Displaying publications 21 - 40 of 69 in total

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  1. Yee PT, Poh CL
    Curr Pharm Des, 2016;22(44):6694-6700.
    PMID: 27510488 DOI: 10.2174/1381612822666160720165613
    The Hand, Foot and Mouth Disease (HFMD) is caused by Enterovirus 71 (EV-A71) and Coxsackieviruses. Common HFMD symptoms are high fever (≥ 39°C), rashes, and ulcers but complications due to virulent EV-A71 may arise leading to cardiopulmonary failure and death. The lack of vaccines and antiviral drugs against EV-A71 highlights the urgency of developing preventive and treatment agents. Recent studies have reported the emergence of novel antiviral agents and vaccines that utilize microRNAs (miRNAs). They belong to a class of small (19-24 nt) non coding RNA molecules. As miRNAs play a major role in the host regulatory system, there is a huge opportunity for interplay between host miRNAs and EV-A71 expressions. A total of 42 out of 64 miRNAs were up-regulated in EV-A71-infected cells. There was consistent up-regulation of miR-1246 gene expression that targeted the DLG3 gene which contributes to neurological pathogenesis. In contrast, miR-30a that targets calcium channels for membrane transportation was down-regulated. This leads to repression of EV-A71 replication. The impact of host miRNAs on immune activation, shutdown of host protein synthesis, apoptosis, signal transduction and viral replication are discussed. miRNAs have been used in the construction of live attenuated vaccines (LAV) such as the poliovirus LAV that has miRNA binding sites for let-7a or miR-124a. The miRNAbearing vaccine will not replicate in neuronal cells carrying the corresponding miRNA but could still replicate in the gastrointestinal tract and hence remains to act as immunogens. As such, miRNAs are attractive candidates to be developed as vaccines and antivirals.
  2. Soni N, Tekade M, Kesharwani P, Bhattacharya P, Maheshwari R, Dua K, et al.
    Curr Pharm Des, 2017 08 30;23(21):3084-3098.
    PMID: 28356042 DOI: 10.2174/1381612823666170329150201
    BACKGROUND: Disseminated metastatic cancer requires insistent management owing to its reduced responsiveness for chemotherapeutic agents, toxicity to normal cells consequently lower survival rate and hampered quality of life of patients.

    METHODS: Dendrimer mediated cancer therapy is advantageous over conventional chemotherapy, radiotherapy and surgical resection due to reduced systemic toxicity, and molecular level cell injury to cancerous mass, for an appreciable survival of the subject. Recently used dendrimer mediated nanotechnology for oncology aims to conquer these challenges. Dendrimers based nano-constructs are having architectures comparable to that of biological vesicles present in the human body.

    RESULTS: Operating with dendrimer technology, proffers the exclusive and novel strategies with numerous applications in cancer management involving diagnostics, therapeutics, imaging, and prognostics by sub-molecular interactions. Dendrimers are designed to acquire the benefits of the malignant tumor morphology and characteristics, i.e. leaky vasculature of tumor, expression of specific cell surface antigen, and rapid proliferation.

    CONCLUSION: Dendrimers mediated targeted therapy recommends innovatory function equally in diagnostics (imaging, immune-detection) as well as chemotherapy. Currently, dendrimers as nanomedicine has offered a strong assurance and advancement in drastically varying approaches towards cancer imaging and treatment. The present review discusses different approaches for cancer diagnosis and treatment such as, targeted and control therapy, photodynamic therapy, photo-thermal therapy, gene therapy, antiangiogenics therapy, radiotherapy etc.

