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1.
Front Microbiol ; 15: 1404995, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38741740

RESUMO

Multiple Sclerosis (MS) is a neurologic autoimmune disease whose exact pathophysiologic mechanisms remain to be elucidated. Recent studies have shown that the onset and progression of MS are associated with dysbiosis of the gut microbiota. Similarly, a large body of evidence suggests that mitochondrial dysfunction may also have a significant impact on the development of MS. Endosymbiotic theory has found that human mitochondria are microbial in origin and share similar biological characteristics with the gut microbiota. Therefore, gut microbiota and mitochondrial function crosstalk are relevant in the development of MS. However, the relationship between gut microbiota and mitochondrial function in the development of MS is not fully understood. Therefore, by synthesizing previous relevant literature, this paper focuses on the changes in gut microbiota and metabolite composition in the development of MS and the possible mechanisms of the crosstalk between gut microbiota and mitochondrial function in the progression of MS, to provide new therapeutic approaches for the prevention or reduction of MS based on this crosstalk.

2.
Clin Exp Nephrol ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38767689

RESUMO

OBJECTIVE: To investigate the relationship between the aspartate aminotransferase to alanine aminotransferase ratio (AAR) and the prognosis of IgA nephropathy (IgAN). METHODS: Clinical, pathological and follow-up data of 271 patients with IgAN from January 1, 2013, to July 31, 2023, were collected. A 50% decrease in estimated glomerular filtration rate (eGFR) or end-stage renal disease (ESRD) was used as renal composite end point events. A receiver operating characteristic (ROC) curve was plotted to predict the composite end point events by AAR. The optimal cutoff value of 1.24 was determined, and patients were allocated to high AAR and low AAR groups. Kaplan‒Meier (K‒M) curves and Cox proportional hazard models were used to evaluate the predictive effect of AAR on renal composite end point events. RESULTS: After a mean follow-up of 29 months, 39 patients achieved renal composite end point events. Among them, 9 and 30 patients in the low and high AAR groups achieved renal composite end point events, respectively, with a significant difference (P < 0.001). After adjustment for confounding factors, AAR was found to be an independent prognostic factor for renal composite end point events (HR = 3.283, 95% CI: 1.489-7.238, P = 0.003). Kaplan‒Meier analysis showed that high AAR was associated with achieving renal composite end point events in patients with IgAN. Moreover, the clinical features in the high AAR group were more severe. Further subgroup analysis showed that high AAR had a better predictive effect in patients with more severe clinicopathological manifestations. CONCLUSION: AAR is an independent prognostic factor in patients with IgAN.

3.
BMC Infect Dis ; 24(1): 490, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741041

RESUMO

BACKGROUND: Toxoplasma gondii (T. gondii) is capable of infecting nearly all warm-blooded animals and approximately 30% of the global population. Though most infections are subclinical in immunocompetent individuals, congenital contraction can lead to severe consequences such as spontaneous abortion, stillbirth, and a range of cranio-cerebral and/or ocular abnormalities. Previous studies reported that T. gondii-infected pregnancy mice unveiled a deficit in both the amount and suppressive functions of regulatory T (Treg) cells, accompanied with reduced levels of forkhead box p3 (Foxp3). Recently, accumulative studies have demonstrated that microRNAs (miRNAs) are, to some extent, relevant to T. gondii infection. However, the link between alterations in miRNAs and downregulation of Foxp3 triggered by T. gondii has been only sporadically studied. METHODS: Quantitative reverse transcription polymerase chain reaction (RT-qPCR), protein blotting and immunofluorescence were employed to evaluate the impact of T. gondii infection and antigens on miRNA transcription and Foxp3 expression. Dual-luciferase reporter gene assays were performed to examine the fluorescence activity in EL4 cells, which were transfected with recombinant plasmids containing full-length/truncated/mutant microRNA-142a-3p (miR-142a) promoter sequence or wild type/mutant of Foxp3 3' untranslated region (3' UTR). RESULTS: We found a pronounced increase in miR-142a transcription, concurrent with a decrease in Foxp3 expression in T. gondii-infected mouse placental tissue. Similarly, comparable findings have been experimentally confirmed through the treatment of EL4 cells with T. gondii antigens (TgAg) in vitro. Simultaneously, miR-142a mimics attenuated Foxp3 expression, whereas its inhibitors markedly augmented Foxp3 expression. miR-142a promoter activity was elevated upon the stimulation of T. gondii antigens, which mitigated co-transfection of mutant miR-142a promoter lacking P53 target sites. miR-142a mimics deceased the fluorescence activity of Foxp3 3' untranslated region (3' UTR), but it did not affect the fluorescence activity upon the co-transfection of mutant Foxp3 3' UTR lacking miR-142a target site. CONCLUSION: In both in vivo and in vitro studies, a negative correlation was discovered between Foxp3 expression and miR-142a transcription. TgAg enhanced miR-142a promoter activity to facilitate miR-142a transcription through a P53-dependent mechanism. Furthermore, miR-142a directly targeted Foxp3 3' UTR, resulting in the downregulation of Foxp3 expression. Therefore, harnessing miR-142a may be a possible therapeutic approach for adverse pregnancy caused by immune imbalances, particularly those induced by T. gondii infection.


