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1.
Front Neurol ; 15: 1374542, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38765261

RESUMO

Purpose: Traditional Chinese medicine (TCM) therapies, especially acupuncture, have received increasing attention in the field of pain management. This meta-analysis evaluated the effectiveness of acupuncture in the treatment of myofascial pain syndrome. Methods: A comprehensive search was conducted across a number of databases, including PubMed, Cochrane Library, WOS, CNKI, WANFANG, Sinomed, and VIP. Furthermore, articles of studies published from the inception of these databases until November 22, 2023, were examined. This systematic review and meta-analysis encompassed all randomized controlled trials (RCTs) on acupuncture for myofascial pain syndromes, without language or date restrictions. Based on the mean difference (MD) of symptom change, we critically assessed the outcomes reported in these trials. The quality of evidence was assessed using the Cochrane Risk of Bias Tool. The study is registered with PROSPERO under registration number CRD42023484933. Results: Our analysis included 10 RCTs in which 852 patients were divided into two groups: an acupuncture group (427) and a control group (425). The results of the study showed that acupuncture was significantly more effective than the control group in treating myofascial pain syndromes, which was reflected in a greater decrease in VAS scores (MD = -1.29, 95% [-1.65, -0.94], p < 0.00001). In addition, the improvement in PRI and PPI was more pronounced in the acupuncture group (PRI: MD = -2.04, 95% [-3.76, -0.32], p = 0.02) (PPI: MD = -1.03, 95% [-1.26, -0.79], p < 0.00001) compared to the control group. These results suggest that acupuncture is effective in reducing myofascial pain. It is necessary to further study the optimal acupoints and treatment time to achieve the best therapeutic effect. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023484933.

2.
ACS Nano ; 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38761383

RESUMO

Atmospheric water harvesting is a practical strategy that is achieved by removing materials from air moisture to relieve global water scarcity. Here we design a water-harvester (i.e., MOF-303/thiolated polymer composite (MTC)) by using a metal-organic framework (MOF-303) and thiolated chitosan (TC) skeleton. Intermolecular hydrogen bonding between TC and MOF-303 facilitates porous structures with enlarged air-polymer interfaces for long cycling life and high capacity at low relative humidity. Benefiting from synergetic effects on porosity and anchorage for accelerating the uptake-release of moisture, MTC exhibits a rapid water uptake capacity of 0.135 g/g in 60 min under 12.5 RH% and ultrafast water desorption kinetics of 0.003 g/g/min at 8.5 RH%, which is superior to the as-reported MOF-303 based adsorbents. At low heat (∼40 °C), the water desorption and collection rate, respectively, are 0.0195 and 0.0168 g/g/min within 210 min, showing ultrahigh harvesting efficiency. These results highlight the enormous potential as promising materials for solving the world's water scarcity crisis. This study offers an insight into the design of AWH materials, which can be extended into applications in some realms, e.g., freshwater development for industry in arid areas, water engineering-related devices and systems, etc.

3.
Nat Commun ; 15(1): 4159, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755225

RESUMO

Metal-hydrogen systems have attracted intense interest for diverse energy-related applications. However, metals usually reduce their ductility after hydrogenation. Here, we show that hydrogen can take the form of nano-sized ordered hydrides (NOH) homogeneously dispersed in a stable glassy shell, leading to remarkable enhancement in both strength and ductility. The yield strength is enhanced by 44% and the plastic strain is substantially improved from almost zero to over 70%, which is attributed to the created NOH and their interplay with the glassy shell. Moreover, the hydride-glass composite GdCoAlH possesses a giant magnetic entropy change (-ΔSM) of 18.7 J kg-1K-1 under a field change of 5 T, which is 105.5% larger than the hydrogen-free sample and is the largest value among amorphous alloys and related composites. The prominent ΔSM-ductility combination overcomes the bottlenecks of amorphous alloys as magnetic refrigerants. These results provide a promising strategy for property breakthrough of structural-functional alloys.

