Simvastatin induces degradation of the extracellular matrix in human leiomyomata: novel in vitro, in vivo, and patient level evidence of matrix metalloproteinase involvement.

OBJECTIVES: To assess the effect of simvastatin on uterine leiomyoma growth and extracellular matrix (ECM) deposition. DESIGN: Laboratory analysis of human leiomyoma cell culture, xenograft in a mouse model, and patient tissue from a clinical trial. SETTING: Academic research center. PATIENT(S): Tissue culture from human leiomyoma tissue and surgical leiomyoma tissue sections from a placebo-controlled randomized clinical trial. INTERVENTION(S): Simvastatin treatment. MAIN OUTCOME MEASURE(S): Serum concentrations, xenograft volumes, and protein expression. RESULTS: Mice xenografted with 3-dimensional human leiomyoma cultures were divided as follows: 7 untreated controls; 12 treated with activated simvastatin at 10 mg/kg body weight; and 15 at 20 mg/kg body weight. Simvastatin was detected in the serum of mice injected at the highest dose. Xenograft volumes were significantly smaller (mean 53% smaller at the highest concentration). There was dissolution of compact ECM, decreased ECM formation, and lower collagen protein expression in xenografts. Membrane type 1 matrix metalloproteinase was increased in vitro and in vivo. Matrix metalloproteinase 2 and low-density lipoprotein receptor-related protein 1 were increased in vitro. CONCLUSIONS: Simvastatin exhibited antitumoral activity with ECM degradation and decreased leiomyoma tumor volume in vivo. Activation of the matrix metalloproteinase 2, membrane type 1 matrix metalloproteinase, and low-density lipoprotein receptor-related protein 1 pathway may explain these findings.

Low-density Lipoprotein Receptor Activities, Lipids, Apolipoprotein, and Clinical Course of Patients with Steroid-resistant Nephrotic Syndrome Treated with Low-density Lipoprotein Apheresis: A Case Series.

We herein report three cases of steroid-resistant nephrotic syndrome successfully treated with low-density lipoprotein apheresis (LDL-A). All patients were treated with a combination of steroids, cyclosporine, and LDL-A. In all cases, the serum concentrations of LDL, total and high-density lipoprotein cholesterol, and triglycerides were significantly lowered following LDL-A administration. Furthermore, the estimated LDL receptor activity increased, while both serum LDL and total cholesterol levels decreased, suggesting that LDL-A increases LDL receptor activity by driving changes in serum cholesterol concentration. This case series suggests that LDL-A increases LDL receptor activity, which may improve the intracellular uptake of cyclosporine.

Prognosis of Idiopathic Sudden Sensorineural Hearing Loss: The Nomogram Perspective.

OBJECTIVE: The aim of this study is to create a nomogram for accurately predicting the prognosis of idiopathic sudden sensorineural hearing loss (ISSNHL) and provide a reference for clinical treatment. METHODS: Three hundred and twenty-three patients with ISSNHL were admitted from September 2014 to November 2020. The clinical data were retrospectively reviewed. Prognostic factors for ISSNHL were assessed based on univariate and multivariate logistic regression analysis and used to create a nomogram. Nomogram performance in terms of predictive and discriminatory ability was evaluated by calculating the concordance index (C-index) and generating calibration plots. RESULTS: The overall hearing improvement rate was 41.4%, comprising complete recovery (13.3%), marked recovery (17.0%), and slight recovery (11.1%). Multivariate logistic regression analysis showed that age, symptoms of vertigo, interval between onset and treatment, low-density lipoprotein, and type of hearing loss were independent predictors of ISSNHL. A nomogram based on these 5 factors had a C index of 0.798 (95% confidence interval 0.750-0.845). CONCLUSIONS: Age, vertigo, interval between onset and treatment, low-density lipoprotein level, and type of hearing loss are closely associated with hearing recovery. The nomogram may enable prediction of the prognosis of ISSNHL and facilitate clinical decision-making.

Effect Of Tamoxifen On Plasma Lipid Profile In Patients Of Breast Cancer.

