The Effects of Plasma Exosomes of Young Individuals Compared to Old Ones on Age-Related Inflammation and Lineage Differentiation of CD34+ Umbilical Cord Blood Hematopoietic Stem Cells.

Sepsis-induced acute lung injury (S-ALI) is one of the diseases with a very high fatality rate. However, the traditional Chinese medicine compound Buzhong Yiqi Decoction (BZYQD) has an excellent effect in the treatment of S-ALI. Nevertheless, its mechanism of action is still unclear. In this study, we explored the molecular mechanisms of S-ALI injury treated with buzhong yiqi decoction through network pharmacology, in combination with in vivo experimental validation. Traditional Chinese medicine system pharmacology (TCMSP) database was used to screen the chemical composition of BZYQD and its action targets; Multiple databases were used to collect target genes for-S-ALI, including OMIM, TTD, GeneCards, and DrugBank; The STRING database was used for the protein- protein interaction (PPI) analysis of the common targets of the BZYQD and the S-ALI; The DAVID database was used for GO and KEGG analysis; molecular docking was used to detect the binding capacity of core components and targets. HE staining was used to visualize the pathology of lung tissue in each group; ELISA was used to detect the levels of inflammatory factors (IL-1β, IL-6, IL-8, NF-κB and TNF-α) and oxidative stressrelated factors (LDH, CK-MB, SOD, GSH-Px); The qPCR and Western blot were used to examine the mRNA and protein expression of IL-1β, IL-6, TNF-α NF-κB, p-NF-κB, PI3K, p-PI3K, AKT, and IKKα. 113 chemical components and 226 targets were screened from BZYQD; 9059 S-ALI-related genes were screened out, with a total of 228 intersecting targets between BZYQD and S-ALI. Stigmasterol, quercetin, and isorhamnetin are the core components of BZYQD, PPI analysis shows that AKT1, IL6, TNF, and IL1B are the core targets of BZYQD for treating S-ALI, and molecular docking results show that the core components have high binding activity with the target; Enrichment analysis shows that these core targets are related to the TNF signaling pathway. In vivo experimental studies have found that BZYQD can improve the degree of inflammatory infiltration and edema in lung tissue of S-ALI model mice, reduce the expression of IL-6, IL-1β, IL-8, TNF-α, LDH, CK-MB, and NF-κB in serum (P<0.05), as well as the mRNA and protein expression of IL-6, IL-1β, TNF-α, NF-κB, p-NF-κB, PI3K, p-PI3K, AKT, and IKKα in lung tissue (P<0.05), and levels of SOD and GSH-Px were increased (P<0.05). The action targets of the main chemical components of BZYQD are TNF, AKT, and IL6. These targets can promote the activation of PI3K and TNF pathways and mediate the occurrence of inflammation and oxidative stress, which provides inspiration for the treatment of S-ALI. However, the results of this study still need to be verified in combination with in vitro approaches. This study suggests that the mechanism of BZYQD in treating S-ALI may be achieved by inhibiting the TNF and PI3K signaling pathway and reducing inflammation and oxidative stress levels.

