Publications by authors named "Imran Kazmi"

70 Publications

UPLC-MS/MS Method Validation for Estimation of Resveratrol in Rat Skin from Liposphere Gel Formulation and Its Application to Dermatokinetic Studies in Rats.

J Chromatogr Sci 2021 Sep 11. Epub 2021 Sep 11.

Department of Pharmaceutics, School of Pharmaceutical Education and Research, Nanomedicine Research Lab, Jamia Hamdard, New Delhi-110062, India.

For the quantification of resveratrol (RV) in the Wistar rat skin, an ultra-performance liquid chromatography-mass spectrometric (UPLC-MS/MS) method was developed and validated on ACQUITY UPLC BEH C18 column (1.7 μm). The mobile phase ratio of methanol (A) and 2% formic acid (B) (ratio 10: 90% v/v, 80: 20 v/v) at isocratic elution with flow rate 0.3 mL/min, and run time 3 min was used for analysis. In addition, the use of multiple reaction monitoring (MRM)/ES+ mode to detect the analytes and to track parents to daughter ion transition of 229.17 > 107.04 m/z (time scan 3 min, retention time 1.48) for RV and curcumin as an internal standard shows 369.16 > 176.93m/z (scan time is 2.80 min, retention time is 1.11), respectively. Linearity was observed in the range of 2.5 to 2,000 ng/mL (R2 = 0.987). Precision and accuracy on rat skin were within the acceptability range (RE%: ±15; RSD%: ±15). Moreover, it showed a good percentage recovery and found within acceptance limit 90-110%. Lower limit of detection and quantitation for the method observed to be 2.5 and 20 ng.mL-1, respectively. Method application indicated successful determination of dermatokinetics parameters of RV from lipospheres gel and suspension in the rats.
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http://dx.doi.org/10.1093/chromsci/bmab105DOI Listing
September 2021

Disruption of the biological activity of protease-activated receptors2/4 in adults rather than children in SARS CoV-2 virus-mediated mortality in COVID-19 infection.

Drug Dev Res 2021 Sep 1. Epub 2021 Sep 1.

Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.

One of the most remarkable results in 2019 is the reduced prevalence and death of children from coronavirus infection (COVID-19). In 2019, a worldwide pandemic impacted around 0.1 billion individuals, with over 3.5 million mortality reported in the literature. There is minimal knowledge on SARS-CoV-2 infection immunological responses in kids. Studies have been focused mostly on adults and children since the course of pediatric sickness is often short. In adults, severe COVID-19 is related to an excessive inflammatory reaction. Macrophages and monocytes are well known to contribute to this systemic response, although numerous lines are indicative of the importance of neutrophils. An increased number of neutrophils and neutrophil to lymphocyte ratios are early signs of SARS-CoV-2 and a worse prognosis. In this study that it is crucial to monitor PAR2 and PAR4 expression and function (since nursing children have elevated levels) and the inhibiting the normal physiology through the use of anticoagulants may exacerbate the problem in adults. Thus, in COVID-19 infection, we propose the use of antiplatelet (thromboxane A2 inhibitors), if required rather than anticoagulants (FXa and thrombin Inhibitors).
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http://dx.doi.org/10.1002/ddr.21874DOI Listing
September 2021

Nano lipidic carriers for codelivery of sorafenib and ganoderic acid for enhanced synergistic antitumor efficacy against hepatocellular carcinoma.

Saudi Pharm J 2021 Aug 30;29(8):843-856. Epub 2021 Jun 30.

Department of Pharmaceutical Sciences, Shalom Institute of Health & Allied Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, India.

The current study focuses on the development and evaluation of nano lipidic carriers (NLCs) for codelivery of sorafenib (SRF) and ganoderic acid (GA) therapy in order to treat hepatocellular carcinoma (HCC). The dual drug-loaded NLCs were prepared by hot microemulsion technique, where SRF and GA as the drugs, Precirol ATO5, Capmul PG8 as the lipids, while Solutol HS15 and ethanol was used as surfactant and cosolvents. The optimized drug-loaded NLCs were extensively characterized through and studies. The optimized formulation had particle size 29.28 nm, entrapment efficiency 93.1%, and loading capacity 14.21%. drug release studies revealed>64% of the drug was released in the first 6 h. The enzymatic stability analysis revealed stable nature of NLCs in various gastric pH, while accelerated stability analysis at 25C/60% RH indicated the insignificant effect of studied condition on particle size, entrapment efficiency, and loading capacity of NLCs. The cytotoxicity performed on HepG2 cells indicated higher cytotoxicity of SRF and GA-loaded NLCs as compared to the free drugs (p < 0.05). Furthermore, the optimized formulation suppressed the development of hepatic nodules in the Wistar rats and significantly reduced the levels of hepatic enzymes and nonhepatic elements against DEN intoxication. The SRF and GA-loaded NLCs also showed a significant effect in suppressing the tumor growth and inflammatory cytokines in the experimental study. Further, histopathology study of rats treated SRF and GA-loaded NLCs and DEN showed absence of necrosis, apoptosis, and disorganized hepatic parenchyma, etc. over other treated groups of rats. Overall, the dual drug-loaded NLCs outperformed over the plain drugs in terms of chemoprotection, implying superior therapeutic action and most significantly eliminating the hepatic toxicity induced by DEN in Wistar rat model.
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http://dx.doi.org/10.1016/j.jsps.2021.06.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363106PMC
August 2021

Role of Epithelial-to-Mesenchymal Transition Markers in Different Stages of Endometriosis: Expression of the Snail, Slug, ZEB1, and Twist Genes.

Crit Rev Eukaryot Gene Expr 2021 ;31(2):89-95

School of Pharmacy, Suresh Gyan Vihar University, Mahal Road, Jagatpura-302017, Jaipur, India.