BACKGROUND: To evaluate the effect of Tamoxifen on plasma lipid profile in breast cancer patients presenting at tertiary care hospitals. METHODS: It was a longitudinal study conducted at the Department of Oncology of Jinnah Postgraduate Medical Center from December 2018 to November 2019. Eighty-eight females aged 26-66 years diagnosed with breast cancer were included in the study using a non-probability consecutive sampling technique. Detailed gynaecological and clinical investigations and detailed history were taken. The blood samples of all the patients were collected and the plasma lipid profile was measured before initiation of Tamoxifen treatment and three- and six-months post-treatment at the clinical laboratory. The plasma lipid profile includes the measurement of Total cholesterol (mg/dl), Triglyceride(mg/dl), High-density Lipoprotein (mg/dl) & Low-density Lipoprotein (mg/dl). SPSS version 23 was used to analyse data. RESULTS: After treatment, there was a significant reduction in serum cholesterol & Low-density Lipoprotein level by 20.54 mg/dl & 16.46 mg/dl at 3 months (p<0.05), moreover there was a significant increase in Triglyceride by 22.14 at 3 months (p<0.05). No significant difference was observed in High density lipoprotein level at 3 months after using Tamoxifen. At 6 months there was a significant reduction in serum cholesterol and low-density lipoprotein by 32.29mg/dl and 24.11 mg/dl at 6 months (p<0.05), moreover there was a significant increase in Triglyceride level by 42.19 mg/dl at 6 months (p<0.05). No significant difference was observed in High-density lipoprotein level at 6 months after using Tamoxifen. CONCLUSIONS: Total cholesterol and Low-density Lipoprotein levels showed significant reduction over the period of six months from the baseline with the use of Tamoxifen. Hence Tamoxifen should be considered to have an added advantage on lipid metabolism and therefore, can reduce the risk of cardiovascular events.

Regulation of Intestinal Flora and Immune Response by Cyanidin Exhibits Protective Effect against Type-2 Diabetes in Rat Model.

In the current study the effects of metformin and cyanidin on the immune system and intestinal flora in rats with type-2 diabetes was investigated. The findings showed that metformin or cyanidin treatment considerably reduced the rise in body weight and glucose levels induced by type-2 diabetes. The type-2 diabetic rats' glucose tolerance was significantly increased by cyanidin administration comparable to that of metformin. Cyanidin administration resulted in a significant reduction in serum cholesterol and low-density lipoprotein (LDL) levels in rats with type-2 diabetes. Treatment with cyanidin significantly increased the ratio of high-density lipoprotein to low-density lipoprotein in type-2 diabetes rats. Cyanidin administration significantly raised the ratio of Firmicutes to Bacteroidetes in the fecal samples of type-2 diabetic rats compared to the model group. In comparison to the model group, it also significantly raised the levels of Lactobacillus intestinalis, Lactobacillus gasseri, and Lactobacillus reuteri in the type-2 diabetes rats. In type-2 diabetes rat fecal samples, the abundance of Christensenellaceae significantly increased while Enterobacteriaceae and Proteobacteria were found to decrease upon cyanidin administration. Furthermore, cyanidin administration to the rats with type-2 diabetes significantly improved the glucose homeostasis. In conclusion, the study demonstrates that cyanidin enhances glucose homeostasis in rats with type-2 diabetes, potentially through controlling intestinal flora. Thus, cyanidin may be looked into more as a possible therapeutic agent for type 2 diabetes.

Simvastatin and non-segmental vitiligo: A new potential treatment option?

