Displaying publications 1 - 20 of 92 in total

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  1. Muhammad A, Khan B, Iqbal Z, Khan AZ, Khan I, Khan K, et al.
    ACS Omega, 2019 Sep 03;4(10):14188-14192.
    PMID: 31508540 DOI: 10.1021/acsomega.9b01041
    The antipyretic potential of viscosine, a natural product isolated from the medicinal plant Dodonaea viscosa, was investigated using yeast-induced pyrexia rat model, and its structure-activity relationship was investigated through molecular docking analyses with the target enzymes cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and microsomal prostaglandin E synthase-1 (mPGES-1). The in vivo antipyretic experiments showed a progressive dose-dependent reduction in body temperatures of the hyperthermic test animals when injected with viscosine. Comparison of docking analyses with target enzymes showed strongest bonding interactions (binding energy -17.34 kcal/mol) of viscosine with the active-site pocket of mPGES-1. These findings suggest that viscosine shows antipyretic properties by reducing the concentration of prostaglandin E2 in brain through its mPGES-1 inhibitory action and make it a potential lead compound for developing effective and safer antipyretic drugs for treating fever and related pathological conditions.
  2. Hyder A, Lim YJ, Khan I, Shafie S
    ACS Omega, 2023 Aug 15;8(32):29424-29436.
    PMID: 37599919 DOI: 10.1021/acsomega.3c02949
    The use of melting heat transfer (MHT) and nanofluids for electronics cooling and energy storage efficiency has gained the attention of numerous researchers. This study investigates the effects of MHD, mixed convection, thermal radiation, stretching, and shrinking on the heat transfer characteristics of a Cu-water-based nanofluid over a stretching/shrinking sheet with MHT effects. The governing equations are transformed into nonlinear ordinary differential equations and solved numerically using the Keller Box method. To the best of our knowledge, this comprehensive analysis, encompassing all of these factors, including the utilization of a robust numerical method, in a single study, has not been previously reported in the literature. Our findings demonstrate that an increase in the melting parameter leads to an enhanced rate of heat transfer, while an increase in the stretching/shrinking parameter results in a decrease in the rate of heat transfer. Additionally, we present a comprehensive analysis of the influences of all of the mentioned driving parameters. The results are presented through graphical and tabulated representations and compared with existing literature.
  3. Bashir A, Asif M, Saadullah M, Saleem M, Khalid SH, Hussain L, et al.
    ACS Omega, 2022 Jul 26;7(29):25772-25782.
    PMID: 35910099 DOI: 10.1021/acsomega.2c03053
    Melilotus indicus (L.) All. is known to have anti-inflammatory and anticancer properties. The present study explored the in vivo skin carcinogenesis attenuating potential of ethanolic extract of M. indicus (L.) All. (Miet) in a 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin cancer model. The ethanolic extract of the plant was prepared by a maceration method. HPLC analysis indicated the presence of quercetin in abundance and also various other phytoconstituents. DPPH radical scavenging assay results showed moderate antioxidant potential (IC50 = 93.55 ± 5.59 μg/mL). A topical acute skin irritation study showed the nonirritant nature of Miet. Data for the skin carcinogenic model showed marked improvement in skin architecture in Miet and its primary phytochemicals (quercetin and coumarin) treated groups. Miet 50% showed comparable effects with 5-fluorouracil. Significant (p < 0.05) anticancerous effects were seen in coumarin-quercetin combination-treated animals than in single agent (coumarin and quercetin alone)-treated animals. Chorioallantoic membrane (CAM) assay results showed the antiangiogenic potential of Miet. Treatment with Miet significantly down-regulated the serum levels of CEA (carcinoembryonic antigen) and TNF-α (Tumor necrosis factor-α). Data for the docking study indicated the binding potential of quercetin and coumarin with TNF-α, EGFR, VEGF, and BCL2 proteins. Thus, it is concluded that Miet has skin cancer attenuating potential that is proposed to be due to the synergistic actions of its bioactive molecules. Further studies to explore the effects of Miet and its bioactive molecules as an adjuvant therapy with low dose anticancer drugs are warranted, which may lead to a new area of research.
  4. Jamila N, Khan N, Khan AA, Khan I, Khan SN, Zakaria ZA, et al.
    PMID: 28573253 DOI: 10.21010/ajtcam.v14i2.38
    BACKGROUND: Garcinia hombroniana, known as "manggis hutan" (jungle mangosteen) in Malaysia, is distributed in tropical Asia, Borneo, Thailand, Andaman, Nicobar Islands, Vietnam and India. In Malaysia, its ripened crimson sour fruit rind is used as a seasoning agent in curries and culinary dishes. Its roots and leaves decoction is used against skin infections and after child birth. This study aimed to evaluate in vivo hepatoprotective and in vitro cytotoxic activities of 20% methanolic ethyl acetate (MEA) G. hombroniana bark extract.

