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Background: Current studies mostly suggest that hyperhidrosis is caused by relative sympathetic hyperactivity. Sympathetic radiofrequency thermocoagulation is widely used in clinics. Previous studies have demonstrated that surgery at T3 is effective and safe compared with higher levels, so craniofacial hyperhidrosis in our hospital is selected to be treated at T3. However, some patients pursue repeat medical treatment due to an increase in hyperhidrosis at the original site after surgery. Previous studies have demonstrated the significance of Perfusion index (PI) value in the recurrence of palmar hyperhidrosis, but there is no relevant study on craniofacial hyperhidrosis. Methods: Clinical data from patients with craniofacial hyperhidrosis, who underwent T3 sympathetic radiofrequency thermocoagulation at Jiaxing First Hospital (Jiaxing, China) between January 1, 2018 and December 31, 2021, were analyzed. Recurrence in patients 1 year after surgery was recorded through a case search and telephone follow-up system that registered patient information. Clinical data were analyzed using binary logistic regression analysis to investigate risk factors associated with recurrence in patients with craniofacial hyperhidrosis 1 year after surgery. Results: Of 83 patients included in the present study, 34 (40%) experienced increased craniofacial sweating 1 year after surgery. Results of univariate logistic regression analysis revealed that computed tomography (CT) scan count, increase in pulse index (PI) at the fingertips, and differences in forehead temperature were potential risk factors for postoperative recurrence in patients with craniofacial hyperhidrosis (p<0.2), and the results were consistent on both sides. Three potential risk factors were included in the multivariate logistic regression analysis and results revealed that the risk for recurrence was reduced by 48% (left side) and 67% (right side) for every 1 unit increase in PI value. Conclusion: A small increase in PI was an independent risk factor for recurrence of hyperhidrosis in patients with craniofacial hyperhidrosis after undergoing T3 sympathetic radiofrequency thermocoagulation.
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Objectives: Herpes zoster vaccination is critical in preventing herpes zoster virus infection and its associated consequences. Despite its relevance, global herpes zoster immunisation coverage remains alarmingly low. Understanding the factors that drive vaccine scepticism and acceptance is crucial for increasing immunisation rates and improving public health outcomes. Methods: This scoping review, following Joanna Briggs Institute guidelines, included 18 studies examining vaccine hesitancy, acceptance, and associated factors. Meticulous data analysis revealed hesitancy's intricate dynamics across countries and demographics. Results: Studies displayed a wide range of acceptance rates (2.8%-89.02%), showcasing the complex interplay of attitudes and behaviors towards vaccination. Reasons for vaccine refusal were repeatedly identified in this setting, including worries about potential adverse effects, views of vaccine necessity, and vaccine supply constraints. Notably, individuals' patterns of vaccine acceptance and hesitancy differed among countries, vaccines, and vaccination-related factors. Conclusion: Addressing acceptance hurdles by improving accessibility, providing accurate information, and strengthening healthcare recommendations is crucial. Understanding the multifaceted factors influencing hesitancy allows for targeted interventions, elevating immunization rates and enhancing public health globally.
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The relationship of ozone (O3), particularly the long-term exposure, with impacting metabolic homeostasis in population was understudied and under-recognised. Here, we used data from ChinaHEART, a nationwide, population-based cohort study, combined with O3 and PM2.5 concentration data with high spatiotemporal resolution, to explore the independent association of exposure to O3 with the prevalence of insulin resistance (IR). Among the 271 540 participants included, the crude prevalence of IR was 39.1%, while the age and sex standardized prevalence stood at 33.0%. Higher IR prevalence was observed with each increase of 10.0 µg/m3 in long-term O3 exposure, yielding adjusted odds ratios (OR) of 1.084 (95% CI: 1.079-1.089) in the one-pollutant model and 1.073 (95% CI: 1.067-1.079) in the two-pollutant model. Notably, a significant additive interaction between O3 and PM2.5 on the prevalence of IR was observed (P for additive interaction < 0.001). Our main findings remained consistent and robust in the sensitivity analyses. Our study suggests long-term exposure to O3 was independently and positively associated with prevalence of IR. It emphasized the benefits of policy interventions to reduce O3 and PM2.5 exposure jointly, which could ultimately alleviate the health and economic burden related to DM.
