BACKGROUND Treatment of thin endometrium with granular leukocyte-colony stimulating factor(G-CSF)remains controversial.AIM To investigate the effect of G-CSF on the outcome of frozen embryo transfer in patients with t...BACKGROUND Treatment of thin endometrium with granular leukocyte-colony stimulating factor(G-CSF)remains controversial.AIM To investigate the effect of G-CSF on the outcome of frozen embryo transfer in patients with thin endometrium.METHODS A retrospective propensity score matching(PSM)study was performed to assess patients administered frozen embryo transfer at the Reproductive Medicine Center of the Affiliated Drum Tower Hospital of Nanjing University Medical School,in 2012-2018.The patients were divided into G-CSF intrauterine perfusion(G-CSF)and non-G-CSF groups,and clinical pregnancy,implantation,ectopic pregnancy,and early abortion rates between the two groups were compared.RESULTS Before PSM,372 cycles were enrolled,including 242 and 130 cycles in the G-CSF and non-G-CSF groups,respectively.Age(34.23±5.76 vs 32.99±5.59 years;P=0.047)and the blastula/cleavage stage embryo ratio(0.68 vs 0.37;P=0.011)were significantly elevated in the G-CSF group compared with the non-G-CSF group;however,clinical pregnancy(46.28%vs 51.54%;P=0.371)and embryo implantation(35.21%vs 35.65%;P=0.910)rates were similar in both groups.After PSM by age and blastula/cleavage stage embryo ratio,244 cycles were included(122 cases each in the G-CSF and non-G-CSF groups).The clinical pregnancy(50.82%vs 48.36%;P=0.701)and embryo implantation(37.38%vs 34.11%;P=0.480)remained similar in both groups.CONCLUSION Intrauterine infusion of G-CSF does not improve the clinical outcome of frozen embryo transfer in patients with thin endometrium.展开更多
Objective: To verify the antigen association of MAF-J6-1 receptor with M-CSFR and to further study the role of M-CSF and its receptor mediated juxtacrine in promoting leukemic cell proliferation. Methods: Monoclonal a...Objective: To verify the antigen association of MAF-J6-1 receptor with M-CSFR and to further study the role of M-CSF and its receptor mediated juxtacrine in promoting leukemic cell proliferation. Methods: Monoclonal antibody (McAb) of MAF-J6-1R RE2 and polyclonal antibody (PolyAb) of rhM-CSFR were prepared. The specificity of McAb RE2 to M-CSFR was confirmed by indirect ELISA, cross-neutralizing assay with J6-1 cell colony formation and neutralization test by ELISA. Results: the reactive activity of purified RE2 to M-CSFR was over 1: 16000. The inhibitory activity of M-CSFR and MAF-J6-1R could be blocked by RE2 and anti-M-CSFR antibody. The reactivity of RE2 to M-CSFR could be reduced by M-CSFR. Conclusion: The specificity of RE2 to M-CSFR was confirmed and the antigen association of MAF-J6-1R with M-CSFR was proved. It suggests that M-CSF and its receptor mediated auto-juxtacrine stimulation could be an operative mechanism in either leukemia or nonhematological malignancies.展开更多
The interactions between granulocyte-colony stimulating factor (G-CSF) and dextran sulfate / κ-carrageenan oligosaccharide were studied by capillary zone electrophoresis. Dextran sulfate could strongly interact with ...The interactions between granulocyte-colony stimulating factor (G-CSF) and dextran sulfate / κ-carrageenan oligosaccharide were studied by capillary zone electrophoresis. Dextran sulfate could strongly interact with G-CSF and the complex was detected. The binding constant and stoichiometry were determined to be 1.2×106 (mol/L)-1 and 3:1, respectively. However, the interaction between κ-carrageenan oligosaccharide and G-CSF was not found.展开更多
AIM： To investigate the effects of granulocyte-colony stimulating factor （G-CSF） on peritoneal defense mechanisms and bacterial translocation after systemic 5-Fluorouracil （5-FU） administration. METHODS： Thirty ...AIM： To investigate the effects of granulocyte-colony stimulating factor （G-CSF） on peritoneal defense mechanisms and bacterial translocation after systemic 5-Fluorouracil （5-FU） administration. METHODS： Thirty Wistar albino rats were divided into three groups; the control, 5-FU and 5-FU ＋ G-CSF groups. We measured bactericidal activity of the peritoneal fluid, phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid, total peritoneal cell counts and cell types of peritoneal washing fluid. Bacterial translocation was quantified by mesenteric lymph node, liver and spleen tissue cultures. RESULTS： Systemic 5-FU reduced total peritoneal cell counts, neutrophUs and macrophage numbers. It also altered bactericidal activity of the peritoneal fluid and phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid. 5-FU also caused significant increase in frequencies of bacterial translocation at the liver and mesenteric lymph nodes. G-CSF decreased bacterial translocation, it significantly enhanced bactericidal activity of the peritoneal fluid and phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid. It also increased total peritoneal cell counts, neutrophils and macrophage numbers. CONCLUSION： Systemic 5-FU administration caused bacterial translocation, decreased the bactericidal activity of peritoneal fluid and phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid. G-CSF increased both bactericidal activity of the peritoneal fluid and phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid, and prevented the bacterial translocation. We conclude that intraperitoneal GCSF administration protects the effects of systemic 5-FU on peritoneal defense mechanisms.展开更多
Recombinant human granulocyte-colony stimulating factor （hG-CSF） has been shown to protect the nervous system after brain ischemia. However, the neuroprotective mechanism of hG-CSF remains unclear. The present study...Recombinant human granulocyte-colony stimulating factor （hG-CSF） has been shown to protect the nervous system after brain ischemia. However, the neuroprotective mechanism of hG-CSF remains unclear. The present study established a rat model of cerebral ischemia/reperfusion and subcutaneously injected recombinant hG-CSF after reperfusion for 2 hours. Cerebral cortical protein was extracted following 14 days of reperfusion and subjected to two-dimensional electrophoresis. In brain ischemic rats, 56 different protein spots were screened, including 17 that were upregulated and 17 that were downregulated, compared with the sham-surgery group. Matrix assisted laser desorption ionization/time of flight mass spectrometry was used to determine peptide mass fingerprinting. Following a National Center for Biotechnology Information database search and confirmation with the Swiss-Prot database, 19 spots were identified as known proteins. Following hG-CSF treatment, 35 different protein spots were found, including 16 that were downregulated and 19 that were upregulated. Six were known proteins, including dihydropyrimidinase-associated protein 2, glial fibrillary acidic protein, endomucin, Rho GDP dissociation inhibitor, Rab GDP dissociation inhibitor and guanine-nucleotide-binding protein. Results indicate that hG-CSF is involved in neuroprotection after brain ischemia, possibly by regulating the expression of various neural regeneration-associated proteins at the subacute stage.展开更多
