Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 24, Issue 9, 2024

The aetiology of a progressive neuronal Parkinson's disease has been discussed in several studies. However, due to the multiple risk factors involved in its development, such as environmental toxicity, parental inheritance, misfolding of protein, ageing, generation of reactive oxygen species, degradation of dopaminergic neurons, formation of neurotoxins, mitochondria dysfunction, and genetic mutations, its mechanism of involvement is still discernible. Therefore, this study aimed to review the processes or systems that are crucially implicated in the conversion of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) into its lethal form, which directly blockades the performance of mitochondria, leading to the formation of oxidative stress in the dopaminergic neurons of substantia nigra pars compacta (SNpc) and resulting in the progression of an incurable Parkinson’s disease. This review also comprises an overview of the mutated genes that are frequently associated with mitochondrial dysfunction and the progression of Parkinson’s disease. Altogether, this review would help future researchers to develop an efficient therapeutic approach for the management of Parkinson's disease via identifying potent prognostic and diagnostic biomarkers.

The scientific world has recently shown wider attention to elucidating the anticancerous potential of numerous plant-based bioactive compounds. Many research studies have suggested that consuming foods high in polyphenols, which are present in large amounts in grains, legumes, vegetables, and fruits, may delay the onset of various illnesses, including cancer. Normal cells with genetic abnormalities begin the meticulously organized path leading to cancer, which causes the cells to constantly multiply, colonize, and metastasize to other organs like the liver, lungs, colon, and brain. Resveratrol is a naturally occurring stilbene and non-flavonoid polyphenol, a phytoestrogen with antioxidant, anti-inflammatory, cardioprotective, and anticancer properties. Resveratrol makes cancer cells more susceptible to common chemotherapeutic treatments by reversing multidrug resistance in cancer cells. This is especially true when combined with clinically used medications. Several new resveratrol analogs with enhanced anticancer effectiveness, absorption, and pharmacokinetic profile have been discovered. The present emphasis of this review is the modulation of intracellular molecular targets by resveratrol in vivo and in vitro in various malignancies. This review would help future researchers develop a potent lead candidate for efficiently managing human cancers.

>Background: The "diabetic lung" has been identified as a possible target organ in diabetes, with abnormalities in ventilation control, bronchomotor tone, lung volume, pulmonary diffusing capacity, and neuroadrenergic bronchial innervation. Objective: This review summarizes studies related to diabetic pneumopathy, pathophysiology and a number of pulmonary disorders including type 1 and type 2 diabetes. Methods: Electronic searches were conducted on databases such as Pub Med, Wiley Online Library (WOL), Scopus, Elsevier, ScienceDirect, and Google Scholar using standard keywords “diabetes,” “diabetes Pneumopathy,” “Pathophysiology,” “Lung diseases,” “lung infection” for review articles published between 1978 to 2023 very few previous review articles based their focus on diabetic pneumopathy and its pathophysiology. Results: Globally, the incidence of diabetes mellitus has been rising. It is a chronic, progressive metabolic disease. The "diabetic lung" may serve as a model of accelerated ageing since diabetics' rate of respiratory function deterioration is two to three-times higher than that of normal, non-smoking people. Conclusion: Diabetes-induced pulmonary dysfunction has not gained the attention it deserves due to a lack of proven causality and changes in cellular properties. The mechanism underlying a particular lung illness can still only be partially activated by diabetes but there is evidence that hyperglycemia is linked to pulmonary fibrosis in diabetic people.

Obesity is rapidly becoming a global health problem affecting about 13% of the world’s population affecting women and children the most. Recent studies have stated that obese asthmatic subjects suffer from an increased risk of asthma, encounter severe symptoms, respond poorly to anti-asthmatic drugs, and ultimately their quality-of-life decreases. Although, the association between airway hyperresponsiveness (AHR) and obesity is a growing concern among the public due to lifestyle and environmental etiologies, however, the precise mechanism underlying this association is yet to establish. Apart from aiming at the conventional antiasthmatic targets, treatment should be directed towards ameliorating obesity pathogenesis too. Understanding the pathogenesis underlying the association between obesity and AHR is limited, however, a plethora of obesity pathologies have been reported viz., increased pro-inflammatory and decreased anti-inflammatory adipokines, depletion of ROS controller Nrf2/HO-1 axis, NLRP3 associated macrophage polarization, hypertrophy of WAT, and down-regulation of UCP1 in BAT following down-regulated AMPKα and melanocortin pathway that may be correlated with AHR. Increased waist circumference (WC) or central obesity was thought to be related to severe AHR, however, some recent reports suggest body mass index (BMI), not WC tends to exaggerate airway closure in AHR due to some unknown mechanisms. This review aims to co-relate the above-mentioned mechanisms that may explain the copious relation underlying obesity and AHR with the help of published reports. A proper understanding of these mechanisms discussed in this review will ensure an appropriate treatment plan for patients through advanced pharmacological interventions.

