Displaying publications 81 - 100 of 167 in total

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  1. Fulltext XGBoost-enhanced ensemble model using discriminative hybrid features for the prediction of sumoylation sites
    Khan S, Noor S, Javed T, Naseem A, Aslam F, AlQahtani SA, et al.
    BioData Min, 2025 Feb 03;18(1):12.
    PMID: 39901279 DOI: 10.1186/s13040-024-00415-8
    Posttranslational modifications (PTMs) are essential for regulating protein localization and stability, significantly affecting gene expression, biological functions, and genome replication. Among these, sumoylation a PTM that attaches a chemical group to protein sequences-plays a critical role in protein function. Identifying sumoylation sites is particularly important due to their links to Parkinson's and Alzheimer's. This study introduces XGBoost-Sumo, a robust model to predict sumoylation sites by integrating protein structure and sequence data. The model utilizes a transformer-based attention mechanism to encode peptides and extract evolutionary features through the PsePSSM-DWT approach. By fusing word embeddings with evolutionary descriptors, it applies the SHapley Additive exPlanations (SHAP) algorithm for optimal feature selection and uses eXtreme Gradient Boosting (XGBoost) for classification. XGBoost-Sumo achieved an impressive accuracy of 99.68% on benchmark datasets using 10-fold cross-validation and 96.08% on independent samples. This marks a significant improvement, outperforming existing models by 10.31% on training data and 2.74% on independent tests. The model's reliability and high performance make it a valuable resource for researchers, with strong potential for applications in pharmaceutical development.
  2. Fulltext CD44-Receptors-Mediated Multiprong Targeting Strategy Against Breast Cancer and Tumor-Associated Macrophages: Design, Optimization, Characterization, and Cytologic Evaluation
    Hussain Z, Abdulrahim Abdul Moti L, Jagal J, Thu HE, Khan S, Kazi M
    Int J Nanomedicine, 2025;20:991-1020.
    PMID: 39881963 DOI: 10.2147/IJN.S480553
    INTRODUCTION: Owing to its high prevalence, colossal potential of chemoresistance, metastasis, and relapse, breast cancer (BC) is the second leading cause of cancer-related fatalities in women. Several treatments (eg, chemotherapy, surgery, radiations, hormonal therapy, etc.) are conventionally prescribed for the treatment of BC; however, these are associated with serious systemic aftermaths. In this research, we aimed to design a multiprong targeting strategy for concurrent action against different phenotypes of BC (MCF-7 and SK-BR-3) and tumor-associated macrophages (TAMs) for relapse-free treatment of BC.

    METHODS: Paclitaxel (PTX) and tamoxifen (TMX) co-loaded chitosan (CS) nanoparticles (NPs) were prepared using the ionic-gelation method and optimized using the Design Expert® software by controlling different material attributes. For selective targeting through CD44-receptors that are heavily expressed on the BC cells and TAMs, the fabricated NPs (PTX-TMX-CS-NPs) were functionalized with hyaluronic acid (HA) as a targeting ligand.

    RESULTS: The optimized HA-PTX-TMX-CS-NPs exhibited desired physicochemical properties (PS ~230 nm, PDI 0.30, zeta potential ~21.5 mV), smooth spherical morphology, high encapsulation efficiency (PTX ~72% and TMX ~97%), good colloidal stability, and biphasic release kinetics. Moreover, the lowest cell viability depicted in MCF-7 (~25%), SK-BR-3 (~20%), and RAW 264.7 cells (~20%), induction of apoptosis, cell cycle arrest, enhanced cell internalization, and alleviation of MCF-7 and SK-BR-3 migration proved the superior anticancer potential of HA-PTX-TMX-CS-NPs compared to unfunctionalized NPs and other control medicines.

    CONCLUSION: HA-functionalization of NPs is a promising multiprong strategy for CD44-receptors-mediated targeting of BC cells and TAMs to mitigate the progression, metastasis, and relapse in the BC.

  3. Fulltext Dynamic Learning Framework for Smooth-Aided Machine-Learning-Based Backbone Traffic Forecasts
    Hassan MK, Syed Ariffin SH, Ghazali NE, Hamad M, Hamdan M, Hamdi M, et al.
    Sensors (Basel), 2022 May 09;22(9).