  3. Hussain MA, Ashraf MU, Muhammad G, Tahir MN, Bukhari SNA
    Curr Pharm Des, 2017;23(16):2377-2388.
    PMID: 27779081 DOI: 10.2174/1381612822666160928143328
    The therapy of various diseases by the drugs entrapped in calixarene derivatives is gaining attraction of researchers nowadays. Calixarenes are macrocyclic nano-baskets which belong to cavitands class of host-guest chemistry. They are the marvelous hosts with distinct hydrophobic three dimensional cavities to entrap and encapsulate biologically active guest drugs. Calixarene and its derivatives develop inclusion complexes with various types of drugs and vitamins for their sustained/targeted release. Calixarene and its derivatives are used as carriers for anti-cancer, anti-convulsant, anti-hypertensive, anthelmentic, anti-inflammatory, antimicrobial and antipsychotic drugs. They are the important biocompatible receptors to improve solubility, chemical reactivity and decrease cytotoxicity of poorly soluble drugs in supramolecular chemistry. This review focuses on the calixarene and its derivatives as the state-of-the-art in host-guest interactions for important drugs. We have also critically evaluated calixarenes for the development of prodrugs.
  4. Perumalsamy S, Aqilah Mohd Zin NA, Widodo RT, Wan Ahmad WA, Vethakkan SRDB, Huri HZ
    Curr Pharm Des, 2017;23(25):3689-3698.
    PMID: 28625137 DOI: 10.2174/1381612823666170616081256
    BACKGROUND: Chemerin is an adipokine that induces insulin resistance by the mechanism of inflammation in adipose tissue but these are still unclear. A high level of chemerin in humans is considered as a marker of inflammation in insulin resistance and obesity as well as in type 2 diabetes mellitus. Despite the role of chemerin in insulin resistance progression, chemerin as one of the novel adipokines is proposed to be involved in high cancer risk and mortality.

    AIM: The aim of this paper was to review the role of CMKLR-1 receptor and the potential therapeutic target in the management of chemerin induced type 2 diabetes mellitus and cancer.

    PATHOPHYSIOLOGY: Increased chemerin secretion activates an inflammatory response. The inflammatory response will increase the oxidative stress in adipose tissue and consequently results in an insulin-resistant state. The occurrence of inflammation, oxidative stress and insulin resistance leads to the progression of cancers.

    CONCLUSION: Chemerin is one of the markers that may involve in development of both cancer and insulin resistance. Chemokine like receptor- 1 (CMKLR-1) receptor that regulates chemerin levels exhibits a potential therapeutic target for insulin resistance, type 2 diabetes and cancer treatment.

