Berberine-loaded engineered nanoparticles attenuate TGF-ß-induced remodelling in human bronchial epithelial cells.

Airway remodelling occurs in chronic respiratory diseases (CRDs) such as asthma and chronic obstructive pulmonary disease (COPD). It is characterized by aberrant activation of epithelial reparation, excessive extracellular matrix (ECM) deposition, epithelial-to-mesenchymal transition (EMT), and airway obstruction. The master regulator is Transforming Growth Factor-ß (TGF-ß), which activates tissue repair, release of growth factors, EMT, increased cell proliferation, and reduced nitric oxide (NO) secretion. Due to its fundamental role in remodelling, TGF-ß is an emerging target in the treatment of CRDs. Berberine is a benzylisoquinoline alkaloid with antioxidant, anti-inflammatory, and anti-fibrotic activities whose clinical application is hampered by poor permeability. To overcome these limitations, in this study, berberine was encapsulated in monoolein-based liquid crystalline nanoparticles (BM-LCNs). The potential of BM-LCNs in inhibiting TGF-ß-induced remodelling features in human bronchial epithelial cells (BEAS-2B) was tested. BM-LCNs significantly inhibited TGF-ß-induced migration, reducing the levels of proteins upregulated by TGF-ß including endoglin, thrombospondin-1, basic fibroblast growth factor, vascular-endothelial growth factor, and myeloperoxidase, and increasing the levels of cystatin C, a protein whose expression was downregulated by TGF-ß. Furthermore, BM-LCNs restored baseline NO levels downregulated by TGF-ß. The results prove the in vitro therapeutic efficacy of BM-LCNs in counteracting TGF-ß-induced remodelling features. This study supports the suitability of berberine-loaded drug delivery systems to counteract airway remodelling, with potential application as a treatment strategy against CRDs.

Multifaceted role of synbiotics as nutraceuticals, therapeutics and carrier for drug delivery.

Synbiotics, are a combination of probiotics and prebiotics. They play an important role in metabolizing different nutritional substrates and thus helps in the maintenance of human health. Any disbalance in the gut microflora, known as dysbiosis, is known to lead to a number of diseased conditions. It can be reverted by the administration of synbiotics. Present review highlights various mechanistic pathways through which synbiotics act as therapeutics. The dual role of synbiotics as nutraceutical and excipient in developing oral formulations are entailed with case studies. The findings entailed that there exist numerous studies on prebiotics as well as probiotics have been carried out to show their effects in several diseases. However, the concept of combining together them for prevention and treatment of various pathological conditions accruing from dysbiosis is relatively new. Synbiotics, however, face challenge of low stability during their sojourn in the GIT, which is generally overcome by various encapsulation techniques. Various studies also showed potential role of synbiotics in drug delivery. However, it is an emerging area and lacks clinical correlation. It is important to focus on clinical trials of formulations wherein synbiotics have been used as therapeutic moiety as well as pharmaceutical carrier for treating various diseases.

Attenuation of Cigarette-Smoke-Induced Oxidative Stress, Senescence, and Inflammation by Berberine-Loaded Liquid Crystalline Nanoparticles: In Vitro Study in 16HBE and RAW264.7 Cells.

Cigarette smoke is considered a primary risk factor for chronic obstructive pulmonary disease. Numerous toxicants present in cigarette smoke are known to induce oxidative stress and airway inflammation that further exacerbate disease progression. Generally, the broncho-epithelial cells and alveolar macrophages exposed to cigarette smoke release massive amounts of oxidative stress and inflammation mediators. Chronic exposure of cigarette smoke leads to premature senescence of airway epithelial cells. This impairs cellular function and ultimately leads to the progression of chronic lung diseases. Therefore, an ideal therapeutic candidate should prevent disease progression by controlling oxidative stress, inflammation, and senescence during the initial stage of damage. In our study, we explored if berberine (an alkaloid)-loaded liquid crystalline nanoparticles (berberine-LCNs)-based treatment to human broncho-epithelial cells and macrophage inhibits oxidative stress, inflammation, and senescence induced by cigarette-smoke extract. The developed berberine-LCNs were found to have favourable physiochemical parameters, such as high entrapment efficiency and sustained in vitro release. The cellular-assay observations revealed that berberine-LCNs showed potent antioxidant activity by suppressing the generation of reactive oxygen species in both broncho-epithelial cells (16HBE) and macrophages (RAW264.7), and modulating the genes involved in inflammation and oxidative stress. Similarly, in 16HBE cells, berberine-LCNs inhibited the cigarette smoke-induced senescence as revealed by X-gal staining, gene expression of CDKN1A (p21), and immunofluorescent staining of p21. Further in-depth mechanistic investigations into antioxidative, anti-inflammatory, and antisenescence research will diversify the current findings of berberine as a promising therapeutic approach for inflammatory lung diseases caused by cigarette smoking.

