Khan J

References (6)

Title : Optimization and characterization of alkaliphilic lipase from a novel Bacillus cereus NC7401 strain isolated from diesel fuel polluted soil - Akhter_2022_PLoS.One_17_e0273368
Author(s) : Akhter K , Karim I , Aziz B , Bibi A , Khan J , Akhtar T
Ref : PLoS ONE , 17 :e0273368 , 2022
Abstract : Five Bacillus cereus strains including B. cereus AVP12, B. cereus NC7401, B. cereus BDBCO1, B. cereus JF70 and B. specie JL47 isolated from the diesel fuel polluted soil adhered to the roots of Tagetes minuta were screened for lipase production with phenol red agar method. B. cereus NC7401 strain successfully expressing and secreting lipase with maximal lipolytic activity was subjected to a submerged fermentation process with five different carbon (starch, glucose, maltose, fructose, and lactose) and five different nitrogen (tryptone, ammonium nitrate, peptone, urea, yeast extract) sources to produce lipase enzyme. Maximum enzyme activity was found with starch (30.6 UmL-1), maltose (40 UmL-1), and tryptone (38.6 UmL-1), and the lipases produced using these sources were named lipase A, B, and C respectively. The total protein content of 8.56, 8.86, and 2.75 microg mL-1 were obtained from B. cereus NC7401 cultured using starch, maltose, and tryptone respectively. Lipase was stable between temperature range 30-80 degreesC and pH 5-10 whereas optimally active at 55 degreesC and pH 8.0. The enzyme was relatively stable for 10 days at 4 degreesC and its optimum reaction time with the substrate was 30 minutes. It was tolerant to 1.5% (v/v) methanol as an organic solvent, 1.5% (v/v) Triton X-100 as a media additive and 1.5% (w/v) Ni2+ as a metal ion. SDS, n-hexane, and Ag+ inhibited lipolytic activity. Oil stains were removed from cotton fabric which showed oil removal efficiency enhancement in the presence of a lipase. Fat hydrolysis of 20, 24, and 30% was achieved following 6 hours of incubation of the fat particles with lipase A, B, and C respectively at a concentration of 20 mg mL-1. To as best of our knowledge, this study on lipases extracted from bacteria of Azad Kashmir, Pakistan origin has never been reported before.
ESTHER : Akhter_2022_PLoS.One_17_e0273368
PubMedSearch : Akhter_2022_PLoS.One_17_e0273368
PubMedID: 36040973

Title : Involvement of endoplasmic reticulum stress in amyloid beta ((1-42))-induced Alzheimer's like neuropathological process in rat brain - Goswami_2020_Brain.Res.Bull_165_108
Author(s) : Goswami P , Afjal MA , Akhter J , Mangla A , Khan J , Parvez S , Raisuddin S
Ref : Brain Research Bulletin , 165 :108 , 2020
Abstract : Amyloid-beta (Abeta) accumulation in the brain is a pathological hallmark of Alzheimer's disease (AD). Endoplasmic reticulum (ER) stress has been implicated in aetiology of neurodegenerative disorders. We studied the involvement of ER stress in Abeta-induced neuronal degeneration in rat brain to correlate it with cellular and molecular modifications in Abeta-induced Alzheimer's like neuropathological process. Abeta ((1-42)) (5 microg) was administered by bilateral intracerebroventricular (icv) injection in the brain of adult male Wistar rats. Acetylcholinesterase (AChE) activity and histological alterations were observed in different brain regions. ER stress-associated proteins- glucose regulated protein-78 (GRP78), eukaryotic translation initiation factor-2alpha (eIF2alpha) and growth arrest and DNA damage-inducible protein-153 (GADD153), neuronal marker- microtubule associated protein-2 (MAP-2) and microglial protein- ionized calcium binding adaptor molecule-1 (Iba-1) were measured by western blot. Reduced glutathione (GSH), nitrite level and levels of caspase-12 and caspase-3 were also measured. ER stress inhibitor, salubrinal (1 mg/kg, intraperitoneally, ip) was used to assess the specific role of ER stress. Abeta ((1-42))-induced increase in AChE activity, GRP78 and GADD protein levels, dephosphorylation of eIF2-alpha and caspase-12 and caspase-3 levels and decrease in GSH and MAP-2 levels were attenuated by salubrinal. Increase in Iba-1 protein and nitrite levels after Abeta ((1-42)) administration were partially attenuated by salubrinal. Abeta ((1-42))-induced histological alterations were correlated with findings of ER stress. Results of present study implicate ER stress as a potential molecular mechanism in Abeta-induced Alzheimer's like neuropathology which could serve as surrogate biomarker for study of AD progression and efficacy of therapeutic interventions for AD management.
ESTHER : Goswami_2020_Brain.Res.Bull_165_108
PubMedSearch : Goswami_2020_Brain.Res.Bull_165_108
PubMedID: 33011197

