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  5. Volume 25, Issue 1, 2025

Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 25, Issue 1, 2025

Volume 25, Issue 1

Volume 25, Issue 1, 2025

    • Beneficial Effects of PIN1 Inhibition on Diabetes Mellitus: A Concise Review

      https://doi.org/10.2174/0118715303297663240307060019

      Type 2 diabetes mellitus is a long-term medical illness in which the body either becomes resistant to insulin or fails to produce it sufficiently. Mostly, combinatorial therapy is required to control blood glucose levels. However, combinatorial therapy has detrimental side effects. The prevalence of the cases and subsequent increases in medical costs of the same intimidate human health globally. While there have been a lot of studies focused on developing diabetic regimens that work to lower blood glucose levels, their effectiveness is short-lived because of unfavorable side effects, such as weight gain and hypoglycemia. In recent years, the PIN1 (protein interacting with NIMA) enzyme has attracted the attention of researchers. Previous studies suggested that PIN1 may act on the various substrates that are involved in the progression of T2DM and also help in the management of diabetes-related disorders. Thus, the focus of the current review is to examine the correlation between PIN1, T2DM and its related disorders and explore the possibility of developing novel therapeutic targets through PIN1 inhibition.

    • Obesity in Prediabetic Patients: Management of Metabolic Complications and Strategies for Prevention of Overt Diabetes

      https://doi.org/10.2174/0118715303282327240507184902

      Obesity and prediabetes affect a substantial part of the general population, but are largely underdiagnosed, underestimated, and undertreated. Prediabetes differs from diabetes only in the degree of hyperglycaemia consequent to the progressive decline in residual beta-cell function. Both prediabetes and diabetes occur as a consequence of insulin resistance that starts several years before the clinical onset of overt diabetes. Macrovascular complications in patients with diabetes are mainly caused by insulin resistance. This is why in prediabetes, the overall cardiovascular risk is, by all means, similar to that in patients with diabetes. It is important, therefore, to identify prediabetes and treat patients not only to prevent or delay the onset of diabetes, but to reduce the cardiovascular risk associated with prediabetes. This review provides an overview of the pathophysiology of prediabetes in patients with obesity and the progression toward overt diabetes. We have reviewed nutritional and pharmacological approaches to the management of obesity and reduced glucose tolerance, and the treatment of the major comorbidities in these patients, including hypertension, dyslipidaemia, and Metabolic dysfunction-associated Steatotic Liver Disease (MASLD), has also been reviewed. In patients with obesity and prediabetes, the nutritional approach is similar to that adopted for patients with obesity and diabetes; treatments of dyslipidaemia and hypertension also have the same targets compared to patients with diabetes. MASLD is a critical issue in these patients; in the prediabetic state, MASLD rarely progresses into fibrosis. This highlights the importance of the early recognition of this pathological condition before patients become diabetic when the risk of fibrosis is much higher. It is necessary to raise awareness of the clinical relevance of this pathological condition in order to prompt early intervention before complications occur. The single most important therapeutic goal is weight loss, which must be early and persistent.

    • Androgen Signaling in Prostate Cancer: When a Friend Turns Foe

      https://doi.org/10.2174/0118715303313528240523101940

      Androgen (AR) signaling is the main signaling for the development of the prostate and its normal functioning. AR is highly specific for testosterone and dihydrotestosterone, significantly contributing to prostate development, physiology, and cancer. All these receptors have emerged as crucial therapeutic targets for PCa. In the year 1966, the Noble prize was awarded to Huggins and Hodge for their groundbreaking discovery of AR. As it is a pioneer transcription factor, it belongs to the steroid hormone receptor family and consists of domains, including DNA binding (), hormone response elements (), ligand binding (), and N-terminal regulatory domains. Structural variations in AR, such as AR gene amplification, LBD mutations, alternative splicing of exons, hypermethylation of AR, and co- regulators, are major contributors to PCa. It’s signaling is crucial for the development and functioning of the prostate gland, with the AR being the key player. The specificity of AR for testosterone and dihydrotestosterone is important in prostate physiology. However, when it is dysregulated, AR contributes significantly to PCa. However, the structural variations in AR, such as gene amplification, mutations, alternative splicing, and epigenetic modifications, drive the PCa progression. Therefore, understanding AR function and dysregulation is essential for developing effective therapeutic strategies. Thus, the aim of this review was to examine how AR was initially pivotal for prostate development and how it turned out to show both positive and detrimental implications for the prostate.

    • Is Low-free Triiodothyronine (fT3) Associated with Increased Morbidity in Patients Admitted to Coronary Care Units?

      https://doi.org/10.2174/0118715303287732240201122412
      Background

      The effects of thyroid hormone on patients hospitalized in coronary intensive care units are still controversial.

      Objective

      We retrospectively examined thyroid hormone levels and their impact on cardiovascular morbidity in patients admitted to coronary intensive care units.

      Methods

      A total of 208 (Female/Male; 46.6%/53.4%) patients without any history of thyroid disease were enrolled and screened. Patients with specific heart disease and existing thyroid hormone parameters were included in the study. Low triiodothyronine syndrome is characterized by reduced serum total or free T3 (fT3) concentrations in normal free T4 (fT4) and TSH levels.

