Endometriosis (EM) is a hormone-dependent gynecological disease associated with chronic pelvic pain and altered immuno-inflammatory processes. It shares some cancer-like characteristics such as increased proline biosynthesis and activated glutaminolysis. Both proline and glutamine are interconvertible metabolically, and studies have shown their roles in cancer cell metabolic reprogramming, redox homeostasis, occurrence/development of endometrial carcinoma, and its further progression toward the malignant state. So based on this, we hypothesized that the circulatory proline to glutamine ratio (PQR) would be altered in EM and may serve as an indicative biomarker to improve the clinical diagnosis of EM. In present study, the circulatory-PQR levels were estimated for 39 EM patients and 48 age matched healthy female subjects using 800 MHz NMR spectroscopy. Among 39 EM patients, 15 were in the clinical stages I to II and referred to here as moderate EM (MEM) patients and 24 were in the clinical stages III to IV and referred here as severe EM (SEM) patients. The circulatory-PQR levels were significantly increased in EM patients (0.99 ± 0.13 μM in MEM; 1.39 ± 0.22 μM in SEM) compared to normal control (NC) subjects (0.52 ± 0.05 μM in NC). Further, the circulatory PQR levels exhibit the highest diagnostic potential with area under receiver operating characteristic (AUROC) curve values equal to 0.87 ± 0.04 [95%CI = 0.79-0.96] for MEM and 0.89 ± 0.04 [95% CI = 0.82-0.96] for SEM. These results suggested that circulatory-PQR has significant potential to serve as a noninvasive biomarker for diagnostic/prognostic screening of EM and further underscored the importance of these two nonessential amino acids (proline and glutamine) in cancer metabolism.
1 September 2024 in Journal of Inflammation Research
Purpose: Short stature is prevalent among children worldwide, particularly in developing countries. Various trace elements, including zinc, magnesium, iron, copper, chromium and selenium, are crucial for proper body development. The aim of this study is to explore the relationship between trace elements and TNF-α and IL-6 to elicit and possible pathway responsible for short stature. Methods: Two hundred and twenty samples were recruited for this study, 100 short statures and 120 controls were randomly selected. Six trace elements were measured using graphite furnace atomic absorption spectrometry. The concentrations of IL-6 and TNF-α in serum were assessed utilizing the Enzyme-Linked-Immunosorbent Assay (ELISA). Superoxide dismutase was also analysed to determine the oxidative stress response. Results: The study revealed notable distinctions in serum trace element levels of short stature. They exhibited significant lower levels of zinc and magnesium, alongside higher levels of copper. The altered Cu/Zn ratio seemed to have a positive correlation with short stature. Conversely, no significant disparities were observed in iron, chromium, and selenium levels. Furthermore, a significant rise was noted in proinflammatory marker TNF-α and cytokine IL-6. Additionally, superoxide dismutase was low in the short statures In silico study shows a high affinity of Zinc with TNF alpha. It may be suggested that inflammation at any time during childhood, with the rise in TNF alpha tightly binds with zinc and may have led to a decrease in zinc serum levels, altered redox homeostasis and resulted in short stature. Conclusion: The altered Cu/Zn ratio along with high TNF alpha and IL6 may be used as a marker for short stature in the initial years of growth in children before they reach maturity at the age of 18. Thereafter, introducing zinc supplementation could potentially enhance stature by mitigating TNF-alpha level. Further experimental studies will help to establish the exact role of zinc with TNF alpha in short stature.
The Diabetes Mellitus (DM) is increasing in incidence and prevalence worldwide, taking the shape of the pandemic proportions, which is expected to increase further over a couple of decades. In 2019, an estimated 9.3% of the population (463 million people), globally had DM. Projection of future DM burden may increase to 10.2% (578 million people) by 2030 and 10.9% (700 million people) by next 25 years 045). The decrease in immunity in diabetic patients has been a significant concern for physicians and patients alike. The role of mitochondria and it is cellular signaling can elaborate on this problem in depth. Mitochondria is a rich source of reactive oxygen species (ROS) and plays a crucial role in cellular metabolism for energy. They are targets of ROS and many different cellular signals like mitochondrial membrane apoptosis due to hyperglycemia and ROS. The interplay between oxidative stress and diabetes further activated, leading to increased permeability of mitochondrial membrane & apoptosis; this leads to a decrease in immunity in diabetic patients leading to increased mortality and morbidity. Hyperglycemia and ROS major pathways of apoptosis through mitochondrial activation in diabetic patients leading to decreased immunity. They can become drug targets for further intervention of this problem in Diabetic patients.
23 November 2020 in International Journal of Advances in Medicine
Endometriosis is an estrogen-dependent chronic inflammatory disease associated with substantial morbidity, including dyspareunia, dysmenorrhea, pelvic pain, multiple surgery, and infertility. This disease has a high impact on both woman’s physical and mental wellbeing. The etiology of endometriosis is complex and multifactorial. The risk factors associated with the development of endometriosis include family history, menstrual and reproductive cycle, low body mass index (BMI), diet, alcohol uses, smoking, environmental factors, immune system, genetic factors and intrinsic abnormalities in the endometrium. There exist many theories on the initiation and propagation of different types of endometriotic lesions and consequent biological disturbances, of which the most common is the Sampson’s theory according to which the retrograde flow of menstrual blood is linked to the development of endometriosis. Endometriosis affected women have a higher risk than the general female population, for ovarian cancer, coronary heart disease (CHD), and other long-term disease risks as well for autoimmune and atopic disorders. Therefore it becomes a necessity for the clinician not only to attain right diagnosis but also follow up for the other associated disorders. In this review, we have considered the crucial risk factors and biomarkers of the endometriosis as well as the possible pathogenesis towards the development of endometriosis and its prevention strategies. The currently available therapies for the control and treatment of endometriosis have also been elaborated.