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Berberine (BBR), as a natural isoquinoline alkaloid, has demonstrated various pharmacological activities, and is widely applied in the treatment of diseases. The quantitative analysis of BBR is important for pharmacological studies and clinical applications. In this work, utilizing the specific interaction between BBR and triplex DNA, a sensitive and selective fluorescent detecting method was established with DNA-templated silver nanoclusters (DNA-AgNCs). After binding with the triplex structure in the template of DNA-AgNCs, BBR quenched the fluorescence of DNA-AgNCs and formed BBR-triplex complex with yellow-green fluorescence. The ratiometric fluorescence signal showed a linear relationship with BBR concentration in a range from 10 nM to 1000 nM, with a detection limit of 10 nM. Our method exhibited excellent sensitivity and selectivity, and was further applied in BBR detection in real samples.
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Berberina , DNA , Nanopartículas Metálicas , Prata , Espectrometria de Fluorescência , Berberina/química , Berberina/análise , Prata/química , Nanopartículas Metálicas/química , DNA/química , DNA/análise , Espectrometria de Fluorescência/métodos , Fluorescência , Limite de Detecção , HumanosRESUMO
AIM: Choosing the initial treatment for type 2 diabetes (T2D) is pivotal, requiring consideration of solid clinical evidence and patient characteristics. Despite metformin's historical preference, its efficacy in preventing cerebrovascular events lacked empirical validation. This study aimed to evaluate the associations between first-line monotherapy (metformin or non-metformin antidiabetic medications) and cerebrovascular complications in patients with T2D without diabetic complications. METHODS: We analysed 9090 patients with T2D without complications who were prescribed either metformin or non-metformin medications as initial therapy. Propensity score matching ensured group comparability. Cox regression analyses, stratified by initial metformin use, assessed cerebrovascular disease risk, adjusting for multiple covariates and using competing risk analysis. Metformin exposure was measured using cumulative defined daily doses. RESULTS: Metformin users had a significantly lower crude incidence of cerebrovascular diseases compared with non-users (p < .0001). Adjusted hazard ratios (aHRs) consistently showed an association between metformin use and a lower risk of overall cerebrovascular diseases (aHRs: 0.67-0.69) and severe events (aHRs: 0.67-0.69). The association with reduced risk of mild cerebrovascular diseases was significant across all models (aHRs: 0.73-0.74). Higher cumulative defined daily doses of metformin correlated with reduced cerebrovascular risk (incidence rate ratio: 0.62-0.94, p < .0001), indicating a dose-dependent effect. CONCLUSION: Metformin monotherapy is associated with a reduced risk of cerebrovascular diseases in early-stage T2D, highlighting its dose-dependent efficacy. However, the observed benefits might also be influenced by baseline differences and the increased risks associated with other medications, such as sulphonylureas. These findings emphasize the need for personalized diabetes management, particularly in mitigating cerebrovascular risk in early T2D stages.
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Transtornos Cerebrovasculares , Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Metformina , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Metformina/uso terapêutico , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Feminino , Masculino , Pessoa de Meia-Idade , Transtornos Cerebrovasculares/prevenção & controle , Transtornos Cerebrovasculares/epidemiologia , Idoso , Incidência , Fatores de Risco , Angiopatias Diabéticas/prevenção & controle , Angiopatias Diabéticas/epidemiologiaRESUMO
To address the challenges posed by solid waste generated from coal gasification ash, a pyrolysis self-activation method was employed to prepare activated carbon by gasification ash, followed by the modification with manganese oxide to enhance its adsorption performance. Subsequently, the removal efficiency and mechanism for copper citrate were investigated. The results demonstrated the successful preparation of manganese oxides modified gasification ash-derived activated carbon (GAC-MnOx), exhibiting a specific surface area of 158.3 m2/g and a pore volume of 0.1948 cm³/g. The kinetic process could be described by the pseudo-second-order kinetic model (R2 = 0.958). High removal efficiency and low concentration of dissolved Mn were observed within the pH range of 3-10, where the adsorption capacity of GAC-MnOx for copper citrate exhibited an inverse relationship with pH. Notably, the fitting results of the Langmuir model demonstrated that the maximum adsorption capacity of GAC-MnOx for copper citrate is determined to be 7.196 mg/g at pH 3. The adsorption capacity of GAC-MnOx was found to be significantly reduced to 0.26 mg/g as the pH decreased below 2, potentially attributed to the dissolution of Mn. The findings of the Dual-Mode model demonstrated that the copper citrate removal mechanism by GAC-MnOx involved both surface adsorption and precipitation processes as follows: the porous structure of activated carbon enables physical adsorption of copper citrate, the MnOx or oxygen-containing functional groups establish chemical bonds with copper citrate and subsequently precipitate onto the surface of the adsorbent. The physical adsorption remains predominant in the removal of copper citrate, despite a gradual decrease in its proportion with increasing pH and equilibrium concentrations. Moreover, the X-ray photoelectron spectroscopy results indicated that copper citrate might be oxidized by MnOx to release copper ions and be retained on the surface of the adsorbent, meaning the adsorption efficiency of Cu(II)-Cit by GAC was enhanced through MnOx oxidation. This study could provide a new strategy for the high-value resource utilization of gasification ash.
