Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 24, Issue 13, 2024

Endocrine-disrupting chemicals (EDCs) are environmental pollutants. Since EDCs are present in various consumer products, contamination of human beings is very common. EDCs have deleterious effects on various systems of the body, especially the endocrine and reproductive systems. EDCs interfere with the synthesis, metabolism, binding, or cellular responses of natural estrogens and alter various pathways. Biological samples such as blood, saliva, milk, placental tissue, and hair are frequently used for biomonitoring and the detection of EDCs. Early detection and intervention may help in preventing congenital anomalies and birth defects. The common methods for determining the presence of EDCs in body fluids include gas chromatography, high-performance liquid chromatography, and mass spectrometry. Understanding the health effects and dangers of EDC is important, given their widespread use. This mini-review aims to summarize the adverse biological effects of several important classes of EDCs and highlights future perspectives for appropriate control.

Organelle-specific targeted drug delivery has emerged as a promising approach in the field of drug delivery and therapeutics. This innovative strategy involves the precise delivery of therapeutic agents to specific organelles within cells, such as the nucleus, mitochondria, endoplasmic reticulum, or lysosomes, with the aim of enhancing drug efficacy while minimizing offtarget effects. Despite its tremendous potential, organelle-specific drug delivery faces several key challenges. One major challenge is the development of delivery systems that can accurately navigate the complex intracellular environment and deliver drugs exclusively to the desired organelles. Achieving this level of precision demands advanced nanotechnology and biomaterials engineering. Furthermore, ensuring the safety and biocompatibility of these delivery systems is paramount. Recent advancements in this field include the development of nanocarriers, such as liposomes, nanoparticles, and dendrimers, designed to target specific organelles through ligandreceptor interactions or pH-responsive mechanisms. Additionally, advancements in molecular biology and genetic engineering have enabled the design of genetically encoded organellespecific drug delivery systems. The therapeutic implications of organelle-specific drug delivery are vast. This approach has the potential to revolutionize the treatment of diseases with organelle- specific pathologies, such as neurodegenerative disorders, cancer, and mitochondrial diseases. By precisely targeting the organelles involved in disease progression, the efficacy of therapies can be significantly improved while minimizing collateral damage to healthy tissues.

The respiratory illness known as COVID-19 is caused by the novel coronavirus, SARS-CoV-2. While the precise pathogenic mechanism of COVID-19 remains unclear, the occurrence of a cytokine storm subsequent to viral infection plays a pivotal role in the initiation and advancement of the disease. The infection of SARS-CoV-2 induces a state of immune system hyperactivity, leading to an excessive production of inflammatory cytokines. Consequently, the identification of the various signaling pathways implicated in the inflammation induced by COVID-19 will enable researchers to investigate new targets for therapeutic intervention.

Backgrounds: Postbiotics produced by gut microbiota have exhibited diverse pharmacological activities. Valeric acid, a postbiotic material produced by gut microbiota and some plant species like valerian, has been explored to have diverse pharmacological activities. Methods: This narrative review aims to summarise the beneficial role of valeric acid for different health conditions along with its underlying mechanism. In order to get ample scientific evidence, various databases like Science Direct, PubMed, Scopus, Google Scholar and Google were exhaustively explored to collect relevant information. Collected data were arranged and analyzed to reach a meaningful conclusion regarding the bioactivity profiling of valeric acid, its mechanism, and future prospects. Results: Valeric acid belongs to short-chain fatty acids (SCFAs) compounds like acetate, propionate, butyrate, pentanoic (valeric) acid, and hexanoic (caproic) acid. Valeric acid has been identified as one of the potent histone deacetylase (HDAC) inhibitors. In different preclinical in -vitro and in-vivo studies, valeric acid has been found to have anti-cancer, anti-diabetic, antihypertensive, anti-inflammatory, and immunomodulatory activity and affects molecular pathways of different diseases like Alzheimer's, Parkinson's, and epilepsy. Conclusion: These findings highlight the role of valeric acid as a potential novel therapeutic agent for endocrine, metabolic and immunity-related health conditions, and it must be tested under clinical conditions to develop as a promising drug.

