Displaying publications 21 - 40 of 110 in total

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  1. Saifullah B, Hussein MZ, Hussein-Al-Ali SH, Arulselvan P, Fakurazi S
    Drug Des Devel Ther, 2013;7:1365-75.
    PMID: 24255593 DOI: 10.2147/DDDT.S50665
    We report the intercalation and characterization of para-amino salicylic acid (PASA) into zinc/aluminum-layered double hydroxides (ZLDHs) by two methods, direct and indirect, to form nanocomposites: PASA nanocomposite prepared by a direct method (PASA-D) and PASA nanocomposite prepared by an indirect method (PASA-I). Powder X-ray diffraction, Fourier-transform infrared spectroscopy, and thermogravimetric analysis revealed that the PASA drugs were accommodated within the ZLDH interlayers. The anions of the drug were accommodated as an alternate monolayer (along the long-axis orientation) between ZLDH interlayers. Drug loading was estimated to be 22.8% and 16.6% for PASA-D and PASA-I, respectively. The in vitro release properties of the drug were investigated in physiological simulated phosphate-buffered saline solution of pH 7.4 and 4.8. The release followed the pseudo-second-order model for both nanocomposites. Cell viability (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide [MTT] assays) was assessed against normal human lung fibroblast MRC-5 and 3T3 mouse fibroblast cells at 24, 48, and 72 hours. The results showed that the nanocomposite formulations did not possess any cytotoxicity, at least up to 72 hours.
  2. Muhammad SI, Maznah I, Mahmud RB, Saeed MI, Imam MU, Ishaka A
    Drug Des Devel Ther, 2013;7:1409-20.
    PMID: 24324328 DOI: 10.2147/DDDT.S50861
    The expression of genes regulated by estrogen in the uterus was studied in ovariectomized (OVX) rats treated with germinated brown rice (GBR) bioactives, and compared to Remifemin or estrogen at different doses to identify the regulation of these genes in the uterus and their molecular mechanisms.
  3. Sahib MN, Abdulameer SA, Darwis Y, Peh KK, Tan YT
    Drug Des Devel Ther, 2012;6:29-42.
    PMID: 22393583
    The local treatment of lung disorders such as asthma and chronic obstructive pulmonary disease via pulmonary drug delivery offers many advantages over oral or intravenous routes of administration. This is because direct deposition of a drug at the diseased site increases local drug concentrations, which improves the pulmonary receptor occupancy and reduces the overall dose required, therefore reducing the side effects that result from high drug doses. From a clinical point of view, although jet nebulizers have been used for aerosol delivery of water-soluble compounds and micronized suspensions, their use with hydrophobic drugs has been inadequate.
  4. Yeow ST, Shahar A, Abdul Aziz N, Anuar MS, Yusof YA, Taip FS
    Drug Des Devel Ther, 2011;5:465-9.
    PMID: 22162640 DOI: 10.2147/DDDT.S25047
    To investigate the effect of feed preparation characteristics and operational parameters on mixing homogeneity in a convective batch ribbon mixer.
  5. Mahdi ES, Sakeena MH, Abdulkarim MF, Abdullah GZ, Sattar MA, Noor AM
    Drug Des Devel Ther, 2011;5:311-23.
    PMID: 21792294 DOI: 10.2147/DDDT.S15698
    The purpose of this study was to select appropriate surfactants or blends of surfactants to study the ternary phase diagram behavior of newly introduced palm kernel oil esters.
  6. Hussein Al Ali SH, Al-Qubaisi M, Hussein MZ, Ismail M, Bullo S
    Drug Des Devel Ther, 2013;7:25-31.
    PMID: 23345969 DOI: 10.2147/DDDT.S37070
    The aim of the current study is to design a new nanocomposite for inducing cytotoxicity of doxorubicin and oxaliplatin toward MDA-MB231, MCF-7, and Caco2 cell lines. A hippuric acid (HA) zinc layered hydroxide (ZLH) nanocomposite was synthesized under an aqueous environment using HA and zinc oxide (ZnO) as the precursors.
  7. Hemn HO, Noordin MM, Rahman HS, Hazilawati H, Zuki A, Chartrand MS
    Drug Des Devel Ther, 2015;9:4173-208.
