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1.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(3): 417-425, 2024 Mar 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38970516

RESUMO

OBJECTIVES: Rejection remains the most important factor limiting the survival of transplanted kidneys. Although a pathological biopsy of the transplanted kidney is the gold standard for diagnosing rejection, its limitations prevent it from being used as a routine monitoring method. Recently, peripheral blood lymphocyte subpopulation testing has become an important means of assessing the body's immune system, however, its application value and strategy in the field of kidney transplantation need further exploration. Additionally, the development and utilization of routine test parameters are also important methods for exploring diagnostic strategies and predictive models for kidney transplant diseases. This study aims to explore the correlation between peripheral blood lymphocyte subpopulations and T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR), as well as their diagnostic value, in conjunction with routine blood tests. METHODS: A total of 154 kidney transplant recipients, who met the inclusion and exclusion criteria and were treated at the Second Xiangya Hospital of Central South University from January to December, 2021, were selected as the study subjects. They were assigned into a stable group, a TCMR group, and an ABMR group, based on the occurrence and type of rejection. The basic and clinical data of these recipients were retrospectively analyzed and compared among the 3 groups. The transplant kidney function, routine blood tests, and peripheral blood lymphocyte subpopulation data of the TCMR group and the ABMR group before rejection treatment were compared with those of the stable group. RESULTS: The stable, TCMR group, and ABMR group showed no statistically significant differences in immunosuppressive maintenance regimens or sources of transplanted kidneys (all P>0.05). However, the post-transplant duration was significantly longer in the ABMR group compared with the stable group (P<0.001) and the TCMR group (P<0.05). Regarding kidney function, serum creatinine levels in the ABMR group were higher than in the stable group and the TCMR group (both P<0.01), with the TCMR group also showing higher levels than the stable group (P<0.01). Both TCMR and ABMR groups had significantly higher blood urea nitrogen levels than the stable group (P<0.01), with no statistically significant difference between TCMR and ABMR groups (P>0.05). The estimated glomerular filtration rate (eGFR) was lower in both TCMR and ABMR groups compared with the stable group (both P<0.01). In routine blood tests, the ABMR group had lower hemoglobin, red blood cell count, and platelet count than the stable group (all P<0.05). The TCMR group had higher neutrophil percentage (P<0.05) and count (P<0.05) than the stable group, and the ABMR group had a higher neutrophil percentage than the stable group (P<0.05). The eosinophil percentage and count in the TCMR group were lower than in the stable and ABMR groups (all P<0.05). Both TCMR and ABMR groups had lower basophil percentage and count, as well as lower lymphocyte percentage and count, compared with the stable group (all P<0.05). There were no significant differences in monocyte percentage and count among the 3 groups (all P>0.05). In lymphocyte subpopulations, the TCMR and ABMR groups had lower counts of CD45+ cells and T cells compared with the stable group (all P<0.05). The TCMR group also had lower counts of CD4+ T cells, NK cells, and B cells than the stable group (all P<0.05). There were no significant differences in the T cell percentage, CD4+ T cell percentage, CD8+ T cell percentage and their counts, CD4+/CD8+ T cell ratio, NK cell percentage, and B cell percentage among the stable, TCMR, and ABMR groups (all P>0.05). CONCLUSIONS: The occurrence of rejection leads to impaired transplant kidney function, accompanied by characteristic changes in some parameters of routine blood tests and peripheral blood lymphocyte subpopulations in kidney transplant recipients. The different characteristics of changes in some parameters of routine blood tests and peripheral blood lymphocyte subpopulations during TCMR and ABMR may help predict and diagnose rejection and differentiate between TCMR and ABMR.


