RESUMEN
Capsaicin (CAP), the active ingredient in hot chilli peppers, has anti-inflammatory and hepatoprotection effects. Acute alcoholic liver injury (AALI) is liver damage caused by acute alcohol abuse, which can lead to severe liver lesions and even be life-threatening. Pyroptosis is inflammation-related programmed cell death characterized by membrane rupture and plays a key role in AALI. The endosomal sorting complexes required for transport (ESCRT) proteins can gather at damaged areas of the membrane to facilitate the process of sealing the membrane. In this study, we found that CAP could relieve acute alcohol-induced pyroptosis of hepatocytes in vitro and in vivo. Mechanically, we found that CAP could alleviate acute alcohol-induced pyroptosis by activating the ESCRT-III-dependent membrane repair machinery. Furthermore, the data showed that CAP induced ESCRT-III protein expression by activating transient receptor potential vanilloid member 1 (TRPV1) on the cell membrane and Ca2+ influx. TRPV1 inhibitor capsazepine (CPZ) inhibited the relief effect of CAP on acute alcohol-induced pyroptosis. Overall, these results showed that CAP might activate ESCRT-III-dependent membrane repair machinery through Ca2+ influx, which is regulated by TRPV1 calcium channels, therefore mitigating acute alcohol-induced pyroptosis. Our research provides a new perspective on a naturally active food product to promote cell repair and relieve AALI.
Asunto(s)
Capsaicina , Membrana Celular , Complejos de Clasificación Endosomal Requeridos para el Transporte , Hepatocitos , Piroptosis , Canales Catiónicos TRPV , Piroptosis/efectos de los fármacos , Capsaicina/farmacología , Capsaicina/análogos & derivados , Animales , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Ratones , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Canales Catiónicos TRPV/metabolismo , Humanos , Masculino , Ratones Endogámicos C57BL , Etanol , Hepatopatías Alcohólicas/tratamiento farmacológico , Hepatopatías Alcohólicas/metabolismoRESUMEN
BACKGROUND: Ataxia telangiectasia mutated (ATM), an apical DNA damage response gene, is a commonly mutated gene in tumors, and its mutation could strengthen tumor immunogenicity and alter the expression of PD-L1, which potentially contributes to immune checkpoint inhibitors (ICIs) therapy. METHODS: The characteristics of ATM mutation and its relationship with the ICIs-treated clinical prognosis have been analyzed comprehensively in this paper. The overall frequency of ATM mutations has been found to be 4% (554/10953) in the cancer genome atlas (TCGA) cohort. RESULTS: Both the TMB and MSI levels in patients with ATM mutations were significantly higher than those in patients without mutations (P < 0.0001). The median TMB was positively correlated with the frequency of ATM mutations (r = 0.54, P = 0.003). In the TCGA cohort, patients with ATM mutations had better clinical benefits in terms of overall survival (OS, hazard ratio (HR) = 0.736, 95% CI = 0.623 - 0.869), progression-free survival (PFS, HR = 0.761, 95% CI = 0.652 - 0.889), and disease-free survival (DFS, HR = 0.686, 95% CI = 0.512 - 0.919)] than patients without ATM mutations. Subsequently, the verification results showed ATM mutations to be significantly correlated with longer OS in ICIs-treated patients (HR = 0.710, 95% CI = 0.544 - 0.928). Further exploration indicated ATM mutation to be significantly associated with regulated anti-tumor immunity (P < 0.05). CONCLUSION: Our findings highlight the value of ATM mutation as a promising biomarker to predict ICIs therapy in multiple tumors.
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Proteínas de la Ataxia Telangiectasia Mutada , Biomarcadores de Tumor , Inhibidores de Puntos de Control Inmunológico , Mutación , Neoplasias , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas de la Ataxia Telangiectasia Mutada/genética , Biomarcadores de Tumor/genética , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Neoplasias/genética , PronósticoRESUMEN
Microtubules are recognized as one of the most vital and attractive targets in anticancer therapy. The development of novel tubulin-targeting agents with a new action mechanism is imperative. Based on the hydrophobic tagging strategy, the molecular scaffold of tirbanibulin was selected as tubulin target-binding moiety, subsequent to which a series of target compounds were rationally designed by selecting various combinations of linkers and hydrophobic tags. A set of novel molecules were synthesized and most of them exhibited potent antiproliferative activity against tumor cells in vitro. The most active compound 14b inhibited polymerization of purified recombinant tubulin and induced degradation of α- and ß-tubulin in MCF-7 cells. Notably, following treatment with compound 14b, an unexpected phenomenon of "microtubules fragmentation" was observed via immunofluorescence staining. Furthermore, compound 14b possessed antitumor activity in the 4T1 allograft models with TGI of 74.27 % without significant toxicity. In this work, we report the discovery of novel dual-mechanism tubulin-targeting agents.
