Research/Original Articles


Systematic Mining of Gene Co-Expression Network Suggesting a New Drug Repositioning for the Effective Treatment of Duchenne Muscular Dystrophy

Afshin Derakhshani, Maryam Moosavi, Saeed Nasseri, Ebrahim Miri-Moghaddam, Hossein Safarpour, Behzad Baradaran

Iranian Journal of Pharmaceutical Sciences, Vol. 17 No. 1 (2021), 15 January 2021, Page 1-18
https://doi.org/10.22037/ijps.v17.40292

Duchenne Muscular Dystrophy (DMD) is one of the most common inherited disorders worldwide. As there is currently no absolute treatment, the present systems biology study aimed to propose a new drug repositioning for DMD therapy. A microarray dataset of 16 DMD and 6 control samples were analyzed and 208 differentially expressed genes were screened. Weighted gene co-expression network analysis (WGCNA) algorithm, was applied to obtain co-expressed gene networks for the establishment of transcriptional modules related to clinical and demographic data of DMD patients. Results indicated that a maximum of 11 co-expression modules is present in datasets with a varying number of genes. Turquoise module with 3334 genes was strongly correlated with collagen fibril organization as a positive regulator in DMD pathogenesis (r=0.98, p-value=2/00E-15) through which other DMD related hub-genes were identified as COL1A1, FZD10, COL1A2, CRISPLD1, FMO1, COL5A1, COL3A1, COL5A2, TP53I3, PLAGL1, RIPK2, SBF1, MLXIP, CFAP46, and TYRP1. Drug repositioning of the turquoise module identified some candidate drugs which are not presently approved for the treatment of DMD. The targets in the turquoise module indicated that some drugs might greatly affect DMD disease. Furthermore, drug repositioning introduced Zoledronic acid as a potent antagonist for COL1A1.

 

Influential Factors on Pharmacist Profession- Related Errors: a Community Pharmacy Approach

Nima Sarhangi, Shekoufeh Nikfar, Seyed Abolfazl Zakerian, Monireh Afzali

Iranian Journal of Pharmaceutical Sciences, Vol. 17 No. 1 (2021), 15 January 2021, Page 19-26
https://doi.org/10.22037/ijps.v17.40293

Community pharmacy is one of the most important control stations in pharmacotherapy. Hence, Pharmacist mistakes may cause or lead to inappropriate medication use by patients or even permanent harm. Therefore, quality control in pharmacists’ practice is a safety issue and in addition has an added importance for society. This study has been designed to investigate the relationship between age, gender, shift work of pharmacists and the frequency of errors to determine possible defect and planning for them. Job descriptive and analysis were done using Hierarchical Task Analysis (HTA). The study population was observed directly and all the defined mistakes were recorded. The collected data were analyzed using regression and two-sided, chi-square analysis. The pharmacists supervised for 64 determinate mistakes and 3968 mistakes were recorded with a rate 36.7%. Based on the results, occurrence of mistakes are associated with shift work, age, and gender of pharmacists. There are significant increases in incidence of occupational errors in afternoon and night shifts, male population, over 40 years’ old population and long shift. Considering the relationship between pharmacist profession- related error and shift conditions or some of the demographic factors, it seems that further systematic evaluation on community pharmacy administration is necessary.

Information Sharing and Information Quality in the Drugs and Medical Consumables Supply Chain Management (SCM)

Malikeh Nouranian, Sakineh Saghaeiannejad Isfahani, Hoda Memarzadeh

Iranian Journal of Pharmaceutical Sciences, Vol. 17 No. 1 (2021), 15 January 2021, Page 27-42
https://doi.org/10.22037/ijps.v17.40297

Information management is considered as one of the keys to the supply chain management (SCM) success. This study intends to explore the factors affecting the knowledge sharing and knowledge quality in the SCM of the drugs and medical consumables. This applied study was conducted using analytical-survey research method. The research population consisted of 78 people involved in the supply chain of the drug and medical consumables in the teaching hospitals of Isfahan University of Medical Sciences (IUMS). Data were collected by a questionnaire whose face and content validity were both confirmed by pooling the ideas of some professors of Health Information Technology and Health-care Services Management faculties of IUMS. The reliability of the questionnaire was validated by estimating Cornbrash’s alpha coefficient (α=0.93). Data were analyzed using multiple regression analysis method and SPSS software version.23. Based on the results, the environmental uncertainty and intra-organizational facilitators had no impact on information sharing and information quality but inter-organizational relationships influenced the information sharing (p = 0.01) and information quality (p = 0.001). To achieve high-quality information sharing, establishing appropriate relationships with the other chain partners is of critical importance. Based on the results of the study, although there was no statistically significant relationship between the intra-organizational facilitators and environmental uncertainty and the information sharing and information quality, top management support, information technology (IT), appropriate selection of supplier and attention to the drug needs of the patients, should not be neglected.