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Compostos de Manganês , Óxidos , Adsorção , Compostos de Manganês/química , Óxidos/química , Carbono/química , Carvão Vegetal/química , Cinética , Cobre/química , Concentração de Íons de HidrogênioRESUMO
Food safety and human health remain significant concerns in the food industry. Detecting food contaminants and diagnosing diseases are critical aspects. Ferritin, an iron storage protein widely found in nature, offers unique advantages. Its hollow protein nanocage structure, distinct interfaces, hydrophobic or hydrophilic channels, and B-C loop regions recognized by transferrin receptor 1 make ferritin versatile for detecting heavy metals, free radicals, and bioimaging both in vitro and in vivo. This review summarizes ferritin's general characteristics, its specific properties as biosensors, and its applications in food safety and in vivo imaging. It emphasizes not only ferritin's role in detecting heavy metals like mercury and chemical hazards but also its potential in early diagnosing chronic diseases such as tumors, macrophages, and kidney diseases. Further research into ferritin promises advancements in enhancing food safety and improving human health diagnostics.
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Técnicas Biossensoriais , Ferritinas , Ferritinas/química , Humanos , Técnicas Biossensoriais/métodos , Animais , Nanoestruturas/química , Metais Pesados/química , Inocuidade dos Alimentos , Contaminação de Alimentos/análiseRESUMO
The E2F transcription factor family, whose members are encoded by the E2F1-E2F8 genes, plays pivotal roles in the cell cycle, apoptosis, metabolism, stemness, metastasis, aging, angiogenesis, tumor promotion or suppression, and other biological processes. The activity of E2Fs is regulated at multiple levels, with posttranslational modifications being an important regulatory mechanism. There are numerous types of posttranslational modifications, among which phosphorylation, acetylation, methylation, ubiquitination, SUMOylation, neddylation, and poly(ADP-ribosyl)ation are the most commonly studied in the context of the E2F family. Posttranslational modifications of E2F family proteins regulate their biological activity, stability, localization, and interactions with other biomolecules, affecting cell proliferation, apoptosis, DNA damage, etc., and thereby playing roles in physiological and pathological processes. Notably, these modifications do not always act alone but rather form an interactive regulatory network. Currently, several drugs targeting posttranslational modifications are being studied or clinically applied, in which the proteolysis-targeting chimera and molecular glue can target E2Fs. This review aims to summarize the roles and regulatory mechanisms of different PTMs of E2F family members in the physiological state and in cancer and to briefly discuss their clinical significance and potential therapeutic use.
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Fatores de Transcrição E2F , Neoplasias , Processamento de Proteína Pós-Traducional , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Neoplasias/metabolismo , Animais , Fatores de Transcrição E2F/metabolismo , Fatores de Transcrição E2F/genéticaRESUMO
The intestinal microbiota, comprised of bacteria, archaea, and phages, inhabits the gastrointestinal tract of the organism. Male reproductive sterility is currently a prominent topic in medical research. Increasing research suggests that gut microbiota dysbiosis can result in various reproductive health problems. This article specifically investigates the impact of gut microbiota dysbiosis on male reproductive infertility development. Gut microbiota imbalances can disrupt the immune system and immune cell metabolism, affecting testicular growth and sperm production. This dysfunction can compromise the levels of hormones produced and secreted by the endocrine glands, affecting male reproductive health. Furthermore, imbalance of the gut microbiota can disrupt the gut-brain-reproductive axis, resulting in male reproductive infertility. This article explores how the imbalance of the gut microbiota impacts male reproductive infertility through immune regulation, endocrine regulation, and interactions of the gut-brain-reproductive axis, concluding with recommendations for prevention and treatment.