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Contaminantes Atmosféricos , Exposición a Riesgos Ambientales , Resistencia a la Insulina , Ozono , Ozono/toxicidad , Ozono/análisis , Humanos , Masculino , Femenino , Persona de Mediana Edad , Contaminantes Atmosféricos/toxicidad , Contaminantes Atmosféricos/análisis , China/epidemiología , Adulto , Estudios de Cohortes , Material Particulado/toxicidad , Anciano , PrevalenciaRESUMEN
Exercise has many beneficial effects that provide health and metabolic benefits. Signaling molecules are released from organs and tissues in response to exercise stimuli and are widely termed exerkines, which exert influence on a multitude of intricate multi-tissue processes, such as muscle, adipose tissue, pancreas, liver, cardiovascular tissue, kidney, and bone. For the metabolic effect, exerkines regulate the metabolic homeostasis of organisms by increasing glucose uptake and improving fat synthesis. For the anti-inflammatory effect, exerkines positively influence various chronic inflammation-related diseases, such as type 2 diabetes and atherosclerosis. This review highlights the prospective contribution of exerkines in regulating metabolism, augmenting the anti-inflammatory effects, and providing additional advantages associated with exercise. Moreover, a comprehensive overview and analysis of recent advancements are provided in this review, in addition to predicting future applications used as a potential biomarker or therapeutic target to benefit patients with chronic diseases.
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Ejercicio Físico , Inflamación , Humanos , Inflamación/metabolismo , Ejercicio Físico/fisiología , Diabetes Mellitus Tipo 2/metabolismo , Músculo Esquelético/metabolismo , Tejido Adiposo/metabolismo , Tejido Adiposo/inmunologíaRESUMEN
GaN heterostructure is a promising material for next-generation optoelectronic devices, and Indium gallium nitride (InGaN) has been widely used in ultraviolet and blue light emission. However, its applied potential for longer wavelengths still requires exploration. In this work, the ultra-thin InN/GaN superlattices (SL) were designed for long-wavelength light emission and investigated by first-principles simulations. The crystallographic and electronic properties of SL were comprehensively studied, especially the strain state of InN well layers in SL. Different strain states of InN layers were applied to modulate the bandgap of the SL, and the designed InN/GaN heterostructure could theoretically achieve photon emission of at least 650 nm. Additionally, we found the SL had different quantum confinement effects on electrons and holes, but an efficient capture of electron-hole pairs could be realized. Meanwhile, external forces were also considered. The orbital compositions of the valence band maximum (VBM) were changed with the increase in tensile stress. The transverse electric (TE) mode was found to play a leading role in light emission in normal working conditions, and it was advantageous for light extraction. The capacity of ultra-thin InN/GaN SL on long-wavelength light emission was theoretically investigated.
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Enolase-1 (Eno1) plays a critical role in regulating glucose metabolism; however, its specific impact on pancreatic islet ß-cells remains elusive. This study aimed to provide a preliminary exploration of Eno1 function in pancreatic islet ß-cells. The findings revealed that the expression of ENO1 mRNA in type 2 diabetes donors was significantly increased and positively correlated with HbA1C and negatively correlated with insulin gene expression. A high level of Eno1 in human insulin-secreting rat INS-1832/13 cells with co-localization with intracellular insulin proteins was accordingly observed. Silencing of Eno1 using siRNA or inhibiting Eno1 protein activity with an Eno1 antagonist significantly reduced insulin secretion and insulin content in ß-cells, while the proinsulin/insulin content ratio remained unchanged. This reduction in ß-cells function was accompanied by a notable decrease in intracellular ATP and mitochondrial cytochrome C levels. Overall, our findings confirm that Eno1 regulates the insulin secretion process, particularly glucose metabolism and ATP production in the ß-cells. The mechanism primarily involves its influence on insulin production, suggesting that Eno1 represents a potential target for ß-cell protection and diabetes treatment.
