Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 23, Issue 6, 2023

It is well established the importance of stem cells (SCs) in tissue growth, regeneration and repair, given their ability to self-renew and differentiate into mature cells. Stem cells are present in all individuals and are potentially active to the end of life. However, less is known about their unique function within the immune system as immune regulators and their important task in viral protection. Antiviral resistance is a common mechanism in all cells though stem cells utilize an antiviral RNA interference (RNAi) mechanism, while adult cells react by using the interferondependent repression pathway via interferon-associated protein-based response to induce an antiviral response. Therefore, the idea behind this review is to highlight the mechanisms of viral evasion of host defense, which would then allow us to highlight the rationale use of autologous stem cells and their biochemical and immunological ability to reset the subverted immune responses. Recently, scientists have highlighted their use in the field of immune-therapy, establishing the possibilities of using them outside the conventional protocol with the advancement in manipulating these cells in such a way that specific body activity can be restored. This paper describes the remarkable SCs profile and discusses some ideas regarding their promising use in vivo.

Acromegaly is described as the oversecretion of growth hormone (GH) and, subsequently, insulin-like growth factor 1 (IGF-1), ascribed in most cases to a pituitary adenoma. This disease presents a progressive disfigurement, along with other systemic manifestations, which altogether diminishes the quality of life in the patients. Prolonged exposure to abnormally high levels of GH and IGF-1 levels results in cardiovascular, cerebrovascular, and pulmonary dysfunction which overall produces a fall in life expectancy. Timely diagnosis and further treatment decreased the mortality rate of the patients and showed an improvement in the quality of life. Surgical procedures, advanced radiation therapy tools, and the availability of pharmacological compounds that act on pituitary growth hormone-producing cells have enabled an improved approach to treating the disease. Pharmacological treatment is currently an important management option, and it may also be the first-line treatment in patients with acromegaly who do not benefit from or are ineligible for first-line surgical procedures. From its inception until 2021, we used a comprehensive search strategy on Medline/PubMed, Scopus, Embase, Web of Science, and the Cochrane Library electronic databases. All human research articles and review articles published in English were considered for the review. In this review, we describe the clinical implications and management of patients with acromegaly, consisting of scientific improvements underlying the developing understanding of pathogenesis and diagnosis, associated comorbidities and mortality rate with the disease, and major improvements in the treatment of the disease, along with novel strategies including quality of life and patient-reported outcomes.

Oxidative stress is a major cellular and metabolic burden that can really alter cell life and become the base for disease onset and development. Many widespread pathologies can develop from an unresolved oxidative stress situation; thus, addressing this state is paramount for human health. Our antioxidant enzymes sometimes are not just enough. Fortifying our defense and the antioxidant and anti-inflammatory system can make a difference in our health: if this is attainable with our dietary habits, it could be a dream come true. Polyphenols are a fantastic tool indeed in the fight against oxidative stress: they are easy to obtain, with little cost, no side effects, and have a multitude of metabolic actions. This perspective review would shed light on polyphenol’s metabolic and molecular action regarding oxidative stress to help preserve our health.

Background: Since the discovery of penicillin, natural antibiotics have protected humans from malicious microbes. A breakthrough, however, is needed to tackle problems like antimicrobial resistance (AMR). This review introduces one of the new approaches for the prevention of several diseases through a healthy diet, grape phytochemicals, and vitamin D, which nurture the growth of beneficial bacteria, including gut microbiota, suppressing chronic inflammation and up-regulating immunity. Antibiotics provide protection against infectious diseases by preventing the growth of pathogenic microbes. However, inappropriate use of antibiotics increases antimicrobial resistance to bacteria and limits the benefits of antibiotics. In addition, it is well known that antibiotics kill not only pathogenic microbes but also beneficial ones that reside in healthy individuals. As a result, the excess use of antibiotics increases the threat of diseases caused by antibiotic-resistant bacteria. We can reduce the risk of several diseases, including infectious diseases, in the future by nurturing the good microbes that live in the human body, thereby preventing chronic inflammation induced by the proinflammatory cytokine TNF-α, improving predisposition, and up-regulating immunity. Along with human evolution, residing bacteria in the skin, digestive system, and other areas have changed. They defend their hosts from malicious microbes in the surrounding environment. With the progress of medicine, science, and technology, the quality of life and environmental public health have improved over the years. Under these circumstances, it is necessary to reduce the risk of illness and keep ourselves healthy by nurturing the good resident microbiota in our bodies and preventing chronic inflammation through the diet and the intake of phytochemicals and vitamin D. This new approach is important, along with the traditional method for preventing emerging infectious diseases in the future.

