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1.
Front Vet Sci ; 11: 1319854, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38962700

RESUMEN

Introduction: The Wuzhishan ant (MY) chicken exhibits significant differences from other chicken breeds. However, the molecular genetic relationship between the MY breed and other chicken breeds has not been assessed. Methods: Whole-genome resequencing was used to compare genetic diversity, nucleotide diversity, the fixation index, the linkage disequilibrium coefficient, and phylogenetic tree relationships between the MY breed and the Wenchang (WC), Danzhou (DZ), Bawangling (BW), and Longsheng Feng (LF) breeds. Results: A total of 21,586,378 singlenucleotide polymorphisms and 4,253,341 insertions/deletions were screened out among the five breeds. The MY breed had the second highest genomic genetic diversity and nucleotide diversity and the lowest LD coefficient among the five breeds. Moreover, the phylogenetic tree analysis showed that individual birds of each breed clustered together with those of their respective breeds. Discussion: Our data indicated that the MY breed is distinct from the other breeds and can be considered a new genetic resource.

2.
Int J Mol Sci ; 25(13)2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-39000339

RESUMEN

Epithelial-mesenchymal transition (EMT) refers to the transformation of polar epithelial cells into motile mesenchymal cells under specific physiological or pathological conditions, thus promoting the metastasis of cancer cells. Epithelial cadherin (E-cadherin) is a protein that plays an important role in the acquisition of tumor cell motility and serves as a key EMT epithelial marker. In the present study, AW01178, a small-molecule compound with potential therapeutic efficacy, was identified via in-cell Western high-throughput screening technology using E-cadherin as the target. The compound induced the upregulation of E-cadherin at both mRNA and protein levels and inhibited the EMT of breast cancer cells in vitro as well as metastasis in vivo. Mechanistically, AW01178 is a novel benzacetamide histone deacetylase inhibitor (HDACi) mainly targeting class I histone deacetylases. AW01178 promoted the transcription and expression of E-cadherin through enhancing the acetylation level of histone H3 in the E-cadherin promoter region, thereby inhibiting the metastasis of breast cancer cells. The collective findings support the potential utility of the novel HDACi compound identified in this study, AW01178, as a therapeutic drug for breast cancer and highlight its value for the future development of HDACi structures as anticancer drugs.


Asunto(s)
Neoplasias de la Mama , Cadherinas , Transición Epitelial-Mesenquimal , Inhibidores de Histona Desacetilasas , Transición Epitelial-Mesenquimal/efectos de los fármacos , Inhibidores de Histona Desacetilasas/farmacología , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/genética , Femenino , Animales , Cadherinas/metabolismo , Cadherinas/genética , Línea Celular Tumoral , Metástasis de la Neoplasia , Ratones , Movimiento Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Antineoplásicos/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Desnudos , Histonas/metabolismo
4.
BMC Public Health ; 24(1): 1669, 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38909187

RESUMEN

BACKGROUND: With rapid urbanization, massive migration, and non-family-based eldercare involvement, Chinese concepts of eldercare responsibility and filial piety are shifting. We performed age-period-cohort (APC) analyses to assess the transition of old-age pension coverage, eldercare responsibility, and filial piety concepts and its urban-rural differences among Chinese adults using data from the China General Social Survey (2006-2017). METHODS: Old-age pension coverage (yes/no) and primary eldercare responsibility (government/offspring/self/sharing) were investigated in 2010, 2012, 2013, 2015, and 2017. Filial piety was evaluated using customized questionnaires in 2006 and 2017. The APC effects were estimated using mixed effects and generalized additive models. RESULTS: Among 66,182 eligible participants (mean age: 48.8 years, females: 51.7%) in the six waves, APC analyses indicated that old-age pension coverage increased with aging and over time. Across cohort groups, it grew as the cohort was younger in urban residents but decreased in rural residents. The concept of offspring-based (> 50%) and government/self/offspring-shared eldercare (> 30%) predominated. APC analyses revealed that the offspring-based concept declined with aging (OR = 0.81, 95% CI: 0.79-0.84), whereas the government-based (OR = 1.37, 95% CI: 1.33-1.41) and self-based (OR = 1.55, 95% CI: 1.47-1.63) concepts increased with aging. People born around the 1940s have a comparatively higher possibility to perceive that the primary eldercare responsibility should be undertaken by the government and elder parents. In contrast, people born in the younger cohort were more likely to perceive that adult children are responsible for their parents' primary eldercare. Filial piety score slightly increased with aging (ß = 0.18, SD: 0.05) but decreased as the birth cohort was younger. In addition, rural participants were more likely to perceive offspring-based eldercare and maintain filial piety, and the related urban-rural difference was intensified by aging. CONCLUSIONS: The traditional concept that eldercare solely relies on offspring has changed to relying on multiple entities, including the government and self-reliance. Diluted filial piety in people born in the young cohort requires reinforcement. Moreover, future healthy aging policies need to focus more on urban-rural disparities to promote equity in social well-being.