To explore the effect of Buyang Huanwu decoction (BYHWD) on pro-inflammatory cytokines in rats after focal cerebral infarction. Adult Sprague Dawley (SD) rats were randomly divided into following groups: normal control, sham, model, BYHWD. The rats in latter three groups were subdivided into subgroups of 1, 3, and 7 days after medication, with 5 rats in each group. The right side focal cerebral infarction model was reproduced by middle cerebral artery occlusion (MCAO). The rats in BYHWD group were gavaged with BYHWD of 10 ml/kg (14.2 g/kg, once a day) 2 hours after operation. Animals were sacrificed at corresponding time points. The protein and mRNA expression of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were determined by enzyme linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). There were low levels expression of IL-1β and TNF-α protein and mRNA in normal control group and the sham group. After cerebral infarction, the protein and mRNA expression of IL-1β and TNF-α began to increase in rats 1 day after the insult, and the protein and mRNA expression of IL-1β reached the peak on 3rd day, and then lowered, and the protein and mRNA expression of TNF-α reached the peak on 7th day. Compared with model group on 1st, 3rd and 7th day, the protein expression of IL-1β (ng/L: 90.290±8.693 vs. 102.556±13.934 on 1st day, 129.632±11.050 vs. 150.117±8.552 on 3rd day, 66.185±9.020 vs. 91.362±9.901 on 7th day) and TNF-α (ng/L: 210.341±19.247 vs. 236.887±20.137 on 1st day, 267.503±21.006 vs. 322.659±15.068 on 3rd day, 299.637±17.717 vs. 386.678±16.297 on 7th day), and mRNA expression of IL-1β (1 day: 0.54±0.09 vs. 0.64±0.11, 3 days: 0.80±0.06 vs. 0.89±0.07, 7 days : 0.70±0.09 vs. 0.78±0.08) and TNF-α (1 day: 0.64±0.09 vs. 0.73±0.11, 3 days: 0.74±0.13 vs. 0.85±0.07 , 7 days : 0.82±0.07 vs. 0.93±0.08], were all decreased obviously in BYHWD group ( P<0.05 or P<0.01). BYHWD could reduce the protein and mRNA expressions of IL-1β and TNF-α in levels after cerebral infarction. The result shows that it protects brain by modulating expression of pro-inflammatory mediators.

Human periodontal ligament cells (hPDLCs) are important source of periodontal tissue reconstruction. Under chronic inflammation, the multi-directional differentiation potential and chemotaxis in hPDLCs are decreased. Therefore, inhibiting inflammatory microenvironment and improving the functional characteristics of stem cells can better promote periodontal tissue reconstruction. This study was to investigate the effect of astaxanthin (AST) on lipopolysaccharide (LPS)-induced inflammation in hPDLCs and the underlying mechanisms. hPDLCs were isolated and cultured in vitro, and vimentin and keratin immunocytochemical staining were used to identify hPDLCs. CCK-8 assay was used to measure the effects of AST (1, 5, 10, 20, 50, 100, and 200 μmol/L) on proliferation of hPDLCs. Quantitative RT-PCR (RT-qPCR) and ELISA were used to measure the mRNA and protein expression of inflammatory factors (IL-6, IL-1β, and TNF-α) in the control (Con) group, the LPS group, and the LPS+AST (5, 10, 20, and 50 μmol/L) group. Western blotting was used to detect the protein expression of IKBα, phosphorylated IKBα (p-IKBα), and p65 in the Con group, the LPS group, the AST (20 μmol/L) group, and the LPS+AST (20 μmol/L) group. After 10 μmol/L PDTC treatment, the mRNA and protein expressions of IL-6, IL-1β, and TNF-α were detected by RT-qPCR and ELISA. Cell morphology and immunocytochemical staining showed that the cells were in line with the characteristics of hPDLCs. Treatment with AST could promote the proliferation of hPDLCs, which reached the peak at 20 μmol/L. The mRNA and protein expressions of IL-6, IL-1β, and TNF-α in the LPS group were higher than those in the Con group (all P<0.05). Compared with the LPS group, the mRNA and protein expressions of IL-6, IL-1β, and TNF-α in the LPS+AST (5, 10, 20, and 50 μmol/L) group were down-regulated (all P<0.05). Compared with the Con group, the levels of IKBα and p65 in cytoplasm of the LPS group were significantly downregulated (both P<0.05), and the levels of p-IKBα in cytoplasm and p65 in nucleus of the LPS group were significantly up-regulated (both P<0.05). Compared with the LPS group, the levels of IKBα and p65 in cytoplasm of the LPS+AST (20 μmol/L) group were significantly upregulated (both P<0.05), and the levels of p-IKBα in cytoplasm and p65 in nucleus of the LPS+AST (20 μmol/L) group were significantly downregulated (both P<0.05). The mRNA and protein expressions of IL-6, IL-1β, and TNF-α in the LPS+PDTC (10 μmol/L) group were lower than those in the LPS group (all P<0.05). AST promotes the proliferation of hPDLCs, which is related to suppression of LPS-induced the secretion of inflammatory factors via inhibiting the activation of NF-κB signaling pathway.

