Application of CRISPR-Cas9 technology in diabetes research.

Diabetes is a chronic disorder with rapidly increasing prevalence that is a major global issue of our current era. There are two major types of diabetes. Polygenic forms of diabetes include type 1 diabetes (T1D) and type 2 diabetes (T2D) and its monogenic forms are maturity-onset diabetes of the young (MODY) and neonatal diabetes mellitus (NDM). There are no permanent therapeutic approaches for diabetes and current therapies rely on regular administration of various drugs or insulin injection. Recently, gene editing strategies have offered new promise for treating genetic disorders. Targeted genome editing is a fast-growing technology, recruiting programmable nucleases to specifically modify target genomic sequences. These targeted nucleases generate double-strand breaks at target regions in the genome, which induce cellular repair pathways including non-homologous end joining (NHEJ) and homology-directed repair (HDR). Clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) is a novel gene-editing system, permitting precise genome modification. CRISPR/Cas9 has great potential for various applications in diabetic research such as gene screening, generation of diabetic animal models and treatment. In this article, gene-editing strategies are summarized with a focus on the CRISPR/Cas9 approach in diabetes research.

Regulatory effects of curcumin on nitric oxide signaling in the cardiovascular system.

The continuously rising prevalence of cardiovascular disease (CVD) globally substantially impacts the economic growth of developing countries. Indeed, one of the leading causes of death worldwide is unfavorable cardiovascular events. Reduced nitric oxide (NO) generation is the pathogenic foundation of endothelial dysfunction, which is regarded as the first stage in the development of a number of CVDs. Nitric oxide exerts an array of biological effects, including vasodilation, the suppression of vascular smooth muscle cell proliferation and the functional control of cardiac cells. Numerous treatment strategies aim to increase NO synthesis or upregulate downstream NO signaling pathways. The major component of Curcuma longa, curcumin, has long been utilized in traditional medicine to treat various illnesses, especially CVDs. Curcumin improves CV function as well as having important pleiotropic effects, such as anti-inflammatory and antioxidant, through its ability to increase the bioavailability of NO and to positively impact NO-related signaling pathways. In this review, we discuss the scientific literature relating to curcumin's positive effects on NO signaling and vascular endothelial function.

The role of natural products as PCSK9 modulators: A review.

A variety of mechanisms and drugs have been shown to attenuate cardiovascular disease (CVD) onset and/or progression. Recent researchers have identified a potential role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in modulating lipid metabolism and reducing plasma low density lipoprotein (LDL) levels. PCSK9 is the central protein in the metabolism of LDL cholesterol (LDL-C) owing to its major function in LDL receptor (LDLR) degradation. Due to the close correlation of cardiovascular disease with lipid levels, many in vivo and in vitro investigations are currently underway studying the physiological role of PCSK9. Furthermore, many studies are actively investigating the mechanisms of various compounds that influence lipid associated-disorders and their associated cardiovascular diseases. PCSK9 inhibitors have been shown to have significant impact in the prevention of emerging cardiovascular diseases. Natural products can effectively be used as PCSK9 inhibitors to control lipid levels through various mechanisms. In this review, we evaluate the role of phytochemicals and natural products in the regulation of PCSK9, and their ability to prevent cardiovascular diseases. Moreover, we describe their mechanisms of action, which have not to date been delineated.

A Cross-Sectional Exploratory Study of Cardiovascular Risk Biomarkers in Non-Obese Women with and without Polycystic Ovary Syndrome: Association with Vitamin D.