Title : Potential Neuroprotective Peptide Emerged from Dual Neurotherapeutic Targets: A Fusion Approach for the Development of Anti-Alzheimer's Lead - Mondal_2019_ACS.Chem.Neurosci_10_2609
Author(s) : Mondal P , Das G , Khan J , Pradhan K , Mallesh R , Saha A , Jana B , Ghosh S
Ref : ACS Chem Neurosci , 10 :2609 , 2019
Abstract : Amyloid-beta (Abeta) peptide misfolds into fibrillary aggregates (beta-sheet) and is deposited as amyloid plaques in the cellular environment, which severely damages intraneuronal connections leading to Alzheimer's disease (AD) pathogenesis. Furthermore, neurons are rich in tubulin/microtubules, and the intracellular network of microtubules also gets disrupted by the accumulation of Abeta fiber in the brain. Hence, development of new potent molecules, which can simultaneously inhibit Abeta fibrillations and stabilize microtubules, is particularly needed for the efficient therapeutic application in AD. To address these issues, here we introduced an innovative fusion strategy to design and develop next generation anti-AD therapeutic leads. This unexplored fusion strategy entails design and development of a potent nonapeptide by taking into account both the hydrophobic core (17-21) of Abeta peptide and the taxol binding region of beta-tubulin. In vitro results suggest that this newly designed peptide interacts at the taxol binding region of beta-tubulin with a moderate binding affinity and promotes microtubule polymerization. It has the ability to bind at the hydrophobic core (17-21) of Abeta, responsible for its aggregation, and prevent amyloid fibril as well as plaque formation. In addition, it interacts at the CAS site (catalytic anionic site) of acetylcholinesterase (AChE) and significantly inhibits AChE induced Abeta fibrillation, stimulates neurite branching, and provides stability to intracellular microtubules and extensive protection of neurons against nerve growth factor (NGF) deprived neuron toxicity. Moreover, this newly designed peptide shows good stability in serum obtained from humans and efficiently permeates the blood-brain barrier (BBB) without showing any toxicity toward differentiated PC12 neurons as well as primary rat cortical neurons. This excellent feature of protecting the neurons by stabilizing the microtubules without showing any toxicity toward neurons will make this peptide a potent therapeutic agent of AD in the near future.
ESTHER : Mondal_2019_ACS.Chem.Neurosci_10_2609
PubMedSearch : Mondal_2019_ACS.Chem.Neurosci_10_2609
PubMedID: 30840820

Title : The protective effect of alpha-lipoic acid against bisphenol A-induced neurobehavioral toxicity - Khan_2018_Neurochem.Int_118_166
Author(s) : Khan J , Salhotra S , Ahmad S , Sharma S , Abdi SAH , Banerjee BD , Parvez S , Gupta S , Raisuddin S
Ref : Neurochem Int , 118 :166 , 2018
Abstract : Bisphenol A (BPA), a well-known xenoestrogen, is ubiquitously utilized in manufacturing of polycarbonated plastics. Convincing evidence suggests that BPA induces neurotoxicity and certain behavioral deficits. alpha-Lipoic acid (ALA) supplementation has shown protective effect against heart and liver diseases, diabetes, and neurological debility associated with aging. We studied the neuromodulatory effect of ALA against neurotoxicity of BPA in vitro in C8-D1A mouse astrocyte cell line and in vivo in C57BL/6J male mice. In vitro ALA (100muM) protected cells from BPA (30muM)-induced reactive oxygen species generation and increased activity of glial fibrillary acidic protein. ALA showed reduction in cell death in astrocytes treated with BPA. In vivo ALA (50mg/kg) increased the neurospecific acetylcholinesterase activity and decreased the monoamine oxidase activity altered by BPA exposure (10mg/kg, per os x 30 days). In addition to neuroprotective effects, ALA also showed protective effects against BPA-induced oxidative stress. We observed that ALA significantly replenished the declined neurobehavioral and cognitive performances, decreased muscle coordination and alerted short-term recognition memory in mice exposed to BPA. Our results suggest that ALA has a promising role in modulating BPA-induced neurotoxicity in C8-D1A mouse astrocyte cells as well as neurochemical and neurobehavioral deficits in C57BL/6J male mice and its antioxidant and free radical scavenging activities may in part be responsible for such an effect.
ESTHER : Khan_2018_Neurochem.Int_118_166
PubMedSearch : Khan_2018_Neurochem.Int_118_166
PubMedID: 29908256