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Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Humanos , Ratas , Animales , Insulina/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Células Secretoras de Insulina/metabolismo , Fosfopiruvato Hidratasa/genética , Fosfopiruvato Hidratasa/metabolismo , Glucosa/metabolismo , Expresión Génica , Adenosina Trifosfato/metabolismoRESUMEN
AIM: In neuroendocrine cells, large dense-core vesicles (LDCVs) undergo highly regulated pre-fusion processes before releasing hormones via membrane fusion. Significant heterogeneity has been found for LDCV population based on the dynamics of membrane fusion. However, how the pre-fusion status impacts the heterogeneity of LDCVs still remains unclear. Hence, we explored pre-fusion determinants of heterogeneous membrane fusion procedure of LDCV subpopulations. METHODS: We assessed the pre-fusion motion of two LDCV subpopulations with distinct membrane fusion dynamics individually, using total internal reflection fluorescence microscopy. These two subpopulations were isolated by blocking Rho GTPase-dependent actin reorganization using Clostridium difficile toxin B (ToxB), which selectively targets the fast fusion vesicle pool. RESULTS: We found that the fast fusion subpopulation was in an active motion mode prior to release, termed "active" LDCV pool, while vesicles from the slow fusion subpopulation were also moving but in a significantly more confined status, forming an "inert" pool. The depletion of the active pool by ToxB also eliminated fast fusion vesicles and was not rescued by pre-treatment with phorbol ester. A mild actin reorganization blocker, latrunculin A, that partially disrupted the active pool, only slightly attenuated the fast fusion subpopulation. CONCLUSION: The pre-fusion motion state of LDCVs also exhibits heterogeneity and dictates the heterogeneous fusion pore dynamics. Rearrangement of F-actin network mediates vesicle pre-fusion motion and subsequently determines the membrane fusion kinetics.
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Vesículas de Núcleo Denso , Fusión de Membrana , Humanos , Actinas , Exocitosis , Transporte BiológicoRESUMEN
The emergence of graphene quantum dots (GQDs) expands the use of graphene derivatives in nanomedicine for its direct therapeutic applications in treating neurodegeneration, inflammation, metabolic dysfunction, and among others. Nevertheless, the biosafety assessment of GQDs remains deficient mostly because of the diverse surface characteristics of the nanoparticles. Our prior work demonstrated that GQDs can induce strong thigmotactic effects in zebrafish larvae over a wide range of concentrations, yet the underlying metabolic mechanisms remain largely unknown. In this study, we conducted a further exploration about graphene oxide quantum dots (GOQDs) for its potential neurotoxic effect on the behaviors of zebrafish larvae by combining neurotransmitter-targeted metabolomics with locomotion analysis. After continuous exposure to a concentration gradient of GOQDs (12.5 - 25 - 50 - 100 - 200 µg/mL) for 7 days, the thigmotactic activities of zebrafish larvae were observed across all exposure concentrations relative to the control group, while the basal locomotor activities, including distance moved and average velocity, were significantly changed by low concentrations of GOQDs. Targeted metabolomics was performed using zebrafish larvae at 7 days post-fertilization (dpf) that were exposed to 12.5 and 200 µg/mL, both of which were found to perturb the kynurenine pathway by regulating the levels of kynurenine, 3-hydroxyanthranilic acid (3-HAA), and quinolinic acid (QA). Furthermore, the thigmotaxis of larval fish induced by GOQDs during exposure could be counteracted by supplementing Ro-61-8048, an agonist acting on kynurenine 3-monooxygenase (KMO). In conclusion, our study establishes the involvement of the kynurenine pathway in GOQDs-induced thigmotaxis, which is independent of the transcriptional modulation of glutamate receptor families.