Aims and Background: The knowledge about the effective implementation of different exercise training methods on clinical and endocrinological responses in soccer players with chronic low back pain (LBP) is lacking. Hence the study is proposed to find the effects of different exercise training methods on clinical and endocrinological responses in soccer players with chronic low back pain. Methods: Through the three-block randomization method, 60 chronic LBP participants were randomly divided into the isokinetic exercise group (IKE; n = 20), (CSE; n = 20), and conventional exercise group (n = 20). They received respective training for four weeks. Clinical (pain intensity & kinesiophobia) and endocrinological (glucose, insulin, HOMA-IR, growth hormone, prolactin, ACTH, and cortisol) values were measured at baseline, after 4 weeks, and at 3 months follow up. Results: The baseline data between the groups showed no statistical difference (p ≥ 0.05). Four weeks following training IKE group showed significant changes in pain intensity and kinesiophobia than CSE and conventional training groups (p < 0.05). After 4 weeks of training, all the serum hormone variables show significant changes between the groups (glucose; p = 0.049, insulin; p = 0.005, HOMA-IR; p = 0.021, growth hormone; p = 0.006, prolactin; p = 0.001, ACTH; p = 0.001 and cortisol; p = 0.001). At 3 months follow up, the values for Glucose and Insulin (p > 0.05) variables did not show any statistical changes, but the rest of the variables (p = 0.001) showed significant differences. However, the maximum improvement was seen in the IKE group as calculated by the post hoc Tukey-Kramer’s test. Conclusion: Our study suggested that strength training through isokinetic exercises improved pain, kinesiophobia status, and temporary changes in serum stress hormone levels than other training methods in soccer players with chronic low back pain.

Background: Chronic low-grade inflammation is involved in the pathogenesis of postmenopausal osteoporosis, but the cytokines implicated remain elusive. Objective: This study aimed to compare the difference in cytokine profile between postmenopausal women with and without osteoporosis in Klang Valley, Malaysia. Methods: Postmenopausal women with (n = 20) and without osteoporosis (n = 20) were recruited for this study. Their bone health status was determined using dual-energy X-ray absorptiometry. Their fasting blood was collected for proteomic analysis. A protein array was performed for four subjects randomly selected from each group to screen the potential cytokines. Three cytokines at least 20% different between groups and consistently expressed by each subject were selected for validation using enzyme-linked immunosorbent assays (ELISA). Results: The protein array screening demonstrated that platelet-derived growth factor-BB, interleukin- 6 receptor (IL-6R), and tissue inhibitor of metallopeptidase-2 were higher in women with osteoporosis than women without osteoporosis (n = 4 per group), and consistently expressed by all women. Only body mass index (BMI)-adjusted logarithmically transformed IL-6R levels were lower among postmenopausal women with osteoporosis compared to women with normal bone health (p = 0.026) (n = 16 per group) in the ELISA test. Conclusion: IL-6R was lower among postmenopausal women with osteoporosis compared to women with normal bone health after adjusting for BMI. However, a large-scale epidemiological study with proteomic analysis needs to confirm the findings.