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PURPOSE: No study has compared 30-day and 90-day adverse postoperative outcomes between old-age patients with and those without sarcopenia. PATIENTS AND METHODS: We categorize elderly patients receiving major surgery into two groups according to the presence or absence of preoperative sarcopenia that were matched at a 1:4 ratio through propensity score matching (PSM). We analyzed 30-day or 90-day adverse postoperative outcomes and mortality in patients with and without sarcopenia receiving major surgery. RESULTS: Multivariate logistic regression analyses revealed that the patients with preoperative sarcopenia were at significantly higher risk of 30-day postoperative mortality (adjusted odds ratio [aOR]. = 1.25; 95% confidence interval [CI]. = 1.03-1.52) and 30-day major complications such as postoperative pneumonia (aOR = 1.15; 95% CI = 1.00-1.40), postoperative bleeding (aOR = 2.18; 95% CI = 1.04-4.57), septicemia (aOR = 1.31; 95% CI = 1.03-1.66), and overall complications (aOR = 1.13; 95% CI = 1.00-1.46). In addition, surgical patients with sarcopenia were at significantly higher risk of 90-day postoperative mortality (aOR = 1.50; 95% CI = 1.29-1.74) and 90-day major complications such as pneumonia (aOR = 1.27; 95% CI = 1.10-1.47), postoperative bleeding (aOR = 1.90; 95% CI = 1.04-3.48), septicemia (aOR = 1.52; 95% CI = 1.28-1.82), and overall complications (aOR = 1.24; 95% CI = 1.08-1.42). CONCLUSIONS: Sarcopenia is an independent risk factor for 30-day and 90-day adverse postoperative outcomes such as pneumonia, postoperative bleeding, and septicemia and increases 30-day and 90-day postoperative mortality among patients receiving major surgery. No study has compared 30-day and 90-day adverse postoperative outcomes between patients with and those without sarcopenia. We conducted a propensity score?matched (PSM) population-based cohort study to investigate the adverse postoperative outcomes and mortality in patients undergoing major elective surgery with preoperative sarcopenia versus those without preoperative sarcopenia. We demonstrated that sarcopenia is an independent risk factor for 30-day and 90-day adverse postoperative outcomes, such as postoperative pneumonia, bleeding, septicemia, and mortality after major surgery. Therefore, surgeons and anesthesiologists should attempt to correct preoperative sarcopenia, swallowing function, and respiratory muscle training before elective surgery to reduce postoperative complications that contribute to the decrease in surgical mortality.
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Complicações Pós-Operatórias , Sarcopenia , Humanos , Sarcopenia/epidemiologia , Sarcopenia/complicações , Masculino , Idoso , Feminino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Idoso de 80 Anos ou mais , Pontuação de Propensão , Estudos Retrospectivos , Fatores de RiscoRESUMO
Stigmasterol (ST), a phytosterol found in food, has various biological activities. However, the effect of ST on milk synthesis in dairy cows remains unclear. Therefore, bovine primary mammary epithelial cells (BMECs) were isolated, cultured, and treated with ST to determine the effect of ST on milk synthesis. The study revealed that 10 µM ST significantly increased milk synthesis in BMECs by activating the mammalian target of rapamycin (mTOR) signaling pathway. Further investigation revealed that this activation depends on the regulatory role of oxysterol binding protein 5 (ORP5). ST induces the translocation of ORP5 from the cytoplasm to the lysosome, interacts with the mTOR, recruits mTOR to target the lysosomal surface, and promotes the activation of the mTOR signaling pathway. Moreover, ST was found to increase ORP5 protein levels by inhibiting its degradation via the ubiquitin-proteasome pathway. Specifically, the E3 ubiquitin ligase membrane-associated cycle-CH-type finger 4 (MARCH4) promotes the ubiquitination and subsequent degradation of ORP5. ST mitigates the interaction between MARCH4 and ORP5, thereby enhancing the structural stability of ORP5 and reducing its ubiquitination. In summary, ST stabilizes ORP5 by inhibiting the interaction between MARCH4 and ORP5, thereby activating mTOR signaling pathway and enhancing milk synthesis.