Assuntos
Regulação para Baixo , Fatores de Transcrição Forkhead , MicroRNAs , Toxoplasma , MicroRNAs/genética , MicroRNAs/metabolismo , Feminino , Animais , Gravidez , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Camundongos , Toxoplasma/genética , Toxoplasmose/parasitologia , Toxoplasmose/genética , Toxoplasmose/metabolismo , Resultado da Gravidez , Linfócitos T Reguladores/imunologia , Camundongos Endogâmicos C57BL , Regiões 3' não Traduzidas
4.
Artigo em Inglês | MEDLINE | ID: mdl-38581317

RESUMO

Objective: This study aims to explore the impact of immune-enhanced enteral nutrition on postoperative outcomes, focusing on inflammatory response, intestinal mucosal barrier integrity, and immune function following laparoscopic colon cancer surgery in elderly patients. Methods: In this single-center, randomized controlled trial, ninety-six elderly patients undergoing laparoscopic resection of colon tumors were enrolled and equally divided into two groups by random allocation. The control group (n=48) received standard enteral nutrition, while the experimental group (n=46) was administered immune-enhancing enteral nutrition. We assessed and compared specific metrics such as nutritional status (e.g., albumin levels), cellular immune status (CD4+ and CD8+ T-cell counts), inflammatory markers (e.g., C-reactive protein), and indicators of intestinal mucosal barrier function (e.g., D-lactate levels) before and after the intervention in both groups. Results: Initial comparison of baseline characteristics between the two groups showed no significant differences (P > .05). Postoperatively, the experimental group demonstrated significantly lower levels of inflammatory markers and an improved ratio of CD4+/CD8+ T-cells compared to the control group at day 7 (P < .05). Furthermore, nutritional status and markers indicative of intestinal mucosal barrier integrity were notably better in the experimental group at this time point. Conclusion: Immune-enhanced enteral nutrition is effective in enhancing intestinal mucosal barrier function, boosting immune response, and improving nutritional status in elderly patients post-laparoscopic colon cancer surgery. It also contributes to mitigating the inflammatory response, proving its safety and tolerability for clinical use.

5.
Front Pediatr ; 12: 1327118, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590771

RESUMO

Objective: This study aimed to analyze the current state of research on preoperative anxiety in children through CiteSpace, VOSviewer, and the identification of hot spots and frontiers. Method: Relevant data were retrieved from the Web of Science Core Collection using the search terms children and preoperative anxiety. Data were analyzed using VOSviewer (version 1.6.18), CiteSpace (5.7. R5) software, and Scimago Graphica. Results: A total of 622 articles were published between 2007 and 2022, with an increasing trend over time. Kain, Zeev N. (13; 2.09%) and Dalhousie University (15; 2.41%) were the most influential authors and most prolific institutions, respectively. The United States (121; 19.45%) was the country with the most publications. Pediatric anesthesia (55; 8.84%) had the most publications. High-frequency keywords were categorized into three themes, including nonpharmacologic interventions for preoperative anxiety in children, preoperative medications, and risk factors for anxiety; of these, "predictor" (38; 2016) and "sedative premedication" (20; 2016) were the most studied keywords over the past 6 years. "Distraction" (67; 2019) and "dexmedetomidine" (65; 2019) have been the main areas of interest in recent years. Conclusion: Research on preoperative anxiety in children has been the focus of increasing attention over the past fifteen years, with the majority of publications from high-income countries. This review provides a useful perspective for understanding research trends, hot topics, and research gaps in this expanding field.

