Publications by authors named "Iram Khan"

Targeted gene editing to restore CD40L expression via homology-directed repair (HDR) in CD34 hematopoietic stem and progenitor cells (HSPCs) represents a potential long-term therapy for X-linked hyper IgM syndrome. However, clinical translation of HSPC editing is limited by inefficient long-term engraftment of HDR-edited HSPCs. Here, we ameliorate this issue by employing a small-molecule inhibitor of DNA-PKcs, AZD7648, to bias DNA repair mechanisms to facilitate HDR upon CRISPR SpCas9-based gene editing.

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Brassinosteroids (BRs) are crucial plant hormones that play a significant role in regulating various physiological processes, including micronutrient homeostasis. This review delves into the complex roles of BRs in the uptake, distribution, and utilization of essential micronutrients such as iron (Fe), zinc (Zn), manganese (Mn), copper (Cu), and boron (B). BRs influence the expression of key transporter genes responsible for the absorption and internal distribution of these micronutrients.

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Background Lymph node staging is a critical component in managing lung cancer, as it determines prognosis and guides treatment decisions. Fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) has emerged as a highly sensitive and specific imaging modality for evaluating nodal involvement, surpassing conventional imaging techniques. Therefore, this study evaluated the diagnostic accuracy of PET-CT in lymph nodal staging of lung cancer, using histopathology as the gold standard.

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Pathogenic long-lived plasma cells (LLPCs) secrete autoreactive antibodies, exacerbating autoimmune diseases and complicating solid organ transplantation. Targeted elimination of the autoreactive B cell pool represents a promising therapeutic strategy, yet current treatment modalities fall short in depleting mature PCs. Here, we demonstrate that chimeric antigen receptor (CAR) T cells, targeting B cell maturation antigen (BCMA) utilizing a split-receptor design, offer a controlled and effective therapeutic strategy against LLPCs.

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Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a monogenic disorder caused by mutations in the gene, required for generation of regulatory T (T) cells. Loss of T cells leads to immune dysregulation characterized by multi-organ autoimmunity and early mortality. Hematopoietic stem cell (HSC) transplantation can be curative, but success is limited by autoimmune complications, donor availability and/or graft-vs.

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This research work is to evaluate spanlastic-loaded raloxifene (RLX) nanogel administration via the transdermal route to avoid its hepatic metabolism and to enhance the bioavailability for better management of osteoporosis. RLX-loaded spanlastic nanogel was prepared and characterized for its viscosity, pH, spreadability, and texture profile. The formulation was applied on the skin surface of the animal for pharmacokinetic evaluation, and later, the efficacy of the formulation was assessed in ovariectomized female Wistar rats.

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Filamentous targets are internalized via phagocytic cups that last for several minutes before closing to form a phagosome. This characteristic offers the possibility to study key events in phagocytosis with greater spatial and temporal resolution than is possible to achieve using spherical particles, for which the transition from a phagocytic cup to an enclosed phagosome occurs within a few seconds after particle attachment. In this chapter, we provide methodologies to prepare filamentous bacteria and describe how they can be used as targets to study different aspects of phagocytosis.

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Barriers to effective gene therapy for many diseases include the number of modified target cells required to achieve therapeutic outcomes and host immune responses to expressed therapeutic proteins. As long-lived cells specialized for protein secretion, antibody-secreting B cells are an attractive target for foreign protein expression in blood and tissue. To neutralize HIV-1, we developed a lentiviral vector (LV) gene therapy platform for delivery of the anti-HIV-1 immunoadhesin, eCD4-Ig, to B cells.

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Due to their unique longevity and capacity to secrete high levels of protein, plasma B cells have the potential to be used as a cell therapy for protein replacement. Here, we show that ex vivo engineered human plasma cells exhibit single-cell RNA profiles, scanning electron micrograph ultrastructural features, and in vivo homing capacity of long-lived plasma cells. After transferring human plasma cells to immunodeficient mice in the presence of the human cytokines BAFF and IL-6, we observe increases in retention of plasma cells in the bone marrow, with engraftment exceeding a year.

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Adoptive transfer of regulatory T cells (T) is therapeutic in type 1 diabetes (T1D) mouse models. T that are specific for pancreatic islets are more potent than polyclonal T in preventing disease. However, the frequency of antigen-specific natural T is extremely low, and ex vivo expansion may destabilize T, leading to an effector phenotype.

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This study aims to develop chitosan-coated PLGA nanoparticles intended for nose-to-brain delivery of carmustine. Formulations were prepared by the double emulsion solvent evaporation method and optimized by using Box-Behnken Design. The optimized nanoparticles were obtained to satisfactory levels in terms of particle size, PDI, entrapment efficiency, and drug loading.