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Células Epiteliais , Glândulas Mamárias Animais , Leite , Transdução de Sinais , Serina-Treonina Quinases TOR , Ubiquitinação , Animais , Bovinos , Serina-Treonina Quinases TOR/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Ubiquitinação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Feminino , Glândulas Mamárias Animais/metabolismo , Glândulas Mamárias Animais/citologia , Leite/química , Leite/metabolismo , Receptores de Esteroides/metabolismo , Receptores de Esteroides/genéticaRESUMO
AIM: This cohort study aimed to explore the connection between postoperative hyperactive delirium and major complications in elderly patients undergoing emergency hip fracture surgery. METHODS: Elderly patients aged 65 years and older undergoing emergency hip fracture surgery were included in the study. The presence of postoperative hyperactive delirium was assessed, and logistic regression analysis, following propensity score matching, was conducted to investigate the association between postoperative hyperactive delirium and major complications occurring 30 and 90 days post-surgery. The analysis controlled for potential confounding factors. RESULTS: After propensity score matching, the analysis included 13 590 patients, equally distributed with 6795 in each group. The group experiencing postoperative hyperactive delirium exhibited a significantly elevated risk of 30-day postoperative complications, including acute renal failure, pneumonia, septicemia, and stroke, with adjusted odds ratios ranging from 1.64 to 2.39. Furthermore, this group displayed notably higher rates of 90-day postoperative complications, encompassing mortality, acute renal failure, pneumonia, septicemia, and stroke, with a significantly increased incidence of mortality within 90 days. CONCLUSION: Postoperative hyperactive delirium in elderly patients undergoing emergency hip fracture surgery is significantly linked to an increased risk of major complications at both 30 and 90 days post-surgery. These findings underscore the critical importance of delirium prevention and management in this patient population, offering the potential to reduce the occurrence of postoperative complications. Geriatr Gerontol Int 2024; 24: 730-736.
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Delírio , Fraturas do Quadril , Complicações Pós-Operatórias , Humanos , Fraturas do Quadril/cirurgia , Masculino , Idoso , Feminino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Idoso de 80 Anos ou mais , Delírio/epidemiologia , Delírio/etiologia , Estudos de Coortes , Pontuação de Propensão , Fatores de Risco , Incidência , Estudos RetrospectivosRESUMO
Repeated sevoflurane exposure in neonatal mice can leads to neuronal apoptosis and mitochondrial dysfunction. The mitochondria are responsible for energy production to maintain homeostasis in the central nervous system. The mitochondria-associated endoplasmic reticulum membrane (MAM) is located between the mitochondria and endoplasmic reticulum (ER), and it is critical for mitochondrial function and cell survival. MAM malfunction contributes to neurodegeneration, however, whether it is involved in sevoflurane-induced neurotoxicity remains unknown. Our study demonstrated that repeated sevoflurane exposure induced mitochondrial dysfunction and dampened the MAM structure. The upregulated ER-mitochondria tethering enhanced Ca2+ transition from the cytosol to the mitochondria. Overload of mitochondrial Ca2+ contributed to opening of the mitochondrial permeability transition pore (mPTP), which caused neuronal apoptosis. Mitofusin 2(Mfn2), a key regulator of ER-mitochondria contacts, was found to be suppressed after repeated sevoflurane exposure, while restoration of Mfn2 expression alleviated cognitive dysfunction due to repeated sevoflurane exposure in the adult mice. These evidences suggest that sevoflurane-induced MAM malfunction is vulnerable to Mfn2 suppression, and the enhanced ER-mitochondria contacts promotes mitochondrial Ca2+ overload, contributing to mPTP opening and neuronal apoptosis. This paper sheds light on a novel mechanism of sevoflurane-induced neurotoxicity. Furthermore, targeting Mfn2-mediated regulation of the MAM structure and mitochondrial function may provide a therapeutic advantage in sevoflurane-induced neurodegeneration.