Aims: Metformin is the most widely used drug for the first-line treatment of type 2 diabetes mellitus (T2DM), but its use and schedule have been poorly investigated in elderly patients. Methods: We conducted an observational, cross-sectional, multicentric study on metformin in T2DM outpatients older than 65 years who were taking the drug for at least 6 months and referred to Italian Endocrinology and Diabetology Services. The primary endpoint was daily metformin dose, and secondary endpoints were the correlations between metformin dose and age, comorbidities, and concomitant use of other drugs. The study was open to all members of AME (Associazione Medici Endocrinologi). Results: Fifteen Italian centers recruited 751 consecutive participants (42.9% older than 75 years, 48.6% females). T2DM duration was 12.9 ± 9.7 years (longer than 10 years in 53.8%). Metformin had been used for 10.3 ± 6.8 years (longer than 10 years in 52.4%). Metformin dose was 1.6 ± 0.9 g/day (>1.5 g/day in 63.4%). As compared to the youngest, participants older than 75 years did not differ for metformin daily dose or number of administrations. Metformin dose was significantly directly correlated to eGFR, diabetes duration, and metformin treatment duration. Conclusion: In this real-world study, the minimum daily effective dose of metformin was prescribed in more than half of older T2DM outpatients.

Aim: A co-formulation containing insulin degludec and insulin aspart (IDegAsp) is available for the treatment of diabetes in Turkey. We aimed to evaluate the clinical results of switching to IDegAsp treatment for Type 2 diabetes. Methods: A total of 217 patients with type 2 diabetes treated with IDegAsp and having follow-up data were included. The patients were divided into 3 groups. Group 1 switched from basal insulin to IDegAsp, group 2 switched from twice-daily premixed insulin regimen to IDegAsp, and group 3 switched from intensive and thrice-daily premixed insulin regimen to IDegAsp. Groups were evaluated in terms of changes in insulin dose, the number of injections, and changes in HbA1c. Results: The mean follow-up period was 7.5 ± 4.4 months. The mean age was 62.8 ± 12.9 years. The mean duration of diabetes was 15.3 ± 8 years. There was a significant decrease in HbA1c and glucose (p < 0.0001 and p < 0.0001, respectively). HbA1c was significantly reduced in group 1 (p < 0.0001) while insulin dose and the number of injections increased (p < 0.0001 and p < 0.0001, respectively). HbA1c, insulin dose, and the number of injections in group 2 and group 3 (p = 0.001, p = 0.002, p < 0.0001, respectively, and p < 0.0001, p = 0.043, p < 0.0001, respectively) were significantly reduced. Conclusion: This study includes real-life experiences involving a remarkable number of patients in the literature. IDegAsp treatment provided effective blood glucose regulation and caused a significant decrease in the insulin dose and the number of injections, resulting in increased quality of life among those who had to receive twice or more insulin injections.

Background: It has been observed that the lunar phases alter the fasting plasma glucose (FPG) level in type-2 diabetic (T2DM) subjects. Diabetic peripheral neuropathy (DPN) was also reported to be associated with elevated foot temperature (FT), oxidative stress, and inflammation in T2DM subjects. Objectives: The purpose of the present study was to evaluate the changes in FT, oxidative stress, and inflammation levels and assess the relationship of FT with oxidative stress, antioxidant enzyme activity, and inflammatory markers in T2DM subjects at different lunar phases. Methods: The plasma glucose, glycated hemoglobin, and dorsal and plantar surface temperatures of the feet by infrared dermal thermometer were measured in 88 randomly selected T2DM subjects at different lunar phases. The levels of oxidative stress and inflammation were assessed by measuring malondialdehyde (MDA), glucose 6-phosphate dehydrogenase (G6PDH), and tumor necrosis factoralpha (TNF-α). Results: The FTs, MDA, and TNF-α were significantly increased, and G6PDH activity was significantly decreased in the new moon (NM) and full moon (FM) than in the third quarter (TQ) and first quarter (FQ) for both sexes. The FTs, MDA, and TNF-α levels were significantly positively correlated, whereas G6PDH activity was significantly negatively correlated with FPG at NM and FM in both sexes. The MFT was significantly positively correlated with MDA and TNF-α and significantly negatively correlated with G6PDH at NM and FM in T2DM subjects. Conclusion: The lunar phases showed a prominent influence on the FT, oxidative stress, and inflammatory status in T2DM subjects, which might be due to the existence of biological rhythm interaction with lunar electromagnetic radiations.

