bluuebunny/crossref_metadata_2025 huggingface dataset:
Frequency Domain analysis of Ground reaction forces in Deaf and blind people during walking
Authors: barghamadi mohsen , Abdollahpour Darvishani mohammad
Published: September 2021

Background: The link between Frequency domain analysis of ground reaction forces and hearing loss and blind during walking is not well understood. Therefore, the purpose of this study was to investigate frequency domain analysis of ground reaction forces in deaf and blind people during walking. Methods: This study was quasi-experimental. The volunteer participants in current study consisted of thirty male that, were divided into three equal groups: blind, deaf and healthy (control) groups. Frequency Domain analysis of ground reaction forces in three groups was recorded by a foot scan system (sample rate: 300 Hz). The multivariate ANOVA test was used to compare between groups. The significance level was set at p < 0.05 for all analyses. Results: The results showed that, the frequency content with the power 99.5% in the vertical component of ground reaction forces in both deaf (p=0.020) and blind (p=0.021) groups reduced vs. control group. Also, frequency content with the power 99.5% in the Mid-foot in deaf (p=0.020) group was more than the blind group (p=0.036). Conclusion: The present study showed that the frequency content with the power 99.5% in the Mid-foot in deaf group was more than the blind group. It can be stated that the frequency domain analysis of ground reaction forces has the clinical value. Therefore, the use of therapeutic interventions to improve the frequency domain analysis of ground reaction forces in deaf and blind people is suggested.
Investigation of Experimental and In Silico Physicochemical Properties of Thiazole-Pyridinium Anti-Acetylcholinesterase Derivatives with Potential Anti-Alzheimer’s Activity
Authors: Ghotbi Golaleh , Hamzeh-Mivehroud Maryam , Taghvimi Arezou , Davaran Soodabeh , Dastmalchi Siavoush
Published: September 2021

Background: Physicochemical properties play important role in fundamental issues like absorption and distribution of pharmaceuticals to the target tissue. This is particularly importantfor drugs acting in central nervous system (CNS). In this study, physicochemical properties of previously synthesized thiazole-pyridinium derivatives with anti-acetylcholinesterase activity and possible anti-Alzheimer effect were studied. Methods: Partition coefficient (n-octanol/water) and chromatographic Rf values for the studied compounds were determined using shake flask and high performance thin layer chromatography(HPTLC) methods, respectively. Different druglikeness properties of the compounds were also calculated using available software and web-servers. Results: The experimentally determined logarithm of partition coefficients (log P) for the studied compounds were in the range of -1.00 to -0.38. The Rf values for the studied compounds under the applied chromatographic condition ranged between 0.38 to 0.58. Moreover, calculated physicochemical properties, and druglikeness scores of the studied thiazole-pyridiniumderivatives and matching piperidine analogues were predicted. Furthermore, some ADMETfeatures of studied compounds like toxicity and metabolism by CYP450 (2C9, 2D6, 3A4, 1A2and 2C19) enzymes were predicted. Conclusion: The ranges of experimental and calculated LogP values for the studied thiazolepyridinumswere close. However, the determined Rf values showed relatively better correlation to the predicted LogP values indicating the suitability of used chromatographic method for comparing the lipophilicity of the positively charged pyridinium derivatives. The studied compounds were predicted to pass GI membrane and reach the CNS where they can exert their effects. In silico studies indicate that the piperidine counterparts of the studied thiazolepyridiniumsmay represent anti-Alzheimer agents with improved druglikeness properties.
Correction of Mitochondrial Dysfunction by 4-Hydroxy-3,5-Ditretbutyl Cinnamic Acid in Experimental Alzheimer’s Disease Induced by Aβ Injection in Rats
Authors: Pozdnyakov Dmitry Igorevich , Voronkov Andrey
Published: September 2021

Background: Alzheimer’s disease is the main form of dementia, which affects more than46 million people every year. In the pathogenesis of Alzheimer’s disease, a significant roleplayed mitochondrial dysfunction, which is a promising pharmacotherapeutic target ofneuroprotective therapy. In this regard, this study aimed to evaluate the effect of the 4-hydroxy-3,5-ditretbutyl cinnamic acid on changes of mitochondrial function in experimental Alzheimer’sdisease induced by Aβ injection in rats. Methods: Alzheimer’s disease was modeled on Wistar rats by injecting a fragment of β-amyloid(Aß 1-42) into the CA1 part of the hippocampus. The test-compound (4-hydroxy-3,5-ditretbutylcinnamic acid, 100 mg/kg, per os) and the reference drugs (resveratrol, 20 mg/kg, per os andEGB671, 100 mg/kg, per os) were administered for 60 days after surgery. The restoration of amemorable trace in animals was evaluated in the Morris water maze test. The concentrationof β -amyloid, Tau-protein, and changes in parameters characterizing mitochondrial function(cellular respiration, concentration of mitochondrial ROS, activity of apoptosis reactions(caspase-3 and apoptosis induced factor) were also determined. Results: This study showed that the administration of 4-hydroxy-3,5-ditretbutyl cinnamic acidat a dose of 100 mg/kg (per os) in rats with reproduced Alzheimer’s disease contributed to thenormalization of mitochondrial respiratory function. It was expressed in the normalizationof aerobic metabolism, increased activity of respiratory complexes and stabilization ofmitochondrial membrane potential. Also, when animals were treated with 4-hydroxy-3,5-ditretbutyl cinnamic acid, there was a decrease in the concentration of intracellular calcium(by 39.7% (p<0.05)), the intensity of apoptosis reactions, and an increase of the latent time ofthe mitochondrial permeability transition pore opening (by 3.8 times (p<0.05)), and decreasesH2O2 concentration (by 21.2% (p<0.05)). Conclusion: In the course of this study, it was found that 4-hydroxy-3,5-ditretbutyl cinnamicacid exceeds the value of neuroprotective action in compared to the reference agents –resveratrol (20 mg/kg) and Ginkgo biloba extract (EGB671, 100 mg/kg).
In Vitro Studies of Prednisolone Loaded PLGA Nanoparticles-Surface Functionalized With Folic Acid on Glioma and Macrophage Cell Lines
Authors: Acharya Sriprasad , Praveena Joyceline , Guru Bharath Raja
Published: September 2021