4.
Clin Case Rep ; 12(4): e8786, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38645604

RESUMO

Key Clinical Message: This case report provides a rare case of idiopathic root resorption in maxillary first molar and suggests the importance of CBCT in the diagnosis and treatment outcome of complex endodontic diseases. Endodontic surgery is an effective method for treating teeth with persistent apical periodontitis. Abstract: Idiopathic root resorption is an unexplained root resorption when the patient experiences root resorption without any local or systemic factors. Early diagnosis and appropriate treatment are crucial for long-term outcomes.

5.
Biochem Genet ; 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38678487

RESUMO

Sjogren's syndrome (SS) is an autoimmune disorder characterized by dry mouth and dry eyes. Its pathogenic mechanism is currently unclear. This study aims to integrate weighted gene co-expression network analysis (WGCNA) and machine learning to identify key genes associated with SS. We downloaded 3 publicly available datasets from the GEO database comprising the gene expression data of 231 SS and 78 control cases, including GSE84844, GSE48378 and GSE51092, and carried out WGCNA to elucidate differences in the abundant genes. Candidate biomarkers for SS were then identified using a LASSO regression model. Totally 6 machine-learning models were subsequently utilized for validating the biological significance of major genes according to their expression. Finally, immune cell infiltration of the SS tissue was assessed using the CIBERSORT algorithm. A weighted gene co-expression network was built to divide genes into 10 modules. Among them, blue and red modules were most closely associated with SS, and showed significant enrichment in type I interferon signaling, cellular response to type I interferon and response to virus, etc. Combined machine learning identified 5 hub genes, including OAS1, EIF2AK2, IFITM3, TOP2A and STAT1. Immune cell infiltration analysis showed that SS was associated with CD8+ T cell, CD4+ T cell, gamma delta T cell, NK cell and dendritic cell activation. WGCNA was combined with machine learning to uncover genes that may be involved in SS pathogenesis, which can be utilized for developing SS biomarkers and appropriate therapeutic targets.

6.
J Hazard Mater ; 470: 134129, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38565019

RESUMO

Butylparaben, a common endocrine disruptor in the environment, is known to be toxic to the reproductive system, heart, and intestines, but its nephrotoxicity has rarely been reported. In order to study the nephrotoxicity and mechanism of butylparaben, we examined the acute and chronic effects on human embryonic kidney cells (HEK293T) and zebrafish. Additionally, we assessed the potential remedial effects of salidroside against butylparaben-induced nephrotoxicity. Our in vitro findings demonstrated oxidative stress and cytotoxicity to HEK293T cells caused by butylparaben. In the zebrafish model, the concentration of butylparaben exposure ranged from 0.5 to 15 µM. An assortment of experimental techniques was employed, including the assessment of kidney tissue morphology using Hematoxylin-Eosin staining, kidney function analysis via fluorescent dextran injection, and gene expression studies related to kidney injury, development, and function. Additionally, butylparaben caused lipid peroxidation in the kidney, thereby damaging glomeruli and renal tubules, which resulted from the downregulation of the PI3K-AKT signaling pathway. Furthermore, salidroside ameliorated butylparaben-induced nephrotoxicity through the PI3K-AKT signaling pathway. This study reveals the seldom-reported kidney toxicity of butylparaben and the protective effect of salidroside against toxicological reactions related to nephrotoxicity. It offers valuable insights into the risks to kidney health posed by environmental toxins.


