Chronic Diseases and Translational Medicine最新文献

{"title":"A Bayesian network for estimating hypertension risk due to occupational aluminum exposure","authors":"Le Zhao,&nbsp;Jinzhu Yin,&nbsp;Jiaping Huan,&nbsp;Xiao Han,&nbsp;Dan Zhao,&nbsp;Jing Song,&nbsp;Linping Wang,&nbsp;Huifang Zhang,&nbsp;Baolong Pan,&nbsp;Qiao Niu,&nbsp;Xiaoting Lu","doi":"10.1002/cdt3.134","DOIUrl":"https://doi.org/10.1002/cdt3.134","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The correlation between metals and hypertension, such as sodium, zinc, potassium, and magnesium, has been confirmed, while the relationship between aluminum and hypertension is not very clear. This study aimed to evaluate the correlation between plasma aluminum and hypertension in electrolytic aluminum workers by the Bayesian networks (BN).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In 2019, 476 male workers in an aluminum factory were investigated. The plasma aluminum concentration of workers was measured by inductively coupled plasma mass spectrometry. The influencing factors on the prevalence of hypertension were analyzed by the BN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The prevalence of hypertension was 23.9% in 476 male workers. The risk of hypertension from plasma aluminum in the Q2, Q3, and Q4 groups was 5.20 (1.90–14.25), 6.92 (2.51–19.08), and 7.33 (2.69–20.01), respectively, compared with that in the Q1 group. The risk of hypertension from the duration of exposure to aluminum of &gt;10 years was 2.23 (1.09–4.57), compared without aluminum exposure. Area under the curve was 0.80 of plasma aluminum and the duration of exposure to aluminum was based on covariates, indicating that aluminum exposure had important predictive value in the prevalence of hypertension in the occupational population. The results of the study using the BN model showed that if the plasma aluminum of all participants was higher than Q4 (≥47.86 µg/L) and the participants were drinking, smoking, diabetes, central obesity, dyslipidemia, and aged &gt;50 years, the proportion of hypertension was 71.2%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The prevalence of hypertension increased significantly with the increase of plasma aluminum level.</p>\u0000 </section>\u0000 </div>","PeriodicalId":32096,"journal":{"name":"Chronic Diseases and Translational Medicine","volume":"10 2","pages":"130-139"},"PeriodicalIF":0.0,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cdt3.134","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141308921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypertension and human health: Evidence and prospects","authors":"Fangchao Liu,&nbsp;Xiangfeng Lu","doi":"10.1002/cdt3.129","DOIUrl":"https://doi.org/10.1002/cdt3.129","url":null,"abstract":"<p>High blood pressure is a major public health issue and a leading risk factor for death worldwide, with the number of attributable deaths increased from 6.8 million in 1990 to 10.8 million in 2019.<span>^{1, 2}</span> According to the World Health Organization, the age-standardized prevalence of hypertension was estimated to be 33%, affecting approximately 1.3 billion adults aged 30–79 years in 2019 worldwide, doubling from 1990.<span>³</span> In addition to the heavy disease burden, the economic burden associated with hypertension is also substantial, accounting for approximately 10% of the global healthcare expenditure.<span>⁴</span> Furthermore, despite improvements in diagnostic and treatment capacities, the status of hypertension care remains suboptimal, especially in low- and middle-income countries. For instance, in China, in 2019, the awareness, treatment, and control rates of hypertension were 38.3%, 34.6%, and 12.0%, respectively.<span>⁵</span> Accumulating evidence calls for more comprehensive and effective prevention and management of hypertension.</p><p>Multiple risk factors for hypertension have been well established, including genetic background, high sodium intake, smoking, physical inactivity, obesity, and alcohol intake.<span>^{6, 7}</span> Other potential risk factors (e.g., air pollution, psychological disorders, sleep habits, and noise exposure) have received increasing attention in recent years.