Serum Tg Levels Research Articles

Evaluation of the role of hydroxychloroquine as a lipid profile improving and glucose adjusting drug in Egyptian females with inactive rheumatoid arthritis

Background/aim Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that leads to joint destruction and disability with increased risk of cardiovascular disease (CVD), a leading cause of morbidity and mortality in RA. Modifying CVD risk factors, such as lowering plasma glucose and total cholesterol, may be helpful for preventing CVD. A disease-modifying antirheumatic drugs (DMARD) hydroxychloroquine (HCQ) with a good safety profile and low cost has been reported to improve lipid profiles and glucose level in RA. The study was designed to evaluate the responsibility of HCQ in the improvement of lipid profile and glucose level in Egyptian Inactive Rheumatoid Arthritis (RA) females. Subjects and methods This trial study included fifty adult RA females in remission treated with 400 mg daily of HCQ orally for 6 months. The patients are regular visiting outpatient clinic of rheumatology unit at the department of Rheumatology and Rehabilitation, Mataria Teaching Hospital, National Institute of Neuro-Motor System (NINMS) and Rheumatology clinic at Centre of Medical Excellence of National Research Centre, Cairo, Egypt. Visits and follow-up are monthly to ensure adherence to treatment. All the patients have been evaluated at the start of the trial, after 3 and 6 months. Lipid profile, fasting blood sugar (FBS), anthropometric parameters and systolic and diastolic blood pressure were assessed. Results After 3 months of treatment, most of the metabolic characteristics were improved significantly. FBS level was significantly lowered (P<0.001), and lipid profiles were significantly improved as total cholesterol (P<0.001), HDL-cholesterol (P<0.001), LDL-cholesterol (P<0.001) and artherogenic index (TC/HDL-cholesterol (P<0.001) and LDL-C/HDL-cholesterol(P<0.001). The triglyceride level and the anthropometric variables were significant statistically as (P<0.001). Moreover after 6 months, all metabolic parameters were statistically improved as FBS (P<0.001), TC (P<0.001), TG (P<0.001), HDL-Cholesterol, LDL-cholesterol and artherogenic index (P<0.0001). Moreover, the best improvement was at 6 months of treatment. Conclusion HCQ significantly improved the blood glucose level in patients with inactive RA, in addition to the serum levels of TC, TG, HDL-Cholesterol, LDL-Cholesterol and arthrogenic index. Moreover, lessen the use of anti-lipids and diabetic medications.

Lipid Profile in Chronic Renal Failure Patients on Haemodialysis

Objective: This study aims to evaluate the levels of lipid profile parameters in Chronic Renal Failure patients on Maintenance hemodialysis and to compare its level with age matched healthy control population. Method: Cross sectional study involving 262 Individuals between the age 46 -75 years in the population of Bengaluru, India between February 2022 to May 2023. Venous blood was collected from 131 CRF patients on MHD and from 131 healthy individuals and analyzed for lipid profile parameters TC, TG, VLDL,LDL,HDL.and urea,creatinine. Results: In MHD patients, serum TG and VLDL levels were found to be significantly elevated compared to healthy control population. HDL was significantly reduced compared to control healthy population. There was no significant change in the levels of TC and LDL. Conclusion: Frequent monitoring of these lipid profile parameters may help in better treatment, hence itmay reduce the morbidity and mortality of Patients on MHD.

Tiaogan Jiejiu Tongluo Formula attenuated alcohol-induced chronic liver injury by regulating lipid metabolism in rats

Ethnopharmacological relevanceTiaogan Jiejiu Tongluo Formula (TJTF), a traditional Chinese medicine formula, is modified from the well-known ancient prescription Danzhi-Xiaoyao Powder (DXP). Owing to its ability to regulate liver, strengthen spleen, detoxicating, and dredge collaterals in Chinese medicine, TJTF is usually used to treat anxiety, hypertension, alcoholic fatty liver disease in clinical application. However, the protective effect and potential molecular mechanism of TJTF on alcoholic liver injury has not fully been clarified. Aim of the studyTo explore the effect of TJTF on chronic alcoholic liver injury and figure out whether its effects were due to the regulation of lipid metabolism. Material and methods75 male SD rats were divided into the following five groups, control group, EtOH group, TJTF high dose group, TJTF low dose group and silybin group. Then a chronic alcoholic liver injury model was established by increasing concentration of 56% ethanol in rats. The rats in each TJTF group were given the corresponding dose of TJTF, the rats in the silybin group were given silybin, the rats in the control group and the EtOH group were given distilled water by gavage, once a day for 8 consecutive weeks. The components of TJTF were analyzed by UPLC-Q-TOF-MS. Hematoxylin and Eosin (H&E) was used to assess the severity of liver injury. in the pathological examination. Periodic acid-Schiff (PAS) and oil red O staining were used to evaluate the degree of the liver glycogen accumulation and lipid deposition, respectively. The serum ALT, AST, T-CHO, TG, LDL-C, ADH, HDL-C, and ALDH levels as well as liver tissue GSH, MDA, and SOD levels were analyzed in rats. Immunohistochemistry and western blotting were used to detect lipid metabolism-related proteins expressed in rat liver. ResultsTJTF significantly alleviated the chronic liver injury caused by alcohol in rats, and enhanced liver function. TJTF significantly decreased AST, ALT, ADH levels and increased ALDH level of serum, and increased GSH, SOD levels and decreased MDA level of liver tissue. In addition, TJTF significantly decreased the serum T-CHO, TG and LDL-C levels and increased HDL-C level in chronic alcoholic liver injury rats by regulating the expression of lipid metabolism associated proteins including p-LKB1, p-AMPKα, p-ACC, FAS, HMGCR, SREBP-1c, PPARα and CPT-1A. The results of western blot and immunohistochemical staining confirmed that TJTF can inhibit lipid production and promote fatty acid oxidation in the liver tissue of chronic alcoholic liver injury rats by activating the LKB1-AMPKα axis and then downregulating the protein expressions of p-ACC, FAS, HMGCR and SREBP-1c, as well as promoting the protein expressions of PPARα and CPT-1A. Meanwhile, TJTF also increased the glycogen content of liver and alleviated the liver damage. ConclusionAccording to current research, TJTF is effective in treating chronic liver damage induced by alcohol in rats. Additionally, TJTF exhibits the protective benefits by modulating LKB1-AMPKα signal axis, which in turn inhibits the synthesis of lipids and promotes the oxidation of fatty acids.