There is a paucity of data about the impact of systemic statins on vitiliginous lesions in non-segmental vitiligo (NSV) patients. To the best of our knowledge, no other studies have considered the correlation between lipid disturbances in vitiligo and vitiligo disease activity (VIDA) score. We sought in this study to evaluate the influence of simvastatin on vitiliginous lesions in NSV patients with dyslipidemia and study the correlation between VIDA score and lipid profile. This clinical trial started with 120 patients with NSV, 79 patients had dyslipidemia and received simvastatin 80 mg daily (till normalization of lipid profile or for 4 months, which came first) and only 63 patients continued till the end of the study. Lipid profile, vitiligo area severity index and VIDA were assessed before and 6 months after the end of simvastatin use. Serum total cholesterol (TC), triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), very low-density lipoprotein, and LDL/HDL ratio showed statistically significant increases in the NSV than in the control group (p Ë‚ 0.001). There was a statistically significant positive correlation between VIDA and serum levels of TC and LDL and with LDL/HDL ratio. Simvastatin significantly improved the lipid profile and significantly decreased VIDA (p < 0.011). Negative moderate correlation was found between the decrease in VIDA and duration of disease (r = -0.562, p < 0.001). Simvastatin 80 mg daily could be a helpful treatment for NSV patients with dyslipidemia, controlling the vitiligo activity and protecting against the hazardous effects of dyslipidemia. Better results can be obtained in patients with short duration of the disease.

Glucagon receptor antagonist volagidemab in type 1 diabetes: a 12-week, randomized, double-blind, phase 2 trial.

Hyperglucagonemia contributes to hyperglycemia in patients with type 1 diabetes (T1D); however, novel therapeutics that block glucagon action could improve glycemic control. This phase 2 study evaluated the safety and efficacy of volagidemab, an antagonistic monoclonal glucagon receptor (GCGR) antibody, as an adjunct to insulin therapy in adults with T1D. The primary endpoint was change in daily insulin use at week 12. Secondary endpoints included changes in hemoglobin A1c (HbA1c) at week 13, in average daily blood glucose concentration and time within target range as assessed by continuous blood glucose monitoring (CGM) and seven-point glucose profile at week 12, incidence of hypoglycemic events, the proportion of subjects who achieve HbA1c reduction of ≥0.4%, volagidemab drug concentrations and incidence of anti-drug antibodies. Eligible participants (n = 79) were randomized to receive weekly subcutaneous injections of placebo, 35 mg volagidemab or 70 mg volagidemab. Volagidemab produced a reduction in total daily insulin use at week 12 (35 mg volagidemab: -7.59 units (U) (95% confidence interval (CI) -11.79, -3.39; P = 0.040 versus placebo); 70 mg volagidemab: -6.64 U (95% CI -10.99, -2.29; P = 0.084 versus placebo); placebo: -1.27 U (95% CI -5.4, 2.9)) without meeting the prespecified significance level (P < 0.025). At week 13, the placebo-corrected reduction in HbA1c percentage was -0.53 (95% CI -0.89 to -0.17, nominal P = 0.004) in the 35 mg volagidemab group and -0.49 (95% CI -0.85 to -0.12, nominal P = 0.010) in the 70 mg volagidemab group. No increase in hypoglycemia was observed with volagidemab therapy; however, increases in serum transaminases, low-density lipoprotein (LDL)-cholesterol and blood pressure were observed. Although the primary endpoint did not meet the prespecified significance level, we believe that the observed reduction in HbA1c and tolerable safety profile provide a rationale for further randomized studies to define the long-term efficacy and safety of volagidemab in patients with T1D.

Serum cholesterol loading capacity on macrophages is linked to coronary atherosclerosis and cardiovascular event risk in rheumatoid arthritis.