Vitamin D is proposed to have a protective effect against cardiovascular disease, though the mechanism is unclear. Vitamin D deficiency is common in polycystic ovary syndrome (PCOS), where it is strongly related to obesity, insulin resistance (IR) and risk of cardiovascular disease. To determine if the inherent pathophysiology of PCOS or vitamin D levels are linked to dysregulation of cardiovascular risk proteins (CVRPs), a study in non-obese women with PCOS and without IR was undertaken. Our hypothesis was that the levels of vitamin D3 and its active metabolite would be associated with CVRPs comparably in women with and without PCOS. In women with PCOS (n = 29) and controls (n = 29), 54 CVRPs were determined by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement and correlated to 25-hydroxyvitamin D3 (25(OH)D3) and the active 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) measured by gold standard isotope-dilution liquid chromatography tandem mass spectrometry. Women with PCOS had comparable IR and systemic inflammation (normal C-reactive protein) to control women, though had higher free androgen index and anti-Mullerian hormone levels. 25(OH)D3 and 1,25(OH)2D3 levels did not differ between groups. Nine CVRPs were higher in PCOS (p < 0.05) (Galectin-9, Brother of CDO, C-motif chemokine 3, Interleukin-18 receptor-1, Thrombopoietin, Interleukin-1 receptor antagonist protein, Programmed cell death 1 ligand-2, Low-affinity immunoglobulin gamma Fc-region receptor II-b and human growth hormone), whilst 45 CVRPs did not differ. 25(OH)D3 correlated with five CVRPs in PCOS and one in controls (p < 0.05). Despite the women with PCOS not exhibiting overt systemic inflammation, 9 of 54 CVRPs were elevated, all relating to inflammation, and 5 of these correlated with 25(OH)D3, suggesting an ongoing underlying inflammatory process in PCOS even in the absence of obesity/IR.

The Role of MicroRNA, Long Non-Coding RNA and Circular RNA in the Pathogenesis of Polycystic Ovary Syndrome: A Literature Review.

Polycystic ovary syndrome (PCOS) is the most common endocrine-metabolic disease in females of reproductive age, affecting 4-20% of pre-menopausal women worldwide. MicroRNAs (miRNAs) are endogenous, single-stranded, non-coding, regulatory ribonucleic acid molecules found in eukaryotic cells. Abnormal miRNA expression has been associated with several diseases and could possibly explain their underlying pathophysiology. MiRNAs have been extensively studied for their potential diagnostic, prognostic, and therapeutic uses in many diseases, such as type 2 diabetes, obesity, cardiovascular disease, PCOS, and endometriosis. In women with PCOS, miRNAs were found to be abnormally expressed in theca cells, follicular fluid, granulosa cells, peripheral blood leukocytes, serum, and adipose tissue when compared to those without PCOS, making miRNAs a useful potential biomarker for the disease. Key pathways involved in PCOS, such as folliculogenesis, steroidogenesis, and cellular adhesion, are regulated by miRNA. This also highlights their importance as potential prognostic markers. In addition, recent evidence suggests a role for miRNAs in regulating the circadian rhythm (CR). CR is crucial for regulating reproduction through the various functions of the hypothalamic-pituitary-gonadal (HPG) axis and the ovaries. A disordered CR affects reproductive outcomes by inducing insulin resistance, oxidative stress, and systemic inflammation. Moreover, miRNAs were demonstrated to interact with lncRNA and circRNAs, which are thought to play a role in the pathogenesis of PCOS. This review discusses what is currently understood about miRNAs in PCOS, the cellular pathways involved, and their potential role as biomarkers and therapeutic targets.

A Cross-Sectional Study of Alzheimer-Related Proteins in Women with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine condition in women of reproductive age, and several risk factors found in PCOS are associated with an increased risk of Alzheimer's disease (AD). Proteins increased in AD have been reported to include fibronectin (FN) fragments 3 and 4 (FN1.3 and FN1.4, respectively) and ApoE. We hypothesized that Alzheimer-related proteins would be dysregulated in PCOS because of associated insulin resistance and obesity. In this comparative cross-sectional analysis, aptamer-based SomaScan proteomic analysis for the detection of plasma Alzheimer-related proteins was undertaken in a PCOS biobank of 143 women with PCOS and 97 control women. Amyloid precursor protein (APP) (p < 0.05) and amyloid P-component (APCS) (p < 0.001) were elevated in PCOS, while alpha-synuclein (SNCA) (p < 0.05) was reduced in PCOS. Associations with protective heat shock proteins (HSPs) showed that SNCA positively correlated with HSP90 (p < 0.0001) and HSP60 (p < 0.0001) in both the PCOS and control women. Correlations with markers of inflammation showed that APCS correlated with interleukin 6 (IL6) (p = 0.04), while Apolipoprotein (Apo) E3 correlated with TNF-alpha (p = 0.02). FN, FN1.3, FN1.4 and ApoE were all elevated significantly (p < 0.05). An AD-associated protein pattern with elevated FN, FN1.3, FN1.4 and ApoE was found in PCOS, in addition to elevated APP and reduced SNCA, which was the same as reported for type 2 diabetes (T2D) with, additionally, an elevation in APCS. With the AD biomarker pattern in PCOS being very similar to that in T2D, where there is an association between AD and T2D, this suggests that larger prospective cohort studies are needed in women with PCOS to determine if there is a causal association with AD.