Objective Triple-negative breast cancer(TNBC)is the breast cancer subtype with the worst prognosis,and lacks effective therapeutic targets.Colony stimulating factors(CSFs)are cytokines that can regulate the production...Objective Triple-negative breast cancer(TNBC)is the breast cancer subtype with the worst prognosis,and lacks effective therapeutic targets.Colony stimulating factors(CSFs)are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells,playing an important role in the malignant progression of TNBC.This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes(CRGs),and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy.Methods We downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database.Through LASSO Cox regression analysis,we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score(CRRS).We further analyzed the correlation between CRRS and patient prognosis,clinical features,tumor microenvironment(TME)in both high-risk and low-risk groups,and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy.Results We identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model.Kaplan-Meier survival curves,time-dependent receiver operating characteristic curves,and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival,and the predictive ability of CRRS prognostic model was further validated using the GEO dataset.Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients.Moreover,patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil,ipatasertib,and paclitaxel.Conclusion We have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs,which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment.Moreover,the key genes within this model may represent potential molecular targets for future therapies of TNBC.展开更多
AIM： Recently it has been reported that granulocyte colony stimulating factor （G-CSF） can induce hypercoagulability in healthy bone marrow donors. It is conceivable that the induction of a prothrombotic state in a ...AIM： Recently it has been reported that granulocyte colony stimulating factor （G-CSF） can induce hypercoagulability in healthy bone marrow donors. It is conceivable that the induction of a prothrombotic state in a recipient of an organ graft with already impaired perfusion might cause further deterioration in the transplanted organ. This study evaluated whether G-CSF treatment worsens liver perfusion following liver transplantation in the rat model. METHODS： A non-arterialized rat liver transplantation model was employed to evaluate the effect of G-CSF treatment on the liver in a syngeneic and allogeneic strain combination. Study outcomes included survival time and liver damage as investigated by liver enzymes and liver histology. Observation times were 1 d, 1 wk and 12 wk. RESULTS： Rats treated with G-CSF had increased incidence and severity of biliary damage following liver transplantation. In these animals, hepatocellular necrosis was accentuated in the centrilobular region. These lesions are indicative of impaired perfusion in G-CSF treated animals. CONCLUSION： G-CSF should be used with caution in recipients of liver transplantation, as treatment might enhance preexisting, undetected perfusion problems and ultimately lead to ischemia induced biliary complications .展开更多
Objective: To explore the effects of nuclear M-CSF on the process of tumorigenesis. Methods: Functional part of M-CSF cDNA was inserted into an eukaryotic expression plasmid pCMV/myc/nuc, which can add three NLS to t...Objective: To explore the effects of nuclear M-CSF on the process of tumorigenesis. Methods: Functional part of M-CSF cDNA was inserted into an eukaryotic expression plasmid pCMV/myc/nuc, which can add three NLS to the C-terminal of the expressed protein and direct the protein into the cell nuclei. The constructed plasmid was transferred into NIH3T3 cells and the cell clones were selected by G-418 selection. Cell clones stable expressing target protein were identified by RT-PCR, ABC immunohistochemistry assayand Western blot. Cell growth kinetics analyses throughgrowth curves, cell doubling time, MTT test and anti-sense oligodeoxynucleotide (ASODN) inhibiting cell growth testwere performed to identify cells proliferation potential.Results: The transfected cells showed elevated proliferation potential over the control cells. Conclusion: Abnormalappearance of M-CSF in nucleus could enhance cellproliferation, which suggests that cytokine isoforms within cell nucleus might play transcription factor-like role.展开更多
Objective: To study the effects of quercetin on hepatocyte stimulating factor production from mouse peritoneal macrophages. Methods: Hepatocyte stimulating factor was evaluated by the amount of fibrinogen synthesized ...Objective: To study the effects of quercetin on hepatocyte stimulating factor production from mouse peritoneal macrophages. Methods: Hepatocyte stimulating factor was evaluated by the amount of fibrinogen synthesized in Hep3B cells. Interleukin-6 activity was measured by B9 cell proliferation methyl thiazolyl tetrazolium colorimetric method. Hep3B cell supernatant fibrinogen was quantitated with ELISA. Results: LPS induced the synthesis of hepatocyte stimulating factor in mouse peritoneal macrophages, and hepatocyte stimulating factor promotes the synthesis of fibrinogen from Hep3B cells. Quercetin(5 to 40μmol/ L) inhibited the synthesis of hepatocyte stimulating factor stimulated by LPS. Quercetin(5 to 20μmol/ L) inhibited release of interleukin-6 from mouse peritoneal macrophages induced by 0. 5 g/ L fibrin fibrinogen degradation products. Conclusion: Quercetin inhibits the synthesis of hepatocyte stimulating factor in macrophages.展开更多
Background and Aim: Despite the fact that acute appendicitis is the most common surgical emergency all around the world, its diagnosis is still based on clinical evaluation and accuracy of the diagnosis depending on e...Background and Aim: Despite the fact that acute appendicitis is the most common surgical emergency all around the world, its diagnosis is still based on clinical evaluation and accuracy of the diagnosis depending on experience. The aim of this study is to evaluate the role of inflammatory markers in diagnosis of acute appendicitis. Material and Method: The study includes 77 cases with histopathologically proven acute appendicitis and 17 control cases. Blood samples were obtained from all cases and C-reactive protein (CRP), Granulocyte Colony Stimulating Factor (G-CSF) and Total Antioxidant Capacity (TAC) were measured. Findings: In cases with acute appendicitis, CRP and G-CSF levels were found to be related to acute appendicitis;however, TAC was not affected by the disease process. Moreover, CRP and G-CSF levels were correlated with the disease severity. Conclusion: Both CRP and G-CSF can be used in diagnosis of acute appendicitis. Furthermore, increased CRP level can be a marker to show advanced cases. However, G-CSF is not an effective marker to show disease severity.展开更多
Idiopathic pulmonary fibrosis(IPF)is a fatal lung disease characterized by excessive ECM deposition and myofibroblast accumulation driven by cytokine dysregulation.This study identified granulocyte colony-stimulating ...Idiopathic pulmonary fibrosis(IPF)is a fatal lung disease characterized by excessive ECM deposition and myofibroblast accumulation driven by cytokine dysregulation.This study identified granulocyte colony-stimulating factor 3(CSF3)as a key mediator of IPF progression.Elevated CSF3 expression was observed in the lung tissues of IPF patients.Recombinant CSF3 promoted myofibrogenesis in lung fibroblasts,whereas CSF3-deficient mice were protected from bleomycin-induced pulmonary fibrosis.Treatment with novel CSF3-neutralizing antibodies significantly restored fibrosis in IPF mice by suppressing myofibroblast differentiation and reducing ECM deposition.Here,we demonstrated a reciprocal regulatory relationship between CSF3 and TGF-βthat amplifies pro-fibrotic signaling.Our mechanistic studies revealed that CSF3 acts as an upstream regulator of TGF-β,forming a positive feedback loop that significantly accelerates the fibrotic process.Knockout or neutralization of CSF3 suppressed fibrosis by reducing TGF-βlevels,whereas treatment with recombinant CSF3 promoted fibrosis with increased TGF-βexpression.Notably,while CSF3 inhibition reduced TGF-βexpression levels,it did not decrease them below normal levels.This finding suggests that inhibiting CSF3 could simultaneously reduce fibrosis by suppressing excessive TGF-βexpression while also minimizing side effects by maintaining TGF-βhomeostasis.Taken together,these results provide strong evidence that CSF3 is a critical driver of IPF pathogenesis and that targeting CSF3 may provide a therapeutic strategy by modulating TGF-βsignaling and restoring the ECM and cellular homeostasis.展开更多
Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in s...Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.展开更多
Radiotherapy(RT)serves as the primary treatment for solid tumors.Its potential to incite an immune response against tumors both locally and distally profoundly impacts clinical outcomes.However,RT may also promote the...Radiotherapy(RT)serves as the primary treatment for solid tumors.Its potential to incite an immune response against tumors both locally and distally profoundly impacts clinical outcomes.However,RT may also promote the accumulation of immunosuppressive cytokines and immunosuppressive cells,greatly impeding the activation of antitumor immune responses and substantially limiting the effectiveness of RT.Therefore,regulating post-RT immunosuppression to steer the immune milieu toward heightened activation potentially enhances RT's therapeutic potential.Cytokines,potent orchestrators of diverse cellular responses,play a pivotal role in regulating this immunosuppressive response.Identifying and promptly neutralizing early released immunosuppressive cytokines are a crucial development in augmenting RT's immunomodulatory effects.To this end,we conducted a screen of immunosuppressive cytokines following RT and identified macrophage colony-stimulating factor(MCSF)as an early up-regulated and persistent immune suppressor.Single-cell sequencing revealed that the main source of up-regulated McSF derived from tumor cells.Mechanistic exploration revealed that irradiation-dependent phosphorylation of the p65 protein facilitated its binding to the McSF gene promoter,enhancing transcription.Knockdown and chemical inhibitor experiments conclusively demonstrated that suppressing tumor cell-derived McSF amplifies RT's immune-activating effects,with optimal results achieved by early MCSF blockade after irradiation.Additionally,we validated that MCSF acted on macrophages,inducing the secretion of a large number of inhibitory cytokines.In summary,we propose a novel approach to enhance the immune activation effects of RT by blocking the MCSF-CSF1R signaling pathway early after irradiation.展开更多
To the Editor:After chimeric antigen receptor T(CAR-T)cell therapy,over 90%of patients experience either mild or severe cytopenia,with the prevalence of Grades 3–4 neutropenia ranging from 53%to 94.3%.[1,2]Granulocyt...To the Editor:After chimeric antigen receptor T(CAR-T)cell therapy,over 90%of patients experience either mild or severe cytopenia,with the prevalence of Grades 3–4 neutropenia ranging from 53%to 94.3%.[1,2]Granulocyte colony-stimulating factor(G-CSF),known for its ability to enhance the proliferation and differentiation of neutrophils,has been extensively employed for the prevention and treatment of neutropenia in various contexts.However,its application in patients with refractory/relapsing B-cell acute lymphoblastic leukemia(R/R B-ALL)after CAR-T cell therapy remains a topic of debate.[3]Several studies have suggested that G-CSF may exert anti-inflammatory effects by modulating the release of inflammatory factors,such as interleukin-12(IL-12),TNF-α,and IFN-γ,or by influencing the differentiation of T-cell subsets.[4]However,other researchers have posited that G-CSF could exacerbate cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)through the augmentation of antigen-presenting cell function.展开更多
Objective To observe the efficacy of treating intrauterine infected chronic hepatitis B virus (HBV) carrier children with a combination of granulocyte macrophage colony stimulating factor (GM CSF) or hepatitis B i...Objective To observe the efficacy of treating intrauterine infected chronic hepatitis B virus (HBV) carrier children with a combination of granulocyte macrophage colony stimulating factor (GM CSF) or hepatitis B immunoglobulin (HBIG) plus recombinant hepatitis B vaccine (rHBvac) Methods A total of 27 chronic HBV infected children, who were born to HBV carrier mothers and received hepatitis B immunoprophylaxis at birth, were randomized into 2 groups: one receiving a combined therapy of 50 μg of GM CSF plus 10 μg of rHBvac injected intramuscularly at the same location (GM CSF group, 14 children) or 200 IU HBIG and 10 μg rHBvac in different muscles (HBIG group, 13 children) on a monthly four dose schedule HBV DNA quantification and other HBV serological markers were tested before and after the four dose therapy Results Twelve children in each group completed the study Of them, 3 children in the GM CSF group and 4 in the HBIG group had elevated serum alanine transaminase (ALT) before the trial, and then 2 in each group became ALT normal after the treatment Before the therapy, hepatitis B e antigen (HBeAg) positivity was found in nine children in the GM CSF group and 10 in the HBIG group One from each group had an HBeAg/anti HBe seroconversion after the treatment The quantity of HBV DNA was significantly lower after the treatment ( P =0 023) in GM CSF group, but was not significantly reduced in HBIG group No subjects were found to be negative for hepatitis B surface antigen (HBsAg) after the treatment, and no serious adverse events occurred in either group Conclusion Combined GM CSF and rHBvac therapy inhibit HBV replication in carrier children who were not protected after treatment with immunoprophylaxis展开更多
The dysfunction of vascular endothelial cells plays a key role in startingand facilitating restenosis. The acceleration of intima repair and the recovery of endothelialfunction would reduce the restenosis rate. This s...The dysfunction of vascular endothelial cells plays a key role in startingand facilitating restenosis. The acceleration of intima repair and the recovery of endothelialfunction would reduce the restenosis rate. This study was undertaken to assess the effect ofgranulocyte-macrophage colony stimulating factor ( GM-CSF) on the repair of damaged iliac arteries.Twenty-four male New Zealand white rabbits undergoing primary iliac artery deendothelialization wererandomly divided into two groups ( GM-CSF group and control group) . The GM-CSF group received asubcutaneous injection of GM-CSF (10 μg ? kg^(-1) ? d^(-1) ) , and the control groupwas given a subcutaneous injection of equivalent saline. The iliac arteries of all animals weredamaged by balloon after 7 days. The levels of nitric oxide ( NO) were detected before, 1 week, 2weeks and 4 weeks after angioplasty. The repair and hyperplasia of the intima were observedmicroscopically and the indices of stenosis were evaluated by computerized planimetry after 4 weeksof angioplasty. The NO levels of the GM-CSF group were higher than those of the control group 2weeks and 4 weeks after angioplasty [91.92 +-11.57) μmol/L vs. (81. 67 +- 12. 18) μmol/L; (97. 67+- 10. 13 ) ( μmol/L vs. (83. 16 +-12. 64) μmol/L]. Four weeks after balloon damage,histological examination showed that neointima formation, vascular smooth muscle cells and fibroustissue of the GM-CSF group were less than those of the control group. The endothelium of the GM-CSFgroup was more integrated, and stenosis of lumen was slighter than that of the control group.Morphometry showed the lumen area of the GM-CSF group was larger than that of the control group[(1.27 +-0. 31) mm^2 vs. (0. 92 +- 0. 24) mm^2 ] , the neointimal area and percent of intimahyperplasia were significantly smaller than those of the control group [ (0. 85 +-0. 34) mm vs. (1.18 +-0. 38) mm^2; (40 +- 7)% vs. (55 +- 6)%]. GM-CSF could facilitate the repair of the intima,reduce neointima formation, better the function of the endothelium, and decrease the rate ofrestenosis.展开更多