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Retículo Endoplasmático , GTP Fosfo-Hidrolases , Mitocôndrias , Sevoflurano , Animais , Sevoflurano/toxicidade , Sevoflurano/farmacologia , GTP Fosfo-Hidrolases/metabolismo , Camundongos , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Camundongos Endogâmicos C57BL , Apoptose/efeitos dos fármacos , Anestésicos Inalatórios/toxicidade , Anestésicos Inalatórios/farmacologia , Masculino , Cálcio/metabolismo , Membranas Intracelulares/efeitos dos fármacos , Membranas Intracelulares/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/efeitos dos fármacosRESUMO
BACKGROUND AND HYPOTHESIS: The potential role of anesthesia as an independent risk factor for childhood bipolar disorder (BD) remains unclear. To address this, we conducted a population-based cohort study employing propensity score matching to compare BD incidence between pediatric patients undergoing surgery with and without general anesthesia. STUDY DESIGN: Our study included patients aged 0-3 years who received at least 1 episode of general anesthesia and were hospitalized for over 1 day in Taiwan between January 2004 and December 2014. They were matched 1:1 with a population not receiving general anesthesia to assess pediatric BD incidence. STUDY RESULTS: The study cohort comprised 15 070 patients, equally distributed between the general anesthesia and nongeneral anesthesia groups (7535 each). Multivariate Cox regression analysis revealed adjusted hazard ratios (aHRs; 95% CIs) for pediatric BD in the general anesthesia group as 1.26 (1.04-1.54; Pâ =â .021) compared to the nongeneral anesthesia group. Moreover, the incidence rate ratio (95% CI) for the general anesthesia group was 1.26 (1.03-1.53) compared to the nongeneral anesthesia group. CONCLUSIONS: Early childhood exposure to general anesthesia is significantly associated with an increased risk of pediatric BD. This expands understanding of pediatric BD's complex development, informing preventive strategies, and enhancing mental health outcomes for vulnerable young patients and global pediatric healthcare.
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Anestesia Geral , Transtorno Bipolar , Pontuação de Propensão , Humanos , Anestesia Geral/efeitos adversos , Anestesia Geral/estatística & dados numéricos , Lactente , Transtorno Bipolar/epidemiologia , Feminino , Masculino , Taiwan/epidemiologia , Pré-Escolar , Incidência , Recém-Nascido , Estudos de Coortes , Fatores de RiscoRESUMO
OBJECTIVE: This study investigated the association between aspirin use and diabetes-associated dementia in older patients with type 2 diabetes mellitus (T2DM), assessing aspirin's potential protective effects, intensity of use, and dose-dependency against dementia. DESIGN: A cohort study evaluating the dose-dependent protective impact of aspirin against dementia in a population-based sample. SETTING AND PARTICIPANTS: Older patients with T2DM (≥60 years), comparing aspirin users with nonusers. METHODS: Used a time-varying Cox hazards model to assess dementia incidence. RESULTS: Older aspirin users exhibited a significant reduction in dementia risk (adjusted hazard ratio [aHR], 0.44; 95% CI, 0.41-0.46). The lowest aHRs for dementia were observed at a daily intensity of 0.91 defined daily doses (DDDs), and higher daily dosages (>0.91 DDD) showed gradually increasing aHRs (although still <1). Analysis of cumulative DDD revealed a dose-response relationship, with progressively lower aHRs across quartiles (0.16, 0.42, 0.57, and 0.63 for quartiles 4, 3, 2, and 1, respectively) compared with never aspirin users (P for trend < .0001). CONCLUSIONS AND IMPLICATIONS: Aspirin use in older patients with T2DM significantly reduces dementia risk. The optimal daily intensity of aspirin use (0.91 DDD) is associated with the lowest aHR for dementia. These findings suggest a dose-dependent relationship, supporting the potential benefits of higher cumulative dosages of aspirin in reducing dementia risk in this population.