Asunto(s)
Población Rural , Población Urbana , Humanos , China , Femenino , Masculino , Persona de Mediana Edad , Población Rural/estadística & datos numéricos , Anciano , Población Urbana/estadística & datos numéricos , Adulto , Estudios de Cohortes , Relaciones Intergeneracionales , Pensiones/estadística & datos numéricos , Encuestas y Cuestionarios , Responsabilidad Social
6.
BMC Med Inform Decis Mak ; 24(1): 125, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750562

RESUMEN

BACKGROUND: The Longshi Scale is a pictorial assessment tool for evaluating activities of daily living (ADL) in patients with stroke. The paper-based version presents challenges; thus, the WeChat version was created to enhance accessibility. Herein, we aimed to validate the inter-rater and test-retest reliabilities of the WeChat version of the Longshi Scale and explore its potential clinical applications. METHODS: We recruited 115 patients with stroke in the study. The ADL results of each patient were assessed using both the WeChat and paper-based version of the Longshi Scale; each evaluation was conducted by 28 health professionals and 115 caregivers separately. To explore the test-retest reliability of the WeChat version, 22 patients were randomly selected and re-evaluated by health professionals using the WeChat version. All evaluation criteria were recorded, and all evaluators were surveyed to indicate their preference between the two versions. RESULTS: Consistency between WeChat and the paper-based Longshi Scale was high for ADL scores by health professionals (ICC2,1 = 0.803-0.988) and caregivers (ICC2,1 = 0.845-0.983), as well as for degrees of disability (κw = 0.870 by professionals; κw = 0.800 by caregivers). Bland-Altman analysis showed no significant discrepancies. The WeChat version exhibited good test-retest reliability (κw = 0.880). The WeChat version showed similar inter-rater reliability in terms of the ADL score evaluated using the paper-based version (ICC2,1 = 0.781-0.941). The time to complete assessments did not differ significantly, although the WeChat version had a shorter information entry time (P < 0.001, 95% confidence interval: -43.463 to -15.488). Health professionals favored the WeChat version (53.6%), whereas caregivers had no significant preference. CONCLUSIONS: The WeChat version of the Longshi Scale is reliable and serves as a suitable alternative for health professionals and caregivers to assess ADL levels in patients with stroke. The WeChat version of the Longshi Scale is considered user-friendly by health professionals, although it is not preferred by caregivers. TRIAL REGISTRATION: This study was approved by the Ethics Committee of the Second People's Hospital of Shenzhen (approval number: 20210812003-FS01) and registered on the Clinical Trial Register Center website: clinicaltrials.gov on January 31, 2022 (registration no.: NCT05214638).