Background: A far more common disease than Cushing's syndrome is subclinical hypercortisolism or mild autonomous cortisol secretion (MACS), with an overall prevalence of 0.2-2%. Objective: This review aims to shed light on the prevalence, screening and diagnostic criteria, comorbidities, and management of Mild Autonomous Cortisol Secretion (MACS). Methods: Studies eligible targeted MACS regarding prevalence, screening, comorbidities, management, and clinical outcome. This is a narrative-review. IRB approval was not needed. Results: The 1 mg Dexamethasone suppression test (DST) remains the first screening test. MACS is associated with adverse cardiometabolic and renal outcomes, osteoporosis and osteopenia, immunodeficiency, depression, coagulopathy, and sarcopenia. Surgery is the gold standard treatment. Medical therapy is recommended when surgery is contraindicated or not feasible. Clinically silent hypercortisolism is a frequent entity that necessitates early detection and treatment. The production of cortisol should be looked at as a spectrum where subtle, undetectable levels can still be produced. They know its association with adverse health outcomes. Conclusion: MACS is no longer considered an asymptomatic disorder; repeated hormonal and functional tests are crucial to prevent multiorgan damage.

Background: Inflammation is considered to be a link between diabetes and central nervous system (CNS) disorders, including depression and anxiety. Metformin is suggested to have antioxidant, anti-inflammatory, and mood-improving effects. The aim of the current research was to investigate the effects of the antidiabetic drug metformin on depressive- and anxiety- like behaviors and oxidative stress in the brain in a rodent model of inflammation induced by lipopolysaccharide (LPS) in male rats. Materials and Methods: The rats were treated as follows: (1) Vehicle instead of metformin and lipopolysaccharide, (2) Lipopolysaccharide (1 mg/ kg) + vehicle instead of metformin, (3-5) Lipopolysaccharide + 50, 100, or 150 mg/ kg of metformin. After the behavioral tests, including open field (OF), elevated pulse maze (EPM), and force swimming (FS) tests, the brains were removed, and malondialdehyde (MDA), nitric oxide (NO) metabolites, total thiol, catalase (CAT) activity, interleukin-6 (IL-6) and superoxide dismutase (SOD) activity were determined. Results: In the EPM, metformin increased the open arm time and entry and decreased closed arm time and entry. In the FS test, metformin lowered the immobility and increased active time compared to lipopolysaccharide. In the OF test, metformin increased total crossing and total distance, time spent, traveled distance, and crossing number in the central zone. As a result of metformin administration, IL-6, MDA, and NO metabolites were decreased while thiol content, SOD, and CAT activity were increased. Conclusion: The results indicated that the well-known antidiabetic drug metformin attenuated depressive- and anxiety-like behaviors induced by inflammation in rats. These beneficial effects are suggested to be due to their attenuating effects on neuroinflammation, oxidative stress, and NO in the brain.

Background: Soccer match requires anaerobic and aerobic energetic metabolism. The aim of this pilot study was to investigate the changes in blood lactate concentration in young male soccer players in different playing roles at different time points after the soccer match. Methods: Following an initial screening of 134 young soccer athletes, 8 male athletes (average age of 15.5 ± 5 SD) were chosen for their characteristics similar to those of competitive athletes. Players were categorized as goalkeeper, central defender, central midfielder, and forward. Blood lactate concentrations were determined using a portable device at different times (10 min, 5 and 16 h) after the soccer match by a maximum effort test on a treadmill. The data were analyzed by one-way analysis of variance ANOVA, followed by Bonferroni's post-hoc test. Results: The following results (mean ± SD) were obtained: VO2max (%) 60.33 ± 3.10; blood lactate (mM) end match (10 min) 2.17 ± 0.78, post-match-early (after 5 h) 2.2 ± 0.42, postmatch- late (16 h) 3.2 ± 0.84. ANOVA analysis indicated that the blood LA concentrations at end-match (10 min) and post-match-early (5 h) were statistically significative lower than those determined at post-match-late (16 h) (p < 0.05). Conclusion: These results suggest that aerobic mechanisms can also use LA as an energy source, contributing to the reduction of its blood concentration. This effect can be due to reduced maximal work during a soccer match and to the LA removal during exercise at reduced intensity. These data can provide indications for planning suitable training strategies for young male soccer players.

