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The regulation of glycometabolism homeostasis is vital to maintain health and development of animal and humans; however, the molecular mechanisms by which organisms regulate the glucose metabolism homeostasis from a feeding state switching to a non-feeding state are not fully understood. Using the holometabolous lepidopteran insect Helicoverpa armigera, cotton bollworm, as a model, we revealed that the steroid hormone 20-hydroxyecdysone (20E) upregulated the expression of transcription factor Krüppel-like factor (identified as Klf15) to promote macroautophagy/autophagy, apoptosis and gluconeogenesis during metamorphosis. 20E via its nuclear receptor EcR upregulated Klf15 transcription in the fat body during metamorphosis. Knockdown of Klf15 using RNA interference delayed pupation and repressed autophagy and apoptosis of larval fat body during metamorphosis. KLF15 promoted autophagic flux and transiting to apoptosis. KLF15 bound to the KLF binding site (KLF bs) in the promoter of Atg8 (autophagy-related gene 8/LC3) to upregulate Atg8 expression. Knockdown Atg8 reduced free fatty acids (FFAs), glycerol, free amino acids (FAAs) and glucose levels. However, knockdown of Klf15 accumulated FFAs, glycerol, and FAAs. Glycolysis was switched to gluconeogenesis, trehalose and glycogen synthesis were changed to degradation during metamorphosis, which were accompanied by the variation of the related genes expression. KLF15 upregulated phosphoenolpyruvate carboxykinase (Pepck) expression by binding to KLF bs in the Pepck promoter for gluconeogenesis, which utilised FFAs, glycerol, and FAAs directly or indirectly to increase glucose in the hemolymph. Taken together, 20E via KLF15 integrated autophagy and gluconeogenesis by promoting autophagy-related and gluconeogenesis-related genes expression.
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Ecdisterona , Mariposas , Animais , Autofagia/genética , Ecdisterona/metabolismo , Técnicas de Silenciamento de Genes , Gluconeogênese/genética , Glucose/metabolismo , Glicerol/metabolismo , Homeostase/genética , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Mariposas/genéticaRESUMO
Cardiomyocyte injury is closely related to various myocardial diseases, and S-Allyl-L-cysteine (SAC) has been found to have myocardial protective effects, but its mechanism is currently unclear. Meanwhile, copper also has various physiological functions, and this study found that copper inhibited cell viability in a concentration and time-dependent manner, and was associated with multiple modes of death. Elesclomol plus CuCl2 (ES + Cu) significantly inhibited cell viability, and this effect could only be blocked by copper chelator TTM, indicating that "ES + Cu" induced cuproptosis in cardiomyocytes. SAC reduced the inhibitory effects of high concentration copper and "ES + Cu" on cell viability in a concentration and time-dependent manner, indicating that SAC plays a cardioprotective role under stress. Further mechanism study showed that high concentration of copper significantly induced cardiomyocyte apoptosis and increased the levels of LDH, MDA and ROS, while SAC inhibited the apoptosis and injury of cardiomyocytes induced by copper. "ES + Cu" significantly increased intracellular copper levels and decreased the expression of FDX1, LIAS, Lip-DLST and Lip-DLAT; FDX1 siRNA did not affect the expression of LIAS, but further reduced the expression of Lip-DLST and Lip-DLAT; SAC did not affect the expression of these genes, but enhanced the effect of "ES + Cu" in down-regulating these gene expression and restored intracellular copper levels. In addition, "ES + Cu" reduced ATP production, weakened the activity of mitochondrial complex I and III, inhibited cell viability, and increased the contents of injury markers LDH, MDA, CK-MB and cTnI, while SAC significantly improved mitochondrial function injury and cardiomyocyte injury induced by "ES + Cu". Therefore, SAC can inhibit apoptosis and cuproptosis to play a cardioprotective role.