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Grafito , Puntos Cuánticos , Animales , Pez Cebra , Grafito/toxicidad , Puntos Cuánticos/toxicidad , Quinurenina/farmacología , LarvaRESUMEN
We propose two novel transferability metrics fast optimal transport-based conditional entropy (F-OTCE) and joint correspondence OTCE (JC-OTCE) to evaluate how much the source model (task) can benefit the learning of the target task and to learn more generalizable representations for cross-domain cross-task transfer learning. Unlike the original OTCE metric that requires evaluating the empirical transferability on auxiliary tasks, our metrics are auxiliary-free such that they can be computed much more efficiently. Specifically, F-OTCE estimates transferability by first solving an optimal transport (OT) problem between source and target distributions and then uses the optimal coupling to compute the negative conditional entropy (NCE) between the source and target labels. It can also serve as an objective function to enhance downstream transfer learning tasks including model finetuning and domain generalization (DG). Meanwhile, JC-OTCE improves the transferability accuracy of F-OTCE by including label distances in the OT problem, though it incurs additional computation costs. Extensive experiments demonstrate that F-OTCE and JC-OTCE outperform state-of-the-art auxiliary-free metrics by 21.1% and 25.8% , respectively, in correlation coefficient with the ground-truth transfer accuracy. By eliminating the training cost of auxiliary tasks, the two metrics reduce the total computation time of the previous method from 43 min to 9.32 and 10.78 s, respectively, for a pair of tasks. When applied in the model finetuning and DG tasks, F-OTCE shows significant improvements in the transfer accuracy in few-shot classification experiments, with up to 4.41% and 2.34% accuracy gains, respectively.
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Diabetic muscle atrophy is an inflammation-related complication of type-2 diabetes mellitus (T2DM). Even though regular exercise prevents further deterioration of atrophic status, there is no effective mediator available for treatment and the underlying cellular mechanisms are less explored. In this study, we investigated the therapeutic potential of MCC950, a specific, small-molecule inhibitor of NLRP3, to treat pyroptosis and diabetic muscle atrophy in mice. Furthermore, we used MCC950 to intervene in the protective effects of aerobic exercise against muscle atrophy in diabetic mice. Blood and gastrocnemius muscle (GAS) samples were collected after 12 weeks of intervention and the atrophic state was assessed. We initially corroborated a diabetic muscle atrophy phenotype in db/db mice (D) by comparison with control m/m mice (W) by examining parameters such as fasting blood glucose (D vs. W: 24.47 ± 0.45 mmol L-1 vs. 4.26 ± 0.6 mmol L-1, p < 0.05), grip strength (D vs. W: 166.87 ± 15.19 g vs. 191.76 ± 14.13 g, p < 0.05), exercise time (D vs. W: 1082.38 ± 104.67 s vs. 1716 ± 168.55 s, p < 0.05) and exercise speed to exhaustion (D vs. W: 24.25 ± 2.12 m min-1 vs. 34.75 ± 2.66 m min-1, p < 0.05), GAS wet weight (D vs. W: 0.07 ± 0.01 g vs. 0.13 ± 0.01 g, p < 0.05), the ratio of GAS wet weight to body weight (D vs. W: 0.18 ± 0.01% vs. 0.54 ± 0.02%, p < 0.05), and muscle fiber cross-sectional area (FCSA) (D vs. W: 1875 ± 368.19 µm2 vs. 2747.83 ± 406.44 µm2, p < 0.05). We found that both MCC950 (10 mg kg-1) treatment and exercise improved the atrophic parameters that had deteriorated in the db/db mice, inhibited serum inflammatory markers and significantly attenuated pyroptosis in atrophic GAS. In addition, a combined MCC950 treatment with exercise (DEI) exhibited a further improvement in glucose uptake capacity and muscle performance. This combined treatment also improved the FCSA of GAS muscle indicated by Laminin immunofluorescence compared to the group with the inhibitor treatment alone (DI) (DEI vs. DI: 2597 ± 310.97 vs. 1974.67 ± 326.15 µm2, p < 0.05) or exercise only (DE) (DEI vs. DE: 2597 ± 310.97 vs. 2006.33 ± 263.468 µm2, p < 0.05). Intriguingly, the combination of MCC950 treatment and exercise significantly reduced NLRP3-mediated inflammatory factors such as cleaved-Caspase-1, GSDMD-N and prevented apoptosis and pyroptosis in atrophic GAS. These findings for the first time demonstrate that targeting NLRP3-mediated pyroptosis with MCC950 improves diabetic muscle homeostasis and muscle function. We also report that inhibiting pyroptosis by MCC950 can enhance the beneficial effects of aerobic exercise on diabetic muscle atrophy. Since T2DM and muscle atrophy are age-related diseases, the young mice used in the current study do not seem to fully reflect the characteristics of diabetic muscle atrophy. Considering the fragile nature of db/db mice and for the complete implementation of the exercise intervention, we used relatively young db/db mice and the atrophic state in the mice was thoroughly confirmed. Taken together, the current study comprehensively investigated the therapeutic effect of NLRP3-mediated pyroptosis inhibited by MCC950 on diabetic muscle mass, strength and exercise performance, as well as the synergistic effects of MCC950 and exercise intervention, therefore providing a novel strategy for the treatment of the disease.