Polysaccharide Peptide Extract From Coriolus versicolor Increased Tmax of Tamoxifen and Maintained Biochemical Serum Parameters, With No Change in the Metabolism of Tamoxifen in the Rat.

Background: Polysaccharide peptide (PSP) extract of Coriolus versicolor (L.) Quél. (1886) (Trametes; Polyporaceae) is increasingly used in cancer to support the immune system. However, its interaction with tamoxifen is unknown. Aim of the study: To investigate the effect of a PSP extract on the pharmacokinetics, biochemical parameters, and depletion of tamoxifen. Methods: The pharmacokinetic and biochemical parameters of tamoxifen (20 mg/mL oral single dose and repeated dosing for 12 days) was investigated in female Sprague Dawley rats with or without PSP (340 mg/kg orally for 7 days) (n = 5 per group). Tamoxifen (5 µM) depletion rate with PSP (10-100 µg/mL) was measured in female rat hepatic microsomes in vitro. Results: Compared to tamoxifen alone, the time to reach maximum concentration (Tmax) significantly increased by 228% (4.15 ± 1.15 versus 13.6 ± 2.71 h) in the single tamoxifen dose with PSP and 93% (6 ± 2.17 versus 11.6 ± 0.4 h) in the repeated tamoxifen dosing with PSP (p < 0.05). No significant changes in the area-under-curve and maximum concentration were observed in the single dose and repeated tamoxifen dosing plus PSP compared to tamoxifen alone. Pharmacodynamically, the repeated tamoxifen dosing with PSP maintained 19 out of 23 hepatic, renal and cardiac biochemical serum parameters in rats compared to untreated rats (p > 0.05). PSP extract did not significantly alter in vitro intrinsic clearance of tamoxifen compared to tamoxifen control. Conclusion: With the increased use of PSP as an adjunct therapy, this study highlights the importance of clinician's knowledge of its interaction with tamoxifen to avoid compromising clinical actions and enhancing clinical therapy.

The Effects of Curcumin Supplementation on Metabolic Biomarkers and Body Mass Index in Patients with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND AND AIMS: Curcumin is one of the most commonly used indigenous molecules endowed with various shielding functionalities that protect the liver. In the present research, we aimed to investigate the effects of curcumin on metabolic factors and body mass index (BMI) in patients with non-alcoholic fatty liver disease (NAFLD) using a meta-analysis of randomized, controlled trials. METHODS: Online databases PubMed, Embase, Web of Science, and Science Direct were searched until April 2021 to identify eligible articles. Fourteen trials were included. RESULTS: The results showed that curcumin consumption can significantly reduce AST (-0.35, (-0.57 to -0.14)), total cholesterol (-0.81, (-1.34 to -0.27)), TG (-0.49, (-0.71 to -0.27)), and FBS (-0.28, (-0.46 to -0.09)) in patients with NAFLD. However, the improvements in ALT (-0.29, (-0.58 to 0.00)), LDL (-0.48, (-0.97 to 0.01)), HDL (0.03, (-0.38 to 0.44)), and BMI (-0.13, (-0.29 to 0.02)) were not statistically significant. Furthermore, the findings revealed that the optimal dose and duration of curcumin consumption for patients with NAFLD is <500 mg/d for less than 10 weeks. CONCLUSION: The present study suggests that consuming curcumin can improve liver enzymes, lipid profile, FBS, and BMI in patients with NAFLD. Moreover, curcumin supplementation may provide beneficial effects on metabolic biomarkers and body weight if used at the appropriate dose and duration. Further RCTs are required to confirm our findings.

Hypoxia-Inducible Factor (HIF): Fuel for Cancer Progression.

