Displaying publications 1 - 20 of 38 in total

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  1. Abutayyem H, Alam MK, Kanwal B, Alswairki HJ, Alogaibi YA
    J Orthod Sci, 2023;12:51.
    PMID: 37881658 DOI: 10.4103/jos.jos_53_23
    Infection control is essential to protect both the doctor and the patient by preventing the spread of infectious diseases. There is no exception in the field of dentistry, particularly in orthodontics, where numerous appliances are used for a variety of functions and also because the mouth cavity has the highest concentration of bacteria of any body part. Through this systematic review, we aimed to assess the various methods of sterilization employed in an orthodontic setting. Using relevant keywords, reference searches, and citation searches, the databases such as PubMed, MEDLINE, Web of Science, Cochrane, and Scopus were all searched; a total of 206 documents were found, of which 113 were initially selected. The remaining 23 distinct papers were initially made available after 90 publications that were identical to or similar to one another were eliminated. The final selection was made from eight documents that met all inclusion and exclusion requirements. The existing methods of sterilization were found to be competent in dealing with the microorganisms found in a typical orthodontic setting. The chemical method of sterilization was the norm in most of the studies that we assessed, with glutaraldehyde and peracetic acid (PAA) being the most commonly employed compounds for disinfection. PROSPERO Registration Number: CRD42022380831.
  2. Abutayyem H, Alam MK, Kanwal B, Alswairki HJ, Alogaibi YA
    J Orthod Sci, 2023;12:50.
    PMID: 37881657 DOI: 10.4103/jos.jos_52_23
    A variety of metals and alloys are employed in the field of orthodontics, primary of which happen to be the construction of wires. Through this systematic review, we aimed to assess the various metallurgical characteristics of the said metals and alloys. Four hundred and eighty-two documents in total were found after a thorough search of the online journals, and 169 of the papers were initially chosen. Ultimately, 16 documents were selected that satisfied the necessary inclusion and exclusion criteria, primarily in vitro studies, literature reviews, and comparative analyses. NiTi alloy was found to be the most commonly used alloy in construction of orthodontic wires across all the studies that we had selected for our review. It also had better performance and consistency in terms of its usage as depicted by the meta-analysis performed, with stainless steel wires being a close second primarily due to its lesser cost compared to the former. Metallurgy and orthodontics are inextricably linked with one another. The various components of orthodontics such as wires, pliers, and other instruments utilize the metallurgical characteristics of metals and alloys that are specially prepared for the challenges of this field. PROSPERO Registration Number: CRD42022378444.
  3. Adegboye AA, Khan KM, Salar U, Aboaba SA, Kanwal, Chigurupati S, et al.
    Eur J Med Chem, 2018 Apr 25;150:248-260.
    PMID: 29533872 DOI: 10.1016/j.ejmech.2018.03.011
    Despite of many diverse biological activities exhibited by benzimidazole scaffold, it is rarely explored for the α-amylase inhibitory activity. For that purpose, 2-aryl benzimidazole derivatives 1-45 were synthesized and screened for in vitro α-amylase inhibitory activity. Structures of all synthetic compounds were deduced by various spectroscopic techniques. All compounds revealed inhibition potential with IC50 values of 1.48 ± 0.38-2.99 ± 0.14 μM, when compared to the standard acarbose (IC50 = 1.46 ± 0.26 μM). Limited SAR suggested that the variation in the inhibitory activities of the compounds are the result of different substitutions on aryl ring. In order to rationalize the binding interactions of most active compounds with the active site of α-amylase enzyme, in silico study was conducted.
  4. Al-Mekhlafi AA, Isha ASN, Al-Quraishi MS, Kanwal N
    Front Public Health, 2023;11:1160317.
    PMID: 37869200 DOI: 10.3389/fpubh.2023.1160317
    INTRODUCTION: Driving fatigue has been shown to increase the risk of accidents and potentially fatal crashes. Fatigue is a serious risk that some drivers do not take seriously. Previous studies investigated the effects of driving fatigue in the Malaysian oil and gas transportation industry by employing survey questionnaires. However, they did not explain the behavior of fatigue. Besides, these results required validation by a more reliable method that can describe how fatigue occurs.

