👤 Iffat Naz

Nanoplastics are emerging aquatic contaminants capable of inducing subtle but physiologically relevant disruptions in fish. This study evaluated the effects of a chronic exposure to 44 nm polystyrene nanoplastics (PS-NPs) at 100 µg/L for 30 days on goldfish (Carassius auratus), integrating hepatic transcriptional responses land biochemical markers and intestinal metabolomics. Goldfish (n = 7 per group) showed no changes in weight, length or Fulton's condition factor, yet displayed distinct molecular and metabolic alterations. In the liver, PS-NPs significantly increased activities of ALT, AST, ALP, and EA (p < 0.05), indicating mild hepatocellular stress. Transcriptional analysis revealed upregulation of pparα, lpl, and cat, alongside downregulation of apoa1 and il1β, reflecting adjustments in lipid metabolism, antioxidant pathways and inflammatory tone. Systemic oxidative indicators (TAC, TOS, OSI) remained unchanged, suggesting the absence of whole-organism redox imbalance. Intestinal metabolomic profiling detected 255 metabolites, of which 53 were confidently identified. Significant changes occurred in six amino acids such as Asn, Arg, Pro decreased; Asp, Ser, Ala increased (p < 0.05) together with alterations in TCA-cycle intermediates such as malic acid. These shifts illustrate reorganization of nitrogen and carbon flow under PS-NP exposure, highlighting the intestine as the more metabolically responsive tissue compared with the liver. Overall, despite stable somatic growth, chronic PS-NPs elicited coordinated, tissue-specific physiological adjustments indicative of subclinical metabolic strain. Show less

The MAPK/ERK pathway plays a critical role in the regulation of milk production by controlling cellular processes such as proliferation, differentiation and survival, which are essential for lactogenesis and mammary gland function. Bubalus bubalis (Water buffalo), known for its unique physiological and ecological characteristics, serves as an ideal model to explore the evolutionary and molecular roles of MAPK/ERK pathway genes. This study presents the first comprehensive computational analysis of MAPK/ERK genes in B. bubalis, identifying 21 key genes involved in the pathway. Phylogenetic analysis clustered these genes into 13 distinct clades, such as MST1, GRB2, RAS, ETS1, JUN and FOS, and revealed close evolutionary relationships with Bos taurus and Camelus bactrianus. Structural characterization identified 10 conserved motifs, including essential domains like protein kinase, ETS and RAS, reflecting their functional significance. Gene structure analysis revealed substantial variation in exon-intron patterns, while synteny analysis confirmed collinearity with human orthologs, indicating genomic conservation. Physicochemical analysis highlighted a broad range of molecular weights and isoelectric points, with most proteins classified as hydrophilic and thermostable. Gene duplication and selection analyses revealed seven segmentally duplicated gene pairs, with the JUN-ETS1 and DUSP6-MST1 pairs showing evidence of positive selection, suggesting functional divergence. These findings establish a foundational understanding of MAPK/ERK pathway genes in B. bubalis and provide valuable insights into potential targets for genetic improvement, selective breeding and sustainable dairy management strategies aimed at enhancing milk production and quality. Show less

Systemic lupus erythematosus (SLE) increases cardiovascular disease (CVD) risk, and this is not explained by traditional risk factors. Characterization of blood immunologic signatures that associate with subclinical CVD and predict its progression has been challenging and may help identify subgroups at risk. Patients with SLE (n = 77) and healthy controls (HCs) (n = 27) underwent assessments of arterial stiffness, vascular wall inflammation, and coronary atherosclerosis burden with cardio-ankle vascular index (CAVI); fluorodeoxyglucose-positron emission tomography/computed tomography (CT) (target-to-background ratio [TBR]); and coronary CT angiography. Whole blood bulk RNA sequencing was performed in a subset of study participants (HC n = 10, SLE n = 20). In a partially overlapping subset (HC n = 24, SLE n = 64), serum inflammatory protein biomarkers were quantified with an Olink platform. CAVI, TBR, and noncalcified coronary plaque burden (NCB) were increased in patients with SLE compared to HCs. When comparing patients with SLE with high CAVI scores to those with low CAVI scores or to HCs, there was a down-regulation of genes in pathways involved in the cell cycle and differentially regulated pathways related to metabolism. Distinct serum proteins associated with increased CAVI (CCL23, colony-stimulating factor 1, latency-activating peptide transforming growth factor β1, interleukin 33 [IL-33], CD8A, and IL-12B), NCB (monocyte chemotactic protein 4 and FMS-like tyrosine kinase 3 ligand [Flt3L]), and TBR (CD5, IL-1α, AXIN1, cystatin D [CST5], and tumor necrosis factor receptor superfamily 9; P < 0.05). Blood gene expression patterns and serum proteins that associate with worse vascular phenotypes suggest dysregulated immune and metabolic pathways linked to premature CVD. Cytokines and chemokines identified in associations with arterial stiffness, inflammation, and NCB in SLE may allow for characterization of new CVD biomarkers in lupus. Show less

