Metabolic-dysfunction-associated steatotic liver disease (MASLD) is becoming the most common chronic liver disease worldwide and is of concern among African Americans (AA) in the United States. This pilot study evaluated the differential gene expressions and identified the signature genes in the disease pathways of AA individuals with MASLD. Blood samples were obtained from MASLD patients (n = 23) and non-MASLD controls (n = 24) along with their sociodemographic and medical details. Whole-blood transcriptomic analysis was carried out using Affymetrix Clarion-S Assay. A validation study was performed utilizing TaqMan Arrays coupled with Ingenuity Pathway Analysis (IPA) to identify the major disease pathways. Out of 21,448 genes in total, 535 genes (2.5%) were significantly (p < 0.05) and differentially expressed when we compared the cases and controls. A significant overlap in the predominant differentially expressed genes and pathways identified in previous studies using hepatic tissue was observed. Of note, TGFB1 and E2F1 genes were upregulated, and HMBS was downregulated significantly. Hepatic fibrosis signaling is the top canonical pathway, and its corresponding biofunction contributes to the development of hepatocellular carcinoma. The findings address the knowledge gaps regarding how signature genes and functional pathways can be detected in blood samples (‘liquid biopsy’) in AA MASLD patients, demonstrating the potential of the blood samples as an alternative non-invasive source of material for future studies.

Poor glycemic control and dyslipidemia are hallmarks of type 2 diabetes mellitus (T2DM), which predispose to cardiovascular diseases. Peroxisome proliferator-activated receptor-α (PPARα) has been associated with atherosclerosis, but its role in T2DM is less clear. Previously, we studied PPARα expression levels in diabetics with and without dyslipidemia (DD). In this study we described the association with fasting blood glucose, HbA1c levels and lipid levels of the study population. Patient demography and biochemical data were collected from hospitals in Islamabad, Pakistan, and RT-PCR data of PPARα expression were retrieved from our previous study from the same cohort. We performed t-tests and regression analysis to evaluate the relationships between PPARα expression and demographic and clinical variables. As expected, body mass index and HbA1c were elevated in T2DM and DD patients compared to controls. Blood lipids (total cholesterol, triglycerides, LDL and HDL) were significantly higher in the DD group compared to the other two groups. In the T2DM and DD groups, the PPARα expression was not associated with any of the physical and biochemical parameters measured in this study. Expression of the PPARα gene was independent of blood lipids and glycemic control in this study. Further research is necessary to better understand the biological parameters of PPARα expression.

Background: Metabolic diseases like chronic Type 2 Diabetes Mellitus (T2DM) are now a serious global health concern In the United States. African Americans (AA) are being affected at a disproportionate rate with the condition compared to other ethnic groups, yet there are relatively few studies that have specifically focused on this group. Our previous findings have suggested that AA patients with T2DM had gene expression signals associated with Alzheimer’s Disease (AD). The current pilot study aimed to examine the amyloidogenic processing pathways (APP) and cholesterol biosynthesis‐related marker genes in the circulation of clinically identified T2DM AA patients in the Washington DC area.Method: A total of 12 confirmed T2DM AA patients and matched healthy controls were recruited from a regional hospital's outpatient departments, with sociodemographic and medical details obtained for analysis. Whole blood was collected in DNA/RNA Shield™ Blood Collection Tube for RNA extraction and isolation. The APP and cholesterol biosynthesis‐related gene expression patterns were examined using profiler array gene expression (qRT‐PCR). The affected pathways were identified using Ingenuity Pathway Analysis (IPA).Result: We identified Amyloid Processing, Neuroinflammation Signaling, ERB4 Signaling, Interleukin signaling, and nNos signaling as the top canonical pathways. The top diseases and their functions were Metabolic disease, Neurological disease, Organismal Injury and Abnormalities, Psychological disorders, and cardiovascular diseases. APP, CDK5R1, PSENEN, and MAPT were the key genes that were differentially expressed (≥2‐fold change at p <0.05) in APP pathways, with PHLPP2, IL33, APP, CRP, & TAC1 as the top upstream regulators.Conclusion: The results suggest that T2DM may influence the risk of developing AD in AA patients. Further studies on larger multi‐ethnic populations would be of interest to validate and extend these findings. Information from such biochemical and genetic studies will be crucial to the development of therapeutic targets to assess future AD risks.

