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1.
Front Endocrinol (Lausanne) ; 15: 1295677, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38572473

RESUMO

The liver plays pivotal roles in nutrient metabolism, and correct hepatic adaptations are required in maternal nutrient metabolism during pregnancy. In this review, hepatic nutrient metabolism, including glucose metabolism, lipid and cholesterol metabolism, and protein and amino acid metabolism, is first addressed. In addition, recent progress on maternal hepatic adaptations in nutrient metabolism during pregnancy is discussed. Finally, the factors that regulate hepatic nutrient metabolism during pregnancy are highlighted, and the factors include follicle-stimulating hormone, estrogen, progesterone, insulin-like growth factor 1, prostaglandins fibroblast growth factor 21, serotonin, growth hormone, adrenocorticotropic hormone, prolactin, thyroid stimulating hormone, melatonin, adrenal hormone, leptin, glucagon-like peptide-1, insulin glucagon and thyroid hormone. Our vision is that more attention should be paid to liver nutrient metabolism during pregnancy, which will be helpful for utilizing nutrient appropriately and efficiently, and avoiding liver diseases during pregnancy.


Assuntos
Insulina , Fígado , Gravidez , Feminino , Humanos , Fígado/metabolismo , Insulina/metabolismo , Hormônio do Crescimento/metabolismo , Glucagon/metabolismo , Nutrientes
2.
Eur J Med Chem ; 271: 116428, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38653068

RESUMO

Recent evidence suggests that histone deacetylases (HDACs) are important regulators of autosomal dominant polycystic kidney disease (ADPKD). In the present study, a series of benzothiazole-bearing compounds were designed and synthesized as potential HDAC inhibitors. Given the multiple participation of HDACs in ADPKD cyst progression, we embarked on a targeted screen using HeLa nuclear extracts to identify potent pan-HDAC inhibitors. Compound 26 emerged as the most efficacious candidate. Subsequent pharmacological characterization showed that compound 26 effectively inhibits several HDACs, notably HDAC1, HDAC2, and HDAC6 (IC50 < 150 nM), displaying a particularly high sensitivity towards HDAC6 (IC50 = 11 nM). The selected compound significantly prevented cyst formation and expansion in an in vitro cyst model and was efficacious in reducing cyst growth in both an embryonic kidney cyst model and an in vivo ADPKD mouse model. Our results provided compelling evidence that compound 26 represents a new HDAC inhibitor for the treatment of ADPKD.

3.
Fitoterapia ; 175: 105960, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38621426

RESUMO

Five undescribed eremophilane-type sesquiterpenes, remophilanetriols E-I (1-5), along with seven known compounds (6-12) were isolated from the fresh roots of Rehmannia glutinosa. Their structures were characterized by extensive spectroscopic data analysis and their absolute configurations were determined by comparing their calculated electronic circular dichroism (ECD) spectra and experimental ECD spectra. The anti-pulmonary fibrosis activities of all compounds were evaluated in vitro by MTT methods, and compounds 2, 8, 10, and 12 exhibited excellent anti-pulmonary fibrosis activities. In addition, compound 2 can reduce the levels of ROS and apoptosis in TGF-ß1-induced BEAS-2B cells.

4.
Biochem Pharmacol ; 224: 116200, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38604258

RESUMO

Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenic kidney disease. Emerging research indicates that the Notch signaling pathway plays an indispensable role in the pathogenesis of numerous kidney diseases, including ADPKD. Herein, we identified that Notch3 but not other Notch receptors was overexpressed in renal tissues from mice with ADPKD and ADPKD patients. Inhibiting Notch3 with γ-secretase inhibitors, which block a proteolytic cleavage required for Notch3 activation, or shRNA knockdown of Notch3 significantly delayed renal cyst growth in vitro and in vivo. Subsequent mechanistic study elucidated that the cleaved intracellular domain of Notch3 (N3ICD) and Hes1 could bind to the PTEN promoter, leading to transcriptional inhibition of PTEN. This further activated the downstream PI3K-AKT-mTOR pathway and promoted renal epithelial cell proliferation. Overall, Notch3 was identified as a novel contributor to renal epithelial cell proliferation and cystogenesis in ADPKD. We envision that Notch3 represents a promising target for ADPKD treatment.

