فهرست مطالب
Advanced Pharmaceutical Bulletin
Volume:12 Issue: 2, Mar 2022
- تاریخ انتشار: 1401/01/23
- تعداد عناوین: 22
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Pages 206-216
After SARS and MERS outbreaks, COVID-19 is the third coronavirus epidemic that soon turned into a pandemic. This virus causes acute respiratory syndrome in infected people. The mortality rate of SARS-CoV-2 infection will probably rise unless efficient treatments or vaccines are developed. The global funding and medical communities have started performing more than five hundred clinical examinations on a broad spectrum of repurposed drugs to acquire effective treatments. Besides, other novel treatment approaches have also recently emerged, including cellular host-directed therapies. They counteract the unwanted responses of the host immune system that led to the severe pathogenesis of SARS-CoV-2. This brief review focuses on Mesenchymal stem cell (MSC) principles in treating the COVID-19. The US clinical trials database and the world health organization database for clinical trials have reported 82 clinical trials (altogether) exploring the effects of MSCs in COVID-19 treatment. MSCs also had better be tried for treating other pathogens worldwide. MSC treatment may have the potential to end the high mortality rate of COVID-19. Besides, it also limits the long-term inability of survivors.
Keywords: COVID-19, SARS-CoV-2, Stem cell therapy, Mesenchymal Stem cell, Cytokine Storm -
Pages 219-236
Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has been recently identified as a novel member of beta coronaviruses (CoVs) and the cause of coronavirus disease 2019 (COVID-19). It has been first discovered in China and soon has spread across continents with an escalating number of mortalities. There is an urgent need for developing a COVID-19 vaccine to control the rapid transmission and the deleterious impact of the virus. The potent vaccine should have a good tolerable and efficacious profile to induce target-specific humoral and cellular immune responses. It should also exhibit no or minimal detrimental effects in children, young adults, and elderly people with or without co-morbidities from different racial backgrounds. Previously published findings of SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) played vital role in the characterization of surface spike proteins as the tool of entry of the SARS-CoV-2 into host cells. It has become evident that SARS-CoVs have high genetic similarity and this implies antecedent vaccination strategies could be implicated in the production of COVID-19 vaccines. Although several vaccines have been approved and rolled out, only a handful of them have passed the three phases of clinical studies. This review highlights the completed, and ongoing clinical trials of COVID-19 vaccines and efforts are being made globally to avert the pandemic.
Keywords: SARS-CoV-2, Coronavirus, COVID-19 vaccines, Clinical trials -
Pages 237-247
ype 2 diabetes mellitus (T2DM) is a chronic metabolic abnormality leading to microvascular and macrovascular complications. Non-insulin Incretin mimic synthetic peptide exendin-4 was introduced as an anti-diabetic drug which helped diabetic patients with triggering insulin secretion; further researches have revealed an effective role of exendin-4 in treatment of T2DM related diseases. Exendin-4 is approximately similar to Glucagon-like peptide, thus it can bind to the glucagon-like peptide-1 receptor (GLP-1R) and activated different signaling pathways that are involved in various bioactivities such as apoptosis, insulin secretion and inactivation of microglial. In this review, we investigated the interesting role of exendin-4 in various kinds of T2DM related disorders through the activation of different signaling pathways.