    METHODS: Thus, in this study, we used the Psychomotor Vigilance Test (PVT-192) and a short survey to address driving fatigue behavior and identify the influences of driving fatigue on driving performance in real life (on the road) with actual oil and gas tanker drivers. The total participants in the experimental study were 58 drivers.

    RESULTS: For the analysis, a Wilcoxon Signed Ranks Test, Z value and Spearman's rho were used to measure the significant difference between the pre and post-tests of PVT and the correlation between the fatigue variables and driving performance.

    DISCUSSION: During the experiment's first and second days, this study's results indicated that driving fatigue gradually escalated. Likewise, there was a negative correlation based on the test of the relationship between the PVT data and the driving performance survey data. Additionally, the drivers suffer from accumulative fatigue, which requires more effort from the transportation company management to promote the drivers awareness of fatigue consequences.

  5. Alam MK, Alfawzan AA, Abutayyem H, Kanwal B, Alswairki HJ, Verma S, et al.
    Sci Prog, 2023;106(1):368504231156297.
    PMID: 36803068 DOI: 10.1177/00368504231156297
    The purpose of this meta-analysis was to strengthen the credibility of primary research results by combining open-source scientific material, namely a comparison of craniofacial features (Cfc) between Crouzon's syndrome (CS) patients and non-CS populations. All articles published up to October 7, 2021, were included in the search of PubMed, Google Scholar, Scopus, Medline, and Web of Science. The PRISMA guidelines were followed to conduct this study. PECO framework was applied in the following ways: Those who have CS are denoted by the letter P, those who have been diagnosed with CS via clinical or genetic means by the letter E, those who do not have CS by the letter C, and those who have a Cfc of CS by the letter O. Independent reviewers collected the data and ranked the publications based on their adherence to the Newcastle-Ottawa Quality Assessment Scale. A total of six case-control studies were reviewed for this meta-analysis. Due to the large variation in cephalometric measures, only those published in at least two previous studies were included. This analysis found that CS patients had a smaller skull and mandible volumes than those without CS.in terms of SNA° (MD = -2.33, p = <0.001, I2 = 83.6%) and ANB°(MD = -1.89, p = <0.005, I2 = 93.1%)), as well as ANS (MD = -1.87, p = 0.001, I2 = 96.5%)) and SN/PP (MD = -1.99, p = 0.036, I2 = 77.3%)). In comparison to the general population, people with CS tend to have shorter and flatter cranial bases, smaller orbital volumes, and cleft palates. They differ from the general population in having a shorter skull base and more V-shaped maxillary arches.
  6. Anwar A, Shahbaz MS, Saad SM, Kanwal, Khan KM, Siddiqui R, et al.
    Eur J Med Chem, 2019 Nov 15;182:111575.
    PMID: 31415900 DOI: 10.1016/j.ejmech.2019.111575
    We report one-pot synthesis of a series of new 3-aryl-8-methylquinazolin-4(3H)-ones (QNZ) and their antimicrobial activity against Acanthamoeba castellanii belonging to T4 genotype. A library of fifteen synthetic derivatives of QNZs was synthesized, and their structural elucidation was performed by using nuclear magnetic resonance (NMR) spectroscopy and electron impact mass spectrometry (EI-MS). Elemental analyses and high-resolution mass spectrometry data of all derivatives were found to be in agreeable range. Amoebicidal assays performed at concentrations ranging from 50 to 100 μg/mL revealed that all derivatives of QNZ significantly decreased the viability of A. castellanii and QNZ 2, 5, 8, and 13 were found to have efficient antiamoebic effects. Field emission scanning electron microscopy (FESEM) imaging of amoeba treated with compounds 5 and 15 showed that these compounds cause structural alterations on the walls of A. castellanii. Furthermore, several QNZs inhibited the encystation and excystationas as well as abolished A. castellanii-mediated host cells cytopathogenicity in human cells. Whereas, these QNZs showed negligible cytotoxicity when tested against human cells in vitro. Hence, this study identified potential lead molecules having promising properties for drug development against A. castellanii. A brief structure-activity relationship is also developed to optimize the hit of most potent compounds from the library. To the best of our knowledge, it is first of its kind medicinal chemistry approach on a single class of compounds i.e., quinazolinone against keratitis and brain infection causing free-living amoeba, A. castellanii.
  7. Anwar A, Mungroo MR, Khan S, Fatima I, Rafique R, Kanwal, et al.
    Antibiotics (Basel), 2020 Apr 17;9(4).
    PMID: 32316387 DOI: 10.3390/antibiotics9040188
    Balamuthia mandrillaris and Naegleriafowleri are opportunistic protozoan pathogens capable of producing infection of the central nervous system with more than 95% mortality rate. Previously, we have synthesized several compounds with antiamoebic properties; however, synthesis of compounds that are analogues of clinically used drugs is a highly desirable approach that can lead to effective drug development against these devastating infections. In this regard, compounds belonging to the azole class possess wide range of antimicrobial properties and used clinically. In this study, six novel benzimidazole, indazole, and tetrazole derivatives were synthesized and tested against brain-eating amoebae. These compounds were tested for their amoebicidal and static properties against N. fowleri and B. mandrillaris. Furthermore, the compounds were conjugated with silver nanoparticles and characterized. The synthetic heterocyclic compounds showed up to 72% and 65% amoebicidal activities against N. fowleri and B. mandrillaris respectively, while expressing up to 75% and 70% amoebistatic activities, respectively. Following conjugation with silver nanoparticles, amoebicidal activities of the drugs increased by up to 46 and 36% versus B. mandrillaris and N. fowleri. Minimal effects were observed when the compounds were evaluated against human cells using cytotoxicity assays. In summary, azole compounds exhibited potent activity against N. fowleri and B. mandrillaris. Moreover, conjugation of the azole compounds with silver nanoparticles further augmented the capabilities of the compounds against amoebae.