Background: Glucocorticoids are employed for their anti-inflammatory effects in treatingglioma, whose cells are known to overexpress the folate receptors. Some glucocorticoids haveshown inhibitory effects, but the efficacy of prednisolone when delivered via folate receptormediateduptake, has not been attempted. The study aimed to assess the efficacy of targeteddelivery of prednisolone on glioma cell lines like C6 and U87 via the folate receptors. Methods: Targeted delivery of prednisolone was achieved by initially conjugating folic acid (FA)to the di-block copolymer of polylactic acid (PLA) – polyethylene glycol (PEG). This moietycarrying di-block copolymer was incorporated on the surface of the drug-loaded poly lactic-coglycolicacid (PLGA) nanoparticle (NP) by employing the Interfacial Activity Assisted SurfaceFunctionalization (IAASF) technique. The NPs were evaluated for size, zeta potential, and drugloading. It was characterized using particle size analyser, SEM, 1H-NMR, and XRD. cell uptake,cytotoxicity, and anti-inflammatory activities were studied for various formulations. Results: The cytotoxicity assay indicated a high cell growth inhibitory effect of drug encapsulatedNPs with FA moiety as compared to free drug and NPs without the moiety for an incubationperiod of three, five, and six days. The growth-inhibitory effect of the free drug was short-lived,whereas FA functionalized NPs showed higher uptake and sustained inhibitory effect, and werealso able to significantly control the release of pro-inflammatory cytokines like tumour necrosisfactor-alpha (TNF-α) and nitric oxide (NO). Conclusion: Uptake, attenuation of pro-inflammatory signals, and the inhibitory effect ofprednisolone on the cells were more effective when targeted with the FA moiety on the surfaceof NPs as compared to free drug and NPs without the moiety.
Efavirenz Loaded Nanostructured Lipid Carriers for Efficient and Prolonged Viral Inhibition in HIV-Infected Macrophages
Authors: Mahajan Ketan , Rojekar Satish , Desai Dipen , Kulkarni Smita , Vavia Pradeep
Published: September 2021

Background: The clinical outcome of anti-HIV therapy is poor due to the inherent fallouts ofanti-HIV therapy. It is further worsened due to the presence of viral reservoirs in immune cellslike the macrophages. An ideal anti-HIV therapy must reach, deliver the drug and exert itsaction inside macrophages. To address this, we developed novel cationic nanostructured lipidcarriers of efavirenz (cationic EFV-NLC). Methods: The developed cationic EFV NLCs were evaluated for particle size, zeta potential,encapsulation efficiency, in-vitro drug release, DSC, XRD, TEM, cytotoxicity, cellular uptakestudies and anti-HIV efficacy in a monocyte-derived macrophage cell line (THP-1). Results: Cationic EFV-NLCs showed high encapsulation efficiency (90.54 ± 1.7%), uniformparticle size distribution (PDI 0.3-0.5 range) and high colloidal stability with positive zetapotential (+23.86 ± 0.49 mV). DSC and XRD studies confirmed the encapsulation of EFVwithin NLCs. Cytotoxicity studies (MTT assay) revealed excellent cytocompatibility (CC5013.23 ± 0.54 μg/mL). Fluorescence microscopy confirmed the efficient uptake of cationic EFVNLCs,while flow cytometry revealed time and concentration dependant uptake within THP-1cells. Cationic EFV-NLCs showed higher retention and sustained release with 2.32-fold higherpercent inhibition of HIV-1 in infected macrophages as compared to EFV solution at equimolarconcentrations. Interestingly, they demonstrated 1.23-fold superior anti-HIV efficacy over EFVloadedNLCs at equimolar concentrations. Conclusion: Cationic NLCs were capable of inhibiting the viral replication at higher limitsconsistently for 6 days suggesting successful prevention of HIV-1 replication in infectedmacrophages and thus can prove to be an attractive tool for promising anti-HIV therapy.
The Integration of Pharmacophore-Based 3D QSAR Modeling and Virtual Screening in Identification of Natural Product Inhibitors against SARS-CoV-2
Authors: Norouzi Samira , Farahani Maryam , Nejad Ebrahimi Samad
Published: September 2021

