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Molecular Medicine Reports Aug 2024Osteoarthritis (OA) is a chronic disease that involves chondrocyte injury. ADAMTS5 has been confirmed to mediate chondrocyte injury and thus regulate OA progression, but...
Osteoarthritis (OA) is a chronic disease that involves chondrocyte injury. ADAMTS5 has been confirmed to mediate chondrocyte injury and thus regulate OA progression, but its underlying molecular mechanisms remain unclear. In the present study, interleukin‑1β (IL‑1β)‑induced chondrocytes were used to mimic OA . Cell proliferation and apoptosis were assessed by MTT assay, EdU assay and flow cytometry, and protein levels of ADAMTS5, specificity protein 1 (SP1), matrix‑related markers and Wnt/β‑catenin pathway‑related markers were examined using western blotting. In addition, ELISA was performed to measure the concentrations of inflammation factors, and oxidative stress was evaluated by detecting SOD activity and MDA levels. The mRNA expression levels of ADAMTS5 and SP1 were determined by reverse transcription‑quantitative PCR, and the interaction between SP1 and ADAMTS5 was analyzed using a dual‑luciferase reporter assay and chromatin immunoprecipitation assay. IL‑1β suppressed proliferation, but promoted apoptosis, extracellular matrix degradation, inflammation and oxidative stress in chondrocytes. ADAMTS5 was upregulated in IL‑1β‑induced chondrocytes, and its knockdown alleviated IL‑1β‑induced chondrocyte injury. SP1 could bind to the ADAMTS5 promoter region to promote its transcription, and SP1 knockdown relieved IL‑1β‑induced chondrocyte injury by reducing ADAMTS5 expression. The SP1/ADAMTS5 axis activated the Wnt/β‑catenin pathway, and the Wnt/β‑catenin pathway agonist, SKL2001, reversed the protective effect of ADAMTS5 knockdown on chondrocyte injury induced by IL‑1β. To the best of our knowledge, the present study was the first to reveal the interaction between SP1 and ADAMTS5 in OA progression and indicated that the SP1/ADAMTS5 axis mediates OA progression by regulating the Wnt/β‑catenin pathway.
Topics: Chondrocytes; Sp1 Transcription Factor; ADAMTS5 Protein; Interleukin-1beta; Wnt Signaling Pathway; Osteoarthritis; Humans; Cell Proliferation; Apoptosis; Oxidative Stress; beta Catenin
PubMed: 38940327
DOI: 10.3892/mmr.2024.13273 -
Biomeditsinskaia Khimiia Jun 2024Renalase (RNLS) is a recently discovered protein that plays an important role in the regulation of blood pressure by acting inside and outside cells. Intracellular RNLS...
Renalase (RNLS) is a recently discovered protein that plays an important role in the regulation of blood pressure by acting inside and outside cells. Intracellular RNLS is a FAD-dependent oxidoreductase that oxidizes isomeric forms of β-NAD(P)H. Extracellular renalase lacking its N-terminal peptide and cofactor FAD exerts various protective effects via non-catalytic mechanisms. Certain experimental evidence exists in the literature that the RP220 peptide (a 20-mer peptide corresponding to the amino acid sequence RNLS 220-239) reproduces a number of non-catalytic effects of this protein, acting on receptor proteins of the plasma membrane. The possibility of interaction of this peptide with intracellular proteins has not been studied. Taking into consideration the known role of RNLS as a possible antihypertensive factor, the aim of this study was to perform proteomic profiling of the kidneys of normotensive and hypertensive rats using RP220 as an affinity ligand. Proteomic (semi-quantitative) identification revealed changes in the relative content of about 200 individual proteins in the kidneys of hypertensive rats bound to the affinity sorbent as compared to the kidneys of normotensive animals. Increased binding of SHR renal proteins to RP220 over the normotensive control was found for proteins involved in the development of cardiovascular pathology. Decreased binding of the kidney proteins from hypertensive animals to RP220 was noted for components of the ubiquitin-proteasome system, ribosomes, and cytoskeleton.