OBJECTIVES: Cholesterol loading capacity (CLC) describes the ability of serum to deliver cholesterol to cells. It is linked to foam cell formation, a pivotal step in atherosclerotic plaque development. We evaluate the associations of CLC with coronary atherosclerosis presence, burden and cardiovascular risk in patients with rheumatoid arthritis (RA). METHODS: Coronary atherosclerosis (any, high-risk low-attenuation plaque and obstructive plaque) was evaluated with CT angiography in 141 patients. Participants were prospectively followed for 6.0±2.4 years and cardiovascular events including cardiac death, myocardial infarction, unstable angina, stroke, claudication, revascularisation and hospitalised heart failure were recorded. CLC was quantified as intracellular cholesterol in human macrophages after incubation with patient serum. RESULTS: CLC was not linked to overall plaque presence or burden after adjustments for atherosclerotic cardiovascular disease (ASCVD) score, statin use and low-density lipoprotein cholesterol. However, CLC associated with presence and numbers of any, low-attenuation and obstructive plaques exclusively in biologic disease-modifying antirheumatic drugs (bDMARD) non-users (p for interaction ≤0.018). CLC associated with cardiovascular event risk overall after adjustments for ASCVD and number of segments with plaque (HR=1.76 (95% CI 1.16 to 2.67) per 1 SD increase in CLC, p=0.008). Additionally, bDMARD use modified the impact of CLC on event risk; CLC associated with events in bDMARD non-users (HR=2.52 (95% CI 1.36 to 4.65) per 1SD increase in CLC, p=0.003) but not users. CONCLUSION: CLC was linked to long-term cardiovascular event risk in RA and associated with high-risk low attenuation and obstructive coronary plaque presence and burden in bDMARD non-users. Its prospective validation as a predictive biomarker may be, therefore, warranted.

Efficacy of Yishen Huashi Granules Combined with Linagliptin Tablets on Blood Glucose and Renal Function in Patients with Type 2 Diabetic Nephropathy.

Objective: To probe into the efficacy of Yishen Huashi granules combined with linagliptin tablets in the treatment of type 2 diabetic nephropathy (DN) and its effect on blood glucose and renal function in patients. Methods: 70 patients with type 2 DN at our hospital between May 2020 and May 2022 were chosen as the research objects and separated into the control group and the research group based on their treatments. With 35 cases in each group, the patients treated with initial therapy and linagliptin tablets were enrolled in the control group, and those who received the above treatments and also Yishen Huashi granules were included in the research group. Their clinical indexes such as blood glucose and renal function were compared with both groups after treatment. Results: After treatment, the research group had remarkably lower fasting blood glucose (FPG), 2 h-postprandial blood glucose (2 h-PBG), and glycosylated hemoglobin A1c (HbA1c) levels than those in the control group (P < 0.05). After treatment, the research group had remarkably lower levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) (P < 0.05) and higher high-density lipoprotein (HDL) levels (P < 0.05) than those in the control group. After treatment, the urinary microalbumin (u-mALB) level was remarkably lower in both groups (P < 0.05) and was distinctly lower in the research group than in the control group (P < 0.05). After treatment, the research group had remarkably lower renal function indexes such as serum creatinine (SCr), blood urea nitrogen (BUN), urinary protein (UPro), and urinary albumin excretion rate (UAER) (P < 0.05) and a higher estimated glomerular filtration rate (eGFR) level (P < 0.05) than those in the control group. The efficacy was evaluated by the traditional Chinese medicine (TCM) syndrome score after treatment. There were no patients in complete remission between both the groups, where slight differences were found in the proportion of significant remission (P > 0.05), with the total effective rate of the research group remarkably higher than that of the control group (P < 0.05). Conclusion: The combination of Yishen Huashi granules and linagliptin tablets can reduce the blood glucose and blood lipid levels in patients with type 2 DN and lower UPro and protect renal function at the same time, which provides a new idea and a method for clinical treatment of type 2 DN with integrated traditional Chinese and Western medicine.

Cucumis melo var. momordica as a Potent Antidiabetic, Antioxidant and Possible Anticovid Alternative: Investigation through Experimental and Computational Methods.

