Endocrine, metabolic & immune disorders drug targets最新文献

Background and objectives: Rheumatoid arthritis (RA) is a type of arthritis that damages joints and can affect the thymus and the spleen. RA is an autoimmune disorder in which the immune system targets the body's own tissues. The causes of RA are unknown, although a genetic link is thought to be involved. The objective of this research was to evaluate the effect of curcumin, mesenchymal stem cells (MSCs), and their combination on the disruption of serum cytokines, ankle joint, thymus and spleen histopathology, and affected genes in complete Freund's adjuvant (CFA)-induced arthritis in male and female Wistar rats.

Methods: Experimental animals were organized into 16 groups (6 animals for each), eight groups including male rats and the other eight groups including females rats. The groups are normal control, CMC, curcumin, MSCs, CFA, CFA/curcumin, CFA/ MSCs and the arthritic group treated with MSCs and curcumin. One subcutaneous injection of 0.1 mL CFA was given to rats into the right hind leg footpad to induce RA. The arthritic rats were intravenously injected three times with bone marrow-derived MSCs (BM-MSCs) and/or treated orally with curcumin daily (100 mg per kg body weight per day) for 21 days.

Results: Curcumin and BM-MSCs work together to dramatically (P < 0.05) restore the high serum PGE2 and IL-17 levels and lower the IL-13 level in arthritic rats to normal levels. Deleterious effects on the spleen and thymus histological structure were counteracted. Gene expression of COX-1 and IL-6 was increased and IL-4 was decreased; these changes were improved by the combination treatment (P < 0.05).

Conclusion: Based on these findings, additive therapeutic effects on RA occur from the combined treatment of curcumin and BM-MSCs compared with their individual use (P < 0.05). Thus, it can be said that both curcumin and BM-MSCs are effective at reducing inflammation while also having beneficial effects on the ankle joint, thymus and spleen.

Introduction: Amyloid goiter is a rare disease characterized by amyloid deposits that cause sudden growth in the thyroid gland.

Case presentation: Here we present a case of a 26-year-old woman with euthyroid amyloid goiter who presented with subacute granulomatous thyroiditis clinic. Amyloid goiter was detected as a result of core biopsy from the thyroid parenchyma of the patient with sudden thyroid enlargement. Surgery was not applied to the patient who had no pressure symptoms or signs. In systemic amyloidosis secondary to Familial Mediterranean fever, heart and kidney involvement, as well as the thyroid gland, were detected.

Conclusion: Amyloid accumulation should be considered in addition to anaplastic thyroid cancer and lymphoma in patients with sudden thyroid enlargement. It should not be overlooked that amyloid goiter may mimic subacute thyroiditis clinic. Systemic amyloidosis should be considered in patients with amyloid goiter, and an examination should be made to assess the presence of amyloid accumulations in other organs.

Background: The medicinal plants of the Cucurbitaceae family, such as Solena heterophylla Lour. fruits, have significant ethnobotanical value and are readily accessible in North East India.

Aims: We conducted a study on Solena heterophylla Lour. fruits to evaluate their anti-diabetic activity in vivo, standardize their HPTLC, and profile their metabolites using LC-QTOF-MS. We aimed to explore the molecular mechanism behind their effects on oxidative stress and glycosylated hemoglobin (HbA1c).

Methods: Firstly, the ethyl acetate fraction of Solena heterophylla Lour. fruits was standardized using Cucurbitacin B as a standard marker by conducting HPTLC evaluation. Next, we delved into analyzing metabolite profiling. In addition, the standardized fraction was utilized in an experimental study to investigate the molecular mechanism of action in an in vivo high-fat diet and a low dose of streptozotocin-induced diabetic model.