    PMID: 26347047 DOI: 10.2147/DDDT.S76225
    Owing to the high incidence of cholesterol-induced cardiovascular disease, particularly atherosclerosis, the current study was designed to investigate the preventive and therapeutic efficacies of dietary zerumbone (ZER) supplementation on the formation and development of atherosclerosis in rabbits fed with a high cholesterol diet. A total of 72 New Zealand white rabbits were divided randomly on two experimental studies carried out 8 weeks apart. The first experiment was designed to investigate the prophylactic efficacy of ZER in preventing early developed atheromatous lesion. The second experimental trial was aimed at investigating the therapeutic effect of ZER in reducing the atherosclerotic lesion progression and establishment. Sudanophilia, histopathological, and ultrastructural changes showed pronounced reduction in the plaque size in ZER-medicated aortas. On the other hand, dietary supplementation of ZER for almost 10 weeks as a prophylactic measure indicated substantially decreasing lipid profile values, and similarly, plaque size in comparison with high-cholesterol non-supplemented rabbits. Furthermore, the results of oxidative stress and antioxidant biomarker evaluation indicated that ZER is a potent antioxidant in suppressing the generation of free radicals in terms of atherosclerosis prevention and treatment. ZER significantly reduced the value of malondialdehyde and augmented the value of superoxide dismutase. In conclusion, our data indicated that dietary supplementation of ZER at doses of 8, 16, and 20 mg/kg alone as a prophylactic measure, and as a supplementary treatment with simvastatin, significantly reduced early plague formation, development, and establishment via significant reduction in serum lipid profile, together with suppression of oxidative damage, and therefore alleviated atherosclerosis lesions.
  8. Ilangkovan M, Jantan I, Mesaik MA, Bukhari SN
    Drug Des Devel Ther, 2015;9:4917-30.
    PMID: 26347462 DOI: 10.2147/DDDT.S88189
    Phyllanthus amarus (family: Euphorbiaceae) is of immense interest due to its wide spectrum of biological activities. In the present study, the standardized 80% ethanol extract of P. amarus was investigated for its modulatory activity on various cellular immune parameters, including chemotaxis of neutrophils, engulfment of Escherichia coli by neutrophils, and Mac-1 expression, in leukocytes isolated from treated/nontreated Wistar-Kyoto rats. The detailed cell-mediated activity of P. amarus was also investigated, including analysis of the effects on T- and B-cell proliferation and CD4(+) and CD8(+) T-cell subsets in splenic mononuclear cells, and estimation of serum cytokine production by activated T-cells. The main components of the extract, phyllanthin, hypophyllanthin, corilagin, geraniin, ellagic acid, and gallic acid were identified and quantitatively analyzed in the extracts, using validated reversed-phase high-performance liquid chromatography (HPLC) methods. N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced neutrophils isolated from rats administered with the extract of P. amarus, at doses ranging from 100 to 400 mg/kg for 14 days, revealed a significant dose-dependent reduction in neutrophil migration (P<0.05). Similar patterns of inhibition were also observed in phagocytic activity and in fMLP-induced changes in expression of β2 integrin polymorphonuclear neutrophils. The results in P. amarus-treated rats also demonstrated a dose-dependent inhibition of both lipopolysaccharide-stimulated B-cell proliferation and concanavalin A-stimulated T-cell proliferation as compared with sensitized control. At a dose of 400 mg/kg (P<0.01), there was a significant decrease in the (%) expression of CD4(+) and CD8(+) in splenocytes and in serum cytokines of T helper (Th1) (IL-2 and IFN-γ) and Th2 (IL-4). In conclusion, P. amarus showed effective immunosuppressive activities in cellular immune response, by various immune regulatory mechanisms, and may be useful for improvement of immune-related disorders.
  9. Hou Z, Imam MU, Ismail M, Ooi DJ, Ideris A, Mahmud R
    Drug Des Devel Ther, 2015;9:4115-25.