    PMID: 35591282 DOI: 10.3390/s22093592
    Recently, there has been an increasing need for new applications and services such as big data, blockchains, vehicle-to-everything (V2X), the Internet of things, 5G, and beyond. Therefore, to maintain quality of service (QoS), accurate network resource planning and forecasting are essential steps for resource allocation. This study proposes a reliable hybrid dynamic bandwidth slice forecasting framework that combines the long short-term memory (LSTM) neural network and local smoothing methods to improve the network forecasting model. Moreover, the proposed framework can dynamically react to all the changes occurring in the data series. Backbone traffic was used to validate the proposed method. As a result, the forecasting accuracy improved significantly with the proposed framework and with minimal data loss from the smoothing process. The results showed that the hybrid moving average LSTM (MLSTM) achieved the most remarkable improvement in the training and testing forecasts, with 28% and 24% for long-term evolution (LTE) time series and with 35% and 32% for the multiprotocol label switching (MPLS) time series, respectively, while robust locally weighted scatter plot smoothing and LSTM (RLWLSTM) achieved the most significant improvement for upstream traffic with 45%; moreover, the dynamic learning framework achieved improvement percentages that can reach up to 100%.
  4. Fulltext The effect of laparoscopic vertical sleeve gastrectomy and laparoscopic roux-en-Y gastric bypass on gastroesophageal reflux disease: An updated meta-analysis and systematic review of 5-year post-operative data from randomized controlled trials
    Memon MA, Osland E, Yunus RM, Hoque Z, Alam K, Khan S
    Surg Endosc, 2024 Nov;38(11):6254-6269.
    PMID: 39384655 DOI: 10.1007/s00464-024-11303-x
    BACKGROUND: To evaluate 5-year effect of laparoscopic vertical sleeve gastrectomy (LVSG) versus laparoscopic roux-en-Y gastric bypass (LRYGB) on gastroesophageal reflux disease (GERD) solely based on randomized controlled trials (RCTs).

    METHODS: A systematic review and meta-analysis of 5-year postoperative GERD data comparing LVSG and LRYGB in adults were undertaken. Electronic databases were searched from January 2015 to March 2024 for publications meeting inclusion criteria. The Hartung-Knapp-Sidik-Jonkman random effects model was applied to estimate pooled odds ratio where meta-analysis was possible. Bias and certainty of evidence were assessed using the Cochrane Risk of Bias Tool 2 and GRADE.

    RESULTS: Five RCTs were analysed (LVSG n = 554, LRYGB n = 539). LVSG was associated with increased adverse GERD outcomes compared to LRYGB at 5 years. The odds for revisional surgery to treat GERD in LVSG patients were 11 times higher compared to LRYGB (OR 11.47, 95% CI 1.83 to 71.69; p = 0.02; I2 = 0% High level of certainty). Similarly pharmacological management for increasing GERD was significantly more frequent in LVSG patients compared to LRYGB (OR 3.89, 95% CI 2.31 to 6.55; p ≤ 0.01; I2 = 0% Moderate level of certainty). Overall, LVSG was associated with significantly more interventions (both medical and surgical) for either worsening GERD and/or development of de novo GERD compared to LRYGB (OR 5.98, 95% CI 3.48 to 10.29; p ≤ 0.01; I2 = 0%) Moderate level of certainty).

    CONCLUSIONS: The development and worsening of GERD symptoms are frequently associated with LVSG compared to LRYGB at 5 years postoperatively requiring either initiation or increase of pharmacotherapy or failing that revisional bariatric surgery. Appropriate patient/surgical selection is crucial to reduce these postoperative risks of GERD.

  5. Fulltext Domain decomposition and mortar mixed approach for nonlinear elliptic equations modeling flow in porous media
    Arshad M, Mehmood A, Salleh Z, Akhtar SS, Khan S, Inc M
    Heliyon, 2025 Feb 28;11(4):e42724.
    PMID: 40066045 DOI: 10.1016/j.heliyon.2025.e42724
    The equations describe the behavior of steady state flow in porous medium generally results in elliptic partial differential equations with coefficient represents the permeability of the medium. This article presents the extension of mortar mixed method for second order nonlinear elliptic equations that describes flow in porous media. The domain is decomposed into non-overlapping regions with each partitioned independently. The grids on subdomains are allowed to be non-matching across the subdomains internal boundaries. The fixed point argument (FPA) is employed to establish the existence and uniqueness of discrete problem, and optimal order error estimates are provided for approximations. The computational results are given to validate the theory.
