A study of blood group conversion in patients with ABO incompatible hematopoietic stem cell transplantation-A decade survey.

BACKGROUND: ABO incompatibility is not a contraindication but would affect the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The dynamic change of blood phenotype is not only related to the patient's status, but also the basis for the implementation of compatible blood transfusion. The criteria for judging a complete transformation to donor-type and the principle of blood transfusion at relapse need to be unified. We aimed to illustrate the significance of blood group monitoring after allo-HSCT. MATERIAL AND METHODS: We collected 263 patients underwent ABO incompatible allo-HSCT from January 2010 to December 2019, and monitored blood type regularly according to the frequency of the patient's return visits till complete conversion or death. Non-parametric test was used to find differences among incompatible groups. We analyzed factors potentially influence blood type conversion by Binary Logistic model. Cox regression model was used to illustrate the relationship between blood-type conversion and prognosis. RESULTS: The median days of conversion were 107, 91 and 108 in major-, minor- and bidirectional groups respectively. Blood type conversion correlated with HLA compatibility (P = 0.012, OR=2.69) and acute graft-versus-host-disease (P = 0.001, OR=0.06). Patients with incomplete blood type conversion had a higher death rate than those with complete blood type conversion(P = 0.003, OR=3.703). DISCUSSION: Blood type monitoring can help to evaluate the prognosis of transplantation and assess the risk of death. It is recommended to monitor the changes of blood group antigens and antibodies, especially within a year after transplantation, to predict the risk of adverse events (such as GVHD, recurrence, death, etc.).

Inhibition of TREM-1 attenuates inflammation and lipid accumulation in diet-induced nonalcoholic fatty liver disease.

In the liver tissues of obese diabetic or nondiabetic patients, triggering receptor expressed on myeloid cells-1 (TREM-1) is usually found to be upregulated, thus leading to upregulation of various inflammatory cytokines and lipid accumulation. On the other hand, nonalcoholic fatty liver disease (NAFLD), characterized by excess lipid accumulation, and inflammatory injury in liver, is becoming an epidemic disease, globally. In the present study, we aimed to investigate the biological role and the underlying mechanisms of TREM-1 in NAFLD. upregulation of TREM-1 occurred in high-fat diet (HFD)-induced mice NAFLD model and oleic acid-treated HepG2 and primary mouse hepatocytes cell model at messenger RNA and protein levels. Functional studies established that overexpression of TREM-1 displayed hyperlipidemia, and increased in inflammatory indicators and lipid accumulation-related genes, which was ameliorated by knockdown of TREM-1. Our results also showed that obvious lipid accumulation and inflammatory injury occurred in the liver tissue of HFD-fed mice, while treatment with lentiviral vector short hairpin TREM showed marked improvement in tissue morphology and architecture and less lipid accumulation, thus deciphering the mechanism through which knockdown of TREM-1 ameliorated the inflammatory response and lipid accumulation of NAFLD mice through inactivation of the nuclear factor-κB (NF-κB) and PI3K/AKT signal pathways, respectively. In conclusion, TREM-1/NF-κB and TREM-1/PI3K/AKT axis could be an important mechanism in ameliorating the inflammatory response and lipid accumulation, respectively, thus shedding light on the development of novel therapeutics to the treatment of NAFLD.

Circ_0056618 and CXCR4 act as competing endogenous in gastric cancer by regulating miR-206.

Circular RNAs (circRNAs) have proved to play an important role in gastric cancer. In this study, we found that circ_0056618 took part in gastric cancer cell proliferation and survival. The real-time polymerase chain reaction result showed that circ_0056618 was overexpressed in tumor tissues or cells compared with adjacent normal tissues or normal cells and had a negative relationship to gastric cancer patients' survival time. Meanwhile, the inhibition of circ_0056618 suppressed the proliferation and metastasis of gastric cancer cells. Further bioinformatical analysis indicated that circ_0056618 sponged miR-206 to regulate CXCR4 according to the prediction of TargetScan and miRanda. Dual-luciferase reporter assay and Western blot analysis revealed the underlying relationship of circ_0056618, miR-206, and CXCR4. Hence, circ_0056618 negatively regulated miR-206 expression promoting CXCR4 expression. Altogether, circ_0056618 is a potential gastric cancer prognostic marker, as well as a potential therapeutic target to inhibit gastric cancer metastasis.

Recombinant Human Bone Morphogenic Protein-2 Immobilized Fabrication of Magnesium Functionalized Injectable Hydrogels for Controlled-Delivery and Osteogenic Differentiation of Rat Bone Marrow-Derived Mesenchymal Stem Cells in Femoral Head Necrosis Repair.