The role of chemokine activation of Rac GTPases in hematopoietic stem cell marrow homing, retention, and peripheral mobilization

Human bone marrow and umbilical cord blood are sources of allogeneic hematopoietic stem cells for transplantation, which is a life-saving treatment in a variety of diseases but is burdened by delayed T-cell reconstitution. Observational studies evaluating T-cell reconstitution in post-transplant recipients suggest that cord blood hematopoietic stem cells have a more effective capacity for T-cell reconstitution. This study focuses on the comparison of the capacity of cord blood and bone marrow hematopoietic stem cells to generate T cells in vitro. Hematopoietic stem cells were cultured in OP9-delta-like-1 and OP9-green fluorescent protein co-cultures to estimate T and myeloid generation capacity, respectively. Phenotypic markers of T-lineage or myeloid differentiation were measured by flow cytometry and used to analyze their kinetics as a function of culture time. Hematopoietic stem cells were labeled with carboxyfluorescein diacetate succinamidyl ester and analyzed after culture to track their phenotypic progression in consecutive generations. Mixed OP9-delta-like-1 co-cultures were done with either carboxyfluorescein diacetate succinamidyl ester-labeled bone marrow and unlabeled cord blood hematopoietic stem cells, or vice versa, to evaluate their mutual influence on T-lineage differentiation. The T-cell potential of hematopoietic stem cells was addressed quantitatively by limiting dilution analysis. Bulk cultures showed faster and more extensive T-cell differentiation by cord blood hematopoietic stem cells. Furthermore, the T-lymphoid differentiation capacity of cord blood and bone marrow hematopoietic stem cells can be discriminated very early based on the coordinated expression of CD34 and CD7. Mixing experiments with cord blood hematopoietic stem cells and bone marrow hematopoietic stem cells showed that these differences are cell intrinsic. Quantitative clonal analyses demonstrated that CD34(+)CD38(-/lo) hematopoietic stem cells from cord blood contained a two-fold higher T-lineage generation capacity than CD34(+)CD38(-/lo) bone marrow hematopoietic stem cells, whereas the myeloid differentiation was similar. Our data shows that cord blood hematopoietic stem cells have higher T-lymphoid differentiation potential than bone marrow hematopoietic stem cells and that this property is cell autonomous.

Objective: To illuminate the effect of NALP3 inflammasome on regulating the expression of cytokines of macrophages in periodontitis. Methods: RAW264.7 cells were cultured and divided into three groups. The first group stayed normal as control, the second group was stimulated by 1 mg/L Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS), the third group was pretreated with AC-YVAD-CMK (caspase-1 inhibitor) before stimulated with 1 mg/L Pg LPS. RAW264.7 cells pretreated with various concentrations (0, 5, 10, 25, 50, 75, 100, 200 μmol/L) of AC-YVAD-CMK for 2 h, and stimulated by 1 mg/L Pg LPS for 24 h in the third group. After that, cell survival rate were detected by cell counting kit-8. Every group cells gene transcription of NALP3 and interleukin-1β (IL-1β) were detected by quantitative real-time PCR (qPCR) after 6 h, protein expression of NALP3 and IL-1β were separately detected by Western blotting and enzyme linked immunosorbent assay (ELISA) after 24 h, respectively. Results: It is observed that treatment with 5, 10, 25, 50, 75, 100, 200 μmol/L AC-YVAD-CMK did not significantly affect the viability of RAW264.7 cells. qPCR showed that mRNA expression of IL-1β level (1.03±0.08, 5.48±0.22, 4.31±0.20) and NALP3 level (0.96±0.05, 2.62±0.44, 1.73±0.09). Western blotting showed that protein expression of NALP3 level (1.00±0.10, 2.34±0.04, 1.64±0.04), ELISA showed protein secretion of IL-1β level ([40.20±0.25], [61.50±1.81], [52.40±1.91] ng/L). After stimulated by Pg LPS, mRNA and protein expression of IL-1β (P<0.01, P<0.01) and NALP3 (P<0.01, P<0.01) significantly increased; but the expression of IL-1β (P=0.002, P=0.027) and NALP3 (P<0.01, P<0.01) were decreased when pretreated with AC-YVAD-CMK. Conclusions: NALP3 inflammasome signal pathway can be activated by Pg LPS in RAW264.7. Block of the pathway can inhibit Pg LPS-induced secretion of cytokines.