Keywords: Diabetes Complications, Exendin-4, Signaling Pathways -
Pages 248-261
Cancer was predicted as the leading cause of death and the most important obstacle to the increased life expectancy in the 21st century worldwide. The World Health Organization (WHO) estimated number of new cases of cancers in 2020 about 19 million, and this number is estimated to be more than 295 300 000 people up to 2040 (more than 55% increase during next 20 years). Standard treatments for cancer include surgery, radiotherapy, and chemotherapy. However, all of these methods have dangerous side effects, so researchers are more interested in finding novel and less risky therapies. In recent years, there has been a great deal of interest in the development of anticancer agents obtained from foods or natural products. The relative safety of natural and food-derived compounds makes them attractive alternatives to conventional cancer treatment drugs. As a result, the majority of people are advised to use complementary and alternative medicine to treat and prevent cancer. In recent years, honey, as a natural product, has attracted many researchers’ attention as an alternative to conventional anticancer drugs. Natural honey has long been used as a medicine and nutrient and its beneficial effects on various diseases in animal and human models have been studied. It was found that it has a wide range of therapeutic properties, including antioxidant, antibacterial, antiviral, anti-fungal, anti-diabetic, anti-inflammatory, anti-hypertensive, antiarrhythmic, wound healing, and liver protection benefits. This article aimed to review the role of natural honey in the prevention and treatment of a number of important cancers and their subsequent complications
Keywords: Natural honey, Human diseases, Cancer prevention, Cancer treatment -
Pages 262-273
Lung cancer (LC) is the most common cause of cancer-related death worldwide. Patients with LC are usually diagnosed at advanced phases. Five-year survival rate in LC patients is approximately 16%. Despite decades of research on LC treatments, clinical outcomes are still very poor, necessitating to develop novel technologies to manage the disease. Considering the role of genetic and epigenetic changes in oncogenes and tumor-suppressor genes in cancer progression, gene therapy provides a hot spot in cancer treatment research. Gene therapy offers less side effects compared to conventional methods such as chemotherapy. Unlike the traditional approaches of gene therapy that have temporary effects, using genetic modification tools can offer persistent cure. Over the past a few years, many studies have effectively used the CRISPR–Cas9 approach to modify gene expression in cells. This system is applied to induce site-specific mutagenesis and epigenetic modifications and regulate gene expression. In this review, we discuss recent applications of the CRISPR–Cas9 technology in treating LC.
Keywords: CRISPR, CAS, Lung, Cancer, Genetic modification, eticman2005@gma -
Pages 274-282
Vaccination is one of the important approaches in the prevention and control of diseases. Although the capacity to present antigens other than the disease-specific antigen in the traditional vaccine composition provides a potential benefit by increasing its protective efficacy, many components that are not needed for the related disease are also transferred. These components can reduce vaccine activity by lowering immunity against protective antigens. The reasons such as the low effectiveness of traditional vaccines and the high cost of production and time-consuming reasons show that it is necessary to develop a new vaccine method for our world, which is struggling with epidemics almost every year. Among nucleic acids, mRNA has many advantages, such as genomic integration, induction of anti-DNA autoantibodies, and immune tolerance induced by long-term antigen expression. mRNA vaccines have become a therapeutic target for reasons such as efficacy, safety, fast and non-expensive production. The fact that mRNA triggers both humoral and cellular immunity and goes only to the cytoplasm, not to the nucleus, makes it highly efficient. The mRNA must cross the lipid bilayer barrier and entry to the cytoplasm where it is translated into protein. There are two main ways of mRNA vaccine delivery for this: ex vivo loading of mRNA into dendritic cells and direct injection of mRNA with or without a carrier. Studies continue to understand which delivery system is therapeutically more efficient. Preclinical and clinical trials showed that mRNA vaccines trigger a long-lasting and safe immune response.
Keywords: mRNA vaccine, Antigen-presenting cell, Dendritic cells, Vaccine delivery systems, Cancer therapy -
Pages 283-297
Human schistosomiasis is a disease that mostly plagues the destitute of various tropical and sub-tropical countries, particularly in sub-Saharan Africa and South America. It has significant effects on various health and economic-related matters. Globally, the burden of schistosomiasis has been controlled with a single chemotherapeutic drug, Praziquantel, which has recently demonstrated several clinical issues, including its inability to destroy juvenile schistosome worms and drug resistance because of its extensive use. The use of organometallic moieties in biological and medicinal chemistry has developed greatly and has led to their use in various anti-cancer and anti-infectious agents. The abundance of a range of organometallic compounds that can cause damage to the parasite has received tremendous feedback, with many already at clinical trials. The distinct redox biology of the schistosome parasite is a vulnerable element to the survival of the worm and has steered attempts toward the use of redox-directed bioorganometallic compounds. Disruption of the schistosome redox homeostasis through organometallic ions provides a novel drug target that could be used in overcoming the drawbacks of the mainstream drug and one that could possibly bypass the emergence of drug resistance.
