UNASSIGNED: Autologous hematopoietic stem cell transplantation (ASCT) has become the mainstay treatment for many hematological malignancies and solid tumors. An adequate number of stem cells must be collected for better ASCT outcomes, which is challenging in 5%-30% of patients. To improve mobilization, plerixafor is used along with granulocyte colony-stimulating factor (G-CSF).
UNASSIGNED: We conducted a retrospective single center study involving patients who received plerixafor pre-ASCTs between January 2013 and December 2020 at a tertiary care center in Lebanon. We identified a total of 84 consecutive adult patients. All patients identified were poor mobilizers and have eventually received plerixafor either as pre-emptive use before first apheresis in those with peripheral CD34 + of less than 20 cells/ul, or after failure of first apheresis in those with peripheral stem cells (PSC) >2.0 × 106 cells/Kg.
UNASSIGNED: The median age at ASCT was 52.7 years (22-74) with 61% male predominance. Multiple myeloma was the most prevalent disease 64% followed by Lymphoma 32%. The majority of patients were in complete remission 64% at the time of ASCT. Most patients received proteasome inhibitor-based induction therapy 67% and Melphalan-based conditioning therapy 68%. The median follow-up from ASCT was 9 months (1-59). It was noted that greater body mass index (BMI) is a significant factor for better PSC collection whether premobilization (P = 0.003), or post plerixafor mobilization (P = 0.024). Moreover, Multiple Myeloma patients showed better mobilization using Plerixafor (P = 0.049). Using Plerixafor along with G-CSF in poor mobilizers post G-CSF alone showed a statistically significant increase in the collected PSC mean from 0.67 × 106 cells/Kg to 4.90 × 106 cells/Kg (P < 0.001) with a failure rate only for 12 patients (15%). The infusion of PSC > 2.5 × 106 cells/Kg has shown 3 days decrease in time to platelet engraftment (P = 0.021) and a 36% decrease in progression/relapse rate (P = 0.025).
UNASSIGNED: Plerixafor is effective in increasing the PSC yield in poor mobilizers. Low BMI and hematologic malignancies other than Multiple Myeloma are risk factors for poor mobilization. More studies should be performed to establish more risk factors, helping us to identify poor mobilizers more accurately and initiate plerixafor mobilization early on.

No reports on granulocyte colony-stimulating factor-producing lung cancer associated with antiphospholipid antibody syndrome. A 73-year-old man was referred to our department to undergo surgery for lung cancer in the right upper lobe. His examination results suggested that his condition was caused by an elevated white blood cell count and an increased inflammatory response due to granulocyte colony-stimulating factor production. The presence of antiphospholipid antibody syndrome was suspected, and the decrease in coagulation factors was considered to be inhibited by the lupus anticoagulant. Perioperatively, the patient was treated with heparin and steroids, and a thoracoscopically assisted right upper lobectomy was performed. Postoperatively, histopathological examination revealed pleomorphic carcinoma, and the patient tested negative for anticardiolipin IgG antibodies. In lung cancer patients with elevated white blood cell counts, fever, and an inflammatory response, granulocyte colony-stimulating factor-producing lung cancer is an important differential diagnosis. Additionally, when coagulation abnormalities are observed preoperatively, a thorough examination is necessary to prepare for perioperative management.

Cutaneous leishmaniasis (CL), caused by Leishmania braziliensis, in recent decades has shown decreasing cure rates after treatment with meglumine antimoniate (MA). Granulocyte colony-stimulating factor (G-CSF) is a cytokine associated with epithelialization and healing processes.
METHODS: This study compares the effectiveness of G-CSF associated with MA in the treatment of CL. A total of 32 patients aged between 18 and 50 years with CL confirmed for L. braziliensis were included in this study. G-CSF or placebo (0.9% saline) was applied by intralesional infiltration at four equidistant points on the edges of the largest ulcer on days 0 and 15 of treatment associated with intravenous MA.
RESULTS: Males predominated in the G-CSF group (59%), while females predominated in the control group (53%). Injuries to the lower limbs predominated in both study groups. The cure rate in the G-CSF group was 65% and in the control group it was 47%, 90 days after initiation of therapy.
CONCLUSIONS: Our data indicate that the association of G-CSF with MA is not superior to MA monotherapy. Although not significant, the potential benefit of this combination deserves further investigation. The use of higher doses or other routes of application of G-CSF in a greater number of patients should contribute to a definitive response.

