م.د ضياء رحيم التميمي
السيرة الذاتية
الاهتمامات البحثية
البحوث المنشورة
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[email protected] : الايميل
م د ضياء رحيم التميمي دكتوراه صيدلانيات جامعة بغداد تدريسي لفرع الصيدلانيات منذ عام ٢٠١٤ ، مهتم بالبحث العلمي وكل ما يتعلق بالاختصاص لدي اكثر من 35 بحث منشور في مختلف المستوعبات العالمية عضو جمعية النانو تكنولوجيا وسلامته الايرانية
Nanotechnology, biotechnology, cancer research, drug delivery systems, pharmaceutics research , targeting drug delivery systems
Formulation and evaluation of meloxicam liquisolid compact
Objective: The aim of the present research was to improve dissolution of poorly soluble meloxicam a BCS (Biopharmaceutical Classification System) Class-II drug by utilizing liquisolid technique. Different liquisolid (LS) compacts were prepared using a mathematical model to calculate the required quantities of powder and liquid ingredients to produce acceptably flow able and compressible admixture. Methods: Liquisolid compact was prepared from; microcrystalline cellulose (Avicel PH 102) as carrier, colloidal silicon dioxide (Aerosil 200) and silica (cab-O-sil) as coating material, sodium starch glycol ate and cross povidon as superdisintegrants, PVP-K25 and HPMC E5 as additives to increase loading capacity, polyethylene glycol 400, propylene glycol and tween 80 as liquid vehicles. The ratio of carrier to coating material was kept constant in all formulations at 25: 1, this ratio was chosen after testing the ratios 5: 1, 10: 1, 15: 1, 20: 1 and 25: 1. The ratio 25; 1 give optimal results relative to other ratios.
Synthesis and Characterization of Silk Fibroin-Coated Mesoporous Silica Nanoparticles for Tioguanine Targeting to Leukemia.
Mesoporous silica nanoparticles (MSNs) are known as carriers with high loading capacity and large functionalizable surface area for target-directed delivery. In this work, large pore size MSNs were prepared by the co-condensation method. Tioguanine (TG) as a hydrophobic drug was loaded into the synthesized MSNs to prepare TG@ MSNs. The results show MSNs were successfully synthesized and they have good loading efficiency and capacity for TG. Silk fibroin (SF) as an active targeting agent and pH-sensitive targeting release, is a natural protein from silkworm cocoons. It was used to coating MSNs to prepare SF/TG@ MSNs. SF was Degummed and it was characterized by nuclear magnetic resonance (NMR), fourier transform infrared (FTIR) and field emission scanning electron microscopy (FESEM) methods. The MSNs were fully characterized by FESEM, transmission electron microscopy (TEM), zeta potential analysis, dynamic light scattering (DLS), nitrogen adsorption/desorption analysis, thermogravimetric analysis (TGA), X-ray diffraction (XRD) analysis, FTIR and UV-visible spectroscopies. The mechanism of TG release from SF/TG@ MSNs were pH-sensitive. The in vitro release modeling revealed that TG released via the Higuchi model with fickian diffusion mechanism. In conclusion, SF/TG@ MSNs exhibited a well synthesized and good payload for use in targeted drug delivery for leukemia.
In-vitro Evaluation of Metronidazole loaded Mesoporous Silica Nanoparticles Against Trichomonas Vaginalis.
Mesoporous silica nanoparticles (MSNs) are known as carriers with high loading capacity and large functionalizable surface area for more efficient drug delivery. In this study, the efficacy of metronidazole-loaded mesoporous silica nanoparticles (MSNs/MTZ) with a pH-sensitive release against Trichomonas vaginalis trophozoites was investigated. MSNs were prepared by the sol-gel method and final particles were characterized by Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Brunauer Emmett Teller (BET), Fourier Transform Infrared (FT-IR) spectroscopy and X-ray Diffraction (XRD) methods. MSNs were loaded with metronidazole (MTZ) to MSNs/MTZ preparation. In vitro susceptibility assay of MTZ/MSNs in Trichomonas vaginalis trophozoites was done to obtain inhibitory concentration (IC50). SEM results show particles with an approximate size of 50 nm and XRD results prove the crystalline structure of MSNs. The BET results show that pore size and surface area of these particles are 2.8 nm and 800 m2/g respectively. Other FTIR results confirm the chemical structure of the nanoparticles. The loading capacity of MSNs was 33% and the release of MTZ from the nanoparticles affected by the pH. Toxicity assay results on Trichomonas vaginalis trophozoites show increased cytotoxicity in MSNs-MTZ compared to free MTZ, whereas this evaluation confirmed that MSNs toxicity was insignificant. According to the results, it can be said that the use of MSNs is a good option for drug delivery to Trichomonas vaginalis trophozoites, and the use of these nanoparticles make MTZ more effective and performable.