    PMID: 26316695 DOI: 10.2147/DDDT.S80743
    Estrogen deficiency alters quality of life during menopause. Hormone replacement therapy has been used to improve quality of life and prevent complications, but side effects limit its use. In this study, we evaluated the use of edible bird's nest (EBN) for prevention of cardiometabolic problems in rats with ovariectomy-induced menopause. Ovariectomized female rats were fed for 12 weeks with normal rat chow, EBN, or estrogen and compared with normal non-ovariectomized rats. Metabolic indices (insulin, estrogen, superoxide dismutase, malondialdehyde, oral glucose tolerance test, and lipid profile) were measured at the end of the experiment from serum and liver tissue homogenate, and transcriptional levels of hepatic insulin signaling genes were measured. The results showed that ovariectomy worsened metabolic indices and disrupted the normal transcriptional pattern of hepatic insulin signaling genes. EBN improved the metabolic indices and also produced transcriptional changes in hepatic insulin signaling genes that tended toward enhanced insulin sensitivity, and glucose and lipid homeostasis, even better than estrogen. The data suggest that EBN could meliorate estrogen deficiency-associated increase in risk of cardiometabolic disease in rats, and may in fact be useful as a functional food for the prevention of such a problem in humans. The clinical validity of these findings is worth studying further.
  10. Lee JS, Bukhari SN, Fauzi NM
    Drug Des Devel Ther, 2015;9:4761-78.
    PMID: 26316713 DOI: 10.2147/DDDT.S86242
    The immune system is the defense mechanism in living organisms that protects against the invasion of foreign materials, microorganisms, and pathogens. It involves multiple organs and tissues in human body, such as lymph nodes, spleen, and mucosa-associated lymphoid tissues. However, the execution of immune activities depends on a number of specific cell types, such as B cells, T cells, macrophages, and granulocytes, which provide various immune responses against pathogens. In addition to normal physiological functions, abnormal proliferation, migration, and differentiation of these cells (in response to various chemical stimuli produced by invading pathogens) have been associated with several pathological disorders. The unwanted conditions related to these cells have made them prominent targets in the development of new therapeutic interventions against various pathological implications, such as atherosclerosis and autoimmune diseases. Chalcone derivatives exhibit a broad spectrum of pharmacological activities, such as immunomodulation, as well as anti-inflammatory, anticancer, antiviral, and antimicrobial properties. Many studies have been conducted to determine their inhibitory or stimulatory activities in immune cells, and the findings are of significance to provide a new direction for subsequent research. This review highlights the effects of chalcone derivatives in different types of immune cells.
  11. Meor Mohd Affandi MM, Tripathy M, Shah SA, Majeed AB
    Drug Des Devel Ther, 2016;10:959-69.
    PMID: 27041998 DOI: 10.2147/DDDT.S94701
    We examined the solubility of simvastatin in water in 0.01 mol·dm(-3), 0.02 mol·dm(-3), 0.04 mol·dm(-3), 0.09 mol·dm(-3), 0.18 mol·dm(-3), 0.36 mol·dm(-3), and 0.73 mol·dm(-3) arginine (ARG) solutions. The investigated drug is termed the solute, whereas ARG the cosolute. Phase solubility studies illustrated a higher extent of solubility enhancement for simvastatin. The aforementioned system was subjected to conductometric and volumetric measurements at temperatures (T) of 298.15 K, 303.15 K, 308.15 K, and 313.15 K to illustrate the thermodynamics involved and related solute-solvent interactions. The conductance values were used to evaluate the limiting molar conductance and association constants. Thermodynamic parameters (ΔG (0), ΔH (0), ΔS (0), and E s) for the association process of the solute in the aqueous solutions of ARG were calculated. Limiting partial molar volumes and expansibilities were evaluated from the density values. These values are discussed in terms of the solute-solvent and solute-cosolute interactions. Further, these systems were analyzed using ultraviolet-visible analysis, Fourier-transform infrared spectroscopy, and (13)C, (1)H, and two-dimensional nuclear overhauser effect spectroscopy nuclear magnetic resonance to complement thermophysical explanation.
  12. Muhammad AA, Arulselvan P, Cheah PS, Abas F, Fakurazi S
    Drug Des Devel Ther, 2016;10:1715-30.