Assuntos
Rim , Parabenos , Transdução de Sinais , Peixe-Zebra , Animais , Humanos , Regulação para Baixo/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Glucosídeos/farmacologia , Células HEK293 , Rim/efeitos dos fármacos , Rim/patologia , Nefropatias/induzido quimicamente , Nefropatias/patologia , Nefropatias/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Parabenos/toxicidade , Fenóis/toxicidade , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos
7.
Adv Sci (Weinh) ; : e2306917, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38439601

RESUMO

Nature presents the most beautiful patterns through evolving. Here, a layered porous pattern in golden ratio (0.618) is reported from a type of mushroom -Dictyophora Rubrovalvata stipe (DRS). The hierarchical structure shows a mathematical correlation with the golden ratio. This unique structure leads to superior mechanical properties. The gradient porous structure from outside to innermost endows it with asymmetrical hydrophilicity. A mathematical model is then developed to predict and apply to 3D printed structures. The mushroom is then explored to repair gastric perforation because the stomach is a continuous peristaltic organ, and the perforated site is subject to repeated mechanical movements and pressure changes. At present, endoscopic clipping is ineffective in treating ulcerative perforation with fragile surrounding tissues. Although endoscopic implant occlusion provides a new direction for the treatment of gastric ulcers, but the metal or plastic occluder needs to be removed, requiring a second intervention. Decellularized DRS (DDRS) is found with asymmetric water absorption rate, super-compressive elasticity, shape memory, and biocompatibility, making it a suitable occluder for the gastric perforation. The efficacy in blocking gastric perforation and promoting healing is confirmed by endoscopic observation and tissue analysis during a 2-month study.

8.
J Affect Disord ; 354: 563-573, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38484886

RESUMO

BACKGROUND: We aimed to develop a clinical predictive model based on the cognitive neuropsychological (CNP) theory and machine-learning to examine SSRI efficacy in the treatment of MDD. METHODS: Baseline assessments including clinical symptoms (HAMD, HAMA, BDI, and TEPS scores), negative biases (NEO-PI-R-N and NCPBQ scores), sociodemographic characteristics (social support and SES), and a 5-min eye-opening resting-state EEG were completed by 69 participants with first-episode major depressive disorder (MDD) and 36 healthy controls. The clinical symptoms and negative bias were again assessed after an 8-week treatment of depression with selective serotonin reuptake inhibitors (SSRIs). A multi-modality machine-learning model was developed to predict the effectiveness of SSRI antidepressants. RESULTS: At baseline, we observed significant differences between MDD patients and healthy controls in terms of social support, clinical symptoms, and negative bias characteristics (p < 0.001). A negative association was found (p < 0.05) between neuroticism and alpha asymmetry in both the central and central-parietal areas, as well as between negative cognitive processing bias and alpha asymmetry in the parietal region. Compared to responders, non-responders exhibited less negative cognitive processing bias and greater alpha asymmetry in both central and central-parietal regions. Importantly, we developed a multi-modality machine-learning model with 83 % specificity using the above salient features. CONCLUSIONS: Research results support the CNP theory of depression treatment. To some extent, the multimodal clinical model constructed based on the CNP theory effectively predicted the efficacy of this treatment in this population. LIMITATIONS: Small sample and only focus on the mechanisms of delayed-onset SSRI treatment.


Assuntos
Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/terapia , Antidepressivos/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Cognição
9.
J Psychiatry Neurosci ; 49(1): E45-E58, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38359932

RESUMO

BACKGROUND: Environmental modification of genetic information (epigenetics) is often invoked to explain interindividual differences in the phenotype of schizophrenia. In clinical practice, such variability is most prominent in the symptom profile and the treatment response. Epigenetic regulation of immune function is of particular interest, given the therapeutic relevance of this mechanism in schizophrenia. METHODS: We analyzed the DNA methylation data of immune-relevant genes in patients with schizophrenia whose disease duration was less than 3 years, with previous lifetime antipsychotic treatment of no more than 2 weeks total. RESULTS: A total of 441 patients met the inclusion criteria. Core symptoms were consistently associated with 206 methylation positions, many of which had previously been implicated in inflammatory responses. Of these, 24 methylation positions were located either in regulatory regions or near the CpG islands of 20 genes, including the SRC gene, which is a key player in glutamatergic signalling. These symptom-associated immune genes were enriched in neuronal development functions, such as neuronal migration and glutamatergic synapse. Compared with using only clinical information (including scores on the Positive and Negative Syndrome Scale), integrating methylation data into the model significantly improved the predictive ability (as indicated by area under the curve) for response to 8 weeks of antipsychotic treatment. LIMITATIONS: We focused on a small number of methylation probes (immune-centred search) and lacked nutritional data and direct brain-based measures. CONCLUSION: Epigenetic modifications of the immune system are associated with symptom severity at onset and subsequent treatment response in schizophrenia.