5.
New Phytol ; 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38481316

RESUMO

In terrestrial ecosystems, most plant species can form beneficial associations with arbuscular mycorrhizal (AM) fungi. Arbuscular mycorrhizal fungi benefit plant nutrient acquisition and enhance plant tolerance to drought. The high osmolarity glycerol 1 mitogen-activated protein kinase (HOG1-MAPK) cascade genes have been characterized in Rhizophagus irregularis. However, the upstream receptor of the HOG1-MAPK cascade remains to be investigated. We identify the receptor kinase RiSho1 from R. irregularis, containing four transmembrane domains and one Src homology 3 (SH3) domain, corresponding to the homologue of Saccharomyces cerevisiae. Higher expression levels of RiSho1 were detected during the in planta phase in response to drought. RiSho1 protein was localized in the plasma membrane of yeast, and interacted with the HOG1-MAPK module RiPbs2 directly by protein-protein interaction. RiSho1 complemented the growth defect of the yeast mutant ∆sho1 under sorbitol conditions. Knock-down of RiSho1 led to the decreased expression of downstream HOG1-MAPK cascade (RiSte11, RiPbs2, RiHog1) and drought-resistant genes (RiAQPs, RiTPSs, RiNTH1 and Ri14-3-3), hampered arbuscule development and decreased plants antioxidation ability under drought stress. Our study reveals the role of RiSho1 in regulating arbuscule development and drought-resistant genes via the HOG1-MAPK cascade. These findings provide new perspectives on the mechanisms by which AM fungi respond to drought.

6.
Materials (Basel) ; 17(6)2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38541465

RESUMO

Concurrently achieving high growth rate and high quality in single-crystal diamonds (SCDs) is significantly challenging. The growth rate of SCDs synthesized by microwave plasma chemical vapor deposition (MPCVD) was enhanced by introducing N2 into the typical CH4-H2 gas mixtures. The impact of nitrogen vacancy (NV) center concentration on growth rate, surface morphology, and lattice binding structure was investigated. The SCDs were characterized through Raman spectroscopy, photoluminescence (PL) spectroscopy, and X-ray photoelectron spectroscopy. It was found that the saturation growth rate was increased up to 45 µm/h by incorporating 0.8-1.2% N2 into the gas atmosphere, which is 4.5 times higher than the case without nitrogen addition. Nitrogen addition altered the growth mode from step-flow to bidimensional nucleation, leading to clustered steps and a rough surface morphology, followed by macroscopically pyramidal hillock formation. The elevation of nitrogen content results in a simultaneous escalation of internal stress and defects. XPS analysis confirmed chemical bonding between nitrogen and carbon, as well as non-diamond carbon phase formation at 0.8% of nitrogen doping. Furthermore, the emission intensity of NV-related defects from PL spectra changed synchronously with N2 concentrations (0-1.5%) during diamond growth, indicating that the formation of NV centers activated the diamond lattice and facilitated nitrogen incorporation into it, thereby accelerating chemical reaction rates for achieving high-growth-rate SCDs.

7.
Sci Total Environ ; 925: 171812, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38508267

RESUMO

Salvia miltiorrhiza, a widely used medicinal herb renowned for its properties in promoting blood circulation, removing blood stasis and alleviating pain, is currently facing quality degradation due to excessive heavy metal levels, posing a threat to medication safety. In order to investigate the effects of microbial inoculant, microalgae and biochar on the growth of Salvia miltiorrhiza under copper (Cu) stress, as well as its Cu absorption, antioxidant activity, active component contents and rhizosphere microbial community, a pot experiment was conducted. Salvia miltiorrhiza plants were cultivated in the soil containing 400 mg/kg of Cu for six months and treated with microbial inoculant, microalgae and biochar, either individually or in combination. Almost all soil amendment treatments led to an increase in root biomass. Notably, co-application of microbial inoculant and microalgae had the optimal effect with a 63.07 % increase compared to the group treated solely with Cu. Moreover, when microbial inoculant was applied alone or in combination with microalgae, the Cu content in plant roots was reduced by 19.29 % and 25.37 %, respectively, whereas other treatments failed to show a decreasing trend. Intriguingly, Cu stress increased the active component contents in plant roots, and they could also be enhanced beyond non-stress levels when microbial inoculant and microalgae were applied together or in combination with biochar. Analyses of plant antioxidant activity, soil properties and rhizosphere microorganisms indicated that these amendments may alleviate Cu stress by enhancing peroxidase activity, facilitating plant nutrient absorption, and enriching beneficial microorganisms capable of promoting plant growth and mitigating heavy metal-induced damage. This study suggests that the combined application of microbial inoculant and microalgae can reduce Cu levels in Salvia miltiorrhiza while enhancing its quality under Cu stress.