<span>⁴</span> To enhance the efficacy of prevention, identifying the potential risk factors for hypertension within specific populations and developing advanced tools to improve adherence to interventions remain imperative. In addition to lifestyle modifications, pharmacological treatment is essential for managing hypertension. Moreover, hypertension may cause other diseases such as cardiovascular disease, chronic kidney disease, and dementia.<span>^{8, 9}</span> Additionally, hypertension during pregnancy is associated with adverse consequences for offspring, including preterm birth, vascular dysfunction, and cognitive impairment.<span>^{10, 11}</span> Therefore, it is important to systematically understand the current research status of hypertension and related diseases.</p><p>In this special issue, authors from the United States, United Kingdom, China, India, and Pakistan report the latest research findings on hypertension and related diseases. The issue comprises eight publications, including four original articles, two brief reports, one study protocol, and one correspondence. In summary, the aforementioned studies employed different epidemiological designs to assess the risk factors for hypertension, identify molecular biomarkers for pre-eclampsia (PE), depict the adverse impact of blood pressure on various outcomes, and provide potential evidence for hypertension management and treatment.</p><p>Zhang et al.<span>¹²</span> offered valuable ","PeriodicalId":32096,"journal":{"name":"Chronic Diseases and Translational Medicine","volume":"10 2","pages":"89-91"},"PeriodicalIF":0.0,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cdt3.129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141308922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical activity, long-term fine particulate matter exposure and type 2 diabetes incidence: A prospective cohort study","authors":"Qian Li,&nbsp;Fangchao Liu,&nbsp;Keyong Huang,&nbsp;Fengchao Liang,&nbsp;Chong Shen,&nbsp;Jian Liao,&nbsp;Jianxin Li,&nbsp;Chenxi Yuan,&nbsp;Xueli Yang,&nbsp;Jie Cao,&nbsp;Shufeng Chen,&nbsp;Dongsheng Hu,&nbsp;Jianfeng Huang,&nbsp;Yang Liu,&nbsp;Xiangfeng Lu,&nbsp;Dongfeng Gu","doi":"10.1002/cdt3.128","DOIUrl":"https://doi.org/10.1002/cdt3.128","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Despite the adverse effects of ambient fine particulate matter (PM_2.5) on type 2 diabetes and the beneficial role of physical activity (PA), the influence of PM_2.5 on the relationship between PA and type 2 diabetes remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this prospective study with 71,689 participants, PA was assessed by a questionnaire and was categorized into quartiles for volume and three groups for intensity. Long-term PM_2.5 exposure was calculated using 1-km resolution satellite-based PM_2.5 estimates. PM_2.5 exposure and PA's effect on type 2 diabetes were assessed by cohort-stratified Cox proportional hazards models, individually and in combination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In 488,166 person-years of follow-up, 5487 incident type 2 diabetes cases were observed. The association between PA and type 2 diabetes was modified by PM_2.5. Compared with the lowest quartile of PA volume, the highest quartile was associated with reduced type 2 diabetes risk in low PM_2.5 stratification (≤65.02 µg/m³) other than in high PM_2.5 stratification (&gt;65.02 µg/m³), with the hazard ratio (HR) of 0.75 (95% confidence interval [CI]: 0.66–0.85) and 1.10 (95% CI: 0.99–1.22), respectively. Similar results were observed for PA intensity. High PM_2.5 exposure combined with the highest PA levels increased the risk of type 2 diabetes the most (HR = 1.79, 95% CI: 1.59–2.01 for PA volume; HR = 1.82, 95% CI: 1.64–2.02 for PA intensity).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>PA could reduce type 2 diabetes risk in low-pollution areas, but high PM_2.5 exposure may weaken or even reverse the protective effects of PA. Safety and health benefits of PA should be thoroughly assessed for long-term polluted residents.</p>\u0000 </section>\u0000 </div>","PeriodicalId":32096,"journal":{"name":"Chronic Diseases and Translational Medicine","volume":"10 3","pages":"205-215"},"PeriodicalIF":0.0,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cdt3.128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141639646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of long-term blood pressure variability on renal function in community population","authors":"Zhao Feng,&nbsp;Zhiquan Jing,&nbsp;Zeya Li,&nbsp;Gang Wang,&nbsp;Shanshan Wu,&nbsp; Dan Li,&nbsp;Jing Hao,&nbsp;Chunlei Yang,&nbsp;Jiashu Song,&nbsp;Xianzhong Gu,&nbsp;Rongchong Huang","doi":"10.1002/cdt3.127","DOIUrl":"10.1002/cdt3.127","url":null,"abstract":"<p>High blood pressure is a significant contributor to premature mortality, resulting in nearly 10 million deaths and over 200 million disabilities worldwide.