  5. Teoh SL, Das S
    Curr Pharm Des, 2017;23(12):1845-1859.
    PMID: 28231756 DOI: 10.2174/1381612822666161027120043
    The incidence and mortality due to breast cancer is increasing worldwide. There is a constant quest to know the underlying molecular biology of breast cancer in order to arrive at diagnosis and plan better treatment options. MicroRNAs (miRNAs) are small non-coding and single stranded RNAs which influence the gene expression and physiological condition in any tumor. The miRNAs may act on different pathways in various cancers. Recently, there are research reports on various miRNAs being linked to breast cancers. The important miRNAs associated with breast cancers include miR-21, miR-155, miR-27a, miR-205, miR-145 and miR-320a. In the present review we discuss the role of miRNAs in breast cancer, its importance as diagnostic markers, prognosis and metastasis markers. We also highlight the role of miRNAs with regard to resistance to few anticancerous drugs such as Tamoxifen and Trastuzumab. The role of miRNA in resistance to treatment is one of the core issues discussed in the present review. Much information on the miRNA roles is available particularly in the neoadjuvant chemotherapy setting, because this protocol allows the rapid association of miRNA expression with the treatment response. This review opens the door for designing better therapeutic options in drug resistance cases in breast cancer.
  6. Asiful Islam M, Alam F, Kamal MA, Gan SH, Wong KK, Sasongko TH
    Curr Pharm Des, 2017;23(11):1598-1609.
    PMID: 27875971 DOI: 10.2174/1381612823666161122142950
    Nonsense mutations contribute to approximately 10-30% of the total human inherited diseases via disruption of protein translation. If any of the three termination codons (UGA, UAG and UAA) emerges prematurely [known as premature termination codon (PTC)] before the natural canonical stop codon, truncated nonfunctional proteins or proteins with deleterious loss or gain-of-function activities are synthesized, followed by the development of nonsense mutation-mediated diseases. In the past decade, PTC-associated diseases captured much attention in biomedical research, especially as molecular therapeutic targets via nonsense suppression (i.e. translational readthrough) regimens. In this review, we highlighted different treatment strategies of PTC targeting readthrough therapeutics including the use of aminoglycosides, ataluren (formerly known as PTC124), suppressor tRNAs, nonsense-mediated mRNA decay, pseudouridylation and CRISPR/Cas9 system to treat PTC-mediated diseases. In addition, as thrombotic disorders are a group of disease with major burdens worldwide, 19 potential genes containing a total of 705 PTCs that cause 21 thrombotic disorders have been listed based on the data reanalysis from the 'GeneCards® - Human Gene Database' and 'Human Gene Mutation Database' (HGMD®). These PTC-containing genes can be potential targets amenable for different readthrough therapeutic strategies in the future.
  7. Hajiaghaalipour F, Faraj FL, Bagheri E, Ali HM, Abdulla MA, Majid NA
    Curr Pharm Des, 2017;23(41):6358-6365.
    PMID: 28325143 DOI: 10.2174/1381612823666170321093345
    BACKGROUND: Colorectal cancer is the third most common form of cancer in both men and women around the world. The chemistry and biological study of heterocyclic compounds have been an interesting area for a long time in pharmaceutical and medicinal chemistry.

    METHODS: A new synthetic compound, 2-(1,1-dimethyl-1H-benzo[e]indol-2-yl)-3-((2-hydroxyphenyl)amino) acrylaldehyde, abbreviated as DBID, was prepared through the reaction of 2-(diformylmethylidene)-1,1- dimethylbenzo[e]indole with 2-aminophenol. The chemical structure of the synthesized compound was characterized by 1H NMR, 13C NMR and APT-NMR spectroscopy and confirmed by elemental analysis (CHN). The compound was screened for the antiproliferation effect against colorectal cancer cell line, HCT 116 and its possible mechanism of action was elucidated. To determine the IC50 value, the MTT assay was used and its apoptosisinducing effect was investigated.

    RESULTS: DBID inhibited the proliferation of HCT 116 cells with an IC50 of 9.32 µg/ml and significantly increased the levels of caspase -8, -9 and -3/7 in the treated cells compared to untreated cells. Apoptosis features in HCT 116 cell was detected in treated cells by using the AO/PI staining that confirmed that the cells had undergone remarkable morphological changes in apoptotic bodies. Furthermore, this changes in expression of caspase -8, -9 and -3 were confirmed by gene and protein quantification using RT-PCR and western blot analysis, respectively.

    CONCLUSION: The current study showed that the DBID compound has demonstrated chemotherapeutic activity which was evidenced by significant increases in the expression and activation of caspase and exploit the apoptotic signaling pathways to trigger cancer cell death.

  8. 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.

  9. Choudhury H, Gorain B, Chatterjee B, Mandal UK, Sengupta P, Tekade RK
    Curr Pharm Des, 2017;23(17):2504-2531.
    PMID: 27908273 DOI: 10.2174/1381612822666161201143600
    BACKGROUND: Most of the active pharmaceutical ingredients discovered recently in pharmaceutical field exhibits poor aqueous solubility that pose major problem in their oral administration. The oral administration of these drugs gets further complicated due to their short bioavailability, inconsistent absorption and inter/intra subject variability.

    METHODS: Pharmaceutical emulsion holds a significant place as a primary choice of oral drug delivery system for lipophilic drugs used in pediatric and geriatric patients. Pharmacokinetic studies on nanoemulsion mediated drugs delivery approach indicates practical feasibility in regards to their clinical translation and commercialization.

