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Recently, we reviewed the important role of carbohydrates and lipids metabolism in different clinical aspects of multiple sclerosis (MS) disease. In the current paper, we aimed to review the contribution of amino acids and their major derivatives to different clinical outcomes of the disease, including etiology, pathogenesis, diagnosis, prognosis, and treatment. In this line, Thr (threonine), Phe (phenylalanine), Glu (glutamate), Trp (tryptophan), and Sero (serotonin) are the main examples of biomolecules that have been suggested for MS therapy. It has been concluded that different amino acids and their derivatives might be considered prominent tools for the clinical management of MS disease.

Cellular stress can lead to the production of reactive oxygen species (ROS) while autophagy, as a catabolic pathway, protects the cells against stress. Autophagy in its turn plays a pivotal role in the pathophysiology of multiple sclerosis (MS). In the current review, we first summarized the contribution of ROS and autophagy to MS pathogenesis. Then probable crosstalk between these two pathways through HIF-1α for the first time has been proposed with the hope of employing a better understanding of MS pathophysiology and probable therapeutic approaches.

Cluster of differentiation 147 (CD147) or extracellular matrix metalloproteinase inducer (EMMPRIN) is a transmembrane glycoprotein that induces the synthesis of matrix metalloproteinases (MMPs). MMPs, as zinc-dependent proteases and versatile enzymes, play critical roles in the degradation of the extracellular matrix (ECM) components, cleaving of the receptors of cellular surfaces, signaling molecules, and other precursor proteins, which may lead to attenuation or activation of such targets. CD147 and MMPs play essential roles in physiological and pathological conditions and any disorder in the expression, synthesis, or function of CD147 and MMPs may be associated with various types of disease. In this review, we have focused on the roles of CD147 and MMPs in some major physiological and pathological processes.

Background Non-Hodgkin's lymphomas comprise the most common hematological cancers worldwide and consist of a heterogenous group of malignancies affecting the lymphoid system. Treatment of non-Hodgkin's lymphoma has been significantly enhanced with the addition of Rituximab to the standard chemotherapy regimen. However, even with the advancement of treatment patients continue to relapse and develop resistance to Rituximab, rendering subsequent treatments unsuccessful. The use of novel drugs with unique antitumor mechanisms has gained considerable attention. In this study, we explored the in vitro anti-cancer effects of the combined therapy of Rituximab and Nisin on human Burkitt's lymphoma cells. Methods The human Burkitt's lymphoma cells lines, Raji and Daudi, were treated with Nisin, Rituximab, or a combination of the two agents at various concentrations. Cytotoxicity following treatment was determined using cell viability assay. The degree of apoptosis was verified via flow cytometric analysis using FITC annexin V/PI staining. Results Our findings show that the combined treatment of Rituximab and Nisin results in a more significant reduction in the survival of Raji and Daudi Burkitt's lymphoma cells, compared to Nisin or Rituximab treatment alone. Additionally, our results indicate that Nisin can induce a significant degree of apoptosis in the Burkitt's lymphoma cells compared to the negative controls. However, the addition of Nisin to the Rituximab treatment synergistically enhances the apoptotic antitumor effect. Conclusion This study demonstrates the synergistic antitumor effect of Nisin treatment in vitro to enhance tumor cell apoptosis and the potential value of Nisin as an adjunct therapy in the treatment of lymphoma.

Escherichia coli is a widely-used cell factory for recombinant protein production, nevertheless, high amount of produced protein is seen in aggregated form. The purpose of this study was to improve the solubility of recombinant bovine sex-determining region Y protein (rbSRY) by exploring the effect of temperature, inducer, and water-arginine mixed solvent. Codon-optimized rbSRY expressed in Rosetta-gami B (DE3) pLysS and purified by NI–NTA His-select affinity chromatography in the native and denaturing conditions. A three-dimensional model of SRY was built and studied through molecular dynamics simulations in water and in the presence of l-arginine as co-solvent. Results indicated the significant effects of temperature and IPTG concentration (P