<span>¹</span> In recent years, hypertension treatment has shifted focus not only to average blood pressure but also to blood pressure variability (BPV), categorized into very short-term, short-term, and long-term BPV based on the time period of occurrence.<span>^{2, 3}</span> Long-term BPV has emerged as clinically significant, with studies demonstrating its superiority in predicting long-term cardiovascular events, stroke, and mortality compared to short-term variability. Given its association with pre-renal function decline, reducing blood pressure fluctuations is imperative.</p><p>Chronic kidney disease (CKD) poses a global public health challenge, with its incidence rising alongside aging populations and increasing rates of conditions like diabetes and hypertension. Hypertension and kidney disease are closely intertwined, with hypertension exacerbating renal damage. At present, the management of hypertension mainly focuses on average blood pressure, but the average blood level does not accurately reflect the long-term control status of blood pressure. Notably, some patients with ostensibly controlled average blood pressure still experience renal function deterioration within 5–10 years, potentially due to blood pressure fluctuations. Emerging evidence suggests a link between cardiovascular events, renal injury, and BPV, independent of average blood pressure.<span>^{4, 5}</span> However, the precise relationship between BPV and renal function remains elusive. This study aimed to explore the association between fluctuating blood pressure and rapid renal function decline in a prospective community health checkup-based cohort.</p><p>A total of 7153 patients aged ≥18 years who received at least twice regular physical examinations at the Community Health Service Centre in Beijing, between 2015 and 2021, were recruited consecutively in this study. Exclusion criteria included CKD stage 4–5, acute stroke, myocardial infarction, and heart failure (&lt;3 months). Finally, 7130 patients were enrolled in the analysis (Figure S1).</p><p>Sociodemographic information, comorbidities, and lifestyle habits were obtained through questionnaires. Blood pressure was measured twice during each visit, and BPV indices were calculated based on measurements across all visits. Additionally, blood samples were collected after an 8-h fast for biochemical analyses. We calculated several indicators as measures of BPV based on data from all visits, including standard deviation (SD), coefficient of variation (CV), variation independent of the mean (VIM), and average successive variability (ASV). The measures have been used in previous studies.<span>^{6, 7}</span></p><p>Baseline data for this study were derived from the results of the initial annual health checkup, while endpoint data we","PeriodicalId":32096,"journal":{"name":"Chronic Diseases and Translational Medicine","volume":"10 2","pages":"149-152"},"PeriodicalIF":0.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cdt3.127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141104764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between plasma growth differentiation factor 15 levels and pre-eclampsia in China","authors":"Shuhong Xu,&nbsp;Yicheng Lu,&nbsp;Mengxin Yao,&nbsp;Zhuoqiao Yang,&nbsp;Yan Chen,&nbsp;Yaling Ding,&nbsp;Yue Xiao,&nbsp;Fei Liang,&nbsp;Jiani Qian,&nbsp;Jinchun Ma,&nbsp;Songliang Liu,&nbsp;Shilan Yan,&nbsp;Jieyun Yin,&nbsp;Qiuping Ma","doi":"10.1002/cdt3.126","DOIUrl":"10.1002/cdt3.126","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Growth differentiation factor-15 (GDF-15) is a stress response protein and is related to cardiovascular diseases (CVD). This study aimed to investigate the association between GDF-15 and pre-eclampsia (PE).