6.
Purinergic Signal ; 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38676825

RESUMO

P2X7 receptor (P2X7R) plays an important role in modulating inflammation and fibrosis, but information is limited whether Zusanli (ST36) can inhibit inflammation and fibrosis by regulating P2X7R. Isoprenaline at 5 mg/kg was subcutaneously injected to wild-type and P2X7R knockout mice for 7 days, while treatment groups received electroacupuncture (EA) stimulation at ST36 for 7 sessions. Following 7-session treatment, Masson's trichrome staining was performed to assess the fibrosis. Morphology, electrocardiogram, and echocardiography were carried out to evaluate the cardiac function and structure. Western blotting, hematoxylin and eosin staining, immunohistochemistry, and biochemical analysis of inflammatory cytokine and transmission electron microscopy were carried out to characterize the effect of ST36 on inflammation. P2X7R was overexpressed in ISO-treated mice. EA at ST36, but not at non-points, reduced ISO-induced cardiac fibrosis, increases in HW/BW, R+S wave relative to mice in ISO groups. In addition, EA at ST36 downregulated ISO-upregulated P2X7R and NLRP3 in ventricle. Moreover, EA reduced cytokines of IL-1ß, IL-6, and IL-18 in serum, and inhibited foam cell gathering, inflammatory cell infiltration, and autophagy. However, EA at ST36 failed to attenuate the cardiac fibrosis and hypertrophy in P2X7R knockout mice. In conclusion, EA at ST36 attenuated ISO-induced fibrosis possibly via P2X7R.

7.
Parasit Vectors ; 17(1): 189, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632598

RESUMO

BACKGROUND: Toxoplasma gondii, an obligate intracellular parasitic protozoa, infects approximately 30% of the global population. Contracting T. gondii at the primary infection of the mother can result in neonatal microcephaly, chorioretinitis, hydrocephalus, or mortality. Our previous study indicated that pregnant mice infected with T. gondii displayed a decrease in both the number and the suppressive ability of regulatory T cells, accompanied by the reduced Forkhead box P3 (Foxp3). Numerous studies have proved that microRNAs (miRNAs) are implicated in T. gondii infection, but there is meager evidence on the relationship between alterations of miRNAs and downregulation of Foxp3 induced by T. gondii. METHODS: Quantitative reverse transcription polymerase chain reaction was utilized to detect the transcriptions of miRNAs and Foxp3. Protein blotting and immunofluorescence were used to detect the expressions of Foxp3 and related transcription factors. The structure of mouse placenta was observed by hematoxylin and eosin (HE) staining. To examine the activity of miR-7b promoter and whether miR-7b-5p targets Sp1 to suppress Foxp3 expression, we constructed recombinant plasmids containing the full-length/truncated/mutant miR-7b promoter sequence or wildtype/mutant of Sp1 3' untranslated region (3' UTR) to detect the fluorescence activity in EL4 cells. RESULTS: In T. gondii-infected mice, miR-7b transcription was significantly elevated, while Foxp3 expression was decreased in the placenta. In vitro, miR-7b mimics downregulated Foxp3 expression, whereas its inhibitors significantly upregulated Foxp3 expression. miR-7b promoter activity was elevated upon the stimulation of T. gondii antigens, which was mitigated by co-transfection of mutant miR-7b promoter lacking peroxisome proliferator-activated receptor γ (PPARγ) target sites. Additionally, miR-7b mimics diminished Sp1 expression, while miR-7b inhibitors elevated its expression. miR-7b mimics deceased the fluorescence activity of Sp1 3' untranslated region (3' UTR), but it failed to impact the fluorescence activity upon the co-transfection of mutant Sp1 3' UTR lacking miR-7b target site. CONCLUSIONS: T. gondii infection and antigens promote miR-7b transcription but inhibit Foxp3 protein and gene levels. T. gondii antigens promote miR-7b promoter activity by a PPARγ-dependent mechanism. miR-7b directly binds to Sp1 3' UTR to repress Sp1 expression. Understanding the regulatory functions by which T. gondii-induced miR-7b suppresses Foxp3 expression can provide new perspectives for the possible therapeutic avenue of T. gondii-induced adverse pregnancy outcomes.