Assuntos
Rejeição de Enxerto , Transplante de Rim , Humanos , Rejeição de Enxerto/sangue , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/imunologia , Estudos Retrospectivos , Feminino , Masculino , Subpopulações de Linfócitos/imunologia , Adulto , Pessoa de Meia-Idade , Linfócitos T/imunologia
2.
Chin J Integr Med ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38910189

RESUMO

OBJECTIVE: To examine the effectiveness of Chinese medicine (CM) Lianhua Qingwen Granule (LHQW) and Jingyin Gubiao Prescription (JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital. METHODS: This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group (23,702 cases), LHQW group (11,576 cases), JYGB group (12,112 cases), and dual combination of LHQW and JYGB group (8,854 cases). The length of stay (LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection. RESULTS: Patients aged 41-60 years, with nadir threshold cycle (CT) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching (PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS (both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups (P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS (P=0.032). CONCLUSIONS: Patients with a nadir CT value <25 were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.

3.
BMC Neurol ; 24(1): 177, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802769

RESUMO

BACKGROUND: Early prediction of delayed cerebral ischemia (DCI) is critical to improving the prognosis of aneurysmal subarachnoid hemorrhage (aSAH). Machine learning (ML) algorithms can learn from intricate information unbiasedly and facilitate the early identification of clinical outcomes. This study aimed to construct and compare the ability of different ML models to predict DCI after aSAH. Then, we identified and analyzed the essential risk of DCI occurrence by preoperative clinical scores and postoperative laboratory test results. METHODS: This was a multicenter, retrospective cohort study. A total of 1039 post-operation patients with aSAH were finally included from three hospitals in China. The training group contained 919 patients, and the test group comprised 120 patients. We used five popular machine-learning algorithms to construct the models. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, precision, and f1 score were used to evaluate and compare the five models. Finally, we performed a Shapley Additive exPlanations analysis for the model with the best performance and significance analysis for each feature. RESULTS: A total of 239 patients with aSAH (23.003%) developed DCI after the operation. Our results showed that in the test cohort, Random Forest (RF) had an AUC of 0.79, which was better than other models. The five most important features for predicting DCI in the RF model were the admitted modified Rankin Scale, D-Dimer, intracranial parenchymal hematoma, neutrophil/lymphocyte ratio, and Fisher score. Interestingly, clamping or embolization for the aneurysm treatment was the fourth button-down risk factor in the ML model. CONCLUSIONS: In this multicenter study, we compared five ML methods, among which RF performed the best in DCI prediction. In addition, the essential risks were identified to help clinicians monitor the patients at high risk for DCI more precisely and facilitate timely intervention.


Assuntos
Isquemia Encefálica , Aprendizado de Máquina , Hemorragia Subaracnóidea , Humanos , Hemorragia Subaracnóidea/epidemiologia , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/complicações , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/etiologia , Isquemia Encefálica/diagnóstico , Adulto , Idoso , Estudos de Coortes , Prognóstico , China/epidemiologia
4.
J Sci Med Sport ; 27(7): 458-465, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38584010

RESUMO

OBJECTIVES: This study aimed to compare and rank the effectiveness of aerobic exercise, resistance training, combined aerobic and resistance exercise, and high-intensity interval training on inflammatory marker levels in women with overweight and obesity by using network meta-analysis. DESIGN: Systematic review with network meta-analysis and Grading Recommendations Assessment, Development, and Evaluation of the evidence. METHODS: Literature as of April 2023 was searched from databases such as Cochrane, Embase, Pubmed, Web of Science, and EBSCO, and English-language randomized controlled trials that meet the inclusion criteria were selected. A random-effects network meta-analysis was performed within a frequentist framework. RESULTS: A total of 75 articles and 4048 participants were included. Resistance training was the most recommended type of exercise to decrease C-reactive protein levels (surface under cumulative ranking = 90.1; standardized mean difference = -0.79, 95 % confidence interval: -1.17, -0.42); aerobic exercise was the most effective exercise type to reduce tumor necrosis factor-α levels (surface under cumulative ranking = 87.9; standardized mean difference = -0.79, 95 % confidence interval: -1.19, -0.39); combined aerobic and resistance exercise was the most effective type of exercise to reduce interleukin-6 levels (surface under cumulative ranking = 75.8; standardized mean difference = -0.77, 95 % confidence interval: -1.38, -0.16) and leptin levels (surface under cumulative ranking = 77.1; standardized mean difference = -0.96, 95 % confidence interval: -1.72, -0.20), and high-intensity interval training was the type of exercise that was well suited to increase adiponectin levels (surface under cumulative ranking = 87.2; standardized mean difference = 0.99, 95 % confidence interval: 0.27, 1.71). CONCLUSIONS: This network meta-analysis based on randomized controlled trials confirmed that different exercise types have different efficacies on inflammation indicators among women with overweight and obesity. The findings may provide clinicians and healthcare professionals with insights into the implementation of exercise programs for women struggling with overweight and obesity.


