Hypercholesterolemia Research Articles

Cholesterol synthesis is essential for the growth of liver metastasis-prone colorectal cancer cells.

Metastasis to the liver is a leading cause of death in patients with colorectal cancer. To investigate the characteristics of cancer cells prone to metastasis, we utilized an isogenic model of BALB/c and colon tumor 26 (C26) cells carrying an active KRAS mutation. Liver metastatic (LM) 1 cells were isolated from mice following intrasplenic transplantation of C26 cells. Subsequent injections of LM1 cells generated LM2 cells, and after four cycles, LM4 cells were obtained. Invitro, using a perfusable capillary network system, we found comparable extravasation frequencies between C26 and LM4 cells. Both cell lines showed similar growth rates invitro. However, C26 cells showed higher glucose consumption, whereas LM4 cells incorporated more fluorescent fatty acids (FAs). Biochemical analysis revealed that LM4 cells had higher cholesterol levels than C26 cells. A correlation was observed between fluorescent FAs and cholesterol levels detected using filipin III. LM4 cells utilized FAs as a source for cholesterol synthesis through acetyl-CoA metabolism. In cellular analysis, cholesterol accumulated in punctate regions, and upregulation of NLRP3 and STING proteins, but not mTOR, was observed in LM4 cells. Treatment with a cholesterol synthesis inhibitor (statin) induced LM4 cell death invitro and suppressed LM4 cell growth in the livers of nude mice. These findings indicate that colorectal cancer cells prone to liver metastasis show cholesterol-dependent growth and that statin therapy could help treat liver metastasis in immunocompromised patients.

Abstract B014: Cannabis use among cancer survivors and its association with cardiometabolic risk factors: Findings from the All of Us Research Program

Abstract Purpose: Cannabis use has been linked to alleviating symptoms such as sleep issues, mental health, and physical problems resulting from cancer treatment among cancer survivors. However, in the US general population, evidence suggests that an increase in cannabis use increases the risk for cardiovascular disease including high blood pressure, type 2 diabetes, and high cholesterol. This is even more alarming since users who have been diagnosed with cancer have an even greater independent risk of cardiovascular events due to the toxicities of cancer therapeutic drugs. Given the US trend in cannabis legalization and decriminalization and the limited knowledge of the association between cannabis use and cardiometabolic biomarkers among cancer survivors, we aim to assess the independent associations between cannabis use and several cardiometabolic biomarkers and explore racial/ethnic and sex differences among a sample of cancer survivors from the All of Us (AoU) Program. Methods: Cross-sectional cannabis data and cardiometabolic risk factor biomarkers were obtained from adult cancer survivors in the AoU Research Program from 2018-2022. Cannabis use was defined as never use (in a lifetime or past three months), occasional use (twice or monthly in the past three months), and frequent/regular use (weekly or daily). Cardiometabolic outcomes included cardiovascular (e.g., systolic, diastolic blood pressure, hypertension), immune (i.e., White Blood Cell [WBC] counts, C-reactive protein [CRP]), and metabolic systems biomarkers (e.g. waist-to-hip ratio, lipids, HbA1c), were dichotomized from continuous values to elevated vs normal where high values, defined by clinically established cutoffs or >75th percentile, represented elevated biomarkers. Multivariable logistic regression and stratified models if interactions were statistically significant, adjusting for treatment, smoking, hazardous alcohol use, and sociodemographic variables were used. Results: Our cohort (N=6,985) consisted of 7.6% Hispanic, 6.2% Black, and 86.2% White survivors. Overall, 8.2% of survivors reported occasional and frequent/regular cannabis use, with Black survivors (9.7%) reporting a greater proportion of frequent/regular use compared to White (3.2%) and Hispanic (4.7%) survivors. Similarly, female (2.8%) survivors reported a lower frequency of frequent/regular cannabis use compared to male (4.2%) survivors. Compared to never users, frequent/regular users were 3.35(95% CI=1.10-10.53) times as likely to report elevated WBC count. No significant associations were found between cannabis use and CRP, cardiovascular, and metabolic systems biomarkers. Similarly, no race/ethnicity or sex (both pinteraction > 0.05) differences were found in the cannabis and WBC association. Conclusion: Our results underscore that more frequent cannabis use may have a detrimental effect on immune risk factors like WBC counts among survivors. Being that high WBC may be predictive of cardiovascular diseases and mortality, future studies should explore the longitudinal effects of cannabis use on WBC. Citation Format: Angel Arizpe, Claudia M. Toledo-Corral, Carol Y. Ochoa-Dominguez, Stephanie Navarro, Sue E. Kim, Albert J. Farias. Cannabis use among cancer survivors and its association with cardiometabolic risk factors: Findings from the All of Us Research Program [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B014.