    MATERIALS AND METHODS: In hepatoprotective activity, liver damage was induced by treating rats with 1.0 mL carbon tetrachloride (CCl4)/kg and MEA extract was administered at a dose of 50, 250 and 500 mg/kg 24 h before intoxication with CCl4. Cytotoxicity study was performed on MCF-7 (human breast cancer), DBTRG (human glioblastoma), PC-3 (human prostate cancer) and U2OS (human osteosarcoma) cell lines. 1H, 13C-NMR (nuclear magnetic resonance), and IR (infrared) spectral analyses were also conducted for MEA extract.

    RESULTS: In hepatoprotective activity evaluation, MEA extract at a higher dose level of 500 mg/kg showed significant (p<0.05) potency. In cytotoxicity study, MEA extract was more toxic towards MCF-7 and DBTRG cell lines causing 78.7% and 64.3% cell death, respectively. MEA extract in 1H, 13C-NMR, and IR spectra exhibited bands, signals and J (coupling constant) values representing aromatic/phenolic constituents.

    CONCLUSIONS: From the results, it could be concluded that MEA extract has potency to inhibit hepatotoxicity and MCF-7 and DBTRG cancer cell lines which might be due to the phenolic compounds depicted from NMR and IR spectra.

  5. Adil SO, Musa KI, Uddin F, Khan A, Khan I, Shakeel A, et al.
    Arch Public Health, 2024 Feb 20;82(1):22.
    PMID: 38378657 DOI: 10.1186/s13690-024-01250-3
    OBJECTIVE: To determine the prevalence and associated risk factors of undiagnosed metabolic syndrome (MetS) using three different definitions among apparently healthy adults of Karachi, Pakistan.

    METHODS: This community-based cross-sectional survey was conducted in Karachi, Pakistan, from January 2022 to August 2022. A total of 1065 healthy individuals aged 25-80 years of any gender were consecutively included. MetS was assessed using the National Cholesterol Education Program for Adult Treatment Panel (NCEP-ATP) III guidelines, International Diabetes Federation (IDF), and modified NCEP-ATP III.

    RESULTS: The prevalence of MetS was highest with the modified NCEP-ATP III definition at 33.9% (95% CI: 31-36), followed by the IDF definition at 32.2% (95% CI: 29-35). In contrast, the prevalence was lower at 22.4% (95% CI: 19-25) when using the NCEP ATP III definition. The risk of MetS significantly increases with higher BMI, as defined by the IDF criteria (adjusted OR [ORadj] 1.13, 95% CI 1.09-2.43), NCEP-ATP III criteria (ORadj 1.15, 95% CI 1.11-1.19), and modified NCEP-ATP III criteria (ORadj 1.16, 95% CI 1.12-1.20). Current smokers had significantly higher odds of MetS according to the IDF (ORadj 2.72, 95% CI 1.84-4.03), NCEP-ATP III (ORadj 3.93, 95% CI 2.55-6.06), and modified NCEP-ATP III (ORadj 0.62, 95% CI 0.43-0.88). Areca nut use was associated with higher odds of MetS according to both IDF (ORadj 1.71, 95% CI 1.19-2.47) and modified NCEP-ATP III criteria (ORadj 1.58, 95% CI 1.10-2.72). Furthermore, low physical activity had significantly higher odds of MetS according to the NCEP-ATP III (ORadj 1.36, 95% CI 1.01-1.84) and modified NCEP-ATP III criteria (ORadj 1.56, 95% CI 1.08-2.26).

    CONCLUSION: One-third of the healthy individuals were diagnosed with MetS based on IDF, NCEP-ATP III, and modified NCEP-ATP III criteria. A higher BMI, current smoking, areca nut use, and low physical activity were significant factors.

  6. Naqvi AA, Hassali MA, Naqvi SBS, Shakeel S, Zia M, Fatima M, et al.
    BMC Musculoskelet Disord, 2020 Feb 01;21(1):65.
    PMID: 32007095 DOI: 10.1186/s12891-020-3078-y
    BACKGROUND: Non-adherence to physical therapy ranges from 14 to 70%. This could adversely affect physical functioning and requires careful monitoring. Studies that describe designing and validation of adherence measuring scales are scant. There is a growing need to formulate adherence measures for this population. The aim was to develop and validate a novel tool named as the General Rehabilitation Adherence Scale (GRAS) to measure adherence to physical therapy treatment in Pakistani patients attending rehabilitation clinics for musculoskeletal disorders.

