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1.
Sci Rep ; 14(1): 14312, 2024 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-38906907

RESUMO

Limited studies have triangulated the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and systolic blood pressure (SBP), diastolic blood pressure (DBP) or hypertension risk utilizing both observational and Mendelian randomization (MR) approaches. We employed data from the Norwegian Trøndelag Health Study (HUNT) to conduct cross-sectional (n = 5854) and prospective (n = 3592) analyses, as well as one-sample MR (n = 86,324). We also used largest publicly available data for two-sample MR. Our cross-sectional analyses showed a 25 nmol/L increase in 25(OH)D was associated with a 1.73 mmHg decrease in SBP (95% CI - 2.46 to - 1.01), a 0.91 mmHg decrease in DBP (95% CI - 1.35 to - 0.47) and 19% lower prevalence of hypertension (OR 0.81, 95% CI 0.74 to 0.90) after adjusting for important confounders. However, these associations disappeared in prospective analyses. One-sample and two-sample MR results further suggested no causal relationship between serum vitamin D levels and blood pressure or hypertension risk in the general population.


Assuntos
Pressão Sanguínea , Hipertensão , Análise da Randomização Mendeliana , Vitamina D , Humanos , Vitamina D/sangue , Vitamina D/análogos & derivados , Hipertensão/sangue , Hipertensão/epidemiologia , Hipertensão/genética , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Transversais , Noruega/epidemiologia , Idoso , Estudos Prospectivos , Fatores de Risco , Adulto
3.
Front Immunol ; 15: 1369969, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38915395

RESUMO

Background: This study aims to explore the clinical value of low disease activity state (LDAS) in the treat-to-target strategy of pediatric systemic lupus erythematosus (pSLE) and find the risk factors for never reaching LDAS. Methods: A total of 272 children with SLE who were diagnosed and followed up in two tertiary hospitals in China during the period from January 2012 to December 2019 were involved in this study, and the clinical presentation, pathology, and treatment were retrospectively studied. Results: The male-to-female ratio was 1:5.2, the age at diagnosis was 11.1 years (IQR, 9.8-13.1 years), the disease duration was 1.0 month (IQR, 0.5-2.0 months), and follow-up was 36.5 months (IQR, 25.7-50.9 months). During follow-up, 230 children achieved LDAS, and 42 were never been in. Male (P = 0.018), mucosal ulcer (P = 0.048), liver function damage (P = 0.026), cardiac effusion (P = 0.034), anemia (P = 0.048), urine red blood cells (P = 0.017), urinary leukocytes (P = 0.032), and endothelial cell proliferation in renal biopsy (P = 0.004)-these indexes have statistical differences between the two groups in the baseline. At baseline, endothelial cell proliferation (P = 0.02) is an independent risk factor for never achieving LDAS by multivariate logistic analysis. During follow-up, non-compliance was a risk factor for never achieving LDAS by comparing between groups. Children with biologics achieved LDAS at a higher rate than children without biologics (P = 0.038). The proportion of organ damage in patients never been in LDAS was significantly higher than that in patients who achieved LDAS (P < 0.001). Conclusion: Endothelial cell proliferation in renal biopsy and non-compliance during follow-up were independent risk factors for never achieving LDAS. At the end of the follow-up, the organ damage in the remission group was similar to that in the LDAS group, indicating that LDAS can be used as a target for pSLE treatment.


Assuntos
Lúpus Eritematoso Sistêmico , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Feminino , Criança , Estudos Retrospectivos , Adolescente , China/epidemiologia , Fatores de Risco , Índice de Gravidade de Doença , Seguimentos , Prognóstico , Resultado do Tratamento , População do Leste Asiático
4.
Indian J Dermatol ; 69(2): 201, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38841228