>Background: Chronic glomerulonephritis (CGN) is a primary glomerular disease. As a circulating protein, growth and differentiation factor 15 (GDF15) participates in a variety of biological processes. Objective: We aimed to investigate the role of GDF15 in CGN. Methods: HBZY-1 cells were induced by lipopolysaccharide (LPS). Cell viability was detected using a cell counting kit-8 (CCK-8) assay, and a western blot was applied for the detection of GDF15 protein expression. After GDF15 silencing, cell proliferation was evaluated by CCK-8 assay and 5-ethynyl-2'-deoxyuridine (EDU) staining. Enzyme-linked immunosorbent assay (ELISA) kits were used to detect the levels of inflammatory cytokines. Autophagy was assessed by GFP-LC3B assay. Besides, the expression of NF-ΚB signaling-, autophagy- (LC3II/I, Beclin l and p62) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling-related proteins were measured by western blot. Afterwards, PI3K agonist 740Y-P was used to clarify whether GDF15 affected LPS-induced HBZY-1 cells via PI3K/AKT/mTOR signaling. Results: LPS induction increased cell viability and elevated GDF15 expression in HBZY-1 cells. After GDF15 expression depletion, the increased proliferation of LPS-induced HBZY-1 cells was decreased. Additionally, GDF15 knockdown suppressed the release of inflammatory factors in LPS-induced HBZY-1 cells and activated autophagy. Moreover, the PI3K/AKT/ mTOR signal was evidenced to be activated by GDF15 deficiency. The further addition of 740Y-P reversed the impacts of GDF15 deficiency on the proliferation, inflammation, and autophagy of LPS-induced HBZY-1. Conclusion: Collectively, GDF15 downregulation could protect against CGN via blocking PI3K/AKT/mTOR signaling.

>Objectives: In this study, we employed a multi-dimensional data mining approach to examine the clinical instances where Professor Xu Zhiyin treated thyroid nodules. Our aim is to understand the patterns of symptoms, underlying causes, and treatment approaches used for thyroid nodules. By doing so, the intention is to distill the essential aspects, compile Professor Xu Zhiyin's clinical insights, and investigate his scholarly perspectives. Methods: Professor Xu Zhiyin's clinical diagnoses and treatments spanning from 2009 to 2019 were entered into Microsoft Excel. Subsequently, the collected data was imported into the Medcase V5.2 system to facilitate data mining. Various techniques, such as frequency-based method, association rule analysis, and clustering, including a decentralized system clustering approach, were employed on a set of 346 cases involving patients with thyroid nodules that conformed to the specified criteria. The primary focus was on extracting insights regarding symptoms and the underlying causes from the medical records. By integrating these findings with Professor Xu Zhiyin's clinical expertise, we examined and summarized the outcomes of the data mining process. Results: The fundamental prescriptions were successfully extracted using the techniques for mining across multiple dimensions. Utilizing the scattered grouping of these prescriptions and with reference to the cluster analysis of the frequency-linked system, the fundamental prescriptions proposed by Professor Xu Zhiyin for addressing thyroid nodules encompass the following ingredients: Glycyrrhiza uralensis Fisch, Cortex Moutan, Paeoniae radix rubra, Curcuma longa L., Radix Curcumae, persica seed, Citri Reticulatae Viride Pericarpium, Pinellia ternata, Spica Prunellae, Ostreae concha, Gleditsia sinensis spine, Tuckahoe and Radix Codonopsis. Conclusion: The fundamental prescriptions were acquired using the frequency approach, association rule technique, k-means clustering approach, and systematic clustering approach. The research findings corroborate one another, demonstrating that Professor Xu Zhiyin's approach to distinguishing and treating thyroid nodules is embodied in distinct prescriptions tailored to specific diseases.

>Aim: To evaluate the associations of the pathogenic variants in Kruppel-like Factor 14 (KLF 14) and Adiponectin (ADIPOQ) with susceptibility to type 2 diabetes mellitus (T2DM). Background: Type 2 diabetes mellitus (T2DM) is a pandemic metabolic disease characterized by increased blood sugar and caused by resistance to insulin in peripheral tissues and damage to pancreatic beta cells. Kruppel-like Factor 14 (KLF-14) is proposed to be a regulator of metabolic diseases, such as diabetes mellitus (DM) and obesity. Adiponectin (ADIPOQ) is an adipocytokine produced by the adipocytes and other tissues and was reported to be involved in T2DM. Objectives: To study the possible association of the KLF-14 rs972283 and ADIPOQ-rs266729 with the risk of T2DM in the Saudi population. Methods: We have evaluated the association of KLF-14 rs972283 C>T and ADIPOQ-rs266729 C>G SNV with the risk to T2D in the Saudi population using the Amplification Refractory Mutation System PCR (ARMS-PCR), and blood biochemistry analysis. For the KLF-14 rs972283 C>T SNV we included 115 cases and 116 healthy controls, and ADIPOQ-rs266729 C>G SNV, 103 cases and 104 healthy controls were included. Results: Results indicated that the KLF-14 rs972283 GA genotype and A allele were associated with T2D risk with OR=2.14, p-value= 0.014 and OR=1.99, p-value=0.0003, respectively. Results also ADIPOQ-rs266729 CG genotype and C allele were associated with an elevated T2D risk with an OR=2.53, p=0.003 and OR=1.66, p-value =0.012, respectively. Conclusion: We conclude that SNVs in KLF-14 and ADIPOQ are potential loci for T2D risk. Future large-scale studies to verify these findings are recommended. These results need further verifications in protein functional and large-scale case control studies before being introduced for genetic testing.

