microRNA 1307 Is a Potential Target for SARS-CoV-2 Infection: An <i>in Vitro</i> Model

microRNAs (miRs) are proposed as critical molecular targets in SARS-CoV-2 infection. Our recent in silico studies identified seven SARS-CoV-2 specific miR-like sequences, which are highly conserved with humans, including miR-1307-3p, with critical roles in COVID-19. In this current study, Vero cells were infected with SARS-CoV-2, and miR expression profiles were thereafter confirmed by qRT-PCR. miR-1307-3p was the most highly expressed miR in the infected cells; we, therefore, transiently inhibited its expression in both infected and uninfected cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cell proliferation assay assessed cell viability following SARS-CoV-2 infection, identifying that miR-1307 expression is inversely correlated with cell viability. Lastly, changes in miR-1307-dependent pathways were analyzed through a detailed miRNOME and associated in silico analysis. In addition to our previously identified miRs, including miR-1307-3p, the upregulation of miR-193a-5p, miR-5100, and miR-23a-5p and downregulation of miR-130b-5p, miR34a-5p, miR-505-3p, miR181a-2-3p, miR-1271-5p, miR-598-3p, miR-34c-3p, and miR-129-5p were also established in Vero cells related to general lung disease-related genes following SARS-CoV-2 infection. Targeted anti-miR-1307-3p treatment rescued cell viability in infection when compared to SARS CoV-2 mediated cell cytotoxicity only. We furthermore identified by in silico analysis that miR-1307-3p is conserved in all SARS-CoV-2 sequences/strains, except in the BA.2 variant, possibly contributing to the lower disease severity of this variant, which warrants further investigation. Small RNA seq analysis was next used to evaluate alterations in the miRNOME, following miR-1307-3p manipulation, identifying critical pathobiological pathways linked to SARS-CoV-2 infection-mediated upregulation of this miR. On the basis of our findings, miRNAs like miR-1307-3p play a critical role in SARS-CoV-2 infection, including via effects on disease progression and severity

Effect of pathologic fractures on survival in multiple myeloma patients: a case control study

<p>Abstract</p> <p>Background</p> <p>Multiple Myeloma (MM) is a B cell neoplasm characterized by the clonal proliferation of plasma cells. Skeletal complications are found in up to 80% of myeloma patients at presentation and are major cause of morbidity.</p> <p>Methods</p> <p>49 patients were enrolled with MM admitted to Black Sea Technical University Hospital between 2002–2005. Pathologic fractures (PFs) were determined and the patients with or without PF were followed up minumum 3 years for survival analysis.</p> <p>Results</p> <p>PF was observed in 24 patients (49%) and not observed in 25 patients (51%). The risk of death was increased in the patients with PF compared with patients who had no fractures. While overall survival was 17.6 months in the patients with PFs, it was 57.3 months in the patients with no PFs.</p> <p>Conclusion</p> <p>These findings suggest that PFs may induce reduced survival and increased mortality in the MM patients, however, larger sample size is essential to draw clearer conclusions added to these data.</p

Crimean-Congo Hemorrhagic Fever in Turkey

Nineteen cases of suspected Crimean-Congo hemorrhagic fever reported from Turkey

Mesenchymal stem cell experience in acute GVHD: a case report

6th Meeting of the EBMT Paediatric Diseases Working Party/1st Meeting of the EBMT Paediatric Nurses -- JUN 02-04, 2008 -- Poznan, POLANDWOS: 000261232600069…European Grp Blood & Marrow Transplantat, Paediat Dis Working Part

Mesenchymal Stem Cell Treatment for Steroid Refractory Graft-versus-Host Disease in Children: A Pilot and First Study from Turkey

This study evaluated the efficacy of mesenchymal stem cells (MSCs) from bone marrow of a third-party donor for refractory aGVHD. We report the first experience using MSCs to treat refractory aGVHD in 33 pediatric patients undergoing allogeneic HSCT from Turkey. Totally, 68 doses of bone marrow derived MSCs were infused. The median dose of MSC was 1.18×106 cells per kg body weight. Overall, complete response (CR) was documented in 18 patients, partial response (PR) was documented in 7 patients, and no response (NR) was documented in 8 patients. The 2-year estimated probability of overall survival (OS) for patients achieving CR and PR/NR was 63.8% and 29.4%, respectively p=0.0002. While the cumulative incidence of transplant related mortality (TRM) at day 100 after first MSC infusion was 46.6% in PR/NR patients, there was no any TRM at day 100 after first MSC infusion in CR patients p=0.001. Twelve patients developed chronic GVHD (cGVHD); eight of them were alive, with five having extensive disease and three having limited disease. In conclusion, MSCs appear to be safe and effective treatment option for pediatric patients with steroid refractory aGVHD. But the efficacy of MSCs on cGVHD in aGVHD patients treated with MSCs seems to be limited

Mesenchymal Stem Cells: a Potential Treatment Approach for Refractory Chronic Spontaneous Urticaria