RESUMO

Background: Condyloma acuminatum (CA), which is a highly contagious sexually transmitted illness generated by human papillomavirus (HPV) infection, is characterized by abnormal proliferation of keratinocytes resulting in verrucous lesions. Although solute carrier family 30 member 1 (ZNT1) is highly expressed in CA tissues, the function of ZNT1 in CA remains unclear. Methods: HPV transfection was performed in HaCaT to simulate the CA pathological environment. The mRNA and protein levels were monitored using RT-qPCR and immunoblotting. Cell viability was found using the MTT test. Cell invasion and migration were probed using the transwell and wound healing. Results: ZNT1 expression was up-regulated in CA tissues, and HPV transfection increased the expression of ZNT1. Overexpression of ZNT1 promoted the proliferation, migration and invasion of Human immortalized keratinocyte (HaCaT) transfected with HPV. Meanwhile, ZNT1 knockdown repressed the proliferation, migration and invasion of HaCaT that HPV transfected. Further research displayed that ZNT1 promoted the proliferation, migration and invasion of HaCaT transfected with HPV through the PI3K/Akt pathway. Conclusion: Our research confirmed that ZNT1 regulated the proliferation, migration and invasion of HaCaT transfected with HPV through the PI3K/Akt pathway, providing a new target for the effective remedy of CA.

5.
Cancers (Basel) ; 16(11)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38893212

RESUMO

Total neoadjuvant therapy (TNT) is a novel strategy for rectal cancer that administers both (chemo)radiotherapy and systemic chemotherapy before surgery. TNT is expected to improve treatment compliance, tumor regression, organ preservation, and oncologic outcomes. Multiple TNT regimens are currently available with various combinations of the treatments including induction or consolidation chemotherapy, triplet or doublet chemotherapy, and long-course chemoradiotherapy or short-course radiotherapy. Evidence on TNT is rapidly evolving with new data on clinical trials, and no definitive consensus has been established on which regimens to use for improving outcomes. Clinicians need to understand the advantages and limitations of the available regimens for multidisciplinary decision making. This article reviews currently available evidence on TNT for rectal cancer. A decision making flow chart is provided for tailor-made use of TNT regimens based on tumor location and local and systemic risk.

6.
Aging (Albany NY) ; 162024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38925660

RESUMO

Iridocyclitis and the use of glucocorticoid medication have been widely studied as susceptibility factors for cataracts. However, the causal relationship between them remains unclear. This study aimed to investigate the causal relationship between the development of iridocyclitis and the genetic liability of glucocorticoid medication use on the risk of senile cataracts occurrence by performing Two-sample Mendelian randomization (MR) analyses. Instrumental variables (IVs) significantly associated with exposure factors (P < 5 × 10-8) were identified using published genome-wide association data from the FinnGen database and UK Biobank. Reliability analyses were conducted using five approaches, including inverse-variance weighted (IVW), MR-Egger regression, simple median, weighted median, and weighted mode. A sensitivity analysis using the leave-one-out method was also performed. Genetic susceptibility to glucocorticoid use was associated with an increased risk of developing senile cataracts (OR, 1.10; 95% CI, 1.02-1.17; P < 0.05). Moreover, iridocyclitis was significantly associated with a higher risk of developing senile cataracts (OR, 1.03; 95% CI, 1.01-1.05; P < 0.05). Nonetheless, some heterogeneity in the IVs was observed, but the MR results remained consistent after penalizing for outliers. The estimates were consistent in multivariate analyses by adjusting for body mass index (BMI) and diabetes mellitus type 2 (T2DM). This study provides new insights into the prevention and management of senile cataracts by highlighting the increased risk associated with iridocyclitis and the use of glucocorticoids.

7.
Chem Commun (Camb) ; 60(45): 5856-5859, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38752695

RESUMO

The membrane emulsification technique enables the self-assembly of cellulose nanocrystals (CNCs) confined within a spherical geometry for large-scale production. The resulting solid microspheres show long-range ordering with chiral nematic structures, and this fascinating hierarchical architecture can even be transferred to mesoporous carbon or silica microparticles by a sacrificial template method.

