Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 20, Issue 10, 2020

Objective: Energy metabolism disorder is one of the causes of Parkinson's disease (PD). Rodents, such as rats and mice are often used to establish animal models of PD. This paper used a bibliometric method to analyze the studies of rat and mouse PD models published between 2009 and 2018 in the Web of Science (WOS) database using CiteSpace V software. In addition, we conducted a literature review on the development status and research hotspots in this field in the past ten years. Methods: The related articles on rat and mouse PD models were retrieved from the WOS database, and an analysis of the keywords in these articles was conducted using CiteSpace V. A timeline graph was developed by the software in order to show the focus of researchers in the PD field. Results: A total of 8,636 articles were obtained. Results of the cluster analysis in the PD field such as neuroinflammation, oxidative stress, and autophagy, contributed to the systematic review about the pathogenesis of PD. At the same time, based on the property of the model drug, this review has summarized and compared different administration techniques and mechanisms of 6-hydroxydopamine (6- OHDA), 1-methyl-4-phenyl-1, 2, 4, 5-tetrahydropyridine (MPTP), paraquat and rotenone. Conclusion: According to the bibliometric analysis, studies on PD were focused on the mechanisms of oxidative stress, neuroinflammation, and autophagy. Activated microglia releases inflammatory cytokines; mitochondrial dysfunction is caused by oxidative damage of mitochondrial protein; abnormal autophagy-lysosome pathway can lead to abnormal protein deposition in dopaminergic neurons. In addition, although many animal models of PD have been established, there are some limitations of such models. Therefore, it is necessary to develop models that accurately mimic human PD.

Type 2 diabetes (T2D) is a chronic non-communicable disease that is of major health concern with a steadily rising prevalence across the globe. It is a metabolic disorder characterized by high blood glucose level either as a result of impaired insulin secretion and/or insulin action usually termed insulin resistance. This disease is influenced by lifestyle/feeding habit changes and genetic factors that cause physiological changes in glucose and lipid metabolism. As such, antidiabetic treatments have targeted specific enzymes, receptors, transport proteins, hormones, transcription factors, etc. that are related to glucose metabolism, fat metabolism, insulin secretion and insulin signalization. Genetic variations due to mutations in certain target genes have been shown to influence the pathogenesis of T2D but also these polymorphisms have been observed to alter the therapeutic efficacy of drugs as well as their safety. Pharmacogenetic studies have been able to identify specific genetic variants of target genes that affect the metabolism, therapeutic response and adverse effects of antidiabetic drugs with the aim to translate the research findings to clinical practice. However, pharmacogenetic studies have not fully been able to identify distinct genetic markers that can serve as biomarkers for genetic screening, thus, limiting personalised medicine. As we advocate personalised medicine for the management of T2D in the future, pharmacogenetic studies should lay emphasis on addressing challenges of genetic screening and its translation to personalised therapy.

The application of medicinal plants has captured the interest of researchers in recent times due to their potent therapeutic properties and a better safety profile. The prominent role of herbal products in treating and preventing multiple diseases dates back to ancient history and most of the modern drugs today originated from their significant sources owing to their ability to control multiple targets via different signalling pathways. Among them, flavonoids consist of a large group of polyphenols, which are well known for their various therapeutic benefits. Rutin is considered one of the attractive phytochemicals and important flavonoids in the pharmaceutical industry due to its diverse pharmacological activities via various underlying molecular mechanisms. It is usually prescribed for various disease conditions such as varicosities, haemorrhoids and internal haemorrhage. In this review, we have discussed and highlighted the different molecular mechanisms attributed to the various pharmacological activities of rutin, such as antioxidant, anti-inflammatory, anticancer, anti-allergic and antidiabetic. This review will be beneficial to herbal, biological and molecular scientists in understanding the pharmacological relevance of rutin at the molecular level.

Regardless of advances in detection and treatment, breast cancer affects about 1.5 million women all over the world. Since the last decade, genome-wide association studies (GWAS) have been extensively conducted for breast cancer to define the role of miRNA as a tool for diagnosis, prognosis and therapeutics. MicroRNAs are small, non-coding RNAs that are associated with the regulation of key cellular processes such as cell multiplication, differentiation, and death. They cause a disturbance in the cell physiology by interfering directly with the translation and stability of a targeted gene transcript. MicroRNAs (miRNAs) constitute a large family of non-coding RNAs, which regulate target gene expression and protein levels that affect several human diseases and are suggested as the novel markers or therapeutic targets, including breast cancer. MicroRNA (miRNA) alterations are not only associated with metastasis, tumor genesis but also used as biomarkers for breast cancer diagnosis or prognosis. These are explained in detail in the following review. This review will also provide an impetus to study the role of microRNAs in breast cancer.