Diabetes mellitus is a typical life threatening of disease, which generate due to the dysfunction of ß cells of pancreas. In 2014, WHO stated that 422 million people were infected with DM. The current pattern of management of diabetes included synthetic or plant based oral hypoglycemic drugs and insulin but drug resentence is become a very big issues in antidiabetic therapy. Thus, it's very earnest to discover now medication for this disease. Now the days, it is well acknowledged that diabetic patients are more prone towards covid and related complications. Thus, medical practitioners reformed the methodology of prescribing medication for covid infected antidiabetic therapy and encouraging the medication contains dual pharmacological properties. It is also well know that polyphenols specifically hold a significant role in oxidative stress and reduced the severity of many inflammatory diseases. Cucumis melo has rich history as ethano-pharmacological use in Indian subcontinent. The fruit and seed are well-known for the treatment of various diseases due to the presence of phenolics. Therefore, in this study, the combined mixture of flower and seeds were used for the extraction of polyphenolic rich extract and tested for antidiabetic activity through the antioxidant and in vivo experiments. The antioxidant potential measurement exhibited that the selected plant extract has the significant competence to down-regulate oxidative stress (DPPH scavenging IC50 at 60.7±1.05 µg/mL, ABTS IC50 at 62.15±0.50 µg/mL). Furthermore, the major polyphenolic phyto-compounds derived from the Cucumis melo were used for in silico anticovid activity, docking, and complementarity studies. The anticovid activity prognosis reflected that selected phyto-compounds amentoflavone and vanillic acid have optimal possibility to interact with 3C-like protease and through this moderate anticovid activity can be exhibit. The docking experiments established that the selected compounds have propensity to interact with protein tyrosine phosphatase 1B, 11ß-Hydroxysteroid dehydrogenase, superoxide dismutase, glutathione peroxidase, and catalase ß-glucuronidase receptor. In vivo experiments showed that 500 mg/kg, Cucumis melo extract ominously amplified body weight, plasma insulin, high-density lipoprotein levels, and biochemical markers. Furthermore, extract significantly downregulate the blood glucose, total cholesterol, triglycerides, low-density lipoprotein, and very low-density lipoprotein.

Acute coronary syndrome in an 8-year-old child with familial hypercholesterolemia: a case report.

BACKGROUND: Familial hypercholesterolemia (FH) is the most commonly inherited metabolic disease and has an autosomal dominant mode of inheritance. Patients with FH usually present with high levels of low-density lipoprotein-cholesterol, xanthomas and early coronary artery disease. Children with FH are subject to developing early and enhanced atherosclerosis, leading to an increased risk of coronary events. We report here an 8-year-old patient with acute coronary syndrome (ACS) who was diagnosed with homozygous FH (HoFH) due to mutations in the low-density lipoprotein receptor (LDLR) gene and subsequently treated with percutaneous transluminal coronary angioplasty (PTCA) after filtration plasma. To the best of our knowledge, this patient is the youngest case of HoFH treated with filtration plasma followed by PTCA reported to date. CASE PRESENTATION: An 8-year-old Asian patient was admitted to Gansu Provincial Hospital presenting symptoms of ACS. Laboratory tests showed that the patient's cholesterol and low-density lipid levels were extremely high. An electrocardiogram (ECG) revealed sinus arrhythmia and electric axis deviation to the right, but the ECG was roughly normal. Multiple cardiac function abnormalities were diagnosed on the ECG. Multiple sites of coronary artery stenosis were determined by computed tomography angiography. DNA sequencing of exons showed a C-to-A substitution at nucleotide 126 in exon 2, resulting in a LDLR mutation in the patient and seven other family members. Following combination treatment with lipid-lowering drugs, anti-thrombosis drugs, filtration plasma and PTCA, the patient's symptoms were significantly improved and the patient discharged. CONCLUSION: We report the rare case of a patient with ACS attributable to HoFH who was treated with PTCA following filtration plasma. The patient was shown to have clinically diagnosed and molecularly confirmed HoFH that resulted from a mutation in the LDLR gene. Children with HoFH have higher risk of early coronary events and death from myocardial infarction due to premature atherosclerosis than adults. Earlier intervention and treatment will bring great benefits to the long-term survival of pediatric patients.

The utility of laboratory testing for pediatric patients undergoing isotretinoin treatment.

Isotretinoin, the most effective treatment for severe cystic acne, involves laboratory monitoring. In this retrospective case series of 130 pediatric patients taking isotretinoin, there were significant increases in cholesterol (143.9 mg/dl to 155.3 mg/dl), triglycerides (81.8 mg/dl to 115.2 mg/dl), and low-density lipoprotein (82.0 mg/dl to 98.1 mg/dl), and a decrease in high-density lipoprotein (50.0 mg/dl to 44.7 mg/dl) from baseline to follow-up (p < .05); there were no significant changes in liver enzymes. None of the patients had clinical sequelae (triglyceride-induced pancreatitis, retinoid-induced hepatotoxicity) related to their abnormal lab values. These findings question the utility of laboratory monitoring for prevention of severe clinical sequelae in pediatric patients, and suggest testing based on individualized risk factors may be more appropriate.