Results: We have reportedly identified 52 metabolites in the ethyl acetate fraction of Solena heterophylla (EASH). In the in vitro tests, it has been observed that this extract from plants possesses notable inhibitory properties against α-amylase and α-glucosidase. Solena heterophylla fruits with high levels of Cucurbitacin B (2.29% w/w) helped lower FBG levels in animals with EASH treatment. EASH treatment reduced HbA1c levels and normalized liver lipid peroxidation and antioxidant enzyme levels. SGOT, SGPT, and SALP serum enzyme levels also returned to normal.

Conclusion: Based on the current evaluation, it was found that EASH exhibited encouraging hypoglycemic effects in diabetic rats induced by a low dose of STZ and high-fat diet, which warrants further investigation.

Background: Plant-derived bioactive molecules have been a major source of therapeutic agents for human and veterinarian purposes. Different traditional medicine system across the globe had relied on natural resources to meet their demand of healthcare. Still in modern world, pharmaceutical industries look for phytochemicals to develop new drugs. The current review explores patuletin, a flavonoid for its diverse reported pharmacological activities along with its analytical techniques.

Methods: Scientific data published on patuletin was collected from Scopus, Science Direct, Pubmed, Google, and Google Scholar. The collected data were analyzed and arranged as per specific pharmacological activities performed using in-vitro or in-vivo methods. Analytical methods of patuletin have been presented next to pharmacological activities Results: Available scientific literature indicates patuletin has anti-inflammatory, cytotoxic, genotoxic, hepatoprotective, antiproliferative, antiplatelet, antinociceptive, and antioxidant activity. In addition to these activities, its biological potential on breast cancer, rheumatoid arthritis, aldose reductase, and different types of microorganisms has been also presented in this work. Analytical data on patuletin signified the importance of patuletin for the standardization of herbal products and derived medicine.

Conclusion: It may be concluded that patuletin with its diverse biological activities and readily available analytical methods, holds the potential to be translated into a new drug entity.

Inborn errors of metabolism (IEMs) are a vast array of inherited/congenital disorders, affecting a wide variety of metabolic pathways and/or biochemical processes inside the cells. Although IEMs are usually rare, they can be represented as serious health problems. During the neonatal period, these inherited defects can give rise to almost all key signs of liver malfunction, including jaundice, coagulopathy, hepato- and splenomegaly, ascites, etc. Since the liver is a vital organ with multiple synthetic, metabolic, and excretory functions, IEM-related hepatic dysfunction could seriously be considered life-threatening. In this context, the identification of those hepatic manifestations and their associated characteristics may promote the differential diagnosis of IEMs immediately after birth, making therapeutic strategies more successful in preventing the occurrence of subsequent events. Among all possible liver defects caused by IEMs, cholestatic jaundice, hepatosplenomegaly, and liver failure have been shown to be manifested more frequently. Therefore, the current study aims to review substantial IEMs that mostly result in the aforementioned hepatic disorders, relying on clinical principles, especially through the first years of life. In this article, a group of uncommon hepatic manifestations linked to IEMs is also discussed in brief.

Background: Chronic stress is a condition of pressure on the brain and whole body, which in the long term may lead to a frank disease status, even including type 2 diabetes (T2D). Stress activates the hypothalamus-pituitary-adrenal axis with release of glucocorticoids (GCs) and catecholamines, as well as activation of the inflammatory pathway of the immune system, which alters glucose and lipid metabolism, ultimately leading to beta-cell destruction, insulin resistance and T2D onset. Alteration of the glucose and lipid metabolism accounts for insulin resistance and T2D outcome. Furthermore, stress-related subversion of the intestinal microbiota leads to an imbalance of the gut-brain-immune axis, as evidenced by the stress-related depression often associated with T2D. A condition of generalized inflammation and subversion of the intestinal microbiota represents another facet of stress-induced disease. In fact, chronic stress acts on the gut-brain axis with multiorgan consequences, as evidenced by the association between depression and T2D. Oxidative stress with the production of reactive oxygen species and cytokine-mediated inflammation represents the main hallmarks of chronic stress. ROS production and pro-inflammatory cytokines represent the main hallmarks of stress-related disorders, and therefore, the use of natural antioxidant and anti-inflammatory substances (nutraceuticals) may offer an alternative therapeutic approach to combat stress-related T2D. Single or combined administration of nutraceuticals would be very beneficial in targeting the neuro-endocrine-immune axis, thus, regulating major pathways involved in T2D onset. However, more clinical trials are needed to establish the effectiveness of nutraceutical treatment, dosage, time of administration and the most favorable combinations of compounds. Therefore, in view of their antioxidant and anti-inflammatory properties, the use of natural products or nutraceuticals for the treatment of stress-related diseases, even including T2D, will be discussed. Several evidences suggest that chronic stress represents one of the main factors responsible for the outcome of T2D.