Topics: Animals; Rats; Kidney; Hypertension; Rats, Inbred SHR; Proteomics; Monoamine Oxidase; Male; Ligands; Peptides; Proteome
PubMed: 38940203
DOI: 10.18097/PBMC20247003145 -
Journal of Integrative Neuroscience Jun 2024The effects of heat acclimation (HA) on the hypothalamus after exertional heatstroke (EHS) and the specific mechanism have not been fully elucidated, and this study...
BACKGROUND
The effects of heat acclimation (HA) on the hypothalamus after exertional heatstroke (EHS) and the specific mechanism have not been fully elucidated, and this study aimed to address these questions.
METHODS
In the present study, rats were randomly assigned to the control, EHS, HA, or HA + EHS groups (n = 9). Hematoxylin and eosin (H&E) staining was used to examine pathology. Tandem mass tag (TMT)-based proteomic analysis was utilized to explore the impact of HA on the protein expression profile of the hypothalamus after EHS. Bioinformatics analysis was used to predict the functions of the differentially expressed proteins. The differential proteins were validated by western blotting. An enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines in the serum.
RESULTS
The H&E staining (n = 5) results revealed that there were less structural changes in hypothalamus in the HA + EHS group compared with the EHS group. Proteomic analysis (n = 4) revealed that proinflammatory proteins such as argininosuccinate synthetase (ASS1), high mobility group protein B2 (HMGB2) and vimentin were evidently downregulated in the HA + EHS group. The levels of interleukin (IL)-1β, IL-1, and IL-8 were decreased in the serum samples (n = 3) from HA + EHS rats.
CONCLUSIONS
HA may alleviate hypothalamic damage caused by heat attack by inhibiting inflammatory activities, and ASS1, HMGB2 and vimentin could be candidate factors involved in the exact mechanism.
Topics: Animals; Hypothalamus; Heat Stroke; Rats; Proteomics; Male; Rats, Sprague-Dawley; Physical Exertion; Disease Models, Animal
PubMed: 38940089
DOI: 10.31083/j.jin2306116 -
Health Care Science Apr 2024Although socioeconomic support is recommended for frailty management, its association with the prognosis of frailty is unclear.
BACKGROUND
Although socioeconomic support is recommended for frailty management, its association with the prognosis of frailty is unclear.
METHODS
Using data from participants aged ≥65 years in the Chinese Longitudinal Healthy Longevity Survey (2008-2018), the associations between socioeconomic support (source of income, medical insurance, community support, living status), onset of prefrailty/frailty, and worsening of prefrailty, were analyzed using multinominal logistic regression models. The associations between self-reported low quality of life (QoL) and reversion of prefrailty/frailty were analyzed using multivariate logistic regression models. Associations with mortality risk were analyzed using Cox proportional hazard regression models.
RESULTS
A total of 13,859 participants (mean age: 85.8 ± 11.1 years) containing 2056 centenarians were included. Financial dependence was a risk factor for low QoL among prefrail/frail individuals, but not among robust individuals. Having commercial or other insurance, and receiving social support from the community were protective factors for low QoL among prefrail/frail individuals and for the worsening of prefrailty. Continuing to work was a risk factor for low QoL, but a protective factor for worsening of prefrailty. A negative association between continuing to work and mortality existed in prefrail individuals aged <85 years and ≥85 years. Living alone was a risk factor for low QoL, but was not significantly associated with frailty prognosis.
CONCLUSIONS
Prefrail and frail individuals were vulnerable to changes in socioeconomic support and more sensitive to it compared with robust individuals. Preferential policies regarding financial support, social support, and medical insurance should be developed for individuals with frailty.
PubMed: 38939613
DOI: 10.1002/hcs2.88 -
Cureus May 2024Background and objective Exposure to sunlight's ultraviolet (UV) radiation poses various health risks, including sunburn, skin damage, and heightened skin cancer risk....
