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Pancreatic ductal adenocarcinoma (PDAC) features substantial matrix stiffening and reprogrammed glucose metabolism, particularly the Warburg effect. However, the complex interplay between these traits and their impact on tumor advancement remains inadequately explored. Here, we integrated clinical, cellular, and bioinformatics approaches to explore the connection between matrix stiffness and the Warburg effect in PDAC, identifying CLIC1 as a key mediator. Elevated CLIC1 expression, induced by matrix stiffness through Wnt/ß-catenin/TCF4 signaling, signifies poorer prognostic outcomes in PDAC. Functionally, CLIC1 serves as a catalyst for glycolytic metabolism, propelling tumor proliferation. Mechanistically, CLIC1 fortifies HIF1α stability by curbing hydroxylation via reactive oxygen species (ROS). Collectively, PDAC cells elevate CLIC1 levels in a matrix-stiffness-responsive manner, bolstering the Warburg effect to drive tumor growth via ROS/HIF1α signaling. Our insights highlight opportunities for targeted therapies that concurrently address matrix properties and metabolic rewiring, with CLIC1 emerging as a promising intervention point.
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BACKGROUND: As a relatively novel approach to enhancing skeletal muscle health, mixed protein supplementation has shown similar responses to whey protein. However, no previous studies have examined its impact on golf swing performance. This study aimed to examine the effect of mixed protein supplementation on the swing performance and muscle strength of casual golfers. METHODS: Sixty participants with a handicap of less than 20 were recruited and randomly assigned to a double-blind, placebo-controlled study design. The participants were divided into two groups: a mixed protein group (MG, n = 30), and a placebo control group (CG, n = 30). They were instructed to ingest either a supplement containing casein calcium, whey protein, and isolated pea protein, or a placebo, once daily for 8 weeks. Pre- and posttests consisted of anthropometric measurements, muscle strength (isokinetic knee and trunk strength, and handgrip strength), 2-minute push-ups, balance, and golf swing performance using a driver and 7-iron. RESULTS: After the 8-week supplementation period, ANCOVA, using baseline values as covariates, revealed significant differences for driver distance (p = .004) and driver ball speed (p < .001). MG significantly increased driver distance by 5.17 ± 12.8 m (p = .046), driver ball speed by 1.36 ± 2.87 m/s (p = .021). Additionally, significantly improvements were observed in hand grip strength (+2.12 ± 3.47 kg, p = .004), two-minute push-ups (+4.89 ± 8.14 reps, p = .004), and balance score (-0.37 ± 0.69 min, p = .009). No significant differences were observed in body composition parameters (p > .05). CONCLUSION: The intake of a mixed protein containing both animal and plant proteins had positive effects on golf performance and muscle function. Therefore, mixed proteins may represent a safe and effective approach to enhancing skeletal muscle health in golf players.
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Desempenho Atlético , Suplementos Nutricionais , Golfe , Força Muscular , Músculo Esquelético , Proteínas do Soro do Leite , Humanos , Golfe/fisiologia , Método Duplo-Cego , Força Muscular/efeitos dos fármacos , Força Muscular/fisiologia , Masculino , Proteínas do Soro do Leite/administração & dosagem , Proteínas do Soro do Leite/farmacologia , Desempenho Atlético/fisiologia , Músculo Esquelético/fisiologia , Músculo Esquelético/efeitos dos fármacos , Adulto , Caseínas/administração & dosagem , Caseínas/farmacologia , Adulto Jovem , Proteínas de Ervilha/administração & dosagem , Fenômenos Fisiológicos da Nutrição Esportiva , Proteínas Alimentares/administração & dosagem , Feminino , Força da Mão/fisiologiaRESUMO
BACKGROUND: Premature aging is a significant concern in adult survivors of childhood cancer as they develop aging-related conditions at a younger age than their peers with no history of childhood cancer. Although modifiable lifestyle factors, such as diet, are postulated to affect aging process, supporting evidence is sparse. METHODS: We examined if the consumption of sugar and sugar-sweetened beverages was related to premature aging in 3322 adult survivors of childhood cancer in the St. Jude Lifetime Cohort. Premature aging was assessed using the Deficit Accumulation Index (DAI) that was a ratio of the number of age-related chronic health conditions each survivor had out of 44 conditions total. Multinomial logistic regressions adjusting for confounders were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: There were 46% of childhood cancer survivors consumed SSBs once or more times per day. High intake of sugar, especially sugars added to foods during preparation or processing, and habitual consumption of sugar-sweetened beverage were associated with an increased risk of premature aging. DISCUSSION: Our findings support a need to include strategies to reduce sugar and sugar-sweetened beverages consumption in lifestyle interventions to promote healthy aging in adult survivors of childhood cancer.
