Advanced Primary Lymphoma of Oral Cavity: Report of a Case

Abstract Usually the oral manifestations of NHL are secondary to a more widespread involvement throughout the body, however, it can rarely present as a primary lesion in the oral cavity, having 0.1% - 0.2% prevalence. In this paper we report a case of highly proliferative oral non-Hodgkin lymphoma which presented with very mild symptoms, but had a sudden and significant progression in less than two weeks with involvement of all four quadrants of the oral cavity. Keywords Lymphoma; Intra Oral Swelling; Four Quadran

Efficacy of topical phenytoin on chemotherapy-induced oral mucositis; a pilot study

"nBackground and the Purpose of the Study: Oral mucositis is one of the most common complications of malignancy chemotherapy. As yet, no absolute treatment has been demonstrated to be effective for chemotherapy- induced oral mucositis. This study evaluates the effectiveness of phenytoin mouthwash as a wound healing agent, on the basis of stimulating effects on fibroblast proliferation. "nMaterials and Methods: In this multicenter, randomized, placebo- controlled clinical trial; twelve patients received phenytoin mouthwash (0.5%) or placebo for about two weeks. Oral pain severity was scored on the daily basis using a VAS (visual analogue scale) of 10 centimeters. National Cancer Institute (NCI) scale was used to grade the intensity of mucositis. To determine the effect of treatment, a quality of life questionnaire, consisting of 35 queries, was filled out for all patients. Statistical analyses of data was performed using Mann- Whitney test. "nResults: The average time for complete remission of mucositis in phenytoin- treated group was less than that of the placebo group. The quality of life improved dramatically in the phenytoin group with the healing process being more evident in the first week. Furthermore, reduction in the wound area was greater in the phenytoin group than controls at the end of the first week of treatment. Both groups eventually demonstrated reduction in pain intensity; however no statistically significant difference was observed between two groups. "nConclusion: Phenytoin mouthwash accelerated wound healing and resolution of mucositis and improved life quality impressively

An ethnobotanical study of medicinal plants administered for the treatment of hypertension

Introduction: The incidence of cardiovascular diseases (CVDs) is very high in human societies and their prevention and treatment are the most important priority in many countries. Hypertension makes an important contribution to the development of CVDs. Objectives: This study aimed to collect the ethno-medicinal knowledge of the traditional healers of Shiraz on medicinal plants used in the treatment of hypertension. Materials and Methods: Ethno-medicinal data were collected from September 2012 to July 2013 through direct interview. Twenty-five healers were interviewed using semi-structured questionnaires and their traditional ethno-medicinal knowledge was recorded. Questionnaires were included apothecary personal information, plant local name, plant parts used, method of preparation, season of harvest and traditional use. Data collected from surveys and interviews were transferred to Microsoft Excel 2007 and analyzed. Results: Analysis of data showed that, 27 medicinal plants from 22 families are used for the treatment of hypertension. The families with most antihypertensive species were Apiaceae (8), Rosaceae (8) and Papaveraceae (8). The most frequently used plant parts were leaves (36) followed by fruits (30), aerial part (17) and branches (7). The most frequently used preparation method was decoction (95). Borago officinalis (51.85), Berberis vulgaris (51.58) had the highest frequency of mention. Conclusion: The ethno-medicinal survey of medicinal plants recommended by traditional healers for the treatment of hypertension provides new areas of research on the antihypertensive effect of medicinal plants. In the case of safety and effectiveness, they can be refined and processed to produce natural drugs

Systematic selection of small molecules to promote differentiation of embryonic stem cells and experimental validation for generating cardiomyocytes.

Small molecules are being increasingly used for inducing the targeted differentiation of stem cells to different cell types. However, until now no systematic method for selecting suitable small molecules for this purpose has been presented. In this work, we propose an integrated and general bioinformatics- and cheminformatics-based approach for selecting small molecules which direct cellular differentiation in the desired way. The approach was successfully experimentally validated for differentiating stem cells into cardiomyocytes. All predicted compounds enhanced expression of cardiac progenitor (Gata4, Nkx2-5 and Mef2c) and mature cardiac markers (Actc1, myh6) significantly during and post-cardiac progenitor formation. The best-performing compound, Famotidine, increased the percentage of Myh6-positive cells from 33 to 56%, and enhanced the expression of Nkx2.5 and Tnnt2 cardiac progenitor and cardiac markers in protein level. The approach employed in the study is applicable to all other stem cell differentiation settings where gene expression data are available.YK and AB thank the European Research Council (ERC Starting Grant 2013 to AB) for funding.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/cddiscovery.2016.