Assuntos
Inoculantes Agrícolas , Microalgas , Salvia miltiorrhiza , Rizosfera , Antioxidantes/metabolismo , Salvia miltiorrhiza/metabolismo , Carvão Vegetal/metabolismo , Solo , Cobre/toxicidade , Cobre/metabolismo
8.
Comput Biol Med ; 172: 108214, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38508057

RESUMO

Calcific aortic valve disease (CAVD) is a heart valve disorder characterized primarily by calcification of the aortic valve, resulting in stiffness and dysfunction of the valve. CAVD is prevalent among aging populations and is linked to factors such as hypertension, dyslipidemia, tobacco use, and genetic predisposition, and can result in becoming a growing economic and health burden. Once aortic valve calcification occurs, it will inevitably progress to aortic stenosis. At present, there are no medications available that have demonstrated effectiveness in managing or delaying the progression of the disease. In this study, we mined four publicly available microarray datasets (GSE12644 GSE51472, GSE77287, GSE233819) associated with CAVD from the GEO database with the aim of identifying hub genes associated with the occurrence of CAVD and searching for possible biological targets for the early prevention and diagnosis of CAVD. This study provides preliminary evidence for therapeutic and preventive targets for CAVD and may provide a solid foundation for subsequent biological studies.


Assuntos
Estenose da Valva Aórtica , Valva Aórtica/patologia , Calcinose , Doenças das Valvas Cardíacas , Humanos , Estenose da Valva Aórtica/genética , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/epidemiologia , Doenças das Valvas Cardíacas/genética , Calcinose/genética
9.
Food Res Int ; 182: 114188, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38519193

RESUMO

Gelsemium elegans (GE) is a widely distributed hypertoxic plant that has caused many food poisoning incidents. Its pollen can also be collected by bees to produce toxic honey, posing a great threat to the health and safety of consumers. However, for the complex matrices such as cooked food and honey, it is challenging to perform composition analysis. It is necessary to establish more effective strategies for investigating GE contamination. In this study, the real-time PCR (qPCR) analysis combined with DNA barcode matK was proposed for the identification and detection of GE. Fifteen honey samples along with twenty-eight individuals of GE and the common confusable objects Lonicera japonica, Ficus hirta, Stellera chamaejasme and Chelidonium majus were gathered. Additionally, the food mixtures treated with 20-min boiling and 30-min digestion were prepared. Specific primers were designed, and the detection capability and sensitivity of qPCR in honey and boiled and digested food matrices were tested. The results demonstrated that the matK sequence with sufficient mutation sites was an effective molecular marker for species differentiation. GE and the confusable species could be clearly classified by the fluorescence signal of qPCR assay with a high sensitivity of 0.001 ng/µl. In addition, this method was successfully employed for the detection of deeply processed food materials and honey containing GE plants which even accounted for only 0.1 %. The sequencing-free qPCR approach undoubtedly can serve as a robust support for the quality supervision of honey industry and the prevention and diagnosis of food poisoning.


Assuntos
Doenças Transmitidas por Alimentos , Gelsemium , Mel , Abelhas , Animais , Mel/análise , Reação em Cadeia da Polimerase em Tempo Real , Alimento Processado , Plantas
10.
Front Public Health ; 12: 1330194, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38487181