    METHODS: A month-long study was conducted in patients attending physical therapy sessions at clinics in two tertiary care hospitals in Karachi, Pakistan. It was done using block randomization technique. Sample size was calculated based on item-to-respondent ratio of 1:20. The GRAS was developed and validated using content validity, factor analyses, known group validity, and sensitivity analysis. Receiver operator curve analysis was used to determine cut-off value. Reliability and internal consistency were measured using test-retest method. Data was analyzed through IBM SPSS version 23. The study was ethically approved (IRB-NOV:15).

    RESULTS: A total of 300 responses were gathered. The response rate was 92%. The final version of GRAS contained 8 items and had a content validity index of 0.89. Sampling adequacy was satisfactory, (KMO 0.7, Bartlett's test p-value 0.95 while absolute fit index of root mean square of error of approximation was

  7. Khan A, Khan AH, Adnan AS, Syed Sulaiman SA, Gan SH, Khan I
    Biomed Res Int, 2016;2016:9710965.
    PMID: 27833921
    Background. Hemodialysis related hemodynamic instability is a major but an underestimated issue. Moreover, cardiovascular events are the leading cause of morbidity and mortality associated with blood pressure in hemodialysis patients. However, there have been many controversies regarding the role and management of hyper- and/or hypotension during hemodialysis that needs to be addressed. Objective. To critically review the available published data on the atypical role of hyper- and/or hypotension in cardiovascular associated morbidity and mortality in patients on hemodialysis and to understand the discrepancies in this context. Methods. A comprehensive search of literature employing electronic as well as manual sources and screening 2783 papers published between Jan 1980 and Oct 2015 was conducted to collect, identify, and analyze relevant information through peer-reviewed research articles, systematic reviews, and other published works. The cardiovascular events, including accelerated atherosclerotic cardiovascular disease (ASCVD), stroke, heart failure, myocardial infarction, myocardial ischemia, and stress induced myocardial dysfunction, leading to death were considered relevant. Results. A total of 23 published articles met the inclusion criteria and were included for in-depth review and analysis to finalize a comprehensive systematic review article. All the studies showed a significant association between the blood pressure and cardiovascular disease events in hemodialysis patients. Conclusions. Both intradialytic hypertension/hypotension episodes are major risk factors for cardiovascular mortality with a high percentage of probable causality; however, clinicians are faced with a dilemma on how to evaluate blood pressure and treat this condition.
  8. Khan W, Khan I, Ullah H, Zain SNM, Panhwar WA, Mehmood SA, et al.
    Braz J Biol, 2021;82:e238665.
    PMID: 33787717 DOI: 10.1590/1519-6984.238665
    Malakand region is an endemic area for cutaneous leishmaniasis (CL). However, there are limited number of studies of this disease in Pakistan. Therefore, a study was conducted to understand the level of awareness attitude and practice among the residents of Makaland towards CL and the disease vectors. This study adopted a cross-sectional approach with a total of 400 respondents (n=93 rural and n= 307 urban). Overall, the population in Malakand region (61.2%) were well-informed in the role of sand fly in transmitting diseases, but most lack knowledge on the vector's behavior and almost a quarter (24.5%) were unable to provide knowledge on proper control measures. Alarmingly, the practice and attitudes of the general population was not satisfactory as close to half (49.8%) of the population did adopt any control method. This study calls for increase in awareness through health education campaign to reduce the risk of cutaneous leishmaniasis outbreaks in the future.
  9. Ishaque A, Salim A, Simjee SU, Khan I, Adli DSH
    Cell Biochem Funct, 2023 Mar;41(2):223-233.
    PMID: 36651266 DOI: 10.1002/cbf.3775
    Central nervous system anomalies give rise to neuropathological consequences with immense damage to the neuronal tissues. Cell based therapeutics have the potential to manage several neuropathologies whereby the differentiated cells are explored for neuronal regeneration. The current study analyzes the effect of a bioactive compound, alpha terpineol (AT) on the differentiation of rat bone marrow derived mesenchymal stem cells (BM-MSCs) toward neuronal lineage, and explores regulation of differentiation process through the study of Wnt pathway mediators. BM-MSCs were cultured and characterized based on their surface markers and tri-lineage differentiation. Safe dose of AT as optimized by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium bromide assay, was used for the treatment of MSCs. Treated cells were analyzed for the neuronal, astroglial and germ layer transition markers at the gene and protein levels, by quantitative polymerase chain reaction and immunocytochemistry, respectively. Temporal expression of Wnt pathway genes was assessed during the course of neuronal differentiation. AT treated group showed significant upregulation of neuron specific (NSE, MAP2, Tau, Nestin, and NefL) and astroglial (GFAP) genes with positive expression of late neuronal markers. Germ layer transition analysis showed the overexpression of ectodermal markers (NCAM, Nestin, and Pax6), whereas endodermal (AFP, MixL1, and Sox17), and mesodermal (Mesp1 and T Brachyury) markers were also found to be upregulated. Wnt signaling pathway was activated during the initial phase (30 min) of differentiation, which later was downregulated at 1, 3, and 5 h. AT efficiently induces neuronal differentiation of BM-MSCs by regulating Wnt signaling. Overexpression of both early and late neuronal markers indicate their neuro-progenitor state and thus can be utilized as a promising approach in cellular therapeutics to treat various neurodegenerative ailments. In addition, exploration of the molecular pathways may be helpful to understand the mechanism of cell-based neuronal regeneration.
  10. Masnoon J, Ishaque A, Khan I, Salim A, Kabir N
    Cell Biochem Funct, 2023 Oct;41(7):833-844.
    PMID: 37814478 DOI: 10.1002/cbf.3833
    Diabetes is one of the major health issues globally. Type 1 diabetes mellitus develops due to the destruction of pancreatic β cells. Mesenchymal stem cells (MSCs) having remarkable self-renewal and differentiation potential, can regenerate β cells. MSCs preconditioned with bioactive small molecules possess enhanced biological features and therapeutic potential under in vivo environment. Interestingly, compounds of naphthoquinone class possess antidiabetic and anti-inflammatory properties, and can be explored as potential candidates for preconditioning MSCs. This study analyzed the effect of lawsone-preconditioned human umbilical cord MSCs (hUMSCs) on the regeneration of β cells in the streptozotocin (STZ)-induced Type 1 diabetes (T1D) rats. hUMSCs were isolated and characterized for the presence of surface markers. MSCs were preconditioned with optimized concentration of lawsone. T1D rat model was established by injecting 50 mg/kg of STZ intraperitoneally. Untreated and lawsone-preconditioned hUMSCs were transplanted into the diabetic rats via tail vein. Fasting blood sugar and body weight were monitored regularly for 4 weeks. Pancreas was harvested and β cell regeneration was evaluated by hematoxylin and eosin staining, and gene expression analysis. Immunohistochemistry was also done to assess the insulin expression. Lawsone-preconditioned hUMSCs showed better anti-hyperglycemic effect in comparison with untreated hUMSCs. Histological analysis presented the regeneration of islets of Langerhans with upregulated expression of βcell genes and reduced expression of inflammatory markers. Immunohistochemistry revealed strong insulin expression in the preconditioned hUMSCs compared with the untreated hUMSCs. It is concluded from the present study that lawsone-preconditioned hMSCs were able to exhibit pronounced anti-hyperglycemic effect in vivo compared with hUMSCs alone.
  11. Malik H, Khan HW, Hassan Shah MU, Ahmad MI, Khan I, Al-Kahtani AA, et al.
    Chemosphere, 2023 Jan;311(Pt 2):136901.
    PMID: 36288769 DOI: 10.1016/j.chemosphere.2022.136901
    Ionic liquids (ILs) have been demonstrated as promising alternatives to conventional entrainers in separation of azeotropic mixtures mostly investigating phase equilibrium and process design scenarios. However, proper selection of ILs for a specific task always remains challenging. Hence a simulation tool, i.e. conductor like screening model for real solvents (COSMO-RS) was applied to address this challenge. Furthermore, screened ILs were simulated as entrainers for ethanol water separation by extractive distillation. The current study also aims to demonstrate a systematic approach to retrofit existing processes, by employing ILs as green entrainers. Screening of twenty-five (25) ILs was carried out using COSMO-RS to select suitable ILs as green entrainers based on activity coefficient, capacity and selectivity. Results illustrated that tetramethylammonium chloride ([TMAm][Cl]) due to its strong hydrogen bonding ability was found to be the best ILs entrainer. Moreover, in order to reduce the operating costs without compromising desired product purity (ethanol purity ≥99.5% in top product), the selected ILs (8 kg/h) in a mixture with ethylene glycol (72 kg/h) were simulated using Aspen plus v.11. The simulation results revealed that by combining tetramethylammonium chloride (2 kg/h) with ethylene glycol (78 kg/h) reduced 7.26 tons of CO2 emissions/year through heat integration by saving 1.49*108 kJ/year energy besides minimizing operating costs. In conclusion, the systematic selection of ILs as green entrainers in combination with ethylene glycol and then the appropriate simulation of the whole system will ultimately reduce the cost of the separation process and reduce the emission of greenhouse gases as well utilization of toxic conventional entrainers.
  12. Khan I, Khan AH, Adnan AS, Naqvi AA, Rehman AU, Ahmad N, et al.
    Clin. Nephrol., 2020 May;93(5):217-226.
    PMID: 32101516 DOI: 10.5414/CN109573
    BACKGROUND: Serum creatinine has been solely used in clinical practice to identify chronic kidney disease (CKD) staging in the elderly population. Serum cystatin C is believed to more accurately define the CKD staging and is also ratified as an endogenous biomarker by Kidney Disease Improving Global Outcomes (KDIGO) guidelines.