Mouse and human spermatogonial stem cells

Spermatogonial stem cells (SSCs) are in the beginning of a complex process in which they transmit genetic information from generation to generation. Any failure in this process can result in infertility. It has been suggested that transplantation of spermatogonial stem cells, following their maintenance and culturing, may restore fertility in some infertile patients. Because fertility restoration through SSCs transplantation has been successfully achieved in animal experiments, we hope human studies can follow in the near future. The isolation and cultivation of SSCs help us study their biological characteristics and their application in therapeutic approaches. In this review, we studied spermatogenesis in rodents and humans. We also compared markers and different SSC culture systems in both

A cell-free SDKP-conjugated self-assembling peptide hydrogel sufficient for improvement of myocardial infarction

Biomaterials in conjunction with stem cell therapy have recently attracted attention as a new therapeutic approach for myocardial infarction (MI), with the aim to solve the delivery challenges that exist with transplanted cells. Self-assembling peptide (SAP) hydrogels comprise a promising class of synthetic biomaterials with cardiac-compatible properties such as mild gelation, injectability, rehealing ability, and potential for sequence modification. Herein, we developed an SAP hydrogel composed of a self-assembling gel-forming core sequence (RADA) modified with SDKP motif with pro-angiogenic and anti-fibrotic activity to be used as a cardioprotective scaffold. The RADA-SDKP hydrogel was intramyocardially injected into the infarct border zone of a rat model of MI induced by left anterior descending artery (LAD) ligation as a cell-free or a cell-delivering scaffold for bone marrow mesenchymal stem cells (BM-MSCs). The left ventricular ejection fraction (LVEF) was markedly improved after transplantation of either free hydrogel or cell-laden hydrogel. This cardiac functional repair coincided very well with substantially lower fibrotic tissue formation, expanded microvasculature, and lower inflammatory response in the infarct area. Interestingly, BM-MSCs alone or in combination with hydrogel could not surpass the cardiac repair effects of the SDKP-modified SAP hydrogel. Taken together, we suggest that the RADA-SDKP hydrogel can be a promising cell-free construct that has the capability for functional restoration in the instances of acute myocardial infarction (AMI) that might minimize the safety concerns of cardiac cell therapy and facilitate clinical extrapolation. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Construction of expression vectors carrying mouse peroxisomal protein gene (PeP) with GST and Flag labels

The aim of this study was to construct expression vectors carrying mouse peroxisomal protein gene (PEP-cDNA) in prokaryotic and mammalian expression vectors in chimeric cDNA types, encompassingGST and FLAG with PEP-cDNA. PEP-cDNA was sub-cloned in pGEX6p2 prokaryotic expression vector in order to label this gene with GST to purify PEP protein for further biochemical analysis and identifying related proteins thereafter. FLAG-PEP recombinant DNA was produced and sub-cloned inpUcD3 eukaryotic expression vector to express tagged-PEP protein for transient transfection analysis and identifying intracellular localization of PEP protein in future experiments. PEP-cDNA was amplifiedin different PCR reactions using pEGFP-PEP vector and 2 sets of primers introducing specific restriction sites at the ends of PEP. PCR products with BamHI/SalI restriction sites were treated by restriction enzymes and inserted into the pGEX6p2, downstream of GST tag. PEP-cDNA containingBamHI/ApaI restriction sites and FLAG gene (which amplified using pUcD3-FLAG-PEX3 vector) were used as templates in secondary PCR for amplifying FLAG-PEP recombinant DNA. FLAG-PEP fragment was treated by enzymatic digestion and inserted into the pUcD3 eukaryotic expression vector.pGEX6p2-PEP and pUcD3-FLAG-PEP constructed vectors were transformed into the one shot TOP10 and JM105 bacterial competent cells, respectively. Positive colonies were selected for plasmid preparation. Results confirmed correct amplification of the expected products. PEP-cDNA in both PCRreactions encompasses 630 bp. FLAG fragment containing designed sites was 77 bp and FLAG-PEP fragment was 700 bp. Sequencing of constructed vectors confirmed that PEP-cDNA was tagged appropriately and inserted free of mutation and in frame with GST and FLAG

