Regulation of ctla-4 and pd-l1 expression in relapsing-remitting multiple sclerosis patients after treatment with fingolimod, ifnβ-1α, glatiramer acetate, and dimethyl fumarate drugs

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) that is characterized by inflammation which typically results in significant impairment in most patients. Immune checkpoints act as co-stimulatory and co-inhibitory molecules and play a fundamental role in keeping the equilibrium of the immune system. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) and Programmed death-ligand 1 (PD-L1), as inhibitory immune checkpoints, participate in terminating the development of numerous autoimmune diseases, including MS. We assessed the CTLA-4 and PD-L1 gene expression in the different cell types of peripheral blood mononuclear cells of MS patients using single-cell RNA-seq data. Additionally, this study outlines how CTLA-4 and PD-L1 expression was altered in the PBMC samples of relapsing-remitting multiple sclerosis (RRMS) patients compared to the healthy group. Finally, it investigates the impact of various MS-related treatments in the CTLA-4 and PD-L1 expression to restrain autoreactive T cells and stop the development of MS autoimmunity

Hybrid poly‐l‐lactic acid/poly(ε‐caprolactone) nanofibrous scaffold can improve biochemical and molecular markers of human induced pluripotent stem cell‐derived hepatocyte‐like cells

A suitable alternative strategy for liver transplantation is the use of nanofibrous scaffolds together with stem cells. In this study, a random hybrid of poly-L-lactic acid (PLLA) and polycaprolactone (PCL) was used as a three-dimensional (3D) culture for hepatocyte-like cells (HLCs) differentiation and compared with routine culture (2D). The expression of the endodermal marker, FOXA2, was assessed on day 3 and the hepatic markers; albumin (ALB), alpha-1 antitrypsin (AAT), and cytokeratin-18 (CK-18) were evaluated on day 18 by (qPCR). As well as, albumin, alpha-fetoprotein, and low-density lipoprotein (LDL) uptake were evaluated by immunocytochemistry; moreover Periodic Acid-Schiff and Oil red were done by cell staining. In addition, alpha-fetoprotein (AFP) and urea production were evaluated by chemiluminescence and colorimetric assays. Light and Scanning Electron Microscopy (SEM) microscope showed changes in the cells in 2D and 3D models. The gene expression of hepatic markers werewas significantly higher in the three-dimensional cultures. In addition, immunocytochemistry and cell staining showed that albumin, alpha-fetoprotein, LDL-uptake, Periodic Acid-Schiff, and Oil red were expressed in both cells derived on 2D and 3D. Furthermore, the evaluation of alpha-fetoprotein and urea secretion was significantly different between 2D and 3D strategies. These findings suggest that functionally cells cultured on a PLLA/PCL scaffold may be suitable for cell therapy and regenerative medicine

Impacts of the Staphylococcal Enterotoxin H on the Apoptosis and lncRNAs in PC3 and ACHN

Cancer is considered as the most lethal disease for human beings, and up to now many attempts were failed for prevention and treatment of this tremendous health problem. Consequently, this study purpose was to investigate novel therapeutic methods for cancer. The bacterial toxin can result in cell death throughout the induction of apoptosis in cancer cell lines. We evaluated apoptosis and the expression levels of long non-coding RNAs (lncRNAs) in PC3, ACHN and HDF cell lines that were transfected with pCDNA3.1(+)-seh and empty plasmid. pCDNA3.1(+)-seh treatment showed overexpression of GAS5 (p = 0.0033 and p = 0.0033) in PC3 and ACHN cells, down regulation of PCA3 and NEAT1 (p = 0.0092 and p = 0.0097) in the PC3 cells, and down regulation of PVT1 and MALAT1 (p = 0.0239 and p = 0.0133) in the ACHN cells in comparison with the empty plasmid, but there was no significant effect on HDF normal cells. Additionally, this study data demonstrated that the cell adhesion was down regulated. The flow cytometry data showed transfection by pCDNA3.1 (+)-seh could elevate PC3 and ACHN cell apoptosis levels in comparison with empty plasmid. This study findings propose that SEH toxin of S. aureus could be a useful candidate for therapeutic researches in cancer vaccine development

Expression and characterization of a novel recombinant cytotoxin II from Naja naja oxiana venom: A potential treatment for breast cancer

Breast cancer (BC) is among the leading causes of mortality from cancer in women. Many of the available anticancer drugs have various side effects. Therefore, researchers are seeking novel anticancer agents particularly from natural compounds and in this regard, snake venom is still one of the main sources of drug discovery. Previous studies showed potential anticancer effects of Cytotoxin II (CTII) from Naja naja oxiana against the different types of cancers. In this study, a pET-SUMO-CTII vector was transformed into SHuffle® T7 Express, an Escherichia coli strain, for recombinant protein expression (rCTII) and the cytotoxic effects of this protein was assessed in MCF-7 cells. The flow cytometry assay was applied to measure the apoptosis and cell cycle. Also, mRNA levels of the Bax, Bcl2, P53, caspase-3, caspase-8, caspase-9, caspase-10, matrix metalloproteinases (MMP)-3, and MMP-9 were analyzed by quantitative real-time PCR to determine the underlying cellular pathways affected by rCTII. The results of this study showed that treatment with 4 μg mL−1 of rCTII enhanced apoptosis through the intrinsic and extrinsic pathways. Also, the increase of the cells' proportion in the sub-G1 phase as well as a reduction in S phase was observed. In addition, the expression of MMP-3 and MMP-9 was decreased in the treated group in comparison to the control group that may contribute to the reduced migratory ability of tumor cells. These experimental results indicate that rCTII has anti-proliferative potential, and so this protein could be a potential drug for BC therapy in combination with other drugs