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Aspirina , Demência , Diabetes Mellitus Tipo 2 , Relação Dose-Resposta a Droga , Humanos , Aspirina/administração & dosagem , Aspirina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Demência/prevenção & controle , Demência/epidemiologia , Masculino , Feminino , Idoso , Estudos de Coortes , Idoso de 80 Anos ou mais , Modelos de Riscos Proporcionais , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND PURPOSE: The classic Shamblin system fails to provide valuable guidance in many Shamblin's III carotid body tumors (III-CBTs) due to the variable forms of carotid arteries and the complex anatomic relationships in parapharyngeal space. We proposed a modified classification to separately divide III-CBTs into different subgroups on the basis of arterial relevant features and anatomical relevant features. MATERIALS AND METHODS: From 2020 to 2023, a total of 129 III-CBTs at a single institution were retrospectively analyzed. All cases were independently classified as arterial-relevant and anatomical-relevant subgroups. The pre-, peri- and postoperative data were summarized and compared accordingly. RESULTS: Among the 129 cases, 69 cases were identified as "Classical type", 23 cases as "Medial type", 27 cases as "Lateral type" and 10 cases as "Enveloped type" according to arterial morphologies. Besides, 76 cases were identified as "Common type", 15 cases as "Pharynx- invasion type", 18 cases as "Skull base-invasion type" and 20 cases as "Mixed type" according to anatomical relationships. "Enveloped type" of tumors in arterial-relevant classification and "Mixed type" of tumors in anatomical-relevant classification are the most challenging cases for surgeons with the lowest resection rate, highest incidence of carotid arteries injury and postoperative stroke. CONCLUSION: The modified classifications provide comprehensive understanding of different III-CBTs which are applicable for individualized treatment in clinical practice.
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Tumor do Corpo Carotídeo , Humanos , Tumor do Corpo Carotídeo/cirurgia , Tumor do Corpo Carotídeo/patologia , Estudos Retrospectivos , Procedimentos Cirúrgicos Vasculares , Artérias Carótidas/patologia , Incidência , Resultado do TratamentoRESUMO
Derived from hazelnuts, hazel leaf has been utilized in traditional folk medicine for centuries in countries such as Portugal, Sweden, and Iran. In our previous investigations, we conducted a preliminary assessment of the hazel leaf polyphenol extract (referred to as ZP) and identified nine compounds, such as kaempferol and chlorogenic acid, in its composition. ZP has shown promising properties as an antioxidant and anti-inflammatory agent. Our research has revealed that ZP has protective effects against cisplatin-induced acute kidney injury (AKI). We conducted a comprehensive examination of both the pathological and ultrastructural aspects and found that ZP effectively ameliorated renal tissue lesions and mitigated mitochondrial damage. Moreover, ZP significantly suppressed malondialdehyde levels while increasing glutathione and catalase concentrations in the kidneys of AKI-induced mice. ZP decreased the number of apoptotic cells and decreased pro-apoptotic protein expression in the kidneys of mice and human renal tubular epithelial cells (HK-2). Furthermore, treatment with ZP increased the levels of proteins marking anti-ferroptosis, such as GPX4, FTH1, and FSP1, in experiments both in vivo and in vitro. We elucidated the underlying mechanisms of ZP's actions, revealing its inhibitory effect on Yap phosphorylation and its regulation of Lats expression, which exert a protective influence on the kidneys. Furthermore, we found that inhibiting the Hippo pathway compromised ZP's nephroprotective effects in both in vitro and in vivo studies. In summary, this research shows that ZP exhibits renoprotective properties, effectively reducing oxidative damage, apoptosis, and ferroptosis in the kidneys by targeting the Hippo pathway.