Assuntos
Fatores de Transcrição Forkhead , MicroRNAs , Toxoplasma , Animais , Feminino , Camundongos , Gravidez , Regiões 3' não Traduzidas , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , MicroRNAs/genética , Placenta/metabolismo , Placenta/parasitologia , Placenta/patologia , PPAR gama/genética , PPAR gama/metabolismo , Transdução de Sinais , Toxoplasma/patogenicidade , Fator de Transcrição Sp1/genética , Fator de Transcrição Sp1/metabolismo , Toxoplasmose/genética , Toxoplasmose/metabolismo , Toxoplasmose/parasitologia
9.
Anal Biochem ; 689: 115502, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38453047

RESUMO

Myoglobin (Myo), creatine kinase-MB (CKMB), and cardiac troponin I (cTnI) are crucial biomarkers for diagnosing acute myocardial infarction (AMI) The accurate and rapid detection of these three targets can greatly improve the prognosis of AMI patients. Herein, this study developed a microfluidic immunofluorescence method that can detect all three targets in 10-15 min. Ultrasonic atomization and spray technology are used to modify the surface of the injection-molded microfluidic chip (MFC), which effectively solves the problem of biological cross-linking and antibody immobilization on the MFC surface. In addition, it improves the hydrophilicity of the chip surface, thus enhancing fluid self-driving effect. The linear response towards Myo, CKMB and cTnI range from 5 ng/mL to 500 ng/mL, 1 ng/mL to 70 ng/mL, and 0.05 ng/mL to 30 ng/mL, respectively. The intra-batch precision is ≤ 10%, and the inter-batch precision is ≤ 15%. Furthermore, this method shows good consistency compared with the BECKMAN ACCESS2 chemiluminescent immunoanalyzer. The present work provides an AMI diagnostic method with high sensitivity, good repeatability, high accuracy and simple operation, which can satisfy the needs of clinical diagnosis, and shows promising application prospects.


Assuntos
Microfluídica , Infarto do Miocárdio , Humanos , Infarto do Miocárdio/diagnóstico , Creatina Quinase Forma MB , Prognóstico , Troponina I , Biomarcadores , Mioglobina , Sensibilidade e Especificidade
10.
Phytomedicine ; 128: 155550, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38522313

RESUMO

BACKGROUND: The pathogenesis of acute liver injury (ALI) has been a pressing issue in the medical scientific community. We previously found that 5-O-methylvisammioside (MeV) from Saposhnikovia divaricata (Turcz.) Schischk has excellent anti-inflammatory properties. However, the mechanism by which MeV protects against ALI still needs to be deeply investigated. PURPOSE: In the present study, we established an acetaminophen (APAP) -induced ALI mouse model and pre-protected the mice with MeV. METHODS & RESULTS: Our findings indicate that MeV (5 and 10 mg/kg) lowered the blood levels of alanine aminotransferase and aspartate aminotransferase and reduced the infiltration of inflammatory cells in the liver. MeV initially showed an inhibitory effect on ALI. We then analyzed the molecular mechanisms underlying the effects of MeV by transcriptomic and metabolomic analyzes. Through transcriptomic analysis, we identified 4675 differentially expressed genes between the APAP+MeV group and the APAP-induced ALI group, which were mainly enriched in the MAPK pathway, the TNF pathway, and the NF-κB pathway. Through metabolomic analysis, we found that 249 metabolites in the liver were differentially regulated between the APAP+MeV group and the APAP- induced ALI group, which were mainly enriched in the arachidonic acid pathway. The mRNA expression levels of key genes (encoding TNF-α, p38, AP-1, RelB, IL-1ß, and Ptges), as determined by RT-PCR analysis, were consistent with the RNA-seq data. The ELISA results indicate that MeV markedly decreased the serum levels of TNF-α and IL-1ß in mice. Finally, the key proteins in the NF-κB and MAPK pathways were examined using immunoblotting. The results showed that MeV decreased IκB-α phosphorylation and inhibited the nuclear translocation of NF-κB. In addition, MeV reduced the hepatic inflammatory burst mainly by inhibiting the phosphorylation of p38 and JNK in the MAPK pathway. CONCLUSION: The present study demonstrated (i) that MeV could ameliorate APAP-induced ALI by inhibiting arachidonic acid metabolism and the TNF, MAPK, and NF-κB pathways, and (ii) that MeV is a promising drug candidate for the prevention of ALI.