Aims: This cross-sectional study aimed to analyze the relationship between live birth and the prevalence of obesity in Chinese women over 40 years of age.

Methods: From April to November 2011, the Endocrinology Branch of the Chinese Medical Association conducted the REACTION project, a national, multicenter, cross-sectional study of Chinese adults aged 40 years and older. Demographic and medical data were collected through validated questionnaires and equipment. Anthropometric indicators, blood pressure, and biochemical data were measured by professional medical personnel. Data were analyzed using descriptive statistics and logistic analysis. Multivariate regression models were used to analyze obesity-related risk factors.

Results: The prevalence of obesity among women increased gradually from 3.8% to 6.0% with an increasing number of live births. Women with two live births had the highest prevalence of overweight at 34.3%. Overall, the obesity and overweight rates were slightly higher in premenopausal women than in postmenopausal women. Univariate regression analysis showed that the risk of obesity in women increased with an increasing number of live births. In addition, multivariate regression analysis showed that the risk of obesity increased with an increasing number of live births in women with systolic blood pressure (SBP) < 121 mmHg or current smoking (P < 0.05).

Conclusion: The risk of obesity increases with the number of live births in Chinese women over 40 years of age with SBP < 121 mmHg or current smoking. Our findings may facilitate the development of interventions to prevent obesity in this population.

Introduction: The prevalence of hypothyroidism increases along with aging, resulting in one of the most common comorbidities among patients over 75 years. The leading causes of hypothyroidism in older adults are iatrogenic, Hashimoto's thyroiditis, and medications. The narrative review aimed to discuss the clinical characteristics of hypothyroidism in older adults and the impact of hormonal replacement therapy on survival rates. Thyroid function declines over time due to physiological changes in the thyroid stimulating hormone signaling, iodine absorption and metabolism, thyroid hormone metabolism, and activity at peripheral sites. A serum TSH value over the upper limit of the normal reference range is not necessarily attributable to hypothyroidism. However, an appropriate diagnosticwork-up is required to rule out true hypothyroidism and discriminate the etiology (i.e., thyroid autoimmune diseases, iodine deficiency, drug-induced hypothyroidism). Levothyroxine treatment should be considered in cases of overt hypothyroidism. A complete risk-to-benefit assessment, particularly considering the overall health status, life expectancy, cognitive function, mood, and cardiovascular and neurological background, should be considered before treating subclinical hypothyroidism with more potential benefits in patients under 75 years old. Levothyroxine formulations facilitating hormone absorption and increasing compliance to long-term treatment should be preferred. TSH target should usually be set over 3 mIU/ml. Defining optimal diagnostic approaches and targeted therapeutic strategies should be considered in the personalized management of aged patients with hypothyroidism.

Background: Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (HR-NSAIDs) are common adverse events related to the widespread use of over-the-counter NSAIDs for the treatment of a variety of inflammatory conditions. Urticaria is the most commonly reported immediate cutaneous clinical sign of HR-NSAIDs, but it can be a manifestation of pathophysiologically different clinical entities that require different therapeutic strategies. The aim of this study is to ease the identification of the correct phenotype of HR-NSAIDs in patients reporting urticaria associated with the intake of NSAIDs and provide updated information about their diagnosis and management.