Title : Peptide-Based Acetylcholinesterase Inhibitor Crosses the Blood-Brain Barrier and Promotes Neuroprotection - Mondal_2018_ACS.Chem.Neurosci_9_2838
Author(s) : Mondal P , Gupta V , Das G , Pradhan K , Khan J , Gharai PK , Ghosh S
Ref : ACS Chem Neurosci , 9 :2838 , 2018
Abstract : Design and development of acetylcholinesterase (AChE) inhibitor has tremendous implications in the treatment of Alzheimer's disease (AD). Here, we have adopted a computational approach for the design of a peptide based AChE inhibitor from its active site. We identified an octapeptide, which interacts with the catalytic anionic site (CAS) of AChE enzyme and inhibits its activity. Interestingly, this peptide also inhibits amyloid aggregation through its interaction at the 17-21 region of amyloid-beta (Abeta) and stabilizes microtubules by interacting with tubulin as well. Eventually, in the PC12 derived neurons, it shows noncytotoxicity, promotes neurite out-growth, stabilizes intracellular microtubules, and confers significant neuroprotection even upon withdrawal of nerve growth factor (NGF). Further, results reveal that this peptide possesses good serum stability, crosses the blood-brain barrier (BBB), and maintains the healthy architecture of the primary cortical neurons. This work shows discovery of an excellent peptide-based AChE inhibitor with additional potential as a microtubule stabilizer, which will pave the way for the development of potential anti-AD therapeutics in the near future.
ESTHER : Mondal_2018_ACS.Chem.Neurosci_9_2838
PubMedSearch : Mondal_2018_ACS.Chem.Neurosci_9_2838
PubMedID: 30015476

Title : Volatile Terpenes and Brain Function: Investigation of the Cognitive and Mood Effects of Mentha x Piperita L. Essential Oil with In Vitro Properties Relevant to Central Nervous System Function - Kennedy_2018_Nutrients_10_
Author(s) : Kennedy D , Okello E , Chazot P , Howes MJ , Ohiomokhare S , Jackson P , Haskell-Ramsay C , Khan J , Forster J , Wightman E
Ref : Nutrients , 10 : , 2018
Abstract : BACKGROUND: Extracts of several members of the monoterpene-rich Lamiaceae sub-family Nepetoideae, including those from the Salvia (sage), Melissa (Lemon balm) and Rosmarinus (rosemary) genera, evince cognitive and mood effects in humans that are potentially related to their effects on cholinergic and GABAergic neurotransmission. To date, despite promising in vitro properties, the cognitive and mood effects of the closely related Mentha spicata (spearmint) and Mentha piperita (peppermint) remain unexplored. This study therefore assessed the human cognitive/mood effects of the M. spicata/piperita essential oil with the most promising, brain-relevant in vitro properties according to pre-trial in vitro screening. Design: Organic spearmint and peppermint (Mentha spicata/piperita) essential oils were pre-screened for neurotransmitter receptor binding and acetylcholinesterase (AChE) inhibition. In a double-blind, placebo-controlled, balanced cross-over study, 24 participants (mean age 25.2 years) consumed single doses of encapsulated placebo and 50 microl and 100 microl of the most promising essential oil (peppermint with nicotinic/GABAA receptor binding and AChE inhibitory properties, that increased calcium influx in a CAD cell neuronal model). Psychological functioning was assessed with mood scales and a range of standardised, cognitively demanding tasks pre-dose and at 1, 3 and 6 h post-dose. Results: The highest (100 microL) dose of essential oil improved performance on the cognitively demanding Rapid Visual Information Processing task (RVIP) at 1 h and 3 h post-dose and both doses attenuated fatigue and improved performance of the Serial 3 s subtraction task at 3 h post-dose. Conclusion: Peppermint (Mentha piperita) essential oil with high levels of menthol/menthone and characteristic in vitro cholinergic inhibitory, calcium regulatory and GABAA/nicotinic receptor binding properties, beneficially modulated performance on demanding cognitive tasks and attenuated the increase in mental fatigue associated with extended cognitive task performance in healthy adults. Future investigations should consider investigating higher doses.
ESTHER : Kennedy_2018_Nutrients_10_
PubMedSearch : Kennedy_2018_Nutrients_10_
PubMedID: 30087294