntaxin5 (Syx5) belongs to SNAREs family, which play important roles in fusion of vesicles to target membranes. Most of what we know about functions of Syx5 originates from studies in fungal or vertebrate cells, how Syx5 operates during the development of insects is poorly understood. In this study, we investigated the role of LmSyx5 in the gut development of the hemimetabolous insect Locusta migratoria. LmSyx5 was expressed in many tissues, with higher levels in the gut. Knockdown of LmSyx5 by RNA interference (RNAi) considerably suppressed feeding in both nymphs and adults. The dsLmSyx5-injected locusts lost body weight and finally died at a mortality of 100%. Furthermore, hematoxylin-eosin staining indicated that the midgut is deformed in dsLmSyx5-treated nymphs and the brush border in midgut epithelial cells is severely damaged, suggesting that LmSyx5 is involved in morphogenesis of the midgut. TEM further showed that the endoplasmic reticulum of midgut cells have a bloated appearance. Taken together, these results suggest that LmSyx5 is essential for midgut epithelial homeostsis that affects growth and development of L. migratoria. Thus, Syx5 is a promising RNAi target for controlling L. migratoria, and even other pests.

Developing oxaliplatin and IL-15 Co-carried gels as drug depots to enable triple-interlocked combination therapy for colorectal cancer.

Chemo-immunotherapy, which involves the simultaneous use of chemotherapy drug and immunotherapeutic agent to achieve synergistic effects, plays a crucial role in cancer treatment. However, the immunosuppressive microenvironment, insufficient tumor specificity, and serious systemic side effects hinder their synergistic therapeutic effects and clinical applications. Herein, T cell and natural killer (NK) cell, which are the most important immune effector cells, were both activated to reverse the immunosuppressive microenvironment. To simplify drug carriers, oxaliplatin was selected as the chemotherapy drug which can both induce the ICD effect and activate T cells. IL-15 was selected to activate NK cells. To enhance the productivity of the carrier and reduce side effects, the easy-prepared thermosensitive hydrogel (OXL/IL-15 TG) was developed to co-load oxaliplatin-loaded liposomes (OXL) and IL-15. Colorectal cancer, suitable for in situ administration, was selected as model cancer. The resulting novel triple-interlocked combination therapy could directly kill the tumor cells, induces ICD effect and activate NK cells. After administration, OXL/IL-15 TG was formed serving as a drug depot, slowing releasing OXL and IL-15 non-interferencely. OXL around 165.47±7.04 nm was passively delivered to tumor tissue, killing tumor cells and inducing ICD effect. The results demonstrated that IL-15 stimulated the activation of NK cells. In tumor-bearing mice models, OXL/IL-15 TG exhibited a remarkable and noteworthy anti-tumor efficacy, and expanded survival rate. Notably, OXL/IL-15 TG led to an enhanced infiltration of CD3+CD8+ T cells and CD3-CD49+ NK cells within the tumor tissue. Overall, the triple-interlocked combination therapy provided a new idea for colorectal cancer therapy.

Post-stroke family resilience is correlated with family functioning among stroke survivors: The mediating role of patient's coping and self-efficacy.

AIM: Family resilience and healthy family functioning are crucial for stroke survivors' rehabilitation. This study aimed to determine the mediating effects of self-efficacy and confrontation coping on the relationship between family resilience and functioning among patients with first-episode stroke. DESIGN: A cross-sectional design was applied. METHODS: 288 patients with first-episode stroke were recruited from 7 hospitals in Shangqiu and Shanghai, China, from July 2020 to October 2020. A shortened Chinese version of the Family Resilience Assessment Scale, family adaptation, partnership, growth, affection and resolve questionnaire, Medical Coping Modes Questionnaire, and Self-efficacy for Chronic Disease 6-item Scale were used to collect the self-reported data. The relationships among the studied variables were studied using spearman correlation and structural equation model. RESULTS: The average level of family functioning among stroke patients was 7.87 (SD = 2.32). About 26.8% (n = 76) of patients reported family dysfunction. The structural equation model showed that family resilience directly affected patients' satisfaction with family functioning (r = 0.406, p < 0.001) and indirectly affected the mediating role of patients' self-efficacy and confrontation coping style (r = 0.119, p < 0.001). The model was with good fit (χ2/df = 2.128, RMSEA = 0.065, GFI = 0.956, AGFI = 0.919, NFI = 0.949, and TLI = 0.956). CONCLUSION: Family resilience and functioning among patients with first-episode stroke are positively associated with the mediating effects of the patients' confrontation coping style and self-efficacy between family resilience and functioning. The findings indicate that the professionals should pay special attention to families exhibiting poor family resilience or with patients who rarely use confrontation coping styles or with poor self-efficacy since they are more likely to suffer from low functioning.