Keywords: Bioorganometallic compounds, Praziquantel, Reactive oxygen species, Schistosoma mansoni, Schistosomiasis, Redox biology -
Pages 298-308
Tyrosine kinase inhibitors (TKIs) are used as targeted therapy for cancer by inhibiting the signaling pathway and tumor growth. Many TKIs got approved by FDA in recent times for the treatment of cancer by oral route. However, the TKIs have formulation challenges leading to compromised bioavailability which can cause a weak therapeutic response. The cancer nanotherapeutics using nanocarriers based drug delivery has emerged as an advanced tool to provide a solution to formulation challenges and a better cancer therapy by overcoming the limitations in conventional cancer therapy. This review describes the various formulation issues of anticancer drugs with a special reference to TKIs, as well as the capability of solid lipid nanoparticles for an efficient nano targeted cancer drug delivery.
Keywords: Solid lipid Nanoparticles (SLNs), Tyrosine kinase inhibitors (TKIs), Bioavailability -
Pages 309-318
Enzymes are one of the main biocatalysts with various applications in the food industry. Stabilization of enzymes on insoluble carriers is important due to the low reuse, low operational stability, and high cost in applications. The immobility and the type of carrier affect the activity of the immobile enzyme. Hydrogels are three-dimensionally cross-linked macromolecular network structures designed from various polymers. Hydrogels can provide a matrix for an immobile enzyme due to their extraordinary properties such as high water absorbing capacity, carrier of bioactive substances and enzymes, biocompatibility, safety, and biodegradability. Therefore, this study mainly focuses on some enzymes (Lactase, Lipases, Amylases, Pectinase, Protease, Glucose oxidase) that are of special importance in the food industry. These enzymes could be immobilized in the hydrogels constructed of macromolecules such as kappa-carrageenan, chitosan, arabic gum, pectin, alginate, and cellulose. At last, in the preparation of these hydrogels, different enzyme immobilization methods in macromolecular hydrogels, and effect of hydrogels on enzyme activity were discussed.
Keywords: Hydrogels, Enzyme immobilization, Food industry -
Pages 319-328
Today the crisis of coronavirus disease 2019 (COVID-19) pandemic represents a threat worldwide because it is a leading cause of human morbidity and mortality. Besides, it possesses a destroying impact on countries’ economies. Therefore, there is an urgent need for hard research work and global collaboration to find a potential therapy. In this review, structural genomic variations in COVID 19 and further therapeutic options of Coronaviridae family or COVID 19 are expressed. Lectins are natural proteins, which can exist in algae, higher plants, banana, actinomycetes, fungi, and archaea, and they have antiviral properties. Griffithsin lectin, isolated from red algae, has noteworthy efficacy against lethal SARS-CoV infection, human coronaviruses, and other animal coronaviruses. Furthermore, all mannose-specific plant lectins have anti-coronaviruses properties except for garlic lectins. However, lectins from mushrooms can act as immunomodulators by activating T-lymphocyte or stimulating dendrites or cytokines. The lectin may hinder glucans on viral spike protein and prevent entry and the virus's release. Lectin's anti-coronavirus activities include a glimmer of hope to tackle the global COVID 19 crisis and inspire more scientific work on carbohydrate-binding agents against SARS-CoV-2.
Keywords: Coronaviruses, Genomic variations, Therapeutic options, Lectins -
Pages 329-335Purpose
Kojic acid a natural metabolite (KA) and its dipalmitate ester, kojic acid dipalmitate (Kadp) are both prescribed to treat skin hyperpigmentation. Stress test reveals the intrinsic stability of active ingredients and leads to selection of the suitable formulations. This research evaluates the comparative stability of KA and its di-palmitate ester under liquid oxidative stress.
MethodsThe HPLC-UV/PDA method with a C18 column was utilized. Liquid oxidative stress was induced using hydrogen peroxide (H2O2). Degradation was separately induced for each drug, and they were compared to each other.
ResultsKadp degraded more rapidly in similar liquid oxidative stress conditions than KA did. The superior degradation model was the first order for both drugs based on the MPE values, indicating the dependency of the reaction rate on the initial concentration of the reactive substance. Ring opening was proposed as the most possible theory for KA and Kadp oxidative degradation.