    RESULTS: This review article is to provide an updated understanding on pharmacokinetic and pharmacodynamic features of nanoemulsion delivered via oral, intravenous, topical and nasal route.

    CONCLUSION: The article is of huge interest to formulation scientists working on range of lipophilic drug molecules intended to be administered through oral, intravenous, topical and nasal routes for vivid medical benefits.

  10. Shadab M, Haque S, Sheshala R, Meng LW, Meka VS, Ali J
    Curr Pharm Des, 2017;23(3):440-453.
    PMID: 27784250 DOI: 10.2174/1381612822666161026163201
    BACKGROUND: The drug delivery of macromolecules such as proteins and peptides has become an important area of research and represents the fastest expanding share of the market for human medicines. The most common method for delivering macromolecules is parenterally. However parenteral administration of some therapeutic macromolecules has not been effective because of their rapid clearance from the body. As a result, most macromolecules are only therapeutically useful after multiple injections, which causes poor compliance and systemic side effects.

    METHOD: Therefore, there is a need to improve delivery of therapeutic macromolecules to enable non-invasive delivery routes, less frequent dosing through controlled-release drug delivery, and improved drug targeting to increase efficacy and reduce side effects.

    RESULT: Non-invasive administration routes such as intranasal, pulmonary, transdermal, ocular and oral delivery have been attempted intensively by formulating macromolecules into nanoparticulate carriers system such as polymeric and lipidic nanoparticles.

    CONCLUSION: This review discusses barriers to drug delivery and current formulation technologies to overcome the unfavorable properties of macromolecules via non-invasive delivery (mainly intranasal, pulmonary, transdermal oral and ocular) with a focus on nanoparticulate carrier systems. This review also provided a summary and discussion of recent data on non-invasive delivery of macromolecules using nanoparticulate formulations.

  11. Mozar FS, Chowdhury EH
    Curr Pharm Des, 2018;24(28):3283-3296.
    PMID: 30062957 DOI: 10.2174/1381612824666180730161721
    PEG-functionalized nanoparticles as carriers of chemotherapeutics agents have been explored with notable successes in preclinical and clinical stages of cancer treatment, with some already approved by FDA, namely PEGylated liposomes and polymers. Half-life extension of therapeutic agents through PEGylation process improves their pharmacokinetic (PK) profiles, thereby reducing their dosing frequency. Protein corona composition of PEGylated nanoparticles (NPs) confers a tremendous influence on their surface characteristics which directly impact tumor accumulation and clearance properties of the drugs. By controlling the size and complexity of PEG molecules, as well as by attaching targeting moieties, the surface characteristics of NPs can be manipulated to improve their tumor uptake without sacrificing the circulation time. This review focuses on design and applications of PEGylated NPs for tumor targeted drug delivery in animal models and clinical setting.
  12. Zeeshan F, Madheswaran T, Pandey M, Gorain B
    Curr Pharm Des, 2018;24(42):5019-5028.
    PMID: 30621558 DOI: 10.2174/1381612825666190101111525
    BACKGROUND: The conventional dosage forms cannot be administered to all patients because of interindividual variability found among people of different race coupled with different metabolism and cultural necessities. Therefore, to address this global issue there is a growing focus on the fabrication of new drug delivery systems customised to individual needs. Medicinal products printed using 3-D technology are transforming the current medicine business to a plausible alternative of conventional medicines.

    METHODS: The PubMed database and Google scholar were browsed by keywords of 3-D printing, drug delivery, and personalised medicine. The data about techniques employed in the manufacturing of 3-D printed medicines and the application of 3-D printing technology in the fabrication of individualised medicine were collected, analysed and discussed.