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BACKGROUND: Researchers have investigated the physical and psychosocial advantages of Taekwondo for older adults. However, prior studies of Taekwondo's impact on physical function and psychological well-being in this demographic have produced inconsistent findings. Thus, this systematic review aimed to assess how Taekwondo practice affects the physical function and psychological well-being of older adults. METHODS: We systematically searched PubMed, EMBASE, CINAHL, SPORTDiscus, Scopus, Korea Education and Research Information Service, Korean Studies Information Service System, Korean National Assembly Library, Research Information Sharing Service, National Digital Science Library, and China National Knowledge Infrastructure from their inception to December 2023. Two reviewers independently selected and extracted data from each study. We calculated effect sizes using a random-effects model with a 95 % confidence interval (CI) and evaluated study quality using the Physiotherapy Evidence Database scale. RESULTS: This review included ten studies with 227 participants aged 66.1-73.6 years. The meta-analysis revealed significant enhancements in cognitive function [Korean Version of Mini-Mental State Examination, standard mean difference (SMD) = 0.700, 95 % CI (0.364-1.037), I2 = 0 %, p < .001], blood indicators [ß-amyloid, SMD = 0.613, 95 % CI (0.103-1.123), I2 = 34.920 %, p < .05; brain-derived neurotrophic factor, SMD = 0.566, 95 % CI (0.166-0.966), I2 = 0 %, p < .01; high-density lipoprotein cholesterol, SMD = 0.677, 95 % CI (0.357-0.966), I2 = 0 %, p < .001; low-density lipoprotein cholesterol, SMD = 0.809, 95 % CI (0.376-1.242), I2 = 42.621 %, p < .001; and total cholesterol, SMD = 0.979, 95 % CI (0.603-1.356), I2 = 22.221 %, p < .001], and physical function [lean body mass, SMD = 0.465, 95 % CI (0.109-0.821), I2 = 0 %, p < .05, and handgrip strength, SMD = 0.929, 95 % CI (0.194-1.663), I2 = 48.217 %, p < .05]. CONCLUSIONS: This meta-analysis indicates that Taekwondo training is a beneficial therapy with protective effects on cognitive function, physical function, and body composition in older adults. These findings highlight its potential significance in cognitive rehabilitation and physiological health promotion among this demographic population.
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HCC is globally recognized as a major health threat. Despite significant progress in the development of treatment strategies for liver cancer, recurrence, metastasis, and drug resistance remain key factors leading to a poor prognosis for the majority of liver cancer patients. Thus, there is an urgent need to develop effective biomarkers and therapeutic targets for HCC. Collagen, the most abundant and diverse protein in the tumor microenvironment, is highly expressed in various solid tumors and plays a crucial role in the initiation and progression of tumors. Recent studies have shown that abnormal expression of collagen in the tumor microenvironment is closely related to the occurrence, development, invasion, metastasis, drug resistance, and treatment of liver cancer, making it a potential therapeutic target and a possible diagnostic and prognostic biomarker for HCC. This article provides a comprehensive review of the structure, classification, and origin of collagen, as well as its role in the progression and treatment of HCC and its potential clinical value, offering new insights into the diagnosis, treatment, and prognosis assessment of liver cancer.