  8. Bano B, Arshia, Khan KM, Kanwal, Fatima B, Taha M, et al.
    Eur J Med Chem, 2017 Oct 20;139:849-864.
    PMID: 28865280 DOI: 10.1016/j.ejmech.2017.08.052
    In this study synthesis and β-glucuronidase inhibitory potential of 3/5/8 sulfonamide and 8-sulfonate derivatives of quinoline (1-40) are discussed. Studies reveal that all the synthetic compounds were found to have good inhibitory activity against β-glucuronidase. Nonetheless, compounds 1, 2, 5, 13, and 22-24 having IC50 values in the range of 1.60-8.40 μM showed superior activity than the standard saccharic acid 1,4-lactone (IC50 = 48.4 ± 1.25 μM). Moreover, molecular docking studies of selected compounds were also performed to see interactions between active compounds and binding sites. Structures of all the synthetic compounds were confirmed through (1)H NMR, EI-MS and HREI-MS spectroscopic techniques.
  9. Bhatti SM, Al Mamun A, Wu M, Naznen F, Kanwal S, Makhbul ZKM
    Environ Sci Pollut Res Int, 2023 Sep;30(44):99855-99874.
    PMID: 37615918 DOI: 10.1007/s11356-023-29353-4
    The current global trend in sustainable business practices is to optimize green innovation performance. To protect the environment and maintain their own survival, organizations must strengthen their green innovation capabilities. Drawing on the recourse-based view and ecology modernization theory (EMT), this study examines the direct effect of green strategic orientations, green entrepreneurial orientation, green market orientation, green innovation orientation, and green organizational culture on the firm's green innovation capability, as well as the mediating effect of green innovation capability on the relationship of these four factors and green innovation performance. Besides, this study also explored the moderating effects of green management system implementation and firm size on the association between green innovation capability and green innovation performance. To test the hypothesized model, a questionnaire survey was administered to gather responses from 293 medium-sized and large manufacturing firms operating in Pakistan. The partial least squares method was used for data analysis. The results revealed that green entrepreneurial orientation, green market orientation, green innovation orientation, and green organizational culture positively impacted green innovation capability, which subsequently positively influenced green innovation performance. Moreover, effective implementation of green management systems can bolster the effect of green innovation capability on green innovation performance, and the mediating effect of green innovation capability has also been confirmed. These indicated that the management of medium and large manufacturing firms operating in Pakistan should focus on encouraging green innovation and training employees regarding the latest eco-friendly technologies to attain performance and sustainable development goals. Policymakers should implement green business development programs and offer rewards or penalties for promoting compliance. The present study contributes greatly to the literature by applying EMT as an alternative to address the mediating role of green innovation capability and the moderating effect of green management system implementation in enhancing firms' green innovation performance.
  10. Hameed S, Kanwal, Seraj F, Rafique R, Chigurupati S, Wadood A, et al.
    Eur J Med Chem, 2019 Dec 01;183:111677.
    PMID: 31514061 DOI: 10.1016/j.ejmech.2019.111677
    Benzotriazoles (4-6) were synthesized which were further reacted with different substituted benzoic acids and phenacyl bromides to synthesize benzotriazole derivatives (7-40). The synthetic compounds (7-40) were characterized via different spectroscopic techniques including EI-MS, HREI-MS, 1H-, and 13C NMR. These molecules were examined for their anti-hyperglycemic potential hence were evaluated for α-glucosidase and α-amylase inhibitory activities. All benzotriazoles displayed moderate to good inhibitory activity in the range of IC50 values of 2.00-5.6 and 2.04-5.72 μM against α-glucosidase and α-amylase enzymes, respectively. The synthetic compounds were divided into two categories "A" and "B", in order to understand the structure-activity relationship. Compounds 25 (IC50 = 2.41 ± 1.31 μM), (IC50 = 2.5 ± 1.21 μM), 36 (IC50 = 2.12 ± 1.35 μM), (IC50 = 2.21 ± 1.08 μM), and 37 (IC50 = 2.00 ± 1.22 μM), (IC50 = 2.04 ± 1.4 μM) with chloro substitution/s at aryl ring were found to be most active against α-glucosidase and α-amylase enzymes. Molecular docking studies on all compounds were performed which revealed that chloro substitutions are playing a pivotal role in the binding interactions. The enzyme inhibition mode was also studied and the kinetic studies revealed that the synthetic molecules have shown competitive mode of inhibition against α-amylase and non-competitive mode of inhibition against α-glucosidase enzyme.
  11. Hussain HU, Kumar KA, Rehan ST, Khan Z, Hashmi MR, Khabir Y, et al.
    Ann Med Surg (Lond), 2023 Nov;85(11):5584-5592.
    PMID: 37915701 DOI: 10.1097/MS9.0000000000001242
    BACKGROUND: HIV makes up a large portion of infectious diseases globally. People injecting drugs in prisons are at high risk for contracting HIV infection. Prisons house ~10.2 million people globally, making them a high-risk setting for HIV transmission. This systematic review summarizes the available data on the odds of developing HIV infection among imprisoned people who inject drugs (PWIDs) in Asian regions.