Hypoxia is an integral part of the tumor microenvironment, caused primarily due to rapidly multiplying tumor cells and a lack of proper blood supply. Among the major hypoxic pathways, HIF-1 transcription factor activation is one of the widely investigated pathways in the hypoxic tumor microenvironment (TME). HIF-1 is known to activate several adaptive reactions in response to oxygen deficiency in tumor cells. HIF-1 has two subunits, HIF-1ß (constitutive) and HIF-1α (inducible). The HIF-1α expression is largely regulated via various cytokines (through PI3K-ACT-mTOR signals), which involves the cascading of several growth factors and oncogenic cascades. These events lead to the loss of cellular tumor suppressant activity through changes in the level of oxygen via oxygen-dependent and oxygen-independent pathways. The significant and crucial role of HIF in cancer progression and its underlying mechanisms have gained much attention lately among the translational researchers in the fields of cancer and biological sciences, which have enabled them to correlate these mechanisms with various other disease modalities. In the present review, we have summarized the key findings related to the role of HIF in the progression of tumors.

Cellular signalling pathways mediating the pathogenesis of chronic inflammatory respiratory diseases: an update.

Respiratory disorders, especially non-communicable, chronic inflammatory diseases, are amongst the leading causes of mortality and morbidity worldwide. Respiratory diseases involve multiple pulmonary components, including airways and lungs that lead to their abnormal physiological functioning. Several signaling pathways have been reported to play an important role in the pathophysiology of respiratory diseases. These pathways, in addition, become the compounding factors contributing to the clinical outcomes in respiratory diseases. A range of signaling components such as Notch, Hedgehog, Wingless/Wnt, bone morphogenetic proteins, epidermal growth factor and fibroblast growth factor is primarily employed by these pathways in the eventual cascade of events. The different aberrations in such cell-signaling processes trigger the onset of respiratory diseases making the conventional therapeutic modalities ineffective. These challenges have prompted us to explore novel and effective approaches for the prevention and/or treatment of respiratory diseases. In this review, we have attempted to deliberate on the current literature describing the role of major cell signaling pathways in the pathogenesis of pulmonary diseases and discuss promising advances in the field of therapeutics that could lead to novel clinical therapies capable of preventing or reversing pulmonary vascular pathology in such patients.

Atorvastatin Improves Hepatic Lipid Metabolism and Protects Renal Damage in Adenine-Induced Chronic Kidney Disease in Sprague-Dawley Rats.

OBJECTIVE: Chronic kidney disease (CKD), including nephrotic syndrome, is a major cause of cardiovascular morbidity and mortality. The literature indicates that CKD is associated with profound lipid disorders largely due to the dysregulation of lipoprotein metabolism which further aggravates the progression of kidney disease. The present study sought to determine the efficacy of atorvastatin treatment on hepatic lipid metabolism and renal tissue damage in CKD rats. METHODS: Serum, hepatic and faecal lipid contents and the expression and enzyme activity of molecules involved in cholesterol and triglyceride metabolism, along with kidney function, were determined in untreated adenine-induced CKD, atorvastatin-treated CKD (10 mg/kg/day oral for 24 days) and control rats. KEY FINDINGS: CKD resulted in metabolic dyslipidaemia, renal insufficiency, hepatic lipid accumulation, upregulation of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, acyl-CoA cholesterol acyltransferase-2 (ACAT2) and the downregulation of LDL receptor protein, VLDL receptor, hepatic lipase, lipoprotein lipase (LPL), lecithin-cholesterol acyltransferase (LCAT) and scavenger receptor class B type 1 (SR-B1). CKD also resulted in increased enzymatic activity of HMG-CoA reductase and ACAT2 together with decreased enzyme activity of lipase and LCAT. Atorvastatin therapy attenuated dyslipidaemia, renal insufficiency, reduced hepatic lipids, HMG-CoA reductase and ACAT2 protein abundance and raised LDL receptor and lipase protein expression. Atorvastatin therapy decreased the enzymatic activity of HMG-CoA reductase and increased enzymatic activity of lipase and LCAT. CONCLUSIONS: Atorvastatin improved hepatic tissue lipid metabolism and renal function in adenine-induced CKD rats.