Objective To study the hematopoietic enhancing effects of recombinant human macrophage colony stimulating factor (rhM CSF) expressed in silkworm. Method Balb/c mice were irradiated with sublethal dose of 60...Objective To study the hematopoietic enhancing effects of recombinant human macrophage colony stimulating factor (rhM CSF) expressed in silkworm. Method Balb/c mice were irradiated with sublethal dose of 60 Coγ rays and then administered intraperitoneally with silkworm expressed rhM CSF (1000 U per individual for 7 days) in treatment group or with normal saline (for 7 days as well) in control group. The hematopoietic recovery of irradiation mice was observed by comparing peripheral white blood cell (WBC) counts, differential counts of WBC and bone marrow hematopoietic progenitor cell colony forming assay in soft agar at different time after irradiation. Results The total WBC counts (×10 9 /L) of treatment group at day 15 and 20 after irradiation (3.42±1.20, 5.56±2.50, respectively) were significantly higher than those of control group (2.03±0.90, 3.72± 2.30; both P<0.05). On days 10, 15, 20, 25 and 30 after irradiation, the monocyte counts (×10 9 /L) of treatment group (0.08±0.06, 0.16±0.10, 0.48± 0.35, 0.47±0.21 and 0.33±0.17, respectively) were all significantly higher than those of control group (0.025±0.016, 0.05±0.04, 0.23±0.16, 0.33± 0.19 and 0.17±0.13; all P<0.05). On days 15, 20 and 25, the granulocyte count (X10 9 /L) of treatment group (1.03±0.61, 2.18±1.19 and 3.28±1.09) were also higher than those of control group (0.62± 0.37, 1.40±0.99 and 2.20±0.74; all P<0.05). On day 9 after irradiation, the bone marrow CFU GM yield of control group (19±11/10 6 cells) was significantly lower than that of treatment group (78±30/10 6 cells, P< 0.05). Conclusion rhM CSF expressed in silkworm could accelerate hematopoietic recovery in irradiated mice.展开更多
Objective To analyze efficacy and safety of CLAG regimen in patients with refractory or relapsed acute myeloid leukemia(AML).Methods Efficacy and adverse events of patients with refractory or relapsed AML who were tre...Objective To analyze efficacy and safety of CLAG regimen in patients with refractory or relapsed acute myeloid leukemia(AML).Methods Efficacy and adverse events of patients with refractory or relapsed AML who were treated with one course of CLAG from April 1st,2014 through December 9th,2015 in our hospital were retrospectively reviewed.Results Thirty-three展开更多
Traumatic brain injury（TBI） can result in poor functional outcomes and death, and overall outcomes are varied. Growth factors, such as angiopoietin-1（Ang-1）, vascular endothelial growth factor（VEGF）, and granulo...Traumatic brain injury（TBI） can result in poor functional outcomes and death, and overall outcomes are varied. Growth factors, such as angiopoietin-1（Ang-1）, vascular endothelial growth factor（VEGF）, and granulocyte-colony stimulating factor（G-CSF）, play important roles in the neurological functions. This study investigated the relationship between serum growth factor levels and long-term outcomes after TBI. Blood samples from 55 patients were collected at 1, 3 and 7 days after TBI. Blood samples from 39 healthy controls were collected as a control group. Serum Ang-1, G-CSF, and VEGF levels were measured using ELISA. Patients were monitored for 3 months using the Glasgow Outcome Scale-Extended（GOSE）. Patients having a GOSE score of 〉 5 at 3 months were categorized as a good outcome, and patients with a GOSE score of 1-5 were categorized as a bad outcome. Our data demonstrated that TBI patients showed significantly increased growth factor levels within 7 days compared with healthy controls. Serum levels of Ang-1 at 1 and 7 days and G-CSF levels at 7 days were significantly higher in patients with good outcomes than in patients with poor outcomes. VEGF levels at 7 days were remarkably higher in patients with poor outcomes than in patients with good outcomes. Receiver operating characteristic analysis showed that the best cut-off points of serum growth factor levels at 7 days to predict functional outcome were 1,333 pg/mL for VEGF, 447.2 pg/mL for G-CSF, and 90.6 ng/mL for Ang-1. These data suggest that patients with elevated levels of serum Ang-1, G-CSF, and decreased VEGF levels had a better prognosis in the acute phase of TBI（within 7 days）. This study was registered with the Chinese Clinical Trial Registry（registration number： ChiCTR1800018251） on September 7, 2018.展开更多
BACKGROUND Human Wharton’s jelly-derived mesenchymal stromal/stem cells(hWJ-MSCs)have gained considerable attention in their applications in cell-based therapy due to several advantages offered by them.Recently,we re...BACKGROUND Human Wharton’s jelly-derived mesenchymal stromal/stem cells(hWJ-MSCs)have gained considerable attention in their applications in cell-based therapy due to several advantages offered by them.Recently,we reported that hWJ-MSCs and their conditioned medium have significant therapeutic radioprotective potential.This finding raised an obvious question to identify unique features of hWJ-MSCs over other sources of stem cells for a better understanding of its radioprotective mechanism.AIM To understand the radioprotective mechanism of soluble factors secreted by hWJMSCs and identification of their unique genes.METHODS Propidium iodide staining,endogenous spleen colony-forming assay,and survival study were carried out for radioprotection studies.Homeostasis-driven proliferation assay was performed for in vivo lymphocyte proliferation.Analysis of RNAseq data was performed to find the unique genes of WJ-MSCs by comparing them with bone marrow mesenchymal stem cells,embryonic stem cells,and human fibroblasts.Gene enrichment analysis and protein-protein interaction network were used for pathway analysis.RESULTS Co-culture of irradiated murine splenic lymphocytes with WJ-MSCs offered significant radioprotection to lymphocytes.WJ-MSC transplantation increased the homeostasis-driven proliferation of the lymphocytes.Neutralization of WJ-MSC conditioned medium with granulocyte-colony stimulating factor antibody abolished therapeutic radioprotection.Transcriptome analysis showed that WJ-MSCs share several common genes with bone marrow MSCs and embryonic stem cells and express high levels of unique genes such as interleukin(IL)1-α,IL1-β,IL-6,CXCL3,CXCL5,CXCL8,CXCL2,CCL2,FLT-1,and IL-33.It was also observed that WJ-MSCs preferentially modulate several cellular pathways and processes that handle the repair and regeneration of damaged tissues compared to stem cells from other sources.Cytokine-based network analysis showed that most of the radiosensitive tissues have a more complex network for the elevated cytokines.CONCLUSION Systemic infusion of WJ-MSC conditioned media will have significant potential for treating accidental radiation exposed victims。展开更多
基金Supported by Chinese Medical Association,No.17020450714Medical Science and Technology Development Foundation,Nanjing Department of Health,No.YKK18090.