Vulvovaginal candidiasis (VVC) caused by Candida albicans and other Candida species is a high-risk event in patients admitted to hospital. Ziziphus genus is a rich source of medicinal compounds, effective for the treatment or prevention of some diseases. This study aimed to evaluate the antifungal effect of topical microemulsion containing Ziziphus spina-Christi L (ZSC) extracts against Candida spp. Z. Spina-Christi was collected and extracted in a Soxhlet apparatus using the ethanol and methanol solvents. Microemulsions were formulated by the composition of surfactant (Tween 80) along with cosurfactant (propylene glycol), oil, and water and were characterized regarding their stability. The The in vitro antifungal study was performed by measuring and comparing the diameter of zones of inhibition (in mm) against C. albicans (ATCC 3153), C. parapsilosis (ATCC 2195) and C. krusei (ATCC 573) using agar well diffusion test, for the various formulations (without extract and containing ZSC extract). The optimal microemulsion was analyzed for the average diameter of droplets, pH, viscosity and zeta potential. The microemulsion containing Ziziphus spina-Christi ethanolic extract had a significant inhibitory effect on the different species of Candida, but the most inhibitory effect was found against C. albicans. The result showed that the ethanolic extract in microemulsion was Light green and, average globule size was 2.93 mm, no separation after centrifugation at 3000 rpm for 30 min, pH at 3.8, and viscosity was 8.523cps. The results of this study indicate that the ethanolic extract has interesting antifungal properties and can used for the treatment of fungal infections. More research is required to check this plant performance to treat the patients with Candidiasis.

Pomegranate (Punica granatum L.) is one of the oldest known fruits native to Iran. In addition to multiple studies carried out on different parts of pomegranate, the peels are noted due to various phytochemicals in different colors and regions. In the present study, major anthocyanins and non-anthocyanins of an Iranian black pomegranate cultivar (i.e., pomegranate samples of Ghaemshahr, Iran) were analyzed using high-performance liquid chromatography-mass spectrometry. In total, 30 compounds were obtained from pomegranate peels. Among these compounds, 5 anthocyanins, 1 gallotannin, 15 ellagitannins, 4 hydroxybenzoic acids, 2 gallagyl esters, 1 dihydroflavonol, and 7 hydroxycinnamic acids were identified based on their fragmentation patterns and ultraviolet spectra. Among the varieties of Iranian pomegranates, the anthocyanins of peonidin-hexoside and cyanidin-pentoside were identified in this species for the first time. Peonidin-hexoside, caffeic acid, coumaric acid-hexoside, and galloyl-hexoside were major phenolic compounds. In addition, the antioxidant activity of different fractions was tested using DPPH free radical scavenging in vitro assay (IC50: 133.13-557.23 μg/mL). The obtained results of this study highlighted that this cultivar can be an important candidate for future new drug discoveries.

Assessment of the Skin and Heart Tissue Damage Following Inhalation of Carbon Nanotubes in Wistar Rats Using Isolated Mitochondria

Fatemeh Samiei, Faezeh Dousti, Enayatollah Seydi, Ali Hayati, Farshad H. Shirazi, Jalal Pourahmad

Iranian Journal of Pharmaceutical Sciences, Vol. 17 No. 1 (2021), 15 January 2021, Page 69-78
https://doi.org/10.22037/ijps.v17.40300

The unique properties of carbon nanotubes (CNTs) have led to their use in various fields. But, the toxicity of CNTs has been reported in biological and environmental systems. The aim of this research is to study the effect of multi-wall carbon nanotubes (MWCNTs) through inhalation chamber on the mitochondrial damage and oxidative stress using the mitochondria obtained from the skin and heart. Rats were exposed to 5 mg/m3 of MWCNTs (10 nm) aerosol for 5 hours /day, 5 days/week for 2 weeks in a whole-body exposure chamber. After 2-weeks exposure, Heart and skin mitochondria were evaluated for evaluation of toxicity parameters. The results showed that nanoparticles significantly decreased mitochondrial succinate dehydrogenase (SDH) activity and increased the level of reactive oxygen species (ROS), collapse in mitochondria membrane potential (MMP), swelling in mitochondria, and cytochrome release. In conclusion, we suggested that 5 mg/m3 of MWCNTs (10 nm) induce ROS mediated cytotoxicity by directly targeting mitochondria in both skin and heart tissue.