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Biomarcadores Tumorais , Carcinoma Hepatocelular , Colágeno , Neoplasias Hepáticas , Microambiente Tumoral , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Biomarcadores Tumorais/análise , Colágeno/metabolismo , Prognóstico , Progressão da DoençaRESUMO
Background: Sarcopenia is a muscle wasting condition that affects elderly individuals. It can lead to changes in movement patterns, which can increase the risk of falls and other injuries. Methods: Elderly women participants aged ≥65 years who could walk independently were recruited and classified into two groups based on knee extension strength (KES). Participants with low KES scores were assigned to the possible sarcopenia group (PSG, n=7) and an 8-week exercise intervention was implemented. Healthy seniors with high KES scores were classified as the reference group (RG, n=4), and a 3-week exercise intervention was conducted. Kinematic movement data were recorded during the intervention period. All participants' exercise repetitions were used in the data analysis (number of data points =1,128). Results: The PSG showed significantly larger movement patterns in knee rotation during wide squats compared to the RG, attributed to weakened lower limb strength. The voting classifier, trained on the movement patterns from wide squats, determined that significant differences in overall movement patterns between the two groups persisted until the end of the exercise intervention. However, after the exercise intervention, significant improvements in lower limb strength in the PSG resulted in reduced knee rotation ROM and Max, thereby stabilizing movements and eliminating significant differences with the RG. Conclusions: This study suggests that exercise interventions can modify the movement patterns in elderly individuals with possible sarcopenia. These findings provide fundamental data for developing an exercise management system that remotely tracks and monitors the movement patterns of older adults during exercise activities.
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Rhei Radix et Rhizoma and Magnoliae Officinalis Cortex have been used together to treat constipation in the clinical practices for more than 2000 years. Nonetheless, their compatibility mechanism is still unclear. In this study, the amelioration of Rhei Radix et Rhizoma combined with Magnoliae Officinalis Cortex on constipation was systematically and comprehensively evaluated. The results showed that their compatibility could markedly shorten gastrointestinal transport time, increase fecal water content and frequency of defecation, improve gastrointestinal hormone disorders and protect colon tissue of constipation rats compared with the single drug. Furthermore, according to 16S rRNA sequencing in conjunction with UPLC-Q-TOF/MS, the combination of two herbal medications could greatly raise the number of salutary bacteria (Lachnospiraceae, Romboutsia and Subdoligranulum) while decreasing the abundance of pathogenic bacteria (Erysipelatoclostridiaceae). And two herb drugs could markedly improve the disorder of fecal metabolic profiles. A total of 7 different metabolites associated with constipation were remarkably shifted by the compatibility of two herbs, which were mainly related to arachidonic acid metabolism, alpha-linolenic acid metabolism, unsaturated fatty acid biosynthesis and other metabolic ways. Thus, the regulation of intestinal microbiome and its metabolism could be a potential target for Rhei Radix et Rhizoma and Magnoliae Officinalis Cortex herb pair to treat constipation. Furthermore, the multi-omics approach utilized in this study, which integrated the microbiome and metabolome, had potential for investigating the mechanism of traditional Chinese medicines.
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Constipação Intestinal , Medicamentos de Ervas Chinesas , Fezes , Microbioma Gastrointestinal , Magnolia , Ratos Sprague-Dawley , Rheum , Ratos , Animais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Magnolia/química , Microbioma Gastrointestinal/efeitos dos fármacos , Constipação Intestinal/tratamento farmacológico , Constipação Intestinal/metabolismo , Masculino , Rheum/química , Fezes/microbiologia , Fezes/química , Cromatografia Líquida de Alta Pressão , Metabolômica , Rizoma/química , Metaboloma/efeitos dos fármacos , MultiômicaRESUMO
BACKGROUND: Sodium voltage-gated channel beta subunit 4 (SCN4B) plays a suppressive role in various tumors. However, the role of SCN4B in non-small cell lung cancer (NSCLC) is not yet clear. This study aims to investigate the expression of SCN4B in NSCLC patients and its correlation with prognosis. METHODS: Firstly, the expression of SCN4B in non-small cell lung cancer (NSCLC) was analyzed using The Cancer Genome Atlas (TCGA) database. Then, differential expression genes (DEGs) were identified using R software. Next, DEG enrichment pathways were analyzed using the R package clusterProfiler. Protein-protein interaction networks were revealed through STRING analysis. A heatmap showed significant differential expression of SCN4B. Further analysis included examining SCN4B expression in a pan-cancer context and its correlation with 24 types of immune cells in NSCLC. Subsequently, quantitative real-time polymerase chain reaction (qRT-PCR), Western Blot, immunohistochemistry, and clinical data were used to validate SCN4B expression and prognostic value in NSCLC patients. RESULTS: SCN4B mRNA expression in non-small cell lung cancer tissues was significantly lower than in adjacent normal tissues (p < 0.001). Clinical correlation analysis confirmed its association with clinical pathology. Gene set enrichment analysis (GSEA) and tumor immune-related analyses indicated that SCN4B is involved in NSCLC-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and participates in immune infiltration. qRT-PCR, Western Blot, and immunohistochemistry also confirmed that SCN4B is downregulated in NSCLC patients and is associated with poor prognosis. CONCLUSION: SCN4B is downregulated in tumor tissues of NSCLC patients and is associated with a poor prognosis.