文摘BACKGROUND Treatment of thin endometrium with granular leukocyte-colony stimulating factor(G-CSF)remains controversial.AIM To investigate the effect of G-CSF on the outcome of frozen embryo transfer in patients with thin endometrium.METHODS A retrospective propensity score matching(PSM)study was performed to assess patients administered frozen embryo transfer at the Reproductive Medicine Center of the Affiliated Drum Tower Hospital of Nanjing University Medical School,in 2012-2018.The patients were divided into G-CSF intrauterine perfusion(G-CSF)and non-G-CSF groups,and clinical pregnancy,implantation,ectopic pregnancy,and early abortion rates between the two groups were compared.RESULTS Before PSM,372 cycles were enrolled,including 242 and 130 cycles in the G-CSF and non-G-CSF groups,respectively.Age(34.23±5.76 vs 32.99±5.59 years;P=0.047)and the blastula/cleavage stage embryo ratio(0.68 vs 0.37;P=0.011)were significantly elevated in the G-CSF group compared with the non-G-CSF group;however,clinical pregnancy(46.28%vs 51.54%;P=0.371)and embryo implantation(35.21%vs 35.65%;P=0.910)rates were similar in both groups.After PSM by age and blastula/cleavage stage embryo ratio,244 cycles were included(122 cases each in the G-CSF and non-G-CSF groups).The clinical pregnancy(50.82%vs 48.36%;P=0.701)and embryo implantation(37.38%vs 34.11%;P=0.480)remained similar in both groups.CONCLUSION Intrauterine infusion of G-CSF does not improve the clinical outcome of frozen embryo transfer in patients with thin endometrium.
文摘Objective: To verify the antigen association of MAF-J6-1 receptor with M-CSFR and to further study the role of M-CSF and its receptor mediated juxtacrine in promoting leukemic cell proliferation. Methods: Monoclonal antibody (McAb) of MAF-J6-1R RE2 and polyclonal antibody (PolyAb) of rhM-CSFR were prepared. The specificity of McAb RE2 to M-CSFR was confirmed by indirect ELISA, cross-neutralizing assay with J6-1 cell colony formation and neutralization test by ELISA. Results: the reactive activity of purified RE2 to M-CSFR was over 1: 16000. The inhibitory activity of M-CSFR and MAF-J6-1R could be blocked by RE2 and anti-M-CSFR antibody. The reactivity of RE2 to M-CSFR could be reduced by M-CSFR. Conclusion: The specificity of RE2 to M-CSFR was confirmed and the antigen association of MAF-J6-1R with M-CSFR was proved. It suggests that M-CSF and its receptor mediated auto-juxtacrine stimulation could be an operative mechanism in either leukemia or nonhematological malignancies.
基金The authors would like to acknowledge the support from the National Natural Science Foundation of China(Project number 20299035,20035010,20275039)Pilot of Knowledge Innovation Program of the Chinese Academy of Science(KSCX 2-3-02-02)on the above work.
文摘The interactions between granulocyte-colony stimulating factor (G-CSF) and dextran sulfate / κ-carrageenan oligosaccharide were studied by capillary zone electrophoresis. Dextran sulfate could strongly interact with G-CSF and the complex was detected. The binding constant and stoichiometry were determined to be 1.2×106 (mol/L)-1 and 3:1, respectively. However, the interaction between κ-carrageenan oligosaccharide and G-CSF was not found.
文摘AIM： To investigate the effects of granulocyte-colony stimulating factor （G-CSF） on peritoneal defense mechanisms and bacterial translocation after systemic 5-Fluorouracil （5-FU） administration. METHODS： Thirty Wistar albino rats were divided into three groups; the control, 5-FU and 5-FU ＋ G-CSF groups. We measured bactericidal activity of the peritoneal fluid, phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid, total peritoneal cell counts and cell types of peritoneal washing fluid. Bacterial translocation was quantified by mesenteric lymph node, liver and spleen tissue cultures. RESULTS： Systemic 5-FU reduced total peritoneal cell counts, neutrophUs and macrophage numbers. It also altered bactericidal activity of the peritoneal fluid and phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid. 5-FU also caused significant increase in frequencies of bacterial translocation at the liver and mesenteric lymph nodes. G-CSF decreased bacterial translocation, it significantly enhanced bactericidal activity of the peritoneal fluid and phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid. It also increased total peritoneal cell counts, neutrophils and macrophage numbers. CONCLUSION： Systemic 5-FU administration caused bacterial translocation, decreased the bactericidal activity of peritoneal fluid and phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid. G-CSF increased both bactericidal activity of the peritoneal fluid and phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid, and prevented the bacterial translocation. We conclude that intraperitoneal GCSF administration protects the effects of systemic 5-FU on peritoneal defense mechanisms.
文摘Recombinant human granulocyte-colony stimulating factor （hG-CSF） has been shown to protect the nervous system after brain ischemia. However, the neuroprotective mechanism of hG-CSF remains unclear. The present study established a rat model of cerebral ischemia/reperfusion and subcutaneously injected recombinant hG-CSF after reperfusion for 2 hours. Cerebral cortical protein was extracted following 14 days of reperfusion and subjected to two-dimensional electrophoresis. In brain ischemic rats, 56 different protein spots were screened, including 17 that were upregulated and 17 that were downregulated, compared with the sham-surgery group. Matrix assisted laser desorption ionization/time of flight mass spectrometry was used to determine peptide mass fingerprinting. Following a National Center for Biotechnology Information database search and confirmation with the Swiss-Prot database, 19 spots were identified as known proteins. Following hG-CSF treatment, 35 different protein spots were found, including 16 that were downregulated and 19 that were upregulated. Six were known proteins, including dihydropyrimidinase-associated protein 2, glial fibrillary acidic protein, endomucin, Rho GDP dissociation inhibitor, Rab GDP dissociation inhibitor and guanine-nucleotide-binding protein. Results indicate that hG-CSF is involved in neuroprotection after brain ischemia, possibly by regulating the expression of various neural regeneration-associated proteins at the subacute stage.