Reduction of radiation dose from medical investigations still remains an important strategy. The combined effect of the reduced injected activity of ¹⁸F – FDG, low tube voltage & iodine concentration with iterative reconstruction on image quality, radiation dose, and DNA damage in patients undergoing PET/CT examination were examined. The study includes 16 patients who underwent PET/CT investigation twice using two different protocols; standard & new. A new protocol was followed during follow-up after 4–6 months. All acquisition and reconstruction parameters were the same in both protocols, except administered activity, iodine concentration and CT tube voltage which was reduced. Image quality was assessed using various parameters. Effective dose from PET/CT was assessed using CTDIvol and ICRP coefficients. DNA damage analysis was performed using comet and γ-H2AX assay. No significant difference was noted in quality parameters between two protocols (p > 0.05) except CT noise level (p < 0.05). Mean iodine dose, total radiation dose, mean foci and TM in the new protocol were found significantly lower than standard PET/CT (p < 0.05). There were 26.68% reduction in radiation dose, 10% reduction in contrast load, 20.31% reduction in the number of foci and 17.67% reduction in TM was noted with optimized protocol.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a growing health concern, yet the role of non-coding RNAs (ncRNAs), including microRNAs (miRNAs), in its pathogenesis remains poorly understood. In this pilot study, we aimed to identify significantly expressed miRNAs and ncRNAs and correlate transcriptomic patterns of the findings with previously identified coding gene expression profiles to explore potential regulatory mechanisms in MASLD. Participants were selected from an existing study population. We conducted transcriptomic profiling of miRNAs and other ncRNAs in whole-blood samples from African American (AA) individuals with MASLD and matched controls (n = 4 per group) as a discovery cohort. A subsequent qRT-PCR validation study was performed in 30 participants, including 14 individuals with MASLD and 16 controls. miRNA sequencing was performed by Zymo, USA, followed by miRNA extraction using the Zymo-Seq™ miRNA Library Kit. Differentially expressed miRNAs and ncRNAs were analyzed using Ingenuity Pathway Analysis (IPA) to identify associated biological pathways. A total of 1412 miRNAs and 5423 other ncRNAs were identified in this study. Among them, 35 miRNAs and 28 other ncRNAs exhibited significant differential expressions (fold-change cutoff 1.5, p < 0.05). miR-206 was consistently upregulated, whereas miR-1343-5p, miR-1299, miR-224-5p, and miR-193a-5p were downregulated across all samples. miR-206 upregulation and miR-185-3p/miR-224-5p/miR-218-5p downregulation were validated, associating with lipid metabolism impairment and hepatic fibrosis via the AMPK/TGF-β pathway, implicating ncRNA-mediated regulation. To our knowledge, this is the first whole-blood non-coding RNA transcriptomic study in AA MASLD, an under-represented population. This small-scale pilot study requires validation in large multi-ethnic cohorts to confirm generalizability.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing health concern, yet the role of non-coding RNAs (ncRNAs), including microRNAs (miRNAs), in its pathogenesis remains poorly understood. In this pilot study, we aimed to identify significantly expressed miRNAs and ncRNAs and correlate transcriptomic patterns of the findings with previously identified coding gene expression profiles to explore potential regulatory mechanisms in MASLD. Participants were selected from an existing study population. We conducted transcriptomic profiling of miRNAs and other ncRNAs in whole-blood samples from African American individuals with MASLD and matched controls (n = 4 per group) as a discovery cohort. A subsequent qRT-PCR validation study was performed in 30 participants, including 14 individuals with MASLD and 16 controls. miRNA sequencing was performed by Zymo, USA followed by miRNA extraction using Zymo-Seq™ miRNA Library Kit. Differentially expressed miRNAs and ncRNAs were analyzed using Ingenuity Pathway Analysis (IPA) to identify associated biological pathways. A total of 1,412 miRNAs and 5,423 other ncRNAs were identified in this study. Among them, 35 miRNAs and 28 other ncRNAs exhibited significant differential expressions (fold change cut off 1.5, p < 0.05). miR-206 was upregulated, potentially compensating for insulin resistance, while miR-1343-5p miR-1299, miR-224-5p, and miR-193a-5p were downregulated, connecting impaired lipid metabolism and fibrosis. The validation study confirmed the upregulation of miR-206 and downregulation of miR-185-3p, miR-224-5p, and miR-218-5p. IPA results identified hepatic fibrosis and cirrhosis pathways enriched with interactions between miRNA and ncRNA. Our findings highlight promising candidates for future biomarker validation and therapeutic targeting. Further large-scale studies are necessary to validate these candidates and elucidate their role in MASLD pathogenesis and ethnic disparities.