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Ratones , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Inflamasomas , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/terapia , Piroptosis , Sulfonamidas/farmacología , Ratones Endogámicos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/terapia , Ejercicio Físico , Atrofia Muscular/tratamiento farmacológico , Atrofia Muscular/etiologíaRESUMEN
The basolateral amygdala (BLA) appears to serve an important function in the pathophysiology of depression. Depressive symptoms, such as anhedonia are largely caused by dysfunction in the brain's reward system, in which the ventral pallidum (VP) participates in by controlling dopamine release. However, the role of the BLA-VP pathway in the development of depression remains poorly understood. To investigate this pathway, we employed the Chronic Unpredictable Mild Stress (CUMS) mouse model, in which we injected retroAAV expressing GFP-Cre into the VP and AAV expressing hM4Di-mCherry into the BLA. We then used CNO to activate the Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) for all behavioral tests. The CUMS procedure resulted in significant depression symptoms such as decreased sucrose preference, limited weight gain, decreased immobile latency, and increased immobile time in the forced swim and tail suspension tests. Inhibition of the BLA-VP glutamatergic projections reversed these depression-like behaviors. We found that suppressing the BLA-VP circuitry had beneficial effects on CUMS-induced depression-like behaviors such as anorexia, anhedonia, and despair. Specifically, upon suppression of glutamatergic projections in the BLA-VP circuitry, these depression-like behaviors were significantly alleviated, which highlights the vital role of this circuitry in the development of depression. Furthermore, the beneficial effects of suppressing this circuitry seem to be associated with the brain's reward system, warranting further investigation.
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Prosencéfalo Basal , Trastorno Depresivo , Ratones , Masculino , Animales , Depresión/etiología , Anhedonia , Trastorno Depresivo/etiología , Amígdala del Cerebelo , Estrés Psicológico/metabolismo , Modelos Animales de EnfermedadRESUMEN
BACKGROUND AND AIMS: Macrophage-derived foam cells play a causal role during the pathogenesis of atherosclerosis. P2Y6 receptor (P2Y6R) highly expressed has been considered as a disease-causing factor in atherogenesis, but the detailed mechanism remains unknown. This study aims to explore P2Y6R in regulation of macrophage foaming, atherogenesis, and its downstream pathways. Furthermore, the present study sought to find a potent P2Y6R antagonist and investigate the feasibility of P2Y6R-targeting therapy for atherosclerosis. METHODS: The P2Y6R expression was examined in human atherosclerotic plaques and mouse artery. Atherosclerosis animal models were established in whole-body P2Y6R or macrophage-specific P2Y6R knockout mice to evaluate the role of P2Y6R. RNA sequencing, DNA pull-down experiments, and proteomic approaches were performed to investigate the downstream mechanisms. High-throughput Glide docking pipeline from repurposing drug library was performed to find potent P2Y6R antagonists. RESULTS: The P2Y6R deficiency alleviated atherogenesis characterized by decreasing plaque formation and lipid deposition of the aorta. Mechanically, deletion of macrophage P2Y6R significantly inhibited uptake of oxidized low-density lipoprotein through decreasing scavenger receptor A expression mediated by phospholipase Cß/store-operated calcium entry pathways. More importantly, P2Y6R deficiency reduced the binding of scavenger receptor A to CALR, accompanied by dissociation of calreticulin and STIM1. Interestingly, thiamine pyrophosphate was found as a potent P2Y6R antagonist with excellent P2Y6R antagonistic activity and binding affinity, of which the pharmacodynamic effect and mechanism on atherosclerosis were verified. CONCLUSIONS: Macrophage P2Y6R regulates phospholipase Cß/store-operated calcium entry/calreticulin signalling pathway to increase scavenger receptor A protein level, thereby improving foam cell formation and atherosclerosis, indicating that the P2Y6R may be a potential therapeutic target for intervention of atherosclerotic diseases using P2Y6R antagonists including thiamine pyrophosphate.