Assuntos
Biomarcadores , Exercício Físico , Metanálise em Rede , Obesidade , Sobrepeso , Ensaios Clínicos Controlados Aleatórios como Assunto , Treinamento Resistido , Humanos , Feminino , Obesidade/sangue , Obesidade/terapia , Sobrepeso/terapia , Sobrepeso/sangue , Biomarcadores/sangue , Proteína C-Reativa/análise , Fator de Necrose Tumoral alfa/sangue , Interleucina-6/sangue , Treinamento Intervalado de Alta Intensidade , Leptina/sangue , Adiponectina/sangue , Inflamação/sangue
5.
Talanta ; 274: 125943, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38564823

RESUMO

Fenton chemistry has aroused widespread concern due to its application in the green oxidation and mineralization of organic wastes. Inorganic pyrophosphatase (PPase) catalyzes the hydrolysis of pyrophosphate ions (PPi) and provides a thermodynamic driving force for many biosynthetic reactions. Fluoride (F-) is widely applied to fight against tooth decay and reduce cavities. The electrochemical determination of PPase activity and F- was realized based on Fenton chemistry in this work. Glassy carbon electrode modified with poly (azure A) and acetylene black (GCE/PAA-AB) was fabricated. Hydroxyl radicals (∙OH) that were generated from a Cu2+-catalyzed Fenton-type reaction could oxidize PAA in the near-neutral medium, leading to a great increase of the cathodic peak current (Ipc). A coordination reaction between PPi and Cu2+ exerted a negative effect on Fenton reaction and hindered the Ipc enhancement. Cu2+-PPi complex was decomposed due to the hydrolysis of PPi induced by PPase, which caused the reappearance of the notably increased current response. F- could effectively inhibit PPase activity. As a result, the stable Cu2+-PPi complex remained and the high Ipc suffered from the decline again. The Ipc difference was used for the highly sensitive determination of PPase activity in the content range of 0.001-20 mU mL-1 with a detection of limit (LOD) at 0.6 µU mL-1 and that of F- in the concentration range of 0.01-100 µM with a LOD at 7 nM. The proposed PPase and F- sensor displayed a good selectivity, stability and reproducibility, and a high accuracy.


Assuntos
Técnicas Eletroquímicas , Fluoretos , Ferro , Fluoretos/química , Ferro/química , Técnicas Eletroquímicas/métodos , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Cobre/química , Eletrodos , Pirofosfatases/metabolismo , Pirofosfatases/análise , Pirofosfatase Inorgânica/metabolismo , Pirofosfatase Inorgânica/química , Limite de Detecção , Ensaios Enzimáticos/métodos
6.
Neuropsychiatr Dis Treat ; 20: 765-775, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38577632

RESUMO

Purpose: The SARS-CoV-2 infection cases are increasing rapidly in neuro-intensive care units (neuro-ICUs) at the beginning of 2023 in China. We aimed to characterize the prevalence, risk factors, and prognosis of critically ill patients treated in neuro-ICUs. Materials and Methods: In the prospective, multicenter, observational registry study, critically ill patients with intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and traumatic brain injury (TBI) admitted to eight Chinese neuro-ICUs between Feb 16, 2023, to Apr 30, 2023 were enrolled for the study. Mortality and ICU stay day were used as the primary outcomes. Results: 131 patients were finally included and analyzed (mean age 60.36 years [SD 13.81], 64.12% male, 39.69% SARS-CoV-2 infected). The mortality is higher in the SARS-CoV-2 infection group without statistical signification (7.69% vs 5.06%, p>0.05). The length of stay (LOS) in neuro-ICUs was significantly longer among the SARS-CoV-2 infection patients (7(1-12) vs 4(1-8), p<0.01), with increased viral pneumonia occurrence (58.54% vs 7.32%, p<0.01). SARS-CoV-2 infection, surgery, and low GCS scores were independent risk factors for prolonged LOS, and respiratory/renal failure were independent risk factors for death. Conclusion: Based on the present neuro-ICU cohort, SARS-CoV-2 infection was a significant risk for the prolonged LOS of neuro-critically ill patients. Trial Registration: Registered with Chictr.org.cn (ChiCTR2300068355) at 16 February 2023, Prospective registration. https://www.chictr.org.cn/showproj.html?proj=188252.

