Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 24, Issue 4, 2024

Mitochondria are essential organelles for the survival of a cell because they produce energy. The cells that need more mitochondria are neurons because they perform a variety of tasks that are necessary to support brain homeostasis. The build-up of abnormal proteins in neurons, as well as their interactions with mitochondrial proteins, or MAM proteins, cause serious health issues. As a result, mitochondrial functions, such as mitophagy, are impaired, resulting in the disorders described in this review. They are also due to mtDNA mutations, which alter the heritability of diseases. The topic of disease prevention, as well as the diagnosis, requires further explanation and exploration. Finally, there are treatments that are quite promising, but more detailed research is needed.

Background: Thyroid nodules are a common disease in endocrine clinical practice. They are often benign, asymptomatic, and do not require any treatment. But, in a non-negligible proportion, they can cause local symptoms of compression or esthetic concerns. In the last two decades, the advent of laser ablation (LA) has become a valid alternative to surgery for these nodules. Moreover, LA has also been successfully used to treat small thyroid cancers and neck recurrence. Objective: This study aims to review and summarize the published literature regarding LA in the treatment of benign and malignant thyroid nodules. Methods: A comprehensive literature search on PubMed from 2000 to 2023 was carried out. The search terms included: thyroid, nodules, laser, cancer, lymph node metastasis, and autonomously functioning nodules. The most relevant investigations in the field were selected. Results: In the last two decades, a very remarkable number of papers consistently demonstrated that LA is able to durably shrink benign nodules on average by about 50%; better results are obtained in spongiform nodules with a volume less than 15 ml; 500 J/ml of tissue should be administered. LA may be a valid option to treat autonomously functioning nodules and papillary thyroid cancers especially if they are <10 mm, and with neck recurrence in patients already submitted to surgery. LA has also been demonstrated to be cost-effective compared to surgical treatment both in benign and malignant lesions, with similar outcomes. Conclusion: Evidence demonstrated that LA is a valid alternative to surgery in benign and malignant thyroid lesions, but also to obtain a successful treatment, a careful selection of the lesion is mandatory.

Obesity is a chronic lifestyle issue with devastating results. Behavioral changes are one of the initial lines of management strategies for obesity, but they are not very efficient management strategies. Many people also use surgical intervention to maintain a healthy weight, now considered to be the most common and effective obesity management. Chemically synthesized medicines fill the gap between lifestyle interventions and minimally invasive surgical management of obesity. The most common issue associated with monotherapy without side effects is its moderate effectiveness and higher dose requirement. Combination therapy is already used for many serious and complicated disease treatments and management and has shown efficacy as well. Generally, we use two or more medicines with different mechanisms of action for a better effect. The commonly used combination therapy for obesity management includes low-dose phentermine and prolonged and slow-releasing mechanism topiramate; naltrexone, and bupropion. Phentermine with inhibitors of Na-glucose cotransporter-2 or glucagon-like peptide-1 (GLP-1) agonists with gastric hormone or Na-glucose cotransporter-2 are two more viable combo therapy. This combination strategy aims to achieve success in bariatric surgery and the scientific community is working in this direction.

