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Identification of biomarkers and molecular mechanisms implicated in genetic variations underlying Alzheimer’s disease pathogenesis

2024-10-28T07:38:39Z

Title: Identification of biomarkers and molecular mechanisms implicated in genetic variations underlying Alzheimer’s disease pathogenesis Authors: Duc Nguyen, Hai; Huong Vu, Giang; Kim, Woong-Ki Abstract: Identification of biomarkers and molecular mechanisms implicated in genetic variations underlying Alzheimer’s disease pathogenesis Hai Duc Nguyen a,*, Giang Huong Vu b, Woong-Ki Kim c a Division of Microbiology, Tulane National Primate Research Center, Tulane University, Covington, LA, USA b Hong Bang Health Center, Hai Phong, Viet Nam c Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, USA A R T I C L E I N F O Handling Editor: Prof A Angelo Azzi Keywords: GWAS Alzheimer’s disease Biomarkers Molecular mechanisms A B S T R A C T We analyzed data from human genome-wide association studies (GWASs) to identify genetic variants and biological pathways linked to Alzheimer’s disease (AD). Ten AD biomarkers (APOE, NECTIN2, APOC1, APOC1P1, TOMM40, RNU4-67P, KRAS, Y_RNA, THORLNC, LINC01956) were found across studies, including six central genetic variants (MAPT (rs242557-A), GRIN2B (rs74442473-G), APOE (rs438811-T), ANK3 (rs438811-T), BIN1 (rs744373-G), and BDNF (rs7481773-A)). ANK3 (rs438811-T) and GRIN2B (rs74442473-G) were essential hub biomarkers for amyloid plaques, while MAPT (rs242557-A) and BIN1 (rs744373-G) were crucial for neurofibrillary tangles (NFTs). Higher-risk AD biomarkers were associated with increased protein-lipid complex formation, while lower-risk AD biomarkers were correlated with improved synaptic function. Six essential miRNAs (hsa-miR-124–3p, 15a-5p, 16–5p, 204–5p, 520g-3p, 520h) and three transcription factors (ZMAT4, ZBED6, FOXG1) emerged as possible candidates to reveal the genetic differences that lead to amyloid plaques, NFTs, and ultimately AD. These findings serve as a basis for potential AD treatments and offer new avenues for therapeutic approaches to directly target the genetic variations and processes associated with the disease.

The interaction between ultra-processed foods and genetic risk score on body adiposity index (BAI), appendicular skeletal muscle mass index (ASM), and lipid profile in overweight and obese women

2024-10-28T07:33:01Z

Title: The interaction between ultra-processed foods and genetic risk score on body adiposity index (BAI), appendicular skeletal muscle mass index (ASM), and lipid profile in overweight and obese women Authors: Gholami, Fatemeh; Lesani, Azadeh; Soveid, Neda Abstract: The interaction between ultra-processed foods and genetic risk score on body adiposity index (BAI), appendicular skeletal muscle mass index (ASM), and lipid profile in overweight and obese women Fatemeh Gholami a,d, Azadeh Lesani a, Neda Soveid a, Niloufar Rasaei a, Mahsa Samadi a, Niki Bahrampour c, Gholamali Javdan b,**, Khadijeh Mirzaei a,* a Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran b Food Health Research Center, Hormozgan University of Medical Sciences, Bandar ʽAbbas, Iran c Department of Nutrition, Science and Research Branch Islamic Azad University (SRBIAU), Tehran, Iran d Department of Clinical Nutrition, Shahid Mohammadi Hospital, Hormozgan University of Medical Sciences, Bandar Abbas, Iran A R T I C L E I N F O Handling Editor: Prof A Angelo Azzi Keywords: Genetic risk score Ultra-processed foods Body composition Body adiposity index Appendicular skeletal muscle mass A B S T R A C T Background & aims: Ultra-processed foods (UPF) are formulations of ingredients, resulting from a series of industrial processes. Excess intake of UPF is associated with an increased risk of obesity and chronic disease. The present study investigates the interaction between the consumption of UPF and genetic risk score with body composition, body adiposity index (BAI), and appendicular skeletal muscle mass (ASM) in overweight and obese women. Method: The study is cross-sectional with 376 overweight and obese women aged 18–65 years. The food consumption was obtained with 147-item food frequency (FFQ), and food items were grouped according to the level of processing as per the NOVA classification. Three single nucleotide polymorphisms (SNPs), including Caveolin_1 (Cav_1), Melanocortin4 receptor (MC4R), and cryptochrome circadian regulator 1 (CRY1), were used to calculate GRS. The individual risk allele for each SNP was calculated using the incremental genetic model. Each SNP was recoded as 0, 1, or 2 based on the number of risk alleles associated with a higher body mass index (BMI). Subsequently, the unweighted GRS was computed by summing the number of risk alleles across the three SNPs. The GRS scale spans from 0 to 6, with each point representing a risk allele.Anthropometric measurements and some blood parameters were measured by standard protocols. Results: After controlling for confounders such as age, energy intake, and BMI a significant interaction was found for appendicular skeletal muscle mass (β = 􀀀 1.65, P = 0.04) and appendicular skeletal muscle mass index (β = 􀀀 0.38, P = 0.07) on the NOVA classification system and GRS. Conclusions: The findings of this study showed a significant interaction between GRS and the NOVA classification system on some body composition, including appendicular skeletal muscle mass. A higher intake of ultraprocessed foods may be associated with lower appendicular skeletal muscle mass in people with high obesity- GRS.