A Cross-Sectional Study of Protein Changes Associated with Dementia in Non-Obese Weight Matched Women with and without Polycystic Ovary Syndrome.

Dysregulated Alzheimer's disease (AD)-associated protein expression is reported in polycystic ovary syndrome (PCOS), paralleling the expression reported in type 2 diabetes (T2D). We hypothesized, however, that these proteins would not differ between women with non-obese and non-insulin resistant PCOS compared to matched control subjects. We measured plasma amyloid-related proteins levels (Amyloid-precursor protein (APP), alpha-synuclein (SNCA), amyloid P-component (APCS), Pappalysin (PAPPA), Microtubule-associated protein tau (MAPT), apolipoprotein E (apoE), apoE2, apoE3, apoE4, Serum amyloid A (SAA), Noggin (NOG) and apoA1) in weight and aged-matched non-obese PCOS (n = 24) and control (n = 24) women. Dementia-related proteins fibronectin (FN), FN1.3, FN1.4, Von Willebrand factor (VWF) and extracellular matrix protein 1 (ECM1) were also measured. Protein levels were determined by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement. Only APCS differed between groups, being elevated in non-obese PCOS women (p = 0.03) relative to the non-obese control women. This differed markedly from the elevated APP, APCS, ApoE, FN, FN1.3, FN1.4 and VWF reported in obese women with PCOS. Non-obese, non-insulin resistant PCOS subjects have a lower AD-associated protein pattern risk profile versus obese insulin resistant PCOS women, and are not dissimilar to non-obese controls, indicating that lifestyle management to maintain optimal body weight could be beneficial to reduce the long-term AD-risk in women with PCOS.

A Cross-Sectional Study of Glomerular Hyperfiltration in Polycystic Ovary Syndrome.

Glomerular hyperfiltration (GH) has been reported to be higher in women with polycystic ovary syndrome (PCOS) and is an independent risk factor for renal function deterioration, metabolic, and cardiovascular disease. The aim of this study was to determine GH in type A PCOS subjects and to identify whether inflammatory markers, markers of CKD, renal tubule injury markers, and complement system proteins were associated. In addition, a secondary cohort study was performed to determine if the eGFR had altered over time. In this comparative cross-sectional analysis, demographic, metabolic, and proteomic data from Caucasian women aged 18-40 years from a PCOS Biobank (137 with PCOS, 97 controls) was analyzed. Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement was undertaken for inflammatory proteins, serum markers of chronic kidney disease (CKD), tubular renal injury markers, and complement system proteins. A total of 44.5% of the PCOS cohort had GH (eGFR ≥ 126 mL/min/1.73 m2 (n = 55)), and 12% (n = 17) eGFR ≥ 142 mL/min/1.73 m2 (super-GH(SGH)). PCOS-GH women were younger and had lower creatinine and urea versus PCOS-nonGH. C-reactive protein (CRP), white cell count (WCC), and systolic blood pressure (SBP) were higher in PCOS versus controls, but CRP correlated only with PCOS-SGH alone. Complement protein changes were seen between controls and PCOS-nonGH, and decay-accelerator factor (DAF) was decreased between PCOS-nonGH and PCOS-GSGH (p < 0.05). CRP correlated with eGFR in the PCOS-SGH group, but not with other inflammatory or complement parameters. Cystatin-c (a marker of CKD) was reduced between PCOS-nonGH and PCOS-GSGH (p < 0.05). No differences in tubular renal injury markers were found. A secondary cohort notes review of the biobank subjects 8.2-9.6 years later showed a reduction in eGFR: controls -6.4 ± 12.6 mL/min/1.73 m2 (-5.3 ± 11.5%; decrease 0.65%/year); PCOS-nonGH -11.3 ± 13.7 mL/min/1.73 m2 (-9.7 ± 12.2%; p < 0.05, decrease 1%/year); PCOS-GH (eGFR 126-140 mL/min/17.3 m2) -27.1 ± 12.8 mL/min/1.73 m2 (-19.1 ± 8.7%; p < 0.0001, decrease 2%/year); PCOS-SGH (eGFR ≥ 142 mL/min/17.3 m2) -33.7 ± 8.9 mL/min/17.3 m2 (-22.8 ± 6.0%; p < 0.0001, decrease 3.5%/year); PCOS-nonGH eGFR versus PCOS-GH and PCOS-SGH, p < 0.001; no difference PCOS-GH versus PCOS-SGH. GH was associated with PCOS and did not appear mediated through tubular renal injury; however, cystatin-c and DAF were decreased, and CRP correlated positively with PCOS-SGH, suggesting inflammation may be involved at higher GH. There were progressive eGFR decrements for PCOS-nonGH, PCOS-GH, and PCOS-SGH in the follow-up period which, in the presence of additional factors affecting renal function, may be clinically important in the development of CKD in PCOS.

