Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 24, Issue 11, 2024

In recent years, dysregulation of the notch pathway has been associated with the development and progression of various cancers. Notch signaling is involved in several cellular processes, such as proliferation, differentiation, apoptosis, and angiogenesis, and its abnormal activation can lead to uncontrolled cell growth and tumorigenesis. In various human cancers, the Notch pathway has been shown to have both tumor-promoting and tumor-suppressive effects, depending on the context and stage of cancer development. Notch signaling has been implicated in tumor initiation, cancer cell proliferation, cell migration and maintenance of cancer stem cells in several human cancers, including leukemia, breast, pancreatic and lung cancer. Understanding the role of the Notch pathway in cancer development and progression may provide new opportunities for the development of potent targeted therapies for cancer treatment. Several drugs targeting the Notch pathway are currently in preclinical or clinical development and may hold promise for anticancer therapy in the future.

Background: The use of herbal remedies, medicinal plants, and their derivatives for the treatment and control of hypertension is well-known and widespread throughout Morocco. Aims: The aim of the study was to review the antihypertensive and vasorelaxant medicinal plants of the Moroccan pharmacopeia. Objective: To date, no review on Moroccan medicinal plants exhibiting antihypertensive effects has been performed, and their mechanism of action has not been specified. The objective of this review was to collect, analyze, and critically assess published publications on experimental and clinical research that explored the blood pressure-reducing abilities of Moroccan medicinal plant extracts. Materials and Methods: This study collected, processed, and critically analyzed published studies related to experimental and clinical research that investigated Moroccan herbal derivatives' blood pressure-lowering abilities using a number of scientific databases, including ScienceDirect, Scopus, PubMed, Google Scholar, and others. Plantlist.org was used to validate the right plant names. Results: The results revealed 22 species of Moroccan medicinal plants belonging to 13 different groups with recognized antihypertensive properties. The species were abundant in a variety of chemical elements. Asteraceae (08 species), Lamiaceae (3 species), Apiaceae (2 species), and 1 species each from the following families: Parmeliaceae, Fabaceae, Cistaceae, Malvaceae, Polygonaceae, Brassicaceae, Myrtaceae, Rutaceae, Amaranthaceae, Rosaceae, and Lauraceae were the most frequently mentioned families for their antihypertensive properties. The most used parts were the leaves and the aerial parts. The two main methods of preparation among Moroccans were decoction and infusion. This study demonstrated the known antihypertensive and vasorelaxant properties of Moroccan medicinal plants in vivo and in vitro, as well as their mechanisms of action. Interestingly, phytochemicals can operate on blood vessels directly via a vasorelaxant impact involving a range of signaling cascades or indirectly by blocking or activating multiple systems, such as an angiotensin-converting enzyme (ACE), renin-angiotensin system (RAS), or diuretic activity. Conclusion: The review of the available data reveals that more work needs to be done to examine all the Moroccan medicinal plants that have been suggested as antihypertensive in published ethnopharmacological surveys. A review of the literature in this area reveals that methodologies of the experimental study need to be standardized, and purified molecules need to be studied. In addition, mechanistic investigations, when they exist, are generally incomplete. In contrast, only a few advanced clinical investigations have been conducted. However, all studies fail to determine the efficacy/safety ratio.

Background: Thyroid nodules are common lesions in benign and malignant thyroid diseases. More and more studies have been conducted on the feasibility of artificial intelligence (AI) in the detection, diagnosis, and evaluation of thyroid nodules. The aim of this study was to use bibliometric methods to analyze and predict the hot spots and frontiers of AI in thyroid nodules. Methods: Articles on the application of artificial intelligence in thyroid nodules were retrieved from the Web of Science core collection database. A website (https://bibliometric.com/), VOSviewer and CiteSpace software were used for bibliometric analyses. The collaboration maps of countries and institutions were analyzed. The cluster and timeline view based on cocitation references and keywords citation bursts visualization map were generated. Results: The study included 601 papers about AI in thyroid nodules. China contributed to more than half (52.41%) of these publications. The cluster view and timeline view of co-citation references were assembled into 9 clusters, “AI”, “deep learning”, “papillary thyroid carcinoma”, “radiomics”, “ultrasound image”, “biomarkers”, “medical image segmentation”, “central lymph node metastasis (CLNM)”, and “self-organizing auto-encoder”. The “AI”, “radiomics”, “medical image segmentation”, “deep learning”, and “CLNM”, emerging in the last 10 years and continuing until recent years. Conclusion: An increasing number of scholars were devoted to this field. The potential future research hotspots include risk factor assessment and CLNM prediction of thyroid carcinoma based on radiomics and deep learning, automatic segmentation based on medical images (especially ultrasound images).