Assuntos
Antipsicóticos , Esquizofrenia , Humanos , Epigênese Genética , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética , Antipsicóticos/uso terapêutico , Metilação de DNA , Ilhas de CpG , Sistema Imunitário
10.
Invest New Drugs ; 42(2): 196-206, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38386170

RESUMO

Patients with metastatic lung adenocarcinoma (MLA) and malignant pleural effusion (MPE) without driver gene mutations have a poor prognosis. None of the standard treatment strategies is recommended for such patients. We retrospectively analyzed the efficacy of the first-line treatment for this specific population: standard platinum-based doublet chemotherapy (CT), CT plus an immune checkpoint inhibitor (CT plus ICI), and CT plus bevacizumab (CT plus Bev). A total of 323 eligible patients were enrolled: CT alone (n = 166), CT plus Bev (n = 72), and CT plus ICI (n = 85). Treatment efficacy assessments were performed every two cycles according to the RECIST guidelines. The endpoints were overall survival (OS) and progression-free survival (PFS). Kaplan-Meier (K‒M) curves and the log-rank test were used to compare OS and PFS. p < 0.05 was the threshold of significance (statistical software: SPSS). The median follow-up was 11.4 months (range, 2.1-49.6 months). PFS and OS in the CT plus ICI/CT plus Bev cohort were significantly longer than those in the CT group (PFS: 7.8/6.4/3.9 months, p < 0.0001; OS: 16.4/15.6/9.6 months, p < 0.0001, respectively). CT plus Bev had better PFS and OS than CT plus ICI/CT in PD-L1 < 1% patients (PFS: 8.4/5.0/3.8 months, p < 0.0001; OS: 15.6/12.9/9.3 months, p < 0.0001). Among patients with PD-L1 1-49%, CT plus ICI led to a longer PFS and OS (PFS: 8.9/5.8/4.2 months, p = 0.009; OS: 24.2/18.8/11.5 months, p = 0.03). In the cohort with PD-L1 ≥ 50%, CT plus ICI was still the best first-line treatment (PFS: 19.7/13.8/9.6 months, p = 0.033; OS: 27.2/19.6/14.9 months, p = 0.047). In driver gene-negative MLA with MPE, CT plus Bev or ICI better controlled MPE and significantly prolonged survival compared to CT alone. PD-L1 expression (negative/positive) may be a key factor influencing the choice of CT plus Bev or ICI.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Derrame Pleural Maligno , Humanos , Bevacizumab , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Antígeno B7-H1 , Derrame Pleural Maligno/patologia , Estudos Retrospectivos , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética
11.
Sci Rep ; 14(1): 2709, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302636

RESUMO

With the aging of the population, sarcopenia has become more common. Studies have shown a broad association between liver disease and sarcopenia. However, this link remains unclear. Our study explored the link between NAFLD and sarcopenia and predicting the pathogenesis. To begin, we investigated the causal relationship and genetic correlation between them using MR and LDSC. Second, each GWAS was annotated by MAGMA. The annotated genes were analyzed for pleiotropy using the PLACO approach. Finally, functional analysis was conducted on the identified pleiotropic genes. We observed a significant genetic correlation between NAFLD and sarcopenia. Subsequently, we conducted gene-level pleiotropy analysis using PLACO and identified a total of 153 genes with pleiotropic effects. Functional analysis revealed enrichment of these genes in various tissues, including pancreas, liver, heart, blood, brain, and muscle, with involvement in cellular regulation, intracellular function, and antigen response. Moreover, our MR analysis provided evidence of a causal relationship between NAFLD and sarcopenia. Our study has discovered the genetic and causal relationships between NAFLD and sarcopenia, providing further insights into their pathophysiological mechanisms. The identification of pleiotropic genes also offers potential targets for future drug therapies aimed at controlling or treating NAFLD and sarcopenia.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Sarcopenia , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Sarcopenia/patologia , Músculo Esquelético/patologia , Envelhecimento
12.
Bioact Mater ; 34: 326-337, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38274294