Acacia jacquemontii ethyl acetate extract reduces hyperglycemia and pro-inflammatory markers while increasing endogenous antioxidant potential in alloxan-induced diabetic rats.

Acacia jacquemontii possess has numerous traditional therapeutic uses. The rationale of this study was to investigate the role of Acacia jacquemontii ethyl acetate extract (AJEAE) in the downregulation of hyperglycemia. The current study was performed in two parts, in vitro, through characterization (high-performance liquid chromatography), estimation of total phenolic content, total flavonoid content, antioxidant (2,2-diphenyl-1-picrylhydrazylassay), and α-amylase inhibitory activities of the studied extract, and in vivo using Wistar rats in which animals were divided into five groups NC, DC, GL, AJEAE 250 mg/kg, and AJEAE 500 mg/kg. The effects of AJEAE on fasting plasma glucose, plasma insulin, HOMA-IR, oral glucose tolerance test, glycated hemoglobin (HBA1c), lipid profile, inflammatory cytokines (Interleukin-6, tumor necrosis factor-alpha), and oxidative stress markers (lipid peroxidation, nitic oxide, superoxide dismutase, catalase, glutathione peroxidase) were evaluated. Our findings confirmed the presence of quercetin, kaempferol, gallic acid, vanillic acid, syringic acid, M-coumaric acid, sinapic acid, chlorogenic acid, cinnamic acid, and ferulic acid in AJEAE. Total flavonoid and phenolic contents in AJEAE were 83.83 mg GAE/g and 77.06 mg QE/g, respectively. Significant inhibition of DPPH (69.470%/1 mg/ml) and α-amylase (71.8%/1 mg/ml) activities were exhibited by AJEAE. Alloxan-injected rats showed marked hyperglycemia and hypoinsulinemia, and increased inflammatory marker levels as compared to normal control (p < 0.001). Additionally, raised levels of triglyceride (139.7 ± 2.771), total cholesterol (198.7 ± 1.856), very low-density lipoprotein (33.43 ± 0.2728), low-density lipoprotein (155.5 ± 2.754), lipid peroxidation, and nitric oxide (p < 0.001) and decreased levels of high-density lipoprotein (17.20 ± 0.1732), superoxide dismutase, catalase, and glutathione peroxidase were observed in diabetic rats (p < 0.001). AJEAE significantly (p < 0.05) improved the aforementioned parameters and the protective efficacy was comparable to glibenclamide. Histopathological findings also evidenced the anti-hyperglycemic properties of AJEAE through regeneration of pancreatic ß cells. Conclusively, our findings demonstrated the antihyperglycemic, antihyperlipidemic, antioxidant, anti-inflammatory, and pancreatic beta ß cell regenerative properties of AJEAE against alloxan-induced diabetes.

Potential therapeutic effects of green tea on obese lipid profile - a systematic review.

Background: Green tea, obtained from the plant Camellis sinensis, is one of the oldest drinks in the world and contains numerous bioactive compounds. Studies have demonstrated the efficacy of green tea in preventing obesity and cardiovascular diseases that may be related to the reduction of lipid levels. Aim: This study aimed to evidence, through a systematic review, the therapeutic potential of green tea on the lipid profile in preclinical studies in obese animals and clinical studies in obese individuals. Methods: This systematic review follows the recommendations of the preferred report items for systematic reviews and meta-analyses. The electronic databases, PubMed (Medline), Science Direct, Scopus, and Web of Science were consulted. Articles from January 2009 to December 2019 were selected. Results: This search resulted in twenty-nine articles were included cirtically reviewed. In experimental studies, green tea administration has been shown to reduce total cholesterol, triglycerides and low-density lipoprotein cholesterol in animals exposed to obesity-inducing diet. In humans' studies green tea was not shown to be effective for obese lipid control. Because supplementation with green tea extract reduced total cholesterol, triglycerides, low-density lipoprotein for three months at a specific dose. Conclusion: Therefore, green tea appears to act as a protective agent for dyslipidemia in obesity-induced animals. In human studies, green tea has not been shown to be effective in controlling obese lipids.