COVID-19 is still a world disaster; however, its vaccination is globally available. Liver and gastrointestinal disturbances occur in patients infected with COVID-19 at varying incidences. Aging decreases the functions of the liver. Thus, the elderly have a weaker response to the COVID-19 virus. The COVID-19 virus affects the liver directly through direct and indirect mechanisms. It directly affects the renin-angiotensin system or indirectly causes sepsis, uncontrolled immune reactions, drug-related hepatic injury, and cytokine storm. Also, COVID-19 vaccines and anti-drugs have adverse effects on the liver too. Thus, this review explores the effect of enhancing aerobic capacity as a nonpharmacological intervention on decreasing COVID- 19-induced liver injury. Enhancing aerobic capacity decreases COVID-19-induced liver injury through the following: 1) downregulating systemic and tissue ACE/ANG II/AT1R axis, upregulating ACE2/ANG 1–7/Mas axis, and moving the renin-angiotensin system to the direction of the ACE2/ANG (1–7)/Mas axis, 2) Improving mitochondrial function and oxygenation to body and lung tissues, causing a decrease in harmful oxidative reactions, 3) Increasing the processing of accumulated free radicals and inhibiting the acute respiratory distress syndrome, 4) Acting as an antioxidant to protect the liver from oxidative stress, 5) Increasing the effect of antiviral drugs and COVID-19 vaccines, which improves the function of immune biomarkers, decreases the viral load, and increases the body's defense against the virus, 6) Decreasing coagulation abnormalities and thrombosis. In conclusion, enhancing aerobic capacity may be an efficient nonpharmacological intervention to decrease COVID-19-induced liver injury in elderlies and regenerate the liver to its normal status after being infected by the COVID-19 virus. It also helps to strengthen the body's immunity for better effects of both COVID-19 vaccination and drugs.

Approximately 50% of the adult global population is projected to suffer from some form of metabolic disease by 2050, including metabolic syndrome and diabetes mellitus. At the same time, this trend indicates a potential increase in the number of patients who will be in need of implant-supported reconstructions of specific bone regions subjected to inflammatory states. Moreover, physiological conditions associated with dysmetabolic subjects have been suggested to contribute to the severity of bone loss after bone implant insertion. However, there is a perspective evidence strengthening the hypothesis that custom-fabricated bioengineered scaffolds may produce favorable bone healing effects in case of altered endocrine or metabolic conditions. This perspective review aims to share a comprehensive knowledge of the mechanisms implicated in bone resorption and remodelling processes, which have driven researchers to develop metallic implants as the cobalt-chromium (Co-Cr) bioscaffolds, presenting optimized geometries that interact in an effective way with the osteogenetic precursor cells, especially in the cases of perturbed endocrine or metabolic conditions.

Background: Diabetes Mellitus (DM) is considered the fourth leading cause of death in Palestine, with a prevalence of 9.1% in patients aged 20-79 years, and has increased to 20.6% in 2020. Aims: This study aims to estimate DM costs, compare DM total health care cost among patient characteristics and DM management (e.g. anti-diabetic medications and alternative medicine), as well as assess MA and its predictors including patient characteristics, DM management, alternative medicine use, and DM costs. Methods: A cross-sectional study was conducted for the past one year among 479 diabetic patients, selected by convenience sampling and snowball sampling methods via electronic post of an online questionnaire, including a web link to the questionnaire page in a Google Form via email or public social media pages and applications. Data on patients’ socio-demographic and clinical characteristics, medication profile, use of medicinal plants as alternative medicine, costs, and Medication Adherence (MA) were collected. The Statistical Package for Social Sciences (SPSS v. 25) was used to perform a descriptive, Kolmogorov-Smirnov test, univariate analysis, Mann-Whitney or Kruskal- Wallis test, multiple linear regression, binary logistic regression, and multiple logistic regression analysis. A p-value < 0.05 was considered statistically significant. Results: More than half of the participants were male and living in villages (50.7%, 59.1%, respectively). Approximately 51.4% received Oral Hypoglycemic Drugs (OHDs) and only 16.1% received insulin. The participants receiving ≤3 medications daily acquired the highest percentage (55.7%), and less than half received medicinal plants as an alternative medicine for the management of DM. The estimated total DM health care cost per year incurred by patients and family members was Israeli Shekel 988,276 (US Dollar 307,590). More than half of the participants were considered adherent with the Eight–Item Morisky Medication Adherence Scale (MMAS–8) score ≥6. It is noteworthy that the use of alternative medicine was significantly associated with total health care cost and MA. Furthermore, DM duration was significantly associated with MA. These results are worth taking into consideration. Conclusion: This study reflects the need for strengthening the patient-health care professionals’ relationship, and to enhance the role of preventive education, and the importance of awareness about MA, DSCMBs, and the use of alternative medicine based on evidence-based strategies to improve MA, glycemic control, meanwhile reducing the costs incurred by patients and family members.