    PMID: 27307703 DOI: 10.2147/DDDT.S96968
    Diabetic foot ulcer is a serious complication of diabetes, which affects a significant percentage (15%) of diabetics and up to 15%-24% of those affected may require amputation. Therefore, the economic burden of diabetic foot ulcers is enormous and is associated with high cost of treatment and prolongs hospitalization. The present study was conducted to evaluate antibacterial and in vivo wound healing activities of an aqueous fraction of Moringa oleifera on a diabetic condition. Antibacterial activity testing was carried out using agar well and tube dilution techniques. The in vivo study was conducted using six groups of animals that comprise of one normal and diabetic control group each, three treatment groups of 0.5%, 1%, and 2% w/w aqueous fraction, and a positive control group (1% w/w silver sulfadiazine). Rats were induced with diabetes using a combination of streptozotocin 65 and 150 mg/kg nicotinamide daily for 2 days, and excision wounds were created and treated with various doses (0.5%, 1%, and 2% w/w aqueous fraction) daily for 21 days. Biophysical, histological, and biochemical parameters were investigated. The results of the study revealed that aqueous fraction possessed antibacterial activity through inhibition of growth of Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli organisms. The topical application of aqueous fraction revealed enhancement of wound healing under sustained hyperglycemic condition for the duration of the experiment. This enhancement was achieved through decreased wound size, improved wound contraction, and tissue regeneration, as well as downregulation of inflammatory mediators, such as tumor necrosis factor-α, interleukin-1β, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2, and upregulation of an angiogenic marker vascular endothelial growth factor in wound tissue treated with various doses of aqueous fraction of M. oleifera. The findings suggest that aqueous fraction of M. oleifera containing Vicenin-2 active compound may accelerate wound healing in hyperglycemic condition.
  13. Sidahmed HM, Hashim NM, Mohan S, Abdelwahab SI, Taha MM, Dehghan F, et al.
    Drug Des Devel Ther, 2016;10:297-313.
    PMID: 26834460 DOI: 10.2147/DDDT.S80625
    PURPOSE: β-Mangostin (BM) from Cratoxylum arborescens demonstrated various pharmacological activities such as anticancer and anti-inflammatory. In this study, we aimed to investigate its antiulcer activity against ethanol ulcer model in rats.

    MATERIALS AND METHODS: BM was isolated from C. arborescens. Gastric acid output, ulcer index, gross evaluation, mucus production, histological evaluation using hematoxylin and eosin and periodic acid-Schiff staining and immunohistochemical localization for heat shock protein 70 (HSP70) and Bax proteins were investigated. Possible involvement of reduced glutathione, lipid peroxidation, prostaglandin E2, antioxidant enzymes, superoxide dismutase and catalase enzymes, radical scavenging, nonprotein sulfhydryl compounds, and anti-Helicobacter pylori were investigated.

    RESULTS: BM showed antisecretory activity against the pylorus ligature model. The pretreatment with BM protect gastric mucosa from ethanol damaging effect as seen by the improved gross and histological appearance. BM significantly reduced the ulcer area formation, the submucosal edema, and the leukocytes infiltration compared to the ulcer control. The compound showed intense periodic acid-Schiff staining to the gastric mucus layer and marked amount of alcian blue binding to free gastric mucus. BM significantly increased the gastric homogenate content of prostaglandin E2 glutathione, superoxide dismutase, catalase, and nonprotein sulfhydryl compounds. The compound inhibited the lipid peroxidation revealed by the reduced gastric content of malondialdehyde. Moreover, BM upregulate HSP70 expression and downregulate Bax expression. Furthermore, the compound showed interesting anti-H. pylori activity.

    CONCLUSION: Thus, it could be concluded that BM possesses gastroprotective activity, which could be attributed to the antisecretory, mucus production, antioxidant, HSP70, antiapoptotic, and anti-H. pylori mechanisms.

  14. Ibrahim IA, Abdulla MA, Hajrezaie M, Bader A, Shahzad N, Al-Ghamdi SS, et al.
    Drug Des Devel Ther, 2016;10:93-105.