Abstract C103: Exploring ethnicity-specific molecular mechanism of cholesterol and fatty acid synthesis pathway in Hispanic colorectal cancer

Abstract Colorectal cancer (CRC) is the most prevalent gastrointestinal cancer, the third most common malignancy and the second leading cause of cancer-related mortality worldwide. The American Cancer Society (ACS) estimates 152,810 new cases of colorectal cancer, with an estimated 53,010 deaths in 2024. Typically diagnosed in older adults, CRC incidence is rising among younger individuals, particularly in Hispanics (16.5%) compared to non-Hispanic whites (8.7%). Due to the lack of timely screenings in this ethnic group, further research is crucial to identify novel biomarkers and therapeutic targets for improved early detection and intervention. To accomplish this goal, we performed RNA-sequencing of Hispanic and non-Hispanic White (NHW) CRC tissues. The transcriptomic analysis revealed differential gene expression patterns in Hispanic and NHW populations when compared to respective normal adjacent tissues (NATs). We identified 3577 differentially expressed genes (DEGs) in Hispanic CRC samples and 2971 DEGs in NHW CRC samples, of which 1831 DEGs were unique to Hispanic. Based on the preliminary analysis we hypothesized that unique DEGs from the Hispanic population could help identify potential pathways contributing to CRC progression. Among these 1831 unique DEGs, many of the genes are associated with cholesterol and fatty acid synthesis pathway. The cholesterol biosynthesis pathway is a highly diverse and interconnected signaling pathway, playing essential roles in cellular function and systemic homeostasis. Its complexity and regulatory mechanisms make it a critical area of study in cancer. Studies indicate that Hispanics and African Americans with high cholesterol tend to have higher Body mass index (BMI) levels compared to Whites which has an increased risk of colorectal cancer. However, the role of cholesterol metabolism and fatty acid metabolism in CRC have not been studied from the Hispanic health disparities perspective. From the 1831 DEGs, we selected those in the cholesterol and fatty acid synthesis pathways with significant log2 fold changes (≤ -2 or ≥ +2) and adjusted p-values (FDR ≤ 0.05). Our bioinformatics analysis identified four key DEGs: LCN2, DHCR7, PCSK9 and SQLE. The expression levels of these genes were examined in Hispanic CRC vs. NHW CRC tissue samples using qRT-PCR. Elevated expression of LCN2 and SQLE was observed in late-stage Hispanic CRC tissues compared to NHW CRC tissues, while DHCR7 exhibited high expression in early-stage Hispanic CRC. On the other hand, PCSK9 showed low expression in both early and late stages of Hispanic CRC, suggesting potential ethnicity-specific molecular signatures in CRC progression. Moving forward, protein level studies and functional analysis of these DEGs in Hispanic CRC tissues and organoids will enhance our understanding of the role of cholesterol and fatty acid synthesis pathway proteins. Thus, elucidating novel molecular mechanisms underlying CRC progression could lead to identification of potential Hispanic specific biomarkers and therapeutic targets for early diagnosis and intervention. Citation Format: Somrita Roy, Soumya Nair, MD Zahirul Islam Khan, Sourav Roy. Exploring ethnicity-specific molecular mechanism of cholesterol and fatty acid synthesis pathway in Hispanic colorectal cancer [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C103.

Role of lymphocyte-to-monocyte ratio as a predictive marker for diabetic coronary artery disease: A cross-sectional study.