8.
Front Cell Infect Microbiol ; 14: 1382029, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38817443

RESUMO

Infections of hepatotropic viruses cause a wide array of liver diseases including acute hepatitis, chronic hepatitis and the consequently developed cirrhosis and hepatocellular carcinoma (HCC). Among the five classical hepatotropic viruses, hepatitis B virus (HBV) and hepatitis C virus (HCV) usually infect human persistently and cause chronic hepatitis, leading to major troubles to humanity. Previous studies have revealed that several types of inflammasomes are involved in the infections of HBV and HCV. Here, we summarize the current knowledge about their roles in hepatitis B and C. NLRP3 inflammasome can be activated and regulated by HBV and HCV. It is found to exert antiviral function or mediates inflammatory response in viral infections depending on different experimental models. Besides NLRP3 inflammasome, IFI16 and AIM2 inflammasomes participate in the pathological process of hepatitis B, and NALP3 inflammasome may sense HCV infection in hepatocytes. The inflammasomes affect the pathological process of viral hepatitis through its downstream secretion of inflammatory cytokines interleukin-1ß (IL-1ß) and IL-18 or induction of pyroptosis resulting from cleaved gasdermin D (GSDMD). However, the roles of inflammasomes in different stages of viral infection remains mainly unclear. More proper experimental models of viral hepatitis should be developed for specific studies in future, so that we can understand more about the complexity of inflammasome regulation and multifunction of inflammasomes and their downstream effectors during HBV and HCV infections.


Assuntos
Hepacivirus , Vírus da Hepatite B , Hepatite B Crônica , Hepatite C Crônica , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Humanos , Inflamassomos/metabolismo , Inflamassomos/imunologia , Hepatite C Crônica/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Hepacivirus/imunologia , Hepatite B Crônica/imunologia , Hepatite B Crônica/metabolismo , Vírus da Hepatite B/imunologia , Proteínas de Ligação a DNA/metabolismo , Interleucina-1beta/metabolismo , Piroptose , Animais , Fosfoproteínas/metabolismo , Proteínas Nucleares/metabolismo , Hepatócitos/virologia , Hepatócitos/imunologia , Interleucina-18/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Gasderminas
9.
BMJ Open ; 14(5): e081399, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38749693

RESUMO

OBJECTIVES: To estimate the shape of the causal relationship between body mass index (BMI) and mortality risk in a Mendelian randomisation framework. DESIGN: Mendelian randomisation analyses of two prospective population-based cohorts. SETTING: Individuals of European ancestries living in Norway or the UK. PARTICIPANTS: 56 150 participants from the Trøndelag Health Study (HUNT) in Norway and 366 385 participants from UK Biobank recruited by postal invitation. OUTCOMES: All-cause mortality and cause-specific mortality (cardiovascular, cancer, non-cardiovascular non-cancer). RESULTS: A previously published non-linear Mendelian randomisation analysis of these data using the residual stratification method suggested a J-shaped association between genetically predicted BMI and mortality outcomes with the lowest mortality risk at a BMI of around 25 kg/m2. However, the 'constant genetic effect' assumption required by this method is violated. The reanalysis of these data using the more reliable doubly-ranked stratification method provided some indication of a J-shaped relationship, but with much less certainty as there was less precision in estimates at the lower end of the BMI distribution. Evidence for a harmful effect of reducing BMI at low BMI levels was only present in some analyses, and where present, only below 20 kg/m2. A harmful effect of increasing BMI for all-cause mortality was evident above 25 kg/m2, for cardiovascular mortality above 24 kg/m2, for cancer mortality above 30 kg/m2 and for non-cardiovascular non-cancer mortality above 26 kg/m2. In UK Biobank, the association between genetically predicted BMI and mortality at high BMI levels was stronger in women than in men. CONCLUSION: This research challenges findings from previous conventional observational epidemiology and Mendelian randomisation investigations that the lowest level of mortality risk is at a BMI level of around 25 kg/m2. Our results provide some evidence that reductions in BMI will increase mortality risk for a small proportion of the population, and clear evidence that increases in BMI will increase mortality risk for those with BMI above 25 kg/m2.