Objective. To investigate the effects of Dendrobium officinale polysaccharides (DOPS) on the expression of inflammatory factors IL-1β and TNF-α and the MKP-1/MAPK signal pathway. Methods. PTZ-induced epileptic rat models were established. The rats were randomly divided into four groups: the control group, the DOPS group, the model group, and the DOPS intervention group. RT-PCR was used to measure the mRNA expression of IL-1β and TNF-α in the hippocampi of all groups; western blot was used to measure the protein expression of IL-1β and TNF-α and phosphorylation of ERK1/2, JNK, p38, and MKP-1 in the hippocampi of all groups at weeks 1, 2, 3, and 4 after modeling. Results. At weeks 1, 2, 3, and 4 after modeling, there were no significant differences between the control group and the DOPS group in the mRNA and protein expression of IL-1β and TNF-α and phosphorylation of ERK1/2, JNK, p38, and MKP-1 (all P&gt;0.05); the mRNA and protein expression of IL-1β and TNF-α and phosphorylation of ERK1/2, JNK, and p38 were significantly increased, while the phosphorylation of MKP-1 was decreased in the model group compared with the control group. The mRNA and protein expression of IL-1β and TNF-α and phosphorylation of ERK1/2, JNK, and p38 were significantly decreased, while the phosphorylation of MKP-1 was increased in the DOPS intervention group compared with the model group. Conclusion. DOPS can reduce PTZ-induced brain inflammation and seizures of epileptic rats by inhibiting IL-1β, TNF-α, and MAPK signal pathways.

Ex vivo expansion of human cord blood (CB) hematopoietic stem cells (HSCs) is one approach to overcome limited numbers of HSCs in single CB units. However, there is still no worldwide acceptable HSC ex vivo expansion system. A main reason is that we still have very limited knowldege regarding mechanisms underlying maintenance and expansion of CB HSCs. Here we report that retinoid X receptor (RXR) activity is of significance for CB HSC ex vivo expansion. RXR antagonist HX531 significantly promoted ex vivo expansion of CB HSCs and progenitor cells (HPCs). RXR agonist Bexarotene notably suppressed ex vivo expansion of CB HSCs. Activation of RXR by Bexarotene significantly blocked expansion of phenotypic HSCs and HPCs and expressed increased functional HPCs as assessed by colony formation induced by UM171 and SR1. In vivo transplantation experiments in immune-deficient mice demonstrated that HX531 expanded CB HSCs possess long-term reconstituting capacities, and Bexarotene treatment inhibited expansion of functional CB HSCs. RNA-seq analysis revealed that RXR regulates expression of FBP1 (a negative regulator of glucose metabolism) and many genes involved in differentation. ECAR analysis showed that HX531 significantly promoted glycolytic activity of CB CD34+ HSCs and HPCs. Our studies suggest that RXR is a negative regulator of ex vivo expansion of CB HSCs and HPCs.

Background:Umbilical cord blood has been widely used in clinical transplantation. Blood gas analysis of umbilical cord blood is routinely used to evaluate neonatal asphyxia. This study aimed to evaluate an improved umbilical cord blood collection method that does not affect the results of umbilical cord blood gas analysis and hematopoietic stem cell transplantation-related indices.Methods:Three hundred pregnant women were recruited between December 2019 and August 2022. In total, 270 umbilical cord blood samples were included and randomly divided into 3 groups. Group A was defined as the group in which both umbilical cord blood samples for hematopoietic stem cell transplantation and blood gas analysis were collected. Group B was defined as the group from which umbilical cord blood was collected for hematopoietic stem cell transplantation. Group C was defined as that wherein umbilical cord blood was collected only for blood gas analysis. Hematopoietic stem cell transplantation-related indices were detected in groups A and B, and blood gas analysis was performed in groups A and C.Results:Hematopoietic stem cell transplantation-related indices were not significantly different between groups A and B. The pH, base excess, and lactic acid values were not significantly different between groups A and C.Conclusion:The cord blood double collection method would not affect the results of umbilical cord blood gas analysis and hematopoietic stem cell transplantation-related indices. It is suitable for cord blood collection when preparing for hematopoietic stem cell transplantation and blood gas analysis.

