Publications by authors named "Mohd Altaf Najar"

Alzheimer's disease, a prevalent neurodegenerative disorder in the elderly, is characterized by the accumulation of senile plaques and neurofibrillary tangles, triggering oxidative stress, neuroinflammation, and neuronal apoptosis. Current therapies focus on symptomatic treatment rather than targeting the underlying disease-modifying molecular mechanisms and are often associated with significant side effects. Bacopa monnieri, a traditional Indian herb with nootropic properties, has shown promise in neurological disorder treatment from ancient times.

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Breast cancer adaptability to the drug environment reduces the chemotherapeutic response and facilitates acquired drug resistance. Cancer-specific therapeutics can be more effective against advanced-stage cancer than standard chemotherapeutics. To extend the paradigm of cancer-specific therapeutics, clinically relevant acquired tamoxifen-resistant MCF-7 proteome was deconstructed to identify possible druggable targets (N = 150).

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The ability to study proteins in a cellular context is crucial to our understanding of biology. Here, we report a new technology for "intracellular protein editing", drawing from intein- mediated protein splicing, genetic code expansion, and endogenous protein tagging. This protein editing approach enables us to rapidly and site specifically install residues and chemical handles into a protein of interest.

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Recently, targeted degradation has emerged as a powerful therapeutic modality. Relying on "event-driven" pharmacology, proteolysis targeting chimeras (PROTACs) can degrade targets and are superior to conventional inhibitors against undruggable proteins. Unfortunately, PROTAC discovery is limited by warhead scarcity and laborious optimization campaigns.

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PRMT1 plays many important roles in both normal and disease biology, thus understanding it's regulation is crucial. Herein, we report the role of p300-mediated acetylation at K228 in triggering PRMT1 degradation through FBXL17-mediated ubiquitination. Utilizing mass-spectrometry, cellular biochemistry, and genetic code-expansion technologies, we elucidate a crucial mechanism independent of PRMT1 transcript levels.

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Article Synopsis
  • Starvation and low-carb diets lead to high levels of β-hydroxybutyrate (BHB) in the blood, which can modify proteins through a process called lysine β-hydroxybutyrylation (Kbhb).
  • Research shows that class I histone deacetylases (HDACs), typically known for removing acetyl groups, also catalyze the addition of BHB to proteins, indicating a novel role for these enzymes.
  • The study suggests that Kbhb formation depends on substrate availability and shares similarities with traditional deacetylation processes, highlighting its relevance for metabolic changes in proteins.
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Aim: Hypoxic Ischemic Encephalopathy (HIE) is one of the principal causes of neonatal mortality and long-term morbidity worldwide. The neonatal signs of mild cerebral injury are subtle, making an early precise diagnosis difficult. Delayed detection, poor prognosis, and lack of specific biomarkers for the disease are increasing mortality rates.

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Clethodim is a widely used and approved class II herbicide, with little information about its impact on the reproductive system. Herein, we investigated the male reproductive toxicity of clethodim using a mouse model. GrassOut Max (26% clethodim-equivalent) or analytical grade clethodim (≥90%) were given orally to male mice for 10 d in varying doses.

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Introduction: Bacterial pathogenicity has for long posed severe effects on patient care. Pseudomonas aeruginosa is a common cause of hospital-acquired infections and nosocomial illnesses. It is known to infect the host by colonizing through quorum sensing and the production of exotoxins.

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Accumulation of Aβ peptides forming plaque in various regions of the brain is a hallmark of Alzheimer's disease (AD) progression. However, to date, there is no effective management strategy reported for attenuation of Aβ-induced toxicity in the early stages of the disease. Alternate medicinal systems such as Ayurveda in the past few decades show promising results in the management of neuronal complications.

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Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) is a serine/threonine protein kinase which functions the calcium-triggered signaling cascade with CAMK1, CAMK4, and AMPKα as the immediate downstream substrates. CAMKK2 is reported to be overexpressed in gastric cancer; however, its signaling mechanism is poorly understood. We carried out label-free quantitative tyrosine phosphoproteomics to investigate tyrosine-mediated molecular signaling associated with CAMKK2 in gastric cancer cells.

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Neutrophils display functional heterogeneity upon responding diversely to physiological and pathological stimulations. During type 2 diabetes (T2D), hyperglycemia constitutively activates neutrophils, leading to reduced response to infections and on the other hand, elevated metabolic intermediates such as homocysteine induce bidirectional activation of platelets and neutrophils leading to thrombosis. Hence, in the context of T2D-associated complications, we examined the influence of high glucose, homocysteine, and LPS representing effector molecules of hyperglycemia, thrombosis, and infection, respectively, on human neutrophil activation to identify distinct signaling pathways by quantitative phosphoproteomics approach.