文摘Objective Triple-negative breast cancer(TNBC)is the breast cancer subtype with the worst prognosis,and lacks effective therapeutic targets.Colony stimulating factors(CSFs)are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells,playing an important role in the malignant progression of TNBC.This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes(CRGs),and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy.Methods We downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database.Through LASSO Cox regression analysis,we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score(CRRS).We further analyzed the correlation between CRRS and patient prognosis,clinical features,tumor microenvironment(TME)in both high-risk and low-risk groups,and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy.Results We identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model.Kaplan-Meier survival curves,time-dependent receiver operating characteristic curves,and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival,and the predictive ability of CRRS prognostic model was further validated using the GEO dataset.Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients.Moreover,patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil,ipatasertib,and paclitaxel.Conclusion We have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs,which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment.Moreover,the key genes within this model may represent potential molecular targets for future therapies of TNBC.
基金Supported by the Deutsche Forschungsgemeinschaft (KFO 117/1) and the IFORES Research Program, University Hospital Essen
文摘AIM： Recently it has been reported that granulocyte colony stimulating factor （G-CSF） can induce hypercoagulability in healthy bone marrow donors. It is conceivable that the induction of a prothrombotic state in a recipient of an organ graft with already impaired perfusion might cause further deterioration in the transplanted organ. This study evaluated whether G-CSF treatment worsens liver perfusion following liver transplantation in the rat model. METHODS： A non-arterialized rat liver transplantation model was employed to evaluate the effect of G-CSF treatment on the liver in a syngeneic and allogeneic strain combination. Study outcomes included survival time and liver damage as investigated by liver enzymes and liver histology. Observation times were 1 d, 1 wk and 12 wk. RESULTS： Rats treated with G-CSF had increased incidence and severity of biliary damage following liver transplantation. In these animals, hepatocellular necrosis was accentuated in the centrilobular region. These lesions are indicative of impaired perfusion in G-CSF treated animals. CONCLUSION： G-CSF should be used with caution in recipients of liver transplantation, as treatment might enhance preexisting, undetected perfusion problems and ultimately lead to ischemia induced biliary complications .
基金This work was supported by a grant from Tianjin Science and Technology Development Project (No. 003119311).
文摘Objective: To explore the effects of nuclear M-CSF on the process of tumorigenesis. Methods: Functional part of M-CSF cDNA was inserted into an eukaryotic expression plasmid pCMV/myc/nuc, which can add three NLS to the C-terminal of the expressed protein and direct the protein into the cell nuclei. The constructed plasmid was transferred into NIH3T3 cells and the cell clones were selected by G-418 selection. Cell clones stable expressing target protein were identified by RT-PCR, ABC immunohistochemistry assayand Western blot. Cell growth kinetics analyses throughgrowth curves, cell doubling time, MTT test and anti-sense oligodeoxynucleotide (ASODN) inhibiting cell growth testwere performed to identify cells proliferation potential.Results: The transfected cells showed elevated proliferation potential over the control cells. Conclusion: Abnormalappearance of M-CSF in nucleus could enhance cellproliferation, which suggests that cytokine isoforms within cell nucleus might play transcription factor-like role.
基金Supported by the National Natural Science Foundation of China(No.39370798,30200344)
文摘Objective: To study the effects of quercetin on hepatocyte stimulating factor production from mouse peritoneal macrophages. Methods: Hepatocyte stimulating factor was evaluated by the amount of fibrinogen synthesized in Hep3B cells. Interleukin-6 activity was measured by B9 cell proliferation methyl thiazolyl tetrazolium colorimetric method. Hep3B cell supernatant fibrinogen was quantitated with ELISA. Results: LPS induced the synthesis of hepatocyte stimulating factor in mouse peritoneal macrophages, and hepatocyte stimulating factor promotes the synthesis of fibrinogen from Hep3B cells. Quercetin(5 to 40μmol/ L) inhibited the synthesis of hepatocyte stimulating factor stimulated by LPS. Quercetin(5 to 20μmol/ L) inhibited release of interleukin-6 from mouse peritoneal macrophages induced by 0. 5 g/ L fibrin fibrinogen degradation products. Conclusion: Quercetin inhibits the synthesis of hepatocyte stimulating factor in macrophages.
文摘Background and Aim: Despite the fact that acute appendicitis is the most common surgical emergency all around the world, its diagnosis is still based on clinical evaluation and accuracy of the diagnosis depending on experience. The aim of this study is to evaluate the role of inflammatory markers in diagnosis of acute appendicitis. Material and Method: The study includes 77 cases with histopathologically proven acute appendicitis and 17 control cases. Blood samples were obtained from all cases and C-reactive protein (CRP), Granulocyte Colony Stimulating Factor (G-CSF) and Total Antioxidant Capacity (TAC) were measured. Findings: In cases with acute appendicitis, CRP and G-CSF levels were found to be related to acute appendicitis;however, TAC was not affected by the disease process. Moreover, CRP and G-CSF levels were correlated with the disease severity. Conclusion: Both CRP and G-CSF can be used in diagnosis of acute appendicitis. Furthermore, increased CRP level can be a marker to show advanced cases. However, G-CSF is not an effective marker to show disease severity.
基金supported by the Korea Drug Development Fund,funded by the Ministry of Science and ICT,Ministry of Trade,Industry,and Energy,and Ministry of Health and Welfare(RS-2024-00461975,Republic of Korea)also supported by the Scale-up Package program of the Korea Health Industry Development Institute(KHIDI)(20316786,Republic of Korea)+2 种基金The human blood serum biospecimens and data used for this study were provided by the Biobank of Korea Institute of Radiological&Medical Sciences(KIRAMSKBN4_A06)Soonchunhyang University Bucheon Hospital,a members of the Korea Biobank Network(KBN4_A06).
文摘Idiopathic pulmonary fibrosis(IPF)is a fatal lung disease characterized by excessive ECM deposition and myofibroblast accumulation driven by cytokine dysregulation.This study identified granulocyte colony-stimulating factor 3(CSF3)as a key mediator of IPF progression.Elevated CSF3 expression was observed in the lung tissues of IPF patients.Recombinant CSF3 promoted myofibrogenesis in lung fibroblasts,whereas CSF3-deficient mice were protected from bleomycin-induced pulmonary fibrosis.Treatment with novel CSF3-neutralizing antibodies significantly restored fibrosis in IPF mice by suppressing myofibroblast differentiation and reducing ECM deposition.Here,we demonstrated a reciprocal regulatory relationship between CSF3 and TGF-βthat amplifies pro-fibrotic signaling.Our mechanistic studies revealed that CSF3 acts as an upstream regulator of TGF-β,forming a positive feedback loop that significantly accelerates the fibrotic process.Knockout or neutralization of CSF3 suppressed fibrosis by reducing TGF-βlevels,whereas treatment with recombinant CSF3 promoted fibrosis with increased TGF-βexpression.Notably,while CSF3 inhibition reduced TGF-βexpression levels,it did not decrease them below normal levels.This finding suggests that inhibiting CSF3 could simultaneously reduce fibrosis by suppressing excessive TGF-βexpression while also minimizing side effects by maintaining TGF-βhomeostasis.Taken together,these results provide strong evidence that CSF3 is a critical driver of IPF pathogenesis and that targeting CSF3 may provide a therapeutic strategy by modulating TGF-βsignaling and restoring the ECM and cellular homeostasis.