Background and Aim: Chronic kidney disease (CKD) is characterized by persistent lowgrade inflammation. Soluble CD14 (sCD14) is involved in many pathological conditions, including inflammation and atherosclerosis. The present study aimed to assess the relationship between sCD14 levels, subclinical atherosclerosis (SCA), inflammation and mortality in Egyptian hemodialysis (HD) patients. Patients and Methods: The present longitudinal study included 62 HD patients. All patients were submitted to careful history taking, thorough clinical examination and laboratory assessment for high-sensitivity C-reactive protein (hsCRP) and sCD14. Carotid intima-media thickness (CIMT) was also assessed. Patients were followed for a maximum of 18 months. The primary outcome is patients’ mortality. Data were statistically analyzed using standard descriptive, comparative, correlative and regression methods. Results: The present study was conducted on 62 HD patients. They comprised 34 males and 28 females with an age of 54.6 ± 9.0 years. At the end of follow-up, 12 patients (19.4 %) died. It was shown that survivors had significantly lower hsCRP levels (104.2 ± 38.2 versus 134.1 ± 15.3 mg/dL, p < 0.001), lower sCD14 levels (32.7 ± 10.3 versus 47.4 ± 18.4 μg/mL, p = 0.02) and lower CIMT (1.32 ± 0.5 versus 1.5 ± 0.2 mm, p = 0.049). sCD14 levels were significantly correlated with hsCRP (r = 0.4, p = 0.001) and CIMT (r = 0.31, p = 0.013). Multivariate analysis identified HD duration [HR (95% CI): 1.02 (1.0-1.04), p = 0.021] and sCD14 levels [HR (95% CI): 1.06 (1.0-1.12), p = 0.026] as significant predictors of patients’ survival. Conclusions: sCD14 levels in this cohort of HD patients are well-correlated with hsCRP levels and CIMT. In addition, they are significant predictors of patients’ mortality.

Background: Type 1 diabetes mellitus (T1DM) is a chronic disease caused by the destruction of insulin-producing pancreatic β-cells. During disease progression, inflammatory insulitis increases the presentation of islet antigens on human leukocyte antigen (HLA) molecules to T lymphocytes. This complex system plays a pivotal role in cellular immunity. Thus, genetic variability in HLA can affect the susceptibility to and clinical outcomes of DM. Aim: This case-control study aimed to assess the role of HLA-DP-rs3077 (A/G) and HLA-DQrs3920 (A/G) polymorphism in T1DM. Subjects and Methods: This study enrolled 400 individuals: 200 patients with T1DM and 200 ageand sex-matched healthy controls. Hemoglobin A1C and random, fasting, and postprandial blood sugar levels were determined for all subjects. Genotypic and allelic distributions of HLA-DPrs3077 (A/G) and HLA-DQrs3920 (A/G) SNPs were determined using real-time polymerase chain reaction (PCR). Results: Frequency of the HLA-DPrs3077A allele was high among the diabetic group (91.3%); however, the difference was non-significant [OR (95% C.I) = 1.422(0.89-2.252), P=0.098]. The frequency of the HLA-DQrs3920 GG genotype was higher in control than the diabetic group (52.5% vs.12%), whereas that of the AA genotype was higher in the person with diabetes than in the control group (34% vs.4%). Individuals carrying the HLA-DQrs3920A allele were 4.5 times more likely to have T1DM than those carrying the G allele [OR (95% C.I) = 4.510 (3.338- 6.094), P<0.001*]. The presence of HLA-DPrs3077A and HLA-DQ rs3920A in the same person increases T1DM risk by 3.6 times that of G allele [OR (95%C.I) = 3.608(2.173-5.991), P<0.001*]. Conclusion: HLA-DPrs3077 and HLA-DQrs3920 SNPs have a role in T1DM as the coexistence of HLA-DPrs3077A and HLA-DQrs3920A alleles increases the risk.