75-OR: Cold-Responsive Proteolytic Rewiring of Mitochondria Safeguards White Fat Thermogenic Remodeling

Mitochondrial proteases are emerging as key regulators of mitochondrial plasticity acting both as protein quality surveillance and regulatory enzymes. It remains unclear, however, whether the regulated mitochondrial proteolysis is mechanistically linked to cell identity switch such as white-to-beige conversion of adipocytes. Here we report that cold-responsive mitochondrial proteolysis is a prerequisite for conversion from white-to-beige adipocytes during white adipose tissue (WAT) browning. MitoTimer reporter and chemical thiol probe analysis reveal that thermogenic stimulation selectively promotes mitochondrial proteostasis in WAT via mitochondrial protease LONP1 both in vivo and in vitro. Disruption of LONP1-dependent proteolysis substantially impairs cold or b3-AR agonist induced adipocyte identity programming, evidenced by the remarkably attenuated formation of UCP1+ multilocular adipocytes in IWAT from Lonp1 f/f/Adipoq-Cre (LONP1 AKO) mice. LONP1 AKO mice exposed to cold had lower body temperature, elevated serum TG and FFA levels. Chow-fed LONP1 AKO mice also developed glucose intolerance. “AdipoChaser” system “pulse-chase” lineage tracing experiments confirm that LONP1 ablation markedly blocks the direct cell fate programming of pre-existing mature adipocytes. Importantly, augmented LONP1 expression corrects aging-related impairments in white-to-beige adipocytes conversion. 10-month-old adipocyte-specific Lonp1 overexpression mice had significantly lower body weight and fat mass as a result of elevated energy expenditure. Thus, the identification of LONP1 as a critical safeguard of WAT beiging holds promise for translational applications in enhancing white-to-beige adipocytes conversion capacity relevant to a variety of metabolic disease states and during aging. Disclosure T.Fu: None. W.Sun: None. Z.Zhou: None. Z.Xu: None. M.Yan: None. L.Yang: None. Y.Yin: None. Z.Gan: None.

1551-P: Association between Short-Term Postprandial C-Peptide Index Recovery during Hospitalization and Future Glycemic Control in Patients with Type 2 Diabetes

Endogenous insulin secretion could be recovered by improving hyperglycemia in patients with type 2 diabetes (T2D). However, no reports have showed the associations between short-term insulin secretion recovery and future glycemic control. In this study, we investigated whether short-term C-peptide index (CPI) recovery during hospitalization could predict future glycemic control. In this study, 117 patients with T2D were included. The recovery of fasting and postprandial CPI were defined as (fasting CPI at discharge - fasting CPI at admission [index-A]) and (postprandial CPI at discharge - postprandial CPI at admission [index-B]). We compared the clinical background between the low-recovery and high-recovery groups of each index and assessed the association between the indices and metabolic parameters after discharge. Using index-A, age was significantly younger (P = 0.017) and body mass index (BMI) was significantly higher (P = 0.004) in the high-recovery group than that in low-recovery group. Using index-B, the age was significantly younger (P = 0.019) and BMI was significantly higher (P = 0.004) in the high-recovery group. Additionally, visceral fat area (P = 0.043), serum TG (P < 0.001), and γ-GTP levels (P = 0.009) were significantly higher in the high-recovery group. Regarding the association between CPI recovery and future glycemic control, GA levels were significantly lower in the high-recovery group than that in low-recovery group at 6 months (16.7 vs 21.1%, P = 0.045) and 12 months (16.8 vs 21.7%, P = 0.033) after discharge in the analysis using index-B. Furthermore, postprandial CPI (cut-off; 3.79 [AUC 0.698, P = 0.007]) at discharge and index-B (cut-off; 1.66 [AUC 0.657, P = 0.018]) were identified as indicators to predict HbA1c ≤ 7.0% at 6 months after discharge. In conclusion, short-term postprandial CPI recovery during hospitalization may predict future glycemic control. Disclosure A.Enkaku: None. D.Chujo: None. M.Kamigishi: None. S.Inagawa: None. W.Sakai: None. S.Matsukoshi: None. A.Takikawa: None. S.Fujisaka: None. K.Tobe: Other Relationship; MSD K.K., Novo Nordisk Pharma Ltd., Takeda Pharmaceutical Company Limited, Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, Suntory Global Corporation, Ltd.,, Taiho Pharmaceutical Co. Ltd., Japan Diabetes Foundation, Japan Association for Diabetes Education and Care.