    RESULTS: Numerous techniques can fabricate 3-D printed medicines however, printing-based inkjet, nozzle-based deposition and laser-based writing systems are the most popular 3-D printing methods which have been employed successfully in the development of tablets, polypills, implants, solutions, nanoparticles, targeted and topical dug delivery. In addition, the approval of Spritam® containing levetiracetam by FDA as the primary 3-D printed drug product has boosted its importance. However, some drawbacks such as suitability of manufacturing techniques and the available excipients for 3-D printing need to be addressed to ensure simple, feasible, reliable and reproducible 3-D printed fabrication.

    CONCLUSION: 3-D printing is a revolutionary in pharmaceutical technology to cater the present and future needs of individualised medicines. Nonetheless, more investigations are required on its manufacturing aspects in terms cost effectiveness, reproducibility and bio-equivalence.

  13. Rezayi M, Farjami Z, Hosseini ZS, Ebrahimi N, Abouzari-Lotf E
    Curr Pharm Des, 2018;24(39):4675-4680.
    PMID: 30636591 DOI: 10.2174/1381612825666190111144525
    Small noncoding microRNAs (miRNAs) are known as noninvasive biomarkers for early detection in various cancers. In fact, miRNAs have key roles in carcinogenicity process such as proliferation, apoptosis and metastasis. After cardiovascular disease, cancer is the second cause of death in the world with an estimated 9.6 million deaths in 2018. So, early diagnosis of cancer is critical for successful treatment. To date, several selective and sensitive laboratory-based methods have been applied for the detection of circulating miRNA, but a simple, short assay time and low-cost method such as a biosensor method as an alternative approach to monitor cancer biomarker is required. In this review, we have highlighted recent advances in biosensors for circulating miRNA detection.
  14. Has ATC, Chebib M
    Curr Pharm Des, 2018;24(17):1839-1844.
    PMID: 29766792 DOI: 10.2174/1381612824666180515123921
    GABAA receptors are members of the Cys-loop family of ligand-gated ion channels which mediate most inhibitory neurotransmission in the central nervous system. These receptors are pentameric assemblies of individual subunits, including α1-6, β1-3, γ1-3, δ, ε, π, θ and ρ1-3. The majority of receptors are comprised of α, β and γ or δ subunits. Depending on the subunit composition, the receptors are located in either the synapses or extrasynaptic regions. The most abundant receptors are α1βγ2 receptors, which are activated and modulated by a variety of pharmacologically and clinically unrelated agents such as benzodiazepines, barbiturates, anaesthetics and neurosteroids, all of which bind at distinct binding sites located within the receptor complex. However, compared to αβγ, the binary αβ receptors lack a benzodiazepine α-γ2 interface. In pentameric αβ receptors, the third subunit is replaced with either an α1 or a β3 subunit leading to two distinct receptors that differ in subunit stoichiometry, 2α:3β or 3α:2β. The consequence of this is that 3α:2β receptors contain an α-α interface whereas 2α:3β receptors contain a β-β interface. Apart from the replacement of γ by α1 or β3 in binary receptors, the incorporation of ε subunit into GABAA receptors might be more complicated. As the ε subunit is not only capable of substituting the γ subunit, but also replacing the α/β subunits, receptors with altered stoichiometry and different pharmacological properties are produced. The different subunit arrangement of the receptors potentially constructs novel binding sites which may become new targets of the current or new drugs.
  15. Maleki A, Ghafourian S, Pakzad I, Badakhsh B, Sadeghifard N
    Curr Pharm Des, 2018;24(11):1204-1210.
    PMID: 29237374 DOI: 10.2174/1381612824666171213094730
    BACKGROUND: Neisseria meningitidis is considered as a dangerous pathogen threatening human health. Nowadays, the new drug target is focused. Toxin antitoxin (TA) system is recently identified as an antimicrobial drug target. Also, in N. meningitidis, iron-uptake system could be an interesting target for drug discovery.