Metabolic syndrome is a common metabolic disorder which has become a public health challenge worldwide. There has been growing interest in medications including natural products as complementary or alternative choices for common chemical therapeutics regarding their limited side effects and ease of access. Nanosizing these compounds may help to increase their solubility, bioavailability, and promisingly enhance their efficacy. This study, for the first time, provides a comprehensive overview of the application of natural-products-based nanoformulations in the management of metabolic syndrome. Different phytochemicals including curcumin, berberine, Capsicum oleoresin, naringenin, emodin, gymnemic acid, resveratrol, quercetin, scutellarin, stevioside, silybin, baicalin, and others have been nanosized hitherto, and their nanosizing method and effect in treatment and alleviating metabolic syndrome have been reviewed and discussed in this study. It has been discovered that there are several pathways or molecular targets relevant to metabolic disorders which are affected by these compounds. Various natural-based nanoformulations have shown promising effect in treatment of metabolic syndrome, and therefore can be considered as future candidates instead of or in conjunction with pharmaceutical drugs if they pass clinical trials successfully.

Immune checkpoint receptors are critical regulators of initiation and termination of effective immune responses as well as maintain self-tolerance. Since the successful use of immune checkpoint inhibitors in cancer immunotherapy, they gained huge interest to be used in autoimmune diseases treatment. Indeed, abatacept (CTLA4-Ig), as immune checkpoint inhibitors has made major advancement in the treatment of rheumatoid arthritis patients who have failed to respond to csDMARDs or TNF-α inhibitor. Over the past decade, an increasing number of new immune checkpoints have been detected and lots of investigations are in progress to address their potential as possible targets of effective novel immunotherapy. Here we focus on the biological functions and structures of these immune checkpoints, their pharmacological mechanisms, pathogenesis, therapeutic effects, and their related adverse events. We also discuss the application of agonistic or antagonistic agents targeting co-inhibitory or co-stimulatory checkpoints for the treatment of autoimmune diseases. Furthermore, we summarize previous and recent clinical trials utilizing these immune checkpoints in autoimmune diseases. Obviously, the characterization of such processes might help to develop more effective therapeutic agents in the future.

Multiple sclerosis (MS) is a complicated autoimmune disease characterized by inflammatory and demyelinating events in the central nervous system. The exact etiology and pathogenesis of MS have not been elucidated. However, a set of metabolic changes and their effects on immune cells and neural functions have been explained. This review highlights the contribution of carbohydrates and lipids metabolism to the etiology and pathogenesis of MS. Then, we have proposed a hypothetical relationship between such metabolic changes and the immune system in patients with MS. Finally, the potential clinical implications of these metabolic changes in diagnosis, prognosis, and discovering therapeutic targets have been discussed. It is concluded that research on the pathophysiological alterations of carbohydrate and lipid metabolism may be a potential strategy for paving the way toward MS treatment.

Despite the unparalleled success of anti-CD20-targeted immunotherapy, the currently available mAbs are not sufficiently efficacious in the treatment of lymphoma. 1F5 is one of a panel of anti-CD20 mAbs that was used in the B-cell lymphoma serotherapy. Despite the efficacy of murine 1F5 mAbs in lymphoma patients, the 1F5 chimeric antibodies with human effector functionality are yet to be approved and widely used in the treatment of lymphoma. In this study, the conversion of 1F5 mAb from mouse IgG2a to human-mouse chimeric IgG1 was achieved and the chimeric antibody was partially characterized. We constructed the 1F5 chimeric mouse-human anti-CD20 antibody genes using an efficient Splicing by overlap extension-polymerase chain reaction (SOE-PCR) technique and cloned the chimeric heavy and light genes in pBudCE4.1 mammalian expression vector, followed by purification of the expressed chimeric 1F5 mAbs using affinity chromatography. Our investigation also included the biological properties of purified chimeric antibodies. The generated 1F5 chimeric mAbs mediate complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) against Raji and Daudi Burkitt's lymphoma cell lines, which were comparable with rituximab and exhibit superior reduction in cell viability in vitro, compared to rituximab. The current study indicated that the generated chimeric 1F5 mAbs has potential CDC and ADCC activity which was comparable with rituximab whereas it exhibits a superior reduction in cell viability, compared to rituximab. Our work contributes to future studies involving in vivo biological functions and the application of the 1F5 chimeric antibody.