Asunto(s)
Actividades Cotidianas , Accidente Cerebrovascular , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de la Discapacidad , Reproducibilidad de los Resultados
7.
Sci Total Environ ; 923: 171358, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38438024

RESUMEN

Tetrabromobisphenol A (TBBPA) and Perfluorooctane sulfonate (PFOS) are emerging contaminants which coexist in marine environments, posing significant risks to ecosystems and human health. The behavior of these contaminants in the presence of dissolved organic matter (DOM), specifically the co-contamination of TBBPA and PFOS, is not well understood. The bioaccumulation, distribution, elimination, and toxic effects of TBBPA and PFOS on thick-shell mussels (Mytilus unguiculatus V.), with the absence and presence of humic acid (HA), a typical DOM, were studied. The results showed that the uptake of TBBPA decreased and the uptake of PFOS increased when exposed to 1 mg/L HA. However, at higher concentrations of HA (5 and 25 mg/L), the opposite effect was observed. Combined exposure to HA, TBBPA, and PFOS resulted in oxidative stress in the digestive gland, with the severity of stress dependent on exposure time and HA dose. Histological analysis revealed a positive correlation between HA concentration and tissue damage caused by TBBPA and PFOS. This study provides insights into the influence of HA on the bioaccumulation-elimination patterns and toxicity of TBBPA and PFOS in marine bivalves, offering valuable data for ecological and health risk assessments of combined pollutants in aquatic environments rich in DOM.


Asunto(s)
Ácidos Alcanesulfónicos , Fluorocarburos , Mytilus , Bifenilos Polibrominados , Contaminantes Químicos del Agua , Animales , Humanos , Sustancias Húmicas , Ecosistema , Bioacumulación , Bifenilos Polibrominados/toxicidad , Contaminantes Químicos del Agua/toxicidad
8.
Adv Mater ; 36(24): e2401505, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38437452

RESUMEN

Lithium-rich manganese-based layered oxides (LRMOs) are promisingly used in high-energy lithium metal pouch cells due to high specific capacity/working voltage. However, the interfacial stability of LRMOs remains challenging. To address this question, a novel armor-like cathode electrolyte interphase (CEI) model is proposed for stabilizing LRMO cathode at 4.9 V by exploring partially fluorinated electrolyte formulation. The fluoroethylene carbonate (FEC) and tris (trimethylsilyl) borate (TMSB) in formulated electrolyte largely contribute to the formation of 4.9 V armor-like CEI with LiBxOy and LixPOyFz outer layer and LiF- and Li3PO4-rich inner part. Such CEI effectively inhibits lattice oxygen loss and facilitates the Li+ migration smoothly for guaranteeing LRMO cathode to deliver superior cycling and rate performance. As expected, Li||LRMO batteries with such electrolyte achieve capacity retention of 85.7% with high average Coulomb efficiency (CE) of 99.64% after 300 cycles at 4.8 V/0.5 C, and even obtain capacity retention of 87.4% after 100 cycles at higher cut-off voltage of 4.9 V. Meanwhile, the 9 Ah-class Li||LRMO pouch cells with formulated electrolyte show over thirty-eight stable cycling life with high energy density of 576 Wh kg-1 at 4.8 V.

10.
Infect Drug Resist ; 17: 919-926, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38481653

RESUMEN

Objective: Drug resistance is the critical determinant for appropriate tuberculosis (TB) treatment regimens and an important indicator of the local TB burden. We aimed to investigate and compare trends in TB drug resistance in the urban Songjiang District of Shanghai from 2011 to 2020, and the rural Wusheng County of Sichuan Province from 2009 to 2020, to assess the effectiveness of local TB control and treatment programs. Methods: Whole-genome sequencing data of Mycobacterium tuberculosis were used to predict drug-resistance profiles and identify genomic clusters. Clustered, retreated cases of drug-resistant TB with identical resistance mutations, as well as all new resistant cases, were defined as transmitted resistance. The Cochran-Armitage trend test was used to identify trends in the proportions. Differences between groups were tested using the Wilcoxon rank sum or chi-square tests. Results: The annual proportions of rifampicin-resistant (RR), isoniazid-resistant (INH-R) and multidrug-resistant (MDR) TB cases did not change significantly in Songjiang. In Wusheng, however, the percentage of total TB cases that were RR decreased from 13.2% in 2009 to 3.7% in 2020, the INH-R cases decreased from 16.5% to 7.3%, and the MDR cases decreased from 10.7% to 3.7%. In retreated cases, the percentage of drug resistance decreased in both Songjiang and Wusheng, suggesting improved treatment programs. Transmitted resistance accounted for more than two thirds of drug-resistant cases over the entire study periods, and in recent years this proportion has increased significantly in Songjiang. Conclusion: In both urban Songjiang and rural Wusheng, drug-resistant TB is mostly the result of transmission of drug resistant strains and the percentage of transmitted resistance will likely increase with on-going improvements in the TB treatment programs. Reducing the prevalence of drug resistance depends principally upon decreasing transmission through the prompt diagnosis and effective treatment of drug-resistant TB cases.