    METHODS: In this study, fbpA and mazE genes were chosen as new antimicrobial targets and treated with antisense peptide nucleic acid (PNA). Firstly, they were evaluated by bioinformatics and then analyzed by experimental procedures. Secondly, the functionality was evaluated by stress conditions.

    RESULTS: Our results interestingly demonstrated that when fbpA and mazE loci of N. meningitidis were targeted by antisense PNA, 8 µM concentration of fbpA-PNA as well as 30 µM concentration of mazE-PNA inhibited the growth of N. meningitides and were found to be bacteriostatic, whereas 10 μM concentration of fbpA-PNA showed bacteriocidal activity.

    CONCLUSION: Our findings demonstrated the bactriocidal activity of fbpA-PNA and bacteriostatic activity of mazEPNA. Therefore, mazE and fbpA genes should be potent antimicrobial targets but further analysis including in vivo analysis should be performed.

  16. Vijayan V, Shalini K, Yugesvaran V, Yee TH, Balakrishnan S, Palanimuthu VR
    Curr Pharm Des, 2018;24(28):3366-3375.
    PMID: 30179118 DOI: 10.2174/1381612824666180903110301
    BACKGROUND: Triple-Negative Breast Cancer is an aggressive type of breast cancer, which is not treatable by chemotherapy drugs, due to the lack of Estrogen Receptor (ER), Progesterone Receptor (PR) expression and Human Epidermal Growth Factor Receptor 2 (HER2) on the cell surface.

    OBJECTIVE: The aim of this study was to compare the effect of paclitaxel loaded PLGA nanoparticle (PTX-NPs) on the cytotoxicity and apoptosis of the different MDA-MB type of cell lines.

    METHOD: PTX-NPs were prepared by nanoprecipitation method and characterized earlier. The cytotoxicity of PTX-NPs was evaluated by MTT and LDH assay, later apoptosis was calculated by flow cytometry analysis.

    RESULTS: The prepared NP size of 317.5 nm and zetapontial of -12.7 mV showed drug release of 89.1 % at 48 h. MDA-MB-231 type cell showed significant cytotoxicity by MTT method of 47.4 ± 1.2 % at 24 h, 34.6 ± 0.8 % at 48 h and 23.5 ± 0.5 % at 72 h and LDH method of 35.9 ± 1.5 % at 24 h, 25.4 ± 0.6 % at 48 h and 19.8 ± 2.2 % at 72 h with apoptosis of 47.3 ± 0.4 %.

    CONCLUSION: We have found that PTX-NPs showed the cytotoxic effect on all the MDA-MB cancer cell lines and showed potent anticancer activities against MDA-MB-231 cell line via induction of apoptosis.