Objective The current research was conducted to study the association between the SNP309 and del1518 polymorphisms with the breast cancer in the patients with the Kurdish ethnic background from western Iran. Also, a systematic review of the relevant case‐control studies on the MDM2 polymorphisms in the patients with breast cancer was performed. Methodology Two mL of peripheral blood was taken from 100 patients with breast cancer and 100 healthy individuals. The frequencies of MDM2 SNP309 and del1518 genotypes and alleles were determined using the PCR‐RFLP and PCR methods, respectively. Results The frequency of the TT, TG, and GG of MDM2‐SNP309 genotypes in the patients was obtained as 23%, 52%, and 25%, and they were equal to 22%, 40%, and 38% in the control group, respectively. Also, considering the MDM2‐del1518 polymorphism, the frequencies of ins/ins, ins/del, and del/del genotypes were equal to 52%, 41%, and 7% in the breast cancer group and they were equal to 62, 30, and 8% in the control group, respectively. Analysis of the results indicated that the GG genotype plays a protective role for the breast cancer in the recessive model (GG vs TT + TG) of SNP309 (χ2 = 3.916, P = .048, and OR = 0.54). Conclusion Our findings revealed that the GG genotype of MDM2‐SNP309 can play a protective role in the breast cancer disease. Also, our systematic review indicated that the SNP309, SNP285, and del1518 of MDM2 gene in different populations mostly did not have a significant association with the risk of breast cancer., Our findings revealed that the GG genotype of MDM2‐SNP309 can play a protective role in the breast cancer disease. Also, our systematic review indicated that the SNP309, SNP285, and del1518 of MDM2 gene in different populations mostly did not have a significant association with the risk of breast cancer.

Since the outbreak of coronavirus disease 2019 (COVID-19) in December 2019, millions of people have been infected and died worldwide. However, no drug has been approved for the treatment of this disease and its complications, which urges the need for finding novel therapeutic agents to combat. Among the complications due to COVID-19, lung injury has attained special attention. Besides, phytochemicals have shown prominent anti-inflammatory effects and thus possess significant effects in reducing lung injury caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Also, the prevailing evidence reveales the antiviral effects of those phytochemicals, including anti-SARS-CoV activity, which could pave the road in providing suitable lead compounds in the treatment of COVID-19. In the present study, candidate phytochemicals and related mechanisms of action have been shown in the treatment/protection of lung injuries induced by various methods. In terms of pharmacological mechanism, phytochemicals have shown potential inhibitory effects on inflammatory and oxidative pathways/mediators, involved in the pathogenesis of lung injury during COVID-19 infection. Also, a brief overview of phytochemicals with anti-SARS-CoV-2 compounds has been presented.

In the present work, we studied the structure-activity relationship and kinetics of thermal inactivation of α-glucosidase A (AglA) in a 50 mM potassium phosphate buffer at pH 6.8 using p-nitropheny...