The lymphocyte to monocyte ratio (LMR) is considered a marker of systemic inflammation in cardiovascular disease and acts as predictor of mortality in coronary artery disease. To investigate the predictive role of LMR in diabetic coronary artery disease patients. This cross-sectional study was conducted at tertiary care super-specialty hospital at New Delhi, India. A total of 200 angiography-proven coronary artery disease (CAD) patients were enrolled and grouped into two categories: Group I [CAD patients with type 2 diabetes mellitus (T2DM) and glycated hemoglobin (HbA1c) levels ≥ 6.5%], and Group II (CAD patients without T2DM and HbA1c levels < 6.5%). Serum lipoproteins, HbA1c, and complete blood count of enrolled patients were analyzed using fully automatic analyzers. The logistic regression analysis showed an odds ratio of 1.48 (95%CI: 1.28-1.72, P < 0.05) for diabetic coronary artery disease patients (Group I) in unadjusted model. After adjusting for age, gender, diet, smoking, and hypertension history, the odds ratio increased to 1.49 (95%CI: 1.29-1.74, P < 0.01) in close association with LMR. Further adjustment for high cholesterol and triglycerides yielded the same odds ratio of 1.49 (95%CI: 1.27-1.75, P < 0.01). Receiver operating characteristic curve analysis revealed 74% sensitivity, 64% specificity, and 0.74 area under the curve (95%CI: 0.67-0.80, P < 0.001), suggesting moderate predictive accuracy for diabetic CAD patients. LMR showed positive association with diabetic coronary artery disease, with moderate predictive accuracy. These findings have implications for improving CAD management in diabetics, necessitating further research and targeted interventions.

Long COVID is not the same for everyone: a hierarchical cluster analysis of Long COVID symptoms 9 and 12 months after SARS-CoV-2 test

BackgroundIdentifying symptom clusters in Long COVID is necessary for developing effective therapies for this diverse condition and improving the quality of life of those affected by this heterogeneous condition. In this study, we aimed to identify and compare symptom clusters at 9 and 12 months after a SARS-CoV-2 positive test and describe each cluster regarding factors at infection.MethodsThis is a cross-sectional study with individuals randomly selected from the Portuguese National System of Epidemiological Surveillance (SINAVE) database. Individuals who had a positive SARS-CoV-2 test in August 2022 were contacted to participate in a telephonic interview approximately 9 and 12 months after the test. A hierarchical clustering analysis was performed, using Euclidean distance and Ward’s linkage. Clustering was performed in the 35 symptoms reported 9 and 12 months after the SARS-CoV-2 positive test and characterised considering age, sex, pre-existing health conditions and symptoms at time of SARS-CoV-2 infection.Results552 individuals were included at 9 months and 458 at 12 months. The median age was 52 years (IQR: 40–64 years) and 59% were female. Hypertension and high cholesterol were the most frequently reported pre-existing health conditions. Memory loss, fatigue or weakness and joint pain were the most frequent symptoms reported 9 and 12 months after the positive test. Four clusters were identified at both times: no or minor symptoms; multi-symptoms; joint pain; and neurocognitive-related symptoms. Clusters remained similar in both times, but, within the neurocognitive cluster, memory loss and concentration issues increased in frequency at 12 months. Multi-symptoms cluster had older people, more females and more pre-existing health conditions at 9 months. However, at 12 months, older people and those with more pre-existing health conditions were in joint pain cluster.ConclusionsOur results suggest that Long COVID is not the same for everyone. In our study, clusters remained similar at 9 and 12 months, except for a slight variation in the frequency of symptoms that composed each cluster. Understanding Long COVID clusters might help identify treatments for this condition. However, further validation of the observed clusters and analysis of its risk factors is needed.

The Effectiveness of Bariatric Surgery on Treating Infertility in Women-A Systematic Review and Meta-Analysis.