Therapeutic Applications of Stem Cell-Derived Exosomes.

Exosomes are extracellular vesicles of endosomal origin, ranging from 30 to 150 nm in diameter, that mediate intercellular transfer of various biomolecules, such as proteins, lipids, nucleic acids, and metabolites. They modulate the functions of recipient cells and participate in diverse physiological and pathological processes, such as immune responses, cell-cell communication, carcinogenesis, and viral infection. Stem cells (SCs) are pluripotent or multipotent cells that can differentiate into various cell types. SCs can also secrete exosomes, which exhibit remarkable therapeutic potential for various diseases, especially in the field of regenerative medicine. For example, exosomes derived from mesenchymal stem cells (MSCs) contain proteins, lipids, and miRNAs that can ameliorate endocrine disorders, such as diabetes and cancer. Exosomes from SCs (sc-exos) may offer similar advantages as SCs, but with reduced risks and challenges. Sc-exos have lower tumorigenicity, immunogenicity, and infectivity. They can also deliver drugs more efficiently and penetrate deeper into tissues. In this review, we provide an overview of the recent advances in sc-exos and their therapeutic applications in various diseases, such as diabetes and cancer. We also elucidate how the biological effects of sc-exos depend on their molecular composition. We also address the current challenges and future directions of using sc-exos.

How statin drugs affect exosomes?

Statins reduce serum cholesterol and isoprenoids by the inhibition of cholesterol synthesis in the mevalonate pathway. Exosomes are extracellular vesicles (30-200 nm) released by all cells that regulate cell-to-cell communication in health and disease by transferring functional proteins, metabolites and nucleic acids to recipient cells. There are many reports that show an effect of statins on exosomes, from their production and release to their content and performance. In this review, we have summarized existing data on the impact of statins on the biosynthesis, secretion, content, uptake and function of exosomes.

The interplay between androgens and the immune response in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a metabolic-reproductive-endocrine disorder that, while having a genetic component, is known to have a complex multifactorial etiology. As PCOS is a diagnosis of exclusion, standardized criteria have been developed for its diagnosis. The general consensus is that hyperandrogenism is the primary feature of PCOS and is associated with an array of physiological dysfunctions; excess androgens, for example, have been correlated with cytokine hypersecretion, adipocyte proliferation, and signaling pathway dysregulation. Another key feature of PCOS is insulin resistance, resulting in aberrant glucose and fatty acid metabolism. Additionally, the immune system plays a key role in PCOS. Hyperandrogenism stimulates some immune cells while it inhibits others, thereby disrupting the normal balance of immune cells and creating a state of chronic inflammation. This low-grade inflammation could contribute to infertility since it induces ovarian dysfunction. This dysregulated immune response in PCOS exhibits autoimmunity characteristics that require further investigation. This review paper examines the relationship between androgens and the immune response and how their malfunction contributes to PCOS.

Establishing Pragmatic Analytical Performance Specifications for Blood Beta-Hydroxybutyrate Testing.