Objective: Chitosan, a natural polymer from shelled crustaceans, has been employed in an array of biomedical applications as it possesses a combination of fascinating attributes such as biocompatibility, biodegradability, non-toxicity and ease of chemical alteration into different active derivatives. The ability of chitosan to be tailored into different shapes has made it a very popular polymer for designing novel drug delivery systems for topical, transdermal and gene delivery. Recently, the multifunctional and immunomodulatory properties of chitosan have attracted a lot of attention. Since there are many patents and publications on medicated scaffolds, films and other topical dressings containing chitosan, an effort has been made to collate and synchronize the immunomodulatory properties of chitosan with its wound healing potential. Methods: Literature and patent search was done using major search engines and websites. Based on the studies conducted by various research groups, the information was classified into important subheadings. Results: Most of the studies suggested that due to remarkable immuno-stimulatory activities, chitosan stimulates the release of anti-inflammatory cytokines, chemokines, growth factors and hence promotes and supports every phase of wound healing, including hemostasis, inflammation, cell migration, proliferation, tissue repair and cell regeneration. Conclusion: An understanding of the immunomodulatory activities of chitosan can help the researchers and formulation scientists to use this natural polymer and its derivatives to design controlled release, medicated, self–decomposable, environment-friendly scaffolds for better patient compliance and promising wound-healing effects.

Cessation of menstruation, widely known as menopause is a significant transition period in women’s life. It leads to the arrest of fertility and creates a depletion of the hormones causing physical, mental, sexual, and social problems which lead to a serious decline in their quality of life. The onset of menopause induces certain sudden changes, while others appear in a phasic manner, henceforth demanding an adequate understanding of its progression, adverse impact on life, and exploration of any remedial measures thereof. Menopause, despite being a natural occurrence, brings in significant changes to women’s life, almost sometimes leading to severe debilitation. However, it is still not attended and remains an ignored health issue that warrants the immediate attention of researchers, practitioners, and health policymakers. The present review is an attempt to draw attention towards these women-centric health issues and diligently explores the causes, symptoms and also describes the various procedures for the management of menopausal and postmenopausal syndromes. The review tries to summarise the currently available pharmaceutical interventions and also dwells into herbal and complementary remedies which could ameliorate and provide respite from the etiolating menopausal symptoms.

Background: Obesity has become a global issue, leading to increased risk of metabolic syndrome, which encompasses diabetes, cardiovascular disease, stroke, hypertension, and certain cancers. However, obesity is difficult to control through diet and exercise alone, as they are difficult to implement. Objective: The objective of this review is to elucidate the active constituents that can be obtained from various natural sources that act as anti-obesity agents. Due to the global rise in the prevalence of obesity, an urgent need to prevent and control it has arisen. Methods: For this review, we compiled information about natural anti-obesity products through an electronic search of the articles available via PubMed, Scopus, and other internet sources for the period 1975-2019 and included our own research. We analyzed and organized data on various natural products in popular use in addition to relevant pharmacognostic and biological studies. The products’ mechanisms of action were also investigated. Conclusion: Consumption of diets that include high amounts of active anti-obesity natural compounds is a promising strategy for the suppression of lipid accumulation and adipogenesis in obese individuals.

Background: Nutraceutical is a term that is a combination of nutrition and pharmaceutical. They are believed to improve physical and mental health and provide therapeutic benefit in disease conditions. Nutraceuticals are claimed to be beneficial in several disease conditions which include cardiovascular disorder, neurodegenerative disorders, metabolic disorders and cancer prevention. Objective: In the current review, we will study the current regulatory framework in some of the major countries of the world by comparing different parameters of these regulations. Findings: Global nutraceutical market is currently expanding at a rapid pace but there are some restraints to the market growth which include poor quality manufacturing and unharmonized regulations leading to trade barriers across the globe. Although there are laws and regulations in place which govern nutraceutical products in different countries, these regulations lack harmonization and differ from country to country. Some of the countries follow stringent regulations, whereas, in some of the countries, well-structured and stern regulations for nutraceuticals are lacking. Conclusion: The development of a well regulated, harmonized and research-driven approach can help boost the confidence of consumers in nutraceutical products in the world thereby driving the nutraceutical market.