Background/Objectives: Obesity is a growing global health concern, which increases the risk of various diseases and has seen a rising prevalence over time. The global prevalence of obesity among adults has doubled over time. Obesity significantly impacts health by increasing the risk of a range of severe medical conditions. Cardiovascular diseases, such as heart attacks and strokes, are more prevalent in individuals with obesity due to factors like high blood pressure and abnormal cholesterol levels. This systematic review and meta-analysis sought to establish the effectiveness of bariatric surgery in treating infertility in women. Methods: This systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. A broad electronic search was conducted through PubMed, Web Science, and Medline databases for studies published between April 2017 and October 2023. The search strategy used the following terms: bariatric surgery, metabolic surgery, bariatric surgical procedures, stomach stapling, infertility, and fertility issues. The data were analyzed using the Revman version 5.1.2 software. Results: The results of the study show that despite the heterogeneity found in the studies, irregular menstrual cycles were found to reduce significantly in patients who underwent bariatric surgery (p = 0.01), with an RR of 0.22, at a 95% CI (0.06, 0.74). With regards to infertility, the results indicate that bariatric surgery reduced the level of infertility among the patients significantly (p = 0.00001), with an RR of 0.55, at a 95% CI (0.45, 0.68). Further, the results show bariatric surgery reduced rate of miscarriages among patients (p = 0.01), with an RR of 0.51, at a 95% CI (0.30, 0.86). Moreover, bariatric surgery reduced the level of congenital malfunction, but the effect was not statistically significant (p = 0.16), with an RR of 0.39, at a 95% CI (0.10, 1.45). However, the overall effect of bariatric surgery on treating infertility was found to be significantly effective (p = 0.0001), with an RR of 0.54, at a 95% CI (0.43, 0.68). This implies that bariatric surgery helps in weight loss, which improves ovulatory dysfunction and irregular menstruation while boosting spontaneous conception. Conclusions: This study found that bariatric surgery helps infertile women of a reproductive age to lose weight, which improves ovulatory dysfunction and irregular menstruation while boosting spontaneous conception. On the other hand, the study noted that after bariatric surgery, spontaneous conception can occur because of a decreased rate of miscarriage, increased fertility, reduced levels of congenital malfunction, and the restoration of regular menstrual cycles. Therefore, this study highlights the need to offer adequate preconception care and counselling to women who are about to be pregnant, both before and after bariatric surgery. Further, based on the fact that this study focused on general bariatric surgery, future research should focus on specific types of bariatric surgery to establish the most effective type of bariatric surgery in treating infertility in women.

When the liver is in poor condition, so is the heart - cardiac remodelling in MASH mouse models.

Metabolic dysfunction-associated steatohepatitis (MASH) confers a risk for cardiovascular diseases in patients. Animal models may help exploring the mechanisms linking liver and heart diseases. Hence, we explored the cardiac phenotype in two MASH mouse models: foz/foz mice fed a high-fat diet (HFD) for 24 or 60 weeks and C57BL/6J mice fed a high-fat-, high-cholesterol-, and high-fructose diet for 60 weeks. Angiotensin II (AngII) was used as an additional cardiovascular stressor for 4 weeks in 10 weeks HFD-fed foz/foz mice. Foz/foz mice with fibrosing MASH developed cardiac hypertrophy with adverse cardiac remodelling not seen in WT similarly fed the HFD. AngII caused hypertension and up-regulated the expression of genes contributing to pathological cardiac hypertrophy (Nppa, Myh7) more severely so in foz/foz mice than in controls. After 60 weeks of HFD, while liver disease had progressed to burn-out non steatotic MASH with hepatocellular carcinoma in 50% of the animals, the cardiomyopathy did not. In an independent model (C57BL/6J mice fed a fat-, cholesterol- and fructose-rich diet), moderate fibrosing MASH is associated with cardiac fibrosis and dysregulation of genes involved in pathological remodelling (Col1a1, Col3a1, Vim, Myh6, Slc2a1). Thus, animals with MASH present consistent adverse structural changes in the heart with no patent alteration of cardiac function even when stressed with exogenous AngII. Liver disease, and likely not overfeeding or aging alone, is associated with this cardiac phenotype. Our findings support foz/foz mice as suitable for studying links between MASH and heart structural changes ahead of heart failure.

Optimalisasi Kampung Organik sebagai Ketahanan Pangan di Kelurahan Rejowinangun Selatan

Bay leaves are one of the toga plants (family medicinal plants) which can be used to stop excessive defecation. Apart from that, bay leaves can also be used to treat gout, stroke, high cholesterol, improve blood circulation, stomach inflammation, itching and diabetes. Therefore, there is a need for education in the form of counseling regarding the use of bay leaves and how to process them as herbal medicine to help cure diseases. Kaffir lime is a natural ingredient in various food and beverage products in Indonesia and other Asian countries. Kaffir lime plants contain compounds including essential oils which are also rich in benefits such as antioxidants, antimicrobials, antileuchemicals, antitussives, insecticides, illaricides and phenolic compounds such as flavonoids, flavanones, flavones, flavonols and glycerolipids which according to research function as a source of antioxidants, anti-inflammatory , antiviral, anti-allergic, and anti-carcinogenic, anti-aging for the human body. The planting of kitchen spices in the form of bay plants and orange leaves is grown using organic and environmentally friendly materials.