Background: The current outbreak of Coronavirus Disease 2019 (SARS-CoV-2) led to public health emergencies all over the world and made it a global concern. Also, the lack of an effective treatment to combat this virus is another concern that has appeared. Today, increasing knowledge of biological structures like increasing computer power brings about a chance to use computational methods efficiently in different phases of the drug discovery and development for helping solve this new global problem. Methods: In this study, 3D pharmacophores were generated based on thirty-one structures with functional affinity inhibition (antiviral drugs used for SARS and MERS) with IC50<250 µM from the literature data. A 3D-QSAR model has been developed and validated to be utilized in virtual screening. Results: The best pharmacophore models have been utilized as 3D queries for virtual screening to gain promising inhibitors from a data set of thousands of natural compounds retrieved from PubChem. The hit compounds were subsequently used for molecular docking studies to investigate their affinity to the 3D structure of the SARS-CoV-2 receptors. The ADMET properties calculate for the hits with high binding affinity. Conclusion: The study outcomes can help understand the molecular characteristics and mechanisms of the binding of hit compounds to SARS-CoV-2 receptors and promising identification inhibitors that are likely to be evolved into drugs.
Investigating the Effects of Salvia chorassanica Bunge and Shoot Extracts on Gastric Cancer Cells: Evidence of Different Behavior on Various Tumor Grades
Authors: Karami Fatemeh , Dourandish Yazdi Ahmad , Salahshourifar Iman , Marvi Beigi Mohsen
Published: September 2021

Background: Different Salvia species have demonstrated anti-proliferative effects on various cancer cells. Owing to the poor literature on the anti-proliferative effects of Salvia species on gastric cancer cells, present study was conducted to determine the anticancer effects of a local Iranian Salvia, Salvia chorassanica, on two different gastric cell lines. Methods: Root, stem and leaf extract of Salvia chorassanica were prepared through maceration method and were then used to treat the AGS and MKN-45 cell lines in different concentrations. MTT assay was employed to determine the toxicity of all the types of extracts on the two studied cell lines. The expression of Bax, Bcl-2, Caspase3, MMP2 and MMP9 genes were determined through reverse transcription Real time PCR (RT-PCR). Results: Bunge and shoot extracts demonstrated toxicity in both cell lines which were more considerable in AGS cells treated with root extract. In contrary to AGS cells, Caspase3 gene was up-regulated in all types of treatment while the MMP2 and MMP9 genes were down-regulated (p-value<0.001). Except of the MKN-45 cells treated with leaf extract, Bax/Bcl-2 expression ratio was decreased in the treatment with all types of Salvia chorassanica extracts (p-value<0.001). Conclusion: Remarkable low IC50 concentration of root extract in MKN-45 cell line is indicating the significant cytotoxicity of Salvia chorassanica against gastric cancer cells. Moreover, gene expression analysis in MKN-45 needs further confirmation on the potential anti-metastatic roles of leaf and root extracts in higher grades of gastric cancer.
Mechanochemical synthesis of a novel eutectic of the antimicrobial nitazoxanide with improved dissolution performance
Authors: Fandiño Octavio E. , Bruno Flavia P , Monti Gustavo A. , Sperandeo Norma R.
Published: September 2021

Background: Nitazoxanide (NTZ) is a broad spectrum antimicrobial agent with poor aqueous solubility and low bioavailability. Thus, the generation of new solid forms of NTZ is relevant to improve its unfavorable properties. The present study deals with the application of mechanochemistry for the preparation of alternate solid forms of NTZ, using saccharine (SAC) as coformer. Methods: NTZ-SAC mixtures were prepared by neat and liquid-assisted grinding (LAG) and characterized using differential scanning calorimetry (DSC), hot stage microscopy (HSM), X-ray Powder Diffraction (XRPD), 13C Solid-state Nuclear Magnetic Resonance (SSNMR) and Diffuse Reflectance Infrared Fourier Transform (DRIFT) spectroscopy. Powder dissolution (PD) profiles were obtained with USP apparatus 2 in buffer phosphate pH 6.5 with 0.25% Tween 80 - 0.25% triethanolamine and in 0.25% sodium lauryl sulfate, at 37 ºC ± 0.5 ºC and 75 rpm. Drug release was characterized in terms of dissolution efficiency (DE). Results: XRPD, SSNMR and DRIFT indicated that NTZ and SAC did not cocrystallize but DSC and HSM revealed that they formed a binary eutectic mixture which melted near 176 °C, a melting temperature lower than those of NTZ and SAC. PD data indicated that the 1:1 NTZ-SAC sample obtained by LAG exhibited a slightly higher DE than pure NTZ in the two assayed media. Conclusion: NTZ and SAC formed a eutectic, the first reported for this drug, which improved its dissolution rate and opened the pathway for studies searching for new eutectics with better biopharmaceutical attributes than NTZ and the NTZ-SAC eutectic reported herein.
Natural products as inhibitors of COVID-19 main protease–A virtual screening by molecular docking
Authors: Omrani Marzieh , Bayati Mohammad , Mehrbod Parvaneh , Asmari Bardazard Kamal , Nejad-Ebrahimi Samad
Published: September 2021