    MATERIAL AND METHODS: A total of 300 elderly Malay participants (age ≥ 65 years) with CKD, attending the Hospital University Sains Malaysia were included in the study. Demographic data and history were also recorded. Serum creatinine was assayed by Chemistry Analyzer Model Architect-C8000 (Jaffe method). While serum cystatin C was examined by Human cystatin C ELISA kit (Sigma-Aldrich) using Thermo Scientific Varioskan Flash ELISA reader.

    RESULTS: Out of 300 study participants, 169 (56.3%) were females. Mean age of patients was 67.6 ± 6.7 years. 64 male (64.6%) and 35 female (35.4%) patients were between 70 and 79 years. When estimated by MDRD equation, the prevalence of CKD stage 3 (defined as eGFR = 30 - 59 mL/min/1.73m2) was 27.7%, while based on CKD-EPIcr, CKD-EPIcys, and CKD-EPIcr-cys equations, it was 28%, 36.3%, and 36.3%, respectively. The prevalence of CKD stage 4 (defined as eGFR = 15 - 29 mL/min/1.73m2) when estimated by MDRD was 37.6%, whereas based on CKD-EPIcr, CKD-EPIcys, and CKD-EPIcr-cys equations, it was 36.3%, 46.4%, and 46.4%, respectively. CKD stage 5 (defined as eGFR < 15 mL/min/1.73m2) when estimated by the MDRD equation was 34.7%. While based on CKD-EPIcr, CKD-EPIcys, and CKD-EPIcr-cys equations, the prevalence of CKD stage 5 was 35.7%, 17.3%, and 17.3%, respectively.

    CONCLUSION: The staging of CKD is different between the creatinine- and cystatin C-based equations. Creatinine-based equations classify patients as having CKD stage 5 twice as often as cystatin C-based equations.

  13. Lund LA, Omar Z, Khan I
    Comput Methods Programs Biomed, 2019 Dec;182:105044.
    PMID: 31491654 DOI: 10.1016/j.cmpb.2019.105044
    BACKGROUND AND OBJECTIVE: The last two and half decades are witnessed a great surge in the use convective fluids for enhancement of heat transfer of minerals ethylene glycol, oil and water due to their numerous applications in the industrial segments including chemical production, microelectronics, power generation, transportation, and air-conditioning. For this purpose, different procedures were applied to upgrade the thermal conductivity of common fluid but could not. Further, Choi and Eastman in 1995 introduced nanofluid which has good thermal properties as compared to common fluids. After that, it can be seen that researchers, mathematicians, and scientists tried to understand the principles of nanofluids and how to implicate them in many different practical applications. In this work, the Buongiorno model has been considered for nanofluid. One of the prime objectives is to consider all possible multiple solutions of the model because these solutions cannot be seen experimentally.

    METHODS: The governing equations of fluid flow have been transformed in the form of ordinary differential equations. These equations have been solved by two methods namely, shooting method and three-stage Lobatto IIIa formula.

    RESULTS: The effects of different parameters on temperature, velocity, concentration profiles, skin friction coefficient, Sherwood number, and reduced Nusselt number were obtained and presented graphically. It was noticed that four solutions existed at definite ranges of the parameters for high suction over both surfaces for the first time. The results of the stability analysis revealed that only the first solution is more stable and possess physical reliability compared to the remaining solutions.

    CONCLUSION: The graphs also indicated that the fluid velocity decreases as the thermophoresis parameter increases but the opposite behavior observed for both temperature and concentration profiles in the first solution. Furthermore, it was detected that the concentration profile declined at the higher values of the Brownian motion parameter.