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Antineoplásicos , Proliferación Celular , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Polimerizacion , Moduladores de Tubulina , Tubulina (Proteína) , Humanos , Tubulina (Proteína)/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Moduladores de Tubulina/farmacología , Moduladores de Tubulina/síntesis química , Moduladores de Tubulina/química , Polimerizacion/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Estructura Molecular , Animales , Relación Dosis-Respuesta a Droga , Proteolisis/efectos de los fármacos , Ratones , Línea Celular Tumoral , Células MCF-7 , FemeninoRESUMEN
Lactoferrin is widely found in milk and has the ability to bind iron. Previous studies have reported that lactoferrin was effective in the prevention and treatment of acute alcohol-induced liver injury (AALI). Ferroptosis is a recently discovered cell death and is involved in the development of AALI. However, the potential role of lactoferrin in acute alcohol-induced ferroptosis is still unclear. In this study, we observed that lactoferrin (10, 20, and 40 µg/mL) significantly mitigated alcohol (300 mM)-induced injury in vitro. Additionally, lactoferrin (100 and 200 mg/kg BW) significantly alleviated alcohol (4.8 g/kg BW)-induced injury in vivo. Our results showed that lactoferrin inhibited alcohol-induced upregulation of the ferroptosis marker protein ACSL4 and downregulation of GPX4. Meanwhile, lactoferrin treatment successfully reversed the elevated malondialdehyde (MDA) levels and the reduced glutathione (GSH) levels caused by alcohol treatment. These results may indicate that lactoferrin significantly decreased ferroptosis in vivo and in vitro. Lactoferrin has the potential to chelate iron, and our results showed that lactoferrin (20 µg/mL) significantly reduced iron ions and the expression of the ferritin heavy chain (FTH) under FeCl3 (100 µM) treatment. It was demonstrated that lactoferrin had a significant iron-chelating effect and reduced iron overload caused by FeCl3 in AML12 cells. Next, we examined iron content and the expression of iron metabolism marker proteins transferrin receptor (TFR), divalent metal transporter 1 (DMT1), FTH, and ferroportin (FPN). Our results showed that lactoferrin alleviated iron overload induced by acute alcohol. The expression of TFR and DMT1 was downregulated, and FPN and FTH were upregulated after lactoferrin treatment in vivo and in vitro. Above all, the study suggested that lactoferrin can alleviate AALI by mitigating acute alcohol-induced ferroptosis. Lactoferrin may offer new strategies for the prevention or treatment of AALI.
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Hierro , Lactoferrina , Lactoferrina/farmacología , Lactoferrina/uso terapéutico , Hierro/metabolismo , Animales , Ferroptosis/efectos de los fármacos , Hígado/metabolismo , Hígado/efectos de los fármacos , RatonesRESUMEN
Sodium sulfite (SS) is a biological derivative of the air pollutant sulfur dioxide, and is often used as a food and pharmaceutical additive. Improper or excessive SS exposure in liver cell death. The phenomenon of simultaneous regulation of apoptosis, necroptosis, and pyroptosis is defined as PANoptosis. However, the specific types of programmed cell death (PCD) caused by SS and their interconnections remain unclear. In the present study, C57BL/6 mice were orally administered SS for 30 d, consecutively, to establish an in vivo mouse exposure model. AML-12 cells were treated with SS for 24 h to establish an in vitro exposure model. The results showed that SS-induced mitochondrial reactive oxygen species (mtROS) accumulation activated the BAX/Bcl-2/caspase 3 pathway to trigger apoptosis and RIPK1/RIPK3/p-MLKL to trigger necroptosis. Interestingly, ROS-activated p-MLKL perforated not the cell membrane as well as the lysosomal membrane. We determined that p-MLKL mediates lysosomal membrane permeabilization (LMP), resulting in cathepsin B (CTSB) release. Furthermore, knockdown of MLKL, a CTSB inhibitor (CA074-ME) and an NLRP3 inhibitor (MCC950) alleviated SS-induced pyroptosis. In summary, our study showed that SS induced apoptosis and necroptosis though mtROS accumulation, whereas the activation of p-MLKL mediated NLRP3-dependent pyroptosis by causing CTSB leakage through LMP. This study comprehensively explored the mechanism unerlying SS-induced PCD and provided an experimental basis for p-MLKL as a potential regulatory protein in PANoptosis.