  6. Fulltext New cholinesterase inhibitory constituents from Lonicera quinquelocularis
    Khan D, Khan HU, Khan F, Khan S, Badshah S, Khan AS, et al.
    PLoS One, 2014;9(4):e94952.
    PMID: 24733024 DOI: 10.1371/journal.pone.0094952
    A phytochemical investigation on the ethyl acetate soluble fraction of Lonicera quinquelocularis (whole plant) led to the first time isolation of one new phthalate; bis(7-acetoxy-2-ethyl-5-methylheptyl) phthalate (3) and two new benzoates; neopentyl-4-ethoxy-3, 5-bis (3-methyl-2-butenyl benzoate (4) and neopentyl-4-hydroxy-3, 5-bis (3-methyl-2-butenyl benzoate (5) along with two known compounds bis (2-ethylhexyl phthalate (1) and dioctyl phthalate (2). Their structures were established on the basis of spectroscopic analysis and by comparison with available data in the literature. All the compounds (1-5) were tested for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities in dose dependent manner. The IC50 (50% inhibitory effect) values of compounds 3 and 5 against AChE were 1.65 and 3.43 µM while the values obtained against BChE were 5.98 and 9.84 µM respectively. Compounds 2 and 4 showed weak inhibition profile.
  7. Renal denervation restores the baroreflex control of renal sympathetic nerve activity and heart rate in Wistar-Kyoto rats with cisplatin-induced renal failure
    Khan SA, Sattar MA, Rathore HA, Abdulla MH, Ud Din Ahmad F, Ahmad A, et al.
    Acta Physiol (Oxf), 2014 Mar;210(3):690-700.
    PMID: 24438102 DOI: 10.1111/apha.12237
    There is evidence that in chronic renal failure, the sympathetic nervous system is activated. This study investigated the role of the renal innervation in suppressing high- and low-pressure baroreflex control of renal sympathetic nerve activity and heart rate in cisplatin-induced renal failure.
  8. Fulltext Functional impairment as a proxy measure indicating high rates of trauma exposure, post-migration living difficulties, common mental disorders, and poor health amongst Rohingya refugees in Malaysia
    Tay AK, Rees S, Miah MAA, Khan S, Badrudduza M, Morgan K, et al.
    Transl Psychiatry, 2019 09 02;9(1):213.
    PMID: 31477686 DOI: 10.1038/s41398-019-0537-z
    A major challenge in the refugee field is to ensure that scarce mental health resources are directed to those in greatest need. Based on data from an epidemiological survey of 959 adult Rohingya refugees in Malaysia (response rate: 83%), we examine whether a brief screening instrument of functional impairment, the WHO Disability Assessment Schedule (WHODAS), prove useful as a proxy measure to identify refugees who typically attend community mental health services. Based on estimates of mental disorder requiring interventions from analyses of epidemiological studies conducted worldwide, we selected a WHODAS cutoff that identified the top one-fifth of refugees according to severity of functional impairment, the remainder being distributed to moderate and lower impairment groupings, respectively. Compared to the lower impairment grouping, the severe impairment category comprised more boat arrivals (AOR: 5.96 [95% CI 1.34-26.43); stateless persons (A20·11 [95% CI 7.14-10); those with high exposure to pre-migration traumas (AOR: 4.76 [95% CI 1.64-13.73), peri-migration stressors (AOR: 1.26 [95% CI 1.14-1.39]) and postmigration living difficulties (AOR: 1.43 [95% CI 1.32-1.55); persons with single (AOR: 7.48 [95% CI 4.25-13.17]) and comorbid (AOR: 13.54 [95% CI 6.22-29.45]) common mental disorders; and those reporting poorer general health (AOR: 2.23 [95% CI 1-5.02]). In addition, half of the severe impairment grouping (50.6%) expressed suicidal ideas compared to one in six (16.2 percent) of the lower impairment grouping (OR: 2.39 [95% CI 1.94-2.93]). Differences between the severe and moderate impairment groups were similar but less extreme. In settings where large-scale epidemiological studies are not feasible, the WHODAS may serve as readily administered and brief public health screening tool that assists in stratifying the population according to urgency of mental health needs.