基金supported by the National Natural Science Foundation of China,Nos.82072165 and 82272256(both to XM)the Key Project of Xiangyang Central Hospital,No.2023YZ03(to RM)。
文摘Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.
基金supported by the National Natural Science Foundation of China(grant nos.82102931,82330085,82073354,and 82102201)Hubei Provincial Key Laboratory Open Project Fund for Precision Radiotherapy in Oncology(grant no.jzfs001).
文摘Radiotherapy(RT)serves as the primary treatment for solid tumors.Its potential to incite an immune response against tumors both locally and distally profoundly impacts clinical outcomes.However,RT may also promote the accumulation of immunosuppressive cytokines and immunosuppressive cells,greatly impeding the activation of antitumor immune responses and substantially limiting the effectiveness of RT.Therefore,regulating post-RT immunosuppression to steer the immune milieu toward heightened activation potentially enhances RT's therapeutic potential.Cytokines,potent orchestrators of diverse cellular responses,play a pivotal role in regulating this immunosuppressive response.Identifying and promptly neutralizing early released immunosuppressive cytokines are a crucial development in augmenting RT's immunomodulatory effects.To this end,we conducted a screen of immunosuppressive cytokines following RT and identified macrophage colony-stimulating factor(MCSF)as an early up-regulated and persistent immune suppressor.Single-cell sequencing revealed that the main source of up-regulated McSF derived from tumor cells.Mechanistic exploration revealed that irradiation-dependent phosphorylation of the p65 protein facilitated its binding to the McSF gene promoter,enhancing transcription.Knockdown and chemical inhibitor experiments conclusively demonstrated that suppressing tumor cell-derived McSF amplifies RT's immune-activating effects,with optimal results achieved by early MCSF blockade after irradiation.Additionally,we validated that MCSF acted on macrophages,inducing the secretion of a large number of inhibitory cytokines.In summary,we propose a novel approach to enhance the immune activation effects of RT by blocking the MCSF-CSF1R signaling pathway early after irradiation.
基金supported by grants from the General Project of the National Natural Science Foundation of China(No.81970180)the Science and Technology Project of Tianjin Municipal Health Committee(No.TJWJ2022QN030)+7 种基金the Key projects of Tianjin Applied Basic Research and Multi-Investment Fund(No.21JCZDJC01240)the Science and Technology Project of Tianjin Municipal Health Committee(No.TJWJ2022XK018)Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-056B)Tianjin Municipal Natural Science Foundation(No.22JCQNJC00820)Tianjin Health Research Project(No.TJWJ2023QN027)Tianjin Health Bureau Project(No.ZC20074)Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJWJ2023XK010)Henan Provincial Youth and Middle-aged Health Science and Technology Talents Excellent Youth Program(No.20230273).
文摘To the Editor:After chimeric antigen receptor T(CAR-T)cell therapy,over 90%of patients experience either mild or severe cytopenia,with the prevalence of Grades 3–4 neutropenia ranging from 53%to 94.3%.[1,2]Granulocyte colony-stimulating factor(G-CSF),known for its ability to enhance the proliferation and differentiation of neutrophils,has been extensively employed for the prevention and treatment of neutropenia in various contexts.However,its application in patients with refractory/relapsing B-cell acute lymphoblastic leukemia(R/R B-ALL)after CAR-T cell therapy remains a topic of debate.[3]Several studies have suggested that G-CSF may exert anti-inflammatory effects by modulating the release of inflammatory factors,such as interleukin-12(IL-12),TNF-α,and IFN-γ,or by influencing the differentiation of T-cell subsets.[4]However,other researchers have posited that G-CSF could exacerbate cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)through the augmentation of antigen-presenting cell function.
基金ThisstudywassupportedbyagrantfromtheNationalPublicHealthMinistry (No97030223)andagrantfromtheNationalNaturalScienceFoundationofChina (No 39670 667)
文摘Objective To observe the efficacy of treating intrauterine infected chronic hepatitis B virus (HBV) carrier children with a combination of granulocyte macrophage colony stimulating factor (GM CSF) or hepatitis B immunoglobulin (HBIG) plus recombinant hepatitis B vaccine (rHBvac) Methods A total of 27 chronic HBV infected children, who were born to HBV carrier mothers and received hepatitis B immunoprophylaxis at birth, were randomized into 2 groups: one receiving a combined therapy of 50 μg of GM CSF plus 10 μg of rHBvac injected intramuscularly at the same location (GM CSF group, 14 children) or 200 IU HBIG and 10 μg rHBvac in different muscles (HBIG group, 13 children) on a monthly four dose schedule HBV DNA quantification and other HBV serological markers were tested before and after the four dose therapy Results Twelve children in each group completed the study Of them, 3 children in the GM CSF group and 4 in the HBIG group had elevated serum alanine transaminase (ALT) before the trial, and then 2 in each group became ALT normal after the treatment Before the therapy, hepatitis B e antigen (HBeAg) positivity was found in nine children in the GM CSF group and 10 in the HBIG group One from each group had an HBeAg/anti HBe seroconversion after the treatment The quantity of HBV DNA was significantly lower after the treatment ( P =0 023) in GM CSF group, but was not significantly reduced in HBIG group No subjects were found to be negative for hepatitis B surface antigen (HBsAg) after the treatment, and no serious adverse events occurred in either group Conclusion Combined GM CSF and rHBvac therapy inhibit HBV replication in carrier children who were not protected after treatment with immunoprophylaxis
文摘The dysfunction of vascular endothelial cells plays a key role in startingand facilitating restenosis. The acceleration of intima repair and the recovery of endothelialfunction would reduce the restenosis rate. This study was undertaken to assess the effect ofgranulocyte-macrophage colony stimulating factor ( GM-CSF) on the repair of damaged iliac arteries.Twenty-four male New Zealand white rabbits undergoing primary iliac artery deendothelialization wererandomly divided into two groups ( GM-CSF group and control group) . The GM-CSF group received asubcutaneous injection of GM-CSF (10 μg ? kg^(-1) ? d^(-1) ) , and the control groupwas given a subcutaneous injection of equivalent saline. The iliac arteries of all animals weredamaged by balloon after 7 days. The levels of nitric oxide ( NO) were detected before, 1 week, 2weeks and 4 weeks after angioplasty. The repair and hyperplasia of the intima were observedmicroscopically and the indices of stenosis were evaluated by computerized planimetry after 4 weeksof angioplasty. The NO levels of the GM-CSF group were higher than those of the control group 2weeks and 4 weeks after angioplasty [91.92 +-11.57) μmol/L vs. (81. 67 +- 12. 18) μmol/L; (97. 67+- 10. 13 ) ( μmol/L vs. (83. 16 +-12. 64) μmol/L]. Four weeks after balloon damage,histological examination showed that neointima formation, vascular smooth muscle cells and fibroustissue of the GM-CSF group were less than those of the control group. The endothelium of the GM-CSFgroup was more integrated, and stenosis of lumen was slighter than that of the control group.Morphometry showed the lumen area of the GM-CSF group was larger than that of the control group[(1.27 +-0. 31) mm^2 vs. (0. 92 +- 0. 24) mm^2 ] , the neointimal area and percent of intimahyperplasia were significantly smaller than those of the control group [ (0. 85 +-0. 34) mm vs. (1.18 +-0. 38) mm^2; (40 +- 7)% vs. (55 +- 6)%]. GM-CSF could facilitate the repair of the intima,reduce neointima formation, better the function of the endothelium, and decrease the rate ofrestenosis.