    PMID: 26766904 DOI: 10.2147/DDDT.S91247
    Monolluma quadrangula (Forssk.) Plowes is used in Saudi traditional medicines to treat gastric ulcers. The hydroalcoholic extract of M. quadrangula (MHAE) was used in an in vivo model to investigate its gastroprotective effects against ethanol-induced acute gastric lesions in rats. Five groups of Sprague Dawley rats were used. The first group was treated with 10% Tween 20 as a control. The other four groups included rats treated with absolute ethanol (5 mL/kg) to induce an ulcer, rats treated with 20 mg/kg omeprazole as a reference drug, and rats treated with 150 or 300 mg/kg MHAE. One hour later, the rats were administered absolute ethanol (5 mL/kg) orally. Animals fed with MHAE exhibited a significantly increased pH, gastric wall mucus, and flattening of the gastric mucosa, as well as a decreased area of gastric mucosal damage. Histology confirmed the results; extensive destruction of the gastric mucosa was observed in the ulcer control group, and the lesions penetrated deep into the gastric mucosa with leukocyte infiltration of the submucosal layer and edema. However, gastric protection was observed in the rats pre-fed with plant extracts. Periodic acid-Schiff staining of the gastric wall revealed a remarkably intensive uptake of magenta color in the experimental rats pretreated with MHAE compared to the ulcer control group. Immunohistochemistry staining revealed an upregulation of the Hsp70 protein and a downregulation of the Bax protein in rats pretreated with MHAE compared with the control rats. Gastric homogenate showed significantly increased catalase and superoxide dismutase, and the level of malondialdehyde (MDA) was reduced in the rats pretreated with MHAE compared to the control group. In conclusion, MHAE exhibited a gastroprotective effect against ethanol-induced gastric mucosal injury in rats. The mechanism of this gastroprotection included an increase in pH and gastric wall mucus, an increase in endogenous enzymes, and a decrease in the level of MDA. Furthermore, protection was given through the upregulation of Hsp70 and the downregulation of Bax proteins.
  15. Rouhollahi E, Moghadamtousi SZ, Al-Henhena N, Kunasegaran T, Hasanpourghadi M, Looi CY, et al.
    Drug Des Devel Ther, 2015;9:3911-22.
    PMID: 26251570 DOI: 10.2147/DDDT.S84560
    Curcuma purpurascens BI. rhizome, a member of the Zingiberaceae family, is a popular spice in Indonesia that is traditionally used in assorted remedies. Dichloromethane extract of C. purpurascens BI. rhizome (DECPR) has previously been shown to have an apoptosis-inducing effect on colon cancer cells. In the present study, we examined the potential of DECPR to prevent colon cancer development in rats treated with azoxymethane (AOM) (15 mg/kg) by determining the percentage inhibition in incidence of aberrant crypt foci (ACF). Starting from the day immediately after AOM treatment, three groups of rats were orally administered once a day for 2 months either 10% Tween 20 (5 mL/kg, cancer control), DECPR (250 mg/kg, low dose), or DECPR (500 mg/kg, high dose). Meanwhile, the control group was intraperitoneally injected with 5-fluorouracil (35 mg/kg) for 5 consecutive days. After euthanizing the rats, the number of ACF was enumerated in colon tissues. Bax, Bcl-2, and proliferating cell nuclear antigen (PCNA) protein expressions were examined using immunohistochemical and Western blot analyses. Antioxidant enzymatic activity was measured in colon tissue homogenates and associated with malondialdehyde level. The percentage inhibition of ACF was 56.04% and 68.68% in the low- and high-dose DECPR-treated groups, respectively. The ACF inhibition in the treatment control group was 74.17%. Results revealed that DECPR exposure at both doses significantly decreased AOM-induced ACF formation, which was accompanied by reduced expression of PCNA. Upregulation of Bax and downregulation of Bcl-2 suggested the involvement of apoptosis in the chemopreventive effect of DECPR. In addition, the oxidative stress resulting from AOM treatment was significantly attenuated after administration of DECPR, which was shown by the elevated antioxidant enzymatic activity and reduced malondialdehyde level. Taken together, the present data clearly indicate that DECPR significantly inhibits ACF formation in AOM-treated rats and may offer protection against colon cancer development.
  16. Yida Z, Imam MU, Ismail M, Ismail N, Hou Z
    Drug Des Devel Ther, 2015;9:3951-9.
    PMID: 26251574 DOI: 10.2147/DDDT.S87772
    Edible bird's nest (EBN) is popular in Asia, and has long been used traditionally as a supplement. There are, however, limited evidence-based studies on its efficacy. EBN has been reported to improve dyslipidemia, which is closely linked to hypercoagulation states. In the present study, the effects of EBN on high-fat diet- (HFD-) induced coagulation in rats were evaluated. Rats were fed for 12 weeks with HFD alone or in combination with simvastatin or EBN. Food intake was estimated, and weight measurements were made during the experimental period. After sacrifice, serum oxidized low-density lipoprotein (oxLDL), adiponectin, leptin, von willibrand factor, prostacyclin, thromboxane and lipid profile, and whole blood coagulation indices (bleeding time, prothrombin time, activated partial thromboplastin time, red blood count count, and platelet count) were estimated. Furthermore, hepatic expression of coagulation-related genes was evaluated using multiplex polymerase chain reaction. The results indicated that EBN could attenuate HFD-induced hypercholesterolemia and coagulation similar to simvastatin, partly through transcriptional regulation of coagulation-related genes. The results suggested that EBN has the potential for lowering the risk of cardiovascular disease-related hypercoagulation due to hypercholesterolemia.