  9. In silico and BSA binding study of some new biological analogs of 1,2,4-triazolependant with azinane through microwave and conventional synthesis
    Virk NA, Rehman A, Abbasi MA, Siddiqui SZ, Ashraf A, Lateef M, et al.
    Pak J Pharm Sci, 2018 Nov;31(6 (Supplementary):2645-2654.
    PMID: 30587474
    Microwave and conventional techniques were employed to synthesize a novel array of compounds 7a-g with 1,2,4-triazole and piperidine rings having great biological importance. The microwave assisted method has a better operational scope with respect to time and yield comparative to the conventional method. 1H-NMR, 13C-NMR and IR techniques were employed to justify the structure of synthesized compounds. The antioxidant, butyrylcholinesterase inhibition and urease inhibition potential of every synthesized compound was evaluated. Every member of the synthesized series was found potent against mentioned activities. Compound 7g was the most active anti-urease agent having IC50 (μM) value 16.5±0.09 even better than the thiourea with an IC50(μM) value of 24.3±0.24. The better urease inhibition potential of 7g was also elaborated and explained by docking and bovine serum albumin (BSA) binding studies.
  10. Synthesis, bioactivity and binding energy calculations of novel 3-ethoxysalicylaldehyde based thiosemicarbazone derivatives
    Ishaq M, Taslimi P, Shafiq Z, Khan S, Ekhteiari Salmas R, Zangeneh MM, et al.
    Bioorg Chem, 2020 07;100:103924.
    PMID: 32442818 DOI: 10.1016/j.bioorg.2020.103924
    In recent decade, the entrance of α-N-heterocyclic thiosemicarbazones derivates (Triapne, COTI-2 and DpC) in clinical trials for cancer and HIV-1 has vastly increased the interests of medicinal chemists towards this class of organic compounds. In the given study, a series of eighteen new (3a-r) 3-ethoxy salicylaldehyde-based thiosemicarbazones (TSC), bearing aryl and cycloalkyl substituents, were synthesized and assayed for their pharmacological potential against carbonic anhydrases (hCA I and hCA II), cholinesterases (AChE and BChE) and α-glycosidase. The hCA I isoform was inhibited by these novel 3-ethoxysalicylaldehyde thiosemicarbazone derivatives (3a-r) in low nanomolar levels, the Ki of which differed between 144.18 ± 26.74 and 454.92 ± 48.32 nM. Against the physiologically dominant isoform hCA II, the novel compounds demonstrated Kis varying from 110.54 ± 14.05 to 444.12 ± 36.08 nM. Also, these novel derivatives (3a-r) effectively inhibited AChE, with Ki values in the range of 385.38 ± 45.03 to 983.04 ± 104.64 nM. For BChE was obtained with Ki values in the range of 400.21 ± 35.68 to 1003.02 ± 154.27 nM. For α-glycosidase the most effective Ki values of 3l, 3n, and 3q were with Ki values of 12.85 ± 1.05, 16.03 ± 2.84, and 19.16 ± 2.66 nM, respectively. Moreover, the synthesized TCSs were simulated using force field methods whereas the binding energies of the selected compounds were estimated using MM-GBSA method. The findings indicate the present novel 3-ethoxy salicylaldehyde-based thiosemicarbazones to be excellent hits for pharmaceutical applications.
  11. Nano-scaled materials may induce severe neurotoxicity upon chronic exposure to brain tissues: A critical appraisal and recent updates on predisposing factors, underlying mechanism, and future prospects
    Hussain Z, Thu HE, Elsayed I, Abourehab MAS, Khan S, Sohail M, et al.
    J Control Release, 2020 12 10;328:873-894.
    PMID: 33137366 DOI: 10.1016/j.jconrel.2020.10.053
    Owing to their tremendous potential, the inference of nano-scaled materials has revolutionized many fields including the medicine and health, particularly for development of various types of targeted drug delivery devices for early prognosis and successful treatment of various diseases, including the brain disorders. Owing to their unique characteristic features, a variety of nanomaterials (particularly, ultra-fine particles (UFPs) have shown tremendous success in achieving the prognostic and therapeutic goals for early prognosis and treatment of various brain maladies such as Alzheimer's disease, Parkinson's disease, brain lymphomas, and other ailments. However, serious attention is needful due to innumerable after-effects of the nanomaterials. Despite their immense contribution in optimizing the prognostic and therapeutic modalities, biological interaction of nanomaterials with various body tissues may produce severe nanotoxicity of different organs including the heart, liver, kidney, lungs, immune system, gastro-intestinal system, skin as well as nervous system. However, in this review, we have primarily focused on nanomaterials-induced neurotoxicity of the brain. Following their translocation into different regions of the brain, nanomaterials may induce neurotoxicity through multiple mechanisms including the oxidative stress, DNA damage, lysosomal dysfunction, inflammatory cascade, apoptosis, genotoxicity, and ultimately necrosis of neuronal cells. Our findings indicated that rigorous toxicological evaluations must be carried out prior to clinical translation of nanomaterials-based formulations to avoid serious neurotoxic complications, which may further lead to develop various neuro-degenerative disorders.