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Leucemia Mieloide Aguda , Piroptosis , Sulfitos , Ratones , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Necroptosis , Ratones Endogámicos C57BL , Apoptosis , HígadoRESUMEN
BACKGROUND: The Global Diet Quality Score (GDQS) is a simple and practical dietary metric associated with a number of chronic diseases. The GDQS included various foods related to blood pressure, especially diverse plant-based foods that have shown to lower blood pressure. However, studies on the role of the GDQS in reducing the risk of new-onset hypertension and whether its performance differs from that of other dietary metrics are lacking. OBJECTIVE: We aimed to examine the association between the GDQS and new-onset hypertension and to compare its performance with that of other dietary patterns, including the Plant-based Diet Index (PDI), alternate Mediterranean diet (aMED) score, Alternative Healthy Eating Index-2010, and Dietary Approaches to Stop Hypertension (DASH) score in Chinese adults. METHODS: We included a total of 12,002 participants (5644 males and 6358 females) aged >18 y from the China Health and Nutrition Survey (1997-2015). Dietary intake was estimated using average food intakes from 3 consecutive 24-h dietary recalls. Multivariable relative risks (RRs) were computed for hypertension using modified Poisson regression models. RESULTS: With ≤18 y of follow-up (mean 8.7± 5.4 y), we ascertained 4232 incident cases of hypertension. Compared with participants with a low GDQS score (<15), the multivariable-adjusted RR of hypertension was 0.72 [95% confidence interval (CI): 0.62, 0.83] among participants with a high score (≥23). A 25% increment in the GDQS was associated with a 30% (RR, 0.70; 95% CI: 0.64, 0.76) lower risk of new-onset hypertension, which was comparable with the RRs of new-onset hypertension associated with every 25% increment in the PDI (RR, 0.84; 95% CI: 0.76, 0.93), DASH score (RR, 0.84; 95% CI: 0.78, 0.91), and aMED score (RR, 0.89; 95% CI: 0.84, 0.93). CONCLUSION: A higher GDQS was associated with a lower risk of new-onset hypertension, with comparable associations of new-onset hypertension with PDI, DASH, and aMED scores in Chinese adults.
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Dieta Mediterránea , Enfoques Dietéticos para Detener la Hipertensión , Hipertensión , Adulto , Masculino , Femenino , Humanos , Estudios de Cohortes , Dieta , Hipertensión/epidemiología , Hipertensión/etiología , Dieta SaludableRESUMEN
Excessive alcohol consumption leads to serious liver injury. Necroptosis is a programmed cell death form, which has been confirmed to be involved in alcoholic liver injury. However, the exact mechanism remains still unclear. In this study, we found that ethanol caused hepatocytes necroptosis by activating receptor-interacting serine/threonine-protein kinase 1 and 3 (RIPK1 and RIPK3). Meanwhile, autophagy was activated in ethanol-treated hepatocytes. Accumulative studies have demonstrated a possible link between autophagy and necroptosis. Microtubule-associated protein 1 light chain 3 (LC3), an autophagy marker protein, is essential for autophagosome biogenesis/maturation. But little attention has been paid to its functional role. In this study, we explored whether LC3 was involved in ethanol-induced necroptosis. The data showed that LC3 interacted with RIPK1 and RIPK3 in ethanol-treated AML12 cells and mice liver by co-immunoprecipitation (co-IP) and colocalization assay. Ethanol-induced necrosome formation and subsequent necroptosis were alleviated in hepatocytes by knockdown of LC3 or autophagy inhibitor 3-methyladenine (3-MA). These results demonstrated that LC3 accumulation facilitated the formation of necrosome by LC3-RIPK1 and LC3-RIPK3 interactions, eventually caused hepatocytes necroptosis after acute ethanol exposure. Our current research could potentially offer a new understanding of the intricate mechanisms involved in the development of acute alcoholic liver injury.
