Quantitative tissue analysis reveals AK2, COL1A1, & PLG protein signatures: Targeted therapeutics for meningioma.

BACKGROUND: Meningioma is the most prevalent primary intracranial brain tumor and accounts for one-third of all CNS tumors. Meningioma is known to be the most common yet life-threatening brain tumor with a higher recurrence rate. Globally, there is an increase in the healthcare burden due to meningioma and hence in its research. The present clinical approach includes surgical resection, chemotherapy, and radiation therapies to which the malignancy does not seem to respond efficiently. Targeted therapies and molecular markers provide elite patient treatment and care for individuals suffering from meningiomas as compared to conventional measures. Although there is proteomic data on meningioma the knowledge of potential biomarkers differentiating the grades is scarce. To identify the best set of biomarkers, validation of reported markers in large and independent sample cohorts in the future is necessary. METHODS: A total of 12 samples, 3 each of control (which made pool 1) Meningioma grade I (which made 2 sets: pool 2 and pool 3), and Meningioma grade II (which made pool 4) were taken for LC-MS/MS. After this, the expression of three proteins was checked by immunocytochemistry, flow cytometry, and western blotting. RESULTS: Protein expression was analyzed using various techniques like mass spectrometry, immunocytochemistry, flow cytometry, and western blotting. Mass spectrometry is the most commonly used standard and reliable technique for identifying and quantifying protein expression. We got three highly upregulated proteins namely AK2, COL1A1, and PLG using this technique. The biomarker potential of these proteins was further checked by ICC, western blotting, and flow cytometry. Three important proteins were found to be upregulated namely AK2 (Adenylate Kinase 2), COL1A1 (Collagen 1A1), and PLG (Plasminogen). The order of increased protein expression was control < MG grade I < MG grade II according to mass spectrometry and western blotting. In immunocytochemistry, we found that COL1A1 expression increases significantly with grades in comparison to control. Similarly, AK2 and PLG also showed little increase but not as much as COL1A1. In flow cytometry, PLG showed higher upregulation in grades than control. While AK2 and COL1A1 showed little increase in expression in grades than control. All techniques, especially mass spectrometry and western blotting presented higher expression of these proteins in grades as compared to control. CONCLUSIONS: In the quest to find a suitable therapeutic marker, this study incorporates quantitative labeling and detection followed by flow cytometry, Immunocytochemistry, and western blotting for early diagnosis and treatment of meningioma. The article further explores the efficacy of some proteins namely AK2, COL1A1 & PLG to be the targeted molecules.

Key drivers of hysterectomy among women of reproductive age in three states in India: comparative evidence from NFHS-4 and NFHS-5.

PURPOSE: According to the 4th and 5th rounds of National Family Health Survey (NFHS), there is high prevalence of hysterectomies in the three states of Andhra Pradesh Telangana and Bihar. The three said states have more than double the number of hysterectomies taking place than the national average. Our purpose is to analyse whether these rates are increasing, decreasing or have stabilized and their reasons thereof. Such an analyses will help the policy makers in recommending good clinical practices within their states. MATERIAL AND METHODS: We used data from NFHS-4 (2015-16) and NFHS-5 (2019-2021) rounds. We calculated the differences in predicted probabilities for various factors, performed a Fairlie Decomposition analyses to quantify the positive and negative contributors in the prevalence of hysterectomy across the three states over two time points, and assessed the association of various socio-demographic characteristics to hysterectomy through a multilevel logistic regression model. RESULTS AND CONCLUSION: The results show that out of a total of 80,976 eligible respondents from the states under study, 5826 respondents self-reported that they had a hysterectomy done. It was found that older age, living in rural areas, belonging to other backward classes and higher wealth quintile, and higher parity positively contributed to the increased prevalence of hysterectomies in the three states. Higher educational attainment and previous use of family planning methods acted as protective factors. Characteristics at the household level had the highest intra-class correlation value in the prevalence of hysterectomy among women, followed by the Primary Sampling Unit and District levels, indicating high clustering in the prevalence of hysterectomy at the household level in all three states. Heavy menstrual bleeding/pain was the leading cause of hysterectomies in all three states, followed by fibroids/cysts in Andhra Pradesh and Telangana and Uterine disorder/ prolapse in Bihar. Over 80% of hysterectomies took place in the private hospitals. RECOMMENDATIONS: The study recommends better, more efficient and accountable hysterectomy surveillance to ensure more sustainable woman's reproductive health services in India. Government should adopt and implement standard regulatory guidelines to prevent provider-driven avoidable hysterectomies. Moreover, we recommend informing primary care professionals about the long-term health effects of hysterectomy and promoting alternate therapies for treating uterine fibroids and heavy bleeding.

Donor-Derived Cell-Free DNA as a Non-Invasive Biomarker for Graft Rejection in Kidney Transplant Recipients: A Prospective Study among the Indian Population.