Endocrine disruptors (EDs) disrupt the standard operation of the endocrine systems, resulting in untoward effects. EDs have gained extensive consideration due to their severe adverse impacts on public and wildlife health. A variety of compounds from both natural and synthetic origin may cause endocrine disruptions. These may be found in industrial chemicals, persistent organic pollutants, and products of regular use including pharmaceuticals, medical equipment, implants, medical/surgical and dental devices, cosmetics, food products, other consumer goods, their packaging and processing materials. Apart from direct consumption or use, these chemicals may impact by entering our food chain or ecosystem. These chemicals act by mimicking the hormones or blocking their receptors or interfering in their normal production, absorption, distribution, metabolism and excretion. The implementation of a regulatory framework on the complex multidisciplinary field of EDs brings enormous challenges, which pose barriers to the regulatory process. This study aims to focus on the key public and ecological health concerns presented by EDs, challenges faced by regulators to achieve successful regulatory proposition and the importance of collaboration endeavours to potentially conquer such challenges. Endocrine-disrupting chemicals (EDCs) or EDs can impact at low exposure levels, bringing about a broad range of health issues including disorders related to reproductive, fetal development, neurological, immunological, metabolic and cancer, etc. They may cause health effects across generations. The regulatory frameworks available across major regulators are tackling the identification of EDs and their mechanisms to provide necessary guidance on the safety and disposal of such substances. However, the challenges faced outweigh the regulatory mechanisms in place. The major challenges are related to structural ranges at times leading to no representative structures, active metabolites, substantiate quantum, delayed effects, epigenetic changes, widespread existence, concentration correlation for different biological species, availability of appropriate methods, exposure to a mixture of chemicals, complex endocrinology principles, unknown sources, routes and mechanisms, impacts at early stages of life, geographical movement of EDs, hazard-based vs. risk-based approaches. Regulators of healthcare and environmentalists needs to collaborate amongst them and with wider stakeholders including industry sponsors to find ways of dealing with such challenges and capitalize on the research-based knowledge grid available across institutions. Existence of EDs, their impact on living beings and mechanism of influence are like a tangled web, which induces difficulties in regulating them with conventional mindset. Conquering these challenges necessitates that regulators should join forces amongst themselves, with other institutions operating for environment, with industry sponsors and researchers to achieve success in public health safety.

Osteoporosis is a progressive bone disease that remains unnoticed until a fracture occurs. It is more predominant in the older age population, particularly in females due to reduced estrogen levels and ultimately limited calcium absorption. The cost burden of treating osteoporotic fractures is too high, therefore, primary focus should be treatment at an early stage. Most of the marketed drugs are available as oral delivery dosage forms. The complications, as well as patient non-compliance, limit the use of oral therapy for prolonged drug delivery. Transdermal delivery systems seem to be a promising approach for the delivery of anti-osteoporotic active moieties. One of the confronting barriers is the passage of drugs through the SC layers followed by penetration to deeper dermal layers. The review focuses on how anti-osteoporotic drugs can be molded through different approaches so that they can be exploited for the skin to systemic delivery. Insights into the various challenges in transdermal delivery and how the novel delivery system can be used to overcome these have also been detailed.

Over the past 20 years, Endocrine Metabolic Immune Disorders-Drug Targets (EMIDDT) journal has been covering a broad field of intertwined topics related to pathogenesis, diagnosis, and therapy of endocrine, metabolic, and immune diseases. At first, the journal publications were restricted to reviews only and, then, original article submissions have also been accepted. EMIDDT represents as a successful journal in continuous expansion with 10 issues in 2020 and a current impact factor (IF) equal to 1.973. Moreover, since 2019, EMIDDT is the official journal of the Italian AME (Associazione Medici Endocrinologi), also linked to the American Association of Endocrinologists. Such a connection has given more impetus to the journal in terms of additional higher-quality submissions. In order to celebrate the 20th anniversary of EMIDDT, the content of some original representative articles published by the journal in the past and current years will be illustrated with special emphasis on cellular and molecular bases of drug targeting.

Background: Dysfunction of the thyroid gland has profound effects on the cardiovascular system. Objective: We aimed to explore the relation of serum thyroid peroxidase antibody (TPO-Ab), as a marker of thyroid autoimmunity with incident hypertension among a euthyroid population. Methods: A total of 3681 participants (1647 men) entered the study. Multivariate Cox proportional hazard models were conducted to estimate the association between TPO-Ab and incident hypertension. Results: The mean age (standard deviation) of the participants was 37.5 (12.8) years. During a median follow-up of 12.2 years, 511 men and 519 women developed hypertension. The multivariable hazard ratios (HRs) and related 95% confidence intervals (CIs) of 1-unit increase in natural logarithm (ln) of TPO-Ab for incident hypertension were 1.09 (1.00-1.19), 1.03 (0.97-1.10), and 1.05 (1.00-1.11) for men, women, and total population, respectively. Moreover, considering the TPO-Ab status as a categorical variable (i.e. TPO-Ab positive or TPO-Ab negative), the multivariate-adjusted HRs (95% CIs) of TPO-Ab positivity for incident hypertension, were 1.33 (0.95-1.85), 1.12 (0.86-1.45) and 1.19 (0.97- 1.46) for men, women, and total population, respectively. Conclusion: Elevated serum TPO-Ab level can contribute to the development of hypertension among euthyroid men during a long follow-up; suggesting a role for thyroid autoimmunity.