    METHODS: The authors electronically assessed published studies from January, 2000 to December, 2022, including studies that investigated the odds of HIV in imprisoned PWIDs. We extensively searched PubMed, ERIC, and Cochrane Central and Google Scholar with no constraints in language or time. All the observational studies evaluating the chances of HIV in Asian prisoners with an exposure group of PWIDs and a control group of non-injecting-drug users were included in our analysis.

    RESULTS: The databases search yielded 254 potential studies, 10 observational studies of which having a total of 17 333 participants were included. A low or moderate risk of bias was reported in all the studies except one case-control. The pooled analysis showed a significant association between PWIDs and the chances of contracting HIV infection (Odds ratio=6.40; 95% CI=3.89-10.52; P<0.00001; I2=53%).

    CONCLUSION: This study found a vital correlation between injecting-drug usage during imprisonment and HIV transmission speed. The results of this meta-analysis support the need to prevent HIV and conducting treatment programs in high-risk settings like prisons.

  12. Iqbal K, Abdalla SAO, Anwar A, Iqbal KM, Shah MR, Anwar A, et al.
    Antibiotics (Basel), 2020 May 25;9(5).
    PMID: 32466210 DOI: 10.3390/antibiotics9050276
    The pathogenic free-living amoeba, Acanthamoeba castellanii, is responsible for a rare but deadly central nervous system infection, granulomatous amoebic encephalitis and a blinding eye disease called Acanthamoeba keratitis. Currently, a combination of biguanides, amidine, azoles and antibiotics are used to manage these infections; however, the host cell cytotoxicity of these drugs remains a challenge. Furthermore, Acanthamoeba species are capable of transforming to the cyst form to resist chemotherapy. Herein, we have developed a nano drug delivery system based on iron oxide nanoparticles conjugated with isoniazid, which were further loaded with amphotericin B (ISO-NPs-AMP) to cause potent antiamoebic effects against Acanthamoeba castellanii. The IC50 of isoniazid conjugated with magnetic nanoparticles and loaded with amphotericin B was found to be 45 μg/mL against Acanthamoeba castellanii trophozoites and 50 μg/mL against cysts. The results obtained in this study have promising implications in drug discovery as these nanomaterials exhibited high trophicidal and cysticidal effects, as well as limited cytotoxicity against rat and human cells.
  13. Jahan S, Salman M, Alias YB, Abu Bakar AFB, Mansoor F, Kanwal S
    Dalton Trans, 2020 Jun 23;49(24):8265-8273.
    PMID: 32463410 DOI: 10.1039/d0dt01274b
    Herein, we demonstrate a hydrothermal route to the one-pot synthesis of polymeric mesoporous silica microcubes (P@MSMCs) for the adsorption of heavy metal ions. During the synthesis of P@MSMCs from column silica gel, the roles and combination of the polymer and an etchant were characterized. Moreover, the porosity of P@MSMCs was tailored by adjusting the reaction temperature between 75 °C and 200 °C. The characterization through UV, FTIR, FESEM, XRD, BET, and EDX techniques exhibited that P@MSMCs have a well-ordered mesoporous structure with cubic morphology. The P@MSMCs had a diameter of 2 μm, with an average pore volume and pore size of 0.69 cm3 g-1 and 10.08 nm, respectively. The results indicated that the P@MSMCs have excellent adsorption capacity for Ag(i), Ti(iv), and Zn(ii) due to the formation of an aggregated complex. These aggregations led to affordable density difference-based separation of these metal ions through centrifugation, filtration or simple decantation. The removal efficiencies for Ag(i), Ti(iv), and Zn(ii) were observed to be 520, 720, and 850 mg g-1, respectively. The kinetic studies demonstrated that the adsorption performance fitted well to the pseudo-second-order kinetic model. The as-synthesized P@MSMCs were stable in the wide pH range of 4-8. Significantly, the recycling or reuse results displayed effective adsorption performance of these P@MSMCs for up to 5 cycles. The adsorption results obtained herein will promote the development of similar strategies for the removal of heavy metal ions from natural water.
  14. Kanwal, Mungroo MR, Anwar A, Ali F, Khan S, Abdullah MA, et al.
    Exp Parasitol, 2020 Nov;218:107979.