Despite the unparalleled success of anti-CD20-targeted immunotherapy, the currently available mAbs are not sufficiently efficacious in the treatment of lymphoma. 1F5 is one of a panel of anti-CD20 mAbs that was used in the B-cell lymphoma serotherapy. Despite the efficacy of murine 1F5 mAbs in lymphoma patients, the 1F5 chimeric antibodies with human effector functionality are yet to be approved and widely used in the treatment of lymphoma. In this study, the conversion of 1F5 mAb from mouse IgG2a to human-mouse chimeric IgG1 was achieved and the chimeric antibody was partially characterized. We constructed the 1F5 chimeric mouse-human anti-CD20 antibody genes using an efficient Splicing by overlap extension-polymerase chain reaction (SOE-PCR) technique and cloned the chimeric heavy and light genes in pBudCE4.1mammalian expression vector, followed by purification of the expressed chimeric 1F5 mAbs using affinity chromatography. Our investigation also included the biological properties of purified chimeric antibodies. The generated 1F5 chimeric mAbs mediate complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) against Raji and Daudi Burkitt's lymphoma cell lines, which were comparable with rituximab and exhibit superior reduction in cell viability in vitro, compared to rituximab. The current study indicated that the generated chimeric 1F5 mAbs has potential CDC and ADCC activity which was comparable with rituximab whereas it exhibits a superior reduction in cell viability, compared to rituximab. Our work contributes to future studies involving in vivo biological functions and the application of the 1F5 chimeric antibody.

To date, several new anti-CD20 monoclonal antibodies (mAbs) have been developed for potential efficacies compared with familiar mAb rituximab. Despite the recent advances in development of anti-CD20 mAbs for the treatment of B cell malignancies, the efforts should be continued to develop novel antibodies with improved properties. However, the development of mAbs against CD20 as a multi-transmembrane protein is challenging due to the difficulty of providing a lipid environment that can maintain native epitopes. To overcome this limitation, we describe a simple and efficient DNA immunization strategy for the construction of a novel anti-CD20 mAb with improved anti-tumour properties. Using a DNA immunization strategy that includes intradermal (i.d.) immunization with naked plasmid DNA encoding the CD20 gene, we generated the hybridoma cell line D4, which secretes functional mAbs against an extracellular epitope of CD20. Immunocytochemistry analysis and a cell-based enzyme-linked immunosorbent assay using a Burkitt's lymphoma cell line showed that D4 mAbs are capable of binding to native extracellular epitopes of CD20. Moreover, the binding specificity of D4 mAbs was determined by western blot analysis. Cell proliferation was examined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected by the annexin V/propidium iodide staining and dye exclusion assay. The results showed that D4 anti-CD20 mAbs produced by DNA immunization exhibit potent growth inhibitory activity and have superior direct B-cell cytotoxicity compared to rituximab. We propose that antibody-induced apoptosis is one of the mechanisms of cell growth inhibition. Taken together, the data reported here open the path to DNA-based immunization for generating pharmacologically active monoclonal antibodies against CD20. In addition, the data support future in vivo animal testing and subsequent procedures to produce a potential therapeutic mAb.

Recently, nanomaterials (especially nano-biomaterials) have remarkably attracted attention of researchers for their wide and promising applications in different technologies. Their small size and shape versatility, capability of controlling the release at the targeted site, and capability for selectively loading of a wide ranges of drug molecules, provide phytonanotechnology as a unique opportunity in protection, modification, and productivity of plants and smart delivery of agrochemical. Delivery of particular bioactive to manipulate plant breeding and genetic transformation and decrease of nutrient losses from fertilizers are some of other applications of this technology. However, despite these exciting advancements in the phytonanotechnology, several further studies are needed to overcome the drawbacks of using the nanostructures in plants. Different levels of modifications in the morphology of nanoparticles, their solubility, and sensitivity to pH are yet required to achieve desired formulations. In addition, several studies should focus on the interactions of these nanostructures with cell wall (to facilitate their transfer across cell walls and other barriers), the toxicity and trophic transfer of these particles under environmentally realistic and relevant conditions (to ensure both the safe use and social acceptance of phytonanotechnology). After a profound search on the recent advances in synthesize and utilization of nanoparticles in plants, based on our findings in this area, the limitations and deficiencies of these systems would be evident. This chapter has been prepared to provide an overview about the most recent and possible future advancements and efforts to overcome the drawbacks of engineered nanomaterials.