Background: The novel coronavirus (2019-nCoV) causes a severe respiratory illness unknown to a human before. Its alarmingly quick transmission to many countries across the world has resulted in a global health emergency. Therefore, an imminent need for drugs to combat this disease has been increased. Worldwide collaborative efforts from scientists are underway to determine a therapy to treat COVID-19 infections and reduce mortality rates. Since herbal medicines and purified natural products have been reported to have antiviral activity against Coronaviruses (CoVs), this in silico evaluation was performed for identifying potential natural compounds with promising inhibitory activities against COVID-19. Methods: In this study, a High Throughput Virtual Screening (HTVS) protocol was used as a fast method for discovering novel drug candidates as potential COVID-19 main protease (Mpro) inhibitors. Over 180,000 natural product-based compounds were obtained from the ZINC database and virtually screened against the COVID-19 Mpro. In this study, the Glide docking program was applied for high throughput virtual screening. Also, Extra precision (XP) has been used following the induced-fit docking (IFD) approach. The ADME properties of all compounds were analyzed and a final selection was made based on the Lipinski rule of five. Also, molecular dynamics (MD) simulations were conducted for a virtual complex of the best scoring compound with COVID-19 protease. Results: Nineteen compounds were introduced as new potential inhibitors. Compound ZINC08765174 (1-[3-(1H-indol-3-yl) propanoyl]-N-(4-phenylbutan-2-yl)piperidine-3-carboxamide showed a strong binding affinity (-11.5 kcal/mol) to the COVID-19 Mpro comparing to peramivir (-9.8 kcal/mol) as a positive control. Conclusions: Based on these findings, nineteen compounds were proposed as possible new COVID-19 inhibitors, of which ZINC08765174 had a high affinity to Mpro. Furthermore, the promising ADME properties of the selected compounds emphasize their potential as attractive candidates for the treatments of COVID-19.
Sodium Bicarbonate versus Statins to Prevent Contrast-induced Acute Kidney Injury: A Comprehensive Review
Authors: Dolati Sanam , Mahmoodpoor Ata , Gharizadeh Nafiseh , Gholipouri Saina , Soleimanpour Hassan
Published: September 2021

Iodinated contrast agents are commonly used in diagnostic radiography techniques along with therapeutic interventions. Contrast-Induced Acute Kidney Injury (CI-AKI) is a significant problem of all angiographic procedures, triggered by the use of Iodinated Contrast Media (ICM). There are conflicting data concerning the prevention and treatment of CI-AKI. Numerous approaches have been studied to prevent CI-AKI, but the therapy of choice remains undetermined. The cornerstones of CI-AKI prevention include low-osmolar ICM and intravenous hydration. The recommended hydration must be achieved by means of an isotonic solution of saline. Statins were tested against AKI due to their anti-inflammatory action and antioxidant effect on endothelial function. Novel approaches are required to investigate the short-term effects of high dosage atorvastatin versus sodium bicarbonate on CI-AKI prevention. The objective of this review is to compare the findings of various studies that had applied different doses of statins, sodium bicarbonate, and other agents for preventing CI-AKI.
The Potential Use of Aptamers in The Process of Drug Development
Authors: Gholikhani Tooba , Jimenez Brito Balam , Livingston Frey , Kumar Shalen
Published: September 2021

Single-stranded nucleic acids can fold and create unique 3-dimensional structures when interacting with other molecules. The unique structure can achieve high specificity and affinity for the particular target. Synthetic oligonucleotide binding agents also known as aptamers are generated through the rational process of Systematic Evolution of Ligands by Exponential Enrichment (SELEX.) As this technology matures it shows increasing promise for use in the field of a therapeutic drug, drug discovery, development, and delivery, and this report seeks to detail how this technology may be applied.
Determination of chlorzoxazone crystal growth kinetics and size distribution under controlled supersaturation at 293.15 K
Authors: G Satish , N Dhayananth , Ponnusamy Kalaichelvi , T K Radhakrishnan , S Karthika
Published: September 2021

Background: Chlorzoxazone (CHZ) is a water-insoluble drug having bioavailability problems. The absorption rate of such drugs can be improved by reducing their particle size. In this work, the crystal growth kinetics of CHZ–ethanol for different degrees of supersaturation (SS) has been studied. Method: The equilibrium solubility data of CHZ in ethanol is determined by the shake-flask method within the 283.15–313.15 K temperature range. The mole fraction solubility of CHZ is calculated and correlated with the modified Apelblat equation, λh equation, van’t Hoff equation, Wilson, and non-random two liquid (NRTL) equation. Batch crystallization experiments are performed on three different degrees of SS-1.16, 1.18, and 1.20 at 293.15 K as a function of time. Results: The maximum root mean square difference (RMSD) and relative average deviation (RAD) values of 169.24 x10-6 and 0.699 x10-2, respectively, are observed in the NRTL equation model. The dissolution properties such as standard enthalpy, standard entropy, and Gibbs free energy are predicted using van’t Hoff equation. Using a simple integral technique, the average crystal growth rate constant KG is calculated as 1.58 (μm/min) (mg/ml)-1 and the order n=1 for CHZ–ethanol at 293.15 K. Conclusion: The obtained result concludes that the crystals growth size is found to be varied at different SS ratio in batch crystallization. The particle size control in batch crystallization can be achieved by optimizing the operating conditions to get the desired size crystals.
Fluconazole nanosuspension enhances in vitro antifungal activity against resistant strains of Candida albicans
Authors: Morteza-Semnani Katayoun , Saeedi Majid , Akbari Jafar , Moazeni Maryam , Seraj Houman , Daftarifard Elham , Tajbakhsh Mahgol , Hashemi Seyyed Mohammad Hassan , Babaei Amirhossein
Published: September 2021