  14. Farayola MF, Shafie S, Mohd Siam F, Khan I
    Comput Methods Programs Biomed, 2020 Apr;187:105202.
    PMID: 31835107 DOI: 10.1016/j.cmpb.2019.105202
    Background This paper presents a numerical simulation of normal and cancer cells' population dynamics during radiotherapy. The model used for the simulation was the improved cancer treatment model with radiotherapy. The model simulated the population changes during a fractionated cancer treatment process. The results gave the final populations of the cells, which provided the final volumes of the tumor and normal cells. Method The improved model was obtained by integrating the previous cancer treatment model with the Caputo fractional derivative. In addition, the cells' population decay due to radiation was accounted for by coupling the linear-quadratic model into the improved model. The simulation of the treatment process was done with numerical variables, numerical parameters, and radiation parameters. The numerical variables include the populations of the cells and the time of treatment. The numerical parameters were the model factors which included the proliferation rates of cells, competition coefficients of cells, and perturbation constant for normal cells. The radiation parameters were clinical data based on the treatment procedure. The numerical parameters were obtained from the previous literature while the numerical variables and radiation parameters, which were clinical data, were obtained from reported data of four cancer patients treated with radiotherapy. The four cancer patients had tumor volumes of 28.4 cm3, 18.8 cm3, 30.6 cm3, and 12.6 cm3 and were treated with different treatment plans and a fractionated dose of 1.8 Gy each. The initial populations of cells were obtained by using the tumor volumes. The computer simulations were done with MATLAB. Results The final volumes of the tumors, from the results of the simulations, were 5.67 cm3, 4.36 cm3, 5.74 cm3, and 6.15 cm3 while the normal cells' volumes were 28.17 cm3, 18.68 cm3, 30.34 cm3, and 12.54 cm3. The powers of the derivatives were 0.16774, 0.16557, 0.16835, and 0.16. A variance-based sensitivity analysis was done to corroborate the model with the clinical data. The result showed that the most sensitive factors were the power of the derivative and the cancer cells' proliferation rate. Conclusion The model provided information concerning the status of treatments and can also predict outcomes of other treatment plans.
  15. Farayola MF, Shafie S, Siam FM, Khan I
    Comput Methods Programs Biomed, 2020 May;188:105306.
    PMID: 31901851 DOI: 10.1016/j.cmpb.2019.105306
    BACKGROUND: This paper presents a mathematical model that simulates a radiotherapy cancer treatment process. The model takes into consideration two important radiobiological factors, which are repair and repopulation of cells. The model was used to simulate the fractionated treatment process of six patients. The results gave the population changes in the cells and the final volumes of the normal and cancer cells.

    METHOD: The model was formulated by integrating the Caputo fractional derivative with the previous cancer treatment model. Thereafter, the linear-quadratic with the repopulation model was coupled into the model to account for the cells' population decay due to radiation. The treatment process was then simulated with numerical variables, numerical parameters, and radiation parameters. The numerical parameters which included the proliferation coefficients of the cells, competition coefficients of the cells, and the perturbation constant of the normal cells were obtained from previous literature. The radiation and numerical parameters were obtained from reported clinical data of six patients treated with radiotherapy. The patients had tumor volumes of 24.1cm3, 17.4cm3, 28.4cm3, 18.8cm3, 30.6cm3, and 12.6cm3 with fractionated doses of 2 Gy for the first two patients and 1.8 Gy for the other four. The initial tumor volumes were used to obtain initial populations of cells after which the treatment process was simulated in MATLAB. Subsequently, a global sensitivity analysis was done to corroborate the model with clinical data. Finally, 96 radiation protocols were simulated by using the biologically effective dose formula. These protocols were used to obtain a regression equation connecting the value of the Caputo fractional derivative with the fractionated dose.

    RESULTS: The final tumor volumes, from the results of the simulations, were 3.58cm3, 8.61cm3, 5.68cm3, 4.36cm3, 5.75cm3, and 6.12cm3, while those of the normal cells were 23.87cm3, 17.29cm3, 28.17cm3, 18.68cm3, 30.33cm3, and 12.55cm3. The sensitivity analysis showed that the most sensitive model factors were the value of the Caputo fractional derivative and the proliferation coefficient of the cancer cells. Lastly, the obtained regression equation accounted for 99.14% of the prediction.

    CONCLUSION: The model can simulate a cancer treatment process and predict the results of other radiation protocols.

  16. Fahim I, Ishaque A, Ramzan F, Shamsuddin SABA, Ali A, Salim A, et al.
    Curr Issues Mol Biol, 2023 May 07;45(5):4100-4123.
    PMID: 37232730 DOI: 10.3390/cimb45050261
    BACKGROUND: Demyelinating diseases represent a broad spectrum of disorders and are characterized by the loss of specialized glial cells (oligodendrocytes), which eventually leads to neuronal degeneration. Stem cell-based regenerative approaches provide therapeutic options to regenerate demyelination-induced neurodegeneration.

    OBJECTIVES: The current study aims to explore the role of oligodendrocyte-specific transcription factors (OLIG2 and MYT1L) under suitable media composition to facilitate human umbilical-cord-derived mesenchymal stem cells (hUC-MSCs) differentiation toward oligodendrocyte for their potential use to treat demyelinating disorders.