11.
Cancer Lett ; 586: 216707, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38331088

RESUMEN

Cyclic GMP-AMP synthase (cGAS), promotes non-small cell lung cancer (NSCLC) cell proliferation. However, the specific mechanisms of cGAS-mediated NSCLC cell proliferation are largely unknown. In this study, we found asymmetric dimethylation by protein arginine methyltransferase 1 (PRMT1) at R127 of cGAS. This facilitated the binding of deubiquitinase USP7 and contributed to deubiquitination and stabilization of cGAS. PRMT1-and USP7-dependent cGAS stability, which also played a pivotal role in accelerating NSCLC cell proliferation through activating AKT pathway. We validated that the expression of cGAS and PRMT1 were positive correlated in human non-small cell lung cancer samples. Our study demonstrates a unique mechanism for managing cGAS stability by arginine methylation and indicates that PRMT1-cGAS-USP7 axis is a potential therapeutic target for NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Arginina , Carcinoma de Pulmón de Células no Pequeñas/genética , Proliferación Celular , Neoplasias Pulmonares/genética , Metilación , Proteína-Arginina N-Metiltransferasas/genética , Proteína-Arginina N-Metiltransferasas/metabolismo , Proteínas Represoras/metabolismo , Peptidasa Específica de Ubiquitina 7/metabolismo
12.
NPJ Digit Med ; 7(1): 13, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38225423

RESUMEN

Facial palsy (FP) profoundly influences interpersonal communication and emotional expression, necessitating precise diagnostic and monitoring tools for optimal care. However, current electromyography (EMG) systems are limited by their bulky nature, complex setups, and dependence on skilled technicians. Here we report an innovative biosensing approach that utilizes a PEDOT:PSS-modified flexible microneedle electrode array (P-FMNEA) to overcome the limitations of existing EMG devices. Supple system-level mechanics ensure excellent conformality to the facial curvilinear regions, enabling the detection of targeted muscular ensemble movements for facial paralysis assessment. Moreover, our apparatus adeptly captures each electrical impulse in response to real-time direct nerve stimulation during neurosurgical procedures. The wireless conveyance of EMG signals to medical facilities via a server augments access to patient follow-up evaluation data, fostering prompt treatment suggestions and enabling the access of multiple facial EMG datasets during typical 6-month follow-ups. Furthermore, the device's soft mechanics alleviate issues of spatial intricacy, diminish pain, and minimize soft tissue hematomas associated with traditional needle electrode positioning. This groundbreaking biosensing strategy has the potential to transform FP management by providing an efficient, user-friendly, and less invasive alternative to the prevailing EMG devices. This pioneering technology enables more informed decision-making in FP-management and therapeutic intervention.

13.
IEEE Trans Biomed Eng ; 71(2): 514-523, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37616138

RESUMEN

Glaucoma is the leading cause of irreversible but preventable blindness worldwide, and visual field testing is an important tool for its diagnosis and monitoring. Testing using standard visual field thresholding procedures is time-consuming, and prolonged test duration leads to patient fatigue and decreased test reliability. Different visual field testing algorithms have been developed to shorten testing time while maintaining accuracy. However, the performance of these algorithms depends heavily on prior knowledge and manually crafted rules that determine the intensity of each light stimulus as well as the termination criteria, which is suboptimal. We leverage deep reinforcement learning to find improved decision strategies for visual field testing. In our proposed algorithms, multiple intelligent agents are employed to interact with the patient in an extensive-form game fashion, with each agent controlling the test on one of the testing locations in the patient's visual field. Through training, each agent learns an optimized policy that determines the intensities of light stimuli and the termination criteria, which minimizes the error in sensitivity estimation and test duration at the same time. In simulation experiments, we compare the performance of our algorithms against baseline visual field testing algorithms and show that our algorithms achieve a better trade-off between estimation accuracy and test duration. By retaining testing accuracy with reduced test duration, our algorithms improve test reliability, clinic efficiency, and patient satisfaction, and translationally affect clinical outcomes.