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>The study involved 299 pregnant women, out of which 236 had normal pregnancies, while 63 participants had PE. Maternal serum levels of GDF-15 were measured by using enzyme-linked immunosorbent assay kits and then translated into multiple of median (MOM) to avoid the influence of gestational week at blood sampling. Logistic models were performed to estimate the association between GDF-15 MOM and PE, presenting as odd ratios (ORs) and 95% confidence intervals (CIs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MOM of GDF-15 in PE participants was higher compared with controls (1.588 vs. 1.000, <i>p</i> &lt; 0.001). In the logistic model, pregnant women with higher MOM of GDF-15 (&gt;1) had a 4.74-fold (95% CI = 2.23–10.08, <i>p</i> &lt; 0.001) increased risk of PE, adjusted by age, preconceptional body mass index, gravidity, and parity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results demonstrated that higher levels of serum GDF-15 were associated with PE. GDF-15 may serve as a biomarker for diagnosing PE.</p>\u0000 </section>\u0000 </div>","PeriodicalId":32096,"journal":{"name":"Chronic Diseases and Translational Medicine","volume":"10 2","pages":"140-145"},"PeriodicalIF":0.0,"publicationDate":"2024-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cdt3.126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140986446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem cell secretome restore the adipo-osteo differentiation imbalance in diabetic dental pulp-derived mesenchymal stem cells","authors":"Avinash Sanap,&nbsp;Kalpana Joshi,&nbsp;Supriya Kheur,&nbsp;Ramesh Bhonde","doi":"10.1002/cdt3.125","DOIUrl":"10.1002/cdt3.125","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mesenchymal stem cells (MSCs) from type 2 diabetes mellitus (T2DM) individuals exhibit increased adipogenesis and decreased osteogenesis. We investigated the potential of adipose tissue-derived MSCs (ADMSCs) secretome obtained from healthy individuals in restoring the tumor necrosis factor-α (TNF-α) mediated imbalance in the adipo/osteogenic differentiation in the dental pulp-derived MSCs obtained from T2DM individuals (dDPMSCs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>dDPMSCs were differentiated into adipocytes and osteocytes using a standard cocktail in the presence of (a) induction cocktail, (b) induction cocktail + TNF-α, and (c) induction cocktail+ TNF-α + ADMSCs-secretome (50%) for 15 and 21 days resp. Differentiated adipocytes and osteocytes were stained by oil red O and alizarin red and analyzed by using ImageJ software. Molecular expression of the key genes involved was analyzed by using reverse-transcription polymerase chain reaction (RT-PCR).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Treatment of TNF-α augmented the adipogenesis (9571 ± 765 vs. 19,815 ± 1585 pixel, <i>p</i> &lt; 0.01) and decreased the osteogenesis (15,603 ± 1248 vs. 11,894 ± 951 pixel, <i>p</i> &lt; 0.05) of dDPMSCs as evidenced by the oil red O and alizarin red staining respectively. Interestingly, dDPMSCs differentiated along with TNF-α and 50% ADMSCs secretome exhibited enhanced osteogenesis (11,894 ± 951 vs. 41,808 ± 3344 pixel, <i>p</i> &lt; 0.01) and decreased adipogenesis (19,815 ± 1585 vs. 4480 ± 358 pixel, <i>p</i> &lt; 0.01). Additionally, dDPMSCs differentiated along with ADMSCs secretome exhibited decreased expression of PPARg (<i>p</i> &lt; 0.01), C/EBPa (<i>p</i> &lt; 0.05), and FAS (<i>p</i> &lt; 0.01) whereas mRNA expression of Runx2 (<i>p</i> &lt; 0.05), Osterix (<i>p</i> &lt; 0.01), and OCN (<i>p</i> &lt; 0.05) was upregulated as revealed by the RT-PCR analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>ADMSCs secretome from healthy individuals restore the TNF-α influenced differentiation fate of dDPMSCs and therefore can be explored for T2DM clinical management in the future.</p>\u0000 </section>\u0000 </div>","PeriodicalId":32096,"journal":{"name":"Chronic Diseases and Translational Medicine","volume":"10 4","pages":"340-349"},"PeriodicalIF":0.