Endothelial Dysfunction in Children with Frequently Relapsing and Steroid-Dependent Nephrotic Syndrome

Background Children with frequently relapsing (FR) or steroid-dependent (SD) nephrotic syndrome (NS) show endothelial dysfunction and risk of endothelial injury during relapses, increasing the risk of accelerated atherosclerosis and adverse cardiovascular events. This study examines the plasma levels of markers of endothelial dysfunction [sE-selectin and vascular cell adhesion molecule-1 (VCAM-1)] in children aged 1–16 years with FRNS and SDNS in relapse. Materials and Methods Fifty-six children with FRNS and SDNS between 1 and 16 years were enrolled at the time of relapse and followed till six weeks of steroid-induced remission. Markers of endothelial dysfunction (sE-selectin and VCAM-1) in plasma were measured in these children and in an equal number of controls. Results Plasma sE-selectin and VCAM-1 levels were significantly raised during relapse, declined after six weeks of steroid-induced remission, and became comparable to controls (p &lt; 0.0001). We found high serum total cholesterol and triglycerides levels during relapse that remained elevated even after steroid-induced remission as compared to controls (p &lt; 0.0001). Raised levels of these markers confirm endothelial dysfunction in FRNS and SDNS patients. Conclusion Children with FRNS and SDNS had endothelial dysfunction during relapse, which was largely dependent upon disease activity.

Development and validation of a machine learning-based framework for assessing metabolic-associated fatty liver disease risk

BackgroundThe existing predictive models for metabolic-associated fatty liver disease (MAFLD) possess certain limitations that render them unsuitable for extensive population-wide screening. This study is founded upon population health examination data and employs a comparison of eight distinct machine learning (ML) algorithms to construct the optimal screening model for identifying high-risk individuals with MAFLD in China.MethodsWe collected physical examination data from 5,171,392 adults residing in the northwestern region of China, during the year 2021. Feature selection was conducted through the utilization of the Least Absolute Shrinkage and Selection Operator (LASSO) regression. Additionally, class balancing parameters were incorporated into the models, accompanied by hyperparameter tuning, to effectively address the challenges posed by imbalanced datasets. This study encompassed the development of both tree-based ML models (including Classification and Regression Trees, Random Forest, Adaptive Boosting, Light Gradient Boosting Machine, Extreme Gradient Boosting, and Categorical Boosting) and alternative ML models (specifically, k-Nearest Neighbors and Artificial Neural Network) for the purpose of identifying individuals with MAFLD. Furthermore, we visualized the importance scores of each feature on the selected model.ResultsThe average age (standard deviation) of the 5,171,392 participants was 51.12 (15.00) years, with 52.47% of the participants being females. MAFLD was diagnosed by specialized physicians. 20 variables were finally included for analyses after LASSO regression model. Following ten rounds of cross-validation and parameter optimization for each algorithm, the CatBoost algorithm exhibited the best performance, achieving an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.862. The ranking of feature importance indicates that age, BMI, triglyceride, fasting plasma glucose, waist circumference, occupation, high density lipoprotein cholesterol, low density lipoprotein cholesterol, total cholesterol, systolic blood pressure, diastolic blood pressure, ethnicity and cardiovascular diseases are the top 13 crucial factors for MAFLD screening.ConclusionThis study utilized a large-scale, multi-ethnic physical examination data from the northwestern region of China to establish a more accurate and effective MAFLD risk screening model, offering a new perspective for the prediction and prevention of MAFLD.

Efficient Biosynthesis of Monacolin J through Enzymatic Hydrolysis Using a Recombinant Lovastatin Hydrolase

Simvastatin is a widely used statin medication that is commonly prescribed to lower cholesterol levels and reduce the risk of cardiovascular events. It is marketed under the brand name Zocor and is known for its effectiveness in treating high cholesterol and managing cardiovascular disease. Monacolin J is an important precursor used to synthesize simvastatin and is mainly produced by chemical methods in industry. Here, monacolin J was synthesized through an enzymatic method under optimized reaction conditions. One recombinant Escherichia coli BL21 (DE3) strain containing lovastatin hydrolase (encoded by CDV55_102090) from Aspergillus turcosus was constructed, which effectively transformed 100 g/L of lovastatin to monacolin J within 3.5 h at pH 8.0 and 30 °C, with a conversion rate of &gt;99.8%. Furthermore, the T5010, the temperature at which the residual activity was half of the initial enzymatic activity after 10 min of heat treatment, was &gt;50 °C, indicating the tremendous potential of this bioprocess for synthesizing monacolin J at an industrial scale.