Background: This study aimed to assess the diagnostic capability of insulin surrogate measurements in identifying individuals with metabolic syndrome (MetS) and propose applicable indices derived from fasting values, particularly in large study populations. Methods: Data were collected from the datasets of the Surveillance of Risk Factors of NCDs in Iran Study (STEPS). MetS was defined based on the National Cholesterol Education Program (NCEP) criteria. Various insulin surrogate indices, including Homeostasis Model Assessment (HOMA), Quantitative Insulin Sensitivity Check Index (QUICKI), Fasting glucose to insulin ratio (FGIR), Reynaud, Reciprocal insulin, McAuley, Metabolic Score for Insulin Resistance (METS-IR), Triglyceride-glucose index (TyG), TG/ HDL-C, TG/ BMI, and TG/ WC ratio were assessed. Receiver Operating Characteristic (ROC) curves were used to assess pathologic conditions and determine the optimal cut-off through the highest score of the Youden index. Also, Area Under the Curve (AUC) values were established for each index totally and according to sex, age, and BMI differences. Results: The study population consisted of 373 individuals (49.9% women; 75.1% middle age, 39.1% obese, and 27.3% overweight), of whom 117 (31.4%) had MetS. The METS-IR (AUC: 0.856; 95% CI: 0.817-0.895), TG/ HDL-C (AUC: 0.820; 95% CI: 0.775-0.886), TyG (AUC: 0.808; 95% CI: 0.759-0.857), and McAuley (AUC: 0.804; 95% CI: 0.757-0.852) indices provided the greatest AUC respectively for detection of MetS. The values of AUC for all the indices were higher in men than women. This trend was consistent after data stratification based on BMI categories, middle age, and senile individuals. Conclusion: The present study indicated that indices of insulin, including METS-IR, TG/HDLC, TyG, and McAuley, have an equal or better capacity in determining the risk of MetS than HOMA-IR, are capable of identifying individuals with MetS and may provide a simple approach for identifying populations at risk of insulin resistance.

Background: PPAR-γ is one of three members of the PPAR group of the nuclear receptor superfamily and plays an important regulatory role as a ligand-dependent transcription factor. Objective: This study aimed to identify the top 100 most influential articles in the field of PPAR-γ. We hypothesized that a bibliometric and scientometric analysis of the PPAR-γ research field could render trends that provide researchers and funding agencies valuable insight into the history of the field, and potential future directions. Methods: A literature search of publications was carried out using the Web of Science (WOS) and Scopus database based on specific subject words on September 11, 2023. Articles were listed in descending order of the number of citations. Statistical analysis was performed on the data of the top 100 cited articles in terms of year of publication, journal, research direction, institution, author, and country. Meanwhile, co-authorship networks and co-citation networks were constructed by using VOSviewer software, and keywords were analyzed for co-occurrence. Results: A total of 9,456 articles regarding PPAR-γ were identified and analyzed based on the WOS database, and the top 100 cited articles in the field of PPAR-γ were ranked by citation. The most cited article was published in 1998, with 2,571 citations and a density of 102.80 citations/ year. Of the 100 articles, Harvard University was the institution with the highest number of articles published. Spiegelman, B. M. was the author with the highest number of articles published. Using the VOSviewer software, we found that the most used keywords were geneexpression, activated receptor-gamma, and adipocyte differentiation. PPAR-γ, one of the most widely studied transcription factors, is an important drug target for many diseases. Therefore, screening for small molecule compounds targeting PPAR-γ remains of great value. Conclusion: The present study identified the top 100 most influential articles in the field of PPAR-γ, which help global researchers to better understand research perspectives and develop future research directions of PPAR-γ.

Background: New pathogenesis-related early detection markers are needed to prevent Type 2 Diabetes Mellitus (T2DM). Objective: We aimed to determine phoenixin (PNX)-14 and PNX-20 levels in T2DM patients and investigate their relationship with diabetes. Methods: 36 T2DM patients and 36 healthy controls were included in the study, and PNX-14 and PNX-20 levels in blood samples taken from the groups were measured by ELISA method. Results: Patients' serum PNX-14 and PNX-20 levels were statistically significantly lower than in controls (p <0.001). A negative correlation was detected between PNX-14 and BMI, fasting blood sugar, HbA1c%, and HOMA-IR. A negative correlation was found between PNX-20 and BMI, fasting insulin and glucose, HbA1c%, and HO-MA-IR. A positive correlation was noticed between PNX-14 and PNX-20 levels. In ROC analyses, PNX-14 and PNX-20 performed almost equally in predicting T2DM. In predicting T2DM, the area under the ROC curve for PNX-14 was 0.874 (cutoff value 413.4 ng/L, sensitivity 89 %, specificity 72%), and for PNX-20 was 0.858 (cutoff value 228.7 ng/L, sensitivity 80 %, specificity 83 %). Conclusion: This study shows that serum PNX measurement may have a high level of evidence in predicting T2DM. PNX, related to pathogenesis, may be useful in diagnosing T2DM and other information to support clinical decision-making.