Among various epithelial-to-mesenchymal transition (EMT)-related transcription factors (TFs), altered expression levels of Snail-1, Snail-2/Slug, Twist, and ZEB1 have shown a significant association in different cancers having a higher risk of metastasis. However, their role in the circulation of endometriosis patients is not well understood. Hence, the present study was designed to evaluate the crucial role of these TFs in defining the molecular pathogenesis for endometriosis progression and differentiation from control subjects. The qualitative and quantitative expression analysis of Snail-1, Snail-2/Slug, Twist, and ZEB1 were analyzed in peripheral blood samples of 75 different stages of endometriosis patients and compared with 50 control subjects. Total RNA was extracted and converted into complementary DNA (cDNA) for relative quantification of each gene transcript using SYBRGreen-based reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). The Livak method of relative quantification was used for calculating the fold change in each TF compared with endogenous control. All four selected TFs showed significantly upregulated expression levels in endometriosis patients compared with control subjects. A three-fold increase was observed for Snail-1 (p = 0.0001), and a two-fold increase was observed for Snail-2 (p = 0.01), Twist (p = 0.0002), and ZEB1 (p = 0.001) in stage III and IV compared with stage I and II of endometriosis patients. The present study revealed that EMT-related TFs play a crucial role in the pathogenesis and differentiating different stages of endometriosis patients through expression analysis of specific molecular cascades using non-invasive tools.
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http://dx.doi.org/10.1615/CritRevEukaryotGeneExpr.2021037996DOI Listing
January 2021

Development and Validation of Chemometrics-Assisted Green UPLC-MS/MS Bioanalytical Method for Simultaneous Estimation of Capecitabine and Lapatinib in Rat Plasma.

J Chromatogr Sci 2021 Jul 27. Epub 2021 Jul 27.

Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India.

A chemometrics-oriented green ultra-performance liquid chromatography-mass spectrometry/mass spectrometry method was developed and validated for the first-time simultaneous estimation of capecitabine (CAP) and lapatinib (LPB) along with imatinib (as internal standard (IS)) in rat plasma. Analytes were extracted using ethyl acetate as the liquid-liquid extraction media. In the pre-development phase, principles of analytical eco-scale were used to confirm method greenness. Subsequently, vital method variables, influencing method robustness and performance, were optimized using a chemometrics-based quality-by-design approach. Chromatography was achieved on a BEH C18 (100 × 2.1 mm, 1.7 μm) using isocratic flow (0.5 mL.min-1) of mobile phase acetonitrile (0.1% formic acid):0.002 M ammonium acetate in water as the mobile phase. The mass spectrometric detections were carried out in multiple reaction monitoring modes with precursor-to-product ion transitions with m/z 360.037 → 244.076 for CAP, m/z 581.431 → 365.047 LPB and m/z 494.526 → 394.141 for IS. The bioanalytical method validation studies were performed, ensuring regulatory compliance. Linearity (r2> 0.99) over analyte concentrations ranging from 5 and 40 ng.mL-1 was observed, while acceptable values were obtained for all other validation parameters. In a nutshell, a robust and green bioanalytical method was developed and applied for the simultaneous estimation of two anticancer agents from rat plasma.
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http://dx.doi.org/10.1093/chromsci/bmab094DOI Listing
July 2021

Development of a Validated Bioanalytical UPLC-MS/MS Method for Quantification of Neratinib: A Recent Application to Pharmacokinetic Studies in Rat Plasma.

J Chromatogr Sci 2021 Jul 6. Epub 2021 Jul 6.

Department of Pharmaceutical Sciences, Shalom Institute of Health & Allied Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad 110062, India.

Neratinib, a tyrosine kinase inhibitor, was very recently approved by USFDA in 2017 as an anticancer drug to treat of HER2 positive breast cancers. The present work provides an account on the development of a validated bioanalytical UPLC-MS/MS method for quantification of neratinib and internal standard (imatinib) in rat plasma and tissue homogenates. A UPLC having a 100 mm C18 column (1.7 μm sized particles) was used with acetonitrile (0.1% formic acid): 2 mMol of ammonium acetate in water (pH 3.5) as the mobile phase. An efficient chromatographic separation was performed and detection was achieved by monitoring precursor-to-product ion transitions with m/z 557.29 → 112.06 for neratinib and m/z 494.43 → 294.17 for IS. The method demonstrated excellent linearity in the spiked plasma drug concentrating ranging between 1 and 800 ng.mL-1 (r2 = 0999), with lower limit of quantification (LLOQ) was observed at 1 ng.mL-1. Intra-assay and inter-assay precision relative standard deviations were found to be within 6.58. Mean extraction recovery for neratinib and IS were 99.44 and 99.33%, while matrix effect for neratinib and IS was ranging between -4.35 and - 3.66%, respectively. Overall, the method showed successful applicability in pharmacokinetic analysis of pure various formulations in Wistar rat plasma.
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http://dx.doi.org/10.1093/chromsci/bmab089DOI Listing
July 2021

Systematic development of lectin conjugated microspheres for nose-to-brain delivery of rivastigmine for the treatment of Alzheimer's disease.

Biomed Pharmacother 2021 Sep 17;141:111829. Epub 2021 Jun 17.

Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India. Electronic address:

The current study focuses on development of nasal mucoadhesive microspheres for nose-to-brain delivery of rivastigmine for Alzheimer treatment. A systematic development was employed for optimization of the formulation and process parameters influential on the quality attributes of the microspheres. The risk assessment study revealed major influence of the polymer concentration (ethylcellulose: chitosan), the concentration of surfactant solution (polyvinyl alcohol), and stirring speed as the critical factors for optimization of the microspheres. These factors were systematically optimized using Box-Behnken design and microspheres were evaluated for the particle size, entrapment efficiency, and in vitro drug release as the response variables. The optimized microspheres containing 4.4% wt/vol polymers, 1% wt/vol surfactant, and stirring speed at 1500 rpm showed particle size of 19.9 µm, entrapment efficiency of 77.8%, and drug release parameters as T of 7.3 h. The surface modification of microspheres was performed with lectin by carbodiimide activation reaction and confirmed by difference in surface charge before and after chemical functionalization by zeta potential measurement which was found to be - 25.7 mV and 20.5 mV, respectively. Ex vivo study for bioadhesion strength evaluation on goat nasal mucosa indicated a significant difference (p < 0.001) between the plain (29%) and lectin functionalized microspheres (64%). In vivo behavioral and biochemical studies in the rats treated with lectin functionalized microspheres showed markedly better memory-retention vis-à-vis test and pure drug solution treated rats (p < 0.001). In a nutshell, the present studies showed successful development of nasal microspheres for enhanced brain delivery of rivastigmine for Alzheimer's treatment.
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http://dx.doi.org/10.1016/j.biopha.2021.111829DOI Listing
September 2021

6-Shogaol attenuated ethylene glycol and aluminium chloride induced urolithiasis and renal injuries in rodents.

Saudi J Biol Sci 2021 Jun 14;28(6):3418-3423. Epub 2021 Mar 14.

Department of Pharmaceutics, College of Pharmacy, Jouf University, Aljouf 72341, Saudi Arabia.

The 6-shogaol, is a flavanone type flavonoid that is abundant in citrus fruit and has a wide range of pharmacological effects. The present study attempted to evaluate the antiurolithic effect of 6-shogaol on ethylene glycol (EG) and ammonium chloride (AC)-induced experimental urolithiasis in rats. The efficacy of 6-shogaol 50 mg/kg and 100 mg/kg was studied in EG 0.75% (V/V) and AC 1% (W/V) experimentally induced urolithiasis in rats for 21 days. The weight difference, urine volume, the levels of calcium, phosphate, magnesium, oxalate and uric acid in urine was observed. The blood urea nitrogen, creatinine, uric acid in serum and levels of malondialdehyde (MDA) and glutathione (GSH) were also measured. Histopathological analyses in kidneys were also performed. The rats weights were higher in the 6-shogaol groups than the urolithiasis group. EG caused a significant increase in serum creatinine (p < 0.05), BUN (P < 0.001), and uric acid (p < 0.01) while treatment with Cystone (750 mg/kg), and 6-shogaol (50 and 100 mg/kg) showed the significant reduction in increased serum levels of creatinine (p < 0.001), uric acid (p < 0.01) and BUN (p < 0.001). Administration of EG and AC showed statistically significant (p < 0.001) elevated levels of MDA and reduction in GSH levels. Treatment of Cystone (750 mg/kg), and 6-shogaol (50 and 100 mg/kg) significantly (p < 0.001) reduced MDA levels and an increase GSH levels as compared to EG and AC-treated group. The histological findings further attested antiurolithiatic properties of 6-shogaol. The present study attributed clinical shreds of evidence first time that claiming the significant antiurolithic effect of 6-shogaol and could be a cost-effective candidate for the prevention and treatment of urolithiasis.
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http://dx.doi.org/10.1016/j.sjbs.2021.03.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176042PMC
June 2021

Vitamin D attenuates COVID-19 complications via modulation of proinflammatory cytokines, antiviral proteins, and autophagy.

Expert Rev Anti Infect Ther 2021 Jul 15:1-11. Epub 2021 Jul 15.

Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.

: Global emergence of coronavirus disease-19 (COVID-19) has clearly shown variable severity, mortality, and frequency between and within populations worldwide. These striking differences have made many biological variables attractive for future investigations. One of these variables, vitamin D, has been implicated in COVID-19 with rapidly growing scientific evidence.: The review intended to systematically explore the sources, and immunomodulatory role of vitamin D in COVID-19. Search engines and data sources including Google Scholar, PubMed, NCBI, Scopus, and Web of Science were used for data collection. The search terms used were Vitamin D, COVID-19, immune system, and antiviral mechanism. Overall, 232 sources of information were collected and 188 were included in this review.: Interaction of vitamin D and vitamin D receptor (VDR) triggers the cellular events to modulate the immune system by regulation of many genes. Vitamin D operates as a double-edged sword against COVID-19. First, in macrophages, it promotes the production of antimicrobial and antiviral proteins like β-defensin 2 and cathelicidin, and these proteins inhibit the replication of viral particles and promote the clearance of virus from the cells by autophagy. Second, it suppresses cytokine storm and inflammatory processes in COVID-19.
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http://dx.doi.org/10.1080/14787210.2021.1941871DOI Listing
July 2021

Changes in Hematological Parameters by Quantifying HRCT Chest Results in Patients With COVID-19 in Tertiary Care Hospital.

Altern Ther Health Med 2021 Jun 4. Epub 2021 Jun 4.

Aim: To find changes in hematologic parameters in patients who are COVID-19-positive with respect to high resolution computed tomography (HRCT) chest scan so that the exact picture of the disease course can be identified and an adequate treatment protocol can be planned to combat the COVID-19 pandemic.

Methods: Patients' health-related data including age, gender, symptomatology, associated co-morbidities, laboratory test results and HRCT results were collected.

Results: The radiologic findings showed ground glass opacities (GGOs) was the most common manifestation. Analysis of HRCTs of patients with COVID-19 showed that lesions were mainly confined to the right and left lower lobes, suggesting that the COVID-19 virus is mainly harbored in the basal areas of the lungs.

Conclusion: Radiologic and laboratory investigations can greatly help in early detection of COVID-19, thus allowing for timely interventions.
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June 2021

Methanolic extract of Cucumis melo attenuates ethylene glycol-induced nephrolithiasis in Wistar rats.

Urolithiasis 2021 Aug 9;49(4):301-308. Epub 2021 Apr 9.

Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.

Evaluation of the effects of methanolic extract of Cucumis melo in ethylene glycol-induced nephrolithiasis on Wistar rats. 0.75% solution of ethylene glycol (EG) in payable water was given to produce nephrolithiasis on Wistar rats. The action of oral intake of methanolic extract of Cucumis melo seed in nephrolithiasis is studied and is matched with the action of oral intake of Cystone (standard) on Wistar rats. EG resulted in hyperoxaluria and deposition of calcium oxalate as well as raised urinary excretion of oxalate and calcium. Supplementation with methanolic extract of Cucumis melo seed decreased the increased renal oxalate, indicating a regulatory effect on oxalate formation endogenously. The outcomes stipulate that the seed of Cucumis melo is endowed with antinephrolithiatic action.
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http://dx.doi.org/10.1007/s00240-021-01263-5DOI Listing
August 2021

Scale-up fermentation of Escherichia coli for the production of recombinant endoglucanase from Clostridium thermocellum.

Sci Rep 2021 03 30;11(1):7145. Epub 2021 Mar 30.

Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.

Endoglucanase (EC 3.2.1.4) catalysing the hydrolysis of β-1.4-glycosidic linkage of cellulose molecules is an enzyme of tremendous industrial importance. The present study describes a response surface methodology based predicted model to deduce a set of fermentation conditions for optimum growth and activity of recombinant endoglucanase in E. coli BL21 (DE3). Numerous significant parameters including fermentation media composition, temperature (Celsius), pH and agitation rate (rpm) were analysed systemically by employing central composite design. This effort reports highly efficient recombinant endoglucanase overproduction (6.9 gl of biomass) with 30% expression by E. coli in modified M9NG media incubated at 37 °C and pH 7 agitated at 200 rpm. Addition of 3 mM glucose and 24 mM glycerol in the M9NG media has shown positive effect on the enzyme yield and activity. The CMCase activity experimentally estimated was found to be 1185 U/mg with the optimized parameters. The outcomes of both the responses by the predicted quadratic model were found in consensus with the obtained values. Our results well depicted the favourable conditions to further scale-up the volumetric yield of other relevant recombinant enzymes and proteins.
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http://dx.doi.org/10.1038/s41598-021-86000-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009960PMC
March 2021

Calcium sensing receptor hyperactivation through viral envelop protein E of SARS CoV2: A novel target for cardio-renal damage in COVID-19 infection.

Drug Dev Res 2021 09 9;82(6):784-788. Epub 2021 Mar 9.

School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, Jaipur, India.

Over the recent decades, a number of new pathogens have emerged within specific and diverse populations across the globe, namely, the Nipah virus, the Ebola virus, the Zika virus, and coronaviruses (CoVs) to name a few. Recently, a new form of coronavirus was identified in the city of Wuhan, China. Interestingly, the genomic architecture of the virus did not match with any of the existing genomic sequencing data of previously sequenced CoVs. This had led scientists to confirm the emergence of a new CoV strain. Originally, named as 2019-nCoV, the strain is now called as SARS-CoV-2. High serum levels of proinflammatory mediators, namely, interleukin-12 (IL-12), IL-1β, IL-6, interferon-gamma (IFNγ), chemoattractant protein-1, and IFN-inducible protein, have been repeatedly observed in subjects who were infected with this virus. In addition, the virus demonstrated strong coagulation activation properties, leading to further the understanding on the SARS-CoV2. To our understanding, these findings are unique to the published literature. Numerous studies have reported anomalies, namely, decline in the number of lymphocytes, platelets and albumins; and a rise in neutrophil count, aspartate transaminase, alanine aminotransaminase, lactate dehydrogenase, troponins, creatinine, complete bilirubin, D-dimers, and procalcitonin. Supplementation of calcium during the SARS CoV-2 associated hyperactive stage of calcium-sensing receptors (CaSR) may be harmful to the cardio-renal system. Thus, pharmacological inhibition of CaSR may prevent the increase in the levels of intracellular calcium, oxidative, inflammatory stress, and cardio-renal cellular apoptosis induced by high cytokines level in COVID-19 infection.
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http://dx.doi.org/10.1002/ddr.21810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250664PMC
September 2021

Autism - A Comprehensive Array of Prominent Signs and Symptoms.

Curr Pharm Des 2021 ;27(11):1418-1433

Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

Background: Autism Spectrum Disorder (ASD) is a multifaceted neurodevelopmental condition characterized by multiple psychological and physiological impairments in young children. According to the recent reports, 1 out of every 58 newly-born children is suffering from autism. The aetiology of the disorder is complex and poorly understood, hindering the adaptation of targeted and effective therapies. There are no well- established diagnostic biomarkers for autism. Hence the analysis of symptoms by the pediatricians plays a critical role in the early intervention.

Methods: In the present report, we have emphasized 24 behavioral, psychological and clinical symptoms of autism.

Results: Impaired social interaction, restrictive and narrow interests, anxiety, depression; aggressive, repetitive, rigid and self-injurious behavior, lack of consistency, short attention span, fear, shyness and phobias, hypersensitivity and rapid mood alterations, high level of food and toy selectivity; inability to establish friendships or follow the instructions; fascination by round spinning objects and eating non-food materials are common psychological characteristics of autism. Speech or hearing impairments, poor cognitive function, gastrointestinal problems, weak immunity, disturbed sleep and circadian rhythms, weak motor neuromuscular interaction, lower level of serotonin and neurotransmitters, headache and body pain are common physiological symptoms.

Conclusion: A variable qualitative and quantitative impact of this wide range of symptoms is perceived in each autistic individual, making him/her distinct, incomparable and exceptional. Selection and application of highly personalized medical and psychological therapies are therefore recommended for the management and treatment of autism.
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http://dx.doi.org/10.2174/1381612827666210120095829DOI Listing
June 2021

Development and validation of a new UPLC-MS/MS method for quantification of ganoderic acid-A loaded nanolipidic carrier in rat plasma and application to pharmacokinetic studies.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Jan 18;1163:122501. Epub 2020 Dec 18.