Determination of total antioxidant content of methanolic extracts of Cynara scolymus, Echinacea purpurea and Portulaca oleracea
Background: The unique properties of medicinal plants particularly their effects on human health have attracted the attention of many researchers. The antioxidant properties of medicinal plants is a strong reason to use them in the food and pharmaceutical industries. Hence, the aim of this study was to evaluate the antioxidant properties of methanolic extracts of Cynara scolymus, Echinacea purpurea and Portulaca oleracea. Aerial parts of C. scolymus, E. purpurea and P. oleracea were dried and ground. Methods: Then, plant samples were prepared using homogenizing plant powders in methanol solution. Finally, the total antioxidant capacity of the plants was assessed by ferric iron reducing antioxidant power (FRAP) assay. Results: The results revealed that the total antioxidant capacity was found as 3.45, 1.16 and 1.68 mmol Fe 2+/L for C. scolymus, E. purpurea and P. oleracea, respectively. Based on our results, C. scolymus, E. purpurea and P. oleracea showed a potent antioxidant activity. Conclusion: It is recommended that utilization of C. scolymus, E. purpurea and P. oleracea in food and pharmaceutical industries could possibly possess beneficial health effects.
Preparation of Transdermal Patch Containing Selenium Nanoparticles Loaded with Doxycycline and Evaluation of Skin Wound Healing in a Rat Model
The present study aimed to prepare and evaluate a controlled-release system based on a chitosan scaffold containing selenium nanoparticles loaded with doxycycline. Its topical application in skin wound healing in rats was investigated. Therefore, 80 female rats were used and, after creating experimental skin defects on their back, were randomly divided into four equal groups: the control group without any therapeutic intervention; the second group received a chitosan transdermal patch (Ch); the third group received chitosan transdermal patch loaded with selenium nanoparticles (ChSeN), and the last group received chitosan transdermal patch containing selenium nanoparticle loaded by doxycycline (ChSeND). Morphological and structural characteristics of the synthesized patches were evaluated, and in addition to measuring the skin wound area on days 3, 7, and 21, a histopathological examination was performed. On the third day of the study, less hemorrhage and inflammation and more neo-vascularization were seen in the ChSeND group. Moreover, on day 7, less inflammation and collagen formation were recorded in the ChSeN and ChSeND groups than in the other groups. At the same time, more neo-vascularization and re-epithelialization were seen in the ChSeND group on days 7 and 21. In addition, on day 21 of the study, the most collagen formation was in this group. Examination of the wound area also showed that the lowest area belonged to the ChSeND group. The results showed that the simultaneous presence of selenium nanoparticles and doxycycline in the ChSeND group provided the best repair compared to the control …
Anti-influenza and anti-inflammatory effects of green tea (Camellia sinensis L.) extract
Pulmonary complications due to influenza A virus infection, in addition to being caused by the replication of the virus, are partly due to the excess production of pro-inflammatory cytokines. It is therefore helpful to seek out compounds to control the excess production of these cytokines along with administration of antiviral drugs. In this study, the effect of green tea (Camellia sinensis L.) extract on the replication of influenza A (H1N1) virus and on gene expression levels of pro-inflammatory cytokines was studied in Madin-Darby canine kidney (MDCK) cells. Methods In this experimental study, hydroalcoholic extract of C. sinensis leaf was prepared with maceration method. In vitro anti-influenza virus activity of the extract was evaluated by performing hemagglutination (HA) and 50 % tissue culture infectious dose (TCID50) assays at 24 and 48 hours of incubation. The gene expression levels of pro …