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Apoptose , Cobre , Cisteína , Miócitos Cardíacos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Apoptose/efeitos dos fármacos , Animais , Cisteína/análogos & derivados , Cisteína/farmacologia , Ratos , Sobrevivência Celular/efeitos dos fármacos , Ratos Sprague-Dawley , Células Cultivadas , Espécies Reativas de Oxigênio/metabolismo , Cardiotônicos/farmacologiaRESUMO
Methylglyoxal (MG), a reactive metabolic byproduct of glycolysis, is a causative of painful diabetic neuropathy. Patients with diabetes are associated with more frequent severe asthma exacerbation. Stimulation of capsaicin-sensitive lung vagal (CSLV) afferents may contribute to the pathogenesis of hyperreactive airway diseases such as asthma. However, the possibility of the stimulatory effect of MG on CSLV afferents and the underlying mechanisms remain unknown. Our results showed that intravenous injection of MG (25 mg/kg, MG25) in anesthetized, spontaneously breathing rats elicited pulmonary chemoreflexes characterized by apnea, bradycardia, and hypotension. The MG-induced apneic response was reproducible and dose dependent. MG25 no longer evoked these reflex responses after perineural capsaicin treatment of both cervical vagi to block C-fibers' conduction, suggesting that the reflexes were mediated through the stimulation of CSLV afferents. Pretreatment with HC030031 [an antagonist of transient receptor potential ankyrin subtype 1 protein (TRPA1)] or AP18 (another TRPA1 antagonist), but not their vehicle, markedly attenuated the apneic response induced by MG25. Consistently, electrophysiological results showed that pretreatment with HC030031 largely attenuated the intense discharge in CSLV afferents induced by injection of MG25 in open-chest and artificially ventilated rats. In isolated CSLV neurons, the perfusion of MG evoked an abrupt and pronounced increase in calcium transients in a concentration-dependent manner. This stimulatory effect on CSLV neurons was also abolished by HC030031 treatment but not by its vehicle. In conclusion, these results suggest that MG exerts a stimulatory effect on CSLV afferents, inducing pulmonary chemoreflexes, and such stimulation is mediated through the TRPA1 activation.NEW & NOTEWORTHY Methylglyoxal (MG) is implicated in the development of painful diabetic neuropathy. A retrospective cohort study revealed an increased incidence of asthma exacerbations in patients with diabetes. This study demonstrated that elevated circulating MG levels stimulate capsaicin-sensitive lung vagal afferents via activation of TRPA1, which in turn triggers respiratory reflexes. These findings provide new information for understanding the pathogenic mechanism of diabetes-associated hyperreactive airway diseases and potential therapy.
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Acetanilidas , Asma , Neuropatias Diabéticas , Purinas , Humanos , Ratos , Animais , Capsaicina/farmacologia , Ratos Sprague-Dawley , Aldeído Pirúvico/efeitos adversos , Aldeído Pirúvico/metabolismo , Neuropatias Diabéticas/metabolismo , Estudos Retrospectivos , Pulmão , Nervo Vago/fisiologia , Apneia , Asma/metabolismo , Canal de Cátion TRPA1/metabolismoRESUMO
BACKGROUND AND PURPOSE: Liver fibrosis is a wound-healing reaction which is the main cause of chronic liver diseases worldwide. The activated hepatic stellate cell (aHSC) is the main driving factor in the development of liver fibrosis. Inhibiting autophagy of aHSC can prevent the progression of liver fibrosis, but inhibiting autophagy of other liver cells has opposite effects. Hence, targeted inhibition of autophagy in aHSC is quite necessary for the treatment of liver fibrosis, which prompts us to explore the targeted delivery system of small molecule autophagy inhibitor hydroxychloroquine (HCQ) that can target aHSC and alleviate the liver fibrosis. METHODS: The delivery system of HCQ@retinol-liposome nanoparticles (HCQ@ROL-LNPs) targeting aHSC was constructed by the film dispersion and pH-gradient method. TGF-ß-induced HSC activation and thioacetamide (TAA)-induced liver fibrosis mice model were established, and the targeting ability and therapeutic effect of HCQ@ROL-LNPs in liver fibrosis were studied subsequently in vitro and in vivo. RESULTS: HCQ@ROL-LNPs have good homogeneity and stability. They inhibited the autophagy of aHSC selectively by HCQ and reduced the deposition of extracellular matrix (ECM) and the damage to other liver cells. Compared with the free HCQ and HCQ@LNPs, HCQ@ROL-LNPs had good targeting ability, showing enhanced therapeutic effect and low toxicity to other organs. CONCLUSION: Construction of HCQ@ROL-LNPs delivery system lays a theoretical and experimental foundation for the treatment of liver fibrosis and promotes the development of clinical therapeutic drugs for liver diseases.
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Autofagia , Células Estreladas do Fígado , Hidroxicloroquina , Cirrose Hepática , Hidroxicloroquina/farmacologia , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Animais , Autofagia/efeitos dos fármacos , Camundongos , Cirrose Hepática/tratamento farmacológico , Lipossomos , Nanopartículas , Masculino , Modelos Animais de Doenças , Humanos , Tioacetamida , Camundongos Endogâmicos C57BLRESUMO
The COVID-19 pandemic has resulted in huge amounts of face masks worldwide. However, there is a lack of awareness on the additives and their potential risk to aquatic ecosystems of face masks. To address this issue, the additives and their toxicity in 13 face masks (e.g., polypropylene, polyethylene, and polylactic acid) were determined using nontarget analysis and bioassays. A total of 826 organic additives including intermediates (14.8%), surfactants (9.3%), plasticizers (8.2%), and antioxidants (6.1%) were tentatively identified, with 213 compounds being assigned confidence levels of 1 and 2. Interestingly, polylactic acid masks contained more additives than most polypropylene or polyethylene masks. Among these additives, the concentration of tris(2-ethylhexyl) phosphate in masks was 9.4-978.2 ng/g with a 100% detection frequency. Furthermore, 13 metals such as zinc (up to 202.0 µg/g), copper (32.5 µg/g), and chromium (up to 5.7 µg/g) were detected in the face masks. The methanol extracts of the masks showed the developmental toxicity, swimming behavior, and/or endocrine disruption in embryos/larvae of Oryzias melastigma. The findings demonstrate that face masks contain various toxic additives to marine medaka, which deserves close attention to pollution by face masks.