Department of Pharmaceutical Sciences, Shalom Institute of Health & Allied Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, India. Electronic address:

A systematic methodology was used to quantify ganoderic acid-A (GA-A) loaded nano-lipid carriers (NLC) in rat plasma using UPLC-MS/MS. Separation of the analyte was achieved using ACQUITY UPLC BEH C column (1.7 µm) and mobile phase as water containing 0.1% Acetonitrile (40: 60% v/v) at a flow rate of 0.4 mL·min. The analyte was detected using MRM mode to track precursor-to-product ion transitions of 515.37 → 285.31 m/z (time scan of 2 min) for GA-A, and 175.11 → 115.08 m/z (time scan of 4 min) for ascorbic acid as an internal standard (IS), respectively. The developed method was validated for linearity, accuracy, within and between day precisions, limit of quantification and recovery of the analyte. The results indicated intra and inter-day consistency and precision values were found to be within the acceptance limit for the plasma samples. The method applicability for determination of pharmacokinetic parameters of GA-A was assessed after oral administration of free GA-A solution and GA-A-loaded NLC, which indicated significant difference (p < 0.05) in the rate and extent of absorption parameters of GA-A from the NLC formulation vis-à-vis the plain solution. Overall, the studies construed successful development and application of UPLC-MS/MS method for estimation of GA-A in the lipidic formulation.
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http://dx.doi.org/10.1016/j.jchromb.2020.122501DOI Listing
January 2021

Cationic Solid Lipid Nanoparticles of Resveratrol for Hepatocellular Carcinoma Treatment: Systematic Optimization, in vitro Characterization and Preclinical Investigation.

Int J Nanomedicine 2020 23;15:9283-9299. Epub 2020 Nov 23.

Department of Pharmaceutical Science, Collage of Pharmacy, Aden University, Aden, Yemen.

Aim: The present study focuses on the development and evaluation of the resveratrol (RV)-loaded cationic solid lipid nanoparticles (RV-c-SLNs) for the management of hepatocellular carcinoma (HCC).

Materials And Methods: Optimization of formulation was performed using factorial design, and further in vitro drug release, cytotoxicity, biodistribution, in vivo preclinical, and biochemical evaluation were carried out.

Results: The optimized formulation exhibited uniform size, homogeneous disparity, positive zeta potential, and stability over 12-week storage at 25°C/60% RH. The in vitro drug release and cytotoxicity study showed 60% drug release within the first 6 hours and comparatively higher cytotoxicity on HepG2 cell line by resveratrol-solid lipid nanoparticle (RV-SLN) as compared to the RV solution. In addition, an anticancer action and biodistribution study on a rat model of HCC showed significant reduction of tumor volume and higher accumulation in the tumor tissue from RV-c-SLN (<0.01) over RV solution and RV-SLN. Furthermore, RV-c-SLN showed significant down-regulation in the levels of pro-inflammatory cytokines and balancing of antioxidant enzymes. Histopathological investigation showed reduced occurrence of hepatic nodules, necrosis formation, infiltration of inflammatory cells, blood vessels inflammation, and cell swelling.

Conclusion: Overall, the obtained results construed that RV-c-SLN with improved antitumor activity as clearly evident from in vitro, in vivo, and biochemical investigations.
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http://dx.doi.org/10.2147/IJN.S277545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695602PMC
December 2020

Cardioprotective Effect of Tangeretin by Inhibiting PTEN/AKT/mTOR Axis in Experimental Sepsis-Induced Myocardial Dysfunction.

Molecules 2020 Nov 29;25(23). Epub 2020 Nov 29.

Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia.

Sepsis aggregates undesirable immune response causing depression of ventricular myocardium and diastolic dysfunction. This present study examined the effect of a plant-derived flavone tangeretin (TG) on autophagy and reduction in myocardial dysfunction. The sepsis was induced by cecum ligation and puncture (CLP) in male Sprague-Dawley rats. Abnormal changes were seen in the heart after the sepsis induction. These abnormalities were analyzed based on the cardiac markers, namely Cardiac myosin light chain-1 (cMLC1) and Cardiac troponin I (cTnl), echocardiography, and plasma parameters, like Lactate dehydrogenase (LDH) and Creatinine kinase (CK). Microanatomy of the heart was studied using hematoxylin and eosin stained histopathological samples of cardiac tissue. Western blot technique was used to detect the nature and extent of protein with the amount of a specific RNA (gene expression) in the cardiac homogenate. Oxidative damage was analyzed using redox marker, reduced glutathione. This study successfully showed that TG attenuated sepsis-induced myocardial dysfunction by inhibiting myocardial autophagy via silencing the Phosphatase and tensin homolog (PTEN) expression and acting on the AKT/mTOR pathway. The present findings supported that TG is a novel cardioprotective therapeutic target for sepsis induced myocardial dysfunction.
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http://dx.doi.org/10.3390/molecules25235622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729459PMC
November 2020

Systematic development of a bioanalytical UPLC-MS/MS method for estimation of risperidone and its active metabolite in long-acting microsphere formulation in rat plasma.

J Chromatogr B Analyt Technol Biomed Life Sci 2020 Dec 29;1160:122433. Epub 2020 Oct 29.

Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India. Electronic address:

A systematic approach to develop a UPLC-MS/MS method was applied for quantifying of risperidone (RISP), its active metabolite, 9-hydroxy risperidone (9-OH-RISP) and internal standard (propranolol) in rat plasma. Liquid-liquid extraction was performed using methyl tert-butyl ether for quantification of drug and its active metabolite by MS detection in the positive ion mode. Acquity UPLC system with BEH C18 (2.1 mm × 100 mm, particle size 1.7 μm) column was used along with acetonitrile (0.1% formic acid)-2 mM (milli mole) ammonium acetate in isocratic condition was used as the mobile phase. Detection was performed by multiple reactions monitoring with precursor-to-product ion transitions with m/z 411.2 → 191.0 for RISP, m/z 427.2 → 207.0 for 9-OH-RISP and m/z 260.1 → 116.0 for IS. The method was validated as per the FDA guidance on bioanalytical method validation. Linearity (r = 0.999) was observed in the drug concentration ranging between 0.1 and 50 ng mL, while all other parameters were found to be within the acceptable ranges. Method robustness was optimized by Box-Behnken design to monitor the influential variables to achieve maximal recovery of the analytes in the rat plasma. Pharmacokinetic evaluation of the analytes from long-acting microparticles in rat plasma showed two peaks indicating an initial burst effect within 24 h of administration followed by controlled drug release pattern upto 45 days, while marketed formulation (Risperdal Consta®) showed no plasma concentration during the lag-time of 21 days followed by maximal drug absorption between 28 and 40 days.
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http://dx.doi.org/10.1016/j.jchromb.2020.122433DOI Listing
December 2020

Systematic Development and Validation of a RP-HPLC Method for Estimation of Abiraterone Acetate and its Degradation Products.

J Chromatogr Sci 2021 Jan;59(1):79-87

Department of Pharmaceutical Sciences, SIHAS, Faculty of Health Science, Sam Higginbottom University of Agriculture Technology and Sciences, Allahabad 211007, India.

The present study described the development of a reversed-phase liquid chromatographic method for the estimation of abiraterone acetate by Quality by Design (QbD) approach. Using an isocratic solvent system for the mobile phase, the chromatographic estimation of analyte was performed on a Hypersil BDS C18 column using mobile phase mixture containing acetonitrile and water with pH adjusted with 0.1% v/v orthophosphoric acid (15:85%v/v ratio), flow rate 1.0 mL.min-1 and detection at 250 nm using photodiode array detector. Systematic development of the chromatographic method was carried out by factor screening using a half-factorial design which suggested organic modifier (%), flow rate (mL.min-1) and autosampler temperature (°C) as influential variables. Further, the method was optimized by Box-Behnken design and trials performed were evaluated for the area under peak, retention time, theoretical plate count and tailing factor as the responses. Validation of the developed method showed good linearity, accuracy, precision and sensitivity. Evaluation of the stability-indicating profile of the method using forced degradation studies revealed the formation of a possible degradation product under acidic and alkaline conditions, while no such degradation product peaks were observed under the oxidative environment. Overall, the study construed the successful development of HPLC assay method for pharmaceutical applications.
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http://dx.doi.org/10.1093/chromsci/bmaa080DOI Listing
January 2021

Biochemical interaction of salt sensitivity: a key player for the development of essential hypertension.

Mol Cell Biochem 2021 Feb 18;476(2):767-773. Epub 2020 Oct 18.

Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.

Worldwide, more than 1 billion people have elevated blood pressure, with up to 45% of adults affected by the disease. In 2016 the global health study report on patients from 67 countries was released in Lancet, which identified hypertension as the world's leading cause for death and disability-adjusted years since 1990. This paper aims to analyze the pathophysiological connection between hemodynamic inflammatory reactions through sodium balance, salt sensitivity, and potential pathophysiological reactions. Besides, we explore how sodium consumption enhances the expression of transient receptor potential channel 3 (TrpC3) mRNA and facilitates the release of calcium inside immune cell groups, together with elevated blood pressure in essential hypertensive patients.
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http://dx.doi.org/10.1007/s11010-020-03942-0DOI Listing
February 2021

Neuroprotective role of chrysin-loaded poly(lactic-co-glycolic acid) nanoparticle against kindling-induced epilepsy through Nrf2/ARE/HO-1 pathway.

J Biochem Mol Toxicol 2021 Feb 29;35(2):e22634. Epub 2020 Sep 29.

Department of Neurology, Xi'an Central Hospital, Xi'an, Shaanxi, China.

Chrysin is the major bioactive compound of blue passionflower, an important medicinal plant used in traditional herbal formulations since ancient times. In the present study, we report that chrysin nanoparticles (chrysin NPs) protect Wistar rats against kindling-induced epilepsy. Nanoparticles of sizes less than 150 nm with a spherical shape were prepared using poly(d,l-lactic-co-glycolic acid) and polyvinyl alcohol, respectively, as polymer and stabilizer. Rats were injected with subconvulsive doses of pentylenetetrazole (PTZ) (35 mg/kg, intraperitoneal) every second day, with 22 injections in total, and on the same days, they received protective doses of the chrysin NPs (5 and 10 µg/mL, PO), respectively, 45 min before each PTZ injection. After the last PTZ injection, an average of thirteen seizure scores was recorded. Animals were killed by decapitation 24 h after a seizure. The cortex and hippocampus were removed and stored in liquid nitrogen for determining oxidative stress terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, histopathology, and reverse transcription-polymerase chain reaction for messenger RNA expression. The result showed chrysin NPs treatment has counteracted oxidative stress, reduced neuronal apoptosis, and upregulated nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H quinone oxidoreductase 1. In conclusion, our findings demonstrate that the neuroprotective effect of chrysin NPs against kindling-induced epilepsy might be escorted by the alleviation of oxidative stress through the Nrf2/antioxidant response element/HO-1 pathway signal pathway.
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http://dx.doi.org/10.1002/jbt.22634DOI Listing
February 2021

COVID-19: Prospective Challenges and Potential Vaccines.