文摘Objective To study the hematopoietic enhancing effects of recombinant human macrophage colony stimulating factor (rhM CSF) expressed in silkworm. Method Balb/c mice were irradiated with sublethal dose of 60 Coγ rays and then administered intraperitoneally with silkworm expressed rhM CSF (1000 U per individual for 7 days) in treatment group or with normal saline (for 7 days as well) in control group. The hematopoietic recovery of irradiation mice was observed by comparing peripheral white blood cell (WBC) counts, differential counts of WBC and bone marrow hematopoietic progenitor cell colony forming assay in soft agar at different time after irradiation. Results The total WBC counts (×10 9 /L) of treatment group at day 15 and 20 after irradiation (3.42±1.20, 5.56±2.50, respectively) were significantly higher than those of control group (2.03±0.90, 3.72± 2.30; both P<0.05). On days 10, 15, 20, 25 and 30 after irradiation, the monocyte counts (×10 9 /L) of treatment group (0.08±0.06, 0.16±0.10, 0.48± 0.35, 0.47±0.21 and 0.33±0.17, respectively) were all significantly higher than those of control group (0.025±0.016, 0.05±0.04, 0.23±0.16, 0.33± 0.19 and 0.17±0.13; all P<0.05). On days 15, 20 and 25, the granulocyte count (X10 9 /L) of treatment group (1.03±0.61, 2.18±1.19 and 3.28±1.09) were also higher than those of control group (0.62± 0.37, 1.40±0.99 and 2.20±0.74; all P<0.05). On day 9 after irradiation, the bone marrow CFU GM yield of control group (19±11/10 6 cells) was significantly lower than that of treatment group (78±30/10 6 cells, P< 0.05). Conclusion rhM CSF expressed in silkworm could accelerate hematopoietic recovery in irradiated mice.
文摘Objective To analyze efficacy and safety of CLAG regimen in patients with refractory or relapsed acute myeloid leukemia(AML).Methods Efficacy and adverse events of patients with refractory or relapsed AML who were treated with one course of CLAG from April 1st,2014 through December 9th,2015 in our hospital were retrospectively reviewed.Results Thirty-three
基金supported by the National Natural Science Foundation of China,No.81330029(to JNZ),81501057(to YT)the Science&Technology Development Fund of Tianjin Education Commission for Higher Education in China,No.2016YD02(to YW)the Technology Program Fund of Tianjin Health and Family Planning Commission for the Key Field of Traditional Chinese Medicine,No.2018001(to ZGW)
文摘Traumatic brain injury（TBI） can result in poor functional outcomes and death, and overall outcomes are varied. Growth factors, such as angiopoietin-1（Ang-1）, vascular endothelial growth factor（VEGF）, and granulocyte-colony stimulating factor（G-CSF）, play important roles in the neurological functions. This study investigated the relationship between serum growth factor levels and long-term outcomes after TBI. Blood samples from 55 patients were collected at 1, 3 and 7 days after TBI. Blood samples from 39 healthy controls were collected as a control group. Serum Ang-1, G-CSF, and VEGF levels were measured using ELISA. Patients were monitored for 3 months using the Glasgow Outcome Scale-Extended（GOSE）. Patients having a GOSE score of 〉 5 at 3 months were categorized as a good outcome, and patients with a GOSE score of 1-5 were categorized as a bad outcome. Our data demonstrated that TBI patients showed significantly increased growth factor levels within 7 days compared with healthy controls. Serum levels of Ang-1 at 1 and 7 days and G-CSF levels at 7 days were significantly higher in patients with good outcomes than in patients with poor outcomes. VEGF levels at 7 days were remarkably higher in patients with poor outcomes than in patients with good outcomes. Receiver operating characteristic analysis showed that the best cut-off points of serum growth factor levels at 7 days to predict functional outcome were 1,333 pg/mL for VEGF, 447.2 pg/mL for G-CSF, and 90.6 ng/mL for Ang-1. These data suggest that patients with elevated levels of serum Ang-1, G-CSF, and decreased VEGF levels had a better prognosis in the acute phase of TBI（within 7 days）. This study was registered with the Chinese Clinical Trial Registry（registration number： ChiCTR1800018251） on September 7, 2018.
文摘BACKGROUND Human Wharton’s jelly-derived mesenchymal stromal/stem cells(hWJ-MSCs)have gained considerable attention in their applications in cell-based therapy due to several advantages offered by them.Recently,we reported that hWJ-MSCs and their conditioned medium have significant therapeutic radioprotective potential.This finding raised an obvious question to identify unique features of hWJ-MSCs over other sources of stem cells for a better understanding of its radioprotective mechanism.AIM To understand the radioprotective mechanism of soluble factors secreted by hWJMSCs and identification of their unique genes.METHODS Propidium iodide staining,endogenous spleen colony-forming assay,and survival study were carried out for radioprotection studies.Homeostasis-driven proliferation assay was performed for in vivo lymphocyte proliferation.Analysis of RNAseq data was performed to find the unique genes of WJ-MSCs by comparing them with bone marrow mesenchymal stem cells,embryonic stem cells,and human fibroblasts.Gene enrichment analysis and protein-protein interaction network were used for pathway analysis.RESULTS Co-culture of irradiated murine splenic lymphocytes with WJ-MSCs offered significant radioprotection to lymphocytes.WJ-MSC transplantation increased the homeostasis-driven proliferation of the lymphocytes.Neutralization of WJ-MSC conditioned medium with granulocyte-colony stimulating factor antibody abolished therapeutic radioprotection.Transcriptome analysis showed that WJ-MSCs share several common genes with bone marrow MSCs and embryonic stem cells and express high levels of unique genes such as interleukin(IL)1-α,IL1-β,IL-6,CXCL3,CXCL5,CXCL8,CXCL2,CCL2,FLT-1,and IL-33.It was also observed that WJ-MSCs preferentially modulate several cellular pathways and processes that handle the repair and regeneration of damaged tissues compared to stem cells from other sources.Cytokine-based network analysis showed that most of the radiosensitive tissues have a more complex network for the elevated cytokines.CONCLUSION Systemic infusion of WJ-MSC conditioned media will have significant potential for treating accidental radiation exposed victims。