    METHODOLOGY: hUC-MSCs were isolated, cultured, and characterized based on their morphological and phenotypic characteristics. hUC-MSCs were transfected with OLIG2 and MYT1L transcription factors individually and in synergistic (OLIG2 + MYT1L) groups using a lipofectamine-based transfection method and incubated under two different media compositions (normal and oligo induction media). Transfected hUC-MSCs were assessed for lineage specification and differentiation using qPCR. Differentiation was also analyzed via immunocytochemistry by determining the expression of oligodendrocyte-specific proteins.

    RESULTS: All the transfected groups showed significant upregulation of GFAP and OLIG2 with downregulation of NES, demonstrating the MSC commitment toward the glial lineage. Transfected groups also presented significant overexpression of oligodendrocyte-specific markers (SOX10, NKX2.2, GALC, CNP, CSPG4, MBP, and PLP1). Immunocytochemical analysis showed intense expression of OLIG2, MYT1L, and NG2 proteins in both normal and oligo induction media after 3 and 7 days.

    CONCLUSIONS: The study concludes that OLIG2 and MYT1L have the potential to differentiate hUC-MSCs into oligodendrocyte-like cells, which is greatly facilitated by the oligo induction medium. The study may serve as a promising cell-based therapeutic strategy against demyelination-induced neuronal degeneration.

  17. Khan I, Kumar H, Mishra G, Gothwal A, Kesharwani P, Gupta U
    Curr Pharm Des, 2017;23(35):5315-5326.
    PMID: 28875848 DOI: 10.2174/1381612823666170829164828
    BACKGROUND: Delivery of chemotherapeutic drugs for the diagnosis and treatment of cancer is becoming advanced day by day. However, the challenge of the effective delivery system still does exist. In various types of cancers, breast cancer is the most commonly diagnosed cancer among women. Breast cancer is a combination of different diseases. It cannot be considered as only one entity because there are many specific patient factors, which are involved in the development of this disease. Nanotechnology has opened a new area in the effective treatment of breast cancer due to the several benefits offered by this technology.

    METHODS: Polymeric nanocarriers are among one of the effective delivery systems, which has given promising results in the treatment of breast cancers. Nanocarriers does exert their anticancer effect either through active or passive targeting mode.

    RESULTS: The use of nanocarriers has been resolute about the adverse effects of chemotherapeutic drugs such as poor solubility and less penetrability in tumor cells.

    CONCLUSION: The present review is focused on recent developments regarding polymeric nanocarriers, such as polymeric micelles, polymeric nanoparticles, dendrimers, liposomes, nanoshells, fullerenes, carbon nanotubes (CNT) and quantum dots, etc. for their recent advancements in breast cancer therapy.

  18. Mohd Affandi A, Khan I, Ngah Saaya N
    Dermatol Res Pract, 2018;2018:4371471.
    PMID: 29849578 DOI: 10.1155/2018/4371471
    Background: Psoriasis is a chronic inflammatory skin disease affecting 2-3% of the general population.
    Aim: To evaluate the epidemiology and clinical characteristics of patients with psoriasis who seek treatment in outpatient dermatology clinics throughout hospitals in Malaysia.
    Materials and Methods: Data were obtained from the Malaysian Psoriasis Registry (MPR). All patients (aged 18 and above) who were notified to the registry from July 2017 to December 2017 were included in this study.
    Results: Among 15,794 patients, Malays were the most common (50.4%), followed by Chinese (21.4%), Indian (17.6%), and others (10.6%). The mean age onset of psoriasis for our study population was 35.14 ± 16.16 years. Male to female ratio was 1.3 : 1. 23.1% of patients had positive family history of psoriasis. The most common clinical presentation was chronic plaque psoriasis (85.1%), followed by guttate psoriasis (2.9%), erythrodermic psoriasis (1.7%), and pustular psoriasis (1.0%). Majority of our patients (76.6%) had a mild disease with BSA < 10%. 57.1% of patients had nail involvement, while arthropathy was seen in 13.7% of patients. Common triggers of the disease include stress (48.3%), sunlight (24.9%), and infection (9.1%). Comorbidities observed include obesity (24.3%), hypertension (25.6%), hyperlipidemia (18%), diabetes mellitus (17.2%), ischaemic heart disease (5.4%), and cerebrovascular disease (1.6%). The mean DLQI (Dermatology Life Quality Index) was 8.5 ± 6.6. One-third (33.1%) of the patients had a DLQI score of more than 10, while 14.2% of patients reported no effect at all.
    Conclusion: Our study on the epidemiological data of adult patients with psoriasis in Malaysia showed a similar clinical profile and outcome when compared to international published studies on the epidemiology of psoriasis.
  19. Ahmed S, Govender T, Khan I, Rehman NU, Ali W, Shah SMH, et al.
    Drug Des Devel Ther, 2018;12:255-269.
    PMID: 29440875 DOI: 10.2147/DDDT.S148912
    Background and aim: The challenges with current antimicrobial drug therapy and resistance remain a significant global health threat. Nanodrug delivery systems are playing a crucial role in overcoming these challenges and open new avenues for effective antimicrobial therapy. While fluticasone (FLU), a poorly water-soluble corticosteroid, has been reported to have potential antimicrobial activity, approaches to optimize its dissolution profile and antimicrobial activity are lacking in the literature. This study aimed to combine an experimental study with molecular modeling to design stable FLU nanopolymeric particles with enhanced dissolution rates and antimicrobial activity.