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cdt3.125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141008129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling blood pressure-associated genes in aortic cells through integrative analysis of GWAS and RNA modification-associated variants","authors":"Huan Zhang,&nbsp;Yuxi Chen,&nbsp;Peng Xu,&nbsp;Dan Liu,&nbsp;Naqiong Wu,&nbsp;Laiyuan Wang,&nbsp;Xingbo Mo","doi":"10.1002/cdt3.124","DOIUrl":"https://doi.org/10.1002/cdt3.124","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Genome-wide association studies (GWAS) have identified more than a thousand loci for blood pressure (BP). Functional genes in these loci are cell-type specific. The aim of this study was to elucidate potentially functional genes associated with BP in the aorta through the utilization of RNA modification-associated single-nucleotide polymorphisms (RNAm-SNPs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Utilizing large-scale genetic data of 757,601 individuals from the UK Biobank and International Consortium of Blood Pressure consortium, we identified associations between RNAm-SNPs and BP. The association between RNAm-SNPs, gene expression, and BP were examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 355 RNAm-SNPs related to m⁶A, m¹A, m⁵C, m⁷G, and A-to-I modification were associated with BP. The related genes were enriched in the pancreatic secretion pathway and renin secretion pathway. The BP GWAS signals were significantly enriched with m⁶A-SNPs, highlighting the potential functional relevance of m⁶A in physiological processes influencing BP. Notably, m⁶A-SNPs in <i>CYP11B1, PDE3B, HDAC7, ACE, SLC4A7, PDE1A, FRK, MTHFR, NPPA, CACNA1D</i>, and <i>HDAC9</i> were identified. Differential methylation and differential expression of the BP genes in FTO-overexpression and METTL14-knockdown vascular smooth muscle cells were detected. RNAm-SNPs were associated with ascending and descending aorta diameter and the genes showed differential methylation between aortic dissection (AD) cases and controls. In scRNA-seq study, we identified <i>ARID5A, HLA-DPB1, HLA-DRA, IRF1, LINC01091, MCL1, MLF1, MLXIPL, NAA16, NADK, RERG, SRM</i>, and <i>USP53</i> as differential expression genes for AD in aortic cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The present study identified RNAm-SNPs in BP loci and elucidated the associations between the RNAm-SNPs, gene expression, and BP. The identified BP-associated genes in aortic cells were associated with AD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":32096,"journal":{"name":"Chronic Diseases and Translational Medicine","volume":"10 2","pages":"118-129"},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cdt3.124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141308853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular regulation of calcium-sensing receptor (CaSR)-mediated signaling","authors":"Li Tian,&nbsp;Corey Andrews,&nbsp;Qiuyun Yan,&nbsp;Jenny J. Yang","doi":"10.1002/cdt3.123","DOIUrl":"https://doi.org/10.1002/cdt3.123","url":null,"abstract":"<p>Calcium-sensing receptor (CaSR), a family C G-protein-coupled receptor, plays a crucial role in regulating calcium homeostasis by sensing small concentration changes of extracellular Ca²⁺, Mg²⁺, amino acids (e.g., L-Trp and L-Phe), small peptides, anions (e.g., HCO₃⁻ and PO₄³⁻), and pH. CaSR-mediated intracellular Ca²⁺ signaling regulates a diverse set of cellular processes including gene transcription, cell proliferation, differentiation, apoptosis, muscle contraction, and neuronal transmission. Dysfunction of CaSR with mutations results in diseases such as autosomal dominant hypocalcemia, familial hypocalciuric hypercalcemia, and neonatal severe hyperparathyroidism. CaSR also influences calciotropic disorders, such as osteoporosis, and noncalciotropic disorders, such as cancer, Alzheimer's disease, and pulmonary arterial hypertension. This study first reviews recent advances in biochemical and structural determination of the framework of CaSR and its interaction sites with natural ligands, as well as exogenous positive allosteric modulators and negative allosteric modulators. The establishment of the first CaSR protein–protein interactome network revealed 94 novel players involved in protein processing in endoplasmic reticulum, trafficking, cell surface expression, endocytosis, degradation, and signaling pathways. The roles of these proteins in Ca²⁺-dependent cellular physiological processes and in CaSR-dependent cellular signaling provide new insights into the molecular basis of diseases caused by CaSR mutations and dysregulated CaSR activity caused by its protein interactors and facilitate the design of therapeutic agents that target CaSR and other family C G-protein-coupled receptors.