Twin reversed arterial perfusion sequence in a monochorionic monoamniotic twin pregnancy: a very rare condition

Background: Twin reversed arterial perfusion sequence (TRAP) is a very rare congenital anomaly. We present sonographic findings of TRAP sequence in the case of a multiparous woman with a monochorionic monoamniotic twin pregnancy who was referred to our unit for blood sugar control. Case presentation: The patient had a history of co-twin demise at 13 weeks of gestation without appropriate fetal surveillance afterwards. We found a monochorionic placentation with a normal appearing pump twin, an abnormal appearing co-twin without obvious cardiac activity and reversed arterial flow toward instead of away from the anomalous acardiac fetus. Therefore, the sonographic diagnosis of TRAP sequence was confirmed. Conclusions: We recommend considering the potential rare complications of monochorionic twin pregnancy which necessitates proper surveillance and intervention to monitor suitable growth of pump twin. © 2020, The Author(s)

Cytotoxic t-lymphocyte antigen-4 in colorectal cancer: Another therapeutic side of capecitabine

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory immune checkpoint that can be expressed in tumor-infiltrating lymphocytes and colorectal cancer (CRC) cells. This immune checkpoint can attenuate anti-tumoral immune responses and facilitate tumor growth and metastasis. Although capecitabine is an effective chemotherapeutic agent for treating CRC, its effect on the tumoral CTLA-4 expression remains unclear. In the current research, we applied the GSE110224 and GSE25070 datasets to characterize CTLA-4 expression in CRC patients. Then, we analyzed CTLA-4 expression in CRC samples, HT-29, HCT-166, and SW480 cell lines using real-time PCR. Our bioinformatic results have highlighted the overexpression of CTLA-4 in the CRC tissues compared to the adjacent non-tumoral tissues. Our in vitro studies have indicated that SW480 cells can sub-stantially overexpress CTLA-4 compared to HT-29 and HCT 116 cells. In addition, capecitabine can remarkably downregulate the expression of CTLA-4 in SW480 cells. Collectively, capecitabine can inhibit the expression of CTLA-4 in CRC cells and might bridge the immunotherapy approaches with chemotherapy

Functionalized metallic 2D transition metal dichalcogenide-based solid-state electrolyte for flexible all-solid-state supercapacitors

Highly efficient and durable flexible solid-state supercapacitors (FSSSCs) are emerging as low-cost devices for portable and wearable electronics due to the elimination of leakage of toxic/corrosive liquid electrolytes and their capability to withstand elevated mechanical stresses. Nevertheless, the spread of FSSSCs requires the development of durable and highly conductive solid-state electrolytes, whose electrochemical characteristics must be competitive with those of traditional liquid electrolytes. Here, we propose an innovative composite solid-state electrolyte prepared by incorporating metallic two-dimensional group-5 transition metal dichalcogenides, namely, liquid-phase exfoliated functionalized niobium disulfide (f-NbS2) nanoflakes, into a sulfonated poly(ether ether ketone) (SPEEK) polymeric matrix. The terminal sulfonate groups in f-NbS2 nanoflakes interact with the sulfonic acid groups of SPEEK by forming a robust hydrogen bonding network. Consequently, the composite solid-state electrolyte is mechanically/dimensionally stable even at a degree of sulfonation of SPEEK as high as 70.2%. At this degree of sulfonation, the mechanical strength is 38.3 MPa, and thanks to an efficient proton transport through the Grotthuss mechanism, the proton conductivity is as high as 94.4 mS cm–1 at room temperature. To elucidate the importance of the interaction between the electrode materials (including active materials and binders) and the solid-state electrolyte, solid-state supercapacitors were produced using SPEEK and poly(vinylidene fluoride) as proton conducting and nonconducting binders, respectively. The use of our solid-state electrolyte in combination with proton-conducting SPEEK binder and carbonaceous electrode materials (mixture of activated carbon, single/few-layer graphene, and carbon black) results in a solid-state supercapacitor with a specific capacitance of 116 F g–1 at 0.02 A g–1, optimal rate capability (76 F g–1 at 10 A g–1), and electrochemical stability during galvanostatic charge/discharge cycling and folding/bending stresses

The expression pattern of VISTA in the PBMCs of relapsing-remitting multiple sclerosis patients: A single-cell RNA sequencing-based study

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS). Dysregulated immune responses have been implicated in MS development. Growing evidence has indicated that inhibitory immune checkpoint molecules can substantially regulate immune responses and maintain immune tolerance. V-domain Ig suppressor of T cell activation (VISTA) is a novel inhibitory immune checkpoint molecule that can suppress immune responses; however, its expression pattern in the peripheral blood mononuclear cells (PBMCs) of relapsing-remitting multiple sclerosis (RRMS) has not thoroughly been studied. Herein, we evaluated Vsir expression in PBMCs of RRMS patients and characterized the expression pattern of the Vsir in the PBMCs of MS patients. Besides, we investigated the effect of fingolimod, IFNβ-1α, glatiramer acetate (GA), and dimethyl fumarate (DMF) on Vsir expression in PBMCs of RRMS patients. Our results have shown that Vsir expression is significantly downregulated in the PBMCs of patients with RRMS. Besides, the single-cell RNA sequencing results have demonstrated that Vsir expression is downregulated in classical monocyte, intermediate monocytes, non-classical monocytes, myeloid DCs (mDC), Plasmacytoid dendritic cells (pDCs), and naive B-cells of PBMCs of MS patients compared to the control. In addition, DMF, IFNβ-1α, and GA have significantly upregulated Vsir expression in the PBMCs of RRMS patients. Collectively, the current study has shed light on Vsir expression in the PBMCs of MS patients; however, further studies are needed to elucidate the significance of VISTA in the mentioned immune cells