ConclusionIt is suggested to use KA instead of Kadp in less stable formulations, such as extemporaneous preparations. The incorporation of antioxidant excipients in Kadp formulations is recommended for yielding better stability results. Formulating Kadp in the internal phase of o/w emulsion formulations may protect this susceptive molecule from oxidative degradation during the shelf life of the pharmaceutical preparation. Further studies are required to study the exact mechanism of the degradation process.
Keywords: Stress test, Oxidative stress, Pharmaceutical Preformulation, HPLC, Kinetic, Degradation mechanism -
Pages 336-345Purpose
Pulmonary Tuberculosis (TB) is a worldwide life-threatening infection. The recommended anti-TB regimen contains oral administration of classical first-line drugs such as rifampin for 6-24 months which often leads to low patient compliance due to high adverse effects; therefore, lung localized pulmonary delivery of anti-TB agents may be a suitable alternative. Proliposomes free-flowing powders are well-known carriers for lung delivery since they can form liposomes by hydration. Liposomes are safe and useful carriers for lung delivery due to their phospholipid structure.
MethodsPorous lactose and mannitol as proliposome carriers were prepared by spray drying technique using sucrose and citric acid as templating agents. Design expert® software was used to develop forty formulations based on the porous and non-porous carriers, which were characterized with respect to their weight yield, density, and flowability. Rifampin-loaded hydrated liposomes were produced and evaluated for size, morphology, loading capacity and encapsulation efficiency. The optimized proliposomes in vitro release and aerosolization properties were evaluated. Solid-state analysis was confirmed by Differential Scanning Calorimetry (DSC).
ResultsPorous lactose surface area was 80 folds higher than non-porous one, respectively. Optimized porous-based proliposome indicated the acceptable aerosolization properties, including mass median aerodynamic diameter (MMAD) of 6.21±0.36 µm and fine particle fraction (FPF) of 9.17±0.18% with a fast rifampin release (80%) within one hour. DSC results proved that there was no change in the solid-state of rifampin during the production process.
ConclusionHence, it seems; rifampin loaded inhalable proliposomes may be a suitable system for delivering liposomal rifampin into the lungs.
Keywords: aerosolization properties, carrier porosity, dry powder, proliposome, rifampin -
Pages 346-355Purpose
Conventional topical dosage forms face with some challenges like low intraocularbioavailability, which could be overcome by application of novel drug delivery systems.Therefore, this study was conducted to prepare azithromycin (AZM)-loaded chitosan/polyvinylalcohol/polyvinyl pyrrolidone (CS/PVA-PVP) nanofibers with the prolonged antibacterialactivity by electrospinning method.
MethodsAfter preparation of nanofibers, they were characterized in terms of physicochemicaland morphological properties. In vitro and in vivo release of the drug from nanofibers wereevaluated using microbial assay against the Micrococcus luteus. Antibacterial efficacy of thenanofibers was assessed. The ophthalmic irritation test was also performed. MTT test wascarried out to evaluate cytotoxicity of the formulations.
ResultsAll the formulations were found to be stable with uniform thickness, weight, and drugcontent. Nanofibers had a diameter range from 119 ± 29 to 171 ± 39 nm. The inserts were nonirritantand non-toxic to the rabbits’ eye. Based on the obtained results, the crosslinked AZMnanofibers showed slower and more controlled drug release in tear fluid compared to the noncrosslinkedones, within 184 hours.
ConclusionOur results revealed that the prepared nanofibers could be considered as suitableand non-invasive inserts for the prolonged ophthalmic delivery of AZM.
Keywords: Azithromycin, Chitosan, Controlled release, Microbial assay, Nanofibers, Ophthalmic drug delivery -
Pages 356-365Purpose
Stem cells can exhibit restorative effects with the commitment to functional cells. Cell-imprinted topographies provide adaptable templates and certain dimensions for the differentiation and bioactivity of stem cells. Cell sheet technology using the thermo-responsive polymers detaches the "cell sheets" easier with less destructive effects on the extracellular matrix (ECM). Here, we aim to dictate keratinocyte-like differentiation of mesenchymal stem cells by using combined cell imprinting and sheet technology.
MethodsWe developed the poly dimethyl siloxane (PDMS) substrate having keratinocyte cell-imprinted topography grafted with the PNIPAAm polymer. Adipose tissue-derived mesenchymal stem cells (AT-MSCs) were cultured on PDMS substrate for 14 days and keratinocyte-like differentiation monitored via the expression of involucrin, P63, and cytokeratin 14.