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Cancer neuroscience, a promising field dedicated to exploring interactions between cancer and the nervous system, has attracted growing attention. The gastrointestinal tracts exhibit extensive innervation, notably characterized by intrinsic innervation. The gut harbors a substantial population of glial cells, including Schwann cells wrapping axons of neurons in the peripheral nervous system and enteric glial cells intricately associated with intrinsic innervation. Glial cells play a crucial role in maintaining the physiological functions of the intestine, encompassing nutrient absorption, barrier integrity, and immune modulation. Nevertheless, it has only been in recent times that the significance of glial cells within colorectal cancer (CRC) has begun to receive considerable attention. Emerging data suggests that glial cells in the gut contribute to the progression and metastasis of CRC, by interacting with cancer cells, influencing inflammation, and modulating the tumor microenvironment. Here, we summarize the significant roles of glial cells in the development and progression of CRC and discuss the latest technologies that can be integrated into this field for in-depth exploration, as well as potential specific targeted strategies for future exploration to benefit patients.
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NAD(P)H:quinone oxidoreductase 1 (NQO1) is overexpressed in most solid cancers, emerging as a promising target for tumor-selective killing. ß-Lapachone (ß-Lap), an NQO1 bioactivatable drug, exhibits significant antitumor effects on NQO1-positive cancer cells by inducing immunogenic cell death (ICD) and enhancing tumor immunogenicity. However, the interaction between ß-Lap-mediated antitumor immune responses and neutrophils, novel antigen-presenting cells (APCs), remains unknown. This study demonstrates that ß-Lap selectively kills NQO1-positive murine tumor cells by significantly increasing intracellular ROS formation and inducing DNA double strand breaks (DSBs), resulting in DNA damage. Treatment with ß-Lap efficiently eradicates immunocompetent murine tumors and significantly increases the infiltration of tumor-associated neutrophils (TANs) into the tumor microenvironment (TME), which plays a crucial role in the drug's therapeutic efficacy. Further, the presence of ß-Lap-induced antigen medium leads bone marrow-derived neutrophils (BMNs) to directly kill murine tumor cells, aiding in dendritic cells (DCs) recruitment and significantly enhancing CD8+ T cell proliferation. ß-Lap treatment also drives the polarization of TANs toward an antitumor N1 phenotype, characterized by elevated IFN-ß expression and reduced TGF-ß cytokine expression, along with increased CD95 and CD54 surface markers. ß-Lap treatment also induces N1 TAN-mediated T cell cross-priming. The HMGB1/TLR4/MyD88 signaling cascade influences neutrophil infiltration into ß-Lap-treated tumors. Blocking this cascade or depleting neutrophil infiltration abolishes the antigen-specific T cell response induced by ß-Lap treatment. Overall, this study provides comprehensive insights into the role of tumor-infiltrating neutrophils in the ß-Lap-induced antitumor activity against NQO1-positive murine tumors.