NOTCH-mediated exvivo expansion of human hematopoietic stem and progenitor cells by culture under hypoxia.

Microvesicles can transfer their contents, proteins and RNA, to target cells and thereby transform them. This may induce apoptosis or survival depending on cell origin and the target cell. In this study, we investigate the effect of leukemic cell microvesicles on umbilical cord blood hematopoietic stem cells to seek evidence of apoptosis or cell survival. Microvesicles were isolated from both healthy donor bone marrow samples and Jurkat cells by ultra-centrifugation and were added to hematopoietic stem cells sorted from umbilical cord blood samples by magnetic associated cell sorting (MACS) technique. After 7 days, cell count, cell viability, flow cytometry analysis for hematopoietic stem cell markers and qPCR for P53 gene expression were performed. The results showed higher cell number, higher cell viability rate and lower P53 gene expression in leukemia group in comparison with normal and control groups. Also, CD34 expression as the most important hematopoietic stem cell marker, did not change during the treatment and lineage differentiation was not observed. In conclusion, this study showed anti-apoptotic effect of leukemia cell derived microvesicles on umbilical cord blood hematopoietic stem cells.

To observe the effects of moxibustion on colonic mast cell degranulation and inflammatory factor expression in rats with diarrhea-predominant irritable bowel syndrome (IBS-D), and explore the potential mechanism of moxibustion in treating IBS-D. Forty-five rat pups born from 5 healthy SPF-grade pregnant SD rats, with 8 rats were randomly selected as the normal group. The remaining 37 rats were intervened with maternal separation, acetic acid enema, and chronic restraint stress to establish the IBS-D model. The successfully modeled 32 rats were then randomly assigned to a model group, a ketotifen group, a moxibustion group, and a moxibustion-medication group, with 8 rats in each group. The rats in the ketotifen group were intervened with intragastric administration of ketotifen solution (10 mL/kg); the rats in the moxibustion group were intervened with suspended moxibustion on bilateral "Tianshu" (ST 25) and "Shangjuxu" (ST 37); the rats in the moxibustion-medication group were intervened with suspended moxibustion combined with intragastric administration of ketotifen solution. All interventions were administered once daily for 7 consecutive days. The diarrhea rate and minimum volume threshold of abdominal withdrawal reflex (AWR) were calculated before and after modeling, as well as after intervention. After intervention, colonic tissue morphology was observed using HE staining; colonic mucosal ultrastructure was examined by scanning electron microscopy; colonic mast cell ultrastructure was observed using transmission electron microscopy; mast cell degranulation was assessed by toluidine blue staining; serum and colonic levels of histamine, interleukin (IL)-1β, IL-6, IL-1α, trypsin-like enzyme, and protease-activated receptor 2 (PAR-2) were measured by ELISA; the Western