Heat Exposure and Dementia-Related Mortality in China.

Importance: Although existing research has found daily heat to be associated with dementia-related outcomes, there is still a gap in understanding the differing associations of nighttime and daytime heat with dementia-related deaths. Objectives: To quantitatively assess the risk and burden of dementia-related deaths associated with short-term nighttime and daytime heat exposure and identify potential effect modifications. Design, Setting, and Participants: This case-crossover study analyzed individual death records for dementia across all mainland China counties from January 1, 2013, to December 31, 2019, using a time-stratified case-crossover approach. Statistical analysis was conducted from January 1, 2013, to December 31, 2019. Exposures: Two novel heat metrics: hot night excess (HNE) and hot day excess (HDE), representing nighttime and daytime heat intensity, respectively. Main Outcomes and Measures: Main outcomes were the relative risk and burden of dementia-related deaths associated with HNE and HDE under different definitions. Analysis was conducted with conditional logistic regression integrated with the distributed lag nonlinear model. Results: The study involved 132 573 dementia-related deaths (mean [SD] age, 82.5 [22.5] years; 73 086 women [55.1%]). For a 95% threshold, the median hot night threshold was 24.5 °C (IQR, 20.1 °C-26.2 °C) with an HNE of 3.7 °C (IQR, 3.1 °C-4.3 °C), and the median hot day threshold was 33.3 °C (IQR, 29.9 °C-34.7 °C) with an HDE of 0.6 °C (IQR, 0.5 °C-0.8 °C). Both nighttime and daytime heat were associated with increased risk of dementia-related deaths. Hot nights' associations with risk of dementia-related deaths persisted for 6 days, while hot days' associations with risk of dementia-related deaths extended over 10 days. Extreme HDE had a higher relative risk of dementia-related deaths, with a greater burden associated with extreme HNE at more stringent thresholds. At a 97.5% threshold, the odds ratio for dementia-related deaths was 1.38 (95% CI, 1.22-1.55) for extreme HNE and 1.46 (95% CI, 1.27-1.68) for extreme HDE, with an attributable fraction of 1.45% (95% empirical confidence interval [95% eCI], 1.43%-1.47%) for extreme HNE and 1.10% (95% eCI, 1.08%-1.11%) for extreme HDE. Subgroup analyses suggested heightened susceptibility among females, individuals older than 75 years of age, and those with lower educational levels. Regional disparities were observed, with individuals in the south exhibiting greater sensitivity to nighttime heat and those in the north to daytime heat. Conclusions and Relevance: Results of this nationwide case-crossover study suggest that both nighttime and daytime heat are associated with increased risk of dementia-related deaths, with a greater burden associated with nighttime heat. These findings underscore the necessity of time-specific interventions to mitigate extreme heat risk.

Serum metabolomics analysis of patients with chronic obstructive pulmonary disease and 'frequent exacerbator' phenotype.

Chronic obstructive pulmonary disease (COPD) exacerbations accelerate loss of lung function and increased mortality. The complex nature of COPD presents challenges in accurately predicting and understanding frequent exacerbations. The present study aimed to assess the metabolic characteristics of the frequent exacerbation of COPD (COPD­FE) phenotype, identify potential metabolic biomarkers associated with COPD­FE risk and evaluate the underlying pathogenic mechanisms. An internal cohort of 30 stable patients with COPD was recruited. A widely targeted metabolomics approach was used to detect and compare serum metabolite expression profiles between patients with COPD­FE and patients with non­frequent exacerbation of COPD (COPD­NE). Bioinformatics analysis was used for pathway enrichment analysis of the identified metabolites. Spearman's correlation analysis assessed the associations between metabolites and clinical indicators, while receiver operating characteristic (ROC) analysis evaluated the ability of metabolites to distinguish between two groups. An external cohort of 20 patients with COPD validated findings from the internal cohort. Out of the 484 detected metabolites, 25 exhibited significant differences between COPD­FE and COPD­NE. Metabolomic analysis revealed differences in lipid, energy, amino acid and immunity pathways. Spearman's correlation analysis demonstrated associations between metabolites and clinical indicators of acute exacerbation risk. ROC analysis demonstrated that the area under the curve (AUC) values for D­fructose 1,6­bisphosphate (AUC=0.871), arginine (AUC=0.836), L­2­hydroxyglutarate (L­2HG; AUC=0.849), diacylglycerol (DG) (16:0/20:5) (AUC=0.827), DG (16:0/20:4) (AUC=0.818) and carnitine­C18:2 (AUC=0.804) were >0.8, highlighting their discriminative capacity between the two groups. External validation results demonstrated that DG (16:0/20:5), DG (16:0/20:4), carnitine­C18:2 and L­2HG were significantly different between patients with COPD­FE and those with COPD­NE. In conclusion, the present study offers insights into early identification, mechanistic understanding and personalized management of the COPD­FE phenotype.