Background: Kidney stones and thyroid disease are two common diseases in the general population, with multiple common risk factors. The associations between kidney stones and thyroid disease are unclear. Aim: This study aims to assess the association between ‘once had a thyroid disease’ and the odds of kidney stones. Methods: Adult participants from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 with reliable kidney stone and thyroid disease data were included. Adjusting for age, gender, race, education level, and marital status, diabetes, hypertension, gout, angina pectoris, stroke, and asthma, logistic regression was used to examine the relationship between kidney stones and thyroid illness. Results: Using stratified analysis, the association between thyroid illness and kidney stones was investigated further. Among the participants, 4.9% had kidney stones, and 10.1% had thyroid disease. Kidney stone was associated with thyroid disease (OR=1.441, (95% CI:1.294-1.604), p <0.01), which remained significant (OR=1.166, (95% CI:1.041-1.305), p <0.01) after adjustments with age, gender, race, education level and marital status, diabetes, hypertension, gout, angina pectoris, stroke, and asthma. Stratified by blood lead, blood cadmium, and blood urea nitrogen levels in the human body, the odds of kidney stones still increased with once having a previous thyroid disease. Conclusions: In this large nationally representative survey over 10 years, kidney stone was strongly associated with thyroid disease. In this cross-sectional study, we explored the association between thyroid disease and kidney stones, which may help clinicians intervene in them early.

Background: Effects of propionic acid (PA) on the cellular and molecular processes in the small intestine under type 2 diabetes mellitus (T2DM)-induced endoplasmic reticulum (ER) stress remain incompletely studied. Objectives: The aim of the study was to assess the state of unfolded protein response (UPR) system in the small intestine of diabetic rats and to explore PA’s influence on metformin treatment. Methods: Male Wistar rats were divided into 1) control and 2) T2DM groups, and groups receiving (14 days, orally) 3) metformin (60 mg/kg), 4) PA (60 mg/kg), and 5) PA+metformin. Western blotting, RT-PCR, and transmission electron microscopy were performed. Results: We found that T2DM induced elevation of ER intermembrane space and UPR overactivation based on increased GRP78, ATF6 and PERK levels in small intestine. Metformin treatment led to a further UPR activation. PA supplementation partially restored enterocytes functioning via normalization of ATF6 and PERK content, while IRE1 level reached the maximum value, compared to all groups. The most pronounced effect of adaptation to the T2DMinduced ER stress was observed after combined metformin and PA action. In particular, decreased ER intermembrane space in enterocytes was detected compared to separate metformin and PA administration, which was accompanied by restored GRP78, PERK and IRE1 levels. Conclusion: Our study proves the safety of additional therapy with propionic acid in combination with metformin for the functional state of small intestine. Due to its ability to modulate UPR signaling, PA may be considered a safe and perspective candidate for supportive therapy in T2DM, especially for neuroprotection.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection attacks the respiratory and nervous systems. Among patients with SARS-CoV-2 infection, cases with simultaneous central and peripheral nervous system damage are rare, and those with intractable hypophosphatemia and hypokalemia complicating the former have not been reported yet. Case Presentation: A 59-year-old woman presented to the emergency department with incoherent speech evolving for 3 days. She had tested positive for the SARS-CoV-2 RT-PCR assay 8 days earlier. Her physical examination showed progressive limb weakness with diminished tendon reflexes and normal sensory examination. Cranial MRI revealed multiple abnormal signals in the brain. Cerebrospinal fluid (CSF) analysis and electromyography revealed acute motor axonal neuropathy (AMAN), further diagnosed as encephalitis combined with Guillain.Barré syndrome (GBS). The patient received glucocorticoid therapy, intravenous immune globulin (IVIG), and rehabilitation therapy. The patient experienced an intractable hypophosphatemia and hypokalemia during the treatment period, which was not effectively corrected several times. The symptoms improved after 1 month of treatment. Conclusion: Early diagnosis is important for the management of Guillain-Barré syndrome associated with SARS-CoV-2 infection. Moreover, in order to prevent life-threatening long-term persistent electrolyte disturbances in non-seriously ill patients, clinicians should pay particular attention to their electrolyte status.