Assuntos
Ácido Araquidônico , Doença Hepática Induzida por Substâncias e Drogas , NF-kappa B , Fator de Necrose Tumoral alfa , Animais , NF-kappa B/metabolismo , Masculino , Camundongos , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismo , Ácido Araquidônico/metabolismo , Acetaminofen , Modelos Animais de Doenças , Fígado/efeitos dos fármacos , Fígado/metabolismo , Anti-Inflamatórios/farmacologia , Transdução de Sinais/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Multiômica
11.
Transpl Immunol ; 84: 102022, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38452986

RESUMO

BACKGROUND: Mesenchymal stem cell therapy is a new treatment for immune rejection in heart transplantation. The aim of this paper is to investigate the effect of human amniotic mesenchymal stem cells (hAMSCs) on alleviating immune rejection of allogeneic heart transplantation in mice and its possible underlying mechanism. METHODS: We injected hAMSCs into cervical ectopic heart transplantation model mice via tail vein to observe the survival time, the pathological changes of donor myocardium, and the fluorescent distribution of hAMSCs after the transplantation. MicroRNAs (miRs) with significantly differential expression were obtained by RNA sequencing and bioinformatic analysis, and a dual luciferase reporter gene assay together with real-time quantitative PCR (qRT-PCR) was performed to verify the relationship between miRs and their targeting genes. RESULTS: The intervention of hAMSCs prolonged the graft survival time and alleviated the pathological damage of the donor heart. The injected hAMSCs were distributed mainly in the liver, spleen, and kidney, only a very small portion in the donor and recipient hearts. In the allogeneic transplantation models, the expression of miR-34b-5p significantly increased after hAMSC treatment. MiR-34b-5p showed a knockdown effect on gene Fc gamma receptor 2B (FCGR2B). CONCLUSIONS: hAMSCs can reduce the immune rejection injury after allogeneic heart transplantation. This effect may be associated with the upregulation of miR-34b-5p expression to knock down its targeting gene FCGR2B.

12.
J Sci Food Agric ; 104(7): 4453-4464, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38323723

RESUMO

BACKGROUND: It is reported that anti-enterovirus 71 (EV71) drugs have some side effects on human health. Notably, fungi plays a crucial role in promoting human health and anti-virus. Grifola frondosa is a type of large medicinal and edible fungi, rich in active substances. The present study aimed to investigate the anti-EV71 effect of G. frondosa and the potential active substances. RESULTS: In the present study, the water extract of G. frondosa was subjected to ethanol precipitation to obtain the water-extracted supernatant of G. frondosa (GFWS) and water-extracted precipitation of G. frondosa. Their inhibitory effects on EV71 virus were studied based on a cell model. The results showed that GFWS had stronger security and anti-EV71 effects. In addition, the chemical constituents of GFWS were identified by ultra-high performance liquid chromatography-tandem mass spectrometry, which were selected for further separation and purification. Three compounds, N-butylaniline, succinic acid and l-tryptophan, were isolated from GFWS by NMR spectroscopy. It is noteworthy that N-butylaniline and l-tryptophan were isolated and identified from the G. frondosa fruiting bodies for the first time. Our study found that l-tryptophan has anti-EV71 virus activity, which reduced EV71-induced apoptosis and significantly inhibited the replication process after virus adsorption. Furthermore, it could also bind to capsid protein VP1 to prevent the virus from attaching to the cells. CONCLUSION: l-tryptophan was an inhibitor of the EV71 virus, which could be used in infant nutrition and possibly provide a new drug to treat hand, foot and mouth disease. © 2024 Society of Chemical Industry.