  12. Fulltext Treatment Outcomes of Extensively Drug-Resistant Tuberculosis in Pakistan: A Countrywide Retrospective Record Review
    Abubakar M, Ahmad N, Ghafoor A, Latif A, Ahmad I, Atif M, et al.
    Front Pharmacol, 2021;12:640555.
    PMID: 33867989 DOI: 10.3389/fphar.2021.640555
    Background: The current study is conducted with the aim to the fill the gap of information regarding treatment outcomes and variables associated with unsuccessful outcome among XDR-TB patients from Pakistan. Methods: A total of 404 culture confirmed XDR-TB patients who received treatment between 1st May 2010 and June 30, 2017 at 27 treatment centers all over Pakistan were retrospectively followed until their treatment outcomes were reported. A p-value <0.05 reflected a statistical significant association. Results: The patients had a mean age 32.9 ± 14.1 years. The overall treatment success rate was 40.6% (95% confidence interval [CI]:35.80-45.60%). A total of 155 (38.4%) patients were declared cured, 9 (2.2%) completed treatment, 149 (36.9%) died, 60 (14.9%) failed treatment and 31 (7.7%) were lost to follow up (LTFU). The results of the multivariate binary logistic regression analysis revealed that the patients' age of >60 years (OR = 4.69, 95%CI:1.57-15.57) and receiving high dose isoniazid (OR = 2.36, 95%CI:1.14-4.85) had statistically significant positive association with death, whereas baseline body weight >40 kg (OR = 0.43, 95%CI:0.25-0.73) and sputum culture conversion in the initial two months of treatment (OR = 0.33, 95%CI:0.19-0.58) had statistically significant negative association with death. Moreover, male gender had statistically significant positive association (OR = 1.92, 95%CI:1.04-3.54) with LTFU. Conclusion: The treatment success rate (40.6%) of XDR-TB patients in Pakistan was poor. Providing special attention and enhanced clinical management to patients with identified risk factors for death and LTFU in the current cohort may improve the treatment outcomes.
  13. Chitosan based thermosensitive injectable hydrogels for controlled delivery of loxoprofen: development, characterization and in-vivo evaluation
    Ahmad U, Sohail M, Ahmad M, Minhas MU, Khan S, Hussain Z, et al.
    Int J Biol Macromol, 2019 May 15;129:233-245.
    PMID: 30738157 DOI: 10.1016/j.ijbiomac.2019.02.031
    Oral drug delivery is natural, most acceptable and desirable route for nearly all drugs, but many drugs like NSAIDs when delivered by this route cause gastrointestinal irritation, gastric bleeding, ulcers, and many undesirable effects which limits their usage by oral delivery. Moreover, it is almost impossible to control the release of a drug in a targeted location in body. We developed thermo-responsive chitosan-co-poly(N-isopropyl-acrylamide) injectable hydrogel as an alternative for the gastro-protective and controlled delivery of loxoprofen sodium as a model drug. A free radical polymerization technique was used to synthesize thermo-responsive hydrogel by cross-linking chitosan HCl with NIPAAM using glutaraldehyde as cross-linker. Confirmation of crosslinked hydrogel structure was done by Fourier transform infrared spectra (FTIR). The thermal stability of hydrogel was confirmed through thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The scanning electron microscopy (SEM) was performed to evaluate the structural morphology of cross-linked hydrogel. To evaluate the rheological behavior of hydrogel with increasing temperature, rheological study was performed. Swelling and in vitro drug release studies were carried out under various temperature and pH conditions. The swelling study revealed that maximum swelling was observed at low pH (pH 1.2) and low temperature (25 °C) compared to the high range of pH and temperature and it resulted in quick release of the drug. The high range of pH (7.4) and temperature (37 °C) however caused controlled release of the drug. The in vivo evaluation of the developed hydrogel in rabbits demonstrated the controlled release behavior of fabricated system.