Study on the mechanism of Shenling Baizhu powder on the pathogenesis of pregnancy complicated with non-alcoholic fatty liver, based on PI3K/AKT/mTOR signal pathway.

This study investigates the effectiveness of Shenlin Baizhu powder in managing non-alcoholic fatty liver disease (NAFLD) during pregnancy and its mechanism through the PI3K/AKT/mTOR signaling pathway. Eight healthy male and 24 female Sprague-Dawley rats were used. After acclimatization, 6 female rats were fed normal chow, and 18 female rats were fed high-fat chow to induce NAFLD. After 8 weeks, female rats were mated with males to create a pregnant NAFLD model. The rats were divided into four groups: normal feeding, high-fat diet with saline, high-fat diet with 1.6 g/kg Shenlin Baizhu powder, and high-fat diet with 4.8 g/kg Shenlin Baizhu powder. Maternal body weight, serum and liver levels of aspartate aminotransferase (AST), alanine transaminase (ALT), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), related inflammatory indexes interleukin-1 β (IL-1 β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured. Liver tissue was examined using hematoxylin and oil red O staining, and protein expression related to the PI3K/AKT/mTOR pathway was assessed via Western blotting, immunohistochemistry and RT-PCR. Results showed significant weight gain and increases in ALT, AST, TG, TC, LDL-C, IL-1β, TNF-α, and IL-6, along with decreased HDL-C in NAFLD rats compared to controls. The high and low-dose Shenlin Baizhu powder groups exhibited improvements in body weight, liver histopathology, and reductions in serum TG, TC, LDL-C, ALT, AST, IL-1β, TNF-α, and IL-6, with increased HDL-C levels. Notably, the high-dose group showed greater efficacy in reducing hepatic fat accumulation, liver function markers, blood lipids, and inflammatory indexes, and decreased expression of hepatic PPARγ mRNA, SREBP1 mRNA, AKT mRNA, and related proteins. Shenlin Baizhu powder demonstrates potential in ameliorating high-fat diet-induced NAFLD in pregnant rats, likely through modulation of the PI3K/AKT/mTOR pathway, suggesting its therapeutic potential for gestational NAFLD.

Elevated serum cholesterol levels during pregnancy as predictors for postpartum hypercholesterolemia: A prospective cohort study.

To identify the associations between gestational cholesterol levels and the risk of postpartum hypercholesterolemia, and to establish trimester-specific reference values. Serum lipids at gestational weeks 6-8, 16, 24, and 36, and 42 days postpartum were derived from 905 pregnant women of a prospective cohort. The major outcome was postpartum hypercholesterolemia. Logistic regression and restricted cubic splines were conducted to estimate the associations between cholesterol levels at specific gestational ages and postpartum hypercholesterolemia. Associations of the trend of changes in cholesterol levels during pregnancy with postpartum hypercholesterolemia were evaluated by linear mixed-effect model and linear or logistic regression. Reference values were computed by the receiver operating characteristic curves. Serum concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and the ratios of TC/HDL-C and LDL-C/HDL-C all increased during pregnancy and decreased at 42 days postpartum. The elevated levels of TC and LDL-C, decreased levels of HDL-C in pregnancy, and their rapid change rates were positively associated with higher risks of postpartum hypercholesterolemia. The established reference values from the first to the third trimester were below 5.47, 6.35, and 7.22 mmol/L for TC; below 2.83, 3.82, and 4.21 mmol/L for LDL-C; and more than 1.50, 1.55, and 1.50 mmol/L for HDL-C, respectively. Maternal cholesterol levels and their trend of change during pregnancy were predictors of postpartum hypercholesterolemia. Trimester-specific reference values were established in a Chinese population.

Activated PARP1/FAK/COL5A1 signaling facilitates the tumorigenesis of cholesterol-resistant ovarian cancer cells through promoting EMT

Cancer cells require plentiful cholesterol for membrane biogenesis and other functional needs due to fast proliferating, leading to the interaction of cholesterol or its metabolites with cancer-related pathways. However, the impact of long-lasting high cholesterol concentrations on tumorigenesis and its underlying mechanisms remains largely unexplored. To the best of our knowledge, this study is the first to establish a cholesterol-resistant ovarian cancer cells, whose intracellular total cholesterol level up to 6–8 mmol/L. We confirmed that high cholesterol facilitated the progression of ovarian cancer in vitro and in vivo. Notably, our findings revealed significant upregulation of collagen type V alpha 1 chain (COL5A1) expression in cholesterol-resistant ovarian cancer cells and human ovarian cancer tissue, which was depended on FAK/Src activation. Mechanistically, PARP1 directly bound to FAK in response to activate FAK/Src/COL5A1 signaling. Intriguingly, COL5A1 depletion significantly impeded the tumorigenesis of these cells, concomitant with a decrease in epithelial-mesenchymal transition (EMT) progression. In conclusion, PARP1/FAK/COL5A1 signaling activation facilitated progression of cholesterol-resistant ovarian cancer cells by promoting EMT, thereby broadening a new therapeutic opportunity.