A Within-Subject Before-After Study of the Impact of Antidepressants on Hemoglobin A1c and Low-Density Lipoprotein Levels in Type 2 Diabetes.

PURPOSE/BACKGROUND: Data on the effect of treatment with antidepressant drugs on metabolic control in diabetes are sparse. In this controlled within-subject before-after study, the impact of initiation and discontinuation of antidepressant treatment on hemoglobin A1c (HbA1c) and low-density lipoprotein (LDL) levels in type 2 diabetes was estimated. METHODS/PROCEDURES: All individuals with newly developed type 2 diabetes (first HbA1c ≥ 6.5%) between 2000 and 2016 in Northern and Central Denmark were identified using register-based health care data. Among these, we identified individuals initiating and discontinuing antidepressant treatment. Using a within-subject before-after design, we examined HbA1c and LDL in the 16 months leading up to and the 16 months after antidepressant treatment initiation or discontinuation, respectively. For comparison, we ran similar time trend analyses in a reference population of age- and sex-matched type 2 diabetes individuals not receiving antidepressant treatment. FINDINGS/RESULTS: Mean HbA1c decreased after initiation of antidepressant treatment (-0.16%; 95% confidence interval [CI], -0.18 to -0.13%). In the reference population, no material change in HbA1c over time (-0.03%; 95% CI, -0.04 to -0.01%) was seen. Mean LDL decreased not only in antidepressant initiators (-0.17 mmol/L; 95% CI, -0.19 to -0.15 mmol/L) but also in the reference population (-0.15 mmol/L; 95% CI, -0.16 to -0.13 mmol/L). Among antidepressant discontinuers, there was also a decrease in HbA1c (-0.32%; 95% CI, -0.37 to -0.28%), with no change in the reference population (-0.02%; 95% CI, -0.04 to 0.00%). Decreases in LDL were found both in antidepressant discontinuers (-0.09 mmol/L; 95% CI, -0.14 to -0.04 mmol/L) and in the reference population (-0.16 mmol/L0; 95% CI, -0.18 to -0.13 mmol/L). IMPLICATIONS/CONCLUSIONS: Antidepressant treatment in type 2 diabetes may have a beneficial effect on glycemic control, as the decrease in HbA1c after discontinuation of antidepressants likely reflects remission of depression. Conversely, antidepressant treatment does not seem to affect LDL levels.

The association between mental health and metabolic outcomes in youth living with perinatally acquired HIV in the Cape Town Adolescent Antiretroviral Cohort.

Youth living with perinatally acquired HIV (YLPHIV) have been found to have a range of mental disorders. Some adult HIV studies have linked mental health to adverse metabolic outcomes due to dysregulation of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis, but this association has not previously been explored in YLPHIV.We investigated the association of mental health measures with metabolic outcomes in YLPHIV and HIV-uninfected youth (HIV-U) and linear regression was used to assess the adjusted associations.Overall, 203 YLPHIV (median age = 10.7years; 52% female; mean duration on ART 8 years, 12% CD4 count <500 cells/µL, 18% viral load >50 copies/mL) and 44 HIV-U (median age = 10.3 years; 55% female) were enrolled. YLPHIV had higher median total cholesterol (4.2 vs 3.9 mmol/L, p = 0.049) and triglyceride (0.9 vs 0.7 mmol/L, p < 0.001) compared to HIV-U. We found higher percentage of poor functional competence (40% vs 25%, p = 0.02) and self-concept (23% vs 9%, p = 0.03) and higher depression (6% vs 2%, p < 0.01), anger (6% vs 2%, p = 0.04) and disruptive behaviour (4% vs 0%, p < 0.01) in YLPHIV as compared to HIV-U. Among YLPHIV, higher scores of anger were associated with higher total cholesterol and higher low-density lipoprotein (ß = 0.010, p = 0.041 and ß = 0.012, p = 0.048 respectively) and disruptive behaviour with higher low-density lipoprotein (ß = 0.010, p = 0.043) after adjusting for age, sex and BMIZ.This is the one of first study to investigate the association of mental health with metabolic outcomes among YLPHIV. The association of increased anger and disruptive behaviour with increased lipid concentration is a novel finding. Further longitudinal studies are needed to evaluate the causal relationships between mental health and metabolic outcomes.