Background: The best way to lose body weight, without using drugs and/or suffering hunger and stress, has not yet been defined. The present study tested a low carbohydrate diet, enriched with proteins, in subjects with overweight and obesity. Methods: The study enrolled 22 uncomplicated overweight and obese subjects. Several parameters were examined before and after 6 weeks of a low-carbohydrate diet, enriched with 18 g of whey proteins. Anthropometric (body mass index, waist circumference) variables, fasting hormones (insulin, TSH, FT3, FT4), and metabolic (glucose, prealbumin, and lipid levels) parameters were measured. 25- OH-vitamin D (25 (OH) D), parathyroid hormone (PTH) and osteocalcin, were also quantified. Body composition parameters (fat mass, fat-free mass, body cell mass, total body water) were measured by electrical bioimpedance analysis. As cardiovascular parameters, blood pressure, endothelium flowmediated dilation (FMD), and common carotid artery intima-media thickness were also measured. Results: The low-carbohydrate diet integrated with proteins induced a significant decrease in body weight (P < 0.001), waist circumference (P < 0.001), fat mass (P < 0.001), diastolic blood pressure (P < 0.01), triglycerides (P < 0.001), total cholesterol (P < 0.001), pre-albumin (P < 0.001), insulin (P < 0.001), HOMAIR (P < 0.001), FT3 (P < 0.05), and c-IMT (P < 0.001), and a significant increase in FMD (P < 0.001) and 25 (OH) D (P < 0.001) was also observed. Conclusion: All these results suggest that a short-term non-prescriptive low carbohydrate diet, enriched with whey proteins, may be a good way to start losing fat mass and increase health.

Background: Chronic spontaneous urticaria (CSU, or CU) is a disease that significantly affects the quality of life of patients. It is a chronic disease and requires a specialized approach to diagnosis and treatment. In recent years, the disease has been of great interest due to the existence of new targeted therapeutic approaches. Aim: The present study aims at analyzing CU score concerning time, as a time-series. The authors have attempted to model the investigated time-series to unravel possible causative relationships. Methods: 108 patients (25Males/83Females) admitted to our department were diagnosed with CU. CU was estimated on a score basis, which was used to define disease severity. Urticaria score was assessed on the basis of Urticaria Activity Score 7 (UAS7). The mean CU score, the mean CU score rate concerning the first month at diagnosis as well as the monthly CU score rate were calculated. Results: Gender is a factor that influences CU score with time. In addition, there was a significant finding that time-series differ with the administration of monotherapy or complementary therapy. Conclusion: We have found that females are more prone to CU, while omalizumab monotherapy has more beneficial results as compared to the application of concurrent and maintenance therapies. Further, patients with co-morbidities were more likely to interrupt treatment. Finally, and most significantly, it was shown that monthly CU score rate manifested an oscillatory pattern, which was modelled with the sum of sines functions, highlighting a relative immunological pattern.

Objective: Polyphenols extracted by table grape have been demonstrated to decrease cell proliferation in vitro and to exert anti-atherosclerotic and antithrombotic activities, regulating cell functions. A grape polyphenolic profile is affected by climate as well as a grape cultivar. This study was aimed to characterize the berry skin polyphenolic composition, antioxidant activity and antiproliferative properties of two black grape cultivars, Autumn Royal and Egnatia. Methods: The phenolic composition of Grape Skin Extracts (GSEs) was determined by HPLC analyses. The antioxidant activity was determined using DPPH, ABTS and ORAC tests. Caco2, HT29 and SW480 human colon cancer cell lines were used to test the effects of GSEs in vitro. Cell proliferation and cell cycle were assessed with the MTT method and a Muse cell analyzer, respectively. qPCR and Western Blotting analysis were used to evaluate gene and protein expression, respectively. Results: The total polyphenolic content and the total antioxidant capacity were significantly higher in Autumn Royal than in Egnatia. However, table grape Egnatia showed greater ability to affect cell proliferation and apoptosis, as well as to exert a growth arrest in the S phase of the cell cycle, particularly in the Caco2 cell line. Conclusion: These data suggest that the new grape variety Egnatia is an interesting source of phenolic compounds that could be of interest in the food and pharmaceutical industries.