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Apoptosis , Necroptosis , Ratones , Animales , Hepatocitos/metabolismo , Hígado/metabolismo , Etanol/toxicidad , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismoRESUMEN
Sodium sulfite is a widely used preservative in the food industry. Ferroptosis has been a newly discovered form of iron-dependent oxidative cell death in recent years. However, the potential connection between sodium sulfite and ferroptosis has not been explored. In our study, we observed the abnormal expression of ferroptosis marker protein in vivo, suggesting that sodium sulfite caused ferroptosis in vivo. Next, our study revealed that sodium sulfite caused the overproduction of mitochondrial reactive oxygen species (mtROS) in the AML-12 cells. It is well established that reactive oxygen species (ROS) can induce lysosomal membrane permeabilization. After lysosomal membrane permeabilization occurs, the outflow of Fe2+ in lysosomes triggers the Fenton reaction and subsequently results in the increase of intracellular ROS level, which is closely related to ferroptosis. As speculated, acridine orange (AO) staining and LysoTracker red staining showed that sodium sulfite-induced lysosomal membrane permeabilization could be alleviated by mtROS scavenger TEMPO. In addition, TEMPO, lysosomal stabilizer mannose, and lysosomal iron chelator deferoxamine (DFO) inhibited sodium sulfite-induced ferroptosis. Overall, the results showed that sodium sulfite induced lysosomal iron efflux through the mtROS-lysosomal membrane permeabilization pathway and eventually led to ferroptosis. Our study might provide a new mechanism for the hepatotoxicity of sodium sulfite and a theoretical basis for the risk assessment of sodium sulfite as a food additive.
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Ferroptosis , Especies Reactivas de Oxígeno/metabolismo , Hierro/metabolismo , Hepatocitos/metabolismo , Lisosomas/metabolismoRESUMEN
Inequality in access to urban green infrastructures has been a major concern among scholars and governments, especially since the COVID-19 outbreak. There is a lack of knowledge on how people respond to the pandemic regarding the usage of green infrastructure in cities. This paper explores the shifts in visitation to parks and trails, two popular green infrastructures in Salt Lake County, Utah, by analyzing the results of a survey conducted during the pandemic. Our conceptualization considers personal and neighborhood-level factors, including personal socioeconomic status, existing inequalities of green infrastructures, urban form, and neighborhood conditions. People who reside close to the city center tend to go to parks more often, while those living in urban edges use trails more. Visiting green infrastructures less often is more likely in areas with higher COVID-19 infection rates. The regression results confirm the importance of neighborhood-level factors and illustrate the intricate elements influencing people's decisions to visit different green infrastructures during the pandemic, which shows non-linear relationships. Richer, white, and younger people seem to enjoy green infrastructures more often, leading to the concern of amplified inequality. Higher COVID-19 cases result in higher demands for green infrastructures, which are not fulfilled during the pandemic, especially for vulnerable communities, leading to spatial exclusion. The results highlight the importance of smart growth, including compact development, public transit, and pocket parks, in promoting the urban resilience of park and trail visits, as they may provide more access opportunities and alternatives to green infrastructures even in the context of the pandemic.
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The determinants of blood pressure variability (BPV) are complex. We aimed to evaluate whether circulating high-sensitivity C-reactive protein (hsCRP) is associated with short-term BPV during the subacute stage of ischemic stroke. In this observational study, a consecutive series of acute ischemic stroke patients who underwent 24 h ambulator blood pressure monitoring (ABPM) during day 4 to 10 after onset were enrolled. Multivariable linear regression models were constructed to assess relationships between hsCRP and BPV. Among a total of 325 patients analyzed, the mean age was 60 years old and 72% were male. The SD, CV, ARV of 24 h SBP and DBP were more likely to be higher in patients with hsCRP ≥ 2 mg/L, and these predispositions remained unchanged in linear regression analyses after adjusting for possible confounding factors, with a dose-response relationship when patients were additionally categorized into quartiles according to hsCRP levels using the lowest quartile as a reference category. In contrast, similar results were observed for the mean of SBP but not the mean of DBP. These results indicate that hsCRP is dose-dependently associated with short-term BPV during the subacute stage of ischemic stroke. These findings suggested that patients with a higher level of hsCRP tended to have larger blood pressure fluctuations.