Background: Recently, nanoparticles were widely used in drug delivery. Fluconazole (FLZ) is a lipid-soluble antifungal, which is utilized in treating fungal infections. The current work aimed to investigate the characteristics and antifungal activity of FLZ nanosuspension. Methods: FLZ nanosuspensions were prepared by Ultrasonication (simple and containing polymer). Surfactants in various concentrations were dissolved in the deionized water, and the drug powder was dispersed in the surfactant solution by a high-speed homogenizer to achieve nanosuspension. The polymer was added to the selected formula. FLZ nanosuspension characteristics, including polydispersity, mean particle size, entrapment efficacy, and zeta potential, were assessed. The release profile via dialysis membrane, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (ATR-FTIR), and TEM were performed for nanosuspension evaluation. Antifungal activity against resistant strains of C. albicans was defined according to the CLSI document guideline. To analyze the results, one-way ANOVA was used, followed by Tukey test. Results: The results showed that increased sonication time and hydrophilic-lipophilic balance (HLB) significantly affected particle size reduction. Moreover, modification in the formulation components had a significant effect on the drug release process, furthermore affecting the properties of the nanoparticles. ATR-FTIR showed no chemical interaction between FLZ and formulation components. Compare to FLZ, a significant reduction (p < 0.05) was detected in the MIC values of both FLZ-resistant and FLZ-susceptible strains of C. albicans against FLZ nanosuspension. Conclusion: It can be concluded that the ratio and amount of surfactants, the HLB, and the sonication process have effects on the properties of the nanoparticle’s characteristics, and selected nanoparticles show suitable antifungal effect against resistant strains of C. albicans.
Evaluation of the potential role of silver nanoparticles loaded with berberine in improving anti-tumor efficiency
Authors: Othman Mohamed M , Obeidat Sofian , Al-Bagawi Amal , Fareid Mohamed , El-Borady Ola , Kassab Rami , Abdel Moneim Ahmed
Published: September 2021

Background: Cancer is a progressive disease, its incidence and death rates are rapidly increasing globally. Numerous adverse effects are associated with the available interventions. Hence, the current study was undertaken to explore the anticancer effect of silver nanoparticles conjugated with berberine (AgNPs-BER) against Ehrlich solid carcinoma (ESC) in mice. Methods: Male Swiss albino mice were allocated randomly into ESC, ESC+cisplatin (CP; 5 mg/kg), ESC+AgNPs-BER (20 mg/kg), and ESC+cisplatin and AgNPs-BER groups. Results: AgNPs-BER administration increased significantly the survival rate and decreased body weight and tumor size as compared to ESC group. Additionally, AgNPs-BER enhanced the development of oxidative stress in the tumor tissue as indicated by the increased lipid peroxidation (LPO) and nitric oxide (NO) accompanied by a decrease in the examined antioxidant proteins (glutathione (GSH) and its derived enzymes along with superoxide dismutase and catalase). AgNPs-BER was found also to trigger apoptotic cascade in the tumor cells through upregulating the mRNA expression of the pro-apoptotic proteins (Bax and caspase-3) and downregulating the mRNA expression of the anti-apoptotic protein (Bcl-2). Moreover, AgNPs-BER improved partially the histopathological alterations in the developed tumor tissue as compared to ESC group. Conclusion: Collectively, AgNPs-BER could be applied as an antitumor agent due to its pro-oxidant, pro-apoptotic, and antiangiogenic effects.
Molecular docking and dynamics simulations reveal the potential of anti-HCV drugs to inhibit COVID-19 main protease
Authors: Al-Karmalawy Ahmed Ali , Alnajjar Radwan , Dahab Mohammed , Metwaly Ahmed , Eissa Ibrahim
Published: September 2021

Background: Drug repurposing is the fastest effective method to provide treatment for coronavirus disease (COVID-19). Drugs that targeting a closely related virus with similar genetic material such as hepatitis C virus (HCV) and more specifically targeting a similar viral protease would be an excellent choice. Methods: In this study, we carried out a virtual screening for fifteen anti HCV drugs against COVID-19 main protease using computational molecular docking techniques. Moreover, Velpatasvir (4) and Sofosbuvir (13) drugs were further evaluated through molecular dynamics simulations followed by calculating the binding free energy using the molecular mechanics generalised born/solvent accessibility (MM-GBSA) approach. Results: The binding affinity descending order was N3 natural inhibitor (1), Velpatasvir (4), Sofosbuvir (13), Ombitasvir (3), Glecaprevir (2), Asunaprevir (8), Paritaprevir (10), Grazoprevir (11), Elbasvir (6), Ledipasvir (5), Daclatasvir (7), Pibrentasvir (9), Simeprevir (12), Dasabuvir (14), Taribavirin (16) and finally Ribavirin (15). Molecular dynamics simulation reveals that Sofosbuvir (13) has exciting properties and it was stable within the active site; it also showed good MM-GBSA compared to the natural inhibitor N3. Conclusion: Our results could be auspicious for fast repurposing of the examined drugs either alone or in combinations with each other for the treatment of the COVID-19. Furthermore, this work provides a clear spot on the structure-activity relationship (SAR) for targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease and helps the design and synthesis of new drugs in the future targeting it as well.
Solubilization Methods for Paclitaxel and Docetaxel: An Overview
Authors: Pourkarim Fariba , Rahimpour Elaheh , Alvani Sima , Jouyban Abolghasem
Published: September 2021