ResultsData showed the efficiency of the current protocol in the fabrication of PDMS molds. The culture of AT-MSCs induced typical keratinocyte morphology and up-regulated the expression of cytokeratin-14, Involucrin, and P63 compared to AT-MSCs cultured on the plastic surface (p<0.05). Besides, KLC sheets were generated once slight changes occur in the environment temperature.
ConclusionThese data showed the hypothesis that keratinocyte cell imprinted substrate can orient AT-MSCs toward KLCs by providing a specific niche and topography.
Keywords: Adipose tissue-derivedmesenchymal stem cells, Cell-imprinting, Cell sheet engineering, differentiation, poly N-Isopropyl acrylamide(PNIPAAm), Topography -
Pages 366-374Purpose
Universal stress protein from S. mansoni, designated as G4LZI3, was previously hypothesised as a druggable target and vaccine candidate for human schistosomiasis. The purpose of this study is to characterize a purified recombinant G4LZI3 preliminarily for subsequent structural characterisation, which will provide baseline structural data for future functional studies for the discovery, design and development of new schistosomal drugs for the treatment, control and elimination of schistosomiasis.
MethodsRestriction digest analysis of a GenScript-synthesised codon-optimised G4LZI3 gene construct was carried out to ascertain its integrity and size. Thereafter, the pQE30-G4LZI3 construct was transformed into an M15 bacterial expression host. Transformed cells were induced with isopropyl β-D-thiogalactoside for recombinant protein expression of an appreciable amount of pQE30-G4LZI3, which was subsequently purified with fast protein liquid chromatography and a size exclusion chromatographic purification scheme. Preliminary biophysical characterisation of the 6X His-tagged G4LZI3 was done to determine its secondary structure characteristics and protein stability.
ResultsA molecular weight protein of 20.3 kDa was confirmed subsequent to restriction digest analysis, while heterologous protein expression yielded a highly soluble and considerable amount of histidine-tagged G4LZI3 protein, which was successfully purified to homogeneity. Biophysical characterisation indicated that the protein was well folded, heat-stable, had the functional groups and secondary structure composition required and was thus amenable to further structural characterisation and determination.
ConclusionBiophysical characterisation of purified G4LZI3 showed that further structural studies can be embarked upon on the use of G4LZI3 as a druggable target and possibly a vaccine target against schistosomiasis via vaccinomics.
Keywords: Biophysical characterization, G4LZI3, Recombinant proteins, Schistosoma mansoni, Schistosomiasis -
Pages 375-382Purpose
Acute pancreatitis (AP) which is distinguished by local pancreatic necrosis, following by systemic organ failure is known as an inflammatory disease. Up to now, there are only a few treatment options accessible for patients suffering from AP. In this study, we aimed to examine the anti-inflammatory capacities of human bone marrow-derived mesenchymal stromal cells (hBM-MSC) in a detailed AP model experiment.
MethodsAP was induced in C57BL/6 mice by intraperitoneal administration of cerulein (100 µg/kg/h × 7 doses) at intervals of 1 hour (h). Then, 2×105 MSCs were infused in the AP mice by tail vein 6 h after the last cerulein injection. Mice were sacrificed 12 h following the injection of hBM-MSC, and blood samples and pancreas tissues were obtained.
ResultsWe first determined the presence of transplanted hBM-MSC in the pancreas of mice with AP, but not the control mice. Our data indicate that administration of hBM-MSCs to mice with AP lead to (i) decreased serum levels of amylase, lipase and myeloperoxidase activities, (ii) downregulation of proinflammatory cytokine, macrophage inflammatory protein 2 (MIP-2), and (iii) upregulation of the anti-inflammatory cytokine, interleukin 10 (IL-10). Moreover, hBM-MSC administration results in notably attenuated cerulein-induced histopathological alternations and edema.
Conclusionwe demonstrate that hBM-MSC attenuates AP signs and indicating that hMB-MSC therapy could be a suitable approach for the treatment of inflammatory disease such as AP.