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Sodium metabisulphite (SMB) is the most used foods and drugs antioxidant among sulfites. So far, there were few studies about its harm, especially in mast cells. Our study was to investigate the effects of SMB on mitophagy and pyroptosis in mast cells. The results revealed that SMB dose-dependently promoted the expressions of NLRP3, GSDMD-N and other marker proteins of pyroptosis. Knockdown of GSDMD, NLRP3 inhibitor, mitophagy activator and mtROS inhibitor all reversed the changes in pyroptosis indicators caused by SMB. Considering the degranulation characteristics of mast cells and the sensitization of sulfite, we examined the effects of the above inhibitors on the degranulation of mast cells caused by SMB. The results showed that SMB-mediated mast cell degranulation was significantly inhibited by the above inhibitors. Meanwhile, we used immunofluorescence co-localization experiments and found that GSDMD pore-forming protein and histamine co-localized near the cell membrane. Overall, evidence suggested that SMB caused pyroptosis by inhibiting mitophagy, leading to mast cell degranulation. These findings are of great significance to the sensitization mechanism of SMB and provide a new insight into SMB toxicology and mast cell degranulation.
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Mastocitos , Proteína con Dominio Pirina 3 de la Familia NLR , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Piroptosis , Mitofagia , SulfitosRESUMEN
SCOPE: Coenzyme Q10 (CoQ10) has become a popular nutritional supplement due to its wide range of beneficial biological effects. Previous meta-analyses show that the attenuation of CoQ10 on inflammatory biomarkers remains controversial. This meta-analysis aims to assess the efficacy and optimal dose of CoQ10 supplementation on inflammatory indicators in the general population. METHODS AND RESULTS: Databases are searched up to December 2022 resulting in 6713 articles, of which 31 are retrieved for full-text assessment and included 1517 subjects. Double-blind randomized controlled trials (RCTs) of CoQ10 supplementation are eligible if they contain C reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). CoQ10 supplementation can significantly reduce the levels of circulating CRP (SMD: -0.40, 95% CI: [-0.67 to -0.13], p = 0.003), IL-6 (SMD: -0.67, 95% CI: [-1.01 to -0.33], p < 0.001), and TNF-α (SMD: -1.06, 95% CI: [-1.59 to -0.52], p < 0.001) and increase the concentration of circulating CoQ10. CONCLUSION: This meta-analysis provides evidence for CoQ10 supplementation to reduce the level of inflammatory mediators in the general population and proposes that daily supplementation of 300-400 mg CoQ10 show superior inhibition of inflammatory factors.
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Interleucina-6 , Factor de Necrosis Tumoral alfa , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Ubiquinona/farmacología , Biomarcadores , Proteína C-Reactiva/análisis , Suplementos DietéticosRESUMEN
Pyroptosis is characterized as gasdermin-mediated programmed death and has received substantial attention in recent years. Excessive hepatocyte pyroptosis could induce acute liver injury, and there is a lack of efficient natural compounds to alleviate it. Ginsenoside Rb1 is the most prevalent ginsenoside in ginseng with a variety of biological activities and is usually added to functional foods. In spite of the numerous beneficial effects ginsenoside Rb1 exerts, its role in hepatocyte pyroptosis is yet unknown. In this study, we found that ginsenoside Rb1 alleviated concanavalin A-induced hepatocyte pyroptosis and inhibited NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation, which is critical for the process of pyroptosis. Furthermore, with the addition of the mitophagy inhibitor cyclosporin A, we proved that ginsenoside Rb1 promoted PINK1/Parkin-mediated mitophagy to alleviate hepatocyte pyroptosis. The further mechanism was that ginsenoside Rb1 activated mitophagy to eliminate damaged mitochondria. With the clearance of damaged mitochondria, reactive oxygen species production decreased, and then NLRP3 inflammasome expression was inhibited. Our finding demonstrated that ginsenoside Rb1 could alleviate hepatocyte pyroptosis by activating mitophagy, which could provide a basis for formulating effective dietary therapy or dietary recommendation.