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NAD(P)H Desidrogenase (Quinona) , Naftoquinonas , Neutrófilos , Microambiente Tumoral , Animais , Naftoquinonas/farmacologia , Naftoquinonas/uso terapêutico , NAD(P)H Desidrogenase (Quinona)/metabolismo , NAD(P)H Desidrogenase (Quinona)/genética , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Neutrófilos/imunologia , Camundongos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Camundongos Endogâmicos C57BL , Linhagem Celular Tumoral , Infiltração de Neutrófilos/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Humanos , Feminino , FenótipoRESUMO
High average power and peak power solid-state lasers are of great interest in the field of laser cleaning. In this research, a high peak power laser with over 400 W average power using a multi-mode stable resonator in a diode-pumped Nd:YAG master oscillator power amplifier has been demonstrated. A maximum peak power over 1.08 MW was achieved at a repetition frequency of 5 kHz. Delivery fiber with a 400 µm core diameter was utilized for flexible laser transmission. A prototype of the laser cleaning system was developed and inspiring application effects for paint and mold cleaning were achieved.
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BACKGROUND: Alterations caused by face masks on physiological responses vary among different population groups. This study aimed to investigate whether physically active and sedentary individuals respond differently to face mask use during exercise. METHODS: Sixteen healthy college students were divided into two groups: Physically active group (N.=10; 26.50±2.80 years) and Sedentary group (N.=6; 26.33±2.81 years). They performed three maximal cardiopulmonary exercise test (CPET)s following the Bruce protocol: one without a face mask (NON), one with a surgical mask (SUR) and one with a cloth mask (CLO). Cardiorespiratory parameters and heart rate were monitored continuously during the test. Blood pressure, oxygen saturation and lactate level were measured immediately before and after exertion. RESULTS: Significant differences were found between the Physically active and the Sedentary group in peak VO
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Accumulating evidence emphasizes the critical reciprocity between gut microbiota and intestinal barrier function in maintaining the gastrointestinal homeostasis. Given the fundamental role caused by intestinal permeability, which has been scrutinized as a measurable potential indicator of perturbed barrier function in clinical researches, it seems not surprising that recent decades have been marked by augmented efforts to determine the interaction between intestinal microbes and permeability of the individual. However, despite the significant progress in characterizing intestinal permeability and the commensal bacteria in the intestine, the mechanisms involved are still far from being thoroughly revealed. In the present review, based on multiomic methods, high-throughput sequencing and molecular biology techniques, the impacts of gut microbiota on intestinal permeability as well as their complex interaction networks are systematically summarized. Furthermore, the diseases related to intestinal permeability and main causes of changes in intestinal permeability are briefly introduced. The purpose of this review is to provide a novel prospection to elucidate the correlation between intestinal microbiota and permeability, and to explore a promising solution for diagnosis and treatment of gastrointestinal related diseases.
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Gastroenteropatias , Microbioma Gastrointestinal , Mucosa Intestinal , Permeabilidade , Humanos , Animais , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Gastroenteropatias/microbiologia , Gastroenteropatias/terapia , Gastroenteropatias/metabolismo , Função da Barreira IntestinalRESUMO
BACKGROUND: This cross-sectional study aims to explore whether there exists an interaction between selenium and menopause concerning type 2 diabetes (T2D) prevalence and its related indicators such as fasting blood glucose (FBG) and homeostasis model assessment of insulin resistance (HOMA-IR). METHODS: 150 women aged 35-60 years old were finally analyzed in this study. Multivariate linear or logistic regression modeling was conducted to explore the association of selenium and the prevalence of T2D besides its related indicators. Subgroup analyses were conducted based on menopause status to assess the potential impact on the relationship. RESULTS: In the fully adjusted model, serum selenium was positively associated with FBG (ß: 0.03, CI: 0.01-0.05) and the prevalence of T2D (OR: 1.04, CI: 1.00-1.08). After stratifying the data by menopause status, compared with the postmenopausal women group, as the serum selenium concentrations increased, the FBG concentrations were significantly higher in the premenopausal women group (p for interaction = 0.0020). CONCLUSIONS: The present study found serum selenium was positively associated with FBG and the prevalence of T2D. Furthermore, the relationship between serum selenium and FBG was different in the premenopausal and postmenopausal women. More studies are still needed in the future to verify the relationship as well as to explore the specific mechanisms.