RESUMO

Atherosclerosis is a significant contributor to global cardiovascular disease. Reducing the formation of atherosclerotic plaque effectively can lead to a decrease in cardiovascular diseases. Therefore, controlling macrophage function is crucial. This study presents the creation of a bifunctional nanoparticle that is specific to macrophages to achieve intracellular and extracellular synergistic therapy for restoring macrophage functions. The nanoparticle is conjugated with anti-CD47 antibody to modulate extracellular CD47-SIRPα phagocytic signaling axis on the outer surface of macrophages and encapsulates the NLRP3 inhibitor (CY-09) to regulate intracellular inflammation response of macrophages. The results showed that the nanoparticles accumulate in the atherosclerotic plaque, alter macrophage phagocytosis, inhibit NLRP3 inflammasome activation, and decrease the plaque burden in Apoe-/- mice whilst ensuring safety. Examination of single-cell RNA sequencing indicates that this multifunctional nanoparticle decreases the expression of genes linked to inflammation and manages inflammatory pathways in the plaque lesion. This study proposes a synergistic therapeutic approach that utilizes a bifunctional nanoparticle, conjugated with anti-CD47, to regulate the microenvironment of plaques.

13.
J Transl Med ; 22(1): 92, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263233

RESUMO

BACKGROUND: Recent research increasingly highlights a strong correlation between gut microbiota and the risk of gastrointestinal diseases. However, whether this relationship is causal or merely coincidental remains uncertain. To address this, a Mendelian randomization (MR) analysis was undertaken to explore the connections between gut microbiota and prevalent gastrointestinal diseases. METHODS: Genome-wide association study (GWAS) summary statistics for gut microbiota, encompassing a diverse range of 211 taxa (131 genera, 35 families, 20 orders, 16 classes, and 9 phyla), were sourced from the comprehensive MiBioGen study. Genetic associations with 22 gastrointestinal diseases were gathered from the UK Biobank, FinnGen study, and various extensive GWAS studies. MR analysis was meticulously conducted to assess the causal relationship between genetically predicted gut microbiota and these gastrointestinal diseases. To validate the reliability of our findings, sensitivity analyses and tests for heterogeneity were systematically performed. RESULTS: The MR analysis yielded significant evidence for 251 causal relationships between genetically predicted gut microbiota and the risk of gastrointestinal diseases. This included 98 associations with upper gastrointestinal diseases, 81 with lower gastrointestinal diseases, 54 with hepatobiliary diseases, and 18 with pancreatic diseases. Notably, these associations were particularly evident in taxa belonging to the genera Ruminococcus and Eubacterium. Further sensitivity analyses reinforced the robustness of these results. CONCLUSIONS: The findings of this study indicate a potential genetic predisposition linking gut microbiota to gastrointestinal diseases. These insights pave the way for designing future clinical trials focusing on microbiome-related interventions, including the use of microbiome-dependent metabolites, to potentially treat or manage gastrointestinal diseases and their associated risk factors.