Asunto(s)
Glaucoma , Campos Visuales , Humanos , Reproducibilidad de los Resultados , Pruebas del Campo Visual/métodos , Algoritmos
14.
J Biol Chem ; 299(11): 105354, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37858678

RESUMEN

O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, a prevalent protein post-translational modification (PTM) that occurs intracellularly, has been shown to crosstalk with phosphorylation and ubiquitination. However, it is unclear whether it interplays with other PTMs. Here we studied its relationship with ADP-ribosylation, which involves decorating target proteins with the ADP-ribose moiety. We discovered that the poly(ADP-ribosyl)ation "eraser", ADP-ribose glycohydrolase (PARG), is O-GlcNAcylated at Ser26, which is in close proximity to its nuclear localization signal. O-GlcNAcylation of PARG promotes nuclear localization and chromatin association. Upon DNA damage, O-GlcNAcylation augments the recruitment of PARG to DNA damage sites and interacting with proliferating cell nuclear antigen (PCNA). In hepatocellular carcinoma (HCC) cells, PARG O-GlcNAcylation enhances the poly(ADP-ribosyl)ation of DNA damage-binding protein 1 (DDB1) and attenuates its auto-ubiquitination, thereby stabilizing DDB1 and allowing it to degrade its downstream targets, such as c-Myc. We further demonstrated that PARG-S26A, the O-GlcNAc-deficient mutant, promoted HCC in mouse xenograft models. Our findings thus reveal that PARG O-GlcNAcylation inhibits HCC, and we propose that O-GlcNAc glycosylation may crosstalk with many other PTMs.


Asunto(s)
Carcinoma Hepatocelular , Glicósido Hidrolasas , Neoplasias Hepáticas , Animales , Humanos , Ratones , Acetilglucosamina , ADP-Ribosilación , Glicósido Hidrolasas/genética , Glicósido Hidrolasas/metabolismo , Poli Adenosina Difosfato Ribosa/metabolismo , Glicosilación , Procesamiento Proteico-Postraduccional
15.
BMC Health Serv Res ; 23(1): 953, 2023 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-37674190

RESUMEN

BACKGROUND: Long term care (LTC) services for functionally impaired senior citizens are crucial for addressing the challenges of aging. However, research on eligibility criteria and coverage of LTC in China is lacking. Our objective is to assess the current status of LTC and explore eligibility criteria and coverage for the elderly. METHODS: This is a cross-sectional study conducted in two first-tier cities in China. Residents aged 65 or over were recruited from a nursing home and four primary hospitals. Participants were divided into three groups (bedridden, domestic, and community), then six grades (grade one to six) according to the Longshi Scale, and their functional ability was assessed using the Modified Barthel Index. Information such as diseases, complications, and daily care needs were collected. Nursing staff were invited to indicate patients' needs for care. A one-way ANOVA test, Kruskal Wallis H test and Mann-Whitney U test were used to explore the differences of variables in three Longshi groups or Longshi grades. RESULTS: Among all 1157 participants, with an average age of 80.54, 69.3% were in the bedridden group. The most common diagnosis was stroke (71.4%), with the most prevalent complication being pulmonary infection (25.2%). In the nursing assessment, basic health care, disease care, activity care, complication prevention care and psychosocial care were summarized as the five main aspects of LTC for the elderly. Feeding, bathing, drinking, bowel management and bladder management were identified as the basic care which fulfills participants' basic physical needs in each Longshi group. Mouth care, artificial airway management, and body reposition, which can prevent immobility complications, were highly demanded by bedridden elderly. CONCLUSIONS: The elderly in grade one to three are the ones in need of LTC most. The content of LTC for elderly should include basic care which fulfills their basic physical needs and complication care which can prevent immobility complications. The evidence of this research may contribute to the design of LTC in China. TRIAL REGISTRATION: The study design was registered in the Chinese Clinical Trial Registry (ChiCTR-2000034067, Registered 22 Jun 2020, http://www.chictr.org.cn/showproj.aspx?proj=54770 ).