Berberine as a new neuraminidase inhibitor drug: A systematic review
Influenza as an infectious disease has serious effects on health and human life (1-3). It has caused annual influenza epidemics with significant morbidity and mortality (4). Annually, influenza epidemics result in three to 5 million cases of severe sickness and cause about 290 000 to 650 000 deaths worldwide (5, 6). Influenza viruses are from the Orthomyxoviridae family. The genome of these viruses contains negative-sense RNA segments that encode viral proteins. The envelope of the influenza virus consists of two main surface glycoproteins, neuraminidase (NA) and hemagglutinin (HA)(Figure 1). HA is necessary for receptor binding and for the fusion of the virus and the host membrane. NA cleaves the terminal sialic acid residues on cell surfaces and facilitates the
Selegiline induced differentiation of rat bone marrow mesenchymal stem cells to dopaminergic neurons in vitro
Today, the use of mesenchymal stem cells (MSCs) for treating human diseases has attracted wide attention. The aim of this study is the expression of dopaminergic genes such as Nestin, patched Tumor Suppressor (PTCH), Sonic Hedgehog (SHH), Tyrosine Hydroxylase (TH) and Nuclear receptor-related factor 1 (NURR1) in MSCs after induction with selegiline. Rat bone marrow mesenchymal stem cells (rBMSCs) were extracted from femur and tibia bones and incubated with alpha Minimum Essential Medium (α-MEM) and 10% Fetal bovine serum (FBS). The stemness of cells at passage 4 was determined by the positive response to CD71 and CD90 markers and their differentiation into adipocytes and osteoblasts. The expression of SHH, PTCH, TH, NURR1 and Nestin genes in the cells after induction by 10-8 M selegiline for 48 hours was investigated by Reverse transcription polymerase chain reaction (RT-PCR) and Real Time-PCR methods. Isolated rBMSCs expressed CD71 and CD90 markers in culture conditions and could differentiate into adipocytes and osteoblasts. Induced cells showed neuronal morphology, positive response to Nestin and TH immunostaining. There was a significant increase of dopaminergic genes TH and NURR1 compared to the untreated cells. The results showed that selegiline with a dose of 10-8 M for 48 hours can lead to dopaminergic differentiation in rBMSCs.
NF-κB/RELA Knockout Reveals a Role in Expression of HIF-1α and NES in A172 Cell Line: Suggestion Ecteinascidin-743 as a Suitable Drug
The NF-κB signalling pathway is one of the most critical controllers of the inflammatory response in glioblastoma multiforme (GBM). In this study, the knockout association of the RELA subunit was examined by expressing some genes connected tothe nuclear factor κB (NF-κB) pathway in sustaining hypoxic circumstances and GBM stem cells (GSCs) properties. A suitable drug is also suggested to target RELA. Targeted deletion of the RELAsubunit in human GBM cells (A172) was performed with CRISP R/Cas9. Nestin (NES) and hypoxia inducible factor 1 alpha (HIF-1α) genes expression levels and induction of apoptosis in transfected and control cells were assessed by Real-time PCR and flow cytometry, respectively. Using the Auto Dock Vina software, a molecular docking study was conducted to find the optimum intermolecular interaction between RELA protein and four potential drugs. Real-time PCR results showed a decrease in the expression of HIF-1α and NES genes in the transfected cell population compared to the control cells (p< 0.0102, p< 0.0012, and P< 0.0442, respectively). Flow cytometry results showed a significantly increased induction of apoptosis in the transfected cells compared to the control cell population. The results of docking revealed that Ecteinascidin-743 has the best intermolecular interaction with RELAprotein. In conclusion, the RELA subunit seems to be one of the factors affecting hypoxia, apoptosis, and change in stemness genes expression levels in GBM. Therefore, it is recommended to knock out the NF-κB signalling pathway or to use Ecteinascidin-743 in future studies.