Altern Ther Health Med 2020 Aug;26(S2):72-78

Context: RNA viruses exhibit an extraordinary ability to evolve in a changing environment and to switch from animal hosts to humans. The ongoing COVID-19 pandemic, recognized as a respiratory disease, is an example of zoonotic transmission of the RNA virus known as SARS-CoV-2. The development and regulatory approval of a vaccine against SARS-CoV-2 pose multiple preventive and therapeutic challenges, especially during an ongoing pandemic.

Objective: The review intended to examine the challenges and recent achievements in the development of vaccine candidates against COVID-19.

Design: The research team performed a literature review, searching relevant and up to date information from the literature. The sources of data included Google Scholar, PubMed, NCBI, and Yahoo. The search terms used were COVID-19 challenges, SARS-CoV-2 prospective challenges, RNA viruses adoptability, host switching by RNA viruses, COVID-19 vaccines.

Setting: The study took place at the digital libraries of contributing institutions. The data was combined, selected for further analysis and manuscript preparation at King Abdulaziz University.

Results: RNA viruses with high rate of genome alterations and evolution have better chances to survive in the adverse environmental conditions by adopting the alternate host species. The recent epidemics such as SARS, MERS, and COVID-19 are examples of zoonotic transmission of RNA viruses from animal species to the humans. However, the mechanisms involved in the switching-on to new host species need further investigations to control the zoonotic transmissions in near future. As of April 2020, 115 candidate vaccines were being evaluated; 78 of them had been found to be active, and a few of them are in Phase I trials. In the development of different types of vaccine candidates against COVID-19, multiple international pharmaceutical and biotechnology companies are involved.

Conclusions: Emerging and re-emerging pathogenic RNA viruses pose a serious threat to human health. Little is known about the human-host adoptive mechanism for zoonotic transmission. Deep insights into the molecular mechanism responsible for the switching of animal or bird viruses to humans could provide target molecules or events to prevent such transmissions in the near future. Fast development and approval of efficacious and safe vaccines is key to the effort to provide preventive measures against COVID-19 and future viruses. However, the development and availability of a vaccine candidate is a time-consuming process and often can't be completed during an epidemic. Currently, several types of vaccines are under development, and most of them won't realistically be available in time for the present COVID-19 pandemic.
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August 2020

Beta-catenin non-canonical pathway: A potential target for inflammatory and hyperproliferative state via expression of transglutaminase 2 in psoriatic skin keratinocyte.

Dermatol Ther 2020 11 7;33(6):e14209. Epub 2020 Sep 7.

Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, New South Wales, Australia.

Psoriasis is a chronic, local as well as a systemic, inflammatory skin condition. Psoriasis influences the quality of life up to 3.8% of the population and occurs often between 15 and 30 years of age. Specific causes are linked to psoriasis, including the interleukin IL-23/IL-17 Axis, human antigen leucocyte (HLA), and tumor necrosis factor-α (TNF-α). Secukinumab is a monoclonal antibody that specifically binds and neutralizes IL-17A required in the treatment of Psoriasis. The signaling pathways of Wnt govern multiple functions of cell-like fate specification, proliferation, polarity, migration, differentiation with their signaling controlled rigorously, given that dysregulation caused by various stimuli, can lead to alterations in cell proliferation, apoptosis, and human inflammatory disease. Current data has supported non-canonical Wnt signaling pathways in psoriasis development, particularly Wnt5a activated signaling cascades. These interconnected factors are significant in interactions between immune cells, keratinocytes, and inflammatory factors due to a higher degree of transglutaminase 2, mediated by activation of the keratinocyte hyperproliferation of the psoriatic patient's epidermis. This study discusses the pathology of Wnt5a signaling and its involvement in the epidermal inflammatory effects of psoriasis with other related pathways.
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http://dx.doi.org/10.1111/dth.14209DOI Listing
November 2020

Impact of COVID-19 on Nephrology Patients: A Mechanistic Outlook for Pathogenesis of Acute Kidney Injury.

Altern Ther Health Med 2020 Aug;26(S2):66-71

Context: Some research has indicated that SARS-CoV-2 has had effects on the various functions of the renal system. Acute kidney injury (AKI) is a dangerous and broadly spread pathological illness.

Objective: In this review, we emphasize that AKI can be a severe complication of COVID-19 and highlight the importance of assessing, defining, and reporting the course of AKI.

Design: The research team performed a literature review, searching relevant literature databases. We searched four databases, PubMed, EMBASE, Web of Science and CNKI (Chinese Database), to identify studies reporting COVID-19. Articles published on or before May 10, 2020 were eligible for inclusion. We used the following search terms: "Coronavirus" or "2019-nCoV" or "COVID-19" or "AKI" or "renal failure" or "nephrology".

Setting: This study was take place at Jouf University, Sakaka, Al-Jouf, Saudi Arabia.

Results: The review showed that AKI patients, who were susceptible to a cytokine storm, showed clinical deterioration. This result allowed the current research team to develop a hypothesis of a set of adverse events in COVID-19 that proposes the modification of inflammatory pathways by stimulation of nAChRα7. The stimulation could occur by way of IL-6 / JAK2 / STAT3 / SOCS3 and NF-κB (p65)/IL-18, which work together to induce AKI and increase overall renal-related diagnostic markers, such as plasma creatinine and tubular cell damage. In addition, the functioning of the cholinergic anti-inflammatory pathway may be determined by nicotine. Pharmacological nicotine products are widely available, and their role in COVID-19-mediated AKI can be further evaluated.

Conclusions: The research team concluded that the dysregulation of the cholinergic anti-inflammatory system could explain most of the clinical features of severe COVID-19.
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August 2020

SARS CoV-2 aggravates cellular metabolism mediated complications in COVID-19 infection.

Dermatol Ther 2020 11 7;33(6):e13871. Epub 2020 Jul 7.

Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney (UTS), Ultimo, New South Wales, Australia.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the primary causative organism in corona virus disease-19 (COVID-19) infections, is a novel member of the human coronavirus family which was first identified in Wuhan, China, towards the end of 2019. This letter reveals new vital missing links in our current understanding of the mechanisms that lead to cell death triggered by ferroptotic stress in COVID-19 infection. It further reveal the importance of homocysteine mediated trans-sulfuration pathway in COVID-19 infection. Hence, Vitamin B6, folic acid, and Vitamin B12 should be incorporated in the treatment regimen for SARS CoV-2 infections to suppress complications, as the virus mediates altered host cell metabolism.
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http://dx.doi.org/10.1111/dth.13871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323108PMC
November 2020

Polio Elimination in North-West Pakistan Faces Setbacks in War-Affected Areas.

Asia Pac J Public Health 2020 07 5;32(5):292-293. Epub 2020 Jun 5.

Garden Campus Hazara University, Mansehra, Pakistan.

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http://dx.doi.org/10.1177/1010539520928183DOI Listing
July 2020

Genotoxic potential of a novel PDE-4B inhibitor Apremilast by chromosomal aberration and micronucleus assay in mice.

Saudi Pharm J 2020 May 2;28(5):615-620. Epub 2020 Apr 2.

Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakakah-72341, Saudi Arabia.

Objective: Researchers have confirmed that chronic administration of drugs at high doses causes genotoxicity which serve as first step in development of cancers. Apremilast, a phosphodiesterase-4 inhibitor is Food and Drug Administration (FDA) approved drug for Psoriatic Arthritis. The present study designed to conduct genotoxicity testing using the genotoxic study which give simple, sensitive, economical and fast tools for the assessment of damage of genetic material.

Methods: To conduct genotoxicity study of Apremilast, 60 Swiss albino male mice divided into 6 groups (n = 10). Group1 served as a normal control group without any treatment, Group 2 treated as a disease control and administered with cyclophosphamide 40 mg/kg, IP. Group 3, 4, 5 and 6 treated as test groups and received 10, 20, 40 and 80 mg/kg/day Apremilast respectively. The total duration of study was 13 weeks. At termination day animals were sacrificed and chromosomal aberration assay (BMCAA) and micronucleus assay (BMMNA) were performed to know the genotoxicity potential of Apremilast.

Results: The results indicates significant rise in chromosomal aberrations (CA) frequency in bone marrow cells and decrease in the MI of the disease control animals as well as Apremilast treated groups. Further significant (p < 0.001; p < 0.0001) increase in score of micronucleated polychromatic erythrocytes (MNPCEs) and percentage of micronucleated PCEs per 1000 PCEs and decrease in the ratio of polychromatic/normochromatic erythrocytes (PCE/NCE) was observed in micronucleus assay. Genotoxic effect increases with the increase of Apremilast dose. Finding of present indicates that Apremilast shows genotoxic potential on high administration although further detailed toxicity studies required for confirmations.
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http://dx.doi.org/10.1016/j.jsps.2020.03.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229325PMC
May 2020

Origin, Potential Therapeutic Targets and Treatment for Coronavirus Disease (COVID-19).

Pathogens 2020 Apr 22;9(4). Epub 2020 Apr 22.

School of Biological Sciences, University of the Punjab, Lahore 54000, Pakistan.

The ongoing episode of coronavirus disease 19 (COVID-19) has imposed a serious threat to global health and the world economy. The disease has rapidly acquired a pandemic status affecting almost all populated areas of the planet. The causative agent of COVID-19 is a novel coronavirus known as SARS-CoV-2. The virus has an approximate 30 kb single-stranded positive-sense RNA genome, which is 74.5% to 99% identical to that of SARS-CoV, CoV-pangolin, and the coronavirus the from horseshoe bat. According to available information, SARS-CoV-2 is inferred to be a recombinant virus that originated from bats and was transmitted to humans, possibly using the pangolin as the intermediate host. The interaction of the SARS-CoV-2 spike protein with the human ACE2 (angiotensin-converting enzyme 2) receptor, and its subsequent cleavage by serine protease and fusion, are the main events in the pathophysiology. The serine protease inhibitors, spike protein-based vaccines, or ACE2 blockers may have therapeutic potential in the near future. At present, no vaccine is available against COVID-19. The disease is being treated with antiviral, antimalarial, anti-inflammatory, herbal medicines, and active plasma antibodies. In this context, the present review article provides a cumulative account of the recent information regarding the viral characteristics, potential therapeutic targets, treatment options, and prospective research questions.
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http://dx.doi.org/10.3390/pathogens9040307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238035PMC
April 2020

Multiple Risk Factors: A Challenge in the Management of Autism.

Curr Pharm Des 2020 ;26(7):743-754

Department of Biochemistry, Faculty of Science, King Abdulaziz University Jeddah 21589, Saudi Arabia.

Autism Spectrum Disorder (ASD) is an emerging health problem involving 1 out of every 68 children. The incidence rate of autism has increased 3 folds during the last 3 decades. Due to the illusive picture of aetiology, a considerable number of autistic children fail to receive proper behavioural and medicational treatment. The present study provides a cumulative account of autism risk factors. Several factors including the gene expression and gene mutations, environmental pollution, metal ion accumulation, exposure to pesticides, immune deficiencies, viral infections, mother's age, health, mental status, mother's interactions with the foetus, vaccination of mother and children, and modulations in gut microbiota have been debated. These risk factors may contribute to the development of autism either independently or synergistically leading to a broad spectrum of characteristics observed in autistic patients. The variable quantitative influence of a wide spectrum of risk factors may result in a unique set of features in each autistic individual. However, the exact mechanism behind the combined impact of various aetiological factors is poorly understood hindering the adaptation of specified and effective therapies.
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http://dx.doi.org/10.2174/1381612826666200226101218DOI Listing
November 2020
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