Keywords: Acute pancreatitis, Cerulein, Inflammation, Human bone marrow-derivedmesenchymal stromal cells -
Pages 383-388Purpose
Calcium-sensing receptor (CaSR) has been associated with breast cancer metastasis to the bone. Targeting chemoattractant factors, such as calcium, that are released in response to bone resorption could prevent metastasis and induce apoptosis of cancer cells. In the present study, we investigated the potential caspase 3/7 activation following treatment with a CaSR antagonist, NPS-2143, in breast cancer cells. In addition, the effects of NPS-2143 on breast cancer cell proliferation, migration and invasion were assessed.
MethodsColorimetric MTT assay was used to evaluate cell viability. Apo-one homogeneous caspase-3/7 assay was used to measure caspase 3/7 activities in breast cancer cells. Cell migration and invasion were assessed using scratch wound assay and matrigel invasion chambers, respectively. The protein expressions of p-ERK1/2, integrin β1 and Bcl-2 were evaluated using western blotting.
ResultsOur study revealed that NPS-2143 significantly reduced cell proliferation with half maximal (50%) inhibitory concentration (IC50) values of 4.08 and 5.71 µM in MDA-MB-231 and MCF-7 cells, respectively. NPS-2143 induced caspase 3/7 activation in MDA-MB-231 breast cancer cells which was accompanied with a remarkable reduction in the expression of Bcl-2 antiapoptotic protein. NPS-2143 suppressed migratory and invasive abilities of MDA-MB-231 cells with a significant reduction in the expression of p-ERK1/2 and integrin β1 proteins.
ConclusionOur study confirms the ability NPS-2143 to suppress proliferative, migratory and invasive effects of breast cancer cells which was accompanied by caspase 3/7 activation and suggests the potential of NPS-2143 as a promising anti-cancer molecule in breast cancer.
Keywords: Breast cancer, Calcium-sensing receptor, NPS-2143, Caspase 3, 7, Proliferation, Invasion -
Pages 389-397Purpose
Promising advances have been made in mesenchymal stem cell transplantation to re-induce the immune tolerance in neuroinflammatory animal models and Multiple Sclerosis patients. The available evidence demonstrated that immunomodulatory effects of mesenchymal stem cell are particularly exerted through releasing exosomes to their environment. We therefore, aimed to comparatively assess the potential effect of mesenchymal stem cells and mesenchymal stem cells-derived exosomes on proliferation and function of the CD4+CD25− conventional T cells, isolated from relapsing-remitting Multiple Sclerosis patients.
MethodsMesenchymal stem cells were isolated from human umbilical cord tissues and used for exosome isolation via ultracentrifugation. Both mesenchymal stem cells and mesenchymal stem cells-derived exosomes were evaluated for their anti-inflammatory effects against the proliferation of T cells isolated from two groups of individuals in vitro, MS patients and healthy subjects. Cytokine production of conventional T cells (interferon-γ, interleukin-10, and interleukin-17) was also assessed, using flow cytometry for the patients and healthy individuals.
ResultsHere, evidence shows that MSCs and MSC-derived exosomes dampen proliferation and percentage of conventional T cells that produce IFN-γ (healthy control: p<0.001) and interleukin-17 (healthy control: p<0.001, MS patients: p<0.001), with a significant increase of IL-10 producing cells in the patients and healthy individuals. Surprisingly, MSC-derived exosomes demonstrated higher immune-modulating properties on conventional T cells responses, compared to MSCs.
ConclusionThe current study, provides a novel approach of exocytosis on autoimmune therapy. In particular, Mesenchymal stem cell -derived exosomes, which are cell-derived biologics, could be considered as an alternative for Mesenchymal stem cells in treating multiple sclerosis.
Keywords: Relapsing-remitting MS, Mesenchymal stem cell, Exosome, Immunomodulation -
Pages 398-403Purpose
To investigate the downregulation of High Mobility Group AT-hook 2 (HMGA2) expression by small interfering RNAs (siRNAs) in PC3 prostate cancer cell line. HMGA2 belongs to the non-histone chromatin-binding protein family that serves as a crucial regulator of gene transcription. The overexpression of this gene is positively correlated with various prostate cancer-related properties. Thus, HMGA2 is an emerging target in prostate cancer treatment. This study aimed to examine the impact of siRNAs targeting HMGA2 on the viability, migration, and apoptosis processes of the PC3 prostate cancer cell line.