Hemostatic abnormalities for predicting and management of disease severity in COVID-19 affected patients: Review

2024-10-28T07:25:53Z

Title: Hemostatic abnormalities for predicting and management of disease severity in COVID-19 affected patients: Review Authors: Umadevi, Kovuri; Clementina, Ruchira; Sundeep, Dola Abstract: Hemostatic abnormalities for predicting and management of disease severity in COVID-19 affected patients: Review Kovuri Umadevi a,*, Ruchira Clementina b, Dola Sundeep c,**, Mohd Imran Ali a, Rajarikam Nagarjuna Chary a, Arundhathi Shankaralingappa d a Department of Pathology, Government Medical College and Hospital, Khaleelwadi, Nizamabad, 503001, Telangana, India b Department of Health Sciences, Palm, BeachAtlantic University, Florida, 33401, USA c Biomedical Research Laboratory, Department of Electronics and Communication Engineering, Indian Institute of Information Technology Design and Manufacturing (IIITDM) Kurnool, Jagannathagattu Hill, Kurnool, 518008, Andhra Pradesh, India d Department of Pathology, All India Institute of Medical Sciences (AIIMS), Managalagiri, 522503, Andhra Pradesh, India A R T I C L E I N F O Handling Editor: Prof A Angelo Azzi Keywords: SARS-COV-2 Hemostatic abnormalities Covid-19 D-dimer Ferritine And fibrinogen A B S T R A C T The recent Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic has posed significant challenges to global healthcare, with a myriad of impacts on the human body, particularly noted in hemostatic abnormalities observed in COVID-19 patients. These abnormalities have been linked to an increased risk of serious thrombotic events like deep vein thrombosis, pulmonary embolism, and stroke. Unlike existing literature, this comprehensive review delves into the long-term implications of these abnormalities, providing invaluable guidance for ongoing patient care as we move into the post-pandemic era. We cover the entire spectrum of hemostatic abnormalities, including elevated levels of aPTT, D-dimer, PT, ferritin, INR, fibrinogen, fibrin, and FDP, all of which create a complex clinical scenario necessitating vigilant monitoring and targeted therapeutic interventions. With a focus on the heightened risk of thrombotic complications, we underscore the importance of timely anticoagulant therapy and other necessary interventions, tailored to the patient’s unique clinical presentation. This review stands as a critical resource for clinicians, hematologists, and healthcare providers, equipping them to navigate the complexities of COVID-19 in both acute and long-term settings, ensuring optimal patient outcomes. As we collectively navigate the lasting impact of the pandemic, this targeted and in-depth analysis becomes an indispensable tool in advancing our understanding and management of COVID-19.

Higher oxidative stress and inflammation in obese compared to lean patients with type 2 diabetes mellitus

2024-10-28T07:19:56Z

Title: Higher oxidative stress and inflammation in obese compared to lean patients with type 2 diabetes mellitus Authors: Mehndiratta, Mohit; Anthonio Almeida, Edelbert; Chawla, Diwesh; S.V. Madhu, S.V. Madhu; Garg, Seema; Kar, Rajarshi Abstract: Higher oxidative stress and inflammation in obese compared to lean patients with type 2 diabetes mellitus Mohit Mehndiratta a,*, Edelbert Anthonio Almeida a, Diwesh Chawla b, S.V. Madhu c, Seema Garg a, Rajarshi Kar a a Department of Biochemistry, UCMS & GTBH, New Delhi, India b Multi-disciplinary Research Unit (MRU), UCMS, New Delhi, India c Department of Endocrinology, UCMS & GTBH, New Delhi, India A R T I C L E I N F O Keywords: Type 2 diabetes mellitus Inflammation Lean Obese Oxidative stress A B S T R A C T Aim: To compare mRNA [messenger RNA] expression of RELA, NFκB1, TNF-α, IL-6 and MCP-1 in whole blood & serum Total Antioxidant status [TAS] in newly diagnosed lean and obese patients with T2DM. Methods: Newly diagnosed treatment naïve patients of T2DM were enrolled in this study. The patients were divided into two groups of 30 patients each, lean (BMI< 18.5 kg/m2) and obese (BMI >25 kg/m2) groups. mRNA expression of RELA, NFκB1, TNF-α, IL-6 and MCP-1 was measured by real time PCR. Serum TAS was measured using a commercially available kit. Results: There was a 2.7-fold increase in mRNA expression of RELA in obese group compared to the lean group. There was a 1.3-fold increase in mRNA expression of NFκB1, a 3.24-fold increase in mRNA expression of TNF-α, a 4.7-fold increase in mRNA expression of IL 6 and a 3.8-fold increase in mRNA expression of MCP-1 in obese group compared to the lean group. Mean fasting serum insulin levels were 16.07 ± 8.39 μIU/mL in the lean group and 27.11 ± 4.91μIU/mL in the obese group (p = 0.001). Mean TAS level was 5.39 ± 2.28 μM Trolox Equivalents in the obese group and 3.85 ± 3.33 μM Trolox Equivalents in the lean group (p = 0.001). Conclusion: Inflammation and OS is higher in obese patients of T2DM compared to lean patients of T2DM. This could be the result of excess adipokines production or resistance to the anti-inflammatory effects of insulin with multiple explanations. Our study suggests a difference in the pathogenic mechanism in lean patients when compared with obese T2DM patients.