Background: Due to changes in lifestyle and dietary habits, the global population with obesity is increasing gradually, resulting in a significant rise in the number of individuals having obesity. Obesity is caused by an imbalance between energy intake and consumption, leading to excessive fat accumulation, which interferes with normal human metabolism. It is also associated with cardiovascular disease, metabolic syndrome, male reproductive endocrine regulation disorders, systemic and local inflammatory reactions, excessive oxidative stress, and apoptosis. All these factors can damage the internal environment for sperm generation and maturation, resulting in male sexual dysfunction, a decline in sperm quality, and lower fertility. This study analyzes the trends and priorities of the effects of obesity on male reproductive disorders from a bibliometric perspective. Methods: This study uses the Web of Science as the statistical source, covering all time spans. Tools like Web of Science, VOSviewer, and CiteSpace are used to analyze countries, institutions, authors, journals, and keywords in the field. Total publications, total citations, and average number of citations are selected for statistics. Results: The results show that the research on the impact of obesity on male reproductive function can be roughly divided into three stages: the initial stage, the slow development stage, and the rapid development stage. Our statistical scope includes 463 highly relevant articles that we have screened. We found that the journal with the most publications in this field is Andrologia, and the institution with the highest total citations is the University of Utah. The most influential countries, institutions, and authors in this field are the United States, the University of Utah, and Carrell, Douglas. Currently, research related to the impact of obesity on male reproduction focuses mainly on three aspects: biochemistry, molecular biology, and reproductive biology. The keyword explosion results indicate that sperm, obesity, and male reproduction are at the forefront and trends of future research in this field. There has been a shift from basic biochemical and molecular research to research on molecular mechanisms relying on omics technologies. However, we have observed that the number of papers published in 2022 is lower than in 2021, indicating a growth interruption during this period. Considering that this deviation may be due to the impact of the COVID-19 pandemic, it may hinder the progress of certain experiments in 2022. In recent years, China has rapidly developed research in this field. However, the average citation rate is relatively low, indicating the need for Chinese scholars to improve the quality of their articles further. Based on our research and in the context of global obesity, men are at risk of increased infertility. Addressing this issue relies on our continued research into the mechanisms of obesity-related male reproductive disorders. Over the past forty-three years, with the contributions of scientists worldwide, research in this field has flourished. Conclusion: The impact of obesity on male reproductive disorders has been extensively studied. Currently, research in this field primarily focuses on male sperm function, sperm quality, and the effects or mechanisms of cells on male reproduction. Future trends in this field should concentrate on the relationship between male fertility and energy metabolism, as well as the endocrine function of adipose tissue. This study comprehensively analyzes the current research status and global trends in obesity and male reproductive disorders. We also discuss the future developments in this field, making it easier for researchers to understand its developmental history, current status, and trends, providing valuable reference for effective exploration in this area.