  17. Pandurangan AK, Mohebali N, Norhaizan ME, Looi CY
    Drug Des Devel Ther, 2015;9:3923-34.
    PMID: 26251571 DOI: 10.2147/DDDT.S86345
    Gallic acid (GA) is a polyhydroxy phenolic compound that has been detected in various natural products, such as green tea, strawberries, grapes, bananas, and many other fruits. In inflammatory bowel disease, inflammation is promoted by oxidative stress. GA is a strong antioxidant; thus, we evaluated the cytoprotective and anti-inflammatory role of GA in a dextran sulfate sodium (DSS)-induced mouse colitis model. Experimental acute colitis was induced in male BALB/c mice by administering 2.5% DSS in the drinking water for 7 days. The disease activity index; colon weight/length ratio; histopathological analysis; mRNA expressions of IL-21 and IL-23; and protein expression of nuclear erythroid 2-related factor 2 (Nrf2) were compared between the control and experimental mice. The colonic content of malondialdehyde and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activity were examined as parameters of the redox state. We determined that GA significantly attenuated the disease activity index and colon shortening, and reduced the histopathological evidence of injury. GA also significantly (P<0.05) reduced the expressions of IL-21 and IL-23. Furthermore, GA activates/upregulates the expression of Nrf2 and its downstream targets, including UDP-GT and NQO1, in DSS-induced mice. The findings of this study demonstrate the protective effect of GA on experimental colitis, which is probably due to an antioxidant nature of GA.
  18. Albaayit SF, Abba Y, Rasedee A, Abdullah N
    Drug Des Devel Ther, 2015;9:3507-18.
    PMID: 26203223 DOI: 10.2147/DDDT.S84770
    Clausena excavata is a well-known plant used in folkloric medicine for the treatment of different ailments. This study aimed to determine the in vitro cytoxicity of its leaf solvent extracts as well as the in vivo wound healing and antioxidant activities of the methanolic extracts of C. excavata (MECE). HaCaT (keratocyte) and Vero cell lines were used for evaluation of the in vitro cytotoxic effects, while the in vivo wound healing and antioxidant activities were determined in skin wounds inflicted on rats. Twenty adult male Sprague-Dawley rats were divided into five groups of four animals each. Approximately 3.14 cm(2) excisional wound was inflicted on the nape of each rat following anesthesia. The treatment groups received topical application of MECE at 50 mg/mL (MECE-LD [low dose]), 100 mg/mL (MECE-MD [medium dose]), and 200 mg/mL (MECE-HD [high dose]), while the negative control group was treated with gum acacia in normal saline and the positive control group with intrasite gel. Wound contraction was evaluated on days 5, 10, and 15 after wound infliction, and tissue from wound area was collected at day 15 post-wound infliction for antioxidant enzyme evaluation and histopathological analyses. Generally, Vero cells were more resistant to the cytotoxic effects of the solvent extracts as compared with HaCaT cells. Chloroform (CH) and ethyl acetate (EA) extracts of C. excavata were toxic to HaCaT cells at 200 and 400 µg/mL, but the same concentrations showed higher (P<0.05) viability in Vero cells. There was significantly (P<0.01) greater wound contraction at days 10 and 15 post-wound infliction in all the treatment groups than in the control groups. Histopathologically, the MECE-HD-treated wound showed significantly (P<0.05) lesser inflammatory cell proliferation, degeneration, and distribution of granulation tissue than other groups. Similarly, the degree of collagen maturation, angiogenesis, and collagen distribution were significantly (P<0.05) lower in MECE-HD than in other groups. The MECE-HD, MECE-MD, and intrasite treatment groups showed a significantly (P<0.05) higher number of VEGF-positive and TGF-β1-positive cells in the skin wound than the control groups. The activities of superoxide dismutase and catalase were significantly (P<0.01) higher in the MECE-HD and intrasite treatment groups than in the other groups. Lipid peroxidase activity of the treated groups was significantly (P<0.01) lower than that in the control group. The study showed that MECE is a potent wound healing agent through anti-inflammatory and antioxidant effects that enhanced the rate of wound contraction, re-epithelialization, and collagen deposition. The effect of MECE is suggested to be due to its high polyphenolic compound content.