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Oryzias , Poluentes Químicos da Água , Animais , Humanos , Ecossistema , Máscaras , Pandemias , Polipropilenos , PolietilenosRESUMO
OBJECTIVE: To compare bone volume and height changes of two types of deproteinized bovine bone mineral (DBBM) for lateral window sinus floor elevation (LSFE) with simultaneous implant placement. MATERIALS AND METHODS: This retrospective cohort study involved 72 patients who underwent LSFE using low-temperature sintered cancellous bone-derived DBBM (C-DBBM) or high-temperature two-step sintered epiphyseal-derived DBBM (E-DBBM). Cone-beam computed tomography (CBCT) was acquired preoperatively, immediately postoperatively, 6 months and 1-4 years post-surgery. Bone volume (BV), apical bone height (ABH), endo-sinus bone gain (ESBG), and crestal bone level (CBL) were evaluated through three-dimensional fitting and superimposition. Linear mixed models (LMM) were employed to analyze factors influencing the reduction of BV (ΔBV) and ESBG (ΔESBG). RESULTS: The E-DBBM group showed no significant change in BV 1-4 years post-surgery, while the C-DBBM group demonstrated a significant reduction (p = .006) with volume stability of 85.86%. Bone height in the E-DBBM group increased at 6 months and subsequently decreased at 1-4 years (p = .003). In the C-DBBM group, it decreased at 6 months (p = .014), then further decreased at 1-4 years (p = .001). ΔESBG was lower in the E-DBBM group than the C-DBBM group from immediate postoperative to 1-4 years (p = .009). LMM showed graft material type was the primary factor influencing ΔBV (p = .026) and ΔESBG (p = .003). CONCLUSIONS: Within the limitations of this study, both types of DBBM could achieve favorable clinical outcomes. E-DBBM demonstrated enhanced stability in maintaining bone volume and height.
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BACKGROUND: Infantile Juvenile polyposis of infantile (JPI) is a rare and aggressive form of juvenile polyposis syndrome (JPS) typically diagnosed in the first year of life. It often carries a poor prognosis due to chronic gastrointestinal bleeding, protein-losing enteropathy, malnutrition and immune deficiency. CASE PRESENTATION: We report a case of a girl initially presented with pallor at 7 months of age, which progressed to gastrointestinal bleeding and protein-losing enteropathy. Endoscopic examination, which included both upper gastrointestinal endoscopy and enteroscopy, showed diffuse polyposis. Histopathology results indicated the presence of juvenile polyps with no dysplasia in all removed polyps. Genetic testing identified a 2.1 Mb deletion on chromosome 10q23.2q23.31 involving the phosphatase and tensin homolog (PTEN) and bone morphogenetic protein receptor type IA (BMPR1A) genes. Treatment with sirolimus initiated at 10 months of age led to a reduction in the need for blood and albumin infusions, improved patient growth, and quality of life. While the frequency of endoscopic evaluations decreased with sirolimus, regular endoscopic polypectomy every 5 months remained necessary. However, discontinuation of sirolimus resulted in polyp recurrence after 2 months due to pneumonia. CONCLUSION: This case highlights sirolimus treatment can alleviate many complications of JPI, it does not eliminate the need for aggressive polypectomy.