Monitoring graft health and detecting graft rejection is crucial for the success of post-transplantation outcomes. In Western countries, the use of donor-derived cell-free DNA (dd-cfDNA) has gained widespread recognition as a diagnostic tool for kidney transplant recipients. However, the role of dd-cfDNA among the Indian population remains unexplored. The recipients were categorized into two groups: the post-transplant recipient (PTR) group (n = 16) and the random recipient (RR) group (n = 87). Blood samples were collected daily from the PTR group over a 7-day period, whereas the RR group's samples were obtained at varying intervals. In this study, we used a targeted approach to identify dd-cfDNA, which eliminated the need for genotyping, and is based on the minor allele frequency of SNP assays. In the PTR group, elevated dd-cfDNA% levels were observed immediately after transplantation, but returned to normal levels within five days. Within the RR group, heightened serum creatinine levels were directly proportional to increased dd-cfDNA%. Sixteen recipients were advised to undergo biopsy due to elevated serum creatinine and other pathological markers. Among these sixteen recipients, six experienced antibody-mediated rejection (ABMR), two exhibited graft dysfunctions, two had active graft injury, and six (37.5%) recipients showed no rejection (NR). In cases of biopsy-proven ABMR and NR, recipients displayed a mean ± SD dd-cfDNA% of 2.80 ± 1.77 and 0.30 ± 0.35, respectively. This study found that the selected SNP assays exhibit a high proficiency in identifying donor DNA. This study also supports the use of dd-cfDNA as a routine diagnostic test for kidney transplant recipients, along with biopsies and serum creatinine, to attain better graft monitoring.

Factors Contributing to the Change in Overweight/Obesity Prevalence Among Indian Adults: A multivariate decomposition analysis of data from the National Family Health Surveys.

INTRODUCTION: Concerns over the escalating burden of non-communicable diseases call for the redressal of behavioral risk factors like increased body mass index. Most studies have failed to quantify the contribution of socio-demographic characteristics in a linear trend. The present study aims to estimate the current prevalence of overweight and obesity in Indian adults and the contribution of different socio-demographic factors to the increasing prevalence. METHODS: We carried out a secondary data analysis of two National Family Health Survey (NFHS) rounds. The final sample includes 558,122 women and 84,477 men from round 4, and 574,099 women and 74,761 men were included from round 5, using a multi-stage stratified random sampling approach. Overweight/obesity was our primary dependent variable. Weighted bivariate analysis was used to ascertain the prevalence, and the adjusted odds ratios were computed to ascertain the potential predictors. The contribution of different factors towards rising burden over two time points was estimated using multivariate decomposition analysis for non-linear response models. RESULTS: Overall weighted prevalence of overweight and obesity in males and females per NFHS-5 was 44.02% and 41.16%, respectively, compared to 37.71% and 36.14% in NFHS-4. Decomposition analyses depict that the proportion of obesity increased by 6.37% and 5.10% points among men and women, respectively, over the two rounds. Compositional differences of participants (endowment) attributed to 16.54 and 49.90% differences, and the difference in coefficient or effect accounted for 83.46 and 50.10%, respectively, of the increase in the prevalence. The most significant factors contributing to increased prevalence were age, improving socio-economic status, smoking, unclean cooking fuel, and diabetes. CONCLUSIONS: The incremental rise in such a short period, mainly attributed to the effect of socio-demographic variables, is concerning. Policy interventions should prioritize health advocacy programs and aggressively target behavioral modifications while preparing the health systems to manage the people living with obesity.

Chronic non-communicable disease burden among reproductive-age women in India: evidence from recent demographic and health survey.

BACKGROUND: Chronic disease burden among women leads to various detrimental consequences, impacting women's health throughout their life course and off-springs. The present study explores the chronic disease profile among reproductive-aged women and analyzes the effects of various covariates on multimorbidity among reproductive-aged women in India. Here, multimorbidity is defined as an individual suffering from two or more chronic conditions. METHODS: The present study employed the most recent National Family Health Survey round, 2019-2021. The study utilized information on 695,707 non-pregnant women aged 15-49 years. The study used descriptive, bivariate, and multivariable ordered logistic regression analysis to explore the burden of chronic non-communicable diseases and multimorbidity. RESULTS: The mean age of women with single chronic condition-related morbidity is 30 years, whereas it was 35 years for those with multimorbidity. Approximately 28% of urban women suffered from multimorbidity. Further, significant factors that affect multimorbidity include age, educational attainment, working status, marital status, parity, menopause, religion, region, wealth index, tobacco use, alcohol consumption, and dietary patterns. CONCLUSIONS: The present study hints that women in the reproductive age group are at very high risk of developing multimorbidity in India. Most of the programs and policies are focused on the elderly population in terms of awareness and facilitating them with better health services. However, right now, one should also prioritize the emerging chronic condition related to chronic conditions other than hypertension, diabetes, and cancer among the study population, which is escalating as soon as women reach 30 years of age.

Cytochrome C as a potential clinical marker for diagnosis and treatment of glioma.

