Pharmacological Inhibition of Caspase and Calpain Proteases: A Novel Strategy to Enhance the Homing Responses of Cord Blood HSPCs during Expansion

Background: Expansion of hematopoietic stem/progenitor cells (HSPCs) is a well-known strategy employed to facilitate the transplantation outcome. We have previously shown that the prevention of apoptosis by the inhibition of cysteine proteases, caspase and calpain played an important role in the expansion and engraftment of cord blood (CB) derived HSPCs. We hypothesize that these protease inhibitors might have maneuvered the adhesive and migratory properties of the cells rendering them to be retained in the bone marrow for sustained engraftment. The current study was aimed to investigate the mechanism of the homing responses of CB cells during expansion. Methodology/Principal Findings: CB derived CD34 + cells were expanded using a combination of growth factors with and without Caspase inhibitor-zVADfmk or Calpain 1 inhibitor- zLLYfmk. The cells were analyzed for the expression of homingrelated molecules. In vitro adhesive/migratory interactions and actin polymerization dynamics of HSPCs were assessed. In vivo homing assays were carried out in NOD/SCID mice to corroborate these observations. We observed that the presence of zVADfmk or zLLYfmk (inhibitors) caused the functional up regulation of CXCR4, integrins, and adhesion molecules, reflecting in a higher migration and adhesive interactions in vitro. The enhanced actin polymerization and the RhoGTPase protein expression complemented these observations. Furthermore, in vivo experiments showed a significantly enhanced homing to the bone marrow of NOD/SCID mice

Panax ginseng Modulates Cytokines in Bone Marrow Toxicity and Myelopoiesis: Ginsenoside Rg1 Partially Supports Myelopoiesis

In this study, we have demonstrated that Korean Panax ginseng (KG) significantly enhances myelopoiesis in vitro and reconstitutes bone marrow after 5-flurouracil-induced (5FU) myelosuppression in mice. KG promoted total white blood cell, lymphocyte, neutrophil and platelet counts and improved body weight, spleen weight, and thymus weight. The number of CFU-GM in bone marrow cells of mice and serum levels of IL-3 and GM-CSF were significantly improved after KG treatment. KG induced significant c-Kit, SCF and IL-1 mRNA expression in spleen. Moreover, treatment with KG led to marked improvements in 5FU-induced histopathological changes in bone marrow and spleen, and partial suppression of thymus damage. The levels of IL-3 and GM-CSF in cultured bone marrow cells after 24 h stimulation with KG were considerably increased. The mechanism underlying promotion of myelopoiesis by KG was assessed by monitoring gene expression at two time-points of 4 and 8 h. Treatment with Rg1 (0.5, 1 and 1.5 µmol) specifically enhanced c-Kit, IL-6 and TNF-α mRNA expression in cultured bone marrow cells. Our results collectively suggest that the anti-myelotoxicity activity and promotion of myelopoiesis by KG are mediated through cytokines. Moreover, the ginsenoside, Rg1, supports the role of KG in myelopoiesis to some extent

Anti-neutrophil cytoplasmic antibody associated vasculitis following rituximab: Outcomes of 50 patients in a tertiary single centre

Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an uncommon condition with heterogeneous multisystem organ involvement and significant morbidity and mortality. This study aimed to characterize the clinical features and laboratory characteristics, including B cell depletion, the ability to reduce corticosteroid dosage, and outcomes, of patients with AAV following rituximab treatment. Methods: Retrospective clinical and laboratory data were collected from patients with AAV who visited our lupus unit, including 50 treated with rituximab. Numeric response variables (median and range) were collected, including age, follow-up duration, disease duration, and Birmingham Vasculitis Activity Score (version 3). Statistical analyses were conducted using the SPSS 25.0 software. Statistical significance was considered a p -value <.05. Results: Of the 50 patients, 40 (80%) had granulomatosis with polyangiitis, 30 (75%) achieved remission, and 10 (25%) had active disease. Fifteen patients (30%) had positive ANCA levels at their last ANCA level assessment follow-up. Thirty-seven patients (74%) had B cell depletion, and 30 (81.1%) were in remission. Their median immunoglobulin levels were 7.6 (2.7–21.2) g/L for IgG, 0.5 (0.07–1.71) g/L for IgM, and 1.83 (0.14–4.87) g/L for IgA. Forty-two patients (84%) were able to lower their steroid dose to <7.5 mg, with 36 (85.7%) in remission and six (14.3%) having active disease ( p = .003). Conclusion: Our data suggests that most patients experience clinical remission after rituximab maintenance treatment. Half the patients were in remission, with normal creatinine levels and inflammatory markers. In addition, our patients could reduce steroid use