Assuntos
Grifola , Humanos , Grifola/química , Triptofano , Água/química , Cromatografia Líquida de Alta Pressão
13.
Arch Gerontol Geriatr ; 121: 105358, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38341956

RESUMO

BACKGROUND: The surge of disabled older people have brought enormous burdens to society. The aim of this study was to examine the impact of long-term care insurance (LTCI) implementation on mortality and changes in physical ability among disabled older adults. METHODS: This was a prospective observational study based on data from the government-led LTCI program in a pilot city of China from 2017 to 2021. Administrative data included the application survey of activities of daily living (ADL), the baseline characteristics and all-cause mortality. Return visit surveys of ADL were conducted between August 2021 and December 2021. A regression discontinuity model was used to analyze the impact of LTCI on mortality. RESULTS: A total of 12,930 individuals older than 65 years were included in this study, and 10,572 individuals were identified with severe disability and participated in the LTCI program. LTCI implementation significantly reduced mortality by 5.10 % (95 % CI, -9.30 % to -0.90 %) and extended the survival time by 33.74 days (95 % CI, 13.501 to 53.970). The ADL scores of the LTCI group dropped by 2.5 points on average, while the ADL scores of those did not participated in LTCI dropped by 25.0 points. The heterogeneity analysis revealed that the impact of LTCI on mortality reduction was more significant among females, individuals of lower age, those who were married, cared for by family members, and who lived in districts with rich care resources. CONCLUSIONS: LTCI implementation had a favorable impact on the mortality and physical ability of participants.


Assuntos
Atividades Cotidianas , Seguro de Assistência de Longo Prazo , Idoso , Feminino , Humanos , China/epidemiologia , Assistência de Longa Duração , Estudos Prospectivos , Masculino
14.
Mol Ther Nucleic Acids ; 35(1): 102125, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38356866

RESUMO

Hepatocellular carcinoma (HCC) is a common malignancy with poor prognosis. In recent years, immune checkpoint inhibitors (ICIs) have enabled breakthroughs in the clinical treatment of patients with HCC, but the overall response rate to ICIs in HCC patients is still low, and no validated biomarker is available to guide clinical decision making. Here, we demonstrated that the long non-coding RNA Lnc-CCNH-8 is highly expressed in HCC and correlates with poor prognosis. Functionally, elevated Lnc-CCNH-8 inactivated co-cultured T cells in vitro and compromised antitumor immunity in an immunocompetent mouse model. Mechanistically, up-regulated Lnc-CCNH-8 can sponge microRNA (miR)-217 to regulate the expression of PD-L1. In addition, Lnc-CCNH-8 can also stabilize PD-L1 through miR-3173/PKP3 axis. Furthermore, mice bearing tumors with high Lnc-CCNH-8 expression had significant therapeutic sensitivity to anti-PD-L1 monoclonal antibody treatment. More important, HCC patients with high levels of plasma exosomal Lnc-CCNH-8 had a better therapeutic response to ICIs. Taken together, our results reveal the function of Lnc-CCNH-8 in inducing immune escape from CD8+ T-cell-mediated killing by up-regulating PD-L1 in a miR-217/miR-3173-dependent manner, which also reveals a novel mechanism of PD-L1 regulation in HCC, and exosomal Lnc-CCNH-8 can serve as a predictive marker for immunotherapy response in HCC.

15.
Biomed Pharmacother ; 172: 116247, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38330710

RESUMO

Cuproptosis provides a new therapeutic strategy for cancer treatment and is thought to have broad clinical application prospects. Nevertheless, some oncological clinical trials have yet to demonstrate favorable outcomes, highlighting the need for further research into the molecular mechanisms underlying cuproptosis in tumors. Cuproptosis primarily hinges on the intracellular accumulation of copper, with lipid metabolism exerting a profound influence on its course. The interaction between copper metabolism and lipid metabolism is closely related to cuproptosis. Copper imbalance can affect mitochondrial respiration and lipid metabolism changes, while lipid accumulation can promote copper uptake and absorption, and inhibit cuproptosis induced by copper. Anomalies in lipid metabolism can disrupt copper homeostasis within cells, potentially triggering cuproptosis. The interaction between cuproptosis and lipid metabolism regulates the occurrence, development, metastasis, chemotherapy drug resistance, and tumor immunity of cancer. Cuproptosis is a promising new target for cancer treatment. However, the influence of lipid metabolism and other factors should be taken into consideration. This review provides a brief overview of the characteristics of the interaction between cuproptosis and lipid metabolism in cancer and analyses potential strategies of applying cuproptosis for cancer treatment.