BACKGROUND: Currently, no authoritative guidelines exist recommending the analytical performance specification (APS) of blood beta-hydroxybutyrate (BOHB) testing in order to meet the clinical needs of patients. This study has applied existing diabetic ketoacidosis (DKA) BOHB diagnostic thresholds and the recommended rates of fall in BOHB concentrations during DKA treatment to establish pragmatic APSs for BOHB testing. METHODS: Required analytical performance was based on 2 clinical requirements: (a) to reliably distinguish between non-adjacent DKA BOHB diagnostic categories of <0.6, 0.6 to 1.5, 1.6 to 2.9, and ≥3 mmol/L, and (b) to be assured that a measured 0.5 mmol/L reduction in BOHB indicates the true concentration is at least falling (meaning >0 mmol/L decline). RESULTS: An analytical coefficient of variation (CV) of <21.5% could reliably distinguish all non-adjacent diagnostic categories with >99% certainty, assuming zero bias. In contrast, within-day CVs of 4.9%, 7.0%, and 9.1% at 3 mmol/L BOHB were required to assure truly falling ketone concentrations with 99% (optimal), 95% (desirable), and 90% (minimal) probability, respectively. These CVs are larger at lower BOHB concentrations and smaller at higher concentrations. CONCLUSIONS: Reliable tracking of changes in BOHB during DKA treatment largely drives the requirement for analytical performance. These data can be used to guide minimal, desirable, and optimal performance targets for BOHB meters and laboratory assays.

Coagulation factor dysregulation in polycystic ovary syndrome is an epiphenomenon of obesity.

OBJECTIVE: Obese women with polycystic ovary syndrome (PCOS) exhibit a hypercoagulable state, with the suggestion that this may be obesity-driven rather than an intrinsic facet of PCOS; however, this has not yet been definitively determined since body mass index (BMI) is so highly correlated with PCOS. Therefore, only a study design where obesity, insulin resistance and inflammation are matched can answer this question. DESIGN: This was a cohort study. Patients Weight and aged-matched nonobese women with PCOS (n = 29) and control women (n = 29) were included. Measurements Plasma coagulation pathway protein levels were measured. Circulating levels of a panel of nine clotting proteins known to differ in obese women with PCOS were determined by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement. RESULTS: Women with PCOS showed a higher free androgen index (FAI) and anti-Müllerian hormone, but measures of insulin resistance, and C reactive protein (as a marker of inflammation), did not differ between the nonobese women with PCOS and the control women. Seven pro-coagulation proteins (plasminogen activator inhibitor-1, fibrinogen, fibrinogen gamma chain, fibronectin, d-dimer, P-selectin and plasma kallikrein) and two anticoagulant proteins (vitamin K-dependent protein-S and heparin cofactor-II) known to be elevated in obese women with PCOS did not differ from controls in this cohort. CONCLUSIONS: This novel data show that clotting system abnormalities do not contribute to the intrinsic mechanisms underlying PCOS in this nonobese noninsulin resistant population of women with PCOS matched for age and BMI, and without evidence of underlying inflammation, but rather the clotting factor changes are an epiphenomenon coincident with obesity; therefore, increased coagulability is unlikely in these nonobese PCOS women.

Association of polychlorinated biphenyls with vitamin D in female subjects.

INTRODUCTION: Polychlorinated biphenyls (PCBs) are known endocrine disrupters. A potentially causal association of PCBs with vitamin D has been reported. Higher body mass index (BMI) is associated with lower PCB levels whilst the strongest association of PCBs with BMI is in non-obese individuals. Therefore, this study examined the association of PCBs with vitamin D3 (25(OH)D3) and the active 1,25-dihydrovitamin D3 (1,25(OH)2D3) in a cohort of non-obese women. METHODS: 58 female participants (age 31.9 ± 4.6 years; BMI 25.7 ± 3.7 kg/m2) had seven indicator PCBs [PCB28, PCB52, PCB101, PCB118, PCB138, PCB153 and PCB180] measured using high resolution gas chromatography, with total PCB level calculated. 25(OH)D3 and 1,25(OH)2D3 levels were determined by isotope-dilution liquid chromatography tandem mass spectrometry. RESULTS: In this cohort, vitamin D3 (25(OH)D3) and 1,25(OH)2D3 levels were 50.7 ± 25.3 nmol/L and 0.05 ± 0.02 ng/ml, respectively. Of those, 28 had vitamin D deficiency [25(OH)D3 level <20 ng/ml (<50nmol/)]. Total PCBs correlated positively with total group 25(OH)D3 (r = 0.22, p = 0.04) as did PCB118 (r = 0.25, p = 0.03). Total PCBs did not correlate with total group 1,25(OH)2D3; however, PCB180 did correlate positively with 1,25(OH)2D3 (r = 0.34, p = 0.03) as did PCB153 (r = 0.33, p < 0.03), with PCB 28 correlating negatively (r = -0.29, p < 0.04). In the vitamin D deficient subgroup, total PCBs, PCB153 and PCB180 positively correlated with 25(OH)D3 (p < 0.05). Multilinear regression analysis indicated all associations could be accounted for by BMI. CONCLUSION: Though certain PCBs associated with 25(OH)D3 and 1,25(OH)2D3, all associations could be accounted for by BMI. This study therefore indicates that the deleterious effects from PCB accumulation are not mediated by effects on 25(OH)D3 or 1,25(OH)2D3.