Is transoral endoscopic thyroidectomy safe for total thyroidectomy compared to open thyroidectomy? A propensity-score matched cohort study with papillary thyroid carcinoma.

Transoral endoscopic thyroidectomy via vestibular approach (TOETVA) has become increasingly popular in the treatment of papillary thyroid cancer (PTC). This study aimed to describe the safety and feasibility of total thyroidectomy between the TOETVA and open thyroidectomy (OT) approaches for the treatment of patients with PTC. We retrospectively reviewed 780 consecutive patients suffering from PTC that had undergone total thyroidectomy using TOETVA (n = 107) and OT (n = 673) between April 2016 and December 2021 at our institute. Afterward, a total of 101 matched patients' surgical outcomes were compared using propensity score matching (PSM) analysis. Before PSM, the patients in the TOETVA group were younger (p < 0.001), had a lower body mass index (p < 0.001) and a greater female population (p < 0.001). After PSM, the TOETVA group was associated with significantly longer operative time (p < 0.001), greater blood loss (p < 0.001), total drainage amount (p < 0.001), higher C-reaction protein level (p < 0.001), better cosmetic satisfaction (p < 0.001) and quality of life (p < 0.001) and lower scar self-consciousness (p < 0.001). There was no statistical difference between the groups in the rate of parathyroid autotransplantation and bilateral lymph node dissection, the positivity of lymph node metastasis, number of dissected lymph nodes and positive lymph nodes, multifocality, postoperative level of blood calcium and parathyroid hormone (PTH), rate of PTH < 15 ng/mL, visual analog scale score, duration of hospital stay, complications, mean thyroid stimulating hormone (TSH)-stimulated Tg level before radioactive iodine, mean Tg level without TSH stimulation, and the proportion of serum Tg level of <1. TOETVA is a safe and feasible technique for better cosmetic effects and similar surgical outcomes compared to conventional open surgery for the studied patients that required total thyroidectomy.

Clinical value of 125I radioactive seed implantation in the treatment of lymph node metastasis of 131I refractory differentiated thyroid cancer

PurposeTo evaluate the clinical value of 1251 seed implantation in the treatment of lymph node metastasis of 111 cases of refractory differentiated thyroid cancer (RAIR-DTC). Methods and materialsFrom January 2015 to June 2016, 42 patients with RAIR-DTC with lymph node metastasis (14 males and 28 females, median age 49 years) were analyzed retrospectively. After CT-guided 1251 seed implantation, CT was reexamined 2,4,6 months after operation, and the changes of metastatic lymph node size, serum thyroglobulin (Tg) level and complications were compared before or after treatment. Paired-Samples T Test, Methods repetitive measure analysis of variance, Spearman correlation coefficient analysis were used to analyze the data. ResultsAmong the 42 patients, 2 had complete remission (4.76%), 9 had partial remission (21.43%), 29 had no change (69.05%), and 2 had disease progression (4.76%), with an overall effective rate of 95.24% (40/42). The diameter of lymph node metastasis was (1.39 ± 0.75) cm after treatment and (1.99 ± 0.38) cm before treatment; the diameter of lymph node metastasis was significantly reduced after treatment compared with that before metastasis (t = 5.557, P< 0.01); the serum Tg at 2, 4 and 6 months after treatment were (53.34 ± 14.05) ug/L, (33.17 + 7.61)ug/L and (25.93 ± 10.91)ug/L, respectively, compared with (57.72 ± 15.23)ug/L before treatment, and the differences between serum Tg after treatment and before treatment were all statistically significant (F = 23.612,P<0.05). Except for the diameter of lymph node metastasis (χ2 = 4.524, P<0.05), the patients' age, gender, metastasis site and the number of implanted particles per lesion were not influential factors in the efficacy (χ2 = 0.569–15.884, rs = 0.277, all P>0.05). Conclusion125I RSIT can significantly alleviate the clinical symptoms of RAIR-DTC patients with LNM, and the LNM lesions size has relevance for the treatment effect. The clinical follow-up time of serum Tg level can be extended to 6 months or even longer.