Analysis of Genetic Risk Factors Associated with Charcot Foot Based on the FinnGen Study R9 Data: A Wide-angle Mendelian Randomization Study.

Charcot foot or Charcot neuropathic joint disease (CN) is a rare and complex foot disease with unknown pathogenesis, hindering early identification and intervention. The study aimed to clarify the causal association between all predominant risk factors and CN. Two-sample Mendelian Randomization (MR), Multivariate MR, and Bidirectional MR analyses investigated the causal association between 36 modifiable risk factors and CN. The causal relationship between CN and Inflammatory cytokine and immune cells was also analyzed. Genetic factors associated with obesity and genetic susceptibility to various autoimmune diseases and non-cancerous thyroid diseases increased the risk of CN (P < .05), genetically associated high basal metabolic rate and high total cholesterol decreased the risk of CN (P < .05). In addition, we found a bi-directional causal relationship between CN and diabetes. In further immune cell analysis, we found 8 CN related immune cells, and in inflammatory cytokine analysis, we found 2 CN related inflammatory cytokines. This comprehensive MR Study supports the causal role of Obesity-related factors, diabetes, autoimmune-related factors, and smoking in the development and progression of CN. This study identifies a potential cause of CN that has not been identified in previous studies and provides a new direction for further research.

A high cholesterol diet aggravates experimental colitis through SREBP2-modulated endocytosis and degradation of occludin and Zo-1 proteins.

Disrupted cholesterol homeostasis plays a critical role in the development of multiple diseases, such as cardiovascular disease and cancer. However, the role of cholesterol in inflammatory bowel disease (IBD) remains unclear. In the present study, we investigated whether and how high levels of cholesterol in the diet affect experimental colitis in mice. A normal diet supplemented with 1.25% cholesterol (high cholesterol diet) caused more severe colitis and aggravated the disruption of intestinal tight junction structure, accompanied by higher colonic tissue total cholesterol (TC) levels in a dextran sulfate sodium (DSS)-induced experimental colitis mouse model. Cholesterol aggravated DSS-induced intestinal epithelial barrier impairment and nuclear sterol regulatory element-binding protein 2 (nSREBP2) inhibition both in vivo and in vitro. In addition, nSREBP2 overexpression ameliorated cholesterol-induced intestinal epithelial barrier disruption in Caco2 cells. Interestingly, inhibition of SREBP2 disrupted intestinal epithelial barrier in the absence of cholesterol. Furthermore, SREBP2 regulated the protein expression of tight junction proteins (occludin/Zo-1) via modulating caveolin-1-mediated endocytosis and lysosomal degradation. Analysis of UK Biobank data indicated that, in fully adjusted models, higher serum TC concentrations were an independent protective factor for IBD incidence. The sterol regulatory element-binding factor 2 (SREBF2) gene rs2228313 (G/C) genetic variant was associated with the incidence of IBD and the CC genotype of SREBF2 rs2228313 was associated with higher serum TC levels and decreased the risk of IBD. In summary, a high cholesterol diet aggravates DSS-induced colitis in mice by down-regulating nSREBP2 expression, thereby promoting the endocytic degradation of tight junction proteins. In humans, SREBF2 gene single nucleotide polymorphism rs2228313 and serum TC levels are associated with IBD incidence.