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Ginsenósidos , Inflamasomas , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Piroptosis , Ginsenósidos/farmacología , Concanavalina A , Mitofagia , Hepatocitos , Especies Reactivas de Oxígeno/metabolismoRESUMEN
We aimed to explore the effect of CD39 expression on CD8+ T cells and on the diagnosis and prognosis of esophageal squamous cell carcinoma (ESCC). The independent prognostic factors for the surgical specimens of the 95 ESCC patients were screened by multivariate Cox regression analysis. Differential gene expression analysis was performed by the NetworkAnalyst platform based on data from the Gene Expression Omnibus (GEO). The expression of CD39 on CD8+ T cells in the CK+ region was higher in cancer tissue than in paracancerous tissue (p = 0.011), and high CD39-expressing CD8+ T cells in the CK+ region (HR, 2.587; p = 0.033) and high CD39-expressing CD8+ T cells in the CK- region (HR, 3.090; p = 0.008) were independent risk factors for prognosis in ESCC patients; the expression of ENTPD1 was upregulated in ESCC tissues compared to normal tissues (adjusted p < 0.001; log2 fold change = 1.99), and its expression was significantly positively correlated with the expression of PDCD1, CTLA4, and HAVCR2. High CD39-expressing CD8+ T cells can be used as a new molecular marker for the diagnosis and prognosis of ESCC, and the restoration of partially exhausted CD8+ T cells by inhibiting CD39 may be a new strategy for treating ESCC.
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We aim to examine the prospective association between the intake of dietary tomatoes and the risk of new-onset hypertension and its modifiable factors in general adults. A total of 11,460 adults without hypertension from the China Health and Nutrition Survey (CHNS) were enrolled, with follow-up beginning in 1997 and ending in 2015. Dietary tomato intake was measured by three consecutive 24-h dietary recalls combined with a household food inventory. The study outcome was new-onset hypertension, defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg or diagnosed by physicians or under anti-hypertensive treatment during the follow-up. Finally, 4015 subjects developed new-onset hypertension during 92,335.5 person-years of follow-up. After multivariate adjustment for dietary and non-dietary risk factors, hazard ratios for increased consumption of dietary tomatoes were 0.42 (95% confidence interval, 0.37−0.47), 0.51 (0.46−0.57), and 0.82 (0.74−0.92) compared with non-consumers. Overall, cubic spline regression suggested a novel J-shaped association between dietary tomato intake and new-onset hypertension, with the lowest risk observed at approximately 10 to 13 g/day (p < 0.001 for curvature). Moreover, the association between dietary tomato intake and risk of new-onset hypertension was stronger in females or individuals who refrained from smoking or drinking (p = 0.024, p = 0.043, and p = 0.044 for interaction, respectively).
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Hipertensión , Solanum lycopersicum , Adulto , Femenino , Humanos , Estudios Prospectivos , Hipertensión/epidemiología , Hipertensión/etiología , Presión Sanguínea , Encuestas NutricionalesRESUMEN
CONTEXT: Previous meta-analyses have suggested that the effects of coenzyme Q10 (CoQ10) on lipid profiles remain debatable. Additionally, no meta-analysis has explored the optimal intake of CoQ10 for attenuating lipid profiles in adults. OBJECTIVE: This study conducted a meta-analysis to determine the effects of CoQ10 on lipid profiles and assess their dose-response relationships in adults. METHODS: Databases (Web of Science, PubMed/Medline, Embase, and the Cochrane Library) were systematically searched until August 10, 2022. The random effects model was used to calculate the mean differences (MDs) and 95% CI for changes in circulating lipid profiles. The novel single-stage restricted cubic spline regression model was applied to explore nonlinear dose-response relationships. RESULTS: Fifty randomized controlled trials with a total of 2794 participants were included in the qualitative synthesis. The pooled analysis revealed that CoQ10 supplementation significantly reduced total cholesterol (TC) (MD -5.53â mg/dL; 95% CI -8.40, -2.66; I2 = 70%), low-density lipoprotein cholesterol (LDL-C) (MD -3.03â mg/dL; 95% CI -5.25, -0.81; I2 = 54%), and triglycerides (TGs) (MD -9.06â mg/dL; 95% CI -14.04, -4.08; I2 = 65%) and increased high-density lipoprotein cholesterol (HDL-C) (MD 0.83â mg/dL; 95% CI 0.01, 1.65; I2 = 82%). The dose-response analysis showed an inverse J-shaped nonlinear pattern between CoQ10 supplementation and TC in which 400-500â mg/day CoQ10 largely reduced TC (χ2 = 48.54, P < .01). CONCLUSION: CoQ10 supplementation decreased the TC, LDL-C, and TG levels, and increased HDL-C levels in adults, and the dosage of 400 to 500â mg/day achieved the greatest effect on TC.