RESUMO

Background: Prehospital emergency care is a critical but often understudied aspect of healthcare. Patient vulnerability in this setting can significantly impact outcomes. The aim of this study was to investigate the vulnerability status and to determine associated affect factors among prehospital emergency patients in China. Methods: In this cross-sectional study conducted in China, from April 2023 to July 2023, we assessed the vulnerability of prehospital emergency patients using the Safety in Prehospital Emergency Care Index (SPECI) scale. We conducted a detailed questionnaire-based survey to gather demographic and disease-related information. We employed the SPECI scale, consisting of two subscales, to evaluate patient vulnerability. Statistical analyses, including t-tests, ANOVA, and multiple linear regression, were used to identify factors associated with vulnerability. Results: The study included a total of 973 prehospital emergency patients, with a response rate of 81.9%. These patients exhibited a low-to-moderate level of vulnerability, with an average SPECI score of 14.46 out of 40. Vulnerability was significantly associated with age (particularly those aged 60 and above), disease severity (severe conditions increased vulnerability), disease type (circulatory diseases correlated with higher vulnerability), alterations in consciousness, and chronic diseases. Unexpectedly, digestive system diseases were negatively correlated with vulnerability. Conclusion: Addressing patient vulnerability in prehospital care is essential. Tailored interventions, EMS provider training, and interdisciplinary collaboration can mitigate vulnerability, especially in older patients and those with severe conditions.


Assuntos
Serviços Médicos de Emergência , Humanos , Idoso , Estudos Transversais , Inquéritos e Questionários , China/epidemiologia
11.
Front Pediatr ; 12: 1348016, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38510081

RESUMO

The symptoms and signs of infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are milder in children than in adults. However, in April 2020, British pediatricians first reported that coronavirus disease 2019 (COVID-19) may present as multisystem inflammatory syndrome in children and adolescents (MIS-C), similar to that observed in Kawasaki disease. MIS-C can be associated with multiple systemic injuries and even death in children. In addition to digestive system involvement, cardiac injury is prominent. This article reviews the pathogenesis, clinical manifestations, and treatment of cardiac injury caused by MIS-C, which may help clinicians in early diagnosis and timely commencement of treatment.

12.
Ren Fail ; 46(1): 2310733, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38357745

RESUMO

AIMS: The effects and relevant mechanisms of Mudan granules in the renal fibrosis of diabetic rats were explored through in vivo experiments, which provided a scientific basis for expanding their clinical indications. METHODS: Male SD rats were given a single intraperitoneal injection of STZ (65 mg/kg) to induce diabetes rat models. After treatment with Mudan granules, the general condition of rats was recorded. Blood glucose, blood lipids, and renal function-related indicators were detected, renal tissue morphological changes and fibrosis-related indicators were observed, and the expression of pathway-related proteins were examined. RESULTS: The general condition of diabetes rats was improved after the treatment of Mudan granules, the 24-h urinary protein and urinary albumin to creatinine ratio were reduced, and the renal function and lipid results were modified. The tissue damage to the rat kidney has been repaired. Expression of TGF-ß1/Smad-related pathway proteins was suppressed in kidney tissues, and the fibrosis factor CO-IV, FN, and LN were reduced in serum. CONCLUSION: Mudan granules may inhibit of TGF-ß1/Smad pathway, inhibit the production of ECM, reduce the levels of fibrosis factors CO-IV, FN, and LN, to have a protective effect on kidney in diabetes rats.


Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Nefropatias , Ratos , Masculino , Animais , Diabetes Mellitus Experimental/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Estreptozocina , Ratos Sprague-Dawley , Nefropatias/patologia , Rim/patologia , Fibrose , Nefropatias Diabéticas/tratamento farmacológico
13.
Colloids Surf B Biointerfaces ; 234: 113752, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38219638

RESUMO

Antibody modification is a common method for endowing drug carriers with the ability to target specific cells. Recent studies suggest that the efficacy of these antibody-modified drug carriers is closely related to their physicochemical properties, such as size, shape, stiffness, charge, and surface chemistry. In this study, we functionalized microcapsules with antibodies to investigate the combined effect of shape and stiffness on their targeting ability. We synthesized hollow microcapsules, both spherical and rod-shaped, with adjustable stiffness using calcium carbonate particles as templates and silk fibroin (SF) as the shell material. These microcapsules were then functionalized with trastuzumab (TTZ) to enhance targeting capabilities. Our analysis revealed that increasing stiffness significantly improved the specificity and avidity of TTZ-coated rod-shaped microcapsules, but not spherical ones, indicating a strong shape-dependent influence of stiffness on these properties. Additionally, we explored the mechanisms of endocytosis using various inhibitors and found that both macropinocytosis and clathrin played critical roles in the cellular uptake of microcapsules. Furthermore, we loaded microcapsules with doxorubicin (DOX) to evaluate their anti-tumor efficacy. The stiffest TTZ-coated, DOX-loaded rod-shaped microcapsules demonstrated the most potent anti-tumor effects on BT-474 cells and the highest uptake in BT-474 3D spheroids. This research contributes to the development of more effective microcapsule-based target delivery systems and the realization of the full potential of microcapsule drug delivery systems.