      Results

      The common diagnosis of the patients in the coronary care unit is acute coronary syndrome (n = 59, 28.2%) and heart failure (n = 46, 23.3%). Patients were divided into two groups according to left ventricular ejection fraction percentages (LVEF ≤39% LVEF ≥40%). Plasma fT3 levels were significantly correlated with low LVEF (≤39%) ( =0.002). fT3 (r = -0.183, =0.013) and hospitalization etiology (r = -0.161, =0.023) were also the most critical parameters affecting the length of hospitalization.

      Conclusion

      Low fT3 was associated with reduced ejection fraction and prolonged hospitalization, which may lead to potential morbidities in HF patients and may be useful in risk stratification and treatment strategies.

    • Integrating Data Mining with Metabolomics to Analyze the Mechanism of the “Pearl-Borneol” Pair in Promoting Healing of Diabetic Wounds

      https://doi.org/10.2174/0118715303295707240614060314
      Introduction

      Chronic diabetic wounds pose a significant threat to the health of diabetic patients, representing severe and enduring complications. Globally, an estimated 2.5% to 15% of the annual health budget is associated to diabetes, with diabetic wounds accounting for a substantial share. Exploring new therapeutic agents and approaches to address delayed and impaired wound healing in diabetes becomes imperative. Traditional Chinese medicine (TCM) has a long history and remarkable efficacy in treating chronic wound healing.

      Methods

      In this study, all topically applied Proprietary Chinese Medicines (pCMs) for wound healing officially approved by China National Medical Products Administration (NMPA) were collected from the NMPA TCM database. Data mining was employed to obtain a high-frequency TCM ingredients pair, Pearl-Borneol (1:1). Subsequently, This study investigated the effect and molecular mechanism of the Pearl-Borneol pair on the healing of diabetic wounds by animal experiments and metabolomics.

      Results

      The animal experiments showed that the Pearl-Borneol pair significantly accelerated diabetic wound healing, exhibiting a more potent effect than the Pearl or Borneol treatment alone. Meanwhile, the metabolomics analysis identified significant differences in metabolic profiles in wounds between the Model and Normal groups, indicating that diabetic wounds had distinct metabolic characteristics from normal wounds. Moreover, Vaseline-treated wounds exhibited similar metabolic profiles to the wounds from the Model group, suggesting that Vaseline might have a negligible impact on diabetic wound metabolism. In addition, wounds treated with Pearl, Borneol, and Pearl-Borneol pair displayed significantly different metabolic profiles from Vaseline-treated wounds, signifying the influence of these treatments on wound metabolism. Subsequent enrichment analysis of the metabolic pathway highlighted the involvement of the arginine metabolic pathway, closely associated with diabetic wounds, in the healing process under Pearl-Borneol pair treatment. Further analysis revealed elevated levels of arginine and citrulline, coupled with reduced nitric oxide (NO) in both the Model and Vaseline-treated wounds compared to normal wounds, pointing to impaired arginine utilization in diabetic wounds. Interestingly, treatment with Pearl and Pearl-Borneol pair lowered arginine and citrulline levels while increasing NO content, suggesting that these treatments may promote the catabolism of arginine to generate NO, thereby facilitating faster wound closure. Additionally, Borneol alone significantly elevated NO content in wounds, potentially due to its ability to directly reduce nitrates/nitrites to NO. Oxidative stress is a defining characteristic of impaired metabolism in diabetic wounds. Our result showed that both Pearl and Pearl-Borneol pair decreased the oxidative stress biomarker methionine sulfoxide level in diabetic wounds compared to those treated with Vaseline, indicating that Pearl alone or combined with Borneol may enhance the oxidative stress microenvironment in diabetic wounds.

      Conclusion

      In summary, the findings validate the effectiveness of the Pearl-Borneol pair in accelerating the healing of diabetic wounds, with effects on reducing oxidative stress, enhancing arginine metabolism, and increasing NO generation, providing a mechanistic basis for this therapeutic approach.

    • Post-surgical Persistent Hyperparathyroidism Successfully Treated with Parathyroid Radiofrequency Ablation: A Case Report

      https://doi.org/10.2174/0118715303308277240419062634
      Background

      Currently, parathyroidectomy is the standard treatment for Primary Hyperparathyroidism (PHPT). Surgical treatment is often effective, although not free of complications and relapses. Minimally invasive techniques, such as Microwave Ablation (MWA) and Radiofrequency Ablation (RFA), are an alternative to surgery in selected patients. We have, herein, reported on the successful use of RFA in a patient with post-surgical persistent hyperparathyroidism.

      Case Presentation

      A 54-year-old woman was referred to our Center for mild hypercalcemia with exams revealing Primary Hyperparathyroidism (PHPT). Neck ultrasound and Technetium-99 Methoxy-isobutyl-isonitrile (99mTc-MIBI) scintigraphy scanning revealed a suspicious right parathyroid hyperplasia/adenoma. She underwent parathyroidectomy and histological examination showed a parathyroid nodular hyperplasia. During the follow-up, she suffered from persistent hyperparathyroidism due to a left parathyroid hyperplasia. Thus she was treated with RFA. Blood tests after the procedure showed the remission of the disease 7 months post-treatment.

      Conclusion

      A minimally invasive technique for PHPT may represent a valid alternative to surgery, especially in patients with an elevated surgery-related risk. More studies are necessary to investigate the benefit of RFA as a first-line treatment in PHPT.

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