7.
JAMA Neurol ; 81(5): 549-550, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38436991

RESUMO

This case report studies a 12-year-old boy with a family history of X-linked adrenal leukodystrophy and his 8-year-old younger brother.


Assuntos
Adrenoleucodistrofia , Humanos , Masculino , Adrenoleucodistrofia/genética , Adrenoleucodistrofia/diagnóstico , Heterozigoto , Cariótipo , Membro 1 da Subfamília D de Transportadores de Cassetes de Ligação de ATP
8.
Int J Surg Protoc ; 28(1): 31-36, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38433866

RESUMO

Background: The aim of this study is to prospectively evaluate the new minimal invasive (MINE) browlift technique with possibly superior results and minimal visible scarring. Study design: A prospective observational study will be performed on all available data from patients who will undergo a browlift procedure in the HMC from 1 June 2021 till 31 May 2024. Our goal is to include at least 50 patients. Inclusion criteria are: patients with medical (i.e. brow ptosis and facial paralysis) or cosmetic indication, patients with sufficient understanding of the Dutch or English language and willingness to participate in extra study specific follow-up moments and filling in of questionnaires. Exclusion criteria are: less than 18 years of age and patients with previous brow or eyelid surgery. Patients will be photographed preoperatively and postoperatively using the VECTRA camera. Outcome measurements: Scarring after procedure; functionality of eyebrow movement; amount of correction in brow ptosis, measured in VECTRA; longevity of procedure in months; aesthetic result as assessed by questionnaires and adverse effects of procedure will be measured. Ethics and dissemination: The database management software 'Castor' will be used to store and collect the data from the questionnaire. The Medical Research Ethics Committee found this study not eligible to be submitted to the Dutch Medical Research Involving Human Subjects Acts (WMO). Written consent will be obtained from all patients.

9.
Neurol Ther ; 13(2): 475-495, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38367176

RESUMO

INTRODUCTION: No evidence has established a direct causal relationship between early microcirculation disturbance after aneurysmal subarachnoid hemorrhage (aSAH) and neurological function prognosis, which is the key pathophysiological mechanism of early brain injury (EBI) in patients with aSAH. METHODS: A total of 252 patients with aSAH were enrolled in the Neurosurgical Intensive Care Unit of Southwest Hospital between January 2020 and December 2022 and divided into the no neurological deterioration, early neurological deterioration, and delayed neurological deterioration groups. Indicators of microcirculation disorders in EBI included regional cerebral oxygen saturation (rSO2) measured by near-infrared spectroscopy (NIRS), brain oxygen monitoring, and other clinical parameters for evaluating neurological function and determining the prognosis of patients with aSAH. RESULTS: Our data suggest that the rSO2 is generally lower in patients who develop neurological deterioration than in those who do not and that there is at least one time point in the population of patients who develop neurological deterioration where left and right cerebral hemisphere differences can be significantly monitored by NIRS. An unordered multiple-classification logistic regression model was constructed, and the results revealed that multiple factors were effective predictors of early neurological deterioration: reoperation, history of brain surgery, World Federation of Neurosurgical Societies (WFNS) grade 4-5, Fisher grade 3-4, SAFIRE grade 3-5, abnormal serum sodium and potassium levels, and reduced rSO2 during the perioperative period. However, for delayed neurological deterioration in patients with aSAH, only a history of brain surgery and perioperative RBC count were predictive indicators. CONCLUSIONS: The rSO2 concentration in patients with neurological deterioration is generally lower than that in patients without neurological deterioration, and at least one time point in the population with neurological deterioration can be significantly monitored via NIRS. However, further studies are needed to determine the role of microcirculation and other predictive factors in the neurocritical management of EBI after aSAH, as these factors can reduce the incidence of adverse outcomes and mortality during hospitalization.