Assuntos
Índice de Massa Corporal , Análise da Randomização Mendeliana , Humanos , Reino Unido/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Noruega/epidemiologia , Bancos de Espécimes Biológicos , Neoplasias/mortalidade , Neoplasias/genética , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/genética , Adulto , Causas de Morte , Mortalidade , Fatores de Risco , Biobanco do Reino Unido
10.
Res Sq ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38659935

RESUMO

The roles of sex hormones such as estradiol, testosterone, and sex hormone-binding globulin (SHBG) in the etiology of lung and colorectal cancers in women, among the most common cancers after breast cancer, are unclear. This Mendelian randomization (MR) study evaluated such potential causal associations in women of European ancestry. We used summary statistics data from genome-wide association studies (GWASs) on sex hormones and from the Trøndelag Health (HUNT) Study and large consortia on cancers. There was suggestive evidence of genetically predicted 1-standard deviation increase in total testosterone levels being associated with a lower risk of lung non-adenocarcinoma (hazard ratio (HR) 0.60, 95% CI 0.37-0.98) in the HUNT Study. However, this was not confirmed by using data from a larger consortium. In general, we did not find convincing evidence to support a causal role of sex hormones on risk of lung and colorectal cancers in women of European ancestry.

11.
Biomed Pharmacother ; 175: 116631, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38663105

RESUMO

Diabetes mellitus (DM) is a prevalent chronic disease in the 21st century due to increased lifespan and unhealthy lifestyle choices. Extensive research indicates that exercise can play a significant role in regulating systemic metabolism by improving energy metabolism and mitigating various metabolic disorders, including DM. Irisin, a well-known exerkine, was initially reported to enhance energy expenditure by indicating the browning of white adipose tissue (WAT) through peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) signaling. In this review, we summarize the potential mechanisms underlying the beneficial effects of Irisin on glucose dysmetabolism, including reducing gluconeogenesis, enhancing insulin energy expenditure, and promoting glycogenesis. Additionally, we highlight Irisin's potential to improve diabetic vascular diseases by stimulating nitric oxide (NO) production, reducing oxidative and nitrosative stress, curbing inflammation, and attenuating endothelial cell aging. Furthermore, we discuss the potential of Irisin to improve diabetic cardiomyopathy by preventing cardiomyocyte loss and reducing myocardial hypertrophy and fibrosis. Given Irisin's promising functions in managing diabetic cardiomyopathy and vascular diseases, targeting Irisin for therapeutic purposes could be a fruitful avenue for future research and clinical interventions.


Assuntos
Cardiomiopatias Diabéticas , Fibronectinas , Humanos , Fibronectinas/metabolismo , Animais , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/patologia , Angiopatias Diabéticas/metabolismo , Metabolismo Energético , Doenças Vasculares/metabolismo , Doenças Vasculares/tratamento farmacológico
12.
Int Dent J ; 74(3): 500-509, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38565436

RESUMO

OBJECTIVE: To study the relationships of serum 25-hydroxyvitamin D [25(OH)D] with dental caries and periodontitis in a general Norwegian adult population. METHODS: We analysed a subsample of 1605 participants from the Trøndelag Health Study (HUNT) in Norway that had serum 25(OH)D levels measured in HUNT3 (2006-08) and oral health assessed in the HUNT4 Oral Health Study (2017-19). Negative binomial and Poisson regression models were used to estimate the ratios of means (RMs; for count oral outcomes) and prevalence ratios (PRs; for dichotomous oral outcomes). RESULTS: Serum 25(OH)D was inversely associated with the number of decayed teeth in a dose-response gradient (<30.0 nmol/L: RM 1.41, 95% CI 1.07-1.85; 30.0-49.9 nmol/L: 1.14, 0.98-1.32 and ≥75.0 nmol/L: 0.84, 0.67-1.04, as compared to the 50.0-74.9 nmol/L group, P for trend <.001). Each 25 nmol/L decrease in 25(OH)D level was associated with a 15% (RM 1.15, 95% CI 1.05-1.26) increase in the mean number of decayed teeth. Serum 25(OH)D <30.0 nmol/L was associated with a 35% higher prevalence of severe periodontitis (PR 1.35, 95% CI 1.00-1.83). No association was observed between 25(OH)D and the number of natural teeth. CONCLUSION: The present study suggested that serum 25(OH)D level had an inverse and dose-response association with the number of decayed teeth, and serum 25(OH)D <30 nmol/L was associated with a higher prevalence of severe periodontitis in this Norwegian adult population.