blot and real-time quantitative PCR were employed to evaluate the protein and mRNA expression of colonic IL-1β, IL-6, IL-1α, trypsin-like enzyme, and PAR-2; the immunofluorescence was used to detect the positive expression of histamine, IL-1β, IL-6, IL-1α, trypsin-like enzyme, and PAR-2 in the colonic tissue. Compared to the normal group, the rats in the model group exhibited extensive infiltration of inflammatory cells in colonic tissue, severe damage to the colonic mucosa, disordered arrangement of villi, reduced electron density, and a significant decrease in granule quantity within mast cells. The diarrhea rate and mast cell degranulation rate were increased (P<0.01), AWR minimum volume threshold was decreased (P<0.01); the serum and colonic levels of histamine, IL-1β, IL-6, IL-1α, trypsin-like enzyme, and PAR-2 were elevated (P<0.01); the positive expression of histamine, as well as protein, mRNA and positive expression of IL-1β, IL-6, IL-1α, trypsin-like enzyme, and PAR-2 in the colon were all elevated (P<0.01). Compared to the model group, the rats in the ketotifen group, the moxibustion group, and the moxibustion-medication group exhibited significantly reduced infiltration of inflammatory cells in colonic tissue, relatively intact colonic mucosa, orderly arranged villi, increased electron density, and an augmented number of mast cell granules; the diarrhea rate and mast cell degranulation rate were decreased (P<0.01), and AWR minimum volume threshold was increased (P<0.01); the serum and colonic levels of histamine, IL-1β, IL-6, IL-1α, trypsin-like enzyme, and PAR-2 were reduced (P<0.01); the positive expression of histamine, as well as protein, mRNA and positive expression of IL-1β, IL-6, IL-1α, trypsin-like enzyme, and PAR-2 in the colon were all decreased (P<0.01). Compared to the ketotifen group, the moxibustion group showed decreased serum levels of histamine, IL-6, and trypsin-like enzyme (P<0.01, P<0.05), as well as reduced colonic levels of IL-1β and IL-6 (P<0.01, P<0.05); the protein expression of colonic IL-1β, IL-1α, and PAR-2 was reduced (P<0.05), and the positive expression of colonic IL-1β and trypsin-like enzyme was reduced (P<0.01, P<0.05). Compared to both the ketotifen group and the moxibustion group, the moxibustion-medication group exhibited decreased diarrhea rate and mast cell degranulation rate (P<0.01), an increased AWR minimum volume threshold (P<0.01), reduced serum and colonic levels of histamine, IL-1β, IL-6, IL-1α, trypsin-like enzyme, and PAR-2 (P<0.01), decreased protein expression of colonic IL-1β, trypsin-like enzyme, and PAR-2 (P<0.01, P<0.05), reduced mRNA and positive expression of colonic IL-1β, IL-6, IL-1α, trypsin-like enzyme, and PAR-2 (P<0.01, P<0.05), and decreased positive expression of colonic histamine (P<0.01). Moxibustion on "Tianshu" (ST 25) and "Shangjuxu" (ST 37) might inhibit low-grade inflammatory reactions in the colon of IBS-D model rats. The mechanism may be related to the inhibition of histamine and trypsin-like enzyme secreted by mast cell, thereby reducing the expression of related inflammatory factors.