OS DESAFIOS ENCONTRADOS EM CRIANÇAS COM EXCESSO DE PESO E PORTADORAS DE DIABETES MELLITUS TIPO 1

Introduction: The increasing incidence of diabetes mellitus and obesity in children is a cause for global concern. These health conditions are interconnected and have serious implications for children's physical and emotional well-being. Additionally, obesity can contribute to other risk factors associated with diabetes, such as high blood pressure and high cholesterol levels. Objective: Discuss childhood obesity, its impacts and its correlation with diabetes mellitus, mainly type 1. Methodology: The integrative review is based on the guiding question ´´ What are the impacts of childhood obesity and its correlation with type 1 diabetes mellitus? 1´´. The research was carried out during the months of January to February 2024, in the LILACS, IBECS and MEDLINE databases with the help of the Boolean AND. After applying the inclusion and exclusion criteria, 06 articles remained used to construct the present study. Results and discussion: It was observed that among the articles selected for the construction of the research, around 66% (04) were published in 2023. While in the years 2022 and 2024, 17% (01) of the selected studies were published in each respective year. Obese children with type 1 diabetes may face additional difficulties adopting a healthy lifestyle. Final considerations: Importance of health education and promotion, as well as changing lifestyle habits.

Association of lipid profile with primary open angle glaucoma in non-obese patients

Hyperlipidemia has been shown to be associated with Glaucoma as well as increased intra ocular pressure (IOP). We conducted a case control study to further study the association of Lipid profile with Primary Open Angle Glaucoma (POAG) in non-obese patients.: With the approval from Institutional Ethics Committee (ICE) and written informed consent, 100 adult patients were included in the case control study. The methods applied in the study adhered to the tenets of the declaration of Helsinki. 50 non-obese POAG patients of above 40 years aged were included as cases and another 50 without Glaucoma were taken as controls. Patients were further subjected to biochemical investigation of the serum lipid profile performed by Vitros 5600.: Mean total cholesterol, triglyceride and low-density lipoprotein (LDL) levels were found to be significantly higher in non-obese POAG cases as compared to that in controls (p&amp;#60;0.05), whereas mean high density lipoprotein (HDL) levels were significantly lower in non-obese POAG cases as compared to that in controls (p&amp;#60;0.001). The odds of high cholesterol levels to be associated with POAG in non-obese are statistically significant (p&amp;#60;0.001).: The study demonstrated a relationship of serum lipid levels with risk of primary open angle glaucoma.

Shotgun Analysis of Gut Microbiota with Body Composition and Lipid Characteristics in Crohn's Disease.

Alterations to intestinal microbiota are assumed to occur in the pathogenesis of inflammatory bowel disease (IBD). This study aims to analyze the association of fecal microbiota composition, body composition, and lipid characteristics in patients with Crohn's disease (CD). In our cross-sectional study, patients with CD were enrolled and blood and fecal samples were collected. Clinical and endoscopic disease activity and body composition were assessed and laboratory tests were made. Fecal bacterial composition was analyzed using the shotgun method. Microbiota alterations based on obesity, lipid parameters, and disease characteristics were analyzed. In this study, 27 patients with CD were analyzed, of which 37.0% were obese based on visceral fat area (VFA). Beta diversities were higher in non-obese patients (p < 0.001), but relative abundances did not differ. C. innocuum had a higher abundance at a high cholesterol level than Bacillota (p = 0.001, p = 0.0034). Adlercreutzia, B. longum, and Blautia alterations were correlated with triglyceride levels. Higher Clostridia (p = 0.009) and B. schinkii (p = 0.032) and lower Lactobacillus (p = 0.035) were connected to high VFA. Disease activity was coupled with dysbiotic elements. Microbiota alterations in obesity highlight the importance of gut microbiota in diseases with a similar inflammatory background and project therapeutic options.

Evaluation of Serum Uric Acid in Patients with Obesity in Nigerian Tertiary Hospital

Background: Obesity has been recognized as an important risk factor for hyperuricemia although the exact mechanism is not well understood. The goal of this study is to evaluate serum uric acid levels in obese subjects. Methods: A total of 100 individuals with 50 obese patients and 50 healthy non-obese controls. Serum uric acid, total cholesterol (TC), low density lipoprotein cholesterol (LDL - C), high density lipoprotein cholesterol (HDL - C) and triglycerides (TGs) were measured. Serum uric acid was evaluated using uricase method. The serum TC was estimated using modified Liebermann – Burchard reaction. HDL – C estimation involved a two – staged procedure using Liebermann Burchard reaction, LDL – C was calculated using Friedwald’s equation while TGs were estimated using enzymatic methods on commercial kits. Results: In this study, serum uric acid levels were significantly higher in the obese group compared to healthy controls (510.0 + 72.5 Vs 320.0 + 34.2: p&lt;0.001). Conclusion: Hyperuricemia has been observed in patients with obesity and therefore the need to screen all obese patients for serum uric acid levels.