10.
ChemSusChem ; 17(11): e202301113, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38287461

RESUMO

Mechanistic studies involving characterization of crucial intermediates are desirable for rational optimization of molecular catalysts toward CO2 reduction, while fundamental challenges are associated with such studies. Herein we present the systematic mechanistic investigations on a pyrene-appended CoII macrocyclic catalyst in comparison with its pyrene-free prototype. The comparative results also verify the reasons of the higher catalytic activity of the pyrene-tethered catalyst in noble-metal-free CO2 photoreduction with various photosensitizers, where a remarkable apparent quantum yield of 36±3 % at 425 nm can be obtained for selective CO production. Electrochemical and spectroelectrochemical studies in conjunction with DFT calculations between the two catalysts have characterized the key CO-bound intermediates and revealed their different CO-binding behavior, demonstrating that the pyrene group endows the corresponding CoII catalyst a lower catalytic potential, a higher stability, and a greater ease in CO release, all of which contribute to its better performance.

11.
Cell Rep ; 43(1): 113658, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38175755

RESUMO

Poor skin wound healing, which is common in patients with diabetes, is related to imbalanced macrophage polarization. Here, we find that nutrition sensor GCN2 (general control nonderepressible 2) and its downstream are significantly upregulated in human skin wound tissue and mouse skin wound macrophages, but skin wound-related GCN2 expression and activity are significantly downregulated by diabetes and hyperglycemia. Using wound healing models of GCN2-deleted mice, bone marrow chimeric mice, and monocyte-transferred mice, we show that GCN2 deletion in macrophages significantly delays skin wound healing compared with wild-type mice by altering M1 and M2a/M2c polarization. Mechanistically, GCN2 inhibits M1 macrophages via OXPHOS-ROS-NF-κB pathway and promotes tissue-repairing M2a/M2c macrophages through eukaryotic translation initiation factor 2 (eIF2α)-hypoxia-inducible factor 1α (HIF1α)-glycolysis pathway. Importantly, local supplementation of GCN2 activator halofuginone efficiently restores wound healing in diabetic mice with re-balancing M1 and M2a/2c polarization. Thus, the decreased macrophage GCN2 expression and activity contribute to poor wound healing in diabetes and targeting GCN2 improves wound healing in diabetes.


Assuntos
Diabetes Mellitus Experimental , Animais , Humanos , Camundongos , Diabetes Mellitus Experimental/metabolismo , Regulação para Baixo , Macrófagos/metabolismo , Pele , Cicatrização
12.
J Chem Phys ; 159(20)2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-37991161

RESUMO

The cooperative emission of interacting nanocrystals is an exciting topic fueled by recent reports of superfluorescence and superradiance in assemblies of perovskite nanocubes. Several studies estimated that coherent coupling is localized to a small fraction of nanocrystals (10-7-10-3) within the assembly, raising questions about the origins of localization and ways to overcome it. In this work, we examine single-excitation superradiance by calculating radiative decays and the distribution of superradiant wave function in two-dimensional CsPbBr3 nanocube superlattices. The calculations reveal that the energy disorder caused by size distribution and large interparticle separations reduces radiative coupling and leads to the excitation localization, with the energy disorder being the dominant factor. The single-excitation model clearly predicts that, in the pursuit of cooperative effects, having identical nanocubes in the superlattice is more important than achieving a perfect spatial order. The monolayers of large CsPbBr3 nanocubes (LNC = 10-20 nm) are proposed as model systems for experimental tests of superradiance under conditions of non-negligible size dispersion, while small nanocubes (LNC = 5-10 nm) are preferred for realizing the Dicke state under ideal conditions.