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Nanotechnology-based drug delivery system has played a very crucial role in overpowering the tasks allied with the conventional dosage form. Spanlastics, an elastic nanovesicle with an ability to carry wide range of drug molecules, make it a potential drug delivery carrier. Spanlastics have extended rising curiosity for diverse sort of route of administration.

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Osteoarthritis is still a disease burden for pharmaceutical scientists and strategy makers. It is associated with the chronic inflammation of joints especially weight-bearing joints like knee, hip, backbone, and phalanges. NSAIDs that are used for the management of inflammation associated with osteoarthritis have high side effects related to gastric upset, gastric ulcer, and long term treatment associated with liver and kidney damage.

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Aim: The purpose of this study was to evaluate force systems to bring about the en masse retraction of maxillary anterior teeth having reduced bone levels using finite element analysis.

Materials And Methods: This is a prospective study. Three-dimensional finite element models of maxillary dentition having normal alveolar bone level and 2, 4, and 6 mm bone loss with first premolar extraction were constructed from a spiral CT scan of a skull.

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Introduction: Sleeve avulsion of patella is extremely rare, limited almost to children. However, few cases have been reported in adults. Rarity of this fracture makes the diagnosis and choice of treatment difficult.

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X-linked agammaglobulinemia (XLA) is an immune disorder caused by mutations in Bruton's tyrosine kinase (). BTK is expressed in B and myeloid cells, and its deficiency results in a lack of mature B cells and protective antibodies. We previously reported a lentivirus (LV) BTK replacement therapy that restored B cell development and function in and double knockout mice (a phenocopy of human XLA).

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Dural sinus thrombosis (DST) is a potentially fatal neurological condition that can be reversed with early diagnosis and prompt treatment. Non-enhanced CT scan is often the first imaging investigation in patients presenting with acute neurological symptoms; however, its poor sensitivity in detecting DST is a major drawback. Magnetic resonance (MR) imaging offers multiple advantages such as excellent contrast resolution and unenhanced venography possibilities, making it the mainstay in the non-invasive diagnosis of DST.

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Posterior reversible encephalopathy syndrome (PRES) has traditionally been described as a reversible leukoencephalopathy with a distinct pattern of posteriorly distributed vasogenic oedema involving the subcortical regions of parietal and occipital lobes. PRES commonly occurs in the setting of hypertensive emergencies, pre-eclampsia/eclampsia, impaired renal function, and immunosuppressive therapy. The various clinical presentations of PRES include encephalopathy, seizures, headache, visual, and focal neurological deficits.

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The isolation of human monoclonal antibodies (mAbs) arising from natural infection with human pathogens has proven to be a powerful technology, facilitating the understanding of the host response to infection at a molecular level. mAbs can reveal sites of vulnerability on pathogens and illuminate the biological function of the antigenic targets. Moreover, mAbs have the potential to be used directly for therapeutic applications such as passive delivery to prevent infection in susceptible target populations, and as treatment of established infection.

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Thymic regulatory T cells (tT) are potent inhibitors of autoreactive immune responses, and loss of tT function results in fatal autoimmune disease. Defects in tT number or function are also implicated in multiple autoimmune diseases, leading to growing interest in use of T as cell therapies to establish immune tolerance. Because tT are present at low numbers in circulating blood and may be challenging to purify and expand and also inherently defective in some subjects, we designed an alternative strategy to create autologous T-like cells from bulk CD4 T cells.

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The above article was published with incorrect list of authors. We have added Seyed Ehasan Saffari and his affiliation as the addition of the new author to the author list was requested at revision stage.

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Purpose: Primary central nervous system lymphoma (PCNSL) presenting with atypical radiological findings often leads to delayed diagnosis. We aim to characterize the radiological features and apparent diffusion coefficient (ADC) values of PCNSL with atypical neuroimaging presentation in our local population.

Methods: We retrospectively reviewed all patients with histological diagnosis of CNS lymphoma at our tertiary center from 2005 to 2016.

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The ability to engineer primary human B cells to differentiate into long-lived plasma cells and secrete a de novo protein may allow the creation of novel plasma cell therapies for protein deficiency diseases and other clinical applications. We initially developed methods for efficient genome editing of primary B cells isolated from peripheral blood. By delivering CRISPR/CRISPR-associated protein 9 (Cas9) ribonucleoprotein (RNP) complexes under conditions of rapid B cell expansion, we achieved site-specific gene disruption at multiple loci in primary human B cells (with editing rates of up to 94%).

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Wiskott-Aldrich syndrome (WAS) is a life-threatening immunodeficiency caused by mutations within the gene. Viral gene therapy to restore WAS protein (WASp) expression in hematopoietic cells of patients with WAS has the potential to improve outcomes relative to the current standard of care, allogeneic bone marrow transplantation. However, the development of viral vectors that are both safe and effective has been problematic.

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