Background: Formation of secondary structure such as DNA hairpins or loops may influence molecular genetics methods and PCR based approaches necessary for genetic engineering, in addition to gene regulation. Materials and Methods: A polymerase chain reaction with splice overlap extension (SOE-PCR) was used to create fully synthetic 1F5 chimeric anti-CD20 heavy- and light-chain genes. The chimeric genes were cloned into the pCR-Blunt II-TOPO vector following by cloning into the pBudCE4.1 expression vector. Prediction of secondary structure was performed with the Vienna RNAfold webserver. PCR and sequencing across the predicted secondary structure of chimeric 1F5 heavy-chain gene was performed with multiple protocols for standard and GC-rich templates. Results: In our attempt to design vectors aimed to generate mouse-human chimeric antibody against CD20 (1F5), we found that the coding sequence of 1F5 chimeric heavy-chain gene constructed by SOE-PCR was resistant to polymerase during both PCR and sequencing reactions. Furthermore, we were also unable to analysis some positive transformants by restriction enzyme digestion. Encountering such difficulties to identify the cloned anti-CD20 chimeric heavy-chain gene, we found that the chimeric heavy-chain sequence is highly GC-rich and predicted to form a stable secondary structure. Conclusion: In conclusion, for the first time, we reported several difficulties with production of therapeutic chimeric 1F5 anti-CD20 antibody due to a predicted hairpin cluster correlates with barriers to PCR, sequencing and possibly restriction analysis. Our findings provide a probable note for researchers experiencing technical difficulties with construction of chimeric anti-CD20 antibody 1F5 gene vectors and also with other genes and molecular biology techniques requiring PCR-based method or restriction enzyme analysis.&nbsp

Background: Pseudomonas aeruginosais a frequent nosocomial pathogen that causes severe diseases in many settings. Carbapenems, including meropenem and imipenem, are effective antibiotics against this organism. However, the use of carbapenems has been hampered by the emergence of strains resistant to carbapenemsvia different mechanisms such as the production of metallo-β-lactamases (MBLs), which hydrolyze all carbapenems. Several kinds of MBLs have been reported, among them VIM and IMP types being the most clinically significant carbapenemases. Objectives: We aimed to determine the distribution of blaVIM-2 and blaIMP-1 transferable genes encoding MBLs in P. aeruginosa isolated from three academic hospitals in Kermanshah. Patients and Methods: From 22nd June to 22nd September 2012, 225 isolates of P. aeruginosa were collected. These isolates were tested for antibiotic susceptibility with the Kirby-Bauer disk-diffusion method, and the MBLs were assessed using the imipenem-EDTA double-disk synergy test. The isolates were investigated for blaVIM-2 and blaIMP-1 genes using polymerase chain reaction. Results: Among the 225 isolates, 33.7% (76/225) and 18.1% (41/225) were resistant to imipenem and meropenem, respectively. Of the 76 imipenem-resistant P. aeruginosa strains, 45 (59.2%) were positive for MBLs, 34 (75%) strains carried the blaIMP-1 gene, and 1 (2.2%) strain carried the blaVIM-2 gene. Conclusions: Our results showed that there was a high frequency of IMP-1 positive P. aeruginosa in the different wards of the hospitals.

Background: Infectious diarrhoeal diseases cause major problems throughout the world and are responsible for considerable morbidity and mortality. Enteropathogenic Escherichia coli (EPEC) may cause infantile diarrhoea among children in developing countries. Objectives: The aim of this study was to define the prevalence of EPEC strains in raw milk samples. Materials and Methods: Raw milk samples collected from various cow farms in Kermanshah, Iran, during the period of 22nd June to 22nd September 2009 and were examined for EPEC presence using PCR reactions targeting eaeA, and then stx1 and stx2. Results: Of the 206 samples, 17 (8.25%) were contaminated with E. coli eaeA positive and stx1 and stx2 negative (EPEC). Conclusions: Our results confirm that raw milk recovered in Kermanshah may be a source for gastrointestinal infections by EPEC and strict preventive measures should be adopted to decrease contamination of milk with EPEC and other bacteria originated from animals.