Thyroglobulin measurement in the needle washout for diagnosis of lymph node metastases of differentiated thyroid cancer

Introduction. Measurement of thyroglobulin (Tg) in a washout after fine-needle aspiration (FNA) is recommended for the diagnosis of metastases of differentiated thyroid cancer (DTC), but the method is not standardized and there is no recommended threshold value of Tg washout, which makes it difficult to interpret the results.Aim. To analyze Tg in the washout after FNA of lesions of different origin on the neck and to determine its optimal cutoff for the diagnosis of DTC metastases.Materials and methods. Ultrasound-guided FNA was performed in 1258 neck masses from 591 patients, 566 of them with confirmed DTC. In 1023 lesions, FNA was performed after thyroidectomy, 22 – after lobectomy, 213 – with preserved thyroid gland. The needle after FNA was washed in 1 ml of saline, in which the concentration of Tg was then examined. The level of Tg in the washout was compared with the histological (n = 522) or cytological diagnosis if no surgery was performed. The cut-off for Tg washout was determined by ROC analysis.Results. DTC lymph node metastases detected in 577 specimens. Nine specimens were obtained from metastases of thyroid cancer (TC) that does not express Tg (anaplastic TC, poorly differentiated TC, columnar-cell variant DTC), 22 – from neck metastases of other malignancy (lung cancer, mucinous soft tissues tumor, ovarian cancer, esophageal cancer, melanoma, neuroendocrine tumor), 6 – from other tumors of the neck (lymphoma, parathyroid adenoma, neurinoma). In 26 cases, the specimen was regarded as normal thyroid tissue left after thyroidectomy, 37 – postoperative seroma or granuloma, 1 – cyst of the neck, 578 – lymph node hyperplasia, 2 – sarcoidosis. The level of Tg washout from DTC metastasis and thyroid remnant significantly differed from that of non-thyroidal origin (p &lt;0.0001). At the cut-off of 7.8 ng/ml, the sensitivity and specificity of Tg washout in the diagnosis of DTC metastases is 94 and 95 %, and at the cut-off of 20 ng/ml, 90 and 98 %, respectively. False-negative results were obtained from DTC with squamous metaplasia or sparse tumor cells in a specimen. False-positive results were obtained more often from lesions of level VI and IV compared with other localizations (8 % versus 4 %; p = 0.04). There were no differences in false positive rate in patients before and after thyroidectomy (p = 0.17), but in patients after thyroidectomy with a serum Tg &gt;200 ng/ml, the false positive rate of Tg washout was significantly higher than that with a lower level of serum Tg (28 % versus 3 %; p = 0.0004). When comparing diagnostic performance of cytology and Tg washout, the advantage of the latter is in the diagnosis of cystic metastases, and the former is in the diagnosis of micrometastases and tumors that do not express Tg. Thyroglobulin in the washout increased the sensitivity of the cytology by 8 %. The combined use of these methods detected DTC metastases in 100 % of patients.Conclusion. Measurement of Tg in the washout is a useful addition to the cytology, increasing the diagnostic performance of the latter, mainly due to better detection of cystic metastases of DTC. The optimal suggested cut-off for Tg washout is 20 ng/mL, at which there are fewer false positives.

EVALUATION OF LIPID PROFILE AND LIVER FUNCTION PARAMETERS IN OBESE AND NON-OBESE HYPERTENSIVE INDIVIDUALS ATTENDED TERTIARY CARE TEACHING HOSPITAL

Objective: In this study, lipid profile parameters and liver function parameters were measured and correlated in hypertensive obese and non-obese patients who were attended a tertiary care teaching hospital.&#x0D; Methods: This study is a retrospective observational, cross-sectional study over the course of a year in a tertiary care hospital. All adult patients with hypertension, both obese and non-obese, are included in the study population. The study involved 150 participants in total, including obese and non-obese people (71 men and 79 women). Standard techniques were used to assess the serum levels of TG, TC, LDL, HDL, and liver enzymes such SGOT, SGPT, bilirubin, and ALP. Moreover, BMI was calculated for both study groups. The association between elevated lipid profile markers and liver enzyme abnormalities was assessed by correlation analysis.&#x0D; Results: Out of 150 samples size comprises 75 obese and 75 non-obese individuals, 71 males and 79 females were reported in the current study. Our study gives very good association between lipid profiles to almost all LFT and the highest is shown between HDL, LDL and VLDL to all LFT. There was a high significant difference was noticed between the obese and non-obese individuals in relation to bilirubin (D) concentration, SGOT and SGPT between the two groups P&lt;0.0001. The levels of albumin were lowered and the significant variations were noticed between the two groups. The mean values of cholesterol, LDL and triglycerides were very high in obese individuals than non-obese individuals and the HDL was lower in obese individuals.&#x0D; Conclusion: The study found that liver function variables and abnormal lipid profiles were highly prevalent in obese hypertension patients. In participants with dyslipidemia, increased liver enzymes were seen more frequently.