Assuntos
Cárie Dentária , Periodontite , Vitamina D , Humanos , Cárie Dentária/epidemiologia , Cárie Dentária/sangue , Noruega/epidemiologia , Vitamina D/sangue , Vitamina D/análogos & derivados , Periodontite/epidemiologia , Periodontite/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Prevalência , Idoso , Índice CPO
13.
World J Clin Oncol ; 15(3): 391-410, 2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38576597

RESUMO

BACKGROUND: Ferroptosis has recently been associated with multiple degenerative diseases. Ferroptosis induction in cancer cells is a feasible method for treating neoplastic diseases. However, the association of iron proliferation-related genes with prognosis in HER2+ breast cancer (BC) patients is unclear. AIM: To identify and evaluate fresh ferroptosis-related biomarkers for HER2+ BC. METHODS: First, we obtained the mRNA expression profiles and clinical information of HER2+ BC patients from the TCGA and METABRIC public databases. A four-gene prediction model comprising PROM2, SLC7A11, FANCD2, and FH was subsequently developed in the TCGA cohort and confirmed in the METABRIC cohort. Patients were stratified into high-risk and low-risk groups based on their median risk score, an independent predictor of overall survival (OS). Based on these findings, immune infiltration, mutations, and medication sensitivity were analyzed in various risk groupings. Additionally, we assessed patient prognosis by combining the tumor mutation burden (TMB) with risk score. Finally, we evaluated the expression of critical genes by analyzing single-cell RNA sequencing (scRNA-seq) data from malignant vs normal epithelial cells. RESULTS: We found that the higher the risk score was, the worse the prognosis was (P < 0.05). We also found that the immune cell infiltration, mutation, and drug sensitivity were different between the different risk groups. The high-risk subgroup was associated with lower immune scores and high TMB. Moreover, we found that the combination of the TMB and risk score could stratify patients into three groups with distinct prognoses. HRisk-HTMB patients had the worst prognosis, whereas LRisk-LTMB patients had the best prognosis (P < 0.0001). Analysis of the scRNA-seq data showed that PROM2, SLC7A11, and FANCD2 were significantly differentially expressed, whereas FH was not, suggesting that these genes are expressed mainly in cancer epithelial cells (P < 0.01). CONCLUSION: Our model helps guide the prognosis of HER2+ breast cancer patients, and its combination with the TMB can aid in more accurate assessment of patient prognosis and provide new ideas for further diagnosis and treatment.