Assuntos
Metabolismo dos Lipídeos , Neoplasias , Cobre , Transporte Biológico , Oncologia , Mitocôndrias , Neoplasias/tratamento farmacológico
16.
Clinicoecon Outcomes Res ; 16: 81-96, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38374959

RESUMO

Background: As healthcare costs are increasingly being shifted from payers to patients, it is important to understand the economic consequences of therapeutic strategies to both payers and patients. Objective: To determine the relative costs to Medicare and Medicare beneficiaries (patients) of warfarin, non-vitamin K oral anticoagulants (NOACs), and left atrial appendage closure (LAAC) for stroke risk reduction in nonvalvular atrial fibrillation. Methods: An economic model was developed to assess costs at 5 and 10 years. For warfarin and NOACs, inputs were derived from published meta-analyses; for LAAC with the Watchman device, inputs were derived from pooled 5-year PROTECT AF and PREVAIL trial results. The model captured therapy costs vs clinical event costs, including procedural complications and follow-up clinical outcomes. Costs were based on 2023 Medicare reimbursement and copayment rates. Results: At 10 years, overall LAAC costs ($48,337) were lower than those of NOACs ($81,198) and warfarin ($52,359). Overall LAAC costs were lower than those of NOACs by year 5 and warfarin by year 9. At 5 years, patient LAAC costs were lowest at $4,764, compared to $7,146 and $6,453 for NOACs and warfarin, respectively. LAAC patient costs were lower than those of NOACs by year 3 and warfarin by year 4. Clinical events comprised 96% of overall warfarin costs vs 48% for LAAC and 40% for NOACs. Conclusion: LAAC yielded the lowest overall and patient costs. Warfarin costs were largely driven by clinical events, which may represent an unplanned financial burden for patients. These considerations should be incorporated into shared decision-making discussions about stroke prophylaxis strategies.

17.
Int J Environ Health Res ; 34(2): 708-718, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36628496

RESUMO

Previous studies have linked exposure to light at night (LAN) with various health outcomes, but evidence is limited for the LAN-obesity association. Thestudy analysed data from 24,845 participants of the 33 Communities Chinese Health Study and obesity (BMI ≥28 kg/m2) was defined according to the Working Group on Obesity in China. The Global Radiance Calibrated Nighttime Lights data were used to estimate participants' LAN exposure. The mixed-effect regression models examined the LAN-BMI and LAN-obesity association. We found that higher LAN exposure was significantly associated with greater BMI and higher risk of obesity. Changes of BMI and the odds ratios (ORs) of obesity and 95% confidence intervals (CIs) for 2nd, 3rd, and 4th against the 1st quartile of LAN exposure were 0.363 (0.208, 0.519), 0.364 (0.211, 0.516) and 0.217 (0.051, 0.383); 1.228 (1.099, 1.371), 1.356 (1.196, 1.538) and 1.269 (1.124, 1.433), respectively. Age and regular exercise showed significant modification effects on the LAN-obesity association.


Assuntos
Luz , Obesidade , Adulto , Humanos , Obesidade/epidemiologia , Saúde Pública , China/epidemiologia
19.
J Affect Disord ; 347: 500-508, 2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-38065477