Assuntos
Doxorrubicina , Portadores de Fármacos , Cápsulas/química , Doxorrubicina/farmacologia , Doxorrubicina/química , Trastuzumab/farmacologia , Linhagem Celular Tumoral , Portadores de Fármacos/química
14.
J Geriatr Oncol ; : 101700, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38218674

RESUMO

INTRODUCTION: The incidence and mortality of cancer is increasing worldwide with studies reporting that cumulative risk of cancer rises as age increases. Against the backdrop of the increasing prevalence of cancer amongst older patients, we conducted a systematic review and meta-analysis examining the depression-mortality relationship in older adults with cancer (OAC). MATERIALS AND METHODS: This PRISMA-adherent systematic review involved a systematic search of PubMed, Medline, EMBASE, and PsycINFO for prospective and retrospective cohort studies comparing the risk of all-cause and cancer-related mortality among OAC with depression. Random effects meta-analyses and meta-regressions were used for the primary analysis. RESULTS: From 5,280 citations, we included 14 cohort studies. Meta-analyses of hazard ratios (HRs) showed an increased incidence of all-cause mortality in OAC with depression (pooled HR: 1.40; 95% confidence interval [CI]: 1.25, 1.55). Subgroup analyses of other categorical study-level characteristics were insignificant. While risk of cancer-related mortality in OAC with depression was insignificantly increased with a pooled HR of 1.21 (95% CI: 0.98, 1.49), subgroup analysis indicated that risk of cancer-related mortality in OAC with depression significantly differed with cancer type. Our systematic review found that having fewer comorbidities, a higher education level, greater socioeconomic status, and positive social supportive factors lowered risk of all-cause mortality in OAC with depression. DISCUSSION: Depression in OAC significantly increases risk of all-cause mortality and cancer-related mortality among different cancer types. It is imperative for healthcare providers and policy makers to recognize vulnerable subgroups among older adults with cancer to individualize interventions.

15.
Environ Geochem Health ; 46(1): 25, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38225511

RESUMO

Deteriorated soil pollution has grown into a worldwide environmental concern over the years. Organochlorine pesticide (OCP) residues, featured with ubiquity, persistence and refractoriness, are one of the main pollution sources, causing soil degradation, fertility decline and nutritional imbalance, and severely impacting soil ecology. Furthermore, residual OCPs in soil may enter the human body along with food chain accumulation and pose a serious health threat. To date, many remediation technologies including physicochemical and biological ways for organochlorine pollution have been developed at home and abroad, but none of them is a panacea suitable for all occasions. Rational selection and scientific decision-making are grounded in in-depth knowledge of various restoration techniques. However, soil pollution treatment often encounters the interference of multiple factors (climate, soil properties, cost, restoration efficiency, etc.) in complex environments, and there is still a lack of systematic summary and comparative analysis of different soil OCP removal methods. Thus, to better guide the remediation of contaminated soil, this review summarized the most commonly used strategies for OCP removal, evaluated their merits and limitations and discussed the application scenarios of different methods. It will facilitate the development of efficient, inexpensive and environmentally friendly soil remediation strategies for sustainable agricultural and ecological development.


Assuntos
Recuperação e Remediação Ambiental , Hidrocarbonetos Clorados , Resíduos de Praguicidas , Praguicidas , Poluentes do Solo , Humanos , Solo/química , Poluentes do Solo/análise , Praguicidas/análise , Resíduos de Praguicidas/análise , Poluição Ambiental/prevenção & controle , Poluição Ambiental/análise , Hidrocarbonetos Clorados/análise
16.
Nurse Educ Pract ; 75: 103882, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38266566