Role of oxidized LDL-induced "trained macrophages" in the pathogenesis of COVID-19 and benefits of pioglitazone: A hypothesis.

BACKGROUND AND AIMS: Older adults and people who have cardiovascular disorders (their common pathogenetic mechanism is progressive atherosclerosis) are at higher risk for severe illness from COVID-19 (coronavirus disease 2019). Their common pathogenetic mechanism is progressive atherosclerosis in which oxLDL (oxidized LDL) plays major role. Receptor-mediated uptake of oxLDL by the monocyte-derived macrophages activates the long-term epigenetic reprogramming of innate immunity, which is termed "trained immunity." The aim of this work is to investigate the mechanisms and treatment possibilities that can control the activities of these specific macrophages. METHODS: Search in Medline and PubMed relevant articles on the trained immunity and cytokine storm of COVID-19. RESULTS AND CONCLUSIONS: When oxLDL-trained macrophages encounter SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in the lung, it causes unregulated cytokine secretion, leading to the alveolar damage. Therefore, blocking macrophage training by pioglitazone, a thiazolidinedione, could control the hyperactivation that the virus would trigger.

High-density lipoprotein or cyclodextrin extraction of cholesterol from aggregated LDL reduces foam cell formation.

Low-density lipoprotein (LDL) deposition, aggregation and retention in the endothelial sub-intima are critical initiating events during atherosclerosis. Macrophages digest aggregated LDL (agLDL) through a process called exophagy. High-density lipoprotein (HDL) plays an atheroprotective role, but studies attempting to exploit it therapeutically have been unsuccessful, highlighting gaps in our current understanding of HDL function. Here, we characterized the role of HDL during exophagy of agLDL. We find that atherosclerotic plaque macrophages contact agLDL and form an extracellular digestive compartment similar to that observed in vitro During macrophage catabolism of agLDL in vitro, levels of free cholesterol in the agLDL are increased. HDL can extract free cholesterol directly from this agLDL and inhibit macrophage foam cell formation. Cholesterol-balanced hydroxypropyl-ß-cyclodextrin similarly reduced macrophage cholesterol uptake and foam cell formation. Finally, we show that HDL can directly extract free cholesterol, but not cholesterol esters, from agLDL in the absence of cells. Together, these results suggest that the actions of HDL can directly extract free cholesterol from agLDL during catabolism, and provide a new context in which to view the complex relationship between HDL and atherosclerosis.

Lipid Lowering Oxopropanylindole Hydrazone Derivatives with Antioxidant and Anti-hyperglycemic Activity.

A series of substituted oxopropanylindole hydrazone derivatives was synthesized and evaluated for anti-oxidant and anti-dyslipidemic activity. Of the 12 tested, 3 compounds (6c, 7b and 7d) showed good anti-oxidant activity, compound 6c attenuated LDL oxidation by 32%. The compounds 6c and 7d also showed good anti-dyslipidemic activity by reducing serum levels of total cholesterol (TC), phospholipids (PL) and triglycerides (TG). These two compounds were further evaluated for antiadipogenic and anti-hyperglycemic activity, where 6c showed 44% reduction in lipid accumulation and 20.5% and 24.3% reduction in blood glucose at 5h and 24h respectively, as compared to standard drug metformin. Thus, compounds 6c and 7d with balanced anti-oxidant and anti-dyslipidimic activities may be excellent candidates for lead optimization and drug development for the treatment of metabolic disorders.