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Aterosclerosis , Células Espumosas , Receptores Purinérgicos P2 , Humanos , Ratones , Animales , Células Espumosas/metabolismo , Células Espumosas/patología , Calcio/metabolismo , Calreticulina/metabolismo , Calreticulina/farmacología , Proteómica , Tiamina Pirofosfato/metabolismo , Tiamina Pirofosfato/farmacología , Aterosclerosis/genética , Macrófagos/metabolismo , Lipoproteínas LDL/metabolismo , Receptores Depuradores/metabolismo , Ratones Noqueados , Fosfolipasas/metabolismo , Fosfolipasas/farmacologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Jin-Si-Wei (JSW), a traditional Chinese medicine (TCM) formula, have cognitive enhancing effect and delay the memory decline in an animal model of ADï¼ which has been reported. However, the therapeutic mechanism of JSW in the treatment of AD remains unclear. AIM OF THE STUDY: This study aimed to verify the pharmacodynamics of JSW in the treatment of AD, and to explore its potential mechanism based on network pharmacology, molecular docking and experimental validation both in vitro and in vivo. MATERIALS AND METHODS: In this study, the underlying mechanism of JSW against AD was investigated by the integration of network pharmacology. Then, the core pathways and biological process of JSW were verified by experiment, including behavioral test and pathological and biochemical assays with 6-month-old APPswe/PS1ΔE9 transgenic (APP/PS1) mice in vivo and verified with Aß1-42-stimulated SH-SY5Y cells in vitro. At last, molecular docking was used to show the binding activity of each active ingredient to the core genes of JSW treatment in AD. RESULTS: A Drug-Ingredient-Target network was established, which included 363 ingredients and 116 targets related to the JSW treatment of AD. The main metabolic pathway of JSW treatment for AD is neuroactive ligand-receptor interaction pathway, and biological processes are mainly involved in Aß metabolic process. In vivo experiments, compared with APP/PS1 mice, the cognitive and memory ability of mice was significantly improved after JSW administration. In brain tissue of APP/PS1 mice, JSW could increase the contents of low-density lipoprotein receptor-related protein 1 (LRP-1), enkephalinase (NEP) and Acetyl choline (ACh), and decrease the contents of Aß1-42, amyloid precursor protein (APP) and receptor for advanced glycation end products (RAGE), decrease the vitality of cholinesterase (AChE) and choline acetyltransferase (ChAT). Besides, JSW could increase α-secretase expression and decrease ß/γ-secretase expression, and improve the number and morphology of synapses in CA1 region of the hippocampus of APP/PS1 mice. In vitro experiments, Drug-Containing Serum (JSW-serum) has a neuroprotective effect by reducing the apoptosis on Aß1-42-stimulated SH-SY5Y cells. Molecular docking results showed that 2-Isopropyl-8-methylphenanthrene-3,4-dione had strong binding activity with PTGS2, which maybe a potential ingredient for the treatment of AD. CONCLUSIONS: JSW improves AD in APP/PS1 mice, and this therapeutic effect may be achieved in part by altering the neuroactive ligand-receptor interaction pathway.