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Polipose Intestinal , Sirolimo , Humanos , Feminino , Sirolimo/uso terapêutico , Polipose Intestinal/congênito , Polipose Intestinal/genética , Polipose Intestinal/tratamento farmacológico , Polipose Intestinal/diagnóstico , Lactente , Síndromes Neoplásicas Hereditárias/tratamento farmacológico , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/genética , Imunossupressores/uso terapêutico , PTEN Fosfo-Hidrolase/genéticaRESUMO
AIMS: To establish a cognitive appraisal path model that examines the impact of stroke knowledge on stigma with the parallel mediating effects of negative and positive coping traits, as well as the moderating effects of family functioning. BACKGROUND: Stroke-related stigma, a 'mixture' of negative emotions involving internal criticism and external judgement, has been shown to impair patients' health outcomes. However, the specific factors underlying cognitive appraisals and their pathways remain unknown. DESIGN: A cross-sectional design. METHODS: The cross-sectional sample was from two stroke centres in China. Questionnaires were administered to collect sociodemographic data, stroke knowledge, coping traits, family functioning and stigma. Hierarchical regression models and the moderated parallel mediation model were constructed to analyse influencing pathways. The study adhered to the strengthening the reporting of observational studies in epidemiology guideline. RESULTS: All 144 samples reported stigma symptoms with a moderate-to-high standardising score. The best hierarchical regression model explains 55.5% of the variance in stigma. The parallel mediation model indicated that negative and positive coping traits co-mediating the association of stroke knowledge and stigma. After adding the family functioning as a moderator, the moderated parallel mediation model was confirmed with adequate fit indices. CONCLUSION: Among the cognitive appraisal factors affecting stroke-related stigma, stroke knowledge reduces stigma by modifying coping traits, while poor family functioning may serve as an opposing moderator. Notably, when family support is insufficient, enhanced stroke knowledge might paradoxically exacerbate the stigma. RELEVANCE TO CLINICAL PRACTICE: This study contributes knowledge on transforming health education and emphasises the pivotal roles of clinical nursing practitioners. In similar global contexts, the study highlights integrating health education, psychological counselling and family support to advance systematic nursing practices. PATIENT OR PUBLIC CONTRIBUTION: None.
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Adaptação Psicológica , Capacidades de Enfrentamento , Humanos , Estudos Transversais , Pacientes , Cognição , Estigma SocialRESUMO
OBJECTIVES: To observe the effects of melatonin on autophagy in cortical neurons of neonatal rats with hypoxic-ischemic brain damage (HIBD) and to explore its mechanisms via the PI3K/AKT signaling pathway, aiming to provide a basis for the clinical application of melatonin. METHODS: Seven-day-old Sprague-Dawley neonatal rats were randomly divided into a sham operation group, an HIBD group, and a melatonin group (n=9 each). The neonatal rat HIBD model was established using the classic Rice-Vannucci method. Neuronal morphology in the neonatal rat cerebral cortex was observed with hematoxylin-eosin staining and Nissl staining. Autophagy-related protein levels of microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 were detected by immunofluorescence staining and Western blot analysis. Phosphorylated phosphoinositide 3-kinase (p-PI3K) and phosphorylated protein kinase B (p-AKT) protein expression levels were measured by immunohistochemistry and Western blot. The correlation between autophagy and the PI3K pathway in the melatonin group and the HIBD group was analyzed using Pearson correlation analysis. RESULTS: Twenty-four hours post-modeling, neurons in the sham operation group displayed normal size and orderly arrangement. In contrast, neurons in the HIBD group showed swelling and disorderly arrangement, while those in the melatonin group had relatively normal morphology and more orderly arrangement. Nissl bodies were normal in the sham operation group but distorted in the HIBD group; however, they remained relatively intact in the melatonin group. The average fluorescence intensity of LC3 and Beclin-1 was higher in the HIBD group compared to the sham operation group, but was reduced in the melatonin group compared to the HIBD group (P<0.05). The number of p-PI3K+ and p-AKT+ cells decreased in the HIBD group compared to the sham operation group but increased in the melatonin group compared to the HIBD group (P<0.05). LC3 and Beclin-1 protein expression levels were higher, and p-PI3K and p-AKT levels were lower in the HIBD group compared to the sham operation group (P<0.05); however, in the melatonin group, LC3 and Beclin-1 levels decreased, and p-PI3K and p-AKT increased compared to the HIBD group (P<0.05). The correlation analysis results showed that the difference of the mean fluorescence intensity of LC3 and Beclin-1 protein in the injured cerebral cortex between the melatonin and HIBD groups was negatively correlated with the difference of the number of p-PI3K+ and p-AKT+ cells between the two groups (P<0.05). CONCLUSIONS: Melatonin can inhibit excessive autophagy in cortical neurons of neonatal rats with HIBD, thereby alleviating HIBD. This mechanism is associated with the PI3K/AKT pathway.