To identify age-related plasma extracellular vehicle (EVs) phenotypes in healthy adults. EV proteomics by high-resolution mass spectrometry to evaluate EV protein stability and discover age-associated EV proteins (n=4 with 4 serial freeze-thaws each); validation by high-resolution flow cytometry and EV cytokine quantification by multiplex ELISA (n=28 healthy donors, aged 18-83 years); quantification of WI-38 fibroblast cell proliferation response to co-culture with PKH67-labeled young and old plasma EVs. The EV samples from these plasma specimens were previously characterized for bilayer structure, intra-vesicle mitochondria and cytokines, and hematopoietic cell-related surface markers. Compared with matched exo-EVs (EV-depleted supernatants), endo-EVs (EV-associated) had higher mean TNF-α and IL-27, lower mean IL-6, IL-11, IFN-γ, and IL-17A/F, and similar mean IL-1β, IL-21, and IL-22 concentrations. Some endo-EV and exo-EV cytokine concentrations were correlated, including TNF-α, IL-27, IL-6, IL-1β, and IFN-γ, but not IL-11, IL-17A/F, IL-21 or IL-22. Endo-EV IFN-γ and exo-EV IL-17A/F and IL-21 declined with age. By proteomics and confirmed by flow cytometry, we identified age-associated decline of fibrinogen (FGA, FGB and FGG) in EVs. Age-related EV proteins indicated predominant origins in the liver and innate immune system. WI-38 cells (>95%) internalized similar amounts of young and old plasma EVs, but cells that internalized PKH67-EVs, particularly young EVs, underwent significantly greater cell proliferation. Endo-EV and exo-EV cytokines function as different biomarkers. The observed healthy aging EV phenotype reflected a downregulation of EV fibrinogen subpopulations consistent with the absence of a pro-coagulant and pro-inflammatory condition common with age-related disease. Show less

The aim of the study was to examine the expression profile of genes (APOE, FTO, and LPL) associated with metabolic syndrome (MetS) in subjects with concomitant atrial fibrillation (AF). A total of 690 subjects were categorized into control, AF without MetS, and AF with MetS. The expression profiles of the APOE, FTO, and LPL genes were decreased in AF subjects and AF subjects with MetS as compared to the controls. In AF without the MetS group, an inverse relationship was found between the expression of the LPL gene with body mass index (BMI) and a positive relationship with creatine kinase-MB, whereas expression of the FTO gene was inversely associated with fasting blood glucose and positively with cardiac troponin I in AF suffering from MetS. Expression of the LPL gene was directly linked with systolic blood pressure (SBP) and high-density lipoprotein-cholesterol (HDL-C), whereas an inverse correlation with heart rate and expression of the FTO gene in AF with MetS were shown. The expression of the LPL gene was inversely related to BMI in subjects with AF. The expression of the LPL gene was positively correlated with SBP and HDL-C and negatively correlated with heart rate, while the expression of the FTO gene was an important predictor of AF with MetS. The decreased expression of APOE, FTO, and LPL genes in AF with and without MetS indicates their potential contributing role in the pathogenesis of AF. 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

Understanding the global metabolic changes during the senescence of tumor cells can have implications for developing effective anti-cancer treatment strategies. Ionizing radiation (IR) was used to induce senescence in a human colon cancer cell line HCT-116 to examine secretome and metabolome profiles. Control proliferating and senescent cancer cells (SCC) exhibited distinct morphological differences and expression of senescent markers. Enhanced secretion of pro-inflammatory chemokines and IL-1, anti-inflammatory IL-27, and TGF-β1 was observed in SCC. Significantly reduced levels of VEGF-A indicated anti-angiogenic activities of SCC. Elevated levels of tissue inhibitors of matrix metalloproteinases from SCC support the maintenance of the extracellular matrix. Adenylate and guanylate energy charge levels and redox components NAD and NADP and glutathione were maintained at near optimal levels indicating the viability of SCC. Significant accumulation of pyruvate, lactate, and suppression of the TCA cycle in SCC indicated aerobic glycolysis as the predominant energy source for SCC. Levels of several key amino acids decreased significantly, suggesting augmented utilization for protein synthesis and for use as intermediates for energy metabolism in SCC. These observations may provide a better understanding of cellular senescence basic mechanisms in tumor tissues and provide opportunities to improve cancer treatment. Show less