Biology subjects

Farooq, S.

Publications and source records attributed to Farooq, S..

5 recordsLinked to original sources

bioRxiv2026

Omics-analyses of Fermented Onion pickle in Shaping Gut Microbiota and Immune Response in Women: A Community-Based Trial in Pakistan

A fermented-food intervention trial conducted in Pakistan suggested beneficial changes in the composition of the gut microbiota in healthy women. Using a subset (n=17) of the same participants, this study further investigates the impact of fermented food (onion pickle) on gene expression levels using RNA transcriptomics, with a focus on host-microbiome interactions. After consuming pickles (50g/day) for eight weeks, blood and stool samples of participants were collected at baseline and post-intervention to assess inflammatory markers, 16S rRNA gene sequencing, clinical parameters, and RNA sequencing. Among inflammatory biomarkers, lipocalin (LCN-2) levels significantly decreased (pre=86.5{+/-}80.1ng/mL, post=61.0{+/-}59.0 ng/mL, p=0.04, paired T-test). Additionally, the intervention downregulated pathways (p<0.05) involved host responses to microbial stimuli, including response to bacterial origin, chemotaxis, and response to lipopolysaccharide. In gut microbiota, observed -diversity significantly increased post-intervention (p=0.02). Linear discriminant analysis effect size (LEfSe) revealed differential expressions (LDA [≥] 2.0) of Olsenella and Coriobacteriales at week-8, where Olsenella sp. showed a significant negative correlation with LCN-2 (R=-0.36, p<0.05, Spearmans correlation). These findings suggest that fermented onion pickle consumption for eight weeks modestly alters gut microbial diversity and composition and is associated with reduced inflammatory markers and altered host immune-related gene expression, potentially improving intestinal health. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/711246v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@18679e0org.highwire.dtl.DTLVardef@1ab62eeorg.highwire.dtl.DTLVardef@ec318forg.highwire.dtl.DTLVardef@a9b94c_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2025

Depot-specific roles for sphingosine kinase 1 in conversion of white adipose to thermogenic adipose

BackgroundAs of 2023, approximately 100.1 million adults and 14.7 million children in the USA are obese. Many comorbidities develop with obesity, which impairs quality of life and burdens the health care system. Consequently, there is an urgent need for interventions and treatments to reverse obesity and its comorbidities and restore health. Sphingosine Kinase 1 (SphK1), a key enzyme in sphingolipid metabolism, produces sphingosine-1-phosphate (S1P), a bioactive lipid implicated in obesity and metabolic dysfunction. While global deletion of Sphk1 protects against diet-induced obesity, adipocyte-specific SPHK1 deficiency paradoxically promotes weight gain, glucose intolerance, and adipose inflammation. Given the known role of sphingolipids in adipose thermogenesis, we investigated whether Sphk1 regulates adipocyte beiging and mitochondrial function. MethodsWe assessed thermogenic responses in SphK1-deficient adipocytes and adipocyte-specific Sphk1 knockout (Ad-SphK1{Delta}) mice under basal and {beta}3-adrenergic stimulation using CL 316,243. Thermoneutral housing (30{degrees}C) and room temperature (23{degrees}C) conditions were used to minimize and assess ambient temperature effects on thermogenesis. Molecular, histological, and bioenergetic analyses were conducted across multiple adipose depots. Results{beta}3-adrenergic stimulation upregulated Sphk1 expression in mature white adipocytes, while SphK1-deficient adipocytes exhibited enhanced Ucp1 expression, indicating a suppressive role for SphK1 in beiging. In vivo, adipocyte-specific Sphk1 knockout (Ad-SphK1{Delta}) mice showed elevated Ucp1 expression in inguinal and gonadal white adipose tissue (iWAT, gWAT), both basally and after CL 316,243 treatment. These changes were accompanied by depot-specific alterations in adipocyte size and increased adiposity, independent of ambient temperature. Despite similar elevation of thermogenic markers, Sphk1 deletion had differential effect on mitochondrial function: iWAT showed increased mitochondrial content but reduced complex IV activity and ATP production, whereas gWAT showed reduced mitochondrial abundance without changes in respiration. ConclusionOur work suggests that Sphk1 may act as a negative regulator of thermogenic expression and affect mitochondrial function in a depot-specific manner. Loss of Sphk1 enhances beiging but compromises mitochondrial efficiency, revealing a complex role for the SphK1/S1P axis in adipose plasticity and metabolic regulation. These insights may inform future therapeutic strategies targeting sphingolipid pathways for obesity and metabolic disease.

biochemistry↗

bioRxiv2023

Prioritization of The Zinc finger domain within BCL11A gene by the Amelioration capability of hemoglobinopathies using CRISPR-Cas9 technology