14.
J Glob Health ; 14: 04091, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587297

RESUMO

Background: Stroke has become a significant public health issue in China. Although studies have shown that women's age at first live birth (AFLB) might be associated with incident stroke, there is limited evidence on this relationship among Chinese parous women. Likewise, the nature of this association across urban-rural socioeconomic status (SES) has yet to be explored. In this prospective study, we sought to investigate the associations of women's AFLB with the risk of incident stroke and its subtypes (ischaemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage) and to explore the differences of these associations as well as the population-level impacts across SES classes. Methods: We used data on 290 932 Chinese parous women from the China Kadoorie Biobank who were recruited in the baseline survey between 2004 and 2008 and followed up until 2015. We used latent class analysis to identify urban-rural SES classes and Cox proportional hazard regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for AFLB's association with incident stroke. We then calculated population attributable fraction (PAF) to demonstrate the population-level impact of later AFLB on stroke. Results: Around 8.9% of parous women developed stroke after AFLB. Compared with women with AFLB <22 years, those with older AFLB had a higher risk of total stroke, with fully adjusted HRs (95% CI) of 1.71 (95% CI = 1.65-1.77) for 22-24 years and 3.37 (95% CI = 3.24-3.51) for ≥25 years. The associations of AFLB with ischaemic stroke were stronger among rural-low-SES participants. We found the highest PAFs of ischaemic stroke (60.1%; 95% CI = 46.2-70.3) associated with later AFLB for urban-high-SES individuals. Conclusions: Older AFLB was associated with higher risks of incident stroke and its subtypes among Chinese parous women, with stronger associations between AFLB and ischaemic stroke among rural-low-SES participants. Targeted medical advice for pregnant women of different ages could have long-term benefits for stroke prevention.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Feminino , Gravidez , Acidente Vascular Cerebral/epidemiologia , Estudos Prospectivos , Disparidades Socioeconômicas em Saúde , Nascido Vivo , China/epidemiologia
15.
Environ Health Perspect ; 132(3): 37001, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38427031

RESUMO

BACKGROUND: There are few studies on the health effects of long-term exposure to neighborhood greenness in a longitudinal setting, especially in Asian countries with high population densities. OBJECTIVES: This study investigates the association between long-term exposure to neighborhood greenness and hypertension among adults in Taiwan. METHODS: We selected 125,537 participants (≥18 years of age) without hypertension from Taiwan who had joined the standard medical examination program between 2001 and 2016. Neighborhood greenness was estimated using the normalized difference vegetation index (NDVI), derived from satellite images at a resolution of 250 m2. The 2-y average NDVI value within a 500-m circular buffer around participants' residences was calculated. A time-varying Cox regression model was used to investigate the association between neighborhood greenness and incident hypertension. Mediation analyses were performed to examine whether the association was explained by air pollution, leisure-time physical exercise, or body mass index (BMI). RESULTS: Compared with living in areas within the first quartile of neighborhood greenness, living in areas within the second, third, and fourth quartiles of neighborhood greenness was found to be associated with a lower risk of hypertension, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 0.95 (95% CI: 0.91, 1.00), 0.95 (95% CI: 0.90, 0.99), and 0.93 (95% CI: 0.88, 0.97), respectively. Each 0.1-unit increase in the NDVI was associated with a 24% lower risk of developing hypertension (HR=0.76; 95% CI: 0.66, 0.87), with this associations being stronger among males and those with higher education levels. This association was slightly mediated by BMI but not by air pollution or leisure-time physical exercise. DISCUSSION: Our findings suggest the protective effects of neighborhood greenness on hypertension development, especially in males and well-educated individuals. Our results reinforced the importance of neighborhood greenness for supporting health. https://doi.org/10.1289/EHP13071.


Assuntos
Poluição do Ar , Hipertensão , Masculino , Adulto , Humanos , Estudos Longitudinais , Taiwan/epidemiologia , Incidência , Estudos de Coortes , Hipertensão/epidemiologia , China/epidemiologia , Material Particulado
16.
J Transl Med ; 22(1): 153, 2024 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355483

RESUMO

Skeletal system disease (SSD) is defined as a class of chronic disorders of skeletal system with poor prognosis and causes heavy economic burden. m6A, methylation at the N6 position of adenosine in RNA, is a reversible and dynamic modification in posttranscriptional mRNA. Evidences suggest that m6A modifications play a crucial role in regulating biological processes of all kinds of diseases, such as malignancy. Recently studies have revealed that as the most abundant epigentic modification, m6A is involved in the progression of SSD. However, the function of m6A modification in SSD is not fully illustrated. Therefore, make clear the relationship between m6A modification and SSD pathogenesis might provide novel sights for prevention and targeted treatment of SSD. This article will summarize the recent advances of m6A regulation in the biological processes of SSD, including osteoporosis, osteosarcoma, rheumatoid arthritis and osteoarthritis, and discuss the potential clinical value, research challenge and future prospect of m6A modification in SSD.