Evaluation of berberine inhibitory effects on influenza neuraminidase enzyme: A molecular dynamics study
Introduction: Due to the high prevalence and drug resistance reported for the influenza virus in recent years, much research is being conducted on the discovery and introduction of more effective drugs against the virus. In this regard, the present bioinformatics study examined the inhibitory effects of berberine, a plant-based alkaloid, on influenza virus neuraminidase using docking and molecular dynamics studies. Methods: To conduct this study, the three-dimensional structure and PDB file of influenza virus neuraminidase were prepared from the protein and molecular information database, and the structure file of the berberine and oseltamivir (as positive control) molecules were prepared from the PubChem database. Using GROMACS software, simulation and molecular dynamics calculations were performed in the absence of an inhibitor. Molecular docking studies were performed using AutoDock software, and re-simulation of the protein-ligand complex was performed using GROMACS software. Results: Berberine was bound to the neuraminidase molecule with three hydrogen bonds and eleven hydrophobic bonds at the binding site. The amount of binding energy (BE) of berberine and oseltamivir was equal to-7.93 and-6.27 kcal/mol with the estimated inhibition constant (EIC) of 1.5 and 25.2 μM, respectively. Over simulation time, the radius of gyration (Rg) of the enzyme at berberine binding increased, but there was no significant difference in system energy changes (TE). Conclusion: Due to berberine binding, structural changes occur in the secondary and tertiary structures of influenza virus neuraminidase. The large number of created …
Preparation of Slow-release Implant of Camellia sinensis Hydroalcoholic Extract for Prevention of Post Laparotomy Intraperitoneal Adhesion in Rat
Najmeh ASGHARZADEH3 & Pegah KHOSRAVIAN3* Alaa A. HASHIM1, Dhiya ALTEMEMY2, Mariyam SAFABAKHSH3, Fatemeh DRISS4, Mehrdad KARIMI5, Mehrdad SHAHRANI3
Evaluation of the Effect of HESA-A on the Prevention and Treatment of Chemotherapy-induced Nausea and Vomiting in Breast Cancer and Lung Cancer Patients
Fateme Salehi CHOLICHE1, Dhiya ALTEMEMY2, Pegah KHOSRAVIAN3, Afsaneh Malekpour TEHRANI4, Maryam Saeedi GHAHE5, Kiavash FEKRI6,* & Ruholah MASUMI1,6
Preparation and Evaluation of Buccal Adhesive Film Containing Smoke of Anbar Nesara (Donkey Dung) for Treatment of Recurrent Aphthous Stomatitis: Preparation a Randomized …
Darab GHOLAMI6 & Pegah KHOSRAVIAN2* Dhiya ALTEMEMY1, Omid KARIMIAN2, Naser KHOSRAVI3, Fatemeh DRISS4, Najmeh SHAHINFARD5
Current Medical Applications of Terminalia Chebula: An Overview
Medicinal plants have long been used, and many of them are known today as drug production sources. The study and research of medicinal plants used in traditional medicine and their various effects in the treatment of some diseases can help produce new drugs. Terminalia chebula, known as the Haritaki plant, has always been at the top of Chinese, Tibetan, Ayurveda, and Iranian traditional medicines. Its classification is based on the size, shape, and growth of the fruit. We have done a thorough literature search in databases and collected the data and research results indexed in PubMed, Elsevier, and Institute for Scientific Information (ISI), Scientific Information Database, Google Scholar databases, and various books up to 2020. It has pharmacological uses such as neuroprotective, hepatoprotective, cardioprotective, antidiabetic, renoprotective, antifungal, antiviral, antibacterial, antimicrobial, antimutagenic, antiproliferative, antioxidant, antiarthritic, and antifertility properties. It also can act as an immunomodulator and anticancer agent. There are some available drugs obtained from T. chebula. Due to the different and wide pharmacological uses of Terminalia chebula, further studies are required to develop new drugs.