  14. Curcumin-laden hyaluronic acid-co-Pullulan-based biomaterials as a potential platform to synergistically enhance the diabetic wound repair
    Shah SA, Sohail M, Minhas MU, Khan S, Hussain Z, Mahmood A, et al.
    Int J Biol Macromol, 2021 Aug 31;185:350-368.
    PMID: 34171251 DOI: 10.1016/j.ijbiomac.2021.06.119
    Injectable hydrogel with multifunctional tunable properties comprising biocompatibility, anti-oxidative, anti-bacterial, and/or anti-infection are highly preferred to efficiently promote diabetic wound repair and its development remains a challenge. In this study, we report hyaluronic acid and Pullulan-based injectable hydrogel loaded with curcumin that could potentiate reepithelization, increase angiogenesis, and collagen deposition at wound microenvironment to endorse healing cascade compared to other treatment groups. The physical interaction and self-assembly of hyaluronic acid-Pullulan-grafted-pluronic F127 injectable hydrogel were confirmed using nuclear magnetic resonance (1H NMR) and Fourier transformed infrared spectroscopy (FT-IR), and cytocompatibility was confirmed by fibroblast viability assay. The CUR-laden hyaluronic acid-Pullulan-g-F127 injectable hydrogel promptly undergoes a sol-gel transition and has proved to potentiate wound healing in a streptozotocin-induced diabetic rat model by promoting 93% of wound closure compared to other groups having 35%, 38%, and 62%. The comparative in vivo study and histological examination was conducted which demonstrated an expeditious recovery rate by significantly reducing the wound healing days i.e. 35 days in a control group, 33 days in the CUR suspension group, 21 days in unloaded injectable, and 13 days was observed in CUR loaded hydrogel group. Furthermore, we suggest that the injectable hydrogel laden with CUR showed a prompt wound healing potential by increasing the cell proliferation and serves as a drug delivery platform for sustained and targeted delivery of hydrophobic moieties.
  15. A Naturalistic Evaluation of Group Integrative Adapt Therapy (IAT-G) with Rohingya Refugees During the Emergency Phase of a Mass Humanitarian Crisis in Cox's Bazar, Bangladesh
    Tay AK, Miah MAA, Khan S, Mohsin M, Alam ANMM, Ozen S, et al.
    EClinicalMedicine, 2021 Aug;38:100999.
    PMID: 34505027 DOI: 10.1016/j.eclinm.2021.100999
    Background: Studies of scalable psychological interventions in humanitarian setting are usually carried out when the acute emergency has stabilized. We report the first evaluation of an evidence-based group psychological intervention, Group Integrative Adapt Therapy (IAT-G), during the emergency phase of a mass humanitarian crisis amongst Rohingya refugees in Cox's Bazar, Bangladesh. Methods: We did a pragmatic naturalistic evaluation (2018-2020) of a seven-session group intervention with adult Rohingya refugees with elevated symptoms of depression (≥10 on the Patient Health Questionnaire) and/or posttraumatic stress disorder, PTSD, (≥3 on the Posttraumatic Stress Disorder-8), and functional impairment (≥17 on WHO Disability Assessment Schedule or WHODAS-brief). Screening was done across the most densely populated campsites. Blind assessments were completed at baseline, posttreatment, and at 3-month follow-up using culturally adapted measures of depression, anxiety, posttraumatic stress symptoms, complicated bereavement, adaptive stress associated with disrupted psychosocial support systems, functional impairment, and resilience. Findings: 383 persons were screened and of the 144 persons who met inclusion criteria all participated in the group intervention. Compared to baseline scores, IAT-G participants recorded significantly lower mean scores on key outcome indices (mental health symptoms, adaptive stress, and functional impairment) at posttreatment and 3-month follow-up (all pairwise tests significant Ps
  16. Probing 4-(diethylamino)-salicylaldehyde-based thiosemicarbazones as multi-target directed ligands against cholinesterases, carbonic anhydrases and α-glycosidase enzymes
    Hashmi S, Khan S, Shafiq Z, Taslimi P, Ishaq M, Sadeghian N, et al.
    Bioorg Chem, 2021 02;107:104554.