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Enfermedad de Alzheimer , Neuroblastoma , Humanos , Animales , Ratones , Enfermedad de Alzheimer/tratamiento farmacológico , Ligandos , Simulación del Acoplamiento Molecular , Farmacología en Red , Precursor de Proteína beta-Amiloide/genética , Secretasas de la Proteína Precursora del AmiloideRESUMEN
With the global Omicron pandemic and the adjustment of the zero-coronavirus disease 2019 (zero-COVID-19) strategy in China, there is a critical need to improve vaccination rates among older adults while addressing the mental health issues associated with vaccination. This study investigated levels of COVID-19-related anxiety, depression, benefit finding, and fear in older adults and explored the relationship between vaccine hesitancy, sociodemographic factors, and mental health. Participants aged 60 and older (n = 658) were recruited from several cities in the eastern, central, and western China regions. Of these, 347 exhibited vaccine hesitancy. The effects of residence, education, health status, and COVID-19 vaccination on anxiety/depression/benefit-finding were found to be mediated/suppressed by vaccine hesitancy. Additionally, in investigating psychological antecedents, older people without vaccine hesitancy showed higher confidence, lower complacency, fewer constraints, and a greater sense of collective responsibility. This study advances our understanding of mental health differences in anxiety, depression, and benefit-finding across sociodemographic characteristics. It is essential to improve population confidence related to vaccines, accessibility to vaccination services, and responsibility to mitigate vaccine hesitancy while paying close attention to the mental health associated with vaccination in older adults.
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COVID-19 , Salud Mental , Anciano , Humanos , Persona de Mediana Edad , Análisis de Mediación , Vacunas contra la COVID-19 , Vacilación a la Vacunación , COVID-19/epidemiología , COVID-19/prevención & control , China/epidemiología , VacunaciónRESUMEN
Cocaine and amphetamine-regulated transcript (CART) is expressed in pancreatic islet cells and neuronal elements. We have previously established insulinotropic actions of CART in human and rodent islets. The receptor for CART in the pancreatic beta cells is unidentified. We used RNA sequencing of Cartpt knockdown (KD) INS-1 832/13 cells and identified GPR162 as the most Cartpt-regulated receptor. We therefore tested if GPR162 mediates the effects of CART in beta cells. Binding of CART to GPR162 was established using proximity ligation assay, radioactive binding, and co-immunoprecipitation, and KD of Gpr162 mRNA caused reduced binding. Gpr162 KD cells had blunted CARTp-induced exocytosis, and reduced CARTp-induced insulin secretion. Furthermore, we identified a hitherto undescribed GPR162-dependent role of CART as a regulator of cytoskeletal arrangement. Thus, our findings provide mechanistic insight into the effect of CART on insulin secretion and show that GPR162 is the CART receptor in beta cells.
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BACKGROUND: Elderly patients with breast cancer often have more unmet needs after receiving common treatments such as surgery and chemotherapy. Type D personality has been related to supportive care needs in the general population. However, its association with supportive care needs in elderly breast cancer patients has not been prospectively explored. This study aimed to address this gap. OBJECTIVES: The aim was to understand the impact of Type D personality on the supportive care needs of elderly breast cancer patients at diagnosis, 2 weeks postoperatively, 3 months postoperatively, and 6 months postoperatively and to analyse the impact of Type D personality on the changing trajectory of supportive care needs after controlling for confounding factors such as demographics, symptom distress and social support. METHODS: A total of 122 elderly patients (≥ 65 years) with breast cancer in Ruijin Hospital, Shanghai, China, were included from September 2021 until August 2022. Supportive care needs were measured by the Supportive Care Needs Survey Short Form and tracked at diagnosis, 2 weeks postoperatively, 3 months postoperatively, and 6 months postoperatively. To investigate changes in the supportive care needs of elderly breast cancer patients and the effect of Type D personality on these needs, a linear mixed model was applied. RESULTS: A total of 122 elderly patients participated. There was an overall decreasing trend in supportive care needs, with Type D personality patients having significantly higher levels of supportive care needs than the non-Type D personality patients at all stages. Through linear mixed models, it was found that the Type D personality group had a lower overall downward trend than the non-Type D personality group, with need levels remaining consistently higher. This difference persisted after controlling for demographic information, symptom burden, social support. CONCLUSIONS: Elderly breast cancer patients with Type D personality had higher levels of supportive care needs and a slower rate of decline that was maintained over a longer period than those with non-Type D personality.