Gliomas are the most prevalent kind of malignant and severe brain cancer. Apoptosis regulating mechanisms are disturbed in malignant gliomas, as they are in added forms of malignancy. Understanding apoptosis and other associated processes are thought to be critical for understanding the origins of malignant tumors and designing anti-cancerous drugs for the treatment. The purpose of this study was to evaluate the variation in the expression level of several apoptotic proteins that are responsible for apoptosis in low to high-grade glioma. This suggests a significant change in the expression of five apoptotic proteins: Clusterin, HSP27, Catalase, Cytochrome C, and SMAC. Cytochrome C, one of the five substantially altered proteins, is a crucial component of the apoptotic cascade. The complex enzyme Cytochrome C is involved in metabolic pathways such as respiration and cell death. The results demonstrated that Cytochrome C expression levels are lower in glioma tissues than in normal tissues. What's more intriguing is that the expression level decreases with an increase in glioma grades. As a result, the discovery shows that Cytochrome C may be a target for glioma prognostic biomarkers.

Plasma-Derived Extracellular Vesicles Reveal Galectin-3 Binding Protein as Potential Biomarker for Early Detection of Glioma.

Gliomas are the most common type of the malignant brain tumor, which arise from glial cells. They make up about 40% of all primary brain tumors and around 70% of all primary malignant brain tumors. They can occur anywhere in the central nervous system (CNS) and have a poor prognosis. The average survival of glioma patients is approximately 6-15 months with poor aspects of life. In this edge, identification of proteins secreted by cancer cells is of special interest because it may provide a better understanding of tumor progression and provide early diagnosis of the diseases. Extracellular vesicles (EVs) were isolated from pooled plasma of healthy controls (n=03) and patients with different grades of glioma (Grade I or II or III, n=03 each). Nanoparticle tracking analysis, western blot, and flow cytometry were performed to determine the size, morphology, the concentration of glioma-derived vesicles and EV marker, CD63. Further, iTRAQ-based LC-MS/MS analysis of EV protein was performed to determine the differential protein abundance in extracellular vesicles across different glioma grades. We further verified galectin-3 binding protein (LGALS3BP) by ELISA in individual blood plasma and plasma-derived vesicles from control and glioma patients (n=40 each). Analysis by Max Quant identified 123 proteins from the pooled patient exosomes, out of which 34, 21, and 14 proteins were found to be differentially abundant by more than 1.3-fold in the different grades of glioma grade I, pilocytic astrocytoma; grade II, diffuse astrocytoma; grade III, anaplastic astrocytoma, respectively, in comparison with the control samples. A total of seven proteins-namely, CRP, SAA2, SERPINA3, SAA1, C4A, LV211, and KV112-showed differential abundance in all the three grades. LGALS3BP was seen to be upregulated across the different grades, and ELISA analysis from individual blood plasma and plasma-derived extracellular vesicles confirmed the increased expression of LGALS3BP in glioma patients (p<0.001). The present study provides LGALS3BP as a potential biomarker for early detection of glioma and improve survival outcome of the patient. The present study further provides the information of progression and monitoring the tumor grades (grade 1, grade II, grade III).

Exploring the role of epidermal growth factor receptor variant III in meningeal tumors.

Meningioma is the second most common type of intracranial brain tumor. Immunohistochemical techniques have shown prodigious results in the role of epidermal growth factor receptor variant III (EGFR vIII) in glioma and other cancers. However, the role of EGFR vIII in meningioma is still in question. This study attempt the confer searches for the position attained by EGFR vIII in progression and expression of meningioma. Immunohistochemistry technique showed that EGFR vIII is highly expressed in benign tumors as compared to the atypical meningioma with a highly significant p-value (p<0.05). Further analysis by flow cytometry results supported these findings thus presented high intensity of EGFR vIII in low grades of meningioma. The study revealed that the significant Ki 67 values, to predictor marker for survival and prognosis of the patients. Higher expression of EGFR vIII in low grades meningiomas as compared to high-grade tumors indicate towards its oncogenic properties. To our knowledge, limited studies reported in literature expressing the EGFR vIII in meningioma tumors. Hence, Opinions regarding the role that EGFR vIII in tumorigenesis and tumor progression are clearly conflicting and, therefore, it is crucial not only to find out its mechanism of action, but also to definitely identify its role in meningioma.

Role of Extracellular Vesicles in Glioma Progression: Deciphering Cellular Biological Processes to Clinical Applications.

Glioma predominantly targets glial cells in the brain and spinal cord. There are grade I, II, III, and IV gliomas with anaplastic astrocytoma and glioblastoma multiforme as the most severe forms of the disease. Current diagnostic methods are limited in their data acquisition and interpretation, markedly affecting treatment modalities, and patient outcomes. Circulating extracellular vesicles (EVs) or "magic bullets" contain bioactive signature molecules such as DNA, RNA, proteins, lipids, and metabolites. These secretory "smart probes" participate in myriad cellular activities, including glioma progression. EVs are released by all cell populations and may serve as novel diagnostic biomarkers and efficient nano-vehicles in the targeted delivery of encapsulated therapeutics. The present review describes the potential of EV-based biomarkers for glioma management.