The role of efferocytosis and transplant rejection: Strategies in promoting transplantation tolerance using apoptotic cell therapy and/or synthetic particles.

Recently, efforts have been made to recognize the precise reason(s) for transplant failure and the process of rejection utilizing the molecular signature. Most transplant recipients do not appreciate the unknown length of survival of allogeneic grafts with the existing standard of care. Two noteworthy immunological pathways occur during allogeneic transplant rejection. A nonspecific innate immune response predominates in the early stages of the immune reaction, and allogeneic antigens initiate a donor-specific adaptive reaction. Though the adaptive response is the major cause of allograft rejection, earlier pro-inflammatory responses that are part of the innate immune response are also regarded as significant in graft loss. The onset of the innate and adaptive immune response causes chronic and acute transplant rejection. Currently employed immunosuppressive medications have shown little or no influence on chronic rejection and, as a result, on overall long-term transplant survival. Furthermore, long-term pharmaceutical immunosuppression is associated with side effects, toxicity, and an increased risk of developing diseases, both infectious and metabolic. As a result, there is a need for the development of innovative donor-specific immunosuppressive medications to regulate the allorecognition pathways that induce graft loss and to reduce the side effects of immunosuppression. Efferocytosis is an immunomodulatory mechanism with fast and efficient clearance of apoptotic cells (ACs). As such, AC therapy strategies have been suggested to limit transplant-related sequelae. Efferocytosis-based medicines/treatments can also decrease the use of immunosuppressive drugs and have no detrimental side effects. Thus, this review aims to investigate the impact of efferocytosis on transplant rejection/tolerance and identify approaches using AC clearance to increase transplant viability.

The COVID-19 Pandemic: SARS-CoV-2 Structure, Infection, Transmission, Symptomology, and Variants of Concern.

Since it was first detected in December 2019, the COVID-19 pandemic has spread across the world and affected virtually every country and territory. The pathogen driving this pandemic is SARS-CoV-2, a positive-sense single-stranded RNA virus which is primarily transmissible though the air and can cause mild to severe respiratory infections in humans. Within the first year of the pandemic, the situation worsened with the emergence of several SARS-CoV-2 variants. Some of these were observed to be more virulent with varying capacities to escape the existing vaccines and were, therefore, denoted as variants of concern. This chapter provides a general overview of the course of the COVID-19 pandemic up to April 2022 with a focus on the structure, infection, transmission, and symptomology of the SARS-CoV-2 virus. The main objectives were to investigate the effects of the variants of concern on the trajectory of the virus and to highlight a potential pathway for coping with the current and future pandemics.

The effect of medicinal plants on cirrhosis: A systematic review of clinical trials.

Medicinal plants with minimal side effects, low cost, and liver-protective effects can be a suitable treatment option for cirrhosis. Therefore, this systematic review aimed to determine the effectiveness of herbal medicines on cirrhosis, a life-threatening liver disease. PubMed, Scopus, Web of Science, and Google Scholar were systematically searched for clinical trials that investigated the effect of medicinal plants on cirrhosis. This review includes 11 clinical trials, of which eight studies including 613 patients assessed the effect of silymarin on cirrhosis. Three of six studies showed the beneficial effects of silymarin on aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Two studies including 118 patients investigated the effect of curcumin on cirrhosis, one showing improvement in quality of life and the other showing improvements in alkaline phosphatase (ALP), bilirubin, prothrombin time (PT), and the international normalized ratio (INR). An article including four patients investigated the effect of ginseng on cirrhosis; two patients reported improvement in the Child-Pugh score, and ascites decreased in two. All studies included here reported no or negligible side effects. Results showed that medicinal plants including silymarin, curcumin, and ginseng have beneficial effects on cirrhosis. However, due to the limited number of studies, further high-quality studies are warranted.