BCL11A/EVI9, a zinc-finger protein primarily expressed in brain and hematopoietic cells, plays a central role in lymphocyte development, gamma-globin suppression, spinal neuron development, sensory innervation, neuronal polarity, migration, and is associated with microcephaly and dysregulated brain-related genes, offering therapeutic potential for sickle cell disease. The function of the transcriptional regulator is intricately linked to its structural organization, which determines its ability to interact with specific DNA sequences and modulate gene expression. BCL11A boasts multiple domains, including six C2H2 zinc fingers, a C2HC zinc finger, a NuRD-interacting domain, an acidic domain, and a proline-rich domain. In the present study, we delve into the intricate structure and function of the zinc finger domains located in the BCL11A gene, which plays a crucial role in regulating the expression of gamma-globin gene. Specifically, three C2H2-type zinc finger domains, Znf4, Znf5, and Znf6, within BCL11A, are known to bind to DNA. Znf4 and Znf5 demonstrate a significant interaction with the TGACCA motif in the gamma-globin -115 HPFH region sequence, contributing substantially to DNA binding specificity. Although Znf3 and Znf6 also interact with DNA, their contributions are comparatively minor. Employing CRISPR-Cas9 technology, targeted genomic deletions of Znf4 exhibit high efficiency, opening doors for further research. Edited CD34+ cells successfully differentiate into erythrocytes without impairments, underscoring CRISPR-Cas9s suitability for studying gene functions in erythropoiesis. Furthermore, BCL11A knockdown via sgRNAs results in elevated gamma-globin expression, offering a promising therapeutic avenue for beta-hemoglobinopathies. HPLC analysis reveals a substantial increase in HbF levels, particularly upon Znf4 deletion, emphasizing BCL11A gene potential as a therapeutic target. These findings also highlight the connection between the function of BCL11A and its structural organization, which can be modulated, and this insight can potentially be extended to uncover its roles in various other domains.

molecular biology↗

bioRxiv2021

Functional single cell selection and annotated profiling of dynamically changing cancer cells

A method connecting single cell genomic or transcriptomic profiles to functional cellular characteristics, in particular time-varying phenotypic changes, would be transformative for single cell and cancer biology. Here, we present fSCS: functional single cell selection. This technology combines a custom-built ultrawide field-of-view optical screening microscope, fast automated image analysis and a new photolabeling method, phototagging, using a newly synthesized visible-light-photoactivatable dye. Using fSCS, we screen, selectively photolabel and isolate cells of interest from large heterogeneous populations based on functional dynamics like fast migration, morphological variation, small molecule uptake or cell division. We combined fSCS with single cell RNA sequencing for functionally annotated transcriptomic profiling of fast migrating and spindle-shaped MCF10A cells with or without TGF{beta} induction. We identified critical genes and pathways driving aggressive migration as well as mesenchymal-like morphology that could not be detected with state-of-the-art single cell transcriptomic analysis. fSCS provides a crucial upstream selection paradigm for single cell sequencing independent of biomarkers, allows enrichment of rare cells and can facilitate the identification and understanding of molecular mechanisms underlying functional phenotypes.

bioengineering↗

bioRxiv2018

Inpatient mobility to predict hospital-onset Clostridium difficile: a network approach

With hospital-onset Clostridium difficile Infection (CDI) still a common occurrence in the U.S., this paper examines the relationship between unit-wide CDI susceptibility and inpatient mobility and creates a predictive measure of CDI called \"Contagion Centrality\". A mobility network was constructed using two years of patient electronic health record (EHR) data within a 739-bed hospital (Jan. 2013 - Dec. 2014; n=72,636 admissions). Network centrality measures were calculated for each hospital unit (node) providing clinical context for each in terms of patient transfers between units (edges). Daily unit-wide CDI susceptibility scores were calculated using logistic regression and compared to network centrality measures to determine the relationship between unit CDI susceptibility and patient mobility. Closeness centrality was a statistically significant measure associated with unit susceptibility (p-value < 0.05), highlighting the importance of incoming patient mobility in CDI prevention at the unit-level. Contagion Centrality (CC) was calculated using incoming inpatient transfer rates, unit-wide susceptibility of CDI, and current hospital CDI infections. This measure is statistically significant (p-value <0.05) with our outcome of hospital-onset CDI cases, and captures the additional opportunities for transmission associated with inpatient transfers. We have used this analysis to create an easily interpretable and informative clinical tool showing this relationship and risk of hospital-onset CDI in real-time. Quantifying and visualizing the combination of inpatient transfers, unit-wide risk, and current infections help identify hospital units at risk of developing a CDI outbreak, and thus provide clinicians and infection prevention staff with advanced warning and specific location data to concentrate prevention efforts.

epidemiology↗