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Animais Recém-Nascidos , Autofagia , Córtex Cerebral , Hipóxia-Isquemia Encefálica , Melatonina , Neurônios , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Ratos Sprague-Dawley , Transdução de Sinais , Animais , Melatonina/farmacologia , Hipóxia-Isquemia Encefálica/patologia , Hipóxia-Isquemia Encefálica/metabolismo , Ratos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Córtex Cerebral/patologia , Autofagia/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Neurônios/patologia , Neurônios/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Masculino , FemininoRESUMO
BACKGROUND: High-power short-duration (HPSD) ablation strategy has emerged as a popular approach for treating atrial fibrillation (AF), with shorter ablation time. The utilized Smart Touch Surround Flow (STSF) catheter, with 56 holes around the electrode, lowers electrode-tissue temperature and thrombus risk. Thus, we conducted this prospective, randomized study to investigate if the HPSD strategy with STSF catheter in AF ablation procedures reduces the silent cerebral embolism (SCE) risk compared to the conventional approach with the Smart Touch (ST) catheter. METHODS: From June 2020 to September 2021, 100 AF patients were randomized 1:1 to the HPSD group using the STSF catheter (power set at 50 W) or the conventional group using the ST catheter (power set at 30 to 35 W). Pulmonary vein isolation was performed in all patients, with additional lesions at operator's discretion. High-resolution cerebral diffusion-weighted magnetic resonance imaging (hDWI) with slice thickness of 1 mm was performed before and 24-72 h after ablation. The incidence of new periprocedural SCE was defined as the primary outcome. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA) test. RESULTS: All enrolled AF patients (median age 63, 60% male, 59% paroxysmal AF) underwent successful ablation. Post-procedural hDWI identified 106 lesions in 42 enrolled patients (42%), with 55 lesions in 22 patients (44%) in the HPSD group and 51 lesions in 20 patients (40%) in the conventional group (p = 0.685). No significant differences were observed between two groups regarding the average number of lesions (p = 0.751), maximum lesion diameter (p = 0.405), and total lesion volume per patient (p = 0.669). Persistent AF and CHA2DS2-VASc score were identified as SCE determinants during AF ablation procedure by multivariable regression analysis. No significant differences in MoCA scores were observed between patients with SCE and those without, both immediately post-procedure (p = 0.572) and at the 3-month follow-up (p = 0.743). CONCLUSIONS: Involving a small sample size of 100 AF patients, this study reveals a similar incidence of SCE in AF ablation procedures, comparing the HPSD strategy using the STSF catheter to the conventional approach with the ST catheter. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04408716. AF = Atrial fibrillation, DWI = Diffusion-weighted magnetic resonance imaging, HPSD = High-power short-duration, ST = Smart Touch, STSF = Smart Touch Surround Flow.
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Técnicas de Ablação , Fibrilação Atrial , Ablação por Cateter , Embolia Intracraniana , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/cirurgia , Fibrilação Atrial/complicações , Estudos Prospectivos , Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/epidemiologia , Embolia Intracraniana/prevenção & controle , Incidência , Técnicas de Ablação/efeitos adversos , Resultado do Tratamento , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , RecidivaRESUMO
The NADPH oxidase activity of phagocytes and its generation of reactive oxygen species (ROS) is critical for host defense, but ROS overproduction can also lead to inflammation and tissue injury. Here we report that TRPM2, a nonselective and redox-sensitive cation channel, inhibited ROS production in phagocytic cells and prevented endotoxin-induced lung inflammation in mice. TRPM2-deficient mice challenged with endotoxin (lipopolysaccharide) had an enhanced inflammatory response and diminished survival relative to that of wild-type mice challenged with endotoxin. TRPM2 functioned by dampening NADPH oxidase-mediated ROS production through depolarization of the plasma membrane in phagocytes. As ROS also activate TRPM2, our findings establish a negative feedback mechanism for the inactivation of ROS production through inhibition of the membrane potential-sensitive NADPH oxidase.
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Inflamação/metabolismo , Fagócitos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Canais de Cátion TRPM/metabolismo , Animais , Cálcio/metabolismo , Inflamação/genética , Inflamação/patologia , Pneumopatias/genética , Pneumopatias/metabolismo , Pneumopatias/patologia , Potenciais da Membrana , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oxirredução , Canais de Cátion TRPM/deficiência , Canais de Cátion TRPM/genéticaRESUMO
Bisphenol 4-[1-(4-hydroxyphenyl)-3,3,5-trimethylcyclohexyl] phenol (BPTMC), as a substitute for bisphenol A, has been detected in environments. However, the ecotoxicological data of BPTMC are extremely scarce. Here, the lethality, developmental toxicity, locomotor behavior, and estrogenic activity of BPTMC at different concentrations (0.25-2000 µg/L) in marine medaka (Oryzias melastigma) embryos were examined. In addition, the in silico binding potentials of O. melastigma estrogen receptors (omEsrs) with BPTMC were assessed by docking study. Low-concentration BPTMC exposure (including an environmentally relevant concentration, 0.25 µg/L) resulted in stimulating effects, including hatching rate, heart rate, malformation rate, and swimming velocity. However, elevated concentrations of BPTMC led to an inflammatory response, changed heart rate and swimming velocity in the embryos and larvae. In the meantime, BPTMC (including 0.25 µg/L) altered the concentrations of estrogen receptor, vitellogenin, and endogenous 17 ß-estradiol as well as the transcriptional levels of estrogen-responsive genes in the embryos or/and larvae. Furthermore, elaborate tertiary structures of omEsrs were built by ab initio modeling, and BPTMC exerted potent binding potential with three omEsrs with -47.23, -49.23, and -50.30 kJ/mol for Esr1, Esr2a, and Esr2b, respectively. This work suggests that BPTMC has potent toxicity and estrogenic effects in O. melastigma.