>Background: International studies have found that the blood triglycerides to highdensity lipoproteins (TG/HDL-C) ratio predicted insulin resistance in children with overweight and obesity. However, there is a lack of such reports on children from China. Objective: The objective of this study is to explore the ability of the TG/HDL-C ratio as a blood biomarker for insulin resistance (IR) in obese children in Beijing. Methods: We evaluated 262 children with obesity from our paediatric outpatient clinic in a cross-sectional study. Detailed medical histories of all children were ascertained, as were clinical examination and laboratory test results, including blood lipids, fasting glucose, insulin, and glycated haemoglobin. We divided them into age groups of 6-9 and 10-13.5 years and then into IR and non-IR groups based on the homeostatic model assessment for IR (HOMA-IR). Analysis was accomplished with SPSS software (version 22.0). Results: The TG/HDL-C ratio was higher in children with IR in the 6-9 and 10-13.5-year age groups (p < 0.001). Univariate and multivariate analyses displayed that the TG/HDL-C ratio and HOMA-IR were correlated in the 6-9 and 10-13.5-year-old groups (p < 0.05). In the 6-9-yearold group, IR identified by a TG/HDL-C ratio ≥ 0.645 had a sensitivity, specificity, and an area under the curve (AUC) of 79.1%, 60.9%, and 0.734, respectively. In the 10–13.5-year-old group, IR identified by a TG/HDL-C ratio ≥ 0.725 had a sensitivity, specificity, and an AUC of 79.4%, 62.9%, and 0.724, respectively. Conclusion: We showed the application of the TG/HDL-C ratio to predict insulin resistance in obese children in Beijing with different diagnostic thresholds based on age (6-9-year-old group with TG/HDL-C ≥ 0.645; 10–13.5-year-old group with TG/HDL-C ≥ 0.725), which were lower compared with the diagnostic threshold for insulin resistance in children reported in other countries.

>Background: Early detection and resection of colorectal polyps by routine colonoscopy screening can be effective in reducing the risk of colorectal cancer (CRC). Objective: This study aimed to determine the association between diabetes mellitus (DM) and different types of colorectal polyps in the Chinese population. Methods: A retrospective analysis was performed on inpatients admitted to the Gastroenterology Department of our hospital from January to December 2019. Clinical data, and colonoscopy and pathology findings of the subjects were collected. Bivariate analysis was used to assess factors associated with colorectal polyps. Significant variables from the bivariate evaluation were included in a stepwise multivariate logistic regression analysis to recognize independent predictors of neoplastic polyps and high-risk adenomas. Results: The proportion of patients with DM was significantly higher in patients with neoplastic polyps and high-risk adenomas than in patients without polyps. Age ≥ 50 years, male gender, and a first-degree relative with a history of CRC were independent risk factors for neoplastic polyps and high-risk adenomas, even in non-smokers. An independent risk factor analysis that did not include a family history of CRC showed that age, gender, and alcohol consumption were independent risk factors for neoplastic polyps and high-risk adenomas. DM was an independent risk factor for high-risk adenomas (OR = 2.902, 95% CI = 1.221-6.899; p = 0.016) after adjusting for age, gender, alcohol consumption, and body mass index. Thus, a history of DM significantly increases the risk of high-risk adenomas. Conclusion: This study demonstrated that patients with DM, age ≥ 50 years, male gender, alcohol consumption, and a first-degree relative with a history of CRC should undergo regular endoscopic screening and colonic polypectomy.

>Introduction: Amyloid goiter is a rare disease characterized by amyloid deposits that cause sudden growth in the thyroid gland. Case Presentation: Here we present a case of a 26-year-old woman with euthyroid amyloid goiter who presented with subacute granulomatous thyroiditis clinic. Amyloid goiter was detected as a result of core biopsy from the thyroid parenchyma of the patient with sudden thyroid enlargement. Surgery was not applied to the patient who had no pressure symptoms or signs. In systemic amyloidosis secondary to Familial Mediterranean fever, heart and kidney involvement, as well as the thyroid gland, were detected. Conclusion: Amyloid accumulation should be considered in addition to anaplastic thyroid cancer and lymphoma in patients with sudden thyroid enlargement. It should not be overlooked that amyloid goiter may mimic subacute thyroiditis clinic. Systemic amyloidosis should be considered in patients with amyloid goiter, and an examination should be made to assess the presence of amyloid accumulations in other organs.