👤 Umar Akram

Obesity is a highly complex, multifactorial disease influenced by dynamic interactions among genetic, epigenetic, environmental, and behavioral determinants that explicitly position genetics as the core. While advances in multi-omic integration have revolutionized our understanding of adiposity pathways, translation into personalized clinical nutrition remains a critical challenge. This review systematically consolidates emerging insights into the molecular and nutrigenomic architecture of obesity by integrating data from large-scale GWAS, functional epigenomics, nutrigenetic interactions, and microbiome-mediated metabolic programming. The primary aim is to systematically organize and synthesize recent genetic and genomic findings in obesity, while also highlighting how these discoveries can be contextualized within precision nutrition frameworks. A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science up to July 2024 using MeSH terms, nutrigenomic-specific queries, and multi-omics filters. Eligible studies were classified into five domains: monogenic obesity, polygenic GWAS findings, epigenomic regulation, nutrigenomic signatures, and gut microbiome contributions. Over 127 candidate genes and 253 QTLs have been implicated in obesity susceptibility. Monogenic variants (e.g., Show less

Intracranial aneurysms (IAs) are the major cause of subarachnoid hemorrhage. Stent-assisted coiling, especially with the Neuroform Atlas stent (NAS), has proved more effective than coiling alone for treating these aneurysms. To perform a systematic review and meta-analysis to investigate the efficacy and safety of the NAS in treating IAs. A comprehensive literature search was conducted on PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and clinicaltrials.gov from inception until June 2024. We included studies on ruptured and unruptured IAs treated with the NAS, covering experimental, observational, and case series across all age groups. The aneurysm occlusion rate was assessed by using the Raymond-Roy classification (RROC). The mRS and adverse events related to stent use were also recorded. The statistical analysis was conducted on R Version 4.3.2 by using the packages "meta" and "metasens." We reported our results as proportions with their corresponding CIs. Meta-regression, leave-one-out, and sensitivity analyses were conducted to confirm the robustness of our results. A total of 42 studies including 2434 participants with a mean age of 51 to 73 years were included. Among angiographic outcomes, the final RROC 1/RROC 2 was achieved in 95% of the patients, final RROC 1 in 82%, RROC 2 in 12%, and RROC 3 in 5% of the patients. Additionally, 93% of the patients showed mRS grade 0, 5% showed mRS grade 1, 3% showed mRS grade 2, 2% showed mRS grade 3, 0% showed mRS grade 4, 0% showed mRS grade 5, and 1% showed mRS grade 6. All adverse events had a ≤5% rate. Due to limited cause-specific data, we were unable to analyze mortality specific to the stent placement and complications. Despite the large number of studies included, comparative studies were still observed to be scarce. Although the generalizability of our findings is limited, this study demonstrates that the NAS is highly effective for treating IAs, with high occlusion rates and a low incidence of adverse events. The stent's performance, supported by comprehensive analysis, highlights its safety and efficacy in managing both ruptured and unruptured aneurysms. Show less

Oxidative stress (OS) and c-Jun N-terminal kinase (JNK) are both key indicators implicated in neuro-inflammatory signalling pathways and their respective neurodegenerative diseases. Drugs targeting these factors can be considered as suitable candidates for treatment of neuronal dysfunction and memory impairment. The present study encompasses beneficial effects of a naturally occurring triterpenoid, friedelin, against scopolamine-induced oxidative stress and neurodegenerative pathologies in mice models. The treated animals were subjected to behavioural tests i.e., Y-maze and Morris water maze (MWM) for memory dysfunction. The underlying mechanism was determined via western blotting, antioxidant enzymes and lipid profile analyses. Molecular docking studies were carried out to predict the binding modes of friedelin in the binding pocket of p-JNK protein. The results reveal that scopolamine caused oxidative stress by (1) inhibiting catalase (CAT), peroxidase enzyme (POD), superoxide dismutase (SOD), and reduced glutathione enzyme (GSH); (2) the up-regulation of thiobarbituric acid reactive substances (TBARS) in mice brain; and (3) affecting the neuronal synapse (both pre- and post-synapse) followed by associated memory dysfunction. In contrast, friedelin administration not only abolished scopolamine-induced oxidative stress, glial cell activation, and neuro-inflammation but also inhibited p-JNK and NF-κB and their downstream signaling molecules. Moreover, friedelin administration improved neuronal synapse and reversed scopolamine-induced memory impairment accompanied by the inhibition of β-secretase enzyme (BACE-1) to halt amyloidogenic pathways of amyloid-β production. In summary, all of the results show that friedelin is a potent naturally isolated neuro-therapeutic agent to reverse scopolamine-induced neuropathology, which is characteristic of Alzheimer's disease. Show less

Tannic acid (TA) is a natural compound present abundantly in fruit such as grapes and green tea. In this study, we have evaluated the therapeutic efficacy of TA against Lipopolysaccharide (LPS)-induced oxidative stress-mediated memory impairment, neuroinflammation, insulin signaling impairment, and Amyloid Beta (Aβ) deposition in adult male mice. The LPS was administered once per week and TA twice a week to adult male mice for three months consecutively. Behavioral studies were performed using different behavioral models such as balance beam, novel object recognition (NOR), Morris water maze (MWM), and Y-maze tests. The protein expression of different mediators such as TNF-α, p-JNK, pIRS636, BACE1, APP, and Aβ was evaluated through western blot and immunofluorescence staining techniques. Biochemical assays were carried out to assess the antioxidant activities of TA. The computational study was conducted to predict the binding mode of TA with target sites of TNF-α. Behavioral studies showed that the TA-treated mice exhibited gradual memory improvement. TA significantly inhibited BACE1 activity and reduced production and accumulation of Aβ in the hippocampus of mice brains. Moreover, the TA significantly inhibited LPS-induced ROS production and enhanced the glutathione levels. Furthermore, we have shown via the computational method for the first time that TA inhibits LPS-triggered TNF-ὰ and its downstream signaling to reduce AD pathology including memory impairment, neuroinflammation, insulin signaling impairment, and Aβ deposition in adult mice. Taken together our current study demonstrates that TA is a potential candidate for the abrogation of LPS-induced neurotoxicity and AD pathology in rodent's models. Show less

The success of immune checkpoint therapy shows tumor-reactive T cells can eliminate cancer cells but are restrained by immunosuppression within the tumor micro-environment (TME). Cancer associated fibroblasts (CAFs) are the dominant stromal cell in the TME and co-localize with T cells in non-small cell lung cancer. We demonstrate the bidirectional nature of CAF/T cell interactions; T cells promote expression of co-inhibitory ligands, MHC molecules and CD73 on CAFs, increasing their production of IL-6 and eliciting production of IL-27. In turn CAFs upregulate co-inhibitory receptors on T cells including the ectonucleotidase CD39 promoting development of an exhausted but highly cytotoxic phenotype. Our results highlight the bidirectional interaction between T cells and CAFs in promoting components of the immunosuppressive CD39, CD73 adenosine pathway and demonstrate IL-27 production can be induced in CAF by activated T cells. Show less