Optimizing Coreopsis tinctoria Flower Extraction and Inhibiting CML Activity: Box-Behnken Design.

BACKGROUND: Chronic myelogenous leukemia (CML) is an uncommon type of cancer of the bone marrow associated with high mortality. Although several effective therapies have been developed to reduce symptoms in patients with CML, many of these methods are associated with side effects. Coreopsis tinctoria Nutt. (C. tinctoria) is a natural medicinal material that possesses antioxidant and anticancer activities. Yet, its effect in treating leukemia has still not been fully explored. OBJECTIVE: To optimize the C. tinctoria flower extraction process and investigate whether these extracts can impair CML cell survival. METHODS: The extraction process of C. tinctoria was optimized by the Box-Behnken design response surface method. K562 cells were treated with different volumes (0, 10, 25, 50, and 100 µL) of C. tinctoria flower extracts. The effect of C. tinctoria extract on cell morphology and cell apoptosis was assessed by light microscopy, laser confocal microscopy, and flow cytometry. RESULTS: We established the following optimized C. tinctoria flower extraction conditions: temperature of 84.4 °C, extraction period of 10 mins, solid-liquid ratio of 1:65, and times 4. These conditions were applied for C. tinctoria flower extraction. Pre-incubation of extracts prepared under the aforementioned optimal conditions with K562 cells induced cell cytotoxicity and cell apoptosis. CONCLUSION: C. tinctoria flower extracts exert obvious anti-leukemia effects in vitro and may be a potential drug candidate for leukemia treatment.

Decoding CLU (Clusterin): Conquering cancer treatment resistance and immunological barriers.

One major obstacle in the treatment of cancer is the presence of proteins resistant to cancer therapy, which can impede the effectiveness of traditional approaches such as radiation and chemotherapy. This resistance can lead to disease progression and cause treatment failure. Extensive research is currently focused on studying these proteins to create tailored treatments that can circumvent resistance mechanisms. CLU (Clusterin), a chaperone protein, has gained notoriety for its role in promoting resistance to a wide range of cancer treatments, including chemotherapy, radiation therapy, and targeted therapy. The protein has also been discovered to have a role in regulating the immunosuppressive environment within tumors. Its ability to influence oncogenic signaling and inhibit cell death bolster cancer cells resistant against treatments, which poses a significant challenge in the field of oncology. Researchers are actively investigating to the mechanisms by which CLU exerts its resistance-promoting effects, with the ultimate goal of developing strategies to circumvent its impact and enhance the effectiveness of cancer therapies. By exploring CLU's impact on cancer, resistance mechanisms, tumor microenvironment (TME), and therapeutic strategies, this review aims to contribute to the ongoing efforts to improve cancer treatment outcomes.

U-shaped association between serum calcium and in-hospital mortality in diabetes patients with congestive heart failure: a cohort study.

Previous studies have reported that the significant association between serum calcium and mortality substantially in patients, especially among those with intensive care unit (ICU). And In diabetes mellitus, congestive heart failure (CHF) is a significant comorbidity. We aim to evaluate the association between serum calcium levels and in-hospital mortality among patients with diabetes and congestive heart failure. The participants in this study were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. To scrutinize potential associations between serum calcium levels and in-hospital mortality, a comprehensive analysis encompassing multivariate logistic regression, cubic spline function model, threshold effect analysis, and subgroup analysis was performed. This retrospective cohort study encompassed 7063 patients, among whom the in-hospital mortality stood at 12.2%. In the multivariate logistic regression, adjusted odds ratios (ORs) were contrasted with the reference category Q6 (8.8-9.1 mg/dL) for serum calcium levels and in-hospital mortality. The adjusted ORs for Q1 (≤ 7.7 mg/dL), Q2 (7.7-8 mg/dL), and Q7 (≥ 9.1 mg/dL) were 1.69 (95% CI 1.17-2.44, p = 0.005), 1.62 (95% CI 1.11-2.36, p = 0.013), and 1.57 (95% CI 1.1-2.24, p = 0.012) respectively. The dose-response analysis uncovered a U-shaped relationship between serum calcium levels and in-hospital mortality in diabetic patients with heart failure. Subgroup analyses confirmed result stability notwithstanding the influence of diverse factors. Our investigation revealed a U-shaped correlation between serum calcium levels and in-hospital mortality in diabetes patients with congestive heart failure, pinpointing a significant inflection point at 9.05 mg/dL.