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Glicemia , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Menopausa , Selênio , Humanos , Feminino , Selênio/sangue , Estudos Transversais , Pessoa de Meia-Idade , Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Adulto , Menopausa/sangue , Resistência à Insulina/fisiologia , Jejum/sangue , Prevalência , Pós-Menopausa/sangue , Pré-Menopausa/sangueRESUMO
The marine antifungal peptide epinecidin-1 (EPI) have been shown to inhibit Botrytis cinerea growth, while the molecular mechanism have not been explored based on omics technology. This study aimed to investigate the molecular mechanism of EPI against B. cinerea by transcriptome technology. Our findings indicated that a total of 1671 differentially expressed genes (DEGs) were detected in the mycelium of B. cinerea treated with 12.5 µmol/L EPI for 3 h, including 773 up-regulated genes and 898 down-regulated genes. Cluster analysis showed that DEGs (including steroid biosynthesis, (unsaturated) fatty acid biosynthesis) related to cell membrane metabolism were significantly down-regulated, and almost all DEGs involved in DNA replication were significantly inhibited. In addition, it also induced the activation of stress-related pathways, such as the antioxidant system, ATP-binding cassette transporter (ABC) and MAPK signaling pathways, and interfered with the tricarboxylic acid (TCA) cycle and oxidative phosphorylation pathways related to mitochondrial function. The decrease of mitochondrial related enzyme activities (succinate dehydrogenase, malate dehydrogenase and adenosine triphosphatase), the decrease of mitochondrial membrane potential and the increase content of hydrogen peroxide further confirmed that EPI treatment may lead to mitochondrial dysfunction and oxidative stress. Based on this, we speculated that EPI may impede the growth of B. cinerea through its influence on gene expression, and may lead to mitochondrial dysfunction and oxidative stress.
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Antifúngicos , Peptídeos Catiônicos Antimicrobianos , Botrytis , Transcriptoma , Transcriptoma/fisiologia , Antifúngicos/metabolismo , Peptídeos Catiônicos Antimicrobianos/toxicidade , Botrytis/efeitos dos fármacos , Botrytis/fisiologia , Reação em Cadeia da Polimerase em Tempo Real , Peróxido de Hidrogênio , Expressão Gênica , Transportadores de Cassetes de Ligação de ATP/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno , Mitocôndrias , Estresse OxidativoRESUMO
Carbon catabolite repression (CCR) is a highly conserved mechanism that regulates carbon source utilization in Streptomyces. CCR has a negative impact on secondary metabolite fermentation, both in industrial and research settings. In this study, CCR was observed in the daunorubicin (DNR)-producing strain Streptomyces coeruleorubidus DM, which was cultivated in high concentration of carbohydrates. Unexpectedly, DM exhibited a high ability for anthraquinone glucuronidation biotransformation under CCR conditions with a maximum bioconversion rate of 95% achieved at pH 6, 30°C for 24 h. The co-utilization of glucose and sucrose resulted in the highest biotransformation rate compared to other carbon source combinations. Three novel anthraquinone glucuronides were obtained, with purpurin-O-glucuronide showing significantly improved water solubility, antioxidant activity, and antibacterial bioactivity. Comparative transcript analysis revealed that glucose and sucrose utilization were significantly upregulated as DM cultivated under CCR condition, which strongly enhance the biosynthetic pathway of the precursors Uridine diphosphate glucuronic acid (UDPGA). Meanwhile, the carbon metabolic flux has significantly enhanced the fatty acid biosynthesis, the exhaust of acetyl coenzyme A may lead to the complete repression of the biosynthesis of DNR, Additionally, the efflux transporter genes were simultaneously downregulated, which may contribute to the anthraquinones intracellular glucuronidation. Overall, our findings demonstrate that utilizing CCR can be a valuable strategy for enhancing the biotransformation efficiency of anthraquinone O-glucuronides by DM. This approach has the potential to improve the bioavailability and therapeutic potential of these compounds, opening up new possibilities for their pharmaceutical applications.