Based on the transforming growth factor β-activated kinase 1 (TAK1)-p38 mitogen-activated protein kinase (p38MAPK)-nucleotide-binding oligo-like receptor protein 3 (NLRP3) signalling pathway, the protective effect and mechanism of isoproterennaline (ISO)-induced cinnamaldehyde on inflammatory injury in ventricular rats were investigated. Fifty male SPF SD rats were randomly assigned to the normal group, model group, propranolol group, cinnamaldehyde low-dose group or cinnamaldehyde high-dose group. The ventricular arrhythmia model was constructed using the "6 + 1" ISO injection method. The rats in the propranolol group were given propranolol 15 mg·(kg d)−1, those in the low and high-dose groups were given cinnamaldehyde 20 mg·(kg d)−1 and 50 mg·(kg d)−1, respectively, and those in the control and model groups received an equal volume of 0.9% NaCl solution. Changes in the serum troponin (cTnI), creatine kinase isoenzyme (CK-MB), and interleukin-1β (IL-1β) levels in SD rats were determined by ELISA. HE staining was used to observe the tissue morphology of heart disease. The mRNA expression of IL-1β and NLRP3 was determined by RT‒PCR. Mitochondrial damage was observed by transmission electron microscopy. The expression of reactive oxygen species (ROS) was detected by immunofluorescence. Western blot or immunohistochemical detection of the protein expression of IL-1β, NLRP3, TAK1, phospho-TAK1 (p-TAK1), p38MAPK, phospho-p38MAPK (p-p38MAPK), nuclear factor-κB (NF-κB),and phospho-NF-κB (p-NF-κB) was also performed. Data analysis was performed using SPSS 25.0 software. In the control SD rats, there were no obvious ventricular arrhythmias on ECG, the cardiac tissue and mitochondria were basically normal, the serum IL-1β level was low, and the expression of myocardial IL-1β, NLRP3, ROS, p-TAK1, p-p38MAPK and p-NF-κB was weak. Compared with the control group, the model group of SD rats had significant increases in ventricular arrhythmia and arrhythmia scores according to ECG (P < 0.01). Myocardial histopathological injury, cardiac weight index (HWI) and increases in serum cTnI and CK-MB levels were detected (P < 0.01). Additionally, mitochondrial damage in myocardial tissue, increased ROS fluorescence intensity, and elevated expression of myocardial p-TAK1, p-p38MAPK and p-NF-κB were detected(P < 0.01). The protein and mRNA expression of inflammation-related factors NLRP3 and IL-1β were increased (P < 0.01 or P < 0.05). Compared with those in the model group, the arrhythmia scores were decreased in the three treatment groups (P < 0.01 or P < 0.05). Cardiac histopathological morphology was significantly improved, and HWI and myocardial injury-related indicators were decreased(P < 0.01 or P < 0.05). Damaged mitochondria were significantly improved, and the expression of ROS, p-TAK1, p-p38MAPK, and p-NF-κB were decreased. The expression of inflammation-related factors in serum and myocardial tissue was decreased (P < 0.01 or P < 0.05). TAK1-p38MAPK-NLRP3 signalling is enhanced in SD rats with ventricular arrhythmia. Cinnamaldehyde can regulate TAK1-p38MAPK-NLRP3 signalling, reduce cardiomyocyte pyroptosis, antagonize myocardial inflammatory injury and protect cardiomyocytes by inhibiting oxidative stress.

Protective effect of Lactobacillus plantarum 21, a probiotic on trinitrobenzenesulfonic acid-induced ulcerative colitis in rats.

Objective To investigate the CD34~+ umbilical cord blood hematopoietic stem cells (CD34~+ UBSC) transfected with interleukin 21 (IL-21) against the ovarian cancer effect in tumor-bearing nude mice. Methods CD34~+ UBSC were obtained from the UBSC by a magnetically activated cell sorting technique and then transfected with recombinant plasmid plRES2-IL-21-EGFP after the CD34~+ UBSC were proliferated in vitro. The therapeutic effect was evaluated by the size of the tumor and the life span in nude mice treated with the CD34~+ UBSC-IL-21. The expression of IL-21 and its bioactivity in CD34~+ UBSC-IL-21 and in local neoplasitc tissues were respectively detected by reverse transcription-polymerase chain reaction (RT-PCR), immune fluorescence technique, ELISA, Western blot, immunohistochemistry and splenocyte proliferative activity. The NK cell cytotoxicity and the numbers of NK cells, serum level of IFN-γ and TNF-αwere simultaneouly detected by FCM and ELISA, respectively. Results CD34~+ UBSC were cultured and transfected with pIRES2-IL-21-EGFP successfully. CD34~+ UBSC-IL-21 could inhibit the tumor growth and extended nude mice life span compared with other groups (P < 0.01). The expression of IL-21 in the neo-plastic tissue, serum level of IFN-γ and TNF-α , NK cell activity and the numbers of NK cells of mice origin and of human origin in splenocytes were increased significantly in the nude mice treated with CD34~+ UBSC-IL-21 compared with other groups(P <0.01). Conclusion The CD34~+ UBSC transfected with IL-21 have competent against ovarian cancer in tumor-bearing nude mice. The findings may establish a foundation for gene therapy of the ovarian cancer by CD34~+ UBSC-IL-21 in clinic application. Key words: CD34~+ umbilical cord blood hematopoietic stem cell ; Interleukin 21 ; Ovarian cancer