</p>","PeriodicalId":32096,"journal":{"name":"Chronic Diseases and Translational Medicine","volume":"10 3","pages":"167-194"},"PeriodicalIF":0.0,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cdt3.123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141639485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive value of total cholesterol to high-density lipoprotein cholesterol ratio for chronic kidney disease among adult male and female in Northwest China","authors":"Yanli Liu,&nbsp;Kang Lyu,&nbsp;Shaodong Liu,&nbsp;Jinlong You,&nbsp;Xue Wang,&nbsp;Minzhen Wang,&nbsp;Desheng Zhang,&nbsp;Yana Bai,&nbsp;Chun Yin,&nbsp;Min Jiang,&nbsp;Shan Zheng","doi":"10.1002/cdt3.122","DOIUrl":"10.1002/cdt3.122","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Studies have found that the ratio of total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) was associated with the development of chronic kidney disease (CKD). However, the relationship in different genders was rarely discussed. The aim of this study was to explore this relationship and assess its predictive power for both males and females.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Based on a prospective cohort platform in northwest China, 32,351 participants without CKD were collected in the baseline and followed up for approximately 5 years. Cox proportional hazard model and restricted cubic spline regression analysis were performed to investigate the association between TC, HDL-C, TC/HDL-C and CKD in adult female and male. The clinical application value of the indicators in predicting CKD was evaluated by the receiver operator characteristic curve.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>During a mean follow-up of 2.2 years, 484 males and 164 females developed CKD. After adjusted for relevant confounders, for every one standard deviation increase in TC, HDL-C and TC/HDL-C, the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for CKD were 1.17 (1.05–1.31), 0.84 (0.71–0.99), and 1.15 (1.06–1.25) for males, 0.94 (0.78–1.13), 0.58 (0.35–0.95), and 1.19 (1.01–1.40) for females, respectively. The results also showed that TC, HDL-C, and TC/HDL-C were associated with CKD in a linear dose–response relationship. The TC/HDL-C had the largest area under the curve (AUC) compared to TC and HDL-C, and the AUC among the females was larger than that among males.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The TC/HDL-C was significantly associated with CKD in adult males and females and has better clinical value in predicting CKD than TC and HDL-C, especially in females.</p>\u0000 </section>\u0000 </div>","PeriodicalId":32096,"journal":{"name":"Chronic Diseases and Translational Medicine","volume":"10 3","pages":"216-226"},"PeriodicalIF":0.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cdt3.122","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140690558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COX-2 in lung cancer: Mechanisms, development, and targeted therapies","authors":"Xueqi Liu,&nbsp;Junli Zhang,&nbsp;Wenwu Sun,&nbsp;Jianping Cao,&nbsp;Zhuang Ma","doi":"10.1002/cdt3.120","DOIUrl":"10.1002/cdt3.120","url":null,"abstract":"<p>Lung cancer (LC) is the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) comprising 85% of all cases. COX-2, an enzyme induced significantly under stress conditions, catalyzes the conversion of free arachidonic acid into prostaglandins. It exhibits high expression in various tumors and is closely linked to LC progression. COX-2 functions as a pivotal driver in cancer pathogenesis by promoting prostaglandin E2 synthesis and facilitating tumor cell occurrence and development. Furthermore, COX-2 holds potential as a predictive marker for early-stage NSCLC, guiding targeted therapy in patients with early COX-2 overexpression. Additionally, combining COX-2 inhibitors with diverse treatment modalities enhances tumor therapeutic efficacy, minimizes adverse effects on healthy tissues, and improves overall patient survival rates posttreatment. In conclusion, combined therapy targeting COX-2 presents a promising novel strategy for NSCLC treatment, offering avenues for improving prognosis and effective tumor treatment. This review provides novel insights and ideas for developing new treatment strategies to improve the prognosis of NSCLC.</p>","PeriodicalId":32096,"journal":{"name":"Chronic Diseases and Translational Medicine","volume":"10 4","pages":"281-292"},"PeriodicalIF":0.0,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cdt3.120","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140251223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}