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Background: Extracorporeal membrane oxygenation (ECMO) has recently emerged as a critical support system for lung function in patients awaiting lung transplantation. This meta-analysis investigates the prognostic factors of lung transplantation following ECMO bridging therapy. Methods: A comprehensive search was conducted in PubMed, Cochrane Library, Embase, CINAHL, Web of Science, Scopus, and ProQuest databases from inception to August 11, 2023. Included were cohort or case-control studies focusing on prognostic factors of lung transplantation with ECMO bridging therapy. Data extraction was performed independently, and study quality was assessed. A meta-analysis was carried out using RevMan 5.4 and Stata17.0 software to aggregate mortality rates and pertinent prognostic factors of ECMO as a bridge to lung transplantation. Results: The search identified eight trials encompassing 1,086 participants. The prognosis of patients undergoing lung transplantation with ECMO bridging was significantly associated with several factors: prolonged ECMO support [odds ratio 1.07, 95% confidence interval (CI): 1.02-1.12, I2=77%], deterioration in liver and kidney function (odds ratio 3.62, 95% CI: 2.37-5.54, I2=0%), and complications during ECMO (odds ratio 2.24, 95% CI: 1.45-3.44, I2=5%). Conclusions: Prolonged ECMO support, declining liver and kidney functions, and complications during ECMO are vital prognostic factors in lung transplantation following ECMO bridging therapy.
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6-Gingerol (6-G), an active ingredient of ginger with anti-inflammation and anti-oxidation properties, can treat ulcerative colitis (UC). However, its underlying mechanism is still unclear. In this study, the pharmacodynamic evaluation of 6-G for treating UC was performed, and the mechanism of 6-G in ameliorating UC was excavated by plasma metabolomics and network pharmacology analysis, which was further validated by experimental and molecular docking. The results showed that 6-G could notably reduce diarrhea, weight loss, colonic pathological damage, and inflammation in UC mice. Plasma metabolomic results indicated that 6-G could regulate 19 differential metabolites, and its metabolic pathways mainly involved linoleic acid metabolism and arachidonic acid metabolism, which were closely associated with ferroptosis. Moreover, 60 potential targets for 6-G intervention on ferroptosis in UC were identified by network pharmacology, and enrichment analysis revealed that 6-G suppressed ferroptosis by modulating lipid peroxidation. Besides, the integration of metabolomics and network pharmacology showed that the regulation of 6-G on ferroptosis focused on 3 key targets, including ALOX5, ALOX15, and PTGS2. Further investigation indicated that 6-G significantly inhibited ferroptosis by decreasing iron load and malondialdehyde (MDA), and enhanced antioxidant capacity by reducing the content of glutathione disulfide (GSSG) and increasing the levels of superoxide dismutase (SOD) and glutathione (GSH) in UC mice and RSL3-induced Caco-2 cells. Furthermore, molecular docking showed the high affinity of 6-G with the identified 3 key targets. Collectively, this study elucidated the potential of 6-G in ameliorating UC by inhibiting ferroptosis. The integrated strategy also provided a theoretical basis for 6-G in treating UC.