Background and objective Exposure to sunlight's ultraviolet (UV) radiation poses various health risks, including sunburn, skin damage, and heightened skin cancer risk. Sunblock usage has surged due to widespread advertising campaigns. Individuals spending time outdoors should employ protective measures like wearing hats, applying sunblock with a high sun protection factor (SPF), covering exposed skin, and seeking shade to mitigate UV exposure's harmful effects. This study's objective is to assess participants' experiences and satisfaction with SPF 100 sunscreen in actual use conditions. Methodology This study employed a prospective, single-center design involving 100 participants aged 18 to 70 years. Eligible individuals had Fitzpatrick skin types I-III and were engaged in outdoor activities, excluding those with certain medical conditions or medication use. Each participant received sunscreen tubes (Solero SPF 100, Helix Pharma Pvt. Ltd., Karachi, Pakistan), and clinical evaluations were conducted on the day before and after and day 22 visits, with sunblock application and UV-induced erythema assessments performed. Results Our study enrolled participants with a mean age of 25.6 ± 7.1 years, ranging from 15 to 55 years, with females comprising 84% (84) of the sample. Results revealed widespread satisfaction and acceptance of SPF 100 sunscreen, without any reported adverse reactions. A significant majority expressed their willingness to purchase and recommend the sunscreen to others. Furthermore, the majority of healthcare providers expressed satisfaction with prescribing this sunscreen. Conclusions In conclusion, SPF 100 sunscreen demonstrated excellent tolerability and acceptability among participants, suggesting its potential utility in both personal sun protection routines and clinical settings.
PubMed: 38939303
DOI: 10.7759/cureus.61212 -
Journal of Child & Adolescent Trauma Jun 2024Traumatic childhood events are some of the few identifiable and to some extent preventable causes of psychiatric illness. Children exposed to severely stressful events...
Traumatic childhood events are some of the few identifiable and to some extent preventable causes of psychiatric illness. Children exposed to severely stressful events may react with post-traumatic stress disorder (PTSD) and this may impact their level of function in daily life, their future development and mental health. The traumatic stress model suggests that traumatic stress in the family, community violence, and other traumas are regarded as additive environmental factors that can outweigh protective compensatory factors and thus interact with individual vulnerabilities. This study is based on prospective panel data including the whole population of children born in Denmark from 1984 to 1994, who are followed from age 7 to age 18 (N = 679,000) in the window between 2001 and 2012. Risk factors for first-time diagnose with PTSD are analyzed by the discrete time log-odd model. We found a lifetime prevalence of 2.3% PTSD in school-age children (n = 15,636). In accordance with the model, indicators of traumatic stress in the family, family disintegration, community violence, and individual vulnerabilities predicted later diagnose with PTSD. Individual neurodevelopmental disorder - especially autism (adjusted Odds Ratio (OR 7.1) and ADHD (OR 10.7) - were predicative of PTSD. The results cooperated the traumatic stress model. Some results were inconsistent with the traumatic stress model e.g., parental substance abuse were associated with less than expected PTSD in school-age children when adjusted for other risk factors. This indicates that PTSD may be underestimated in these groups. PTSD diagnoses in administrative records underestimate the prevalence, systematically. Efforts to increase PTSD screening may allow for better management.
PubMed: 38938938
DOI: 10.1007/s40653-024-00611-y -
PeerJ 2024To determine the association between lipid metabolism and intrahepatic cholestasis of pregnancy (ICP), and explore the value of maternal alanine...
Evaluation of alanine aminotransferase/aspartate aminotransferase ratio and high-density lipoprotein for predicting neonatal adverse outcomes associated with intrahepatic cholestasis of pregnancy.
BACKGROUND
To determine the association between lipid metabolism and intrahepatic cholestasis of pregnancy (ICP), and explore the value of maternal alanine aminotransferase/aspartate aminotransferase (ALT/AST) and high-density lipoprotein (HDL) in predicting adverse neonatal outcomes in women with ICP.
METHODS
A total of 147 pregnant women with ICP admitted to The Fourth Hospital of Shijiazhuang and 120 normal pregnant women in the same period were selected in this study. The Mann-Whitney U test and Chi-square tests were used to compare the differences in clinical data. Multivariate logistic regression was used to analyze the relationship between ALT/AST and the occurrence of adverse pregnancy outcomes in patients with ICP. The combined predictive value of ALT/AST and HDL was determined by receiver operating characteristic (ROC) curve analysis.