  19. Soheili S, Ghafourian S, Sekawi Z, Neela VK, Sadeghifard N, Taherikalani M, et al.
    Drug Des Devel Ther, 2015;9:2553-61.
    PMID: 26005332 DOI: 10.2147/DDDT.S77263
    The toxin-antitoxin (TA) system is a regulatory system where two sets of genes encode the toxin and its corresponding antitoxin. In this study, the prevalence of TA systems in independently isolated clinical isolates of Enterococcus faecium and Enterococcus faecalis was determined, the dominant TA system was identified, different virulence genes in E. faecium and E. faecalis were surveyed, the level of expression of the virulence and TA genes in normal and stress conditions was determined, and finally their associations with the TA genes were defined. Remarkably, the analysis demonstrated higBA and mazEF in all clinical isolates, and their locations were on chromosomes and plasmids, respectively. On the other hand, a quantitative analysis of TA and virulence genes revealed that the expression level in both genes is different under normal and stress conditions. The results obtained by anti-mazF peptide nucleic acids demonstrated that the expression level of virulence genes had decreased. These findings demonstrate an association between TA systems and virulence factors. The mazEF on the plasmids and the higBA TA genes on the chromosomes of all E. faecium and E. faecalis strains were dominant. Additionally, there was a decrease in the expression of virulence genes in the presence of anti-mazF peptide nucleic acids. Therefore, it is suggested that mazEF TA systems are potent and sensitive targets in all E. faecium and E. faecalis strains.
  20. Bagheri A, Kamalidehghan B, Haghshenas M, Azadfar P, Akbari L, Sangtarash MH, et al.
    Drug Des Devel Ther, 2015;9:2627-34.
    PMID: 25999696 DOI: 10.2147/DDDT.S79709
    The presence of polymorphisms in the CYP2D6 gene may modulate enzyme level and activity, thereby affecting individual responses to pharmacological treatment. Here, we compared the prevalence of the CYP2D6*10, *4, and 14* alleles in an Iranian population of different ethnicities with those of other populations. Allele and genotype frequency distributions of CYP2D6*10 variants and predicted phenotypes including extensive metabolizers, intermediate metabolizers, and poor metabolizers were analysed in blood samples of 300 unrelated healthy individuals in an Iranian population using polymerase chain reaction (PCR)-restriction fragment length polymorphism, PCR-single-strand conformation polymorphism, and direct genomic DNA sequencing. The CYP2D6*4 (G1846A) and *14 (G1758A) allelic frequencies were not detected in different ethnicities, demonstrating the absence of a significant contribution of these alleles in Iranian populations. However, the T/T, C/T, and C/C genotype frequencies of the CYP2D6*10 allele were significantly different (P<0.01) in all Iranian ethnic groups. Additionally, the frequency of the homozygous T/T variant of the CYP2D6*10 allele was significantly high in the Lure (P<0.017) and low in the Kurd (P<0.002) ethnicities. The frequency of the T/T variant of the CYP2D6*10 allele in central Iran was the highest (P<0.001), while the south of Iran had the lowest frequency (P<0.001). The frequency of the C/T variant of the CYP2D6*10 allele was significantly a bit high (P<0.001) in females compare to males, while the frequencies of the T/T variant in females is similar to males, which are 24.4% and 24.3%, respectively. In contrast to absence of the CYP2D6*4 (G1846A) and *14 (G1758A) alleles in Iranian populations of different ethnicities, the prediction of the CYP2D6*10 allele is required in drug research and routine treatment, where the information would be helpful for clinicians to optimize therapy or identify persons at risk of adverse drug reactions before clinical trials. Approximately 39.3% of subjects (24.3% homozygous T/T CYP2D6*10 as poor metabolizers and 15% heterozygous C/T CYP2D6*10 as intermediate metabolizers) had this allele; therefore, the harmful effects of drugs are relatively common among Iranians.
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