  17. Kumarasamy V, Anbazhagan D, Subramaniyan V, Vellasamy S
    Curr Pharm Des, 2018;24(27):3172-3175.
    PMID: 30084327 DOI: 10.2174/1381612824666180807101536
    Blastocystis sp. is a unicellular parasitic microorganism commonly found in the gastrointestinal tracts of humans and animals. It causes symptomatic or asymptomatic infection and its route of transmission is via fecal-oral. High prevalence of Blastocystis infection in developing countries is usually due to poor hygiene practices, exposure to animals infected with the parasite and intake of contaminated water or food. Blastocystis infected individuals often suffer from diarrhea, abdominal pain, nausea, and stomach bloating. Even though pathogenicity of Blastocystis is unclear, it is commonly associated with irritable bowel syndrome. In this review, we have analysed the evidence that shows the association between this microorganism and gastrointestinal disorders. There have been a number of studies which showed that the pathogenicity of Blastocystis is related to its different STs. The pathogenicity is speculated to be due to cysteine proteases formation which stimulates mucosal cells to release interleukin-8 which has been associated with extreme dehydration and gut inflammation. In vitro studies on human colonic epithelial cells revealed that incubation of Blastocystis modulated the host immune response by stimulating the formation of pro-inflammatory cytokines and granulocyte macrophage colonystimulating factor. Metronidazole is found to be the first-line drug of choice. Another treatment option is the combination therapy with trimethoprim/sulfamethoxazole.
  18. Kanauchi O, Andoh A, AbuBakar S, Yamamoto N
    Curr Pharm Des, 2018;24(6):710-717.
    PMID: 29345577 DOI: 10.2174/1381612824666180116163411
    Recently, the risk of viral infection has dramatically increased owing to changes in human ecology such as global warming and an increased geographical movement of people and goods. However, the efficacy of vaccines and remedies for infectious diseases is limited by the high mutation rates of viruses, especially, RNA viruses. Here, we comprehensively review the effectiveness of several probiotics and paraprobiotics (sterilized probiotics) for the prevention or treatment of virally-induced infectious diseases. We discuss the unique roles of these agents in modulating the cross-talk between commensal bacteria and the mucosal immune system. In addition, we provide an overview of the unique mechanism by which viruses are eliminated through the stimulation of type 1 interferon production by probiotics and paraprobiotics via the activation of dendritic cells. Although further detailed research is necessary in the future, probiotics and/or paraprobiotics are expected to be among the rational adjunctive options for the treatment of various viral diseases.
  19. Bagheri E, Saremi K, Hajiaghaalipour F, Faraj FL, Ali HM, Abdulla MA, et al.
    Curr Pharm Des, 2018;24(13):1395-1404.
    PMID: 29384057 DOI: 10.2174/1381612824666180130124308
    Quinazoline is an aromatic bicyclic compound exhibiting several pharmaceutical and biological activities. This study was conducted to investigate the potential wound healing properties of Synthetic Quinazoline Compound (SQC) on experimental rats. The toxicity of SQC was determined by MTT cell proliferation assay. The healing effect of SQC was assessed by in vitro wound healing scratch assay on the skin fibroblast cells (BJ-5ta) and in vivo wound healing experiment of low and high dose of SQC on adult Sprague-Dawley rats compared with negative (gum acacia) and positive control (Intrasite-gel). Hematoxylin and Eosin (H&E), Masson's Trichrome (MT) staining and immunohistochemistry analysis were performed to evaluate the histopathological alterations and proteins expression of Bax and Hsp70 on the wound tissue after 10 days. In addition, levels of antioxidant enzymes (catalase, glutathione peroxidase and superoxide dismutase), and malondialdehyde (MDA) were measured in wound tissue homogenates. The SQC significantly enhanced BJ-5ta cell proliferation and accelerated the percentage of wound closure, with less scarring, increased fibroblast and collagen fibers and less inflammatory cells compared with the negative control. The compound also increases endogenous enzymes and decline lipid peroxidation in wound homogenate.
  20. Reginald K, Chan Y, Plebanski M, Poh CL
    Curr Pharm Des, 2018;24(11):1157-1173.
    PMID: 28914200 DOI: 10.2174/1381612823666170913163904
    Dengue is one of the most important arboviral infections worldwide, infecting up to 390 million people and causing 25,000 deaths annually. Although a licensed dengue vaccine is available, it is not efficacious against dengue serotypes that infect people living in South East Asia, where dengue is an endemic disease. Hence, there is an urgent need to develop an efficient dengue vaccine for this region. Data from different clinical trials indicate that a successful dengue vaccine must elicit both neutralizing antibodies and cell mediated immunity. This can be achieved by designing a multi-epitope peptide vaccine comprising B, CD8+ and CD4+ T cell epitopes. As recognition of T cell epitopes are restricted by human leukocyte antigens (HLA), T cell epitopes which are able to recognize several major HLAs will be preferentially included in the vaccine design. While peptide vaccines are safe, biocompatible and cost-effective, it is poorly immunogenic. Strategies to improve its immunogenicity by the use of long peptides, adjuvants and nanoparticle delivery mechanisms are discussed.
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