Femoral head necrosis (FHN) is a clinically progressive disease that leads to overwhelming complications without an effective therapeutic approach. In recent decades, transplantation of mesenchymal stem cells (MSCs) has played a promising role in the treatment of FHN in the initial stage; however, the success rate is still low because of unsuitable cell carriers and abridged osteogenic differentiation of the transplanted MSCs. Biopolymeric-derived hydrogels have been extensively applied as effective cell carriers and drug vesicles; they provide the most promising contributions in the fields of tissue engineering and regenerative medicine. However, the clinical potential of hydrogels may be limited because of inappropriate gelation, swelling, mechanical characteristics, toxicity in the cross-linking process, and self-healing ability. Naturally, gelated commercial hydrogels are not suitable for cell injection and infiltration because of their static network structure. In this study, we designed a novel thermogelling injectable hydrogel using natural silk fibroin-blended chitosan (CS) incorporated with magnesium (Mg) substitutes to improve physical cross-linking, stability, and cell osteogenic compatibility. The presented observations demonstrate that the developed injectable hydrogels can facilitate the controlled delivery of immobilized recombinant human bone morphogenic protein-2 (rhBMP-2) and rat bone marrow-derived MSCs (rBMSCs) with greater cell encapsulation efficiency, compatibility, and osteogenic differentiation. In addition, outcomes of in vivo animal studies established promising osteoinductive, bone mineral density, and bone formation rate after implantation of the injectable hydrogel scaffolds. Therefore, the developed hydrogels have great potential for clinical applications of FHN therapy.

Identification of N-glycoproteins of hip cartilage in patients with osteonecrosis of femoral head using quantitative glycoproteomics.

N-glycosylation is a major post-translational modification of proteins and involved in many diseases, however, the state and role of N-glycosylation in cartilage degeneration of osteonecrosis of femoral head (ONFH) remain unclear. The aim of this study is to identify the glycoproteins of ONFH hip cartilage. Cartilage tissues were collected from nine patients with ONFH and nine individuals with traumatic femoral neck fracture. Cartilage glycoproteins were identified by glycoproteomics based on LC-MS/MS. The differentially N-glycoproteins including glycosites were identified in ONFH and controls. A total of 408 N-glycoproteins with 444 N-glycosites were identified in ONFH and control cartilage. Among them, 104 N-glycoproteins with 130 N-glycosites were significantly differential in ONFH and control cartilage, which including matrix-remodeling-associated protein 5, prolow-density lipoprotein receptor-related protein 1, clusterin and lysosome-associated membrane glycoprotein 2. Gene Ontology analysis revealed the significantly differential glycoproteins mainly belonged to protein metabolic process, single-multicellular organism process, proteolysis, biological adhesion and cell adhesion. KEGG pathway and protein-protein interaction analysis suggested that the significantly differential glycoproteins were associated with PI3K-Akt signalling pathway, ECM-receptor interaction, protein processing in the endoplasmic reticulum and N-glycan biosynthesis. This information provides substantial insight into the role of protein glycosylation in the development of cartilage degeneration of ONFH patients.

Combination of L-gossypol and low-concentration doxorubicin induces apoptosis in human synovial sarcoma cells.

The current study aimed to investigate the function of L-gossypol and low­concentration doxorubicin (LCD) in the apoptosis of SW982 human synovial sarcoma cells (HSSCs). Wright­Giemsa staining, Hoechst 33258 staining and transmission electron microscopy were used to identify cellular morphological alterations. In addition, an MTT assay was performed to measure the inhibitory rate of the drug, flow cytometry was used to detect alterations in apoptosis and the cell cycle, and western blot analysis was used to detect Bcl­2 and Bax protein expression levels. Furthermore, the activity levels of caspase­3 and ­9 were measured in apoptotic cells. Following combination therapy, significant alterations in cellular morphology were observed, including condensation of the nucleus and formation of apoptotic bodies. Cell growth was demonstrated to be inhibited significantly in a dose­ and time­dependent manner. Flow cytometry results indicated that L­gossypol administration resulted in G1 phase arrest, whereas doxorubicin led to S phase arrest. Combination therapy resulted in a significant increase in the number of S phase­arrested cells. Following treatment with the drugs, Bcl­2 protein levels were observed to be reduced whilst Bax levels increased, and significant caspase­3 and ­9 activation was observed during combination therapy. Combination therapy with L­gossypol and LCD inhibited cell proliferation and induced apoptosis in SW982 HSSCs at a significantly greater level compared with either treatment alone. It was hypothesized that these effects are mediated via downregulation of the Bcl-2 protein and upregulation of Bax protein.

[Effect of thalassemia panel reactive antibody on proliferation and apoptosis of cord blood CD34(+) cells].

The study was purposed to explore the effect of panel reactive antibody (PRA) serum from patients with ß-thalassemia on proliferation and apoptosis of the CD34(+)cells from cord blood and its mechanism. CD34(+) cells of umbilical cord blood were incubated with different sera and complement respectively. After incubation, the samples were centrifuged and the supernatants were collected for lactate dehydrogenase (LDH) detection, and the CD34(+) cells were harvested and measured for the apoptosis by flow cytometry with Annexin V/PI. The intracellular DNA synthesis were also quantified by [(3)H]TdR incorporation using liquid scintillation counter. The results showed that concentration of LDH in PRA positive groups was higher as compared with control group, and the DNA synthesis of CD34(+) cells in PRA positive groups were inhibited. There were no differences in the percentage of cell apoptosis and necrosis among different groups. It is concluded that thalassemic serum PRA impairs the cell membrane, inhibits the DNA synthesis, which can be increased by addition of the complement, but PRA had no significant effect on apoptosis of CD34(+) cells.