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Biology subjects

Ahmad, S. M.

Publications and source records attributed to Ahmad, S. M..

4 recordsLinked to original sources

Competence of DNA Tetrahedron and Exosomes as Nanocarriers for Epirubicin drug delivery in Breast Cancer Cells

Epirubicin, a chemotherapeutic agent, is used in treatment of metastatic breast cancer treatment. However, poor intracellular delivery and systemic toxicity are its major limitations. Our study evaluates the use of DNA tetrahedron (TD) structures and exosomes for targeted delivery of epirubicin to enhance its therapeutic efficacy. Increased intracellular concentration of epirubicin was observed in Flow cytometer when delivered via the TD: Epi system compared to free epirubicin. Cell viability assays using Annexin V-FITC and propidium iodide staining revealed higher apoptosis rates in the TD: Epi system. Exosomes, primarily 100 {+/-} 20 nm in size (99% of particles), exhibit a - 28.5 mV zeta potential, ensuring colloidal stability. SEM and TEM confirm their spherical shape, uniform size, and double membrane structure. The TD: Epi system showed the highest efficacy in RT-qPCR analysis, followed by Epirubicin + Exosomes systems and epirubicin alone, further corroborated with western blot results. While exosomes also provided improved delivery and therapeutic outcomes compared to free epirubicin, they were less effective than the TD: Epi system. These results suggest that the TD carrier significantly enhances the delivery and apoptotic efficacy of epirubicin when compared to exosome-based delivery or epirubicin alone offering a promising strategy for improving treatment outcomes. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=178 HEIGHT=200 SRC="FIGDIR/small/637654v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@10e0393org.highwire.dtl.DTLVardef@10ce3eeorg.highwire.dtl.DTLVardef@148552aorg.highwire.dtl.DTLVardef@1cf4664_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

Scavenger receptor B1 facilitates the endocytosis of Escherichia coli via TLR4 signaling in mammary gland infection

SCARB1 belongs to class B of Scavenger receptors (SRs) that are known to be involved in binding and endocytosis of various pathogens. SRs have emerging role in regulating innate immunity and host-pathogen interactions by acting in co-ordination with Toll-like receptors. Little is known about the function of SCARB1 in milk-derived mammary epithelial cells (MECs). This study reports the role of SCARB1 in infection and its potential association in TLR4 signaling on bacterial challenge in Goat mammary epithelial cells (GMECs). The novelty in the establishment of MEC culture lies in the method that aims to enhance the viability of the cells with intact characteristics upto a higher passage number. We represent MEC culture to be used as a potential infection model for deeper understanding of animal physiology especially around the mammary gland. On E.coli challenge the expression of SCARB1 was significant in induced GMECs at 6 h. Endoribonuclease-esiRNA based silencing of SCARB1 affects the expression of TLR4 and its pathways i.e. MyD88 and TRIF pathways on infection. Knockdown also affected the endocytosis of E.coli in GMECs demonstrating that E.coli uses SCARB1 function to gain entry in cells. Furthermore, we predict 3 unique protein structures of uncharacterized SCARB1 (Capra hircus) protein. Overall, we highlight SCARB1 as a main participant in host defence and its function in antibacterial advances to check mammary gland infections.

immunology↗

Alterations of the rewarding actions of amphetamine by prior nicotine and alcohol treatment: The role of age and dopamine

RationaleNicotine and alcohol each can serve as the gateway to other drugs. ObjectiveThe current study was sought to determine if prior nicotine and alcohol exposure alters amphetamine reward and if age and dopaminergic neurotransmission are involved. MethodsMale and female adolescent and adult C57BL/6J mice were tested for baseline place preference, received six conditioning with saline/nicotine (0.25 mg/kg) twice daily followed by six conditioning with saline/ethanol (2 g/kg) in a counterbalance manner. Control mice were conditioned with saline/saline throughout. Finally, mice were conditioned with amphetamine (3 mg/kg) once in the nicotine-alcohol-paired chamber and then tested for CPP 24 h later. The following day, mice were challenged with amphetamine (1 mg/kg) and tested for CPP under a drugged state. Mice were then immediately euthanized, brain removed and nucleus accumbens isolated and processed for the expression of dopamine receptors and transporter, and glutamate receptors. ResultsWe observed a greater amphetamine-induced CPP in adolescent than adult mice but no change in state-dependent CPP between the two age groups. In contrast, amphetamine-induced CPP in mice with prior nicotine-alcohol exposure was greater in adult than adolescent mice under both drug-free and drugged states. The enhanced response in adult mice was associated with greater expression of dopamine-transporter, reduced D2 receptors, and increased D1 receptors with no changes in glutamate receptors. ConclusionsThese results suggest that prior nicotine and alcohol exposure differentially alters the rewarding action of amphetamine in adult and adolescent mice and alterations in dopaminergic neurotransmission may be involved in this phenotype.

neuroscience↗

Accumulation of prelamin A drives inflammation in the heart with implications for treatment of inherited and acquired cardiomyopathies

Cardiomyopathies are complex heart muscle diseases that can be inherited e.g. dilated cardiomyopathy resulting from LMNA gene mutations, or acquired, e.g. cardiomyopathy associated with HIV. In both cases the lamin A precursor, prelamin A, may play a central role: mutations in LMNA and certain HIV protease inhibitors acting via the enzyme ZMPSTE24 both inhibit prelamin A processing. Firstly, we show that myocardial prelamin A accumulation occurs in both these cardiomyopathies in patients. Secondly, we developed a novel mouse model of cardiac specific prelamin A accumulation which mimicked tissue and molecular features of HIV associated cardiomyopathy, including inflammation. These findings: (1) confirm a central pathological role of prelamin A common to genetic and acquired cardiomyopathies; (2) have implications for the management of HIV patients with cardiac disease in whom protease inhibitors with low/no binding to ZMPSTE24 may be preferred; and (3) suggest that targeting inflammation may be a useful treatment strategy for some forms of inherited cardiomyopathy.

pathology↗