    PMID: 33383322 DOI: 10.1016/j.bioorg.2020.104554
    With the fading of 'one drug-one target' approach, Multi-Target-Directed Ligands (MTDL) has become a central idea in modern Medicinal Chemistry. The present study aimed to design, develop and characterize a novel series of 4-(Diethylamino)-salicylaldehyde based thiosemicarbazones (3a-p) and evaluates their biological activity against cholinesterase, carbonic anhydrases and α-glycosidase enzymes. The hCA I isoform was inhibited by these novel 4-(diethylamino)-salicylaldehyde-based thiosemicarbazones (3a-p) in low nanomolar levels, the Ki of which differed between 407.73 ± 43.71 and 1104.11 ± 80.66 nM. Against the physiologically dominant isoform hCA II, the novel compounds demonstrated Kis varying from 323.04 ± 56.88 to 991.62 ± 77.26 nM. Also, these novel 4-(diethylamino)-salicylaldehyde based thiosemicarbazones (3a-p) effectively inhibited AChE, with Ki values in the range of 121.74 ± 23.52 to 548.63 ± 73.74 nM. For BChE, Ki values were obtained with in the range of 132.85 ± 12.53 to 618.53 ± 74.23 nM. For α-glycosidase, the most effective Ki values of 3b, 3k, and 3g were with Ki values of 77.85 ± 10.64, 96.15 ± 9.64, and 124.95 ± 11.44 nM, respectively. We have identified inhibition mechanism of 3b, 3g, 3k, and 3n on α-glycosidase AChE, hCA I, hCA II, and BChE enzyme activities. Hydrazine-1-carbothioamide and hydroxybenzylidene moieties of compounds play an important role in the inhibition of AChE, hCA I, and hCA II enzymes. Hydroxybenzylidene moieties are critical for inhibition of both BChE and α-glycosidase enzymes. The findings of in vitro and in silico evaluations indicate 4-(diethylamino)-salicylaldehyde-based thiosemicarbazone scaffold to be a promising hit for drug development for multifactorial diseases like Alzheimer's disease.
  17. Drug nanocarrier, the future of atopic diseases: Advanced drug delivery systems and smart management of disease
    Shao M, Hussain Z, Thu HE, Khan S, Katas H, Ahmed TA, et al.
    Colloids Surf B Biointerfaces, 2016 Nov 01;147:475-491.
    PMID: 27592075 DOI: 10.1016/j.colsurfb.2016.08.027
    Atopic dermatitis (AD) is a chronically relapsing skin inflammatory disorder characterized by perivascular infiltration of immunoglobulin-E (IgE), T-lymphocytes and mast cells. The key pathophysiological factors causing this disease are immunological disorders and the compromised epidermal barrier integrity. Pruritus, intense itching, psychological stress, deprived physical and mental performance and sleep disturbance are the hallmark features of this dermatological complication. Preventive interventions which include educational programs, avoidance of allergens, exclusive care towards skin, and the rational selection of therapeutic regimen play key roles in the treatment of dermatosis. In last two decades, it is evident from a plethora of studies that scientific focus is being driven from conventional therapies to the advanced nanocarrier-based regimen for an effective management of AD. These nanocarriers which include polymeric nanoparticles (NPs), hydrogel NPs, liposomes, ethosomes, solid lipid nanoparticles (SLNs) and nanoemulsion, provide efficient roles for the target specific delivery of the therapeutic payload. The success of these targeted therapies is due to their pharmaceutical versatility, longer retention time at the target site, avoiding off-target effects and preventing premature degradation of the incorporated drugs. The present review was therefore aimed to summarise convincing evidence for the therapeutic superiority of advanced nanocarrier-mediated strategies over the conventional therapies used in the treatment of AD.
  18. Natural and synthetic polymer-based smart biomaterials for management of ulcerative colitis: a review of recent developments and future prospects
    Sohail M, Mudassir, Minhas MU, Khan S, Hussain Z, de Matas M, et al.
    Drug Deliv Transl Res, 2019 04;9(2):595-614.