Assuntos
Adenina/análogos & derivados , Neoplasias Ósseas , Osteoartrite , Humanos , RNA , Osteoartrite/genética , Metilação
17.
J Biomol Struct Dyn ; : 1-13, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38345053

RESUMO

Pigment epithelium-derived factor (PEDF) could bind to vascular endothelial growth factor receptor 2 (VEGFR2) and inhibit its activation induced by VEGF. But how PEDF affects VEGFR2 pathway is still poorly understood. In this study, we elucidated the precise mechanism underlying the interaction between PEDF and VEGFR2, and subsequently corroborated our findings using a rat AMI model. PEDF prevented endocytosis of VE-cadherin induced by hypoxia, thereby protecting the endothelium integrity. A three-dimensional model of the VEGFR2-PEDF complex was constructed by protein-protein docking method. The results showed that the VEGFR2-PEDF complex was stable during the simulation. Hydrogen bonds, binding energy and binding modes were analyzed during molecular dynamics simulations, which indicated that hydrogen bonds and hydrophobic interactions were important for the recognition of VEGFR2 with PEDF. In addition, the results from exudation of fibrinogen suggested that PEDF inhibits vascular leakage in acute myocardial infarction and confirmed the critical role of key amino acids in the regulation of endothelial cell permeability. This observation is also supported by echocardiography studies showing that the 34mer peptide sustained cardiac function during acute myocardial infarction. Besides, PEDF and 34mer could inhibit the aggregation of myofiber in the heart and promoted the formation of a dense cell layer in cardiomyocytes, which suggested that PEDF and 34mer peptide protect against AMI-induced cardiac dysfunction. These results suggest that PEDF inhibits the phosphorylation of downstream proteins, thereby preventing vascular leakage, which provides a new therapeutic direction for the treatment of acute myocardial infarction.Communicated by Ramaswamy H. Sarma.

18.
Sci Bull (Beijing) ; 69(6): 803-822, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38320897

RESUMO

Patients with high tumor mutational burden (TMB) levels do not consistently respond to immune checkpoint inhibitors (ICIs), possibly because a high TMB level does not necessarily result in adequate infiltration of CD8+ T cells. Using bulk ribonucleic acid sequencing (RNA-seq) data from 9311 tumor samples across 30 cancer types, we developed a novel tool called the modulator of TMB-associated immune infiltration (MOTIF), which comprises genes that can determine the extent of CD8+ T cell infiltration prompted by a certain TMB level. We confirmed that MOTIF can accurately reflect the integrity and defects of the cancer-immunity cycle. By analyzing 84 human single-cell RNA-seq datasets from 32 types of solid tumors, we revealed that MOTIF can provide insights into the diverse roles of various cell types in the modulation of CD8+ T cell infiltration. Using pretreatment RNA-seq data from 13 ICI-treated cohorts, we validated the use of MOTIF in predicting CD8+ T cell infiltration and ICI efficacy. Among the components of MOTIF, we identified EMC3 as a negative regulator of CD8+ T cell infiltration, which was validated via in vivo studies. Additionally, MOTIF provided guidance for the potential combinations of programmed death 1 blockade with certain immunostimulatory drugs to facilitate CD8+ T cell infiltration and improve ICI efficacy.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias , Humanos , Mutação , Neoplasias/tratamento farmacológico , Terapia Combinada , Imunoterapia
19.
BMC Public Health ; 24(1): 246, 2024 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-38254062