Chronic treatment of curcumin improves hepatic lipid metabolism and alleviates the renal damage in adenine-induced chronic kidney disease in Sprague-Dawley rats.

BACKGROUND: Chronic kidney disease (CKD), including nephrotic syndrome, is a major cause of cardiovascular morbidity and mortality. The literature indicates that CKD is associated with profound lipid disorders due to the dysregulation of lipoprotein metabolism which progresses kidney disease. The objective of this study is to evaluate the protective effects of curcumin on dyslipidaemia associated with adenine-induced chronic kidney disease in rats. METHODS: Male SD rats (n = 29) were divided into 5 groups for 24 days: normal control (n = 5, normal diet), CKD control (n = 6, 0.75% w/w adenine-supplemented diet), CUR 50 (n = 6, 50 mg/kg/day curcumin + 0.75% w/w adenine-supplemented diet), CUR 100 (n = 6, 100 mg/kg/day curcumin + 0.75% w/w adenine-supplemented diet), and CUR 150 (n = 6, 150 mg/kg/day curcumin + 0.75% w/w adenine-supplemented diet). The serum and tissue lipid profile, as well as the kidney function test, were measured using commercial diagnostic kits. RESULTS: The marked rise in total cholesterol, low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, triglycerides and free fatty acids in serum, as well as hepatic cholesterol, triglyceride and free fatty acids of CKD control rats were significantly protected by curcumin co-treatment (at the dose of 50, 100 and 150 mg/kg). Furthermore, curcumin significantly increased the serum high-density lipoprotein (HDL) cholesterol compared to the CKD control rats but did not attenuate the CKD-induced weight retardation. Mathematical computational analysis revealed that curcumin significantly reduced indicators for the risk of atherosclerotic lesions (atherogenic index) and coronary atherogenesis (coronary risk index). In addition, curcumin improved kidney function as shown by the reduction in proteinuria and improvement in creatinine clearance. CONCLUSION: The results provide new scientific evidence for the use of curcumin in CKD-associated dyslipidaemia and substantiates the traditional use of curcumin in preventing kidney damage.

Therapeutic potential of Artemisia vulgaris: An insight into underlying immunological mechanisms.

Artemisia vulgaris is a traditional Chinese herb believed to have a wide range of healing properties; it is traditionally used to treat numerous health ailments. The plant is commonly called mugwort or riverside wormwood. The plant is edible, and in addition to its medicinal properties, it is also used as a culinary herb in Asian cooking in the form of a vegetable or in soup. The plant has garnered the attention of researchers in the past few decades, and several research studies have investigated its biological effects, including antioxidant, anti-inflammatory, anticancer, hypolipidemic, and antimicrobial properties. In this review, various studies on these biological effects are discussed along with the tests conducted, compounds involved, and proposed mechanisms of action. This review will be of interest to the researchers working in the field of herbal medicine, pharmacology, medical sciences, and immunology.

Erratum to "Nonpharmacologic Interventions in Prevention and Treatment of Hypertension".

[This corrects the article DOI: 10.1155/2019/6709817.].

Current Status on Immunological Therapies for Type 1 Diabetes Mellitus.

PURPOSE OF REVIEW: Type 1 diabetes (T1D) occurs when there is destruction of beta cells within the islets of Langerhans in the pancreas due to autoimmunity. It is considered a complex disease, and different complications can surface and worsen the condition if T1D is not managed well. Since it is an incurable disease, numerous treatments and therapies have been postulated in order to control T1D by balancing hyperglycemia control while minimizing hypoglycemic episodes. The purpose of this review is to primarily look into the current state of the available immunological therapies and their advantages for the treatment of T1D. RECENT FINDINGS: Over the years, immunological therapy has become the center of attraction to treat T1D. Immunomodulatory approaches on non-antigens involving agents such as cyclosporine A, mycophenolate mofetil, anti-CD20, cytotoxic T cells, anti-TNF, anti-CD3, and anti-thymocyte globulin as well as immunomodulative approaches on antigens such as insulin, glutamic acid decarboxylase, and heat shock protein 60 have been studied. Aside from these two approaches, studies and trials have also been conducted on regulatory T cells, dendritic cells, interleukin 2, interleukin 4, M2 macrophages, and rapamycin/interleukin 2 combination therapy to test their effects on patients with T1D. Many of these agents have successfully suppressed T1D in non-obese diabetic (NOD) mice and in human trials. However, some have shown negative results. To date, the insights into the management of the immune system have been increasing rapidly to search for potential therapies and treatments for T1D. Nevertheless, some of the challenges are still inevitable. A lot of work and effort need to be put into the investigation on T1D through immunological therapy, particularly to reduce complications to improve and enhance clinical outcomes.