Cancer is still a serious disease with high incidence over the past decades. Many anticancer drugs are discovered and used to treat cancer, among them, taxanes such as paclitaxel and docetaxel have high lipophilicity and low aqueous solubility which is further magnified considering the strong need for administering them by intravenous infusion. Currently, the poor water-solubility of taxanes is improved by prodrug formation, conjugation, inclusion complexation, micellar solubilization and liposome-based formulations. Recent achievement for solubilization of taxanes are reviewed and critically discussed regarding their pharmaceutical and chemical applications.
Preventive use of Calcitriol versus cholecalciferol on biochemical markers of Metabolic Bone Disease (MBD) in very low birth weight infants: a pilot randomized clinical trial
Authors: Hosseini Mohammad bagher , Hosseini Nafiseh , Entezari-Maleki Taher , Salimi Zakieh
Published: September 2021

About 55% of extremely-low-birth-weight (birth weight < 1000 g) and 23% of very-low-birth-weight infants (birth weight < 1500 g) suffer from metabolic bone disease (MBD). There are limited data on the use of calcitriol (1, 25-dihydroxycholecalciferol) to prevent or treat MBD in preterm infants. Therefore, this study aimed to compare the preventive effect of calcitriol and cholecalciferol on the biochemical markers of MBD in preterm infants. This study was a pilot randomized controlled trial conducted in the Alzahra teaching hospital of Tabriz University of Medical Sciences. we randomized 72 very-low-birth-weight infants in two groups of calcitriol 0.25 µg/day and cholecalciferol 400 IU/day. Biochemical markers, including serum 25-hydroxyvitamin D, Alkaline phosphatase (ALP), Phosphorus (P), calcium (Ca), Parathyroid hormone (PTH), and tubular reabsorption of phosphate (TRP) levels were checked at baseline, three, and five weeks after medication, consecutively. After three weeks of supplementation, infants in the cholecalciferol group had higher levels of serum 25-hydroxyvitamin D (P=0.001) and lower levels of urine phosphate (P=0.009); There were no significant differences in other biochemical markers. At the end of the fifth week, there was no significant difference between the two groups in terms of biochemical markers. Conclusion: The study indicated that the use of cholecalciferol caused a lower urinary loss of phosphate in very-low-birth-weight infants at a short time; however, these findings were not sustained during the study period.
Nicolau syndrome: a review of case studies
Authors: Mojarrad Paria , Mollazadeh Hamid , Barikbin Behnaz , Oghazian Mohammad Bagher
Published: September 2021

Nicolau syndrome, although it is quite rare, often occurs following intramuscular injections of different medications, especially diclofenac and penicillins. Accordingly, its symptoms usually begin with severe pain during injection, leading to ulceration and necrosis of the local tissue over time. Immediate diagnosis and treatment in the case of this syndrome, are of great importance. There are no established criteria for Nicolau's diagnosis, and preferably, these can be achieved by examining the patient's symptoms and eliminating differential diagnoses. The proposed treatments are primarily symptomatic therapy and measures such as fasciotomy, debridement, and plastic surgery provided in the affected area. The exact cause of this syndrome has not been determined yet. However, since vasospasm, thrombosis, and embolism have been observed in majority of Nicolau syndrome cases, so any intra-arterial/para-arterial injection or any other factor leading to these three conditions could be hypothetically regarded as the cause of this problem. This review aims to provide a comprehensive overview of Nicolau's symptoms, diagnosis, treatment methods, and prevention. It also investigates the association between the incidence of this disease and some factors such as gender, age, injection method, and causative drugs, in order to widen our understanding on this syndrome and help practitioners with a much faster diagnosis method and step-by-step approach to Nicolau syndrome.
Effect of garlic (Allium sativum) extract on salivary streptococcus mutans: a systematic review and meta-analysis
Authors: Torbati Mostafa , Emamverdizadeh Parya , Torbati Mohammadalili , Maghalian Mahsa , Mirghafourvand Mojgan
Published: September 2021

Background: Oral and dental diseases are among the common health conditions which can have different effects on the individuals’ health and quality of life. The objective of this study was to examine the effect of garlic (Allium sativum) extract on saliva Streptococcus mutans (primary outcome) and its side effects (secondary outcome). Methods: In the present systematic review and meta-analysis, English and Persian databases (PubMed, Cochrane Library, Google Scholar, Scopus, Web of Science, SID, and Magiran) were systematically searched until February 25, 2021. The quality of the included studies was examined using Cochrane handbook, and the meta-analysis was carried out using RevMan 5.3. Heterogeneity of the studies was analyzed by index I2. Moreover, the quality of the evidence was assessed through GRADE approach. Results: A total of 93 studies were found on the databases; 89 articles were screened by title and abstract review and were removed as 19 studies were repetitive and 70 studies were unrelated to the subject under study. Ultimately, 4 articles with a sample size of 171 participants were included in this study, and two of the four studies were meta-analyzed. In all the 4 studies, garlic extract was effective in reducing the number of saliva Streptococcus mutans colonies compared to the control group. The results of the meta-analysis showed that using garlic extract mouthwash significantly decreased the average number of saliva Streptococcus mutans colonies (Mean Difference: -3.32; 95%CI: -4.39 to -2.26; P<0.00001). Conclusion: Although this review study indicated the significant effect of garlic extract in reducing saliva Streptococcus mutans, the evidence is not sufficient enough to recommend garlic extract to fight saliva Streptococcus mutans, and more clinical trials with stronger designs and larger sample sizes are needed.
Qualitative and quantitative analysis of anti-viral compounds against SARS-CoV-2 protease enzyme by molecular dynamics simulation and MM/PBSA method
Authors: Sepehri Saghi , Hashemidanesh Niloufar , Mahnam Karim , Asham Hila
Published: September 2021