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Injúria Renal Aguda , Cisplatino , Ferroptose , Via de Sinalização Hippo , Extratos Vegetais , Folhas de Planta , Polifenóis , Transdução de Sinais , Animais , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/induzido quimicamente , Ferroptose/efeitos dos fármacos , Cisplatino/efeitos adversos , Polifenóis/farmacologia , Polifenóis/química , Camundongos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Humanos , Transdução de Sinais/efeitos dos fármacos , Folhas de Planta/química , Proteínas Serina-Treonina Quinases/metabolismo , Masculino , Linhagem Celular , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Estresse Oxidativo/efeitos dos fármacosRESUMO
Autoimmune hepatitis (AIH) is a severe immune-mediated inflammatory liver disease that currently lacks feasible drug treatment methods. Our study aimed to evaluate the protective effect of succinic acid against AIH and provide a reliable method for the clinical treatment of AIH. We performed an in vivo study of the effects of succinic acid on concanavalin A (ConA)-induced liver injury in mice. We examined liver transaminase levels, performed hematoxylin and eosin (HE) staining, and observed apoptotic phenotypes in mice. We performed flow cytometry to detect changes in the number of neutrophils and monocytes, and used liposomes to eliminate the liver Kupffer cells and evaluate their role. We performed bioinformatics analysis, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and western blotting to detect mitochondrial apoptosis-induced changes in proteins from the B-cell lymphoma 2(Bcl-2) family. Succinic acid ameliorated ConA-induced AIH in a concentration-dependent manner, as reflected in the survival curve. HE and TUNEL staining and terminal deoxynucleotidyl transferase dUTP nick end labeling revealed decreased alanine transaminase and aspartate aminotransferase levels, and reduced liver inflammation and apoptosis. RT-qPCR and enzyme-linked immunosorbent assay revealed that succinic acid significantly reduced liver pro-inflammatory cytokine levels. Flow cytometry revealed significantly decreased levels of liver neutrophils. Moreover, the protective effect of succinic acid disappeared after the Kupffer cells were eliminated, confirming their important role in the effect. Bioinformatics analysis, RT-qPCR, and western blotting showed that succinic acid-induced changes in proteins from the Bcl-2 family involved mitochondrial apoptosis, indicating the molecular mechanism underlying the protective effect of succinic acid. Succinic acid ameliorated ConA-induced liver injury by regulating immune balance, inhibiting pro-inflammatory factors, and promoting anti-apoptotic proteins in the liver. This study provides novel insights into the biological functions and therapeutic potential of succinic acid in the treatment of autoimmune liver injury.
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This study investigates the association between postoperative agitated delirium and the risk of dementia in patients who were cognitively intact before undergoing major inpatient surgery. The study included inpatients aged 20 years or older who underwent major surgery requiring general, epidural, or spinal anaesthesia and hospitalization for over one day in Taiwan between 2008 and 2018. Patients were categorized into two groups based on the presence or absence of postoperative agitated delirium. Propensity score matching was conducted to balance various covariates known to influence dementia risk. The final analysis included 10 932 patients (5466 in each group). Multivariate Cox regression analysis was performed to assess the risk of dementia, and incidence rates and incidence rate ratios were calculated. After Propensity score matching, the study cohort comprised 5467 patients without postoperative agitated delirium and 5467 patients with postoperative agitated delirium. In the multivariate Cox regression analysis, the adjusted hazard ratio for dementia were 1.26 (95% confidence intervals, 1.08-1.46; P = 0.003) in the postoperative agitated delirium group compared to the no postoperative agitated delirium group. The incidence rates of dementia was significantly higher in patients with postoperative agitated delirium (97.65 versus 70.85 per 10 000 person-years), with an incidence rate ratio of 1.21 (95% CI: 1.04-1.40). Our study demonstrates a substantial rise in dementia incidence linked to postoperative agitated delirium. These findings stress the need for effective prevention and management strategies. Addressing this issue emerges as a vital clinical approach to reduce subsequent dementia risk, with broad implications for enhancing overall perioperative patient outcomes.
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This study investigated the link between the adapted diabetes complication severity index at the time of type 2 diabetes mellitus diagnosis and diabetes-induced dementia risk in elderly patients. Elderly type 2 diabetes mellitus patients (age ≥ 60) were matched using propensity score matching. Cox regression was used to determine dementia hazard ratios; Kaplan-Meier method to assess cumulative incidence. The cohort included 256 214 elderly type 2 diabetes mellitus patients. Adapted diabetes complication severity index ≥ 1 showed higher dementia risk (adjusted hazard ratio: 1.30; 95% confidence interval: 1.27-1.34), increasing by 1.17-fold per adapted diabetes complication severity index point. Dementia risk rose progressively across adapted diabetes complication severity index scores (P < 0.0001). Higher adapted diabetes complication severity index scores at the time of type 2 diabetes mellitus diagnosis elevated dementia risk in elderly patients. Adapted diabetes complication severity index ≥ 1 is linked to increased dementia risk. Adapted diabetes complication severity index evaluation at the time of type 2 diabetes mellitus diagnosis could predict risk, aiding early interventions. Effective diabetes management is crucial for reducing dementia risk in this population.