A Roadmap for the Production of a GMP-Compatible Cell Bank of Allogeneic Bone Marrow-Derived Clonal Mesenchymal Stromal Cells for Cell Therapy Applications

Background: Allogeneic mesenchymal stromal cells (MSCs) have been used extensively in various clinical trials. Nevertheless, there are concerns about their efficacy, attributed mainly to the heterogeneity of the applied populations. Therefore, producing a consistent population of MSCs is crucial to improve their therapeutic efficacy. This study presents a good manufacturing practice (GMP)-compatible and cost-effective protocol for manufacturing, banking, and lot-release of a homogeneous population of human bone marrow-derived clonal MSCs (cMSCs). Methods: Here, cMSCs were isolated based on the subfractionation culturing method. Afterward, isolated clones that could reproduce up to passage three were stored as the seed stock. To select proliferative clones, we used an innovative, cost-effective screening strategy based on lengthy serial passaging. Finally, the selected clones re-cultured from the seed stock to establish the following four-tired cell banking system: initial, master, working, and end of product cell banks (ICB, MCB, WCB, and EoPCB). Results: Through a rigorous screening strategy, three clones were selected from a total of 21 clones that were stored during the clonal isolation process. The selected clones met the identity, quality, and safety assessments criteria. The validated clones were stored in the four-tiered cell bank system under GMP conditions, and certificates of analysis were provided for the three-individual ready-to-release batches. Finally, a stability study validated the EoPCB, release, and transport process of the frozen final products. Conclusion: Collectively, this study presents a technical and translational overview of a GMP-compatible cMSCs manufacturing technology that could lead to the development of similar products for potential therapeutic applications. Graphical Abstract: [Figure not available: see fulltext.

Two Decades of Global Progress in Authorized Advanced Therapy Medicinal Products: An Emerging Revolution in Therapeutic Strategies

The introduction of advanced therapy medicinal products (ATMPs) to the global pharma market has been revolutionizing the pharmaceutical industry and has opened new routes for treating various types of cancers and incurable diseases. In the past two decades, a noticeable part of clinical practices has been devoting progressively to these products. The first step to develop such an ATMP product is to be familiar with other approved products to obtain a general view about this industry trend. The present paper depicts an overall perspective of approved ATMPs in different countries, while reflecting the degree of their success in a clinical point of view and highlighting their main safety issues and also related market size as a whole. In this regard, published articles regarding safety, efficacy, and market size of approved ATMPs were reviewed using the search engines PubMed, Scopus, and Google Scholar. For some products which the related papers were not available, data on the relevant company website were referenced. In this descriptive study, we have introduced and classified approved cell, gene, and tissue engineering-based products by different regulatory agencies, along with their characteristics, manufacturer, indication, approval date, related regulatory agency, dosage, product description, price and published data about their safety and efficacy. In addition, to gain insights about the commercial situation of each product, we have gathered accessible sale reports and market size information that pertain to some of these products

Phase 1 human trial of autologous bone marrow-hematopoietic stem cell transplantation in patients with decompensated cirrhosis

Aim: To evaluate safety and feasibility of autologous bone marrow-enriched CD34+ hematopoietic stem cell Tx through the hepatic artery in patients with decompensated cirrhosis. Methods: Four patients with decompensated cirrhosis were included. Approximately 200 mL of the bone marrow of the patients was aspirated, and CD34+ stem cells were selected. Between 3 to 10 million CD34+ cells were isolated. The cells were slowly infused through the hepatic artery of the patients. Results: Patient 1 showed marginal improvement in serum albumin and no significant changes in other test results. In patient 2 prothrombin time was decreased; however, her total bilirubin, serum creatinine, and Model of End-Stage Liver Disease (MELD) score worsened at the end of follow up. In patient 3 there was improvement in serum albumin, porthrombin time (PT), and MELD score. Patient 4 developed radiocontrast nephropathy after the procedure, and progressed to type 1 hepatorenal syndrome and died of liver failure a few days later. Because of the major side effects seen in the last patient, the trial was prematurely stopped. Conclusion: Infusion of CD34+ stem cells through the hepatic artery is not safe in decompensated cirrhosis. Radiocontrast nephropathy and hepatorenal syndrome could be major side effects. However, this study does not preclude infusion of CD34+ stem cells through other routes. © 2007 The WJG Press. All rights reserved