Myelodysplastic Syndrome and Autoimmune Disorders: Causal Relationship or Coincidence?

Myelodysplastic syndromes are heterogeneous group of clonal hematologic malignancies characterized by peripheral blood cytopenias secondary to the ineffective hematopoiesis. ADs are frequently reported in MDS, the incidence ranging from 10 to 30%, and particularly ADs are more frequently seen at CMML. ADs may prone patient to MDS, especially when immune suppressors such as azathioprine are used for the underlying AD. Both innate and adaptive immune systems, and different cytokines including interleukins, TNF-α, and C-X-C motif chemokine 10 (CXCL10) contribute in immune dysregulation of MDS. Vasculitis, seronegative rheumatoid arthritis, SLE, Behçet’s disease, RP, and AIHA are just some of the ADs occurring concomitantly with MDS. Although hematopoietic growth factors are recommended by the American Society of Clinical Oncology (ASCO), it has been recognized from several case reports that treatment of the underlying MDS may resolve the associated autoimmune disorders. The heterogeneity and complexity of pathology, clinical manifestations, response to therapy, and prognosis of MDS and its immune dysregulation make the prognosis of MDS with autoimmune diseases a matter of debate. Better understanding of the immune dysregulation of MDS in the molecular level may help to design prospective, double blind clinical trials to find the best treatment options for autoimmune disorders associated with MDS

Vitamin K1 As A Potential Molecule For Reducing Single-Walled Carbon Nanotubes-Stimulated α-Synuclein Structural Changes And Cytotoxicity

Aims: Different kinds of vitamins can be used as promising candidates to mitigate the structural changes of proteins and associated cytotoxicity stimulated by NPs. Therefore, the structural changes of α-syn molecules and their associated cytotoxicity in the presence of SWCNTs either alone or co-incubated with vitamin K1 were studied by spectroscopic, bioinformatical, and cellular assays. Methods: Intrinsic and ThT fluorescence, CD, and Congo red absorption spectroscopic approaches as well as TEM investigation, molecular docking, and molecular dynamics were used to explore the protective effect of vitamin K1 on the structural changes of α-syn induced by SWCNTs. The cytotoxicity of α-syn/SWCNTs co-incubated with vitamin K1 against SHSY5Y cells was also carried out by MTT, LDH, and caspase-3 assays. Results: Fluorescence spectroscopy showed that vitamin K1 has a significant effect in reducing SWCNT-induced fluorescence quenching and aggregation of α- syn. CD, Congo red adsorption, and TEM investigations determined that co-incubation of α- syn with vitamin K1 inhibited the propensity of α-syn into the structural changes and amorphous aggregation in the presence of SWCNT. Docking studies determined the occupation of preferred docked site of SWCNT by vitamin K1 on α- syn conformation. A molecular dynamics study also showed that vitamin K1 reduced the structural changes of α- syn induced by SWCNT. Cellular data exhibited that the cytotoxicity of α- syn co-incubated with vitamin K1 in the presence of SWCNTs is less than the outcomes obtained in the absence of the vitamin K1. Conclusion: It may be concluded that vitamin K1 decreases the propensity of α- syn aggregation in the presence of SWCNTs and induction of cytotoxicity

Exploring the interaction of quercetin-3-O-sophoroside with SARS-CoV-2 main proteins by theoretical studies: A probable prelude to control some variants of coronavirus including Delta

The aim of this study was to investigate the mechanism of interaction between quercetin-3-O-sophoroside and different SARS-CoV-2’s proteins which can bring some useful details about the control of different variants of coronavirus including the recent case, Delta. The chemical structure of the quercetin-3-O-sophoroside was first optimized. Docking studies were performed by CoV disease-2019 (COVID-19) Docking Server. Afterwards, the molecular dynamic study was done using High Throughput Molecular Dynamics (HTMD) tool. The results showed a remarkable stability of the quercetin-3-O-sophoroside based on the calculated parameters. Docking outcomes revealed that the highest affinity of quercetin-3-O-sophoroside was related to the RdRp with RNA. Molecular dynamic studies showed that the target E protein tends to be destabilized in the presence of quercetin-3-O-sophoroside. Based on these results, quercetin-3-O-sophoroside can show promising inhibitory effects on the binding site of the different receptors and may be considered as effective inhibitor of the entry and proliferation of the SARS-CoV-2 and its different variants. Finally, it should be noted, although this paper does not directly deal with the exploring the interaction of main proteins of SARS-CoV-2 Delta variant with quercetin-3-O-sophoroside, at the time of writing, no direct theoretical investigation was reported on the interaction of ligands with the main proteins of Delta variant. Therefore, the present data may provide useful information for designing some theoretical studies in the future for studying the control of SARS-CoV-2 variants due to possible structural similarity between proteins of different variants

Myelodysplastic Syndrome with Myelofibrosis Transformed to a Precursor B-Cell Acute Lymphoblastic Leukemia: A Case Report with Review of the Literature

Myelodysplastic syndromes (MDS) comprise a group of heterogeneous clonal hematopoietic cell disorders characterized by cytopenias, bone marrow hypercellularity, and increased risk of transformation to acute leukemias. MDS usually transformed to acute myeloid leukemia, and transformation to acute lymphoblastic leukemia (ALL) is rare. Herein, we report a unique patient who presented with MDS with myelofibrosis. Two months after the initial diagnosis, she progressed to a precursor B-cell acute lymphoblastic leukemia. She was treated with induction therapy followed by allogenic stem cell transplantation. She was alive and doing well upon last followup. We have also reviewed the literature and discussed the clinicopathologic features of 36 MDS patients who progressed to ALL reported in the literature

Visual problem and low back pain as initial manifestation of multiple myeloma complicating pre-existing systemic sclerosis

Some connective tissue diseases are associated with an increased risk of developing neoplastic disorders. Association of rheumatoid arthritis and systemic lupus erythematosus with lymphoma, and of dermatomyositis with different malignancies including ovarian and lung cancer has been reported in the literature. Here, we describe a 58 years old man with systemic sclerosis (SSc) for 15 years who developed severe lumbar pain when he was admitted for intravenous infusion of prostaglandin E1 for his fingertip ulcers. He was found to have abnormal skeletal imaging. Laboratory tests including bone marrow aspiration and biopsy determined multiple myeloma causing extensive bony infiltration. The patient expired after two cycles of VAD and Bortezomide chemotherapy