Methods: The study is a narrative review conducted by collecting the most relevant and up-todate data related to the classification, pathophysiology, severity, and prognosis of NSAID hypersensitivity reactions. PubMed and Embase scientific databases were used as search engines to select relevant articles.

Results: Patients developing HR-NSAIDs can be divided into two categories: selective responders (SR), who develop reactions after the administration of a single specific NSAID due to an underlying IgE or T-cell mediated hypersensitivity mechanism, or cross-intolerant (CI), who develop reactions to more than one chemically unrelated NSAIDs due to abnormalities in the biochemical pathways related with prostaglandin metabolism, independently from an underlying immunological mechanism. Five major different categories of HR-NSAIDs have been identified: NSAIDs-exacerbated cutaneous disease (NECD), NSAIDs-induced urticaria/angioedema with/without respiratory and systemic symptoms of anaphylaxis (NIUAA), and NSAIDsexacerbated respiratory disease (NERD), which are developed by CI patients, and single NSAIDs-induced urticaria, angioedema and/ or anaphylaxis (SNIUAA) and single NSAIDsinduced delayed hypersensitivity reactions (SNIDHR), which are developed by CI patients. In vivo and in vitro diagnostic tests have rarely been shown to be reliable in all these entities and therefore are not routinely used in clinical practice. The management in SR patients consists of strict avoidance of the culprit drug, while for cross-intolerance reactions oral tolerance tests with safe alternative drugs (e.g. weak COX-1 inhibitors or selective COX-2 inhibitors) can be performed.

Conclusion: HR-NSAIDs are being observed with increasing frequency, however, the pathogenesis behind some NSAIDS-associated clinical entities is still unclear. Diagnosis is mostly based on a thorough clinical history and confirmed by a drug challenge test. Clinical management is based on strict avoidance and use of alternative tolerated medications. Overall, all therapeutic decisions depend on the correct identification of the type of reaction the patient experienced.

Background: Autoimmunity can be the first or predominant manifestation in patients with primary immunodeficiency disorder, also known as inborn errors of immunity (IEI). This study aims to evaluate the immune status of pediatric patients with polyautoimmunity to identify those with underlying immune defects.

Methods: In this cross-sectional study, pediatric patients with polyautoimmunity including at least one confirmed autoimmune endocrine disease were enrolled. Demographic and clinical data were collected using a questionnaire based on medical records and direct family interviews. For each patient, a basic immunologic evaluation was performed. The clinical diagnosis was established according to the criteria of the European Society for Immunodeficiencies (ESID). Based on the presence or absence of a history of severe and/or recurrent infections, patients were divided into two groups for comparison.

Results: Thirty-nine patients, 18 males (46.2%) and 21 females (53.8%), were included. Fourteen patients (35.9%) had consanguineous parents. Fifteen patients (38.5%) had a history of severe and/or recurrent infections. The median (interquartile range: IQR) age of our patients at the time of evaluation was 11.1 (9-16) years. The median (IQR) age at the onset of infections and autoimmunities were 3 (1-10.8) and 5 (2.6-8) years, respectively. The most common infectious complications reported were pneumonia and candidiasis, each in 12.8% of the patients. The most prevalent autoimmune disorders were type 1 diabetes (74.3%) and autoimmune thyroiditis (58.9%). IEI was diagnosed in six patients (15.38%), five of which were from the group with severe or recurrent infections: three with selective IgA deficiency, two with common variable immunodeficiency (CVID), and one with immune dysregulation, polyendocrinopathy, enteropathy, Xlinked (IPEX), but without a history of infections.

Conclusion: The occurrence of early onset polyautoimmunity in association with severe and/or recurrent infections or in patients with a positive family history should be a warning sign for physicians to initiate an evaluation for possible immunodeficiency disorders to prevent complications through early treatment.