PLT counts, cellular morphologies, PLT membranes, cytoplasmic structures, aggregation rates, and hemostatic PLT function stored at 4°C for 10 to 14 days were better than those stored at 22°C for 5 days.
Platelets (PLTs) are classically used in the clinical setting to maintain hemostasis. Recent evidence supports important roles for PLTs in host inflammatory and immune responses, and PLT-rich plasma has been demonstrated to inhibit the growth of bacteria in vitro and in vivo; however, few studies have examined whether PLTs can inhibit bacterial growth directly, and related mechanisms have not been elucidated further. Accordingly, in this study, we evaluated the effects of PLTs on bacterial growth. We washed and purified PLTs from peripheral blood, then confirmed that PLTs significantly inhibited the growth of Staphylococcus aureus when cocultured in vitro. Moreover, PLTs damaged DNA and blocked cell division in S. aureus. During coculture, PLT-derived TGF-β1 was dramatically down-regulated compared with that in PLT culture alone, and the addition of TGF-β1 to the coculture system promoted the inhibition of PLTs on S. aureus. Analysis of a murine S. aureus infection model demonstrated that the depletion of PLTs exacerbated the severity of infection, whereas the transfusion of PLTs alleviated this infection. Our observations demonstrate that PLTs could directly inhibit the growth of S. aureus by damaging DNA and blockage cell division, and that PLT-derived TGF-β1 may play an important role in this machinery.-Xu, J., Yi, J., Zhang, H., Feng, F., Gu, S., Weng, L., Zhang, J., Chen, Y., An, N., Liu, Z., An, Q., Yin, W., Hu, X. Platelets directly regulate DNA damage and division of Staphylococcus aureus.
The widespread use of antibiotics has led to the emergence of drug-resistant bacteria, particularly multidrug-resistant bacteria. MRSA is the most common drug-resistant bacterium that causes suppurative infections in humans.
Background The fate of hematopoietic stem cells (HSCs) is determined by a complex regulatory network that includes both intrinsic and extrinsic signals. In the past decades, many intrinsic key molecules of HSCs have been shown to control hematopoiesis homeostasis. Non-hematopoietic niche cells also contribute to the self-renewal, quiescence, and differentiation of HSCs. Mesenchymal stromal cells (MSCs) have been identified as important components of the niche. However, the regulatory role of MSCs in hematopoiesis has not been fully understood. Methods Caspase-3 and NLRP3 gene knockout mice were generated respectively, and hematopoietic development was evaluated in the peripheral circulation and bone marrow by flow cytometry, colony formation assay, and bone marrow transplantation. Bone-associated MSCs (BA-MSCs) were then isolated from gene knockout mice, and the effect of Caspase-3/NLRP3 deficient BA-MSCs on hematopoiesis regulation was explored in vivo and ex vivo. Results We report that Caspase-3 deficient mice exhibit increased myelopoiesis and an aberrant HSC pool. Ablation of Caspase-3 in BA-MSCs regulates myeloid lineage expansion by altering the expression of hematopoietic retention cytokines, including SCF and CXCL12. Interestingly, NLRP3 gene knockout mice share phenotypic similarities with Caspase-3 deficient mice. Additionally, we found that NLRP3 may play a role in myeloid development by affecting the cell cycle and apoptosis of hematopoietic progenitors. Conclusions Our data demonstrate that the Caspase-3/NLRP3 signaling functions as an important regulator in physiological hematopoiesis, which provides new insights regarding niche signals that influence hematopoiesis regulation in the bone marrow.
During storage in blood banks, red blood cells (RBCs) undergo the mechanical and metabolic damage, which may lead to the diminished capacity to deliver oxygen. At high altitude regions, the above-mentioned damage may get worse. Thus, more attention should be paid to preserve RBCs when these components need transfer from plain to plateau regions. Recently, we found that mesenchymal stromal cells (MSCs) could rescue from anemia, and MSCs have been demonstrated in hematopoietic stem cells (HSCs) transplantation to reconstitute hematopoiesis in vivo by us. Considering the functions and advantages of MSCs mentioned above, we are trying to find out whether they are helpful to RBCs in storage duration at high altitudes. In the present study, we first found that mice MSCs could be preserved in citrate phosphate dextrose adenine-1 (CPDA-1) at 4 ± 2°C for 14 days, and still maintained great viability, even at plateau region. Thus, we attempted to use MSCs as an available supplement to decrease RBCs lesion during storage. We found that MSCs were helpful to support RBCs to maintain biochemical parameters and kept RBCs function well on relieving anemia in an acute hemolytic murine model. Therefore, our investigation developed a method to get a better storage of RBCs through adding MSCs, which may be applied in RBCs storage as a kind of cellular additive into preservation solution.