Background: A significant worry for global public health is the international spread of the coronavirus disease-19 triggered through the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, an attempt was performed to qualitative and quantitative analysis of a series of compounds against SARS-CoV-2 main protease (M<[pro]) by in silico studies. Methods: About one hundred anti-viral compounds were collected from DrugBank database. In the second stage, molecular docking simulation was carried out to identify interactions of the molecules with the key residues in the M<[pro] active site. Finally, the molecular dynamics simulation of four top-ranked compounds and X77 as Co-crystal ligand were investigated. Results:Based on molecular docking studies, four compounds DB00224, DB00220, DB01232 and DB08873 exhibited the best results among compounds against M<[pro] enzyme. Additionally, molecular dynamic simulation and free binding energy were accomplished to compute the interaction energies and stability of the top-ranked compounds at the active site. The binding energy portions of the compounds into the enzyme active site exposed that Van der Waals and non-polar interactions were fundamental factors in the molecule binding. The ligand connections were steadied via hydrophobic interactions and several key hydrogen bonds especially with Glu166 and His41 residues into the active site. Conclusion: According to calculations of docking and MD, it was observed that the active site is mostly hydrophobic, where the value of the ∆Evdw is higher than that of the ∆Eele. Additionally, the results showed the steady of selected ligands binding with SARS-CoV-2 M<[pro] active site.
Anticancer effects of Melissa officinalis: A traditional medicine
Authors: Faraji Parviz , Araj-Khodaei Mostafa , Ghaffari Maryam , Ezzati Nazhad Dolatabadi Jafar
Published: September 2021

Melissa officinalis (M. officinalis) is an herbal-based plant from the family of Lamiaceae and native to Europe and the Mediterranean region, widely used to cure various cancers. Phytochemical investigations proved different compounds such as polyphenolic compounds, flavonoids, and essential oil in the stem and leaves of M. officinalis as main ingredients contributing to different antitumor activity, including antiproliferation and antioxidant antiangiogenetic, antimigratory, antiapoptotic, and change in cell cycle profile of cancer cells. Herbal formulations with colorful ingredients use several types of these mentioned biological processes to display synergistic cancer treatment activities. M. officinalis extracts a wide range from water to ethanol using varied mechanisms to reduce the viability of cancer cells. Hence, scientists are currently interested in evaluating these extracts based on the medical plant to minimize the adverse effects of conventional anti-cancer drugs and discover these mechanisms to pave the way for future studies. This review aimed to discuss the recent studies that M. officinalis have used as an anti-cancer agent to investigate its potential effect on several types of cancer. Therefore, after a short introduction of M. officinalis, we will explain the several biological processes by which M. officinalis exert an anti-cancer effect.
Coumestrol alleviates oxidative stress, apoptosis and cognitive impairments through hippocampal estrogen receptor-beta in male mouse model of chronic restraint stress
Authors: Fekri Kiarash , Mahmoudi Javad , Sadigh-Eteghad Saeed , Farajdokht Fereshteh , Mohajjel Nayebi Alireza
Published: September 2021

Background: Coumestrol is well-known as a natural estrogen receptor-beta modulator. Since the role of estrogen receptors in controlling stressful situations has already been reported and their cognitive functions in hippocampus seem to be independent of sexual tasks, the aim of this study was to investigate the improving effects of this phytoestrogen on negative consequences of exposing male mice to chronic restraint stress. Methods: This study was divided into two separate but consecutive phases. In the first phase, the possible effects of Coumestrol (30, 60, 120 µg.kg-1.day-1, i.p.) and its vehicle (sesame oil) on restraint stress-induced cognitive impairments, oxidative stress and apoptosis were evaluated. During the second phase, a selective estrogen receptor-beta antagonist was used to investigate the possible involvement of beta-type estrogen receptors in these processes. Morris water maze and novel object recognition tests were performed to evaluate memory while elevated plus maze test was used to measure the level of anxiety. Spectroscopy and western blotting methods were also employed to evaluate oxidative and apoptotic status in hippocampal tissue. Furthermore, serum level of corticosterone was measured for each group. Results: Behavioral tests indicated memory enhancing and anxiolytic effects of coumestrol. Biochemical evaluations also proved its antioxidant and anti-apoptotic potential. On the other hand, the mentioned behavioral and biochemical improvements were reversed in the group treated with estrogen receptor-beta antagonist. Conclusion: Coumestrol may ameliorate negative consequences of exposure to chronic stress such as oxidative stress, apoptosis and cognitive impairments, via the modulation of beta-type estrogen receptors in hippocampus.
Impact of storage conditions on a new child-friendly dispersible tablet for treating Tuberculosis in pediatrics.
Authors: González Javier Suárez , Santoveña Estévez Ana , Soriano Mabel , Fariña Jose Bruno
Published: September 2021