RESUMO

BACKGROUND: Research focusing on the association between serum vitamin D and oral health outcomes in children, such as dental caries and molar incisor hypomineralisation (MIH), shows inconsistent results. Previous studies have predominantly investigated dental caries and MIH as dichotomized outcomes, which limits the information on their distribution. In addition, the methods used for analysing serum vitamin D have varied. The present study aimed to investigate potential associations between serum vitamin D status measured by Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) and the prevalence, as well as the number of teeth, affected by dental caries or MIH among 7-9-year-old Norwegian children. METHODS: The study had a cross-sectional design and included 101 children aged 7-9 years. Serum 25-hydroxyvitamin D (25(OH)D) was measured and included as continuous (per 25 nmol/l) and categorised (insufficient (< 50 nmol/l) and sufficient (≥50 nmol/l)) exposure variables. Adjusted negative binomial hurdle models were used to investigate the potential associations between serum vitamin D and the oral health outcomes (dental caries and MIH) adjusted for sex, age, body mass index, season of blood draw, and mother's educational level. RESULTS: Of the 101 children in the total sample, 27% had insufficient vitamin D levels (< 50 nmol/l). The descriptive analysis indicated that the children with insufficient vitamin D levels had a higher prevalence (33.3%) and a higher number of teeth affected by dental caries (mean (SD) = 0.7 (1.4)), compared to children with sufficient levels of vitamin D (21.6% and mean (SD) = 0.4 (0.8), respectively). The same holds for MIH, with a higher prevalence (38.5%) and a higher number of teeth affected (mean (SD) = 1.2 (2.3)), compared to children with sufficient levels of vitamin D (30.1% and mean (SD) = 0.8 (1.6), respectively). However, in the adjusted hurdle model analysis, neither the prevalence or number of teeth affected by caries or MIH showed statistically significant associations with having insufficient or lower vitamin D levels. CONCLUSIONS: Vitamin D status was not significantly associated with the prevalence and number of teeth affected by caries and MIH among the participating children. Large prospective studies with multiple serum vitamin D measurements and oral examinations throughout childhood are warranted to elucidate the relationship.


Assuntos
Cárie Dentária , Hipomineralização Molar , Criança , Humanos , Estudos Transversais , Cromatografia Líquida , Cárie Dentária/epidemiologia , Estudos Prospectivos , Espectrometria de Massas em Tandem , Vitamina D , Vitaminas
20.
Nutr Metab Cardiovasc Dis ; 34(4): 988-997, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38176957

RESUMO

BACKGROUND AND AIMS: No consensus has been reached on the association between serum uric acid (SUA) and hypertension. This study aimed to investigate the associations between SUA and hypertension, including its status, stages, phenotypes and progressions, among middle-aged and older Chinese. METHODS AND RESULTS: Data were obtained from the China Health and Retirement Longitudinal Study 2011-2015. Binary logistic regression was used to evaluate the association between SUA and hypertension status. Multinomial logistic regression was used to explore the associations of SUA with hypertension stages, phenotypes and hypertension status progressions. Models were adjusted for potential confounders and stratified by sex. A total of 7931 individuals aged ≥45 years were included, with 39.16 % of hypertension. Significant associations were found of SUA with stage2 and above hypertension (quartile 4 [Q4] vs quartile 1 [Q1]: odds ratio 1.78, 95 % confidence interval 1.31-2.42, P < 0.001), and systolic diastolic hypertension (SDH) (Q4 vs Q1: 1.53, 1.14-2.06, P = 0.005). In sex stratification, significant associations were found between SUA and stage2 and above hypertension and SDH only for men. Moreover, higher quartiles of baseline SUA showed increased risks of maintained hypertension from 2011 to 2015 (Q3 vs Q1: 1.23, 1.03-1.48, P = 0.024; Q4 vs Q1: 1.73, 1.43-2.10, P < 0.001). CONCLUSION: Higher SUA was associated with hypertension and maintained hypertension among Chinese middle-aged and elderly. Sex-specific associations of SUA with hypertension stages and phenotypes were observed. Regular measurement of SUA in clinical practice may indicate hypertension and its progression, particularly among men.


Assuntos
Hipertensão , Ácido Úrico , Idoso , Pessoa de Meia-Idade , Masculino , Feminino , Humanos , Fatores de Risco , Estudos Longitudinais , Hipertensão/diagnóstico , Hipertensão/epidemiologia , China/epidemiologia , Fenótipo
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