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Oryzias , Poluentes Químicos da Água , Animais , Oryzias/fisiologia , Estrona/metabolismo , Estrogênios/metabolismo , Fenóis/toxicidade , Receptores de Estrogênio/metabolismo , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/metabolismoRESUMO
BACKGROUND: Myopia and obesity in children and adolescents have become serious public health problems that endanger public health, especially in China. Unhealthy lifestyle behaviors are environmental drivers of both myopia and obesity. This protocol describes a study to evaluate the effectiveness of "22510SS", that is 2 h of daytime outdoor activities ('2'); Limit screen time to no more than 2 h per day ('2'); Consume at least 5 servings of fruits and vegetables daily ('5'); Attain 1 h of physical activity daily ('1'); Consume 0 sugar-sweetened beverages ('0'); Reasonable sleep duration ('S'); Regular supervision ('S'). A school-based, multifaceted intervention strategy for myopia and obesity prevention, and to assess and explore the implementation of "22510SS" with regards to acceptability, feasibility, adoption, usage and maintenance. METHODS AND ANALYSIS: This study aims to develop a comprehensive intervention strategy "22510SS" based on the socio-ecological model, and A two-arm cluster randomized trial with a parallel-group of a 1:1 allocation ratio in 36 primary and secondary schools to test its evidence-based intervention programs on the effects and implementation of myopia and obesity epidemics in children and adolescents in grades 4 and 7. The primary outcomes will include differences in visual acuity, body mass index, outdoor activity indicators, screen time, fruit and vegetable intake, high-quality protein intake, sugar-sweetened beverage intake, sleep duration, and level of monitoring among children and adolescents. Secondary outcomes will assess the acceptability, feasibility, uptake, use, and maintenance of the intervention. Effects on the primary and secondary outcomes will be analyzed using linear and logistic regression analyses, as well as difference-in-difference analysis, taking into account cluster effects and possible confounding factors. Process assessments will also be conducted through quantitative and qualitative analyses, including acceptability, feasibility, gender, adoption, implementation, and sustainability. DISCUSSION: This study will evaluate the effectiveness of "22510SS" and examine its implementation in the school-based network nesting family and clinic. Following this intervention study, the integrated intervention program focused on myopia and obesity among children and adolescents have great potential to be implemented in China to promote and support healthy lifestyle behavior change and reduce the risk of myopia and obesity in children and adolescents. TRIAL REGISTRATION: NCT05275959. Registered 23 Mach 2022.
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Miopia , Obesidade Infantil , Humanos , Criança , Adolescente , Obesidade Infantil/prevenção & controle , Pequim , Instituições Acadêmicas , China/epidemiologia , Miopia/epidemiologia , Miopia/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: In response to an aging population, the Chinese government implemented the three-child policy in 2021 based on the comprehensive two-child policy. With the implementation of the new birth policy, people's maternal and child health (MCH) needs will also increase. The allocation and fairness of MCH human resources directly affect people's access to MCH services. The purpose of this study is to analyze the allocation of health human resources in Chinese maternal and child health care institutions, evaluate the fairness of the allocation, to provide a reference for the rational allocation of MCH human resources. METHODS: The data of health technicians, licensed (assistant) physicians, and registered nurses in maternal and child health care institutions nationwide from 2016 to 2020 were included. The health resource density index (HRDI) is used to evaluate the allocation level of MCH human resources. The Gini coefficient (G) and Theil index (T) are used to evaluate the fairness of the allocation of MCH human resources from the perspectives of population and geographic area. RESULTS: From 2016 to 2020, the average annual growth rate of the number of health technicians, licensed (assistant) physicians, and registered nurses in Chinese maternal and child health care institutions was 7.53, 6.88, and 9.12%, respectively. The Gini coefficient (G) of the three types of MCH human resources allocated by population were all below 0.23, and the Gini coefficient (G) allocated by geographical area were all above 0.65. The Theil index (T) of the three types of MCH human resources allocated by population was all lower than 0.06, and the Theil index (T) allocated by geographical area was all higher than 0.53. In addition, the three types of MCH human resources allocated by population and geographic area contributed more than 84% of the Theil index within the group (Tintra) to the Theil index (T). CONCLUSIONS: China's MCH human resources were fair in terms of population allocation, but unfair in terms of geographical area allocation. In the future, more attention should be paid to the geographical accessibility of MCH human resources, and the allocation of resources should comprehensively consider the two factors of serving the population and geographical area.