Background Blood transfusion, a common basic supporting therapy, can lead to acute hemolytic transfusion reaction (AHTR). AHTR poses a great risk to patients through kidney function damage in a short time. Previous reports found that heme from destroyed red blood cells impaired kidney function, and NLR family pyrin domain containing 3 (NLRP3) inflammasome was augmented in case of kidney injury. However, the detailed mechanism regarding whether NLRP3 inflammasome is involved in kidney function injury in AHTR is not fully understood yet. Methods Hemolysis models were established by vein injection with human blood plasma or mouse heme from destroyed red blood cells. The injured renal tubular epithelial cells (RTECs) were evaluated by tubular damage markers staining in hemolysis models and in primary RTECs in vitro. The activation of NLRP3 inflammasome in RTECs by hemes was investigated by Western blot, ELISA, scanning electron microscopy, immunofluorescent staining, flow cytometry, and hemolysis models. NLRP3 gene knockout mice were employed to confirm these observations in vitro and in vivo. The binding between a novel inhibitor (66PR) and NLRP3 was affirmed by molecule docking and co‐immunoprecipitation. The rescue of 66PR on kidney function impairment was explored in murine hemolysis models. Results We found that heme could activate NLRP3 inflammasome in RTECs to induce kidney function injury. NLRP3 gene knockout could prevent the damage of RTECs caused by hemes and recover kidney function in AHTR. Moreover, NLRP3 inflammasome chemical inhibitor, 66PR, could bind to NLRP3 protein and inhibit inflammasome activation in RTECs, which consequently relieved the injury of RTECs caused by hemes, and alleviated kidney function damage in the AHTR model. Conclusions Hemes could activate NLRP3 inflammasome in RTECs, and a novel NLRP3 inflammasome inhibitor named 66PR relieved kidney function damage in AHTR. Our findings provided a new possible strategy to treat kidney function failure in AHTR.
Polylactic acid (PLA) is one of the biodegradable materials that has been used in the areas of surgical healing lines, cancer treatment, and wound healing. However, the application of PLA is still rather limited due to its high hydrophobicity and poor antibacterial activity. In order to enhance the antifouling and antibacterial performances of PLA, here we modified the surface of PLA with various sizes of hydrogel micropatterns in negative or positive mode using plasma treatment, the photomask technique, and UV-graft polymerization. The hydrogel micropatterns consist of poly(ethylene glycol) diacrylate (PEGDA), poly(2m e t h a c r y l o y l o x y e t h y l p h o s p h o r y l c h o l i n e ) ( P M P C ) , a n d p o l y -(methacryloyloxyethyltrimethylammonium chloride) (PDMC). Compared to PLA, the patterned PLA (PLA−PMPC/PDMC/ PEGDA) shows obviously enhanced antifouling and antibacterial activities. For PLA−PMPC/PDMC/PEGDA with either positive or negative micropatterns, the antifouling and antibacterial properties are gradually increasing with decreasing the size of micropatterns. Compared with PLA−PMPC/PDMC/PEGDA bearing positive and negative micropatterns in the same size, the PLA−PMPC/PDMC/PEGDA with negative micropatterns exhibits slightly better biological activity and the PLA−PMPC/PDMC/ PEGDA with 3 μm negative hydrogel micropatterns shows the best hydrophilicity, antifouling, and antibacterial properties. Combining the in vitro hemolysis assay, cytotoxicity, water absorption test, and degradation test results, it is suggested that the fabrication of hydrogel micropatterns onto the PLA surface could significantly improve biological activities of PLA. We expect that this work would provide a new strategy to potentially develop PLA as a promising wound dressing.
The hydrophobicity and inertness of polypropylene (PP) material surface usually encounter serious biofouling and bacterial infections, which hampers its potential application as biomedical polymers. Many strategies have been developed to...
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