Background: Alzheimer's disease is a neurological dysfunction of the brain caused by neurodegeneration and oxidative stress. Some viruses, such as herpes viruses, HSV-1, and HSV-2, are causative agents of Alzheimer's disease and result in β-amyloid peptide and tau protein accumulation in the brain. Some antiviral drugs, such as valacyclovir, acyclovir, and foscarnet, reduce amyloid-beta and P-tau. Pavetta indica leaves are also reported for their antiviral properties. The current study aimed to find out the significance of using Pavetta indica methanolic extract and acyclovir against Alzheimer's disease induced by streptozotocin. Methods: Wistar rats received acyclovir and Pavetta indica methanolic extract orally at different dose ranges (50, 150, 450 mg/kg) and (125, 250, 500 mg/kg), respectively. The standard therapy, Rivastigmine (2 mg/kg), was given orally. Results: Intracerebroventricular-streptozotocin produced significant alternations in behavioral assessments, including locomotor activity test, Morris water maze test, and elevated plus maze test. Moreover, intracerebroventricular-streptozotocin ameliorated the antioxidant defense activity by decreasing levels of catalase, superoxide dismutase, and reduced glutathione while enhancing the oxidative stress markers, including malondialdehyde, and total nitrite levels. Finally, the main findings showed that intracerebroventricular-streptozotocin significantly increased the inflammatory marker, tumor necrosis factor-α, and disturbed neurotransmitter mediators, including levels of acetylcholinesterase, glutamate, and γ-amino butyric acid. Conclusion: In a dose-dependent manner, acyclovir and Pavetta indica methanolic extract treatments abrogated the streptozotocin-induced behavioral and neurological abnormalities in rats. The potential therapeutic effects of PIME and acyclovir administration in intracerebroventricular-streptozotocin-treated rats may be attributed to its potential antiviral, antioxidant, and anti-inflammatory effects. The current study suggests that Pavetta indica methanolic extract and acyclovir are promising therapeutic targets against Alzheimer's disease.

Background and Objective: Ankle sprains, very common injuries occurred especially during sports activities, are mainly caused by indirect trauma, which influences exaggerated stress exceeding the strength of stabilization mechanisms. Up to 85% of such injuries result from a sudden flexion and inversion of the foot. In this study, we analyzed the effectiveness of the platform Pro-kin, an innovative system that has given us the possibility to combine the functionality of the older proprioceptive boards with very accurate software in order to improve and accelerate the recovery after ankle injuries. Methods: 30 patients with moderate ankle sprain outcomes in two groups (A and B) were included in this study. Group A was only treated with proprioceptive exercises for 3 weeks, while the group B was trained with the innovative Pro-kin. In both groups, we evaluated VAS scale, the ratio between the number of circumductions performed by the injured foot and the time spent on doing them and the percentage of load among the injured and the healthy foot in statics and dynamics with electronic baropodometry. Our data has been collected at t0 (beginning of study), t1 (one week later), t2 (two weeks later), t3 (one month later), t4 (two months later), and then analyzed by the two-way analysis of variance (2-way ANOVA) test. Results: At t0 no statistical differences of pain in the 2 groups (3.3 and 3.4); the values were similar, as well as at time t1, t2, t3 and t4. Therefore we deduce that Pro-kin treatment is not painful. The number of circumductions performed was definitely better in B group since the first week; for the A group the values considerably increased only at t3 (one month later). Comparing the load percentages on two feet detected by the electronic baropodometer in statics and in dynamics, we deduced that the patients of A group tend to lean mostly on the healthy foot than B group. Conclusion: This study demonstrates that new technological resources (such as Pro-kin) may be helpful to improve and speed up the recovery of ankle sprain in athletes.

Objectives: Patients with an autism spectrum disorder (ASD) are prone to disruptive behaviors and aggression. A typical antipsychotics are used to treat these difficult ASD conditions. Several psychotropic drugs have been linked to hypothyroidism. The clinical manifestation of hypothyroidism is indistinguishable from that of an antipsychotic's general adverse effect, which can lead to a delayed or missed diagnosis. Conversely, thyroid dysfunction can exhibit an impact on mood, anxiety, depression, and cognitive functions. Case Presentation: We present a case of central hypothyroidism caused by long-term use of valproic acid (VPA) and adding quetiapine to risperidone. The current case had a history of hyperprolactinemia and subclinical hypothyroidism caused by risperidone and VPA, respectively, before the administration of quetiapine. Conclusion: This is the first report of quetiapine-induced central hypothyroidism in a patient with ASD, as determined by a thyrotropin-releasing hormone (TRH) loading test. TRH loading test may be useful in elucidating the pathogenesis of hypothyroidism in patients receiving quetiapine and VPA. Thyroid function monitoring in patients taking quetiapine and VPA may provide an opportunity to begin replacement therapy.