RESUMO

AIM: This study aims to explore the influence of emotion regulation on empathic ability among undergraduate nursing students, as well as the mediating role of emotional intelligence and self-consistency congruence. DESIGN: A cross-sectional study was employed to examine the relationship between the emotion regulation and empathic ability in Chinese nursing students. METHODS: A total of 761 undergraduate nursing students were surveyed using the Interpersonal Reactivity Index (Chinese version), the Gross Emotion Regulation Questionnaire, Wang and Law's Emotional Intelligence Scale and the Self-Harmony Scale. RESULTS: There was a significant positive correlation between emotion regulation, empathic ability and self-harmony. Significant positive correlations were also found between emotion regulation, empathic ability and emotional intelligence. Mediation analysis revealed that self-harmony and emotional intelligence partially mediated the predictive relationship between emotion regulation and empathic ability, with self-harmony showing a more significant mediating effect. CONCLUSION: The findings suggest that emotion regulation among undergraduate nursing students indirectly influences their empathic ability through parallel mediating effects of self-harmony and emotional intelligence.


Assuntos
Bacharelado em Enfermagem , Regulação Emocional , Estudantes de Enfermagem , Humanos , Estudantes de Enfermagem/psicologia , Estudos Transversais , Inteligência Emocional
17.
Kaohsiung J Med Sci ; 40(1): 35-45, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37877496

RESUMO

Sepsis-induced myocardial injury is one of the most difficult complications of sepsis in intensive care units. Annexin A1 (ANXA1) short peptide (ANXA1sp) protects organs during the perioperative period. However, the protective effect of ANXA1sp against sepsis-induced myocardial injury remains unclear. We aimed to explore the protective effects and mechanisms of ANXA1sp against sepsis-induced myocardial injury both in vitro and in vivo. Cellular and animal models of myocardial injury in sepsis were established with lipopolysaccharide. The cardiac function of mice was assessed by high-frequency echocardiography. Elisa assay detected changes in inflammatory mediators and markers of myocardial injury. Western blotting detected autophagy and mitochondrial biosynthesis-related proteins. Autophagic flux changes were observed by confocal microscopy, and autophagosomes were evaluated by TEM. ATP, SOD, ROS, and MDA levels were also detected.ANXA1sp pretreatment enhanced the 7-day survival rate, improved cardiac function, and reduced TNF-α, IL-6, IL-1ß, CK-MB, cTnI, and LDH levels. ANXA1sp significantly increased the expression of sirtuin-3 (SIRT3), mitochondrial biosynthesis-related proteins peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α), and mitochondrial transcription factor A (TFAM). ANXA1sp increased mitochondrial membrane potential (△Ψm), ATP, and SOD, and decreased ROS, autophagy flux, the production of autophagosomes per unit area, and MDA levels. The protective effect of ANXA1sp decreased significantly after SIRT3 silencing in vitro and in vivo, indicating that the key factor in ANXA1sp's protective role is the upregulation of SIRT3. In summary, ANXA1sp attenuated sepsis-induced myocardial injury by upregulating SIRT3 to promote mitochondrial biosynthesis and inhibit oxidative stress and autophagy.


Assuntos
Sepse , Sirtuína 3 , Camundongos , Animais , Sirtuína 3/genética , Sirtuína 3/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima/genética , Mitocôndrias/metabolismo , Estresse Oxidativo , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/farmacologia , Autofagia/genética , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Sepse/complicações , Sepse/genética , Sepse/metabolismo
18.
Acta Pharmacol Sin ; 45(3): 619-632, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37848553