RESULTS
Among 147 women with ICP, 122 women had total bile acid (TBA) levels of 10-39.9 µmol/L, and 25 had TBA ≥ 40 µmol/L. There was significantly lower gestational age in patients with severe ICP than in those with mild and control groups (all < 0.05), and the weight of newborns in the maternal ICP group was significantly lower than in the control group ( < 0.05). Increasing TBA levels was associated with higher AST, ALT, ALT/AST, and lower HDL level (all < 0.05). Meanwhile, higher levels of ALT/AST was positively associated with neonatal hyperbilirubinemia [adjusted odds ratio (AOR) = 4.019, 95% CI [1.757-9.194, = 0.001] and cardiac injury [AOR = 3.500, 95% CI [1.535-7.987], = 0.003]. HDL was a significant protective factor for neonatal hyperbilirubinemia and cardiac injury [AOR = 0.315, 95% CI [0.126-0.788], = 0.014; AOR = 0.134 (0.039-0.461), = 0.001]. The area under the ROC curve (AUC) for prediction of neonatal hyperbilirubinemia by ALT/AST combined with HDL was 0.668 [95% CI [56.3-77.3%], = 0.002], and the sensitivity and specificity were 47.1% and 84.0%, respectively. To predict neonatal cardiac injury, the AUC value was 0.668 [95% CI [56.4-77.1%], = 0.002], with sensitivity and specificity were 41.2% and 87.1%, respectively.
CONCLUSIONS
The levels of higher ALT/AST and lower HDL were significantly associated with the risk of ICP-related adverse neonatal outcomes. Moreover, ALT/AST combined with HDL has moderate clinical value in predicting the adverse outcomes of neonatal hyperbilirubinemia and cardiac injury.
Topics: Humans; Female; Pregnancy; Cholestasis, Intrahepatic; Pregnancy Complications; Alanine Transaminase; Adult; Aspartate Aminotransferases; Infant, Newborn; Lipoproteins, HDL; Pregnancy Outcome; ROC Curve; Predictive Value of Tests; Biomarkers; Case-Control Studies
PubMed: 38938614
DOI: 10.7717/peerj.17613 -
Frontiers in Endocrinology 2024To analyze the influencing factors for progression from newly diagnosed prediabetes (PreDM) to diabetes within 3 years and establish a prediction model to assess the...
INTRODUCTION
To analyze the influencing factors for progression from newly diagnosed prediabetes (PreDM) to diabetes within 3 years and establish a prediction model to assess the 3-year risk of developing diabetes in patients with PreDM.
METHODS
Subjects who were diagnosed with new-onset PreDM at the Physical Examination Center of the First Affiliated Hospital of Soochow University from October 1, 2015 to May 31, 2023 and completed the 3-year follow-up were selected as the study population. Data on gender, age, body mass index (BMI), waist circumference, etc. were collected. After 3 years of follow-up, subjects were divided into a diabetes group and a non-diabetes group. Baseline data between the two groups were compared. A prediction model based on logistic regression was established with nomogram drawn. The calibration was also depicted.
RESULTS
Comparison between diabetes group and non-diabetes group: Differences in 24 indicators including gender, age, history of hypertension, fatty liver, BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, HbA1c, etc. were statistically significant between the two groups (P<0.05). Differences in smoking, creatinine and platelet count were not statistically significant between the two groups (P>0.05). Logistic regression analysis showed that ageing, elevated BMI, male gender, high fasting blood glucose, increased LDL-C, fatty liver, liver dysfunction were risk factors for progression from PreDM to diabetes within 3 years (P<0.05), while HDL-C was a protective factor (P<0.05). The derived formula was: In(p/1-p)=0.181×age (40-54 years old)/0.973×age (55-74 years old)/1.868×age (≥75 years old)-0.192×gender (male)+0.151×blood glucose-0.538×BMI (24-28)-0.538×BMI (≥28)-0.109×HDL-C+0.021×LDL-C+0.365×fatty liver (yes)+0.444×liver dysfunction (yes)-10.038. The AUC of the model for predicting progression from PreDM to diabetes within 3 years was 0.787, indicating good predictive ability of the model.
CONCLUSIONS
The risk prediction model for developing diabetes within 3 years in patients with PreDM constructed based on 8 influencing factors including age, BMI, gender, fasting blood glucose, LDL-C, HDL-C, fatty liver and liver dysfunction showed good discrimination and calibration.