Assuntos
Gastroenteropatias , Microbioma Gastrointestinal , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Reprodutibilidade dos Testes
14.
PNAS Nexus ; 3(1): pgae003, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38292554

RESUMO

Prenatal substance exposure (PSE) has been linked to adverse health outcomes, but its interactions with environmental and genetic factors remain unclear. Using data from the adolescent brain cognitive development cohort (n = 9,838; baseline age: 9.92 ± 0.62 years), we tested for the robust associations of PSE-caffeine/alcohol/tobacco/marijuana with children's health, cognition, and brain metrics after controlling for the environmental and genetic contexts. The environmental context involved birth, familial, and societal risk factors, while the genetic context included family histories and polygenic risk scores (PRSs) of mental disorders. In this sample, PSE-caffeine was observed in 59.8%, PSE-alcohol in 25.7%, PSE-tobacco in 13.2%, and PSE-marijuana in 5.6% of children. PSE-tobacco/marijuana was associated with higher environmental risks, PSE-alcohol was associated with lower familial risks, and all PSEs were associated with higher genetic risks. Controlling for these contexts reduced the number of significant health associations by 100, 91, 84, and 18% for PSE-tobacco/marijuana/caffeine/alcohol. Compared to the baseline, PSE-alcohol had the most health associations that were persistent over a 2-year period from preadolescence to adolescence, including associations with more sleep and mental health problems, improved cognitive functions, and larger brain volumes. These persistent associations with mental health problems and crystallized cognition were mediated by the surface areas of the frontal and the parietal cortices, respectively. Lower risk scores of the familial contexts attenuated associations between PSE-alcohol/marijuana and mental health problems. Higher PRS for substance use disorders enhanced late-onset associations of PSE-marijuana with externalizing problems. Results support the "health in context" concept, emphasizing modifiable factors mitigating adverse PSE effects.

15.
Rep Prog Phys ; 87(2)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38241723

RESUMO

We review the recent advances and current challenges in the field of strong spin-orbit coupled Kitaev materials, with a particular emphasis on the physics beyond the exactly-solvable Kitaev spin liquid point. To this end, we present a comprehensive overview of the key exchange interactions in candidate materials with a specific focus on systems featuring effectiveJeff=1/2magnetic moments. This includes, but not limited to,5d5iridates,4d5ruthenates and3d7cobaltates. Our exploration covers the microscopic origins of these interactions, along with a systematic attempt to map out the most intriguing correlated regimes of the multi-dimensional parameter space. Our approach is guided by robust symmetry and duality transformations as well as insights from a wide spectrum of analytical and numerical studies. We also survey higher spin Kitaev models and recent exciting results on quasi-one-dimensional models and discuss their relevance to higher-dimensional models. Finally, we highlight some of the key questions in the field as well as future directions.

16.
Adv Healthc Mater ; 13(11): e2303955, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38271271

RESUMO

Traditional chemotherapy has faced tough challenges of systemic toxicity, hypoxia resistance, and inadequacy of monotherapy. Developing the tumor-specific O2-supply-enhanced chemotherapy without toxic drugs while combing other precise treatments can substantially improve therapeutic efficacy. Herein, a CeO2-enriched CuO nanozyme with O2 supply and oxidative stress amplification for tumor-specific disulfiram (DSF) chemotherapy and intensified chemodynamic therapy by synergistic in situ "nontoxicity-toxicity" activation is developed. Notably, CeO2 can not only act as a morphological "regulator," but also serve as a cascaded enzyme-mimetic catalyst via tumor-microenvironment-responsive cascaded-logical programmable valence conversion. Once internalized inside tumor cells, the nanozyme can be degraded by lysosomal acidity to release nontoxic DSF and Cu2+, which can trigger in situ "Cu2+-DSF" chelation, generating a highly toxic Cu(DTC)2 for in situ chemotherapy. Moreover, the enriched CeO2 with catalase-mimetic activity can decompose the endogenous H2O2 into O2, which can relieve the hypoxia to enhance the chemotherapeutic efficacy. Furthermore, the simultaneously generated Ce3+ can exert peroxidase-mimetic activity to catalyze H2O2 into hydroxyl radicals (•OH) for chemodynamic therapy. This Fenton-like chemistry is accompanied by the regeneration of Ce4+, which can deplete the intracellular overproduced GSH to amplify the oxidative stress. Therefore, this nanozyme can provide an alternative to precise cancer treatment.