RESUMO

N6-methyladenosine (m6A) modification is a prevalent RNA epigenetic modification, which plays a crucial role in tumor progression including metastasis. Isothiocyanates (ITCs) are natural compounds and inhibit the tumorigenesis of various cancers. Our previous studies show that ITCs inhibit the proliferation and metastasis of non-small cell lung cancer (NSCLC) cells, and have synergistic effects with chemotherapy drugs. In this study, we investigated the molecular mechanisms underlying the inhibitory effects of ITCs on cancer cell metastasis. We showed that phenethyl isothiocyanate (PEITC) dose-dependently inhibited the cell viability of both NSCLC cell lines H1299 and H226 with IC50 values of 17.6 and 15.2 µM, respectively. Furthermore, PEITC dose-dependently inhibited the invasion and migration of H1299 and H226 cells. We demonstrated that PEITC treatment dose-dependently increased m6A methylation levels and inhibited the expression of the m6A demethylase fat mass and obesity-associated protein (FTO) in H1299 and H226 cells. Knockdown of FTO significantly increased m6A methylation in H1299 and H226 cells, impaired their abilities of invasion and migration in vitro, and enhanced the inhibition of PEITC on tumor growth in vivo. Overexpression of FTO promoted the migration of NSCLC cells, and also mitigated the inhibitory effect of PEITC on migration of NSCLC cells. Furthermore, we found that FTO regulated the mRNA m6A modification of a transcriptional co-repressor Transducin-Like Enhancer of split-1 (TLE1) and further affected its stability and expression. TCGA database analysis revealed TLE1 was upregulated in NSCLC tissues compared to normal tissues, which might be correlated with the metastasis status. Moreover, we showed that PEITC suppressed the migration of NSCLC cells by inhibiting TLE1 expression and downstream Akt/NF-κB pathway. This study reveals a novel mechanism underlying ITC's inhibitory effect on metastasis of lung cancer cells, and provided valuable information for developing new therapeutics for lung cancer by targeting m6A methylation.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/patologia , Movimento Celular , Isotiocianatos/farmacologia , Isotiocianatos/uso terapêutico , Linhagem Celular Tumoral , Proteínas Correpressoras/farmacologia , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética
19.
Nanomaterials (Basel) ; 13(23)2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38063739

RESUMO

Boron-doped diamond (BDD) thin film electrodes have great application potential in water treatment. However, the high electrode energy consumption due to high resistance directly limits the application range of existing BDD electrodes. In this paper, the BDD/graphene/BDD (DGD) sandwich structure electrode was prepared, which effectively improved the conductivity of the electrode. Meanwhile, the sandwich electrode can effectively avoid the degradation of electrode performance caused by the large amount of non-diamond carbon introduced by heavy doping, such as the reduction of the electrochemical window and the decrease of physical and chemical stability. The microstructure and composition of the film were characterized by scanning electron microscope (SEM), atomic force microscopy (AFM), Raman spectroscopy, and transmission electron microscopy (TEM). Then, the degradation performance of citric acid (CA), catechol, and tetracycline hydrochloride (TCH) by DGD electrodes was systematically studied by total organic carbon (TOC) and Energy consumption per unit TOC removal (ECTOC). Compared with the single BDD electrode, the new DGD electrode improves the mobility of the electrode and reduces the mass transfer resistance by 1/3, showing better water treatment performance. In the process of dealing with Citric acid, the step current of the DGD electrode was 1.35 times that of the BDD electrode, and the energy utilization ratio of the DGD electrode was 2.4 times that of the BDD electrode. The energy consumption per unit TOC removal (ECTOC) of the DGD electrode was lower than that of BDD, especially Catechol, which was reduced to 66.9% of BDD. The DGD sandwich electrode, as a new electrode material, has good electrochemical degradation performance and can be used for high-efficiency electrocatalytic degradation of organic pollutants.

20.
Biomolecules ; 13(12)2023 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-38136633

RESUMO

The olfactory neuroepithelium (OE) is one of the few neuronal tissues where environmental pathogens can gain direct access. Despite this vulnerable arrangement, little is known about the protective mechanisms in the OE to prevent viral infection and its antiviral responses. We systematically investigated acute responses in the olfactory mucosa upon exposure to vesicular stomatitis virus (VSV) via RNA-seq. VSVs were nasally inoculated into C57BL/6 mice. Olfactory mucosae were dissected for gene expression analysis at different time points after viral inoculation. Interferon functions were determined by comparing the viral load in interferon receptor knockout (Ifnar1-/- and Ifnlr1-/-) with wildtype OE. Antiviral responses were observed as early as 24 h after viral exposure in the olfactory mucosa. The rapidly upregulated transcripts observed included specific type I as well as type III interferons (Ifn) and interferon-stimulated genes. Genetic analyses demonstrated that both type I and type III IFN signaling are required for the suppression of viral replication in the olfactory mucosa. Exogenous IFN application effectively blocks viral replication in the OE. These findings reveal that the OE possesses an innate ability to suppress viral infection. Type I and type III IFNs have prominent roles in OE antiviral functions.


Assuntos
Interferon lambda , Viroses , Animais , Camundongos , Camundongos Endogâmicos C57BL , Interferons , Mucosa Olfatória , Replicação Viral , Antivirais/farmacologia
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