Background: Osteoporosis (OP) is a systemic bone metabolism disorder in which the immune system and bone metabolism interact. Objective: The purpose of this study was to explore the research status, hot spots and trends regarding the influence of the immune system on OP and to provide a basis for research directions and applications in this field. Methods: We searched and collected literature about the immune system and OP published from 2012 to 2022 in the Web of Science Core Collection database. All the included studies were subjected to bibliometrics analysis using Hiplot Pro, VOSviewer and CiteSpace software to produce statistics and visual analyses of the literature output, countries, institutions, authors, keywords and journals. Results: A total of 1201 papers were included, and the number of citations of these articles reached 31,776. The number of publications and citations on the immune system and OP has increased year by year. The top three countries with the greatest number of papers published were China, the United States of America (USA) and Italy. The two institutions with the largest number of papers published were Sichuan University and Soochow University, both located in China. De Martinis Massimo (Italy) and Ginaldi Lia (Italy) are prolific authors in this field. The representative academic journals are Osteoporosis International, Frontiers in Immunology, Journal of Bone and Mineral Research, PloS One and Bone. The results of the keyword cooccurrence analysis showed that the research topics in this field mainly focused on T cells, cytokines, signaling pathways, vitamin D, postmenopausal OP and immune diseases. The keyword burst results showed that zoledronic acid, chain fatty acids and gut microbiota are the frontiers and trends of future research on this topic. Conclusion: The influence of the immune system on OP has been widely studied, and the current research in this field focuses on the effect or mechanism of immune-related cytokines, signaling pathways and vitamin D on OP. Future research trends in this field should focus on the immune regulation mechanism and clinical transformation of zoledronic acid, chain fatty acids and the gut microbiota in OP.

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.

Background: The aim of this study is to analyze the effects of colostrum application on the establishment of normal flora in the intestinal tracts and oral cavities of extremely low birth weight infants (ELBWI). Methods: A prospective cohort study design was adopted following the STROBE guidelines (Supplementary File 1). Colostrum was administered immediately after obtaining maternal breast milk using a special sterile cotton swab. There were no specific treatments for infants who did not receive colostrum. This experiment was completed on day 5 post-birth and the patients were divided into the colostrum and control groups, corresponding to whether or not colostrum was administered. Throat swabs and stool samples were collected on days 1 and 5 post-birth. Results: Using the conventional bacteria cultivation technique, the detection rate of bacteria in 98 cases of meconium at birth was 15.31%. On day 5, the detection rates of Staphylococcus in the colostrum and control groups were 36.54% and 34.78%, with no significant difference between them (P = 0.856), and that of Enterococcus was 26.92% and 13.04%, respectively, with no statistically significant difference (P = 0.089). Likewise, at birth, the detection rate of bacteria in 98 cases of throat swabs was 27.55%. On day 5, the detection rate of Streptococcus in the colostrum and control groups was 78.85% and 50.00%, respectively, recording a statistically significant difference this time (P = 0.003). Conclusion: Colostrum application had limited effects on intestinal flora colonization but contributes to physiological oral flora colonization.

Background: Hereby, we describe the first case of latent mastocytosis triggered by mRNA-based vaccine to prevent COVID-19 infection. Case Presentation: In a 42-year-old Arabian man affected by slight, undiagnosed mastocytosis, the second dose of the COVID-19 vaccine made more blatant his latent disease. The postvaccination diagnostic iter is illustrated and the potential reasons causing the onset of the cutaneous mastocytosis are discussed. Conclusion: Clinicians should keep a longer follow-up of their patients after the COVID-19 vaccination, not related to few hours, for the risk of immediate-type adverse events only.