    PMID: 29611113 DOI: 10.1007/s13346-018-0512-x
    Ulcerative colitis (UC) is an inflammatory disease of the colon that severely affects the quality of life of patients and usually responds well to anti-inflammatory agents for symptomatic relief; however, many patients need colectomy, a surgical procedure to remove whole or part of the colon. Though various types of pharmacological agents have been employed for the management of UC, the lack of effectiveness is usually predisposed to various reasons including lack of target-specific delivery of drugs and insufficient drug accumulation at the target site. To overcome these glitches, many researchers have designed and characterized various types of versatile polymeric biomaterials to achieve target-specific delivery of drugs via oral route to optimize their targeting efficiency to the colon, to improve drug accumulation at the target site, as well as to ameliorate off-target effects of chemotherapy. Therefore, the aim of this review was to summarize and critically discuss the pharmaceutical significance and therapeutic feasibility of a wide range of natural and synthetic biomaterials for efficient drug targeting to colon and rationalized treatment of UC. Among various types of biomaterials, natural and synthetic polymer-based hydrogels have shown promising targeting potential due to their innate pH responsiveness, sustained and controlled release characteristics, and microbial degradation in the colon to release the encapsulated drug moieties. These characteristic features make natural and synthetic polymer-based hydrogels superior to conventional pharmacological strategies for the management of UC.
  19. Nanomedicines as emerging platform for simultaneous delivery of cancer therapeutics: new developments in overcoming drug resistance and optimizing anticancer efficacy
    Hussain Z, Arooj M, Malik A, Hussain F, Safdar H, Khan S, et al.
    Artif Cells Nanomed Biotechnol, 2018;46(sup2):1015-1024.
    PMID: 29873531 DOI: 10.1080/21691401.2018.1478420
    Development and formulation of an efficient and safe therapeutic regimen for cancer theranostics are dynamically challenging. The use of mono-therapeutic cancer regimen is generally restricted to optimal clinical applications, on account of drug resistance and cancer heterogeneity. Combinatorial treatments can employ multi-therapeutics for synergistic anticancer efficacy whilst reducing the potency of individual moieties and diminishing the incidence of associated adverse effects. The combo-delivery of nanotherapeutics can optimize anti-tumor efficacy while reversing the incidence of drug resistance, aiming to homogenize pharmacological profile of drugs, enhance circulatory time, permit targeted drug accumulation, achieve multi-target dynamic approach, optimize target-specific drug binding and ensure sustained drug release at the target site. Numerous nanomedicines/nanotherapeutics have been developed by having dynamic physicochemical, pharmaceutical and pharmacological implications. These innovative delivery approaches have displayed specialized treatment effects, alone or in combination with conventional anticancer approaches (photodynamic therapy, radiotherapy and gene therapy), while reversing drug resistance and potential off-target effects. The current review presents a comprehensive overview of nanocarrier aided multi-drug therapies alongside recent advancements, future prospects, and the pivotal requirements for interdisciplinary research.
  20. Fulltext Efficient and Stable Routing Algorithm Based on User Mobility and Node Density in Urban Vehicular Network
    Al-Mayouf YR, Ismail M, Abdullah NF, Wahab AW, Mahdi OA, Khan S, et al.
    PLoS One, 2016;11(11):e0165966.
    PMID: 27855165 DOI: 10.1371/journal.pone.0165966
    Vehicular ad hoc networks (VANETs) are considered an emerging technology in the industrial and educational fields. This technology is essential in the deployment of the intelligent transportation system, which is targeted to improve safety and efficiency of traffic. The implementation of VANETs can be effectively executed by transmitting data among vehicles with the use of multiple hops. However, the intrinsic characteristics of VANETs, such as its dynamic network topology and intermittent connectivity, limit data delivery. One particular challenge of this network is the possibility that the contributing node may only remain in the network for a limited time. Hence, to prevent data loss from that node, the information must reach the destination node via multi-hop routing techniques. An appropriate, efficient, and stable routing algorithm must be developed for various VANET applications to address the issues of dynamic topology and intermittent connectivity. Therefore, this paper proposes a novel routing algorithm called efficient and stable routing algorithm based on user mobility and node density (ESRA-MD). The proposed algorithm can adapt to significant changes that may occur in the urban vehicular environment. This algorithm works by selecting an optimal route on the basis of hop count and link duration for delivering data from source to destination, thereby satisfying various quality of service considerations. The validity of the proposed algorithm is investigated by its comparison with ARP-QD protocol, which works on the mechanism of optimal route finding in VANETs in urban environments. Simulation results reveal that the proposed ESRA-MD algorithm shows remarkable improvement in terms of delivery ratio, delivery delay, and communication overhead.
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