Assuntos
Cério , Cobre , Dissulfiram , Estresse Oxidativo , Microambiente Tumoral , Dissulfiram/farmacologia , Dissulfiram/química , Cério/química , Cério/farmacologia , Cobre/química , Microambiente Tumoral/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Humanos , Animais , Camundongos , Linhagem Celular Tumoral , Oxigênio/química , Oxigênio/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacologia , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo
17.
Mod Rheumatol ; 34(2): 369-375, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-36976576

RESUMO

OBJECTIVES: The association of inflammation markers with hypertension (HTN) in primary Sjögren's syndrome (pSS) remains controversial. We aimed to investigate whether inflammation markers are at increased risk of developing HTN in pSS patients. METHODS: A retrospective cohort study included pSS patients (n = 380) between May 2011 and May 2020 from the Third People's Hospital of Chengdu. Multivariable Cox regression analyses were used to estimate hazard ratios (HRs) of the potential inflammation markers for pSS-HTN. Subsequently, the dose-response relationships were also used. RESULTS: Out of 380 pSS patients, 171 (45%) developed HTN, and the median follow-up period was 4.16 years. Univariable Cox regression analysis showed that the erythrocyte sedimentation rate (ESR) and neutrophils were significantly associated with the incident HTN (P < 0.05). After adjustment for covariates, this association between ESR (adjusted HR 1.017, 95%CI: 1.005-1.027, P = .003), neutrophils (adjusted HR 1.356, 95%CI: 1.113-1.653, P = .003), and HTN remained significant. The dose-effect relationship was also found between ESR, neutrophils, and HTN (P = .001). CONCLUSIONS: Inflammation markers may play an important role in the incident HTN in pSS.


Assuntos
Hipertensão , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/complicações , Estudos Retrospectivos , Inflamação/complicações , Modelos de Riscos Proporcionais
18.
J Cell Mol Med ; 28(3): e18073, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38063077

RESUMO

Diabetic kidney disease (DKD) can lead to accumulation of glucose upstream metabolites due to dysfunctional glycolysis. But the effects of accumulated glycolysis metabolites on podocytes in DKD remain unknown. The present study examined the effect of dihydroxyacetone phosphate (DHAP) on high glucose induced podocyte pyroptosis. By metabolomics, levels of DHAP, GAP, glucose-6-phosphate and fructose 1, 6-bisphosphate were significantly increased in glomeruli of db/db mice. Furthermore, the expression of LDHA and PKM2 were decreased. mRNA sequencing showed upregulation of pyroptosis-related genes (Nlrp3, Casp1, etc.). Targeted metabolomics demonstrated higher level of DHAP in HG-treated podocytes. In vitro, ALDOB expression in HG-treated podocytes was significantly increased. siALDOB-transfected podocytes showed less DHAP level, mTORC1 activation, reactive oxygen species (ROS) production, and pyroptosis, while overexpression of ALDOB had opposite effects. Furthermore, GAP had no effect on mTORC1 activation, and mTORC1 inhibitor rapamycin alleviated ROS production and pyroptosis in HG-stimulated podocytes. Our findings demonstrate that DHAP represents a critical metabolic product for pyroptosis in HG-stimulated podocytes through regulation of mTORC1 pathway. In addition, the results provide evidence that podocyte injury in DKD may be treated by reducing DHAP.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Podócitos , Camundongos , Animais , Nefropatias Diabéticas/metabolismo , Podócitos/metabolismo , Fosfato de Di-Hidroxiacetona/metabolismo , Fosfato de Di-Hidroxiacetona/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Piroptose , Glucose/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Diabetes Mellitus/metabolismo
19.
Eur Radiol ; 34(1): 715-723, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37581653