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Saúde da Criança , Atenção à Saúde , Feminino , Criança , Humanos , Idoso , Estudos Longitudinais , Mão de Obra em Saúde , Recursos em Saúde , China , Alocação de RecursosRESUMO
BACKGROUND: The rapid increase in the prevalence of diabetes has resulted in more cases of diabetic kidney disease (DKD). Treatment with bone marrow mesenchymal stem cells (BMSCs) may represent an alternative strategy to manage DKD. METHODS: HK-2 cells were treated with 30 mM high glucose (HG). Bone marrow MSC-derived exosomes (BMSC-exos) were isolated and internalized into HK-2 cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) and lactate dehydrogenase (LDH) assays were used to measure viability and cytotoxicity. The secretion of IL-1ß and IL-18 was measured by ELISA. Pyroptosis was assessed by flow cytometry. Quantitative RT-PCR was used to measure the levels of miR-30e-5p, ELAV like RNA binding protein 1 (ELAVL1), IL-1ß, and IL-18. The expression of ELAVL1 and pyroptosis-associated cytokine proteins was determined by western blot analysis. A dual-luciferase reporter gene assay was conducted to confirm the relationship between miR-30e-5p and ELAVL1. RESULTS: BMSC-exos decreased LDH, IL-1ß, and IL-18 secretion and inhibited the expression of the pyroptosis-related factors (IL-1ß, caspase-1, GSDMD-N, and NLRP3) in HG-induced HK-2 cells. Moreover, miR-30e-5p depletion derived from BMSC-exos promoted HK-2 cell pyroptosis. Besides, miR-30e-5p over-expression or ELVAL1 knockdown could directly inhibit pyroptosis. ELAVL1 was a target of miR-30e-5p and knocking down ELAVL1 reversed the effect of miR-30e-5p inhibition in BMSC-exos-treated HK-2 cells. CONCLUSIONS: BMSC-derived exosomal miR-30e-5p inhibits caspase-1-mediated pyroptosis by targeting ELAVL1 in HG-induced HK-2 cells, which might provide a new strategy for treating DKD.
Assuntos
Proteína Semelhante a ELAV 1 , Células-Tronco Mesenquimais , MicroRNAs , Caspases/metabolismo , Caspases/farmacologia , Glucose/farmacologia , Glucose/metabolismo , Interleucina-18/metabolismo , Interleucina-18/farmacologia , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , Piroptose , Humanos , Linhagem Celular , Proteína Semelhante a ELAV 1/genética , Exossomos , Túbulos Renais Proximais/citologiaRESUMO
The evolution of network technologies has witnessed a paradigm shift toward open and intelligent networks, with the Open Radio Access Network (O-RAN) architecture emerging as a promising solution. O-RAN introduces disaggregation and virtualization, enabling network operators to deploy multi-vendor and interoperable solutions. However, managing and automating the complex O-RAN ecosystem presents numerous challenges. To address this, machine learning (ML) techniques have gained considerable attention in recent years, offering promising avenues for network automation in O-RAN. This paper presents a comprehensive survey of the current research efforts on network automation usingML in O-RAN.We begin by providing an overview of the O-RAN architecture and its key components, highlighting the need for automation. Subsequently, we delve into O-RAN support forML techniques. The survey then explores challenges in network automation usingML within the O-RAN environment, followed by the existing research studies discussing application of ML algorithms and frameworks for network automation in O-RAN. The survey further discusses the research opportunities by identifying important aspects whereML techniques can benefit.
RESUMO
Schisandra chinensis, a traditional Chinese medicinal herb, is rich in chemical constituents, including lignans, triterpenes, polysaccharides, and volatile oils. Clinically, it is commonly used to treat cardiovascular, cerebrovascular, liver, gastrointestinal, and respiratory diseases. Modern pharmacological studies have shown that S. chinensis extract and monomers have multiple pharmacological activities in lowering liver fat, alleviating insulin resistance, and resisting oxidative stress, and have good application prospects in alleviating nonalcoholic fatty liver disease(NAFLD). Therefore, this study reviewed the research progress on chemical constituents of S. chinensis and its effect on NAFLD in recent years to provide references for the research on S. chinensis in the treatment of NAFLD.