Long-term results of radiofrequency ablation for locally recurrent papillary thyroid carcinoma

Objective To evaluate the long-term efficacy and safety of ultrasound-guided radiofrequency ablation (RFA) for treating locally recurrent papillary thyroid cancer (PTC). Methods This retrospective study involved 32 patients with pathologically confirmed locally recurrent PTC. The ablation zone was assessed by contrast-enhanced ultrasound (CEUS) after RFA. At baseline, 6 and 12 months and every 6 months or 12 months thereafter, the following results were recorded: recurrence rate, largest diameter, volume, volume reduction rate (VRR) of recurrent lesions, serum thyroglobulin (Tg) level and complications. Results 58 recurrent lesions in 32 patients were successfully ablated with RFA. The mean follow-up time was 73.19 ± 12.68 months (range, 60 to 98 months). At the last follow-up, almost all ablated lesions disappeared completely, and only one lesion showed scar-like changes. Nine (28.13%) patients developed new locally recurrent tumors; they were successfully treated with repeat RFA sessions. No new recurrent lesions were found during the follow-up. The largest diameter and volume of recurrent lesions decreased from 13.71 ± 6.48 mm and 520.43 ± 627.85 mm3 to 0 each at the end of observation period (p < .001). The average VRRs at 6, 12, 24, 36, 48, 60 months and last follow-up after RFA were 54.17%, 72.90%, 82.28%, 89.30%, 92.57%, 96.60%, 96.88%, 98.14% and 100% respectively. The median of serum Tg level was decreased from 1.48 ng/mL to 0.00 ng/mL (p < .05). No complications were reported during the follow-up. Conclusions US-guided RFA is an effective and safe option for treating locally recurrent PTC in selected patients, with favorable long-term outcomes.

Effects of flaxseed powder in improving non-alcoholic fatty liver by regulating gut microbiota-bile acids metabolic pathway through FXR/TGR5 mediating

Non-alcoholic fatty liver disease (NAFLD) is gradually becoming one of the most common and health-endangering diseases. Flaxseed powder (FLA) is rich in α-linolenic acid, dietary fiber, lignans, and other active ingredients, which have lipid-lowering and anti-inflammatory effects. Here, we investigated whether the FLA improves host metabolism by gut bacteria modulation and further bile acid modulation in mice fed a high-fat diet. At the end of the experiment, we found that FLA can significantly reduce the body weight, body fat content, and serum TG, LDL-C, and TNF-α levels of mice, and improve liver steatosis. FLA intervention has a significant effect on preventing and regulating the gut flora disturbance caused by HFD. FLA intervention affects bile acid metabolism in the intestine and causes significant changes in functional bile acids, which can play a lipid-lowering and anti-inflammatory role by activating the intestinal Fxr- Fgfr4-Cyp7a1 and Tgr5-Tlr4-Tnfα pathways.

Remnant cholesterol, stronger than triglycerides, is associated with incident non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is characterized by excess accumulation of triglycerides within the liver. However, whether the circulating levels of triglycerides and cholesterol transported in triglyceride-rich lipoproteins (remnant cholesterol, remnant-C) are related to the occurrence of NAFLD has not yet been studied. This study aims to assess the association of triglycerides and remnant-C with NAFLD in a Chinese cohort of middle aged and elderly individuals. All subjects in the current study are from the 13,876 individuals who recruited in the Shandong cohort of the REACTION study. We included 6,634 participants who had more than one visit during the study period with an average follow-up time of 43.34 months. The association between lipid concentrations and incident NAFLD were evaluated by unadjusted and adjusted Cox proportional hazard models. The potential confounders were adjusted in the models including age, sex, hip circumference (HC), body mass index (BMI), systolic blood pressure, diastolic blood pressure, fasting plasma glucose (FPG), diabetes status and cardiovascular disease (CVD) status. In multivariable-adjusted Cox proportional hazard model analyses, triglycerides (hazard ratio[HR], 95% confidence interval [CI]:1.080,1.047-1.113;p<0.001), high-density lipoprotein cholesterol (HDL-C) (HR, 95% CI: 0.571,0.487-0.670; p<0.001), and remnant-C (HR, 95% CI: 1.143,1.052-1.242; p=0.002), but not total cholesterol (TC) or low-density lipoprotein cholesterol (LDL-C), were associated with incident NAFLD. Atherogenic dyslipidemia (triglycerides>1.69 mmol/L, HDL-C<1.03 mmol/L in men or<1.29 mmol/L in women) was also associated with NAFLD (HR, 95% CI: 1.343,1.177-1.533; p<0.001). Remnant-C levels were higher in females than in males and increased with increasing BMI and in participants with diabetes and CVD compared with those without diabetes or CVD. After adjusting for other factors in the Cox regression models, we found that serum levels of TG and remnant-C, but not TC or LDL-C, were associated with NAFLD outcomes in women group, non-cardiovascular disease status, non-diabetes status and middle BMI categories (24 to 28 kg/m2). In the middle aged and elderly subset of the Chinese population, especially those who were women, non-CVD status, non-diabetes status and middle BMI status (24 to 28 kg/m2), levels of triglycerides and remnant-C, but not TC or LDL-C, were associated with NAFLD outcomes independent of other risk factors.

Anti-Fibrotic Efficacy of Apigenin in a Mice Model of Carbon Tetrachloride-Induced Hepatic Fibrosis by Modulation of Oxidative Stress, Inflammation, and Fibrogenesis: A Preclinical Study.