Evaluation of Wound Healing Properties of Dryopteris filix-mas Leaf and Root Extracts on Albino Rats

Earnest Oghenesuvwe Erhirhie, Cathrine Odinakachi Anyim, Ugochukwu Moses Okezie, Sabastine Obiora Igboeme, Emmanuel Emeka Ilodigwe

Iranian Journal of Pharmaceutical Sciences, Vol. 17 No. 1 (2021), 15 January 2021, Page 79-90
https://doi.org/10.22037/ijps.v17.40301

Dryopteris filix-mas (D. filix-mas), belonging to the family of Dryopteridacea is a swampy fern that is popularly used by the Southern Nigerian dwellers in the treatment of wounds, hemorrhages, boil and other diseases. In order to authenticate its folkloric benefits in wounds, this study evaluated its wound healing activity using excision model. A total of fifty (50) Wistar rats were randomized into ten groups of five animals each. After creation of surface wounds, group 1 received paraffin base (control). Group 2 received Povidon iodine (standard). Groups 3, 4, 5 and 6 received 1.25, 2.5, 5 and 10% (w/w) of an ethanol leaf extract of D. filix-mas formulated with paraffin base respectively. Groups 7, 8, 9, 10 were treated with 1.25, 2.5, 5 and 10% (w/w) of ethanol root extract D. filix-mas formulated with paraffin base respectively. Treatments were topically applied to wounds once daily and healing rate was monitored every 3 days for 21 days. Wound swaps were taken on day 10th and day 20th for bacteria load determination. In-vitro antimicrobial activities of the leaf and root extract were tested against Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli using agar-well diffusion method. Higher concentrations (5 and 10%) of the leaf and root extracts exhibited better wound healing activities more than lower concentrations. The leaf extract produced a better healing rate (wound contraction), antimicrobial activity and body weight regaining activities more than the root extract. This study validates the traditional use of D filix-mas in the treatment of wounds.

The Determination of Antioxidant Activity of Ethanol Extracts of Gynostemma Pentaphyllum

Alfina Ansafovna Nizamova, Elvira Khalitovna Galiakhmetova, Konstantin Sergeevich Mochalov, Dmitry Olegovich Bokov, Golrokh Farnam, Natalia Vladimirovna Kudashkina

Iranian Journal of Pharmaceutical Sciences, Vol. 17 No. 1 (2021), 15 January 2021, Page 91-98
https://doi.org/10.22037/ijps.v17.40302

Inflammatory reactions of active radicals play a primary role in many vital circumstances, and if they are not neutralized and persist in the body, many diseases will occur. Antioxidants are the very critical resources available in the body to eliminate these free radicals. Medicinal herbs have been used extensively in the treatment of diseases for centuries. Gynostemma Pentaphyllum is grown in many different locations of Europe and Asia is an adaptogenic plant that is rich in antioxidants. During this study, the antioxidant effects of Gynostemma Pentaphyllum extract are evaluated using two different methods of adrenaline autooxidation and Chemiluminescence, both patented in Russia. Our results show that the organic solvent is more suitable for the extraction of these antioxidants with the ratio of 70% ethanolic extract being yield in more extraction. This preliminary work might open a new door for future studies on the antioxidant effects of this herb grown in Russia for the treatment of inflammations and other diseases with such pathology.

Hematopoietic stem cell transplantation (HSCT) is an effective treatment for many hematological malignancies. Engraftment is the foremost step in the autologous hematopoietic stem cell transplantation (AHSCT) process in which different granulocyte colony-stimulating factors with various administrations are used. In this study, we evaluated and compared the efficacy and side effects of two forms of recombinant granulocyte colony-stimulating growth factors (GCSF) ,GCSF and Peg GCSF, In this randomized clinical trial, 60 consecutive patients with multiple myeloma, Hodgkin's and non-Hodgkin's lymphoma who underwent AHSCT were included, the average age of the patients was 55; the patients were then divided into two groups so the comparison of efficacy and side effects between the two methods become achievable. The local ethical committee approved the study with the code of SB2019:210291, and the Helsinki declaration was respected across the study. In the first group, patients received peg GCSF at a dose of 6 mg on day five, and the second group received GCSF started with 5μg/kg from day 5. We compared engraftment time and adverse effects in the two groups. Our study demonstrated no difference between the two groups regarding need for transfusion and infection complications; also, the two groups did not differ in terms of the flue-like syndrome, the type of infection and the recorded number of febrile neutropenia. Mean leukocyte engraftment days were 10.97 ± 1 and 11.1 ± 1.1 that was similar in both groups (P=0.328). Mean platelet engraftment days were 11.03 ± 2.4 and 11.1 ± 2.4 without significant difference (P=0.714).it was concluded that Pegfilgrastim has the same efficacy and safety profile in comparison to Filgrastim. Therefore, since Pegfilgrastim has a easier method of injection and can simplify the HSCT process.