Gene therapy and type 1 diabetes mellitus.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is an autoimmune disorder characterized by T cell-mediated self-destruction of insulin-secreting islet ß cells. Management of T1DM is challenging and complicated especially with conventional medications. Gene therapy has emerged as one of the potential therapeutic alternatives to treat T1DM. This review primarily focuses on the current status and the future perspectives of gene therapy in the management of T1DM. A vast number of the studies which are reported on gene therapy for the management of T1DM are done in animal models and in preclinical studies. In addition, the safety of such therapies is yet to be established in humans. Currently, there are several gene level interventions that are being investigated, notably, overexpression of genes and proteins needed against T1DM, transplantation of cells that express the genes against T1DM, stem-cells mediated gene therapy, genetic vaccination, immunological precursor cell-mediated gene therapy and vectors. METHODS: We searched the current literature through searchable online databases, journals and other library sources using relevant keywords and search parameters. Only relevant publications in English, between the years 2000 and 2018, with evidences and proper citations, were considered. The publications were then analyzed and segregated into several subtopics based on common words and content. A total of 126 studies were found suitable for this review. FINDINGS: Generally, the pros and cons of each of the gene-based therapies have been discussed based on the results collected from the literature. However, there are certain interventions that require further detailed studies to ensure their effectiveness. We have also highlighted the future direction and perspectives in gene therapy, which, researchers could benefit from.

Cowpea: an overview on its nutritional facts and health benefits.

Cowpea (Vigna unguiculata) is a legume consumed as a high-quality plant protein source in many parts of the world. High protein and carbohydrate contents with a relatively low fat content and a complementary amino acid pattern to that of cereal grains make cowpea an important nutritional food in the human diet. Cowpea has gained more attention recently from consumers and researchers worldwide as a result of its exerted health beneficial properties, including anti-diabetic, anti-cancer, anti-hyperlipidemic, anti-inflammatory and anti-hypertensive properties. Among the mechanisms that have been proposed in the prevention of chronic diseases, the most proven are attributed to the presence of compounds such as soluble and insoluble dietary fiber, phytochemicals, and proteins and peptides in cowpea. However, studies on the anti-cancer and anti-inflammatory properties of cowpea have produced conflicting results. Some studies support a protective effect of cowpea on the progression of cancer and inflammation, whereas others did not reveal any. Because there are only a few studies addressing health-related effects of cowpea consumption, further studies in this area are suggested. In addition, despite the reported favorable effects of cowpea on diabetes, hyperlipidemia and hypertension, a long-term epidemiological study investigating the association between cowpea consumption and diabetes, cardiovascular disease and cancer is also recommended. © 2018 Society of Chemical Industry.

Attenuation of Glucose-Induced Myoglobin Glycation and the Formation of Advanced Glycation End Products (AGEs) by (R)-α-Lipoic Acid In Vitro.

High-carbohydrate containing diets have become a precursor to glucose-mediated protein glycation which has been linked to an increase in diabetic and cardiovascular complications. The aim of the present study was to evaluate the protective effect of (R)-α-lipoic acid (ALA) against glucose-induced myoglobin glycation and the formation of advanced glycation end products (AGEs) in vitro. METHODS: The effect of ALA on myoglobin glycation was determined via the formation of AGEs fluorescence intensity, iron released from the heme moiety of myoglobin and the level of fructosamine. The extent of glycation-induced myoglobin oxidation was measured via the levels of protein carbonyl and thiol. RESULTS: The results showed that the co-incubation of ALA (1, 2 and 4 mM) with myoglobin (1 mg/mL) and glucose (1 M) significantly decreased the levels of fructosamine, which is directly associated with the decrease in the formation of AGEs. Furthermore, ALA significantly reduced the release of free iron from myoglobin which is attributed to the protection of myoglobin from glucose-induced glycation. The results also demonstrated a significant protective effect of ALA on myoglobin from oxidative damage, as seen from the decreased protein carbonyls and increased protein thiols. CONCLUSION: The anti-glycation properties of ALA suggest that ALA supplementation may be beneficial in the prevention of AGEs-mediated diabetic and cardiovascular complications.