    PMID: 32866583 DOI: 10.1016/j.exppara.2020.107979
    Balamuthia mandrillaris and Naegleria fowleri are free-living amoebae that can cause life-threatening infections involving the central nervous system. The high mortality rates of these infections demonstrate an urgent need for novel treatment options against the amoebae. Considering that indole and thiazole compounds possess wide range of antiparasitic properties, novel bisindole and thiazole derivatives were synthesized and evaluated against the amoebae. The antiamoebic properties of four synthetic compounds i.e., two new bisindoles (2-Bromo-4-(di (1H-indol-3-yl)methyl)phenol (denoted as A1) and 2-Bromo-4-(di (1H-indol-3-yl)methyl)-6-methoxyphenol (A2)) and two known thiazole (4-(3-Nitrophenyl)-2-(2-(pyridin-3-ylmethylene)hydrazinyl)thiazole (A3) and 4-(Biphenyl-4-yl)-2-(2-(1-(pyridin-4-yl)ethylidene)hydrazinyl)thiazole (A4)) were evaluated against B. mandrillaris and N. fowleri. The ability of silver nanoparticle (AgNPs) conjugation to enrich antiamoebic activities of the compounds was also investigated. The synthetic heterocyclic compounds demonstrated up to 53% and 69% antiamoebic activities against B. mandrillaris and N. fowleri respectively, while resulting in up to 57% and 68% amoebistatic activities, respectively. Antiamoebic activities of the compounds were enhanced by up to 71% and 51% against B. mandrillaris and N. fowleri respectively, after conjugation with AgNPs. These compounds exhibited potential antiamoebic effects against B. mandrillaris and N. fowleri and conjugation of synthetic heterocyclic compounds with AgNPs enhanced their activity against the amoebae.
  15. Kanwal, Khan KM, Chigurupati S, Ali F, Younus M, Aldubayan M, et al.
    ACS Omega, 2021 Jan 26;6(3):2264-2275.
    PMID: 33521466 DOI: 10.1021/acsomega.0c05581
    Indole-3-acetamides (1-24) were synthesized via coupling of indole-3-acetic acid with various substituted anilines in the presence of coupling reagent 1,1-carbonyldiimidazole. The structures of synthetic molecules were elucidated through different spectroscopic techniques including electron ionization-mass spectroscopy (EI-MS), 1H-, 13C NMR, and high-resolution EI-MS (HREI-MS). These compounds were screened for their antihyperglycemic and antioxidant potentials. All compounds displayed good to moderate inhibition against α-amylase enzyme with IC50 values ranging between 1.09 ± 0.11 and 2.84 ± 0.1 μM compared to the standard acarbose (IC50 = 0.92 ± 0.4 μM). Compound 15 (IC50 = 1.09 ± 0.11 μM) was the most active compound of the series and exhibited good inhibition against α-amylase; in addition, this compound also exhibited good antioxidant potential with IC50 values of 0.35 ± 0.1 and 0.81 ± 0.25 μM in 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays, respectively. The binding interactions of synthetic molecules with the enzyme's active site were confirmed via in silico studies. The current study had identified a number of lead molecules as potential antihyperglycemic and antioxidant agents.
  16. Kanwal A, Bilal M, Rasool N, Zubair M, Shah SAA, Zakaria ZA
    Pharmaceuticals (Basel), 2022 Nov 11;15(11).
    PMID: 36422521 DOI: 10.3390/ph15111392
    Terpenes are a group of natural products made up of molecules with the formula (C5H8)n that are typically found in plants. They are widely employed in the medicinal, flavor, and fragrance industries. The total synthesis of terpenes as well as their origin and biological potential are discussed in this review.
  17. Kanwal N, Isha ASN
    Front Public Health, 2022;10:805733.
    PMID: 35372179 DOI: 10.3389/fpubh.2022.805733
    BACKGROUND: Social media activities affect every aspect of human life, be it personal, social or professional. Previous studies have confirmed the role of social media in affecting health in terms of releasing stress and providing social support. Increased occupational health disorders and increased time spent on social media activities motivate us to investigate this phenomenon in the context of occupational health. Therefore, the objective of this study is to measure the effects of social media activities related to personal and social life as well as work-life on health and wellbeing of office employees, on their job efforts and job rewards, and in moderating the effect of effort-reward imbalance on health and wellbeing.