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Fluoride at high doses is a well-known toxic agent for the musculoskeletal system, primarily in bone and cartilage cells. Research on fluoride toxicity concerning particularly on the skeletal muscle is scanty. We hypothesized that during skeletal fluorosis, along with bone, muscle is also affected, so we have evaluated the effects of Sodium fluoride (NaF) on mouse skeletal muscles.

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Rice is one of the most important crops worldwide. Crop production is constrained markedly, however, by abiotic stresses such as salinity. To elucidate early stress response signaling networks involved in rice, we report in this study an original quantitative proteomic analysis of the rice seedlings subjected to short-term salt stress.

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Drug-resistant melanoma is very difficult to treat, and a novel approach is needed to overcome resistance. The present study aims at identifying the alternate pathways utilized in the dual drug-resistant mouse melanoma cells (B16F10R) for their survival and proliferation. The dual drug-resistant mouse melanoma, B16F10R, was established by treating the cells with a combination of U0126 (MEK1/2 inhibitor) and LY294002 (PI3K-AKT kinase inhibitor) in a dose-escalating manner till they attained a resistance fold factor of ≥2.

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The Pro-inflammatory cytokine, Interleukin 17A (IL-17A) plays a vital role in the pathogenesis of inflammatory-induced acute lung injury (ALI). But, the mechanisms of this pro-inflammatory cytokine in response to activation after replication stress are not yet known. Control on DNA replication (DR) is vital for maintaining genome stability.

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The dataset presented in this article is associated with the TMT (Tandem mass tag) labeled proteomics of chili pepper plant () infested by a broad mite (). Data was captured using a nano liquid chromatography system coupled with high-resolution Orbitrap FusionTribridmass spectrometer. Proteomics data was analyzed using the Proteome Discoverer version 2.

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Bleomycin (BLM) injury is associated with the severity of acute lung injury (ALI) leading to fibrosis, a high-morbidity, and high-mortality respiratory disease of unknown etiology. BLM-induced ALI is marked by the activation of a potent fibrogenic cytokine transcription growth factor beta-1 (TGFβ-1), which is considered a critical cytokine in the progression of alveolar injury. Previously, our work demonstrated that a diet-derived compound curcumin (diferuloylmethane), represents its antioxidative and antifibrotic application in TGF-β1-mediated BLM-induced alveolar basal epithelial cells.

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Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related death worldwide. We showed previously that calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2), a serine-threonine kinase, is highly expressed in gastric cancer and leads to progression. In the present study, we identified the molecular networks involved in CAMKK2-mediated progression of gastric adenocarcinoma.

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Loss of cell differentiation is a hallmark for the progression of oral squamous cell carcinoma (OSCC). Archival Formalin-Fixed Paraffin-Embedded (FFPE) tissues constitute a valuable resource for studying the differentiation of OSCC and can offer valuable insights into the process of tumor progression. In the current study, we performed LC-MS/MS-based quantitative proteomics of FFPE specimens from pathologically-confirmed well-differentiated, moderately-differentiated, and poorly-differentiated OSCC cases.

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Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) is a serine/threonine-protein kinase belonging to the Ca/calmodulin-dependent protein kinase subfamily. CAMKK2 has an autocatalytic site, which gets exposed when Ca/calmodulin (CAM) binds to it. This results in autophosphorylation and complete activation of CAMKK2.

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Parkinson's disease (PD) is a progressive neurodegenerative disorder, whose treatment with modern therapeutics leads to a plethora of side effects with prolonged usage. Therefore, the management of PD with complementary and alternative medicine is often pursued. In the Ayurveda system of alternative medicine, Yashtimadhu choorna, a (nootropic), prepared from the dried roots of L.

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Mapping the normal eye proteome in healthy persons is essential to unravel the molecular basis of diseases impacting visual health. The vitreous occupies a large portion of the human eye between the lens and the retina and plays a significant role in vitreoretinal diseases as well as maintaining clarity in the visual field, providing nutrition to the lens, and protecting the eye from mechanical shocks. It comprises four distinct anatomical regions, namely the vitreous core, vitreous cortex, vitreous base, and anterior hyaloid.

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Ophthalmology and visual health are new frontiers for postgenomic research and technologies such as proteomics. In this context, the optic nerve and retina extend as the outgrowth of the brain, wherein the latter receives the optical input and the former relays the information for processing. While efforts to understand the optic nerve proteome have been made earlier, there exists a lacuna in its biochemical composition and molecular functions.

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Nontuberculous mycobacterial (NTM) species present a major challenge for global health with serious clinical manifestations ranging from pulmonary to skin infections. Multiomics research and its applications toward clinical microbial proteogenomics offer veritable potentials in this context. For example, the Mycobacterium abscessus, a highly pathogenic NTM, causes bronchopulmonary infection and chronic pulmonary disease.

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