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Neoplasias de la Mama , Personalidad Tipo D , Humanos , Anciano , Femenino , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/terapia , Neoplasias de la Mama/diagnóstico , Estudios Prospectivos , China/epidemiología , Evaluación de Necesidades , Necesidades y Demandas de Servicios de Salud , Apoyo Social , Encuestas y Cuestionarios , Calidad de VidaRESUMEN
BACKGROUND: Extracranial nonsemilunar ganglion radiofrequency thermocoagulation in the treatment of postherpetic trigeminal neuralgia has significant clinical effects. However, the related risk factors for its recurrence have not been studied. OBJECTIVE: This study aimed to investigate the risk factors for the recurrence of postherpetic trigeminal neuralgia after extracranial nonsemilunar ganglion radiofrequency thermocoagulation, and to construct a recurrence prediction model. STUDY DESIGN: This is a single-center, retrospective observational study. SETTING: The study was conducted in the Department of Pain, Affiliated Hospital of Jiaxing College, Jiaxing, People's Republic of China. METHODS: A total of 76 patients with postherpetic trigeminal neuralgia admitted to the First Hospital of Jiaxing from July 2013 through October 2021 were retrospectively analyzed. All patients were treated with computed tomography-guided extracranial nonsemilunar segment radiofrequency therapy. The Kaplan-Meier method was used for survival analysis, the log-rank test was used, and the Cox proportional hazards regression model was used to analyze the clinical factors affecting postherpetic trigeminal neuralgia recurrence after extracranial nosemilunar ganglia radiofrequency thermocoagulation; in addition, a recurrence prediction model was established. RESULTS: Patients were followed-up for 12 months. A univariate analysis showed that age and disease duration are the factors affecting postherpetic trigeminal neuralgia recurrence after extracranial nonsemilunar ganglion radiofrequency thermocoagulation (P < 0.05). A multivariate Cox proportional hazards regression analysis showed that age and disease duration were independent influencing factors. The recurrence risk function model is expressed as follows. H (t) = h0exp (1.116 X1 + 1.340 X2), where X1 and X2 represent age and disease duration, respectively. The likelihood ratio of the model was tested, and the likelihood ratio was 195.776, showing statistical significance. LIMITATIONS: We look forward to increasing the sample size in subsequent studies and exploring relevant conclusions in randomized controlled trials. CONCLUSION: A short disease duration and young age can reduce the risk of recurrence after extracranial nonsemilunar ganglia radiofrequency thermocoagulation in patients with postherpetic trigeminal neuralgia. Our established recurrence prediction model can provide a reference for clinical diagnosis and treatment.
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Herpes Zóster , Neuralgia Posherpética , Neuralgia del Trigémino , Humanos , Neuralgia del Trigémino/cirugía , Resultado del Tratamiento , Estudios Retrospectivos , Factores de Riesgo , Electrocoagulación/métodos , Neuralgia Posherpética/terapia , Neuralgia Posherpética/etiologíaRESUMEN
Glucagon-like peptide 1 receptor agonist exenatide (exendin-4) has potential protective capabilities against diabetic kidney disease (DKD). However, the underlying mechanism has not been fully elucidated. The expression of thioredoxin-interacting protein (Txnip) is upregulated during DKD progression by histone acetylation. Sirtuin 1 (SIRT1) is a deacetylase and is decreased in DKD, which indicates that it may regulate Txnip in this disease. Here, we used whole-body heterozygous Sirt1 knockout (Sirt1+/-) and kidney-specific Sirt1 knockout (KSK) mice to investigate whether SIRT1 regulates Txnip via histone deacetylation in DKD and exenatide-alleviated DKD. Exenatide substantially improved renal pathological damage, decreased the albumin-to-creatinine ratio (ACR), upregulated SIRT1 expression, and downregulated Txnip expression in kidneys of high-fat diet-treated C57BL/6J mice. However, these effects diminished in Sirt1+/- and KSK mice under exenatide treatment. The downregulation of Txnip expression by exendin-4 in high-glucose-treated SV40 MES13 cells was hampered during Sirt1 knockdown. These results demonstrate that kidney SIRT1 is indispensable in exenatide-improved DKD and downregulation of Txnip expression. Exendin-4 mechanistically downregulated Txnip histone 3 lysine 9 acetylation (H3K9ac) in a SIRT1-dependent manner and decreased spliced X-box binding protein 1 (XBP1s) recruitment to the Txnip promoter. These findings provide epigenetic evidence elucidating the specific mechanism for exenatide-mediated DKD alleviation and highlight the importance of Txnip as a promising therapeutic target for DKD.