Thermal efficiency analysis of a nanofluid-based micro combined heat and power system using CNG and biogas

In the present study, a micro combined heat and power (micro-CHP) system using compressed natural gas (CNG) and biogas fuels, was developed. The objective of this research study was to investigate the utilization of nanofluids as a working fluid to improve thermal performance of the micro-CHP system. Three different nanofluids based on the CNT, Al2O3, and SiO2 have been investigated. The nanofluids was used as the circulating fluid to recover the heating power from the micro-CHP system. Three different concentration of nanoparticles (25, 50 and 100 ppm) have been used. The efficiency of separated heat and power (SHP) system was 27.6% while using combined heat and power, the total efficiency increased up to 65.3%. The results showed that by using CNG gas thermal efficiency of micro-CHP improve compared to the biogas. The result of the present study showed that nanofluids enhances the thermal efficiency of the micro-CHP system. By using the Al2O3 nanofluid the efficiency of micro-CHP efficiency is 73%. While by using the SiO2 and CNTs nanofluids the efficiency of micro-CHP efficiency is 70% and 66.3% respectively. So, we can coclude that by using the Al2O3 nanofluid thermal performance of micro-CHP systems improves

Electrodeposition of Lithium-Based Upconversion Nanoparticle Thin Films for Efficient Perovskite Solar Cells

In this work, high-quality lithium-based, LiYF4=Yb3+,Er3+ upconversion (UC) thin film was electrodeposited on fluorene-doped tin oxide (FTO) glass for solar cell applications. A complete perovskite solar cell (PSC) was fabricated on top of the FTO glass coated with UC thin film and named (UC-PSC device). The fabricated UC-PSC device demonstrated a higher power conversion efficiency (PCE) of 19.1%, an additional photocurrent, and a better fill factor (FF) of 76% in comparison to the pristine PSC device (PCE = ~16.57%; FF = 71%). Furthermore, the photovoltaic performance of the UC-PSC device was then tested under concentrated sunlight with a power conversion efficiency (PCE) of 24% without cooling system complexity. The reported results open the door toward efficient PSCs for renewable and green energy applications

Preconditioning by Hydrogen Peroxide Enhances Multiple Properties of Human Decidua Basalis Mesenchymal Stem/Multipotent Stromal Cells

Stem cell-based therapies rely on stem cell ability to repair in an oxidative stress environment. Preconditioning of mesenchymal stem cells (MSCs) to a stress environment has beneficial effects on their ability to repair injured tissues. We previously reported that MSCs from the decidua basalis (DBMSCs) of human placenta have many important cellular functions that make them potentially useful for cell-based therapies. Here, we studied the effect of DBMSC preconditioning to a stress environment. DBMSCs were exposed to various concentrations of hydrogen peroxide (H2O2), and their functions were then assessed. DBMSC expression of immune molecules after preconditioning was also determined. DBMSC preconditioning with H2O2 enhanced their proliferation, colonogenicity, adhesion, and migration. In addition, DBMSCs regardless of H2O2 treatment displayed antiangiogenic activity. H2O2 preconditioning also increased DBMSC expression of genes that promote cellular functions and decreased the expression of genes, which have opposite effect on their functions. Preconditioning also reduced DBMSC expression of IL-1β, but had no effects on the expression of other immune molecules that promote proliferation, adhesion, and migration. These data show that DBMSCs resist a toxic environment, which adds to their potential as a candidate stem cell type for treating various diseases in hostile environments