Asunto(s)
Cuidados a Largo Plazo , Casas de Salud , Anciano , Humanos , Estudios Transversales , Ciudades , China/epidemiología
16.
Front Immunol ; 14: 1185208, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37691929

RESUMEN

Background: Liver metastasis (LM) is a leading cause of cancer-related deaths in CRC patients, whereas the associated mechanisms have not yet been fully elucidated. Therefore, it is urgently needed to deeply explore novel metastasis accelerators and therapeutic targets of LM-CRC. Methods: The bulk RNA sequencing data and clinicopathological information of CRC patients were enrolled from the TCGA and GEO databases. The single-cell RNA sequencing (scRNA-seq) datasets of CRC were collected from and analyzed in the Tumor Immune Single-cell Hub (TISCH) database. The infiltration levels of cancer-associated fibroblasts (CAFs) and macrophages in CRC tissues were estimated by multiple immune deconvolution algorithms. The prognostic values of genes were identified by the Kaplan-Meier curve with a log-rank test. GSEA analysis was carried out to annotate the significantly enriched gene sets. The biological functions of cells were experimentally verified. Results: In the present study, hundreds of differentially expressed genes (DEGs) were selected in LM-CRC compared to primary CRC, and these DEGs were significantly associated with the regulation of endopeptidase activity, blood coagulation, and metabolic processes. Then, SPP1, CAV1, ANGPTL2, and COLEC11 were identified as the characteristic DEGs of LM-CRC, and higher expression levels of SPP1 and ANGPTL2 were significantly associated with worse clinical outcomes of CRC patients. In addition, ANGPTL2 and SPP1 mainly distributed in the tumor microenvironment (TME) of CRC tissues. Subsequent scRNA-seq analysis demonstrated that ANGPTL2 and SPP1 were markedly enriched in the CAFs and macrophages of CRC tissues, respectively. Moreover, we identified the significantly enriched gene sets in LM-CRC, especially those in the SPP1+macrophages and ANGPTL2+CAFs, such as the HALLMARK_EPITHELIAL_MESENCHYMAL_TRANSITION and the HALLMARK_COMPLEMENT. Finally, our in vitro experiments proved that ANGPTL2+CAFs and SPP1+macrophages promote the metastasis of CRC cells. Conclusion: Our study selected four characteristic genes of LM-CRC and identified ANGPTL2+CAFs and SPP1+macrophages subtypes as metastasis accelerators of CRC which provided a potential therapeutic target for LM-CRC.


Asunto(s)
Fibroblastos Asociados al Cáncer , Neoplasias Colorrectales , Neoplasias Hepáticas , Humanos , Algoritmos , Proteína 2 Similar a la Angiopoyetina , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundario , Macrófagos , Osteopontina , Microambiente Tumoral/genética
18.
Biomed Pharmacother ; 167: 115560, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37769392

RESUMEN

OBJECTIVE: The mechanism by which Notopterygium (NE) regulates the nucleotide-binding, oligomerization domain (NOD)-like receptor family and pyrin domain-containing 3 (NLRP3) inflammasome to treat rheumatoid arthritis (RA) was investigated to reveal the scientific implications of NE in RA treatment. METHODS: Adjuvant arthritis (AA) rats were replicated. After NE intervention, the anti-inflammatory efficacy of NE in vivo was determined. The mechanism of NE in RA treatment was predicted by network pharmacology, and the key target for further experiments was found through the analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG). The effect of NE on the NLRP3 inflammasome in AA rats was verified. Furthermore, with the induction of inflammation in RAW264.7 cells by lipopolysaccharide (LPS), several techniques, such as Griess assay, enzyme linked immunosorbent assays, electron microscopy, and fluorescence probe technology, were used to investigate the anti-inflammatory and related mechanisms of NE in RA treatment. RESULTS: NE could inhibit inflammation in AA rats. KEGG results showed that NLRP3 participated in the top three pathways of NE in RA treatment. Through Western blotting and immunofluorescence assays, this study demonstrated that NE can regulate NLRP3, pro-Caspase-1, Caspase-1, and CD11b in the ankle joint of AA rats. NE may significantly reduce the LPS-induced inflammatory response of RAW264.7 cells by alleviating mitochondrial damage, reducing the number of mitochondrial deoxyribonucleic Acid and mitochondrial reactive oxygen species, inhibiting NLRP3 inflammasome activation. CONCLUSION: The anti-inflammatory and antirheumatic effect of NE may involve regulating NLRP3 inflammasome activation through mitochondria. NLRP3 is probably the key target molecule of NE in the treatment of RA.