    Methods: Six different polymers were used to prepare FLU nanopolymeric particles: hydroxyl propyl methylcellulose (HPMC), poly (vinylpyrrolidone) (PVP), poly (vinyl alcohol) (PVA), ethyl cellulose (EC), Eudragit (EUD), and Pluronics®. A low-energy method, nanoprecipitation, was used to prepare the polymeric nanoparticles.

    Results and conclusion: The combination of HPMC-PVP and EUD-PVP was found most effective to produce stable FLU nanoparticles, with particle sizes of 250 nm ±2.0 and 280 nm ±4.2 and polydispersity indices of 0.15 nm ±0.01 and 0.25 nm ±0.03, respectively. The molecular modeling studies endorsed the same results, showing highest polymer drug binding free energies for HPMC-PVP-FLU (-35.22 kcal/mol ±0.79) and EUD-PVP-FLU (-25.17 kcal/mol ±1.12). In addition, it was observed that Ethocel® favored a wrapping mechanism around the drug molecules rather than a linear conformation that was witnessed for other individual polymers. The stability studies conducted for 90 days demonstrated that HPMC-PVP-FLU nanoparticles stored at 2°C-8°C and 25°C were more stable. Crystallinity of the processed FLU nanoparticles was confirmed using differential scanning calorimetry, powder X-ray diffraction analysis and TEM. The Fourier transform infrared spectroscopy (FTIR) studies showed that there was no chemical interaction between the drug and chosen polymer system. The HPMC-PVP-FLU nanoparticles also showed enhanced dissolution rate (P<0.05) compared to the unprocessed counterpart. The in vitro antibacterial studies showed that HPMC-PVP-FLU nanoparticles displayed superior effect against gram-positive bacteria compared to the unprocessed FLU and positive control.

  20. Khanabdali R, Saadat A, Fazilah M, Bazli KF, Qazi RE, Khalid RS, et al.
    Drug Des Devel Ther, 2016;10:81-91.
    PMID: 26766903 DOI: 10.2147/DDDT.S89658
    Small molecules, growth factors, and cytokines have been used to induce differentiation of stem cells into different lineages. Similarly, demethylating agents can trigger differentiation in adult stem cells. Here, we investigated the in vitro differentiation of rat bone marrow mesenchymal stem cells (MSCs) into cardiomyocytes by a demethylating agent, zebularine, as well as neuronal-like cells by β-mercaptoethanol in a growth factor or cytokines-free media. Isolated bone marrow-derived MSCs cultured in Dulbecco's Modified Eagle's Medium exhibited a fibroblast-like morphology. These cells expressed positive markers for CD29, CD44, and CD117 and were negative for CD34 and CD45. After treatment with 1 μM zebularine for 24 hours, the MSCs formed myotube-like structures after 10 days in culture. Expression of cardiac-specific genes showed that treated MSCs expressed significantly higher levels of cardiac troponin-T, Nkx2.5, and GATA-4 compared with untreated cells. Immunocytochemical analysis showed that differentiated cells also expressed cardiac proteins, GATA-4, Nkx 2.5, and cardiac troponin-T. For neuronal differentiation, MSCs were treated with 1 and 10 mM β-mercaptoethanol overnight for 3 hours in complete and serum-free Dulbecco's Modified Eagle's Medium, respectively. Following overnight treatment, neuron-like cells with axonal and dendritic-like projections originating from the cell body toward the neighboring cells were observed in the culture. The mRNA expression of neuronal-specific markers, Map2, Nefl, Tau, and Nestin, was significantly higher, indicating that the treated cells differentiated into neuronal-like cells. Immunostaining showed that differentiated cells were positive for the neuronal markers Flk, Nef, Nestin, and β-tubulin.
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