Ozdemir, Alper Tunga/0000-0002-7708-077XWOS: 000581897300001PubMed: 33089453The etiopathogenesis of chronic spontaneous urticaria (CSU) is not fully elucidated, and almost 30-40% of patients are resistant to treatments; therefore, there is still a need for the development of new and effective treatments. This study aimed to develop experimental cellular therapy for CSU patients resistant to current treatment options. Autologous adipose tissue mesenchymal stem cells (MSC) were administered to 10 refractory CSU patients who were then followed up for six months. the efficacy of treatment was evaluated according to the weekly urticaria activity scores (UAS7) and drug use scores (DUS7). To observe the effect of treatment on immune cells, CD4(+) T cell subsets were analyzed by flow cytometry, and the serum IFN-gamma, TNF-alpha, IL2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17a, IL-21, IL-22, TGF-beta 1, PGE2, IDO and anti-Fc epsilon RI levels were measured using the Luminex and ELISA methods. the values obtained were compared with 10 control refractory CSU patients and five healthy controls. We found that the T cell subsets and inflammatory molecules were not affected by MSC treatment during the follow-up period. in control patients, a significant decrease was detected only at the Th2 subset, TGF-beta 1, PGE2, IDO and anti-Fc epsilon RI levels on the 14th day of treatment. the UAS7 and DUS7 values of the MSC-treated patients significantly decreased during the follow-up period, but in control patients, a significant but temporary decrease was seen. According to our findings, unlike conventional treatment, MSC therapy resulted in longer and more effective recovery. Our data indicate that MSCs may be an alternative and effective approach for treatment-resistant CSU patients.Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [215 S 612]The Scientific and Technological Research Council of Turkey (TUBITAK) financially supported this study with reference number 215 S 612

Betulin Stimulates Osteogenic Differentiation of Human Osteoblasts-Loaded Alginate–Gelatin Microbeads

Osteoporosis, a terminal illness, has emerged as a global public health problem in recent years. The long-term use of bone anabolic drugs to treat osteoporosis causes multi-morbidity in elderly patients. Alternative therapies, such as allogenic and autogenic tissue grafts, face important issues, such as a limited source of allogenic grafts and tissue rejection in autogenic grafts. However, stem cell therapy has been shown to increase bone regeneration and decrease osteoporotic bone formation. Stem cell therapy combined with betulin (BET) supplementation might be adequate for bone remodeling and new bone tissue generation. In this study, the effect of BET on the viability and osteogenic differentiation of hFOB 1.19 cells was investigated. The cells were encapsulated in alginate–gelatin (AlGel) microbeads. In vitro tests were conducted during the 12 d of incubation. While BET showed cytotoxic activity (>1 µM) toward non-encapsulated hFOB 1.19 cells, encapsulated cells retained their functionality for up to 12 days, even at 5 µM BET. Moreover, the expression of osteogenic markers indicates an enhanced osteo-inductive effect of betulin on encapsulated hFOB 1.19, compared to the non-encapsulated cell culture. The 3D micro-environment of the AlGel microcapsules successfully protects the hFOB 1.19 cells against BET cytotoxicity, allowing BET to improve the mineralization and differentiation of osteoblast cells

CAR-T Cells with Phytohemagglutinin (PHA) Provide Anti-Cancer Capacity with Better Proliferation, Rejuvenated Effector Memory, and Reduced Exhausted T Cell Frequencies

The development of genetic modification techniques has led to a new era in cancer treatments that have been limited to conventional treatments such as chemotherapy. intensive efforts are being performed to develop cancer-targeted therapies to avoid the elimination of non-cancerous cells. One of the most promising approaches is genetically modified CAR-T cell therapy. The high central memory T cell (Tcm) and stem cell-like memory T cell (Tscm) ratios in the CAR-T cell population increase the effectiveness of immunotherapy. Therefore, it is important to increase the populations of CAR-expressing Tcm and Tscm cells to ensure that CAR-T cells remain long-term and have cytotoxic (anti-tumor) efficacy. In this study, we aimed to improve CAR-T cell therapy’s time-dependent efficacy and stability, increasing the survival time and reducing the probability of cancer cell growth. To increase the sub-population of Tcm and Tscm in CAR-T cells, we investigated the production of a long-term stable and efficient cytotoxic CAR-T cell by modifications in the cell activation-dependent production using Phytohemagglutinin (PHA). PHA, a lectin that binds to the membranes of T cells and increases metabolic activity and cell division, is studied to increase the Tcm and Tscm population. Although it is known that PHA significantly increases Tcm cells, B-lymphocyte antigen CD19-specific CAR-T cell expansion, its anti-cancer and memory capacity has not yet been tested compared with aCD3/aCD28-amplified CAR-T cells. Two different types of CARs (aCD19 scFv CD8-(CD28 or 4-1BB)-CD3z-EGFRt)-expressing T cells were generated and their immunogenic phenotype, exhausted phenotype, Tcm–Tscm populations, and cytotoxic activities were determined in this study. The proportion of T cell memory phenotype in the CAR-T cell populations generated by PHA was observed to be higher than that of aCD3/aCD28-amplified CAR-T cells with similar and higher proliferation capacity. Here, we show that PHA provides long-term and efficient CAR-T cell production, suggesting a potential alternative to aCD3/aCD28-amplified CAR-T cells