A comparative study of combination treatments in metastatic 4t1 cells: everolimus and 5-fluorouracil versus lithium chloride and 5-fluorouracil
Background: Combination therapy has been one of the most pioneering and strategic approaches implemented for malignancy treatment, which can intentionally influence multiple signaling pathways involved in cancer growth and progression. In the present study, the effects of 5-fluorouracil (5FU) in combination with everolimus (EVE) or lithium chloride (LiCl) were evaluated in 4T1 metastatic breast cancer cells and compared to control and each other. Methods and results: The resazurin assay, CompuSyn, flow cytometry, and real-time PCR were used to investigate cell proliferation, drug synergism, apoptosis, and gene expression. In comparison to the ternary combination of the drugs, the findings showed that cytotoxicity (p-value< 0.0001) and apoptosis (p-value< 0.0001) of two-by-two combinations increased dramatically as a consequence of the extreme synergy between 5FU and EVE or LiCl. Moreover, the hypoxia inducible transcription factor 1-alpha (HIF-1α) and the vascular endothelial growth factor (VEGF) downregulated considerably compared to control (p-value< 0.0001) by combination therapies of EVE-5FU and 5FU-LiCl; however, only VEGF displayed significant downregulation in comparison to single therapies. Conclusion: The findings showed that the combination of 5FU-LiCl increased cell cytotoxicity and apoptosis significantly more than EVE-5FU but suggests a clinical potential for both to treat metastatic breast cancer encouraging validation of these results in pre-clinical models.
Evaluation of humoral immune responses, effective factors on responses and re-infection in recovered COVID-19 patients
The aim of this study was to investigate the humoral immune responses (IgM and IgG antibodies) in recovered COVID-19 patients and the role of risk factors and symptoms with respect to the immune responses. Patients and Methods In this descriptive-analytical study, which was conducted by call-out method, the serum levels of IgM and IgG antibodies were measured using enzyme-linked immunosorbent assay (ELISA) in 248 recovered patients. Effective factors on immune response were determined. Re-infection was investigated through patient follow-up and using information drawn from the hospital information system. Chi-square, t test, ANOVA, and regression analysis in SPSS 15 and Stata 14 were conducted to investigate the relationship between variables. Results IgG positivity was 86.3% among our participants. Among those who did not show antibody response to COVID-19 (IgM-and IgG-), the most common symptoms at admission were fever, muscle pain (90.9%), chills and anorexia (81.8%). IgG levels remained positive in recovered patients for over seven months. IgG response showed a significant relationship with body mass index, hospital stay length, smoking, residence place, mortality rate, vomiting, and appetite (P< 0.05). The re-infection rate after recovery was only 1.6%. Conclusion High seroprevalence of IgG antibody against COVID-19 and low re-infection rate in Chaharmahal and Bakhtiari province was observed. In addition, the effects of factors such as fever, muscle pain, chills, vomiting, and anorexia on immune responses were demonstrated. These results can be used to manage disease control efficiently, and …
Improvement of rat cervicitis using medicinal smoke condensate of jennet feces: animal model set up and vaginal cream production; histopathological study
Introduction: Iranian traditional medicine has recommended the use of smoke from complete burning of jennet feces as a
Ethnobotanical Study for Hypertension Treatment: An Ethnobotanical Study of Abadeh, South Iran
Dhiya Altememy* Neda Dastyar
The restorative effect of titanium dioxide nanoparticles synthesized with Origanum vulgare l., Carvacrol, Hypericum perforatum l., and hypericin loaded in calcium alginate …
In this study, the restorative effect of titanium dioxide nanoparticles (TiO2NPs) synthesized with Origanum vulgare, carvacrol, Hypericum perforatum, and calcium alginate scaffold-loadable calcium alginate on infected wounds with Staphylococcus aureus was investigated in diabetic rats. Eight groups of 12 rats in any group were diabetic by intraperitoneal injection of alloxan. After the rats were anesthetized, 2cm 2 wounds were created and inoculated with bacterial suspension of S. aureus (ATCC 12600) equivalent to the 0.5 MacFarland tube. The hydroalcoholic extracts of Origanum vulgare, Hypericum perforatum, and their active ingredients including carvacrol and hypericin, were prepared, and then TiO2N. Ps. were prepared from them using isopropoxide. The antibiotic methicillin and