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Suplementos Dietéticos , Adulto , Humanos , HDL-Colesterol , LDL-Colesterol , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Background: Coronavirus disease 2019 (COVID-19) have brought great disaster to mankind, and there is currently no globally recognized specific drug or treatment. Severe COVID-19 may trigger a cytokine storm, manifested by increased levels of cytokines including interleukin-17 (IL-17), so a new strategy to treat COVID-19 may be to use existing IL-17 inhibitors, which have demonstrated efficacy, safety and tolerability in the treatment of psoriasis. However, the use of IL-17 inhibitors in patients with psoriasis during the COVID-19 pandemic remains controversial due to reports that IL-17 inhibitors may increase the risk of respiratory tract infections. Objectives: The systematic review and meta-analysis aimed to evaluate the effect of IL-17 inhibitors on the risk of COVID-19 infection, hospitalization, and mortality in patients with psoriasis. Methods: Databases (including Embase, PubMed, SCI-Web of Science, Scopus, CNKI, and the Cochrane Library) were searched up to August 23, 2022, for studies exploring differences in COVID-19 outcomes between psoriasis patients using IL-17 inhibitors and those using non-biologics. Two authors independently extracted data and assessed the risk of bias in a double-blind manner. The risk ratios (RRs) and 95% confidence intervals (CIs) were calculated and heterogeneities were determined by the Q test and I 2 statistic. And the numbers needed to treat (NNTs) were calculated to assess the clinical value of IL-17 inhibitors in preventing SARS-CoV-2 infection and treating COVID-19. Results: Nine observational studies involving 7,106 participants were included. The pooled effect showed no significant differences in the rates of SARS-CoV-2 infection (P = 0.94; I 2 = 19.5%), COVID-19 hospitalization (P = 0.64; I 2 = 0.0%), and COVID-19 mortality (P = 0.32; I 2 = 0.0%) in psoriasis patients using IL-17 inhibitors compared with using non-biologics. Subgroup analyses grouped by age and COVID-19 cases, respectively, revealed consistent results as above. Meanwhile, the pooled NNTs showed no significant differences between the two groups in the clinical value of preventing SARS-CoV-2 infection and treating COVID-19. Conclusion: The use of IL-17 inhibitors in patients with psoriasis does not increase the risk of SARS-CoV-2 infection or worsen the course of COVID-19. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022335195.