Background: The population prevalence of functional alterations and thyroid autoimmunity is high, and numerous genetic and environmental aspects have been described as triggering factors. Objectives: The objective of this study was to determine the prevalence of functional alterations and thyroid autoimmunity in an urban population of Colombia. Materials and Methods: It is a cross-sectional, population-based study (n = 9,638) conducted on an urban population of Popayán-Cauca-Colombia between February 5th, 2018, to December 11th, 2021. The variables evaluated were thyrotropin (TSH), free T4 (FT4), and anti-thyroid antibodies (thyroid peroxidase antibodies: TPOAb, and thyroglobulin antibodies: TgAb). Results: TSH in men was significantly higher than in women. No differences were observed in the values of FT4, TPOAb, and TgAb (according to sex). The prevalence of normal thyroid function and subclinical hypothyroidism was significantly higher in men. The positivity of TPOAb and TgAb was 22.3% and 19.2%, respectively. TSH levels increased with age (both in men and in women). In participants with normal FT4 and negative TPOAb, the TSH was significantly higher. TSH was significantly higher in TPOAb-positive individuals and among those with TPOAb and TgAb positives, as well as in women with positive TPOAb and men with positive TPOAb and TgAb. Conclusion: In an urban population of Colombia, TSH was found to be higher than in populations of other geographical areas, especially in older individuals and in the presence of positive anti-thyroid antibodies, a high prevalence of functional alterations and thyroid autoimmunity was also found. These findings can be explained by excess iodine consumption and some environmental factors.

Background: Hypothyroidism is a commonly encountered endocrine disorder presenting in various clinical settings. It usually presents with classic manifestations, which are readily recognized and, therefore, easy to diagnose. However, occasionally, patients present with unusual symptoms, which becomes a challenge to diagnose. Thyroid dysfunction affects many body organs, including the gut and viscera. Studies show that intestinal motility might be affected by multiple factors, such as neuromuscular dysfunction, myopathy, or alterations in hormone receptors. Case Presentation: Here, we present the first case of a 21-year-old female student who had complaints of recurrent nausea, vomiting, loose stool, abdominal pain, and weight loss. In the second case, a 25-year-old male student presented with recurrent nausea, vomiting, loose stool, and weight loss. Their unremarkable blood routines and gastrointestinal-specific investigations failed to ascertain the diagnosis. Later, primary hypothyroidism was established by typical biochemical abnormalities. Conclusion: Thyroxine replacement treatment successfully resolved the presenting symptoms and normalized biochemical reports.

Aim: This guideline (GL) is aimed at providing a reference for the management of non-functioning, benign thyroid nodules causing local symptoms in adults outside of pregnancy. Methods: This GL has been developed following the methods described in the Manual of the National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology (AME) identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as “critical” and “important” were considered in the systematic review of evidence and only those classified as “critical” were considered in the formulation of recommendations. Results: The present GL contains recommendations about the respective roles of surgery and minimally invasive treatments for the management of benign symptomatic thyroid nodules. We suggest hemithyroidectomy plus isthmectomy as the first-choice surgical treatment, provided that clinically significant disease is not present in the contralateral thyroid lobe. Total thyroidectomy should be considered for patients with clinically significant disease in the contralateral thyroid lobe. We suggest considering thermo-ablation as an alternative option to surgery for patients with a symptomatic, solid, benign, single, or dominant thyroid nodule. These recommendations apply to outpatients, either in primary care or when referred to specialists. Conclusion: The present GL is directed to endocrinologists, surgeons, and interventional radiologists working in hospitals, in territorial services, or private practice, general practitioners, and patients. The available data suggest that the implementation of this GL recommendations will result in the progressive reduction of surgical procedures for benign thyroid nodular disease, with a decreased number of admissions to surgical departments for non-malignant conditions and more rapid access to patients with thyroid cancer. Importantly, a reduction of indirect costs due to long-term replacement therapy and the management of surgical complications may also be speculated.