    METHODS: Initially, to develop constructs related to social media activities, web-based structured interviews were conducted with five office employees working in the oil and gas industry for the last 5 years. Then, using an online questionnaire survey, data was collected from 424 office employees working in the oil and gas industry in Malaysia. Using statistical software for social science (SPSS) and Smart PLS, exploratory factor analysis and confirmatory factor analysis were conducted to identify reliability and validity (discriminant validity, convergent validity and composite validity) of the constructs. Following this, path analysis was conducted and the moderating effects were identified.

    RESULTS: Social media activities related to work-life decrease health and wellbeing by 11% and weaken the negative effect of effort-reward-imbalance on health and wellbeing by 17.6% at a 1% level of significance. The results of social media activities related to personal and social life strengthen the negative effect of effort-reward imbalance on health and wellbeing by 12% and negatively affects health and wellbeing and job rewards by 13, 55%, respectively. The direct effect of effort-reward imbalance and job efforts is significantly negative on health and wellbeing by 59 and 10%, respectively.

    CONCLUSION: It is concluded that social media activities of the office employees significantly moderate the effect of effort-reward imbalance on health and wellbeing and intervene in job rewards in the organizations. Hence, the effect of social media activities reduces the health and wellbeing of office employees.

  18. Khalid K, Poh CL
    Adv Med Sci, 2023 Sep;68(2):213-226.
    PMID: 37364379 DOI: 10.1016/j.advms.2023.05.003
    BACKGROUND: The COVID-19 pandemic exerted significant impacts on public health and global economy. Research efforts to develop vaccines at warp speed against SARS-CoV-2 led to novel mRNA, viral vectored, and inactivated vaccines being administered. The current COVID-19 vaccines incorporate the full S protein of the SARS-CoV-2 Wuhan strain but rapidly emerging variants of concern (VOCs) have led to significant reductions in protective efficacies. There is an urgent need to develop next-generation vaccines which could effectively prevent COVID-19.

    METHODS: PubMed and Google Scholar were systematically reviewed for peer-reviewed papers up to January 2023.