calcium alginate pad was also loaded as control of nanoparticles embedded in the calcium alginate pad and then the restorative effect on the wound was studied. On days 0, 3, 7, 14, and 21, hematoxylin-eosin slides (H&E) of the tissue, angiogenesis rate, and division of fibroblast cells and Masson’s trichrome slides were used to determine the rate of collagenization, wound, and extracellular matrix. After the treatment, the size of the wound in the Tio2 NP synthesis by Origanum vulgare, Tio2 NP synthesis by carvacrol, methicillin, Tio2 NP, and alginate pad groups of diabetic rats and alginate pad group of non-diabetic rats were determined 7.03±1, 11.12±1, 10.72±1±15.48±1, 11±1, and 6.35±1 mm, respectively. The serum level of TNF α in the Tio2 NP synthesis by Hypericum perforatum decreased from 62±1 pg/mm on day 0 to 10±1 pg/mm on day 21. Medicinal …
The Molecular Dynamics Effects of Rutin on CDKS 2, 4 and 6: In Silico Modelling and Molecular Dynamics
Objectives: This simulated study has mechanistically evaluated the molecular dynamics effects of rutin on CDKs 2, 4, and 6 in cell cycling. Methods: Protein Data Bank (http://www. rcsb. org) was used to obtain the PDB file of CDK 2, 4, and 6. After simulation of CDKs in Gromacs software, AutoDock 4.2 was used to run 200 stages of molecular docking of CDKs in the presence of the rutin. CDK 2, 4, and 6 were simulated in the presence of rutin after docking. Results: Rutin had the highest tendency to bind the CDK-2 and CDK-6 via binding 16 and 18 residues in the binding site with hydrogen and hydrophobic bonds (respectively). Also, they had the highest amount of binding energy released. Rutin decreased total energy in CDKs and reduced the radius of gyration in CDK-2 and CDK-6 after docking. The secondary coil structure increased in CDK-2 and decreased in CDK-4 and 6. Conclusion: Conformational changes in CDK2 and 6 via rutin can inhibit the activity of these proteins and subsequently arrest the cell cycle in phases G1, S, and G2, which can lead the damaged cell to cell repair or Apoptosis.
Evaluation Of Curcumin Effects On Bad, Bak, And Bim: A Molecular Dynamics Simulation Study
Javad Saffari-Chaleshtori5* Fateme D. Asl1, Dhiya Altememy2, Pegah Khosravian3, Mehdi Rezaee4
Study of antibacterial effect of the hydroalchoholic extract of Teucrium polium against clinical strain of Gardnerella vaginalis in vitro
Bacterial vaginosis is caused by a change in the dominant and normal flora of the vagina (lactobacilli) to a multimicrobial flora, including G. vaginalis. Today, due to the emergence of antibiotic resistance in pathogenic microbial species and side effects of antibiotic therapy, researchers have turned their attention to natural compounds. Teucrium polium (T.P) is a member of the mint family that has wide applications in traditional medicine and its antimicrobial effects have been shown in previous studies. The aim of this study was to evaluate the antibacterial effect of hydroalcoholic extract of T.P on the clinical strain of G. vaginalis in vitro. In the present experimental study, the hydroalcoholic extract of T.P was prepared by maceration method and total flavonoid content of T.P extract was determined. after preparing concentrations of 0.195–0.195 mg/ml, its antibacterial effect was determined by disk diffusion and …
The In Vitro Cytotoxicity, Hemolysis Assay and Protein Corona Studies of Silk Fibroin-Coated Mesoporous Silica Nanoparticles for Tioguanine Targeting to Leukemia
Leukemia remains among the most deadly of diseases and new therapeutic approaches are required with as much urgency as possible. Nanotechnology has been used to develop diagnostic and therapeutic methods for cancer. On-malignant normal cells damaging and drug resistance are responsible for the treatment of cancer. Since currently using tioguanine (TG) as antineoplastic agent has demonstrated several side effects, there are many approaches available to help reduce or avoid unintended drug effects. Loading of TG within mesoporous silica nanoparticles (MSNs) to prepare TG@ MSNs which possess specific physicochemical properties for transporting and loading anticancer drugs would be a useful technique to resolve the negative effects of this medication. On other hand, silk fibroin (SF) was used, as an active targeting agent and pH-sensitive targeting release, on the surface of TG@ MSNs to …
A Drug‐In‐Adhesive Transdermal Patch Containing Smoke Of Anbar Nesara: Formulation And Evaluation Of Physicochemical Properties
Pegah Khosravian1* Ebrahim Soleiman Dehkordi1 , Dhiya Altememy2 , Fatemeh Driss3, Belgheis Mohammadi4 , Nilofar Shahmohamadi1 , Pooria Mohammadi Arvejeh5 , Sedighe Jamali Gandomani6
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