(R)-α-Lipoic acid inhibits fructose-induced myoglobin fructation and the formation of advanced glycation end products (AGEs) in vitro.

BACKGROUND: Fructose-mediated protein glycation (fructation) has been linked to an increase in diabetic and cardiovascular complications due to over consumption of high-fructose containing diets in recent times. The objective of the present study is to evaluate the protective effect of (R)-α-lipoic acid (ALA) against fructose-induced myoglobin fructation and the formation of advanced glycation end products (AGEs) in vitro. METHODS: The anti-glycation activity of ALA was determined using the formation of AGEs fluorescence intensity, iron released from the heme moiety of myoglobin and the level of fructosamine. The fructation-induced myoglobin oxidation was examined using the level of protein carbonyl content and thiol group estimation. RESULTS: The results showed that co-incubation of myoglobin (1 mg/mL), fructose (1 M) and ALA (1, 2 and 4 mM) significantly inhibited the formation of AGEs during the 30 day study period. ALA markedly decreased the levels of fructosamine, which is directly associated with the reduction of AGEs formation. Furthermore, ALA significantly reduced free iron release from myoglobin which is attributed to the protection of myoglobin from fructose-induced glycation. The results also demonstrated a significant protective effect of ALA on myoglobin oxidative damages, as seen from decreased protein carbonyl content and increased protein thiols. CONCLUSION: These findings provide new insights into the anti-glycation properties of ALA and emphasize that ALA supplementation is beneficial in the prevention of AGEs-mediated diabetic and cardiovascular complications.

Interactions between antidiabetic drugs and herbs: an overview of mechanisms of action and clinical implications.

Diabetes is a complex condition with a variety of causes and pathophysiologies. The current single target approach has not provided ideal clinical outcomes for the treatment of the disease and its complications. Herbal medicine has been used for the management of various diseases such as diabetes over centuries. Many diabetic patients are known to use herbal medicines with antidiabetic properties in addition to their mainstream treatments, which may present both a benefit as well as potential risk to effective management of their disease. In this review we evaluate the clinical and experimental literature on herb-drug interactions in the treatment of diabetes. Pharmacokinetic and pharmacodynamic interactions between drugs and herbs are discussed, and some commonly used herbs which can interact with antidiabetic drugs summarised. Herb-drug interactions can be a double-edged sword presenting both risks (adverse drug events) and benefits (through enhancement). There is a general lack of data on herb-drug interactions. As such, more rigorous scientific research is urgently needed to guide clinical practice as well as to safeguard the wellbeing of diabetes patients.

Chronic treatment of (R)-α-lipoic acid reduces blood glucose and lipid levels in high-fat diet and low-dose streptozotocin-induced metabolic syndrome and type 2 diabetes in Sprague-Dawley rats.

(R)- α -lipoic acid (ALA), an essential cofactor in mitochondrial respiration and a potential antioxidant, possesses a wide array of metabolic benefits including anti-obesity, glucose lowering, insulin-sensitizing, and lipid-lowering effects. In this study, the curative effects of ALA (100 mg/kg) on a spectrum of conditions related to metabolic syndrome and type 2 diabetes (T2D) were investigated in a high-fat diet (HFD)-fed and low-dose streptozotocin (STZ)-induced rat model of metabolic syndrome and T2D. The marked rise in the levels of glucose, triglycerides, total-cholesterol, LDL-cholesterol, and VLDL-cholesterol in the blood of HFD-fed and low-dose STZ-injected rats were significantly reduced by ALA treatment. Furthermore, ALA treatment significantly increased the serum HDL-cholesterol levels and tended to inhibit diabetes-induced weight reduction. Mathematical computational analysis revealed that ALA also significantly improved insulin sensitivity and reduced the risk of atherosclerotic lesions and coronary atherogenesis. This study provides scientific evidence to substantiate the use of ALA to mitigate the glucose and lipid abnormality in metabolic syndrome and T2D.