Gliomas comprise most cases of central nervous system (CNS) tumors. Gliomas afflict both adults and children, and glioblastoma (GBM) in adults represents the clinically most important type of malignant brain cancer, with a very poor prognosis. The cell surface glycoprotein CD114, which is encoded by the CSF3R gene, acts as the receptor for the granulocyte colony stimulating factor (GCSF), and is thus also called GCSFR or CSFR. CD114 is a marker of cancer stem cells (CSCs), and its expression has been reported in several cancer types. In addition, CD114 may represent one among various cases where brain tumors hijack molecular mechanisms involved in neuronal survival and synaptic plasticity. Here, we describe CSF3R mRNA expression in human gliomas and their association with patient prognosis as assessed by overall survival (OS). We found that the levels of CSF3R/CD114 transcripts are higher in a few different types of gliomas, namely astrocytoma, pilocytic astrocytoma, and GBM, in comparison to non-tumoral neural tissue. We also observed that higher expression of CSF3R/CD114 in gliomas is associated with poorer outcome as measured by a shorter OS. Our findings provide early evidence suggesting that CSF3R/CD114 shows a potential role as a prognosis marker of OS in patients with GBM.

OBJECTIVE: To investigate the mechanism of Xuanhusuo powder (XHSP) inhibiting the differentiation of spleen myeloid-derived suppressor cells (MDSCs) in breast cancer mice.
METHODS: Forty-eight BALB/c female mice aged 4-5 weeks were selected, 6 of them were in normal control group, while others were in tumor-bearing models established by orthotopic injection of 4T1 cells into the subcutaneous fat pad of the second pair of left mammary glands. The tumor-bearing mice were divided into granulocyte colony stimulating factor (G-CSF) control group, G-CSF knock-down group, model control group, XHSP small dose group, XHSP medium dose group, XHSP high dose group, and cyclophosphamide (CTX) group, with 6 mice in each group. G-CSF control group and G-CSF knock-down group were constructed by stably transfecting 4T1 cells established by shRNA lentivirus combined with puromycin selection. 48 h after the model was established, XHSP small, medium, high dose group were given 2, 4, 8 g·kg－1·d－1 intragastric administration once a day, respectively. CTX was given 30 mg/kg by intraperitoneal injection, once every other day. The other groups were given an equal volume of 0.5% hydroxymethylcellulose sodium. The drugs in each group were continuously administered for 25 d. Histological changes in spleen were observed by HE staining, the proportion of MDSCs subsets in the spleen were detected by flow cytometry, the co-expression of CD11b and Ly6G in the spleen was detected by immunofluorescence, and the concentration of G-CSF in peripheral blood was detected by ELISA. The spleen of tumor-bearing mice was co-cultured with 4T1 stably transfected cell lines in vitro, treated with XHSP (30 μg/mL) for 24 h, and the co-expression of CD11b and Ly6G in the spleen was detected by immunofluorescence. 4T1 cells were treated by XHSP (10, 30, 100 μg/mL) for 12 h. The mRNA level of G-CSF was detected by realtime RT-PCR.
RESULTS: Compared with normal mice, the red pulp of the spleen in tumor-bearing mice was widened with megakaryocyte infiltration. The proportion of spleen polymorphonucleocyte-like MDSCs (PMN-MDSCs) was significantly increased (P<0.01) and the co-expression of CD11b and Ly6G was increased, and the concentration of G-CSF in peripheral blood was significantly increased (P<0.01). However, XHSP could significantly reduce the proportion of PMN-MDSCs (P<0.05) and the co-expression of CD11b and Ly6G in the spleen, down-regulate the mRNA level of G-CSF in 4T1 cells (P<0.01). The concentration of G-CSF in peripheral blood of tumor-bearing mice also decreased (P<0.05) and tumor volume was reduced and splenomegaly was improved (all P<0.05).
CONCLUSIONS: XHSP may play an anti-breast cancer role by down-regulating G-CSF, negatively regulating the differentiation of MDSCs, and reconstruct the spleen myeloid microenvironment.
目的: 探讨玄胡索散抑制乳腺癌小鼠脾脏髓