Background: In 2020 the composition and procedure to elaborate a new formulation containing Isoniazid, Pyrazinamide and Rifampicin to treat tuberculosis in pediatric patients was published. The temperature and relative humidity in Tuberculosis-endemic countries are high, > 30ºC and > 70% respectively and thus these meteorological conditions required a new dosage form. The objective of this work is to register changes in tablet quality and stability over time when exposed to different storage conditions according to ICH. Method: Tablets were subjected to accelerated, long term and low relative humidity conditions. The effect of light was also tested. Quality was measured by evaluating weight changes tensile strength, disintegration time, and drug content. Hydrazine formation was also evaluated as it is considered a mutagenic degradation product. Results: Tablets stored at low relative humidity showed the best stability. There was no statistically significant difference between tablets exposed to or protected from light. Moreover, the formation of Hydrazine was not detected during stability studies. Conclusion: This new dosage form for treating Tuberculosis is stable and able to maintain its quality when appropriate storage conditions are used.
Enhancement of Cisplatin Sensitivity by Microwave Radiation in Ovarian Cancer Cells
Authors: Tayebi-khorami Mansour , Chegeni Nahid , Tahmasebi Birgani Maryam , Danyaei Amir , Fardid Reza , Zafari Jaber
Published: September 2021

Background: Nowadays, ovarian cancer is the most lethal gynecological cancer worldwide. Tumor debulking surgery followed by Cisplatin-based chemotherapy is the first line of ovarian cancer therapy. However, many patients experience a relapse of the disease due to chemotherapy resistance. Accordingly, this study aims to investigate the ability of microwave (MW) radiation to increase the susceptibility of ovarian cancer cells toward Cisplatin (Cis). Methods: Firstly we designed a hand-made electromagnetic field exposure system and CO2 incubator to irradiate cells with a frequency equal to 2450±30 MHz and a power density of 2.47 mW/cm2 at a distance of 30 cm from the antenna. Two ovarian cancer cell lines A2780 (Cisplatin-sensitive) and A2780CP (Cisplatin-resistant) were subjected to either Cis, MW alone or Cisplatin + microwave radiation (Cis+MW). Cell viability, apoptosis, and P53 gene expression was assessed following drug/radiation exposure. Results: After 48 hours of treatment the combination of Cis and MW radiation has significantly inhibited the growth of the A2780 and A2780CP cell lines in comparison with Cis-control groups. The percentages of early apoptosis induced by Cis+MW was significantly increased in comparison with Cis alone. P53 expression was significantly upregulated after treatment with Cis+MW. Conclusion: It can be concluded that MW radiation has been able to decrease the resistance of ovarian cancer cells to Cis and it may improve the chemotherapy protocol for ovarian cancer treatment.
Structure based virtual docking and molecular dynamics guided identification of potential phytoconstituents from traditionally used female antifertility plant
Authors: Priya Keerthi , Manandhar Suman , Sankhe Runali , Setty M Manjunath , Babu UV , Pai Sreedhara Ranganath
Published: September 2021

Background: Oral contraceptives are very widely used agents to check unwanted pregnancies. They contain synthetic analogues of estrogen and progesterone hormones. Estrogen is an important hormone that plays a significant role in menstrual cycle, ovulation, fertilization and implantation. Estrogen receptor α (ERα) can modulate the ovulation, fertilization or receptivity of the uterus. Oral contraceptives pose mild to severe adverse effects such as menstrual cycle disorders, metabolic alterations and increased risk of cancers. It is essential to identify and screen alternative contraceptives that are safer to use. The present study was aimed at identifying the compounds from Cissampelos pareira that is traditionally used for antifertility activity. Methods: The compounds reported from the plant are collected and prepared using the protein preparation wizard. The protein, ERα was selected from protein data bank (1G5O) and prepared. The ligands were docked with the protein and the hits were selected for further screening of free energy calculation, induced fit docking and molecular dynamics simulations based on the respective scores and various interactions. Results: Among various compounds, Coclaurine and Norruffscine have been identified to interact with ERα and possess similar interactions as that of the endogenous ligand, estradiol. The compounds also showed drug-like properties in Qikprop analysis and promising result in the molecular dynamics simulation studies. Conclusion: Considering the dock scores, molecular interactions with the ERα receptor and energy calculations, the compounds Coclaurine and Norruffscine were found to have good binding properties. Further in vitro and in vivo evaluation are warranted for confirmation.
Lipid Polymeric Hybrid Nanoparticles: Formulation Techniques and Effects on Glioblastoma
Authors: Baghel Yudhishtir Singh , Bhattacharya Sankha
Published: September 2021

Introduction: In the pharmaceutical industry, liposomes and polymeric nanoparticles are the two most commonly studied delivery vehicles. A new technique uses lipid-polymeric hybrid nanoparticles (LPHNPs) with a polymeric core, and a shell made up of lipid-lipid-PEG lipids. They have properties which complement polymer nanoparticles and liposomes, and they have the potential to improve the physical stability and biocompatibility of the active pharmaceutical ingredient encapsulated in them. Evaporating the solvent from a dual-phase solution containing lipid and polymer is one of the most effective methods for producing the lipid polymeric hybrid nanoparticles. The LPHNPs applications has also been significantly expanded to include combinational and active targeted drug delivery, as well as delivery of genetic materials, vaccines, and diagnostic imaging agents, in addition to single drug delivery for anticancer therapy, like Glioblastoma. Main goal: The main agenda of this compilation was to address the effects of LPHNPs on Glioblastoma treatment. This compilation also highlights some of the formulation techniques and issues that arise during the preparation of LPHNPs. This review also discusses recent developments in core-shell lipid-polymer hybrid nanoparticles, which were conferred in considerable detail later in this article. Conclusion: The main issue which arises while using nanoparticles with polymer is entrapment efficiency. Because of their hybrid components, LPHNPs have proven to solve this problem to a large extent. The recent research trends suggest that lipid polymeric hybrid nanoparticles will prove to be highly effective or productive in treating diseases such as Glioblastoma.