Assuntos
Resistência à Insulina , Lignanas , Hepatopatia Gordurosa não Alcoólica , SchisandraRESUMO
To explore the stability characteristics of ß-nicotinamide mononucleotide(NMN) and provide data support for NMN production, preparation, and related product development, this study established a simple HPLC content determination method for NMN in simple substrate and investigated the degradation behavior, degradation products, and degradation kinetics of NMN under various chemical, physical, and biological conditions. The HPLC method employed a Welch Xtimate AQ-C_(18) column(4.6 mm×250 mm, 5 µm), a detection wavelength of 266 nm, a column temperature of 30 â, a flow rate of 1.0 mL·min~(-1), an injection volume of 5 µL, and a mobile phase consisting of methanol(A) and a 10 mmol·L~(-1) ammonium formate aqueous solution(B) with a gradient elution(0-6.7 min, 0-4% A; 6.7-13 min, 4%-18% A; 13-14.2 min, 18% A; 14.2-15 min, 18%-0 A; 15-22 min, 0 A). This method provided good separation between NMN and potential impurities and degradation products, and had a wide linear range, short analysis time, good durability, high accuracy, an average sample recovery rate of 98.71%, and an RSD of 1.2%. The instrument precision had an RSD of 0.26%, and the linearity within the examined range was excellent(R~2≥0.999 9). This method can be applied for NMN content determination in simple substrate. The degradation process of NMN in aqueous solution followed apparent first-order kinetics, with the degradation rate primarily influenced by high temperature and pH. NMN was more stable in low-temperature, neutral, or weakly acidic/alkaline environments. Strong acids or strong alkalis could accelerate its degradation, and its degradation rate was less affected by pepsin and trypsin. In an aqueous solution at room temperature, it followed the kinetic equation lg C_t=0.005 7t + 4.817 2, with t_(0.9) and t_(1/2) values of 95.58, 860.26 h, respectively. The results suggest that pH and temperature are the main factors affecting the stability of NMN in aqueous solution, and low temperature, moisture protection, and a weakly acidic environment are more conducive to the storage and application of NMN and its products.
Assuntos
Ácidos , Mononucleotídeo de Nicotinamida , Mononucleotídeo de Nicotinamida/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , CinéticaRESUMO
The leaves of sea buckthorn(Hippophae rhamnoides), considered as common food raw materials, have records of medicinal use and diverse pharmacological activities, showing a potential medicinal value. However, the active substances in the sea buckthorn leaves and their mechanisms of action remain unclear. In addition, due to the extensive source and large variety variations, the quality evaluation criteria of sea buckthorn leaves remain to be developed. To solve the problems, this study predicted the main active components, core targets, key pathways, and potential pharmacological effects of sea buckthorn leaves by network pharmacology and molecular docking. Furthermore, ultra-performance liquid chromatography with diode-array detection(UPLC-DAD) was employed to determine the content of active components and establish the chemical fingerprint, on the basis of which the quality markers of sea buckthorn leaves were predicted and then verified by the enzyme activity inhibition method. The results indicated that sea buckthorn leaves had potential therapeutic effects on a variety of digestive tract diseases, metabolic diseases, tumors, and autoimmune diseases, which were consistent with the ancient records and the results of modern pharmacological studies. The core targets of sea buckthorn leaves included PTPN11, AKT1, PIK3R1, ESR1, and SRC, which were mainly involved in the PI3K-AKT, MAPK, and HIF-1 signaling pathways. In conclusion, the active components of sea buckthorn leaves are associated with the rich flavonoids and tannins, among which quercitrin, narcissoside, and ellagic acid can be used as the quality markers of sea buckthorn leaves. The findings provide a reference for the quality control and further development and utilization of sea buckthorn leaves as medicinal materials.
Assuntos
Hippophae , Hippophae/química , Farmacologia em Rede , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases/metabolismo , Flavonoides/análise , Frutas/químicaRESUMO
OBJECTIVES: To study the protective effect of melatonin (Mel) against oxygen-induced retinopathy (OIR) in neonatal mice and the role of the HMGB1/NF-κB/NLRP3 axis. METHODS: Neonatal C57BL/6J mice, aged 7 days, were randomly divided into a control group, a model group (OIR group), and a Mel treatment group (OIR+Mel group), with 9 mice in each group. The hyperoxia induction method was used to establish a model of OIR. Hematoxylin and eosin staining and retinal flat-mount preparation were used to observe retinal structure and neovascularization. Immunofluorescent staining was used to measure the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis and lymphocyte antigen 6G. Colorimetry was used to measure the activity of myeloperoxidase. RESULTS: The OIR group had destruction of retinal structure with a large perfusion-free area and neovascularization, while the OIR+Mel group had improvement in destruction of retinal structure with reductions in neovascularization and perfusion-free area. Compared with the control group, the OIR group had significant increases in the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis, the expression of lymphocyte antigen 6G, and the activity of myeloperoxidase (P<0.05). Compared with the OIR group, the OIR+Mel group had significant reductions in the above indices (P<0.05). Compared with the control group, the OIR group had significant reductions in the expression of melatonin receptors in the retina (P<0.05). Compared with the OIR group, the OIR+Mel group had significant increases in the expression of melatonin receptors (P<0.05). CONCLUSIONS: Mel can alleviate OIR-induced retinal damage in neonatal mice by inhibiting the HMGB1/NF-κB/NLRP3 axis and may exert an effect through the melatonin receptor pathway.