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Catecóis , Colite Ulcerativa , Álcoois Graxos , Ferroptose , Metabolômica , Simulação de Acoplamento Molecular , Farmacologia em Rede , Animais , Ferroptose/efeitos dos fármacos , Camundongos , Álcoois Graxos/farmacologia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Catecóis/farmacologia , Masculino , Humanos , Modelos Animais de Doenças , Zingiber officinale/química , Camundongos Endogâmicos C57BL , Células CACO-2RESUMO
Peach fruit is prone to chilling injury (CI) during low-temperature storage, resulting in quality deterioration and economic losses. Our previous studies have found that exogenous trehalose treatment can alleviate the CI symptoms of peach by increasing sucrose accumulation. The purpose of this study was to explore the potential molecular mechanism of trehalose treatment in alleviating CI in postharvest peach fruit. Transcriptome analysis showed that trehalose induced gene expression in pathways of plant MAPK signaling, calcium signaling, and reactive oxygen species (ROS) signaling. Furthermore, molecular docking analysis indicated that PpCDPK24 may activate the ROS signaling pathway by phosphorylating PpRBOHE. Besides, PpWRKY40 mediates the activation of PpMAPKKK2-induced ROS signaling pathway by interacting with the PpRBOHE promoter. Accordingly, trehalose treatment significantly enhanced the activities of antioxidant-related enzymes such as superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and gluathione reductase (GR), as well as the transcription levels AsA-GSH cycle related gene, which led to the reduction of H2O2 and malondialdehyde (MDA) content in peach during cold storage. In summary, our results suggest that the potential molecular mechanism of trehalose treatment is to enhance antioxidant capacity by activating CDPK-mediated Ca2 + -ROS signaling pathway and WRKY-mediated MAPK-WRKY-ROS signaling pathway, thereby reducing the CI in peach fruit.
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Antioxidantes , Temperatura Baixa , Frutas , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Prunus persica , Espécies Reativas de Oxigênio , Transdução de Sinais , Trealose , Trealose/farmacologia , Trealose/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Simulação de Acoplamento Molecular , Malondialdeído/metabolismoRESUMO
BACKGROUND: Glioblastoma multiforme (GBM) is identified as one of the most prevalent and malignant brain tumors, characterized by poor treatment outcomes and a limited prognosis. CMTM6, a membrane protein, has been found to upregulate the expression of programmed cell death 1 ligand 1 protein (PD-L1) and acts as an immune checkpoint inhibitor by inhibiting the programmed death 1 protein/PD-L1 signaling pathway. Recent research has demonstrated a high expression of CMTM6 in GBM, suggesting its potential role in influencing the pathogenesis and progression of GBM, as well as its association with immune cell infiltration in the tumor microenvironment. However, the underlying mechanism of CMTM6 in GBM requires further investigation. METHODS: Data from cancer patients in The Cancer Genome Atlas, Gene Expression Omnibus and Chinese Glioma Genome Atlas cohorts were consolidated for the current study. Through multi-omics analysis, the study systematically examined the expression profile of CMTM6, epigenetic modifications, prognostic significance, biological functions, potential mechanisms of action and alterations in the immune microenvironment. Additionally, the study investigated CMTM6 expression in GBM cell lines and normal cells using reverse transcription PCR and western blot analysis. The impact of CMTM6 on GBM cell proliferation, migration and invasion was evaluated using a combination of cell counting kit-8 assay, clone formation assay, 5-ethynyl-2'-deoxyuridine incorporation assay, wound healing assay and Transwell assay. In order to explore the mechanism of CMTM6, the Wnt/ß-catenin signaling pathway and autophagy-related genes were further verified through western blot analysis. RESULTS: CMTM6 is highly expressed in multiple tumors, particularly GBM. CMTM6 has been shown to be a valuable diagnostic and prognostic biomarker by various bioinformatics approaches. Additionally, CMTM6 plays a pivotal role in the pathogenesis of cancer, specifically GBM, by modulating various biological processes such as DNA methyltransferase expression, RNA modification, copy number variation, genomic heterogeneity, tumor stemness and DNA methylation. The findings of the experiment indicate a significant correlation between elevated CMTM6 expression and the proliferation, invasion, migration and autophagy of GBM cells, with potential key roles mediated through the Wnt/ß-catenin signaling pathway. Furthermore, CMTM6 is implicated in modulating tumor immune cell infiltration and is closely linked to the expression of various immune checkpoint inhibitors and immune modulators, particularly within the context of GBM. High levels of CMTM6 expression also enhance the responsiveness of GBM patients to radiotherapy and chemotherapy, thereby offering valuable insights for guiding treatment strategies for GBM. CONCLUSIONS: Autophagy-related CMTM6 is highly expressed in various types of cancer, especially GBM, and it can regulate GBM progression through the Wnt/ß-catenin signaling pathway and is capable of being used as an underlying target for the diagnosis, treatment selection and prognosis of patients with GBM.