Hepatic fibrosis is a major health problem all over the world, and there is no effective treatment to cure it. Hence, the current study sought to assess the anti-fibrotic efficacy of apigenin against CCl4-induced hepatic fibrosis in mice. Forty-eight mice were put into six groups. G1: Normal Control, G2: CCl4 Control, G3: Silymarin (100 mg/kg), G4 and G5: Apigenin (2 &20 mg/Kg), G6: Apigenin alone (20 mg/Kg). Groups 2, 3, 4, and 5 were given CCl4 (0.5 mL/kg. i.p.) twice/week for six weeks. The level of AST, ALT, TC, TG, and TB in serum and IL-1β, IL-6, and TNF-α in tissue homogenates were assessed. Histological studies by H&E staining and Immunostaining of liver tissues were also performed. The CCl4-challenged group showed increased serum AST (4-fold), ALT (6-fold), and TB (5-fold). Both silymarin and apigenin treatments significantly improved these hepatic biomarkers. The CCl4-challenged group showed reduced levels of CAT (89%), GSH (53%), and increased MDA (3-fold). Both silymarin and apigenin treatments significantly altered these oxidative markers in tissue homogenates. The CCl4-treated group showed a two-fold increase in IL-1β, IL-6, and TNF-α levels. Silymarin and apigenin treatment considerably decreased the IL-1β, IL-6, and TNF-α levels. Apigenin treatment inhibited angiogenic activity, as evidenced by a decrease in VEGF (vascular endothelial growth factor) expression in liver tissues, and a decline in vascular endothelial cell antigen expression (CD34). Finally, these data collectively imply that apigenin may have antifibrotic properties, which may be explained by its anti-inflammatory, antioxidant, and antiangiogenic activities.

Novel Selective PPARα Modulator Pemafibrate for Dyslipidemia, Nonalcoholic Fatty Liver Disease (NAFLD), and Atherosclerosis.

Statins, the intestinal cholesterol transporter inhibitor (ezetimibe), and PCSK9 inhibitors can reduce serum LDL-C levels, leading to a significant reduction in cardiovascular events. However, these events cannot be fully prevented even when maintaining very low LDL-C levels. Hypertriglyceridemia and reduced HDL-C are known as residual risk factors for ASCVD. Hypertriglyceridemia and/or low HDL-C can be treated with fibrates, nicotinic acids, and n-3 polyunsaturated fatty acids. Fibrates were demonstrated to be PPARα agonists and can markedly lower serum TG levels, yet were reported to cause some adverse effects, including an increase in the liver enzyme and creatinine levels. Recent megatrials of fibrates have shown negative findings on the prevention of ASCVD, which were supposed to be due to their low selectivity and potency for binding to PPAR α. To overcome the off-target effects of fibrates, the concept of a selective PPARα modulator (SPPARMα) was proposed. Kowa Company, Ltd. (Tokyo, Japan), has developed pemafibrate (K-877). Compared with fenofibrate, pemafibrate showed more favorable effects on the reduction of TG and an increase in HDL-C. Fibrates worsened liver and kidney function test values, although pemafibrate showed a favorable effect on liver function test values and little effect on serum creatinine levels and eGFR. Minimal drug-drug interactions of pemafibrate with statins were observed. While most of the fibrates are mainly excreted from the kidney, pemafibrate is metabolized in the liver and excreted into the bile. It can be used safely even in patients with CKD, without a significant increase in blood concentration. In the megatrial of pemafibrate, PROMINENT, for dyslipidemic patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia, and low HDL-C and LDL-C levels, the incidence of cardiovascular events did not decrease among those receiving pemafibrate compared to those receiving the placebo; however, the incidence of nonalcoholic fatty liver disease was lower. Pemafibrate may be superior to conventional fibrates and applicable to CKD patients. This current review summarizes the recent findings on pemafibrate.

Triphenyltin (TPT) exposure causes SD rat liver injury via lipid metabolism disorder and ER stress revealed by transcriptome analysis

BackgroundTPT is an environmental endocrine disruptor that can interfere with endocrine function. However, whether TPT can cause damage to liver structure and function and abnormal lipid metabolism and whether it can cause ER stress is still unclear. ObjectiveTo explore the effect of TPT on liver structure, function and lipid metabolism and whether ER stress occurs. MethodsMale SD rats were divided into 4 groups: control group (Ctrl group, TPT-L group (0.5 mg/kg/d), TPT-M group (1 mg/kg/d), and TPT-H group (2 mg/kg/d). After 10 days of continuous gavage, HE staining was used to observe the morphological structure of liver tissue, serum biochemical indicators were detected, gene expression and functional enrichment analysis were performed by RNA-seq, Western Blot was used to detect the protein expression level of liver tissue, and qRT-PCR was used to detect the gene expression. ResultsAfter TPT exposure, the liver structure damaged; serum TBIL, AST and m-AST levels were significantly increased in the TPT-M group, and serum TG levels were significantly decreased in the TPT-H group. TCHO and TG in liver tissues were significantly increased; transcriptomic analysis detected 105 differential genes. Enrichment analysis showed that TPT exposure mainly affected fatty acid metabolism and drug metabolism in liver tissue, and also affected the redox process of liver tissue; the protein expression levels of PPARα, PPARγ, AMPK, RXRα, IRE1α and PERK were significantly increased after TPT exposure; the expression levels of lipid metabolism-related genes Acsl1, Elovl5, Hmgcr, Hmgcs1 and Srebf1 were significantly increased in the TPT-L group, while in the TPT-M and TPT-H groups had no significant change. ConclusionsTPT exposure can cause liver injury, lipid metabolism disorder and ER stress.