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Tratamiento Farmacológico de COVID-19 , Psoriasis , Humanos , Interleucina-17 , Inhibidores de Interleucina , Pandemias , Anticuerpos Monoclonales/uso terapéutico , SARS-CoV-2 , Psoriasis/tratamiento farmacológico , Hospitalización , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Previous studies have shown beneficial effects of coenzyme Q10 (CoQ10) supplementation on blood pressure (BP). However, the optimal intake of CoQ10 for BP regulation in patients with cardiometabolic disorders is unknown, and its effect on circulating CoQ10 is also unclear. We aimed to assess the dose-response relation between CoQ10 and BP, and quantify the effect of CoQ10 supplementation on the concentration of circulating CoQ10 by synthesizing available evidence from randomized controlled trials (RCTs). A comprehensive literature search was performed in 3 databases (PubMed/MEDLINE, Embase, and Cochrane Library) to 21 March, 2022. A novel 1-stage restricted cubic spline regression model was used to evaluate the nonlinear dose-response relation between CoQ10 and BP. Twenty-six studies comprising 1831 subjects were included in our meta-analysis. CoQ10 supplementation significantly reduced systolic blood pressure (SBP) (-4.77 mmHg, 95% CI: -6.57, -2.97) in patients with cardiometabolic diseases; this reduction was accompanied by a 1.62 (95% CI: 1.26, 1.97) µg/mL elevation of circulating CoQ10 compared with the control group. Subgroup analyses revealed that the effects of reducing SBP were more pronounced in patients with diabetes and dyslipidemia and in studies with longer durations (>12 wk). Importantly, a U-shaped dose-response relation was observed between CoQ10 supplementation and SBP level, with an approximate dose of 100-200 mg/d largely reducing SBP (χ2 = 10.84, Pnonlinearity = 0.004). The quality of evidence was rated as moderate, low, and very low for SBP, diastolic blood pressure (DBP), and circulating CoQ10 according to the Grading of Recommendations, Assessment, Development, and Evaluation approach (GRADE), respectively. The current finding demonstrated that the clinically beneficial effects of CoQ10 supplementation may be attributed to the reduction in SBP, and 100-200 mg/d of CoQ10 supplementation may achieve the greatest benefit on SBP in patients with cardiometabolic diseases. This study was registered on PROSPERO as CRD42021252933.
Asunto(s)
Enfermedades Cardiovasculares , Hipertensión , Humanos , Presión Sanguínea , Ensayos Clínicos Controlados Aleatorios como Asunto , Suplementos Dietéticos , Enfermedades Cardiovasculares/prevención & control , Hipertensión/tratamiento farmacológicoRESUMEN
Background: Previous reviews reported that the effects of CoQ10 on glycemic control were inconsistent. There is no review exploring the optimal intake of CoQ10 for glycemic control. We aimed to investigate the efficacy of CoQ10 on glycemic control and evaluate the dose-response relationship via integrating the existing evidence from randomized control trials (RCTs). Methods: Databases (PubMed, Embase, and Cochrane Library) were searched to identify RCTs for investigating the efficacy of CoQ10 on fasting glucose, fasting insulin, HbA1c, and HOMA-IR up to March 12, 2022. We performed a meta-analysis on 40 RCTs of CoQ10. Weighted mean difference (WMD) and 95% confidence intervals (CIs) were calculated for net changes. Evidence certainty was assessed using GRADE. Dose-response relationships were evaluated using 1-stage restricted cubic spline regression model. The protocol was registered in PROSPERO (CRD42021252933). Findings: Forty studies (n = 2,424 participants) were included in this meta-analysis. CoQ10 significantly reduced fasting glucose (WMD: -5.22 [95% CI: -8.33, -2.11] mg/dl; P <0.001; I2 =95.10%), fasting insulin (-1.32 [-2.06, -0.58] µIU/ml; P < 0.001; I2 =78.86%), HbA1c (-0.12% [-0.23, -0.01]; P =0.04; I2 =49.10%), and HOMA-IR (-0.69 [-1.00, -0.38]; P <0.001; I2 =88.80%). The effect of CoQ10 on outcomes was greater in diabetes with lower heterogeneity. A "U" shape dose-response relationship curve revealed that 100-200 mg/day of CoQ10 largely decreased fasting glucose (χ 2 = 12.08, P nonlinearity =0.002), fasting insulin (χ 2 = 9.73, P nonlinearity =0.008), HbA1c (χ 2 = 6.00, P nonlinearity =0.049), HOMA-IR (χ 2 = 25.89, P nonlinearity <0.001). Interpretation: CoQ10 supplementation has beneficial effects on glycemic control, especially in diabetes, and 100-200 mg/day of CoQ10 could achieve the greatest benefit, which could provide a basis for the dietary guidelines of CoQ10 in patients with glycemic disorders. Funding: This work was supported by the National Natural Science Foundation of China (No. 82030098, 81872617 and 81730090), Shenzhen Science, Technology, and Innovation Commission (No. JCYJ20180307153228190), CNS Research Fund for DRI, and National innovation and entrepreneurship training program for undergraduate student (No. 202210558161).