    RESULTS: A promising solution to the problem of emerging variants is a DNA vaccine platform since it can be easily modified. Besides expressing whole protein antigens, DNA vaccines can also be constructed to include specific nucleotide genes encoding highly conserved and immunogenic epitopes from the S protein as well as from other structural/non-structural proteins to develop effective vaccines against VOCs. DNA vaccines are associated with low transfection efficiencies which could be enhanced by chemical, genetic, and molecular adjuvants as well as delivery systems.

    CONCLUSIONS: The DNA vaccine platform offers a promising solution to the design of effective vaccines. The challenge of limited immunogenicity in humans might be solved through the use of genetic modifications such as the addition of nuclear localization signal (NLS) peptide gene, strong promoters, MARs, introns, TLR agonists, CD40L, and the development of appropriate delivery systems utilizing nanoparticles to increase uptake by APCs in enhancing the induction of potent immune responses.

  19. Khalid K, Lim HX, Anwar A, Tan SH, Hwang JS, Ong SK, et al.
    AAPS PharmSciTech, 2024 Mar 12;25(3):60.
    PMID: 38472523 DOI: 10.1208/s12249-024-02778-x
    The protective efficacies of current licensed vaccines against COVID-19 have significantly reduced as a result of SARS-CoV-2 variants of concern (VOCs) which carried multiple mutations in the Spike (S) protein. Considering that these vaccines were developed based on the S protein of the original SARS-CoV-2 Wuhan strain, we designed a recombinant plasmid DNA vaccine based on highly conserved and immunogenic B and T cell epitopes against SARS-CoV-2 Wuhan strain and the Omicron VOC. Literature mining and bioinformatics were used to identify 6 immunogenic peptides from conserved regions of the SARS-CoV-2 S and membrane (M) proteins. Nucleotide sequences encoding these peptides representing highly conserved B and T cell epitopes were cloned into a pVAX1 vector to form the pVAX1/S2-6EHGFP recombinant DNA plasmid vaccine. The DNA vaccine was intranasally or intramuscularly administered to BALB/c mice and evaluations of humoral and cellular immune responses were performed. The intramuscular administration of pVAX1/S2-6EHGFP was associated with a significantly higher percentage of CD8+ T cells expressing IFN-γ when compared with the empty vector and PBS controls. Intramuscular or intranasal administrations of pVAX1/S2-6EHGFP resulted in robust IgG antibody responses. Sera from mice intramuscularly immunized with pVAX1/S2-6EHGFP were found to elicit neutralizing antibodies capable of SARS-CoV-2 Omicron variant with the ACE2 cell surface receptor. This study demonstrated that the DNA vaccine construct encoding highly conserved immunogenic B and T cell epitopes was capable of eliciting potent humoral and cellular immune responses in mice.
  20. Kuang TK, Kang YB, Segarra I, Kanwal U, Ahsan M, Bukhari NI
    Turk J Pharm Sci, 2021 04 20;18(2):167-175.
    PMID: 33902255 DOI: 10.4274/tjps.galenos.2020.48902
    Objectives: This study was conducted to assess the effect of microwave heating on the preparation of paracetamol cross-linked gelatin matrices by using the design of experiment (DoE) approach and explore the influence of the duration of microwave irradiation, the concentrations of crosslinker, and the amount of sodium bicarbonate (salt) on paracetamol release. These parameters were also compared with those of the matrices prepared via conventional heating.

    Materials and Methods: Twenty gel matrices were prepared with different durations of microwave irradiation, amounts of maize, and concentrations of sodium bicarbonate as suggested by Design Expert (DX®). The percentage drug release, the coefficient of variance (CV) in release, and the mean dissolution time (MDT) were the properties explored in the designed experimentation.

    Results: Target responses were dependent on microwave irradiation time, cross-linker amount, and salt concentration. Classical and microwave heating did not demonstrate statistically significant difference in modifying the percentage of drug released from the matrices. However, the CVs of microwave-assisted formulations were lower than those of the gel matrices prepared via classical heating. Thus, microwave heating produced lesser variations in drug release. The optimized gel matrices demonstrated that the observed percentage of drug release, CV, and MDT were within the prediction interval generated by DX®. The release mechanism of the matrix formulations followed the Peppas-Korsmeyer anomalous transport model.

    Conclusion: The DoE-supported microwave-assisted approach could be applied to optimize the critical factors of drug release with less variation.

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