Effect of Vitamin E on Apoptosis of the Endothelial Cells of the Carotid Arteries in Hypercholesterolemic Male Rabbits.

Cardiovascular disease is the principal cause of mortality and morbidity in developed countries, leading to the formation of atherosclerosis plaques and thrombosis. Apoptosis of endothelial cells is one of the primary factors in vascular thrombosis. Lipids, when oxidized by endothelial cells, result in an increased thickness of the arterial wall. Iron is also recognized as an atherogenic element that induces atherosclerosis. There remains uncertainty about the antioxidative role of vitamin E in the formation of atherosclerosis. In this study, the authors evaluated the effect of iron and vitamin E on the apoptosis of endothelial cells in the carotid arteries of hypercholesterolemic male rabbits. Thirty white male rabbits were randomly divided into five groups and fed the following diet for six weeks: Group 1: control, Group 2: cholesterol (1%), Group 3: cholesterol (1%) + vitamin E (50 mg/kg), Group 4: cholesterol (1%) + Iron (50 mg/kg), and Group 5: cholesterol (1%) + vitamin E (50 mg/kg) + Iron (50 mg/kg). Serum cholesterol, TG, HDL, and LDL levels were assessed after six weeks. Finally, the animals were sacrificed with ketamine, and carotid arteries were removed. The samples were fixed in 10% formalin, and TUNEL staining was used after the tissue processing. Cell counts were carried out under a light microscope. Vitamin E decreased Serum cholesterol and apoptotic endothelial cells in the hypercholesterolemic + vitamin E diet (P< 0.05). However, they increased significantly in the interference groups compared to the control group (P< 0.05). According to our findings, vitamin E showed to have a beneficial effect on preventing cardiovascular diseases and may play a positive role in the prevention of atherosclerosis.

Abstract #1397146: Recurrent Thyrotoxicosis in a Woman with a History of Graves - Basedow Disease

Although the most common cause of thyrotoxicosis is Graves - Basedow disease (GBD), the determination of the cause of thyrotoxicosis is important for establishing appropriate management. We present the case of a woman with suspected surreptitious ingestion of thyroid hormones or factitious thyrotoxicosis. A 42-year-old female patient she was diagnosed with hyperthyroidism due to GBD at the age of 14. At age 17 she received RAI (10 mCi), developed hypothyroidism and started levothyroxine (L-T4). At age 38 she presented again with hyperthyroidism: TSH: < 0.004 uIU/mL (VN: 0.4-4) and FT4: 3.19 ng/dl (0.8-1.9). She was suspended L-T4 and started antithyroid drugs (thiamazole). Due to persistence of hyperthyroidism despite 40 mg/d of thiamazole. She was hospitalized for study; thyroid ultrasound showed an atrophic thyroid and thyroid scintigraphy with technetium-99m reported absence of uptake in the thyroid bed, Ab-TPO and Ab-Tg were negative, Thyroglobulin: <0.2 ng/ml (1.6-59.9). After discontinuation of thiamazole and without any other medication, thyroid hormones (FT4 and FT3) normalized within two weeks, factitious thyrotoxicosis was suspected, and she was discharged without medication. At 42 years of age, she returned due to hyperthyroidism with TSH: 0.004uIU/mL, FT4: 2.59 ng/dl, and FT3: 5.05 pg/ml despite having restarted thiamazole in her place of origin; she denied taking thyroid hormone or nutritional supplements. On examination: HR: 105 bpm, mild distal tremor and non-palpable thyroid. The results of the thyroid, thyroid scintigraphy, Ab-TPO, Ab-Tg and levels of Thyroglobulin were similar to the previous ones. Transvaginal ultrasonography and a whole-body scan with RAI ruled out ectopic hyperthyroidism; the FT3/FT4 ratio was always less than 4.4, suggesting factitious thyrotoxicosis. Antithyroid and beta-blockers were suspended, control at 48 hours showed: FT4: 1.77ng/dl (0.8-1.9), FT3: 3.4pg/ml (1.8-4.2) and 25 days post-discharge: TSH: 7.72 ng/dl, FT4: 1.48 ng/dl and FT3: 2.09 pg/ml. The psychiatric evaluation did not show any alteration. The patient was asymptomatic and returned to her place of origin. Cholestyramine was not accepted by the patient. Factitious thyrotoxicosis is difficult to identify, especially when dealing with a patient with a history of GBD. The diagnosis of factitious thyrotoxicosis is based upon the absence of goiter, suppressed serum Tg level, decreased radioactive iodine (RAI) uptake, and excellent response after cholestyramine treatment in cases in which this entity is suspected.