The Role of Heat Shock Proteins in the Pathogenesis of Polycystic Ovarian Syndrome: A Review of the Literature.

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and post-menopausal women. PCOS is a multifactorial heterogeneous disorder associated with a variety of etiologies, outcomes, and clinical manifestations. However, the pathophysiology of PCOS is still unclear. Heat shock proteins (HSPs) have recently been investigated for their role in the pathogenesis of PCOS. HSPs are a class of proteins that act as molecular chaperones and maintain cellular proteostasis. More recently, their actions beyond that of molecular chaperones have highlighted their pathogenic role in several diseases. In PCOS, different HSP family members show abnormal expression that affects the proliferation and apoptotic rates of ovarian cells as well as immunological processes. HSP dysregulation in the ovaries of PCOS subjects leads to a proliferation/apoptosis imbalance that mechanistically impacts follicle stage development, resulting in polycystic ovaries. Moreover, HSPs may play a role in the pathogenesis of PCOS-associated conditions. Recent studies on HSP activity during therapeutic interventions for PCOS suggest that modulating HSP activity may lead to novel treatment strategies. In this review, we summarize what is currently known regarding the role of HSPs in the pathogenesis of PCOS and their potential role in the treatment of PCOS, and we outline areas for future research.

Glycemia-Induced miRNA Changes: A Review.

Diabetes is a rapidly increasing global health concern that significantly strains the health system due to its downstream complications. Dysregulation in glycemia represents one of the fundamental obstacles to achieving glycemic control in diabetic patients. Frequent hyperglycemia and/or hypoglycemia events contribute to pathologies that disrupt cellular and metabolic processes, which may contribute to the development of macrovascular and microvascular complications, worsening the disease burden and mortality. miRNAs are small single-stranded non-coding RNAs that regulate cellular protein expression and have been linked to various diseases, including diabetes mellitus. miRNAs have proven useful in the diagnosis, treatment, and prognosis of diabetes and its complications. There is a vast body of literature examining the role of miRNA biomarkers in diabetes, aiming for earlier diagnoses and improved treatment for diabetic patients. This article reviews the most recent literature discussing the role of specific miRNAs in glycemic control, platelet activity, and macrovascular and microvascular complications. Our review examines the different miRNAs involved in the pathological processes leading to the development of type 2 diabetes mellitus, such as endothelial dysfunction, pancreatic beta-cell dysfunction, and insulin resistance. Furthermore, we discuss the potential applications of miRNAs as next-generation biomarkers in diabetes with the aim of preventing, treating, and reversing diabetes.

Environmental Pollution and the Risk of Developing Metabolic Disorders: Obesity and Diabetes.

To meet the increased need for food and energy because of the economic shift brought about by the Industrial Revolution in the 19th century, there has been an increase in persistent organic pollutants (POPs), atmospheric emissions and metals in the environment. Several studies have reported a relationship between these pollutants and obesity, and diabetes (type 1, type 2 and gestational). All of the major pollutants are considered to be endocrine disruptors because of their interactions with various transcription factors, receptors and tissues that result in alterations of metabolic function. POPs impact adipogenesis, thereby increasing the prevalence of obesity in exposed individuals. Metals impact glucose regulation by disrupting pancreatic ß-cells, causing hyperglycemia and impaired insulin signaling. Additionally, a positive association has been observed between the concentration of endocrine disrupting chemicals (EDCs) in the 12 weeks prior to conception and fasting glucose levels. Here, we evaluate what is currently known regarding the link between environmental pollutants and metabolic disorders. In addition, we indicate where further research is required to improve our understanding of the specific effects of pollutants on these metabolic disorders which would enable implementation of changes to enable their prevention.