19.
Cell Death Discov ; 9(1): 289, 2023 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-37543653

RESUMEN

Chemotherapy has been widely used in small cell lung cancer (SCLC) treatment in the past decades. However, SCLC is easy to recur after chemotherapy. The senescence of cancer cells during chemotherapy is one of the effective therapeutic strategies to inhibit the progression of cancer. Nevertheless, the senescence-associated secretion phenotype (SASP) promotes chronic inflammation of the cancer microenvironment and further accelerates the progression of tumors. Therefore, inducing the senescence of cancer cells and inhibiting the production of SASP factors during anticancer treatment have become effective therapeutic strategies to improve the anticancer effect of drugs. Here we reported that SCLC cells treated with an FDA-approved HDAC inhibitor SAHA underwent senescence and displayed remarkable SASP. In particular, SAHA promoted the formation of cytoplasmic chromatin fragments (CCFs) in SCLC cells. The increased CCFs in SAHA-treated SCLC cells were related to nuclear porin Tpr, which activated the cGAS-STING pathway, and promoted the secretion of SASP in cancer cells. Inhibition of EZH2 suppressed the increase of CCFs in SAHA-treated SCLC cells, weakened the production of SASP, and increased the antiproliferative effect of SAHA. Overall, our work affords new insight into the secretion of SASP in SCLC and establishes a foundation for constructing a new therapeutic strategy for SCLC patients.

20.
J Glob Health ; 13: 04088, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37651631

RESUMEN

Background: Diabetes is more prevalent among overweight/obese individuals, but has become a significant public health challenge among normal weight populations. In this meta-analysis, we aimed to estimate diabetes/prediabetes incidence and its temporal trends by weight status. Methods: PubMed, Embase, Web of Science, and Cochrane Library were searched until 8 December 2021. Prospective cohort studies reporting diabetes incidence by baseline body mass index (BMI) categories in adults were included. The median year of data collection was used to assess the temporal trends. Subgroup analyses and meta-regression were also performed. Results: We included 94 studies involving 3.4 million adults from 22 countries. The pooled diabetes incidence in underweight, normal-weight, and overweight/obese adults was 4.5 (95% confidence interval (CI) = 2.8-7.3), 2.7 (95% CI = 2.2-3.3), and 10.5 (95% CI = 9.3-11.8) per 1000 person-years, respectively. The diabetes incidence in low- and middle-income countries (LMICs) was higher than in high-income countries among normal-weight (5.8 vs 2.0 per 1000 person-years) or overweight/obese (15.9 vs 8.9 per 1000 person-years) adults. European and American regions had a higher diabetes incidence than the non-Western areas, regardless of weight status. Underweight diabetes incidence decreased significantly from 1995-2000 to 2005-2010. Diabetes incidence in normal-weight populations has increased continuously since 1985 by an estimated 36% every five years. In overweight/obese adults, diabetes incidence increased between 1985-1990 and 1995-2000, stabilised between 2000 and 2010, and spiked suddenly after 2010. Conclusions: Diabetes incidence and its temporal trends differed by weight status. The continuous upward trend of diabetes incidence among overweight/obese individuals requires urgent attention, particularly in LMICs. Furthermore, diabetes among normal-weight individuals is becoming a significant public health problem. Registration: PROSPERO (CRD42020215957).


Asunto(s)
Diabetes Mellitus Tipo 2 , Adulto , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Sobrepeso/epidemiología , Incidencia , Estudios Prospectivos , Delgadez , Obesidad/epidemiología
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