Topics: Humans; Prediabetic State; Male; Female; Middle Aged; Risk Factors; Adult; Disease Progression; Follow-Up Studies; Risk Assessment; Diabetes Mellitus, Type 2; Body Mass Index; Blood Glucose; Aged; Waist Circumference; Prognosis; China
PubMed: 38938520
DOI: 10.3389/fendo.2024.1410502 -
JACC. Advances Oct 2023Heart failure (HF) is a leading cause of readmission after cardiac surgery, yet risk factors for HF readmission after cardiac surgery remain poorly characterized.
BACKGROUND
Heart failure (HF) is a leading cause of readmission after cardiac surgery, yet risk factors for HF readmission after cardiac surgery remain poorly characterized.
OBJECTIVES
This study aimed to identify risk factors associated with 30-day HF-specific readmissions after cardiac surgery using a national database.
METHODS
We queried the 2016 to 2018 National Readmissions Database to identify U.S. patients who underwent coronary artery bypass grafting (CABG), mitral valve repair/replacement, and/or aortic valve repair/replacement. Exclusion criteria included history of ventricular assist device or heart transplant, dialysis-dependent renal insufficiency, and death during index admission. Clinical variables were defined using International Classification of Diseases-10th Revision codes. The primary outcome was a 30-day readmission for HF following discharge. Multivariable logistic regression was used to account for relevant clinical and demographic covariates and identify independent risk factors for HF readmissions following cardiac surgery.
RESULTS
Our study included 394,050 patients who underwent cardiac surgery (mean age 66 ± 12 years, 63% isolated CABG, 27% isolated valve, 11% CABG + valve). Of these patients, 7,318 were readmitted within 30 days of discharge for a principal diagnosis of HF. Independent risk factors of HF-specific readmission included older age, female sex, prolonged length of stay, comorbid congestive HF, nondialysis dependent chronic kidney disease, chronic obstructive pulmonary disease, chronic liver disease, obesity, atrial fibrillation, and acute kidney injury. Prior CABG was marginally protective for HF-specific readmission.
CONCLUSIONS
Using a national registry, we identified risk factors associated with HF readmission after cardiac surgery. Further analysis of these risk factors and their association with HF readmission is warranted.
PubMed: 38938350
DOI: 10.1016/j.jacadv.2023.100599 -
International Journal of Inflammation 2024Peptides are widely used as natural bio-small molecules because of their various pharmacological activities such as enhancing immunity, promoting wound healing, and...
Peptides are widely used as natural bio-small molecules because of their various pharmacological activities such as enhancing immunity, promoting wound healing, and improving inflammation. Alcoholic heart injury has become one of the major health problems worldwide, and alcohol consumption is now the main cause of alcoholic cardiomyopathy. In this study, deer heart peptides were extracted from deer hearts by enzymatic digestion and the antioxidant activity of deer heart peptides extracted at different times was evaluated by three in vitro antioxidant methods, and the active peptide with the best enzymatic effect has been selected for in vivo animal experiments. The anti-inflammatory and antioxidant properties of deer heart enzymatic extracts were evaluated in in vivo experiments in mice. In this study, mice were orally gavaged with white wine (12 mL/kg body weight) to induce a mouse model of cardiac injury, while mice were orally administered a single dose of 100 mg/kg/bw and 200 mg/kg/bw of deer heart enzyme digest and were examined for body weight, dietary intake, water intake, and coat gloss, as well as for general behaviors, adverse effects, and mortality. Histology, serum, anti-inflammatory factors, and oxidative stress parameters were subsequently assessed. In all modeled mice, no four-way or any significant behavioral changes were observed in all groups, but in the modeled group, mice showed weight loss, decreased diet and water intake, and decreased cardiac index. For in vivo tests, the extract inhibited the anti-inflammatory activity with a significant decrease in inflammatory factors of TNF-, IL-6, and IL-1 in cardiac tissues, a significant increase in serum levels of both CAT and SOD, an increase in MDA content, and a remarkable increase in the level of the marker CK in the cardiac myocardial enzyme profile. Significant improvement in myocardial disorders by deer heart peptide could be observed from heart tissue sections. The present study emphasizes the anti-inflammatory and antioxidant activity of deer heart peptide, an enzymatic digest of deer heart, which provides empirical as well as supportive role for the anti-inflammatory properties of traditional medicine.
PubMed: 38938287
DOI: 10.1155/2024/6661371