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In recent years, sevoflurane and isoflurane are the most popular anesthetics in general anesthesia for their safe, rapid onset, and well tolerant. Nevertheless, many studies reported their neurotoxicity among pediatric and aged populations. This effect is usually manifested as cognitive impairment such as perioperative neurocognitive disorders. The wide application of sevoflurane and isoflurane during general anesthesia makes their safety a major health concern. Evidence indicates that iron dyshomeostasis and ferroptosis may establish a role in neurotoxicity of sevoflurane and isoflurane. However, the mechanisms of sevoflurane- and isoflurane-induced neuronal injury were not fully understood, which poses a barrier to the treatment of its neurotoxicity. We, therefore, reviewed the current knowledge on mechanisms of iron dyshomeostasis and ferroptosis and aimed to promote a better understanding of their roles in sevoflurane- and isoflurane-induced neurotoxicity.
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Anestésicos Inalatórios , Ferroptose , Isoflurano , Éteres Metílicos , Humanos , Criança , Idoso , Isoflurano/efeitos adversos , Sevoflurano/efeitos adversos , Anestésicos Inalatórios/efeitos adversos , Transtornos Neurocognitivos , HomeostaseRESUMO
Black carbon (BC) exhibits promising potential as a sediment amendment owing to its commendable adsorption capacity for hydrophobic organic contaminants (HOCs), thereby resulting in HOC-laden sediments. Desorption kinetic studies play a crucial role in comprehending the release potential of HOCs from BC-sediment systems. Although the adsorption capacity of BC for HOCs has been found to decrease with aging, there is limited research on its impact on HOC desorption kinetics. In this study, BCs derived from agricultural waste (rice straw carbon, RC) and industrial waste (fly ash carbon, FC), respectively, were used to investigate the desorption kinetics of nonylphenol (NP). Additionally, a predictive model was established using the fitting parameters obtained from the modified two-domain model. The results showed that desorption of NP was divided into three fractions: rapid fraction (Frap), slow fraction (Fslow) and resistant fraction (Fr). BCs significantly decreased, while ageing increased the desorption amount and rate of NP. The performance of RC in controlling NP release was superior to that of FC. The predicted values calculated by the established model exhibit significant positive correlations with the measured values (p < 0.01). Additionally, the correlation analysis between sorption sites and desorption fractions revealed that the concentration of NP in the desorbing fraction was nearly equivalent to that of NP in partition sites within aged sediment/FC-sediment systems. However, the aged RC-sediment systems do not conform well to this rule. In other words, the estimation of NP release risk from sediments with a strong adsorbent would be overestimated, if Frap + Fsolw is considered equivalent to the desorbing fraction.
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Sedimentos Geológicos , Fenóis , Cinética , Sedimentos Geológicos/química , Fenóis/química , Carbono/química , Fuligem/química , AdsorçãoRESUMO
Freeze tolerance is a survival strategy employed by some ectotherms living in extremely cold environments. Some fish in extremely cold areas can recover from their frozen state, but they also have to endure cold stress. Amur sleeper (Perccottus glenii) can recover from a completely frozen state. To explore the response of freeze-resistant fish to low temperatures, we analyzed histological alterations, and antioxidant and carbohydrate-lipid metabolizing enzymes of P. glenii under low temperatures. So far, sensory genes regulating P. glenii during cold stress, freezing, and recovery have not been identified. Ultrastructure results indicated that glycogen content and mitochondrial ridge decreased during cold stress and freezing, whereas the number of endoplasmic reticulum increased during recovery. Plasma glucose and glycerol levels of the three treatment groups significantly increased. Lactate dehydrogenase and pyruvate kinase levels significantly increased during cold stress and freezing, and hexokinase levels significantly increased during cold stress. In total, 30,560 unigenes were found (average length 1724 bp, N50 2843 bp). In addition, 7370 differentially expressed genes (DEGs; including 2938 upregulated genes and 4432 downregulated genes) were identified. KEGG analysis revealed that the DEGs were enriched in carbohydrate and lipid metabolism, lipid synthesis, immune system, and anti-apoptosis. Genes involved in glycolysis and phospholipid metabolism were significantly upregulated during cold stress; genes related to circadian rhythm, oxidative phosphorylation, and lipid synthesis were significantly upregulated during freezing; and genes involved in the immune system and anti-apoptosis were significantly upregulated during recovery. Our results attempt to offer new insights into the physiological mechanisms of complex adaptation in P. glenii and provide useful information for future studies on the mechanism underlying freezing/recovery in animals.