RESUMO

OBJECTIVES: Microwave ablation (MWA) has achieved excellent long-term efficacy in treating unifocal papillary thyroid microcarcinoma (UPTMC). The therapeutic effect of this treatment on multifocal papillary thyroid microcarcinoma (MPTMC) is unknown. Therefore, we evaluated the long-term efficacy of MWA for low-risk MPTMC and to provide evidence-based medicine for the revision of clinical guidelines. METHODS: This study included 66 MPTMC patients with a total of 158 lesions, all of whom received MWA. We collected and retrospectively analyzed the patients' follow-up data before MWA, at 1, 3, 6, and 12 months posttreatment and every 6 months thereafter until 5 years posttreatment. We evaluated the MWA complication rate, technical success rate (TSR), lesion volume reduction rate (VRR), and complete disappearance rate (CDR) during follow-up and in those patients with tumor progression and delayed surgery. RESULTS: After 60 months of follow-up, all 158 lesions disappeared in 66 patients, and the volume was reduced from 43.82 mm3 to 0.00 mm3. The TSR and VRR were both 100%. The CDRs at 1 year, 2 years, and 3 years were 57.59%, 93.67%, and 100%, respectively. The complication rate was 3.03% (2/66), and the incidence of tumor progression was 3.03% (2/66), including one new intrathyroidal lesion and one cervical lymph node metastasis (LNM). These lesions were retreated with MWA, and the lesions disappeared during the follow-up period. CONCLUSIONS: Ultrasound-guided MWA for low-risk MPTMC is safe and effective and may serve as an alternative option for patients who refuse surgery or active surveillance (AS). CLINICAL RELEVANCE STATEMENT: This study concludes that ultrasound-guided microwave ablation for low-risk multifocal papillary thyroid microcarcinoma is safe and effective and may serve as an alternative option for patients who refuse surgery or active surveillance. KEY POINTS: • Ultrasound-guided microwave ablation for low-risk multifocal papillary thyroid microcarcinoma is safe and effective. • During 5 years of follow-up, multifocal papillary thyroid microcarcinoma patients treated with microwave ablation had a favorable prognosis. • To provide evidence-based medicine for the revision of clinical guidelines.


Assuntos
Carcinoma Papilar , Micro-Ondas , Neoplasias da Glândula Tireoide , Humanos , Seguimentos , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Resultado do Tratamento , Ultrassonografia de Intervenção
20.
Psychol Med ; 54(6): 1102-1112, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37997447

RESUMO

BACKGROUND: COVID-19 lockdowns increased the risk of mental health problems, especially for children with autism spectrum disorder (ASD). However, despite its importance, little is known about the protective factors for ASD children during the lockdowns. METHODS: Based on the Shanghai Autism Early Developmental Cohort, 188 ASD children with two visits before and after the strict Omicron lockdown were included; 85 children were lockdown-free, while 52 and 51 children were under the longer and the shorter durations of strict lockdown, respectively. We tested the association of the lockdown group with the clinical improvement and also the modulation effects of parent/family-related factors on this association by linear regression/mixed-effect models. Within the social brain structures, we examined the voxel-wise interaction between the grey matter volume and the identified modulation effects. RESULTS: Compared with the lockdown-free group, the ASD children experienced the longer duration of strict lockdown had less clinical improvement (ß = 0.49, 95% confidence interval (CI) [0.19-0.79], p = 0.001) and this difference was greatest for social cognition (2.62 [0.94-4.30], p = 0.002). We found that this association was modulated by parental agreeableness in a protective way (-0.11 [-0.17 to -0.05], p = 0.002). This protective effect was enhanced in the ASD children with larger grey matter volumes in the brain's mentalizing network, including the temporal pole, the medial superior frontal gyrus, and the superior temporal gyrus. CONCLUSIONS: This longitudinal neuroimaging cohort study identified that the parental agreeableness interacting with the ASD children's social brain development reduced the negative impact on clinical symptoms during the strict lockdown.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , COVID-19 , Criança , Humanos , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/psicologia , Estudos de Coortes , Fatores de Proteção , COVID-19/prevenção & controle , Controle de Doenças Transmissíveis , China/epidemiologia
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