13.
Regen Ther ; 24: 617-629, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38034857

RESUMO

Introduction: Bones are easily damaged. Biomimetic scaffolds are involved in tissue engineering. This study explored polydopamine (PDA)-coated poly lactic-co-glycolic acid (PLGA)-magnesium oxide (MgO) scaffold properties and its effects on bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation. Methods: PLGA/MgO scaffolds were prepared by low-temperature 3D printing technology and PDA coatings were prepared by immersion method. Scaffold structure was observed by scanning electron microscopy with an energy dispersive spectrometer (SEM-EDS), fourier transform infrared spectrometer (FTIR). Scaffold hydrophilicity, compressive/elastic modulus, and degradation rates were analyzed by water contact angle measurement, mechanical tests, and simulated-body fluid immersion. Rat BMSCs were cultured in scaffold extract. Cell activity on days 1, 3, and 7 was detected by MTT. Cells were induced by osteogenic differentiation, followed by evaluation of alkaline phosphatase (ALP) activity on days 3, 7, and 14 of induction and Osteocalcin, Osteocalcin, and Collagen I expressions. Results: The prepared PLGA/MgO scaffolds had dense microparticles. With the increase of MgO contents, the hydrophilicity was enhanced, scaffold degradation rate was accelerated, magnesium ion release rate and scaffold extract pH value were increased, and cytotoxicity was less when magnesium mass ratio was less than 10%. Compared with other scaffolds, compressive and elastic modulus of PLGA/MgO (10%) scaffolds were increased; BMSCs incubated with PLGA/MgO (10%) scaffold extract had higher ALP activity and Osteocalcin, Osteopontin, and Collagen I expressions. PDA coating was prepared in PLGA/MgO (10%) scaffolds and the mechanical properties were not affected. PLGA/MgO (10%)/PDA scaffolds had better hydrophilicity and biocompatibility and promoted BMSC osteogenic differentiation. Conclusion: Low-temperature 3D printing PLGA/MgO (10%)/PDA scaffolds had good hydrophilicity and biocompatibility, and were conducive to BMSC osteogenic differentiation.

14.
Front Pharmacol ; 14: 1288894, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026955

RESUMO

Parkinson's disease (PD) is a common neurodegenerative disorder with motor symptoms, which is caused by the progressive death of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). Accumulating evidence shows that endoplasmic reticulum (ER) stress occurring in the SNpc DA neurons is an early event in the development of PD. ER stress triggers the activation of unfolded protein response (UPR) to reduce stress and restore ER function. However, excessive and continuous ER stress and UPR exacerbate the risk of DA neuron death through crosstalk with other PD events. Thus, ER stress is considered a promising therapeutic target for the treatment of PD. Various strategies targeting ER stress through the modulation of UPR signaling, the increase of ER's protein folding ability, and the enhancement of protein degradation are developed to alleviate neuronal death in PD models. In this review, we summarize the pathological role of ER stress in PD and update the strategies targeting ER stress to improve ER protein homeostasis and PD-related events.

15.
BMJ Open ; 13(10): e075579, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37848300

RESUMO

BACKGROUND: SMARTTOUCH SURROUNDFLOW (STSF) catheter is the new generation of SMARTTOUCH (ST) catheter with an upgraded irrigation system for radiofrequency catheter ablation (RFCA) in patients with atrial fibrillation (AF). METHODS: This systematic literature review searched the major English and Chinese bibliographic databases from 2016 to 2022 for any original clinical studies assessing the STSF catheter for RFCA in AF patients. Meta-analysis with a random effects model was used for evidence synthesis. RESULTS: Pooled outcomes from 19 included studies indicated that STSF catheter was associated with a significantly shorter procedure time (weighted mean difference (WMD): -17.4 min, p<0.001), shorter ablation time (WMD: -6.6 min, p<0.001) and lower catheter irrigation fluid volume (WMD: -492.7 mL, p<0.001) than ST catheter. Pooled outcomes from four included studies with paroxysmal AF patients reported that using the STSF catheter for RFCA was associated with a significantly shorter ablation time (WMD: -5.7 min, p<0.001) and a lower risk of 1-year postablation arrhythmia recurrence (rate ratio: 0.504, p<0.001) than the SURROUNDFLOW (SF) catheter. Significant reductions in procedure time and ablation time associated with the STSF catheter were also reported in the other four studies using non-ST/SF catheters as the control. Overall complications of STSF catheter and control catheters were comparable. CONCLUSIONS: Using the STSF catheter was superior to using the ST catheter to conduct RFCA for AF by significantly reducing procedure time, ablation time, fluoroscopy time and irrigation fluid volume. The superiority of the STSF catheter over the SF catheter and other non-ST/SF catheters for RFCA needs further confirmation.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Humanos , Fibrilação Atrial/etiologia , Resultado do Tratamento , Catéteres , Ablação por Cateter/métodos , Fatores de Tempo , Recidiva
16.
Exp Gerontol ; 183: 112310, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37844768