RESUMO

BACKGROUND: It is unclear about the mutual impact of COVID-19 related psychological stress and infection on mental health of adolescent and youth students. This study aimed to explore the mutual impact of COVID-19 related psychological stress and infection on mental health problems among students. METHODS: This study was conducted from December 14, 2022 to February 28, 2023 in Sichuan, China. Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, PTSD Checklist for DSM-5, Insomnia Severity Index, and Internet Addiction Test were used. Participants were grouped by COVID-19 infection and psychological stress level. The differences among groups were compared, and logistic regression analysis was used to investigate risk factors for depression, anxiety, PTSD and insomnia among groups. RESULTS: Of 90,118 participants, 82,873 (92.0 %) finished the questionnaires and were included in the study. Of 82,873 participants, 33,314 (40.2 %) reported to be infected with COVID-19. Participants had depression symptoms (38.1 %), anxiety symptoms (31.8 %), PTSD (33.9 %), insomnia (34.0 %), and internet addiction (60.3 %). Compared with participants uninfected with low psychological stress level, the risk for symptoms of depression, anxiety, PTSD and insomnia increased by 9.6 %, 12.3 %, 6.6 %, and 12.0 % in participants infected with low psychological stress level (p < 0.001), 106.8 %, 125.9 %, 125.2 %, and 95.7 % in participants uninfected with high psychological stress level (p < 0.001), and 147.3 %, 161.1 %, 158.7 %, and 141.0 % in participants infected with high psychological stress level (p < 0.001). LIMITATION: This study is a cross-sectional design, and no causal associations should be inferred. Infection status was based on self-report of participants with infectious symptoms. CONCLUSION: COVID-19 related psychological stress and infection per se have mutually overlapping impacts on mental health problems among students. Further health policies and psychosocial interventions should be developed to reduce mutually overlapping impact and improve the long-term mental health among students.


Assuntos
COVID-19 , Distúrbios do Início e da Manutenção do Sono , Adolescente , Humanos , COVID-19/epidemiologia , Saúde Mental , SARS-CoV-2 , Pandemias , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Estudos Transversais , Ansiedade/diagnóstico , China/epidemiologia , Depressão/diagnóstico
20.
Ultrasound Q ; 40(1): 61-65, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37771069

RESUMO

ABSTRACT: Transvaginal 4-D hysterosalpingo-contrast sonography (TV 4-D HyCoSy) plays an important role in the detection and diagnosis of clinical female infertility. The purposes of this study were to analyze the influencing factors of TV 4murD HyCoSy complicated with contrast agent reflux and to provide evidence for clinical diagnosis and treatment. Female patients diagnosed as infertility by transvaginal hysterosalpingography from January 2021 to December 2022 were included. The characteristics of patients with and without contrast agent reflux were evaluated. Pearson correlation and logistic regression were conducted to analyze the related factors affecting the occurrence of contrast reflux. A total of 416 patients undergoing TV 4-D HyCoSy were included, and the incidence of contrast agent reflux in patients undergoing TV 4-D HyCoSy was 38.94%. Pearson correlation analysis results indicated that history of uterine cavity operation ( r = 0.556), adenomyosis of uterus ( r = 0.584), examination on less than 5 days after menstruation ( r = 0.602), endometrial thickness ( r = 0.566), and endometrial polyps ( r = 0.575) are all correlated with contrast agent reflux in patients undergoing 4-D HyCoSy (all P < 0.05). Logistic regression analysis showed that history of uterine cavity operation (odds ratio [OR], 1.109; 95% confidence interval [CI], 1.012-1.872), adenomyosis of uterus (OR, 2.026; 95% CI, 1.864-2.425), examination on less than 5 days after menstruation (OR, 2.465; 95% CI, 2.118-2.851), endometrial thickness less than 6 mm (OR, 2.866; 95% CI, 2.095-2.957), and endometrial polyps (OR, 1.587; 95% CI, 1.137-1.744) were the influencing factors of contrast agent reflux in patients undergoing (all P < 0.05). The incidence of contrast agent reflux in TV 4-D HyCoSy is high, and there are many influencing factors. Clinical medical workers should take early measures based on these influencing factors to reduce the contrast agent reflux.


Assuntos
Adenomiose , Infertilidade Feminina , Humanos , Feminino , Meios de Contraste , Tubas Uterinas/diagnóstico por imagem , Testes de Obstrução das Tubas Uterinas/métodos , Capacidades de Enfrentamento , Histerossalpingografia/métodos , Infertilidade Feminina/diagnóstico por imagem , Ultrassonografia/métodos
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