Effects of Fermented Artemisia annua L. and Salicornia herbacea L. on Inhibition of Obesity In Vitro and In Mice

Plant extracts including secondary metabolites have anti-inflammatory and anti-obesity activities. This study was conducted to investigate the anti-obesity properties of fermented Artemisia annua (AW) and Salicornia herbacea (GW) in vitro and in mice. The metabolite profiling of AW and GW extracts was performed using UHPLC−LTQ−Orbitrap–MS/MS, and gene expression was analyzed using real-time PCR for adipocyte difference factors. The anti-obesity effects in mice were measured using serum AST, ALT, glucose, TG, and cholesterol levels. Metabolites of the plant extracts after fermentation showed distinct differences with increasing anti-obesity active substances. The efficacy of inhibitory differentiation adipogenesis of 3T3-L1 adipocytes was better for GW than AW in a concentration-dependent manner. RT-PCR showed that the GW extract significantly reduced the expression of genes involved in adipocyte differentiation and fat accumulation (C/EBPα, PPARγ, and Fas). In C57BL/6 mice fed the HFD, the group supplemented with AW and GW showed reduced liver weight, NAS value, and fatty liver by suppressing liver fat accumulation. The GW group significantly reduced ALT, blood glucose, TG, total cholesterol, and LDL-cholesterol. This study displayed significant metabolite changes through biotransformation in vitro and the increasing anti-obesity effects of GW and AW in mice. GW may be applicable as functional additives for the prevention and treatment of obesity.

Cordycepin reprogramming lipid metabolism to block metastasis and EMT via ERO1A/mTOR/SREBP1 axis in cholangiocarcinoma

Cholangiocarcinoma (CCA) with a high malignancy is usually diagnosed as advanced and is prone to metastasis and leads to a poor prognosis. It is reported that cordycepin has anti-tumor effect. However, the molecular targets and mechanisms of cordycepin in inhibiting CCA metastasis remains unclear. In order to evaluate the therapeutic effect of cordycepin on CCA metastasis, experiments were conducted in vivo and in vitro. The results showed that cordycepin inhibited the migration and EMT progression of HuCCT1 and QBC939 cells. Cordycepin has a strong hypolipidemic effects, therefore, we examined its effect on lipid metabolism in CCA. Cordycepin inhibits SREBP1 mediated fatty acid synthesis through the AKT/mTOR signaling pathway. Meanwhile, cordycepin can reduce ERO1A expression in HuCCT1 and QBC939 cells. ERO1A plays a role in malignant tumors. ERO1A promotes migration and lipid metabolism of CCA cells through AKT/mTOR signaling pathway. In addition, cordycepin significantly inhibited the tumor metastasis and the serum levels of TG and T-CHO in mice. Taken together, we demonstrate that cordycepin mediated ERO1A/mTOR/SREBP1 axis inhibits lipid metabolism and metastasis in CCA cells in vitro and in vivo. These data suggest that cordycepin can be used as a novel drug for the clinical treatment of CCA and to improve the prognosis.

High levels of interleukin-6 and triglycerides and low levels of soluble leptin receptors as risk factors for leptin resistance in obese adolescents

Introduction: Obesity is a nutritional disorder that can affect all ages, including teenagers. Obesity can affect gut microbiota and cause increased intestinal permeability. This process leads to interleukin-6 and TNF-α production which can increase leptin levels. The soluble leptin receptor (sLR) is a leptin receptor in the plasma that transports leptin to the hypothalamus. Low sLR numbers are associated with high leptin levels in obesity. Obesity in hyperleptinemia conditions indicates leptin resistance (defects in leptin receptors) which causes hyperphagia and reduces energy expenditure. This study was conducted to prove high TG and IL-6 serum levels and low sLR levels in obese adolescents who have a higher risk of developing leptin resistance than normal adolescents. Methods: This research is a case-control study. The subjects underwent an assessment including food recall, anthropometric status, and lipid profile. The food recall assessment was obtained by means of a questionnaire given to parents. Blood sampling and laboratory examination are carried out by the Prodia® Clinical Laboratory. Data analysis was performed by computer, using the Independent t-test, Mann-Whitney test. Chi-Square test, and analysis of the ROC curve. Results: ROC curve analysis obtained the optimal cut points for TG and IL-6 levels, respectively 101.5 mg/dL (sensitivity 82.1%, specificity 89.7%) and 11.95 pg/mL (sensitivity 84.6%, specificity of 80%), with area under the curve (AUC) values of 0.96 and 0.89, respectively. ROC curve analysis obtained the optimal cut point for sLR levels of 19.3 ng/mL (sensitivity 64.1%, specificity 71.8%) with an AUC value of 0.77. Multivariate analysis using logistic regression found a significant relationship between TG and IL-6 levels on the incidence of hyperleptinemia. Conclusion: This study reinforces the theory of chronic low-grade inflammation and proved that inflammation and high TG levels play a role in hyperleptinemia in obese adolescents.