MethodssiRNA transfection was conducted with a liposome-mediated approach. The mRNA and protein expression levels for HMGA2 are evaluated by qRT-PCR and western blot analysis. The cytotoxic properties of HMGA2-siRNA were measured by MTT assay on PC3 cells. The migration of PC3 cells was measured by implementing a wound-healing assay. Apoptosis measurement was also quantified by TUNEL assay.
ResultsTransfection with siRNA significantly decreased both mRNA and protein levels of the HMGA2 gene in a dose-dependent manner after 48 hours. Also, we demonstrated that the knockdown of HMGA2 led to a reduction in cell viability, migration ability, and enhanced apoptosis of PC3 cells in vitro.
ConclusionOur findings recommend that the specific siRNA of HMGA2 may efficiently be able to decrease prostate cancer progression. Therefore, it may be a promising adjuvant treatment in prostate cancer.
Keywords: HMGA2, Gene therapy, Small interfering RNA, Prostate cancer, Apoptosis assay, Cell migration -
Pages 404-409Purpose
Apatinib has been utilized in colon cancer therapies but its efficiency and molecularmechanism are not fully understood. Chemotherapy in combination with non-toxic compoundscan be an effective treatment strategy for cancer. Consequently, this study was carried out toevaluate the effects of apatinib and piperine on colorectal cancer (CRC) cell line and theirpotential anti-cancerous mechanisms in vitro.
MethodsThe effects of apatinib and piperine on HCT-116 CRC cells were detected byassessing cell viability using MTT assay. The potential cytotoxic mechanisms of apatinib andpiperine were investigated by evaluating MDM-2 gene expression ratio using real-time PCRassay. Moreover, the glutathione peroxidase (GPX) activity and nitric oxide (NO) levels wereassessed by colorimetric assays.
ResultsThe proliferation rate of CRC cells decreased by increasing the concentrations ofpiperine or apatinib. When HCT-116 cells were treated with different concentrations of apatinibin combination with piperine, the synergistic effects were observed (combination index < 1).In HCT-116 cells treated with apatinib and piperine at the concentrations of 0.5×IC50 and0.2×IC50, the MDM-2 gene expression was downregulated and NO levels increased comparedto the untreated control cells and related single treatments. In addition, GPX activity significantlydecreased in combination treatment at 0.5×IC50 concentration of both agents versus singletreatments.
ConclusionApatinib in combination with piperine could significantly inhibit the growth ofCRC cells. These cytotoxic effects were induced by regulation of MDM-2 gene expression andinhibition of antioxidant marker.
Keywords: Colorectal cancer, Apoptosis, HCT-116 cells, Apatinib, Piperine -
Pages 410-418Purpose
Sulfated polysaccharide (SP) from Codium species has been reported for its anti-inflammatory activities. However, the effect of SP from C. edule on allergic responses has not been studied. The study was conducted to determine the effect of SP (F1) from C. edule on allergic contact dermatitis (ACD) induced by 2,4-dinitrofluorobenzene (DNFB) in female BALB/c mice.
MethodsF1 was isolated using DEAE Sepharose Gel Chromatography and chemically identified by LC-MS analyses. The effects of F1 on changes in ear thickness, allergic responses, and histology were evaluated. The effects of F1 on the production of inflammatory cytokines IFN- γ and TNF-α in serum were also quantified and compared with standard prednisolone therapy.
ResultsF1 was identified as a heteropolysaccharide with β-D-galactans and β-L-arabinans units. F1 was non-toxic at 2000 mg/kg. Administration of F1 in DNFB-challenged mice significantly suppressed the increase in ear thickness, erythema, desquamation, and proliferation of inflammatory cells. F1 significantly decreased the production of inflammatory markers, IFN- γ and TNF-α in a dose-dependent manner when compared to the untreated group (p<0.05).
ConclusionResults suggest that F1 from C. edule is a bioactive sulfated heteropolysaccharide with anti-inflammatory activity and might be a valuable candidate molecule for the treatment of allergic diseases such as ACD.
Keywords: Seaweed, Codium edule, Sulfated polysaccharide, Allergic contact dermatitis, Cytokines, Inflammation