RESUMO

IMPORTANCE: Postmenopausal women affected by overweight and obesity are susceptible to a variety of diseases due to inflammation. Exercise may reduce the risk of disease by attenuating low-grade chronic inflammation. OBJECTIVE: We conducted a systematic review and meta-analysis to investigate the effects of exercise on inflammatory markers in postmenopausal women struggling with overweight and obesity. METHOD: Literature as of May 2023 was searched from databases such as Cochrane, Embase, Pubmed, Web of Science, and EBSCO and English-language randomized controlled trials (RCTs) that meet the inclusion criteria were selected. Studies were included based on the following criteria: (A) Written in English; (B) RCTs; (C) Postmenopausal women impacted by overweight and obesity as research objects; (D) Outcome measurements include CRP, TNF-α, IL-6, and adiponectin; (E) Duration of the exercise intervention is eight weeks. RESULTS: A total of 34 articles and 2229 participants were included. Exercise can significantly reduce the level of C-reactive protein (CRP) (MD: -0.59, 95 % CI: -0.87 to -0.31, p < 0.00001), tumor necrosis factor-α (TNF-α) (MD: -0.65, 95 % CI: -0.94 to -0.35, p < 0.00001), interleukin-6 (IL-6) (MD: -0.48, 95 % CI: -0.75 to -0.21, p < 0.00001), and exercise can significantly increase the level of adiponectin (MD: 0.33, 95 % CI: 0.02 to 0.65, p = 0.04) in women impacted by overweight and obesity. CONCLUSION: These results suggest that exercise may be an effective intervention for reducing pro-inflammatory markers and increasing adiponectin in postmenopausal women impacted by overweight and obesity. The findings may provide clinicians and healthcare professionals with insights into the implementation of exercise programs for postmenopausal women living with overweight and obesity.


Assuntos
Interleucina-6 , Sobrepeso , Feminino , Humanos , Adiponectina , Proteína C-Reativa , Inflamação , Obesidade/terapia , Sobrepeso/terapia , Pós-Menopausa , Fator de Necrose Tumoral alfa
17.
Phys Rev Lett ; 131(8): 085101, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37683150

RESUMO

Warm dense matter (WDM) represents a highly excited state that lies at the intersection of solids, plasmas, and liquids and that cannot be described by equilibrium theories. The transient nature of this state when created in a laboratory, as well as the difficulties in probing the strongly coupled interactions between the electrons and the ions, make it challenging to develop a complete understanding of matter in this regime. In this work, by exciting isolated ∼8 nm copper nanoparticles with a femtosecond laser below the ablation threshold, we create uniformly excited WDM. Using photoelectron spectroscopy, we measure the instantaneous electron temperature and extract the electron-ion coupling of the nanoparticle as it undergoes a solid-to-WDM phase transition. By comparing with state-of-the-art theories, we confirm that the superheated nanoparticles lie at the boundary between hot solids and plasmas, with associated strong electron-ion coupling. This is evidenced both by a fast energy loss of electrons to ions, and a strong modulation of the electron temperature induced by strong acoustic breathing modes that change the nanoparticle volume. This work demonstrates a new route for experimental exploration of the exotic properties of WDM.

18.
J Fungi (Basel) ; 9(8)2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37623622

RESUMO

In this study, a halotolerant yeast that is capable of efficiently decolorizing and detoxifying azo dyes was isolated, identified and characterized for coping with the treatment of azo-dye-containing wastewaters. A characterization of the yeast, including the optimization of its metabolism and growth conditions, its detoxification effectiveness and the degradation pathway of the target azo dye, as well as a determination of the key activities of the enzyme, was performed. Finally, the possible halotolerance mechanisms of the yeast were proposed through a comparative transcriptome analysis. The results show that a halotolerant yeast, A4, which could decolorize various azo dyes, was isolated from a marine environment and was identified as Meyerozyma guilliermondii. Its optimal conditions for dye decolorization were ≥1.0 g/L of sucrose, ≥0.2 g/L of (NH4)2SO4, 0.06 g/L of yeast extract, pH 6.0, a temperature of 35 °C and a rotation speed of ≥160 rpm. The yeast, A4, degraded and detoxified ARB through a series of steps, relying on the key enzymes that might be involved in the degradation of azo dye and aromatic compounds. The halotolerance of the yeast, A4, was mainly related to the regulation of the cell wall components and the excessive uptake of Na+/K+ and/or compatible organic solutes into the cells under different salinity conditions. The up-regulation of genes encoding Ca2+-ATPase and casein kinase II as well as the enrichment of KEGG pathways associated with proteasome and ribosome might also be responsible for its halotolerance.

19.
BMC Nephrol ; 24(1): 200, 2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-37400798

RESUMO

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening disorder characterized by systemic inflammation and organ failure as a result of dysregulated immune cell activation. HLH can be induced by a variety of factors including infection, tumours and autoimmune disease and can also occur in patients following solid organ transplantation. Occurrence of HLH and lupus nephritis (LN) successively within a short period of time after renal transplantation is uncommon. CASE PRESENTATION: We described an 11-year-old female post-transplant patient who presented with hemocytopenia, fever, elevated serum ferritin, splenomegaly, hyperlipidemia, and hypofibrinemia, and was clinically diagnosed with HLH. After comprehensive treatment with corticosteroids, intravenous immunoglobulin (IVIG), and reducing immunosuppressants, her condition improved, but then hematuria ensued. The transplant kidney biopsy showed LN. She was treated with hydroxychloroquine and methylprednisolone while intensive immunosuppressive agents were given. She has remained in remission for two years until now. CONCLUSIONS: The main inducing factors of HLH should be identified as early as possible, and accurate treatment plans should be taken. The long-course IVIG regimen may be one of the effective treatments for virus-induced HLH. After remission of HLH, we need to be alert to the recurrence of autoimmune diseases in patients with underlying diseases, and timely increase immunosuppressants.


Assuntos
Transplante de Rim , Nefrite Lúpica , Linfo-Histiocitose Hemofagocítica , Viroses , Humanos , Criança , Feminino , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/etiologia , Transplante de Rim/efeitos adversos , Nefrite Lúpica/complicações , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Rim , Viroses/complicações
20.
J Med Chem ; 66(9): 6274-6287, 2023 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-37130037

RESUMO

Designed ligands of G protein-coupled receptors can exert a spectrum of modulating effects, varying from full agonists and partial agonists to antagonists and inverse agonists. For the dopamine D2 receptor (D2R), partial agonist activity is the pharmacological feature of the third-generation antipsychotics, including aripiprazole, brexpiprazole, and cariprazine. Started from a benzofuran-derived D2R full agonist O4LE6 (4), which was identified using a structure-based method by us in previous studies, a series of D2R partial agonists were designed and synthesized by introducing different tail groups. Among them, compound 10b showed excellent activity in D2R pharmacological assays. Further optimizations using a structural rigidification approach led to the discovery of brain-penetrant compounds 29c and 29d, which exhibited potent antipsychotic effects in the mouse hyperlocomotion model. Compound 29c also showed excellent drug-like pharmacokinetic properties in rats and qualifies as an antipsychotic agent that is worth further evaluations.


Assuntos
Antipsicóticos , Camundongos , Ratos , Animais , Antipsicóticos/farmacologia , Agonistas de Dopamina/farmacologia , Dopamina , Agonismo Inverso de Drogas , Receptores de Dopamina D2/agonistas
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