Biology subjects

Khan, I. A.

Publications and source records attributed to Khan, I. A..

6 recordsLinked to original sources

bioRxiv2026

Loss of Mast cells and histaminergic signaling link diet to platelet-mediated NETosis and mammary cancer recurrence

Breast cancer recurrence remains a clinical challenge. The period after the treatment of the primary tumor while cancer cells that evaded initial treatment lay dormant, provides a unique window of opportunity for interventions to prevent recurrence. Specific modifiable factors such as consumption of high fat diets or elevated circulating cholesterol are associated with decreased time to recurrence. Mechanistically, oxidized cholesterol and lipid species have been implicated in the regulation of the tumor microenvironment. This suggests that consumption of food prepared under oxidizing conditions such as pan-frying, may be an underappreciated risk. Using murine models of mammary cancer dormancy, we found that a diet enriched with fat from fried, cured bacon (cfBF) decreased dormancy latency times. Resulting lesions had fewer mast cells (MCs). Loss of MCs alone resulted in reemergence from dormancy. Elevated expression of a MC gene signature in breast tumors was associated with improved progression free and overall survival, highlighting the human relevance of these findings. MCs are a major source of tissue histamine, and lesions from mice fed cfBF had decreased concentrations. Importantly, antagonists of the histamine receptor 2 (H2R) sparked reemergence from dormancy. H2R antagonists are over-the-counter drugs are taken to alleviate gastroesophageal reflux disease. Chronic treatment of mice with H2R-antagonists sensitized platelets towards activation and crosstalk with neutrophils, and subsequent formation of neutrophil extracellular traps (NETs). The loss of platelet or NETosis activity mitigated the H2R-antagonist stimulated reemergence from dormancy. Therefore, we establish a novel metastatic axis which links diet to recurrence via MCs, histaminergic signaling and NETosis: Diet -- MC -- H2R -- (decreased) Platelet Activity -- (decreased) Neutrophil-NETosis -- (decreased) Reemergence from Dormancy. Our data reveal several potential intervention strategies: lifestyle, MC stabilization, histaminergic signaling, and neutrophil and platelet activity.

cancer biology↗

bioRxiv2025

Regional patterns of neurodegeneration in a mouse model of proteinopathy

The aggregation of misfolded proteins is a hallmark of many neurodegenerative diseases, suggesting shared pathological mechanisms. However, the pathways by which protein misfolding in these proteinopathies lead to neuronal death remain unclear. Proteinopathies can be modelled in transgenic animals by expressing disease-causing mutations that promote protein aggregation, or in wild-type animals by injecting misfolded proteins (e.g. RML scrapie) that spread in a prion-like manner and recapitulate key neurodegenerative features, including gliosis, ER stress, and neuronal loss. Here, we map region-specific histopathological features of scrapie-induced neurodegeneration in the hippocampus, thalamus, cortex, and cerebellum during early (12 weeks post-inoculation) and late (20 weeks) stages of disease. Using a streamlined time-efficient protocol, we achieve reproducible paired sample collection and high-quality immunohistochemistry that is compatible with best practice in decontamination and containment. We found that among the tested markers of early pathology, thalamic astrocytic activation and spongiform degeneration were the most sensitive. By the late stage, there was widespread upregulation of IBA1+ microglia and GFAP+ astrocytes, accompanied by strong immunoreactivity of lysosomal marker LAMP1. LAMP1 expression in healthy brains was largely neuronal, but by 20 weeks it was significantly upregulated in astrocytes, suggesting their involvement in lysosomal pathology. The ER stress marker p-PERK was elevated in CA1/CA3 pyramidal neurons but minimal in the thalamus and cerebellum, where neuronal loss was most pronounced, suggesting region-specific mechanisms of degeneration. Overall, the thalamus and hippocampal CA1/CA3 areas exhibited the greatest pathological burden. Our shorter time-course, new pathological insights and safe handling protocols, and improved welfare, supports broader adoption of the RML scrapie model for resource-efficient studies of neurodegeneration and its prevention.

neuroscience↗

bioRxiv2024

Divergent CD8 memory T cell subsets in an encephalitis model of Toxoplasma gondii infection

CD8 T cell exhaustion has been reported in mice susceptible to Toxoplasma gondii infection. While the differentiation of CD8 exhausted subsets has been extensively reported, most of these studies have been conducted in chronic viral and cancer models. During chronic T. gondii infection, phenotypic and transcriptomic analyses of the polyclonal antigen-specific CD8 T cell response characterize four populations based on KLRG1 and CD62L expression. Pop1 (KLRG1+CD62Llo) bears the attributes of a terminal effector subset, and pop2 (KLRG1-CD62Llo) is similar to effector memory CD8 T cells. Akin to chronic viral infection and cancer systems, pop3 (KLRG1-CD62Lhi) exhibits the characteristics of stem-like progenitor CD8 T cells (high Tcf7, Slamf6, and Cxcr5 expression), whereas pop4 (KLRG1+CD62Lhi) closely resembles a transitory subset (elevated Tbx21, low Tcf1, and Tox expression). During chronic viral infection, the stem-like progenitor CD8 T cells transition into a terminally differentiated exhausted subset via an intermediate population. However, in our system, pop3 generates pop4, which does not convert into a conventional terminally differentiated exhausted subset but instead transitions into effector pop1. Notably, during the chronic phase of the infection, pop1 cannot retain its functionality, irrespective of its origin, which may hamper its ability to control reactivation. Our observations emphasize that the differentiation of exhausted CD8 T cells in non-viral infections, like chronic toxoplasmosis, follows a different pattern than established models and highlights the need to develop new immune strategies better tailored for a broad range of pathogens.

immunology↗

bioRxiv2023

Relationship between luteal size and plasma progesterone concentration in pregnant and non-pregnant Indian crossbred dairy cows

The relationship between luteal size and plasma progesterone concentration in purebred cows has been investigated previously. However, there is limited information on this topic in Indian crossbred cows. This study aimed to evaluate the relationship between luteal size parameters (diameter and area) and plasma progesterone concentration in healthy pregnant and non-pregnant Indian crossbred cows. Fifty healthy lactating crossbred cows were artificially inseminated after estrus detection and retrospectively classified into pregnant (n=29) and non-pregnant (n=21) based on the results of ultrasonographic pregnancy diagnosis. Data on luteal diameter, luteal area, and plasma progesterone concentration collected on Days 7, 14, and 20 in non-pregnant cows and on Days 7, 14, 20, 25, 30, 35, 40, and 60 in pregnant cows were analyzed. Spearmans correlation test was used to evaluate the association between the corpus luteum size parameters and the plasma progesterone concentration. Luteal area was positively correlated with plasma progesterone concentration in both pregnant ({rho}=0.48, P<0.001) and non-pregnant ({rho}=0.43, P=0.001) cows. Luteal diameter had a relatively weaker correlation with plasma progesterone concentration in both pregnant ({rho}=0.45, P<0.001) and non-pregnant ({rho}=0.24, P=0.058) cows. These results suggest that luteal area is a better indicator of CL function than luteal diameter in healthy Indian crossbred cows.

physiology↗

bioRxiv2021

Surveillance of genetic diversity and evolution in locally transmitted SARS-CoV-2 in Pakistan during the first wave of the COVID-19 pandemic

Surveillance of genetic diversity in the SARS-CoV-2 is extremely important to detect the emergence of more infectious and deadly strains of the virus. In this study, we monitored mutational events in the SARS-CoV-2 genome through whole genome sequencing. The samples (n=48) were collected from the hot spot regions of the metropolitan city Karachi, Pakistan during the four months (May 2020 to August 2020) of first wave of the COVID-19 pandemic. The data analysis highlighted 122 mutations, including 120 single nucleotide variations (SNV), and 2 deletions. Among the 122 mutations, there were 71 singletons, and 51 recurrent mutations. A total of 16 mutations, including 5 nonsynonymous mutations, were detected in spike protein. Notably, the spike protein missense mutation D614G was observed in 31 genomes. The phylogenetic analysis revealed majority of the genomes (36) classified as B lineage, where 2 genomes were from B.6 lineage, 5 genomes from B.1 ancestral lineage and remaining from B.1 sub-lineages. It was noteworthy that three clusters of B.1 sub-lineages were observed, including B.1.36 lineage (10 genomes), B.1.160 lineage (11 genomes), and B.1.255 lineage (5 genomes), which represent independent events of SARS-CoV-2 transmission within the city. The sub-lineage B.1.36 had higher representation from the Asian countries and the UK, B.1.160 correspond to the European countries with highest representation from the UK, Denmark, and lesser representation from India, Saudi Arabia, France and Switzerland, and the third sub-lineage (B.1.255) correspond to the USA. Collectively, our study provides meaningful insight into the evolution of SARS-CoV-2 lineages in spatio-temporal local transmission during the first wave of the pandemic.

genomics↗

bioRxiv2020

Chalcid Hymenopteran parasitoid Dirhinus giffardii Silvestri proficiently disturbed house fly production

ObjectivesMan is always conscious about his health, and is well being challenged by many diseases. These diseases are directly causing hazards and most of them are transmitted through a vector. These vectors (mostly insects) have the ability to transfer / spread pathogenic organisms and that have the potential to cause severe epidemics. The house fly, Musca domestica (Diptera: Muscidae) plays a leading role in spreading more than 100 human and animal diseases. House fly is an eternal issue and mostly the management tactics rely on the use of chemicals either as spray, fumigants or baits. Unauthenticated behavior of these chemicals creates lethal effects on biological ecosystem, furthermore these measures may not be an effective options for outdoor management. For natural and safe option, bio-control strategy is being utilized to make environment healthy and clean. The present study was a part of such effort to use this strategy and validate the biological performance of the potential pupal parasitoid Dirhinus giffardii Silvestri against house fly and provide alternative and safe control of filthy flies. This is the first report on parasitism potential of D. giffardii Silvestri against house fly. ResultsThe D. giffardii Silvestri, 1913 (Hymenoptera: Chalcididae), early reported as an effective pupal parasitoid of tephritid flies, here in the case presented, showed overall 70% reduction in the house fly population by parasitizing pupae. The parasitism efficiency and longevity of hymenopteran parasitoid was remarkably noted two-fold higher on house fly pupae as compared to primary hosts (Tephritids). An amazing results were recorded on house fly parasitism, where, female production was increased one fold as compared to tephritids. Furthermore, sex ratio of the resultant progeny was also confirmed the dominancy of female by 74% as compared to males. Based on the unique and remarkable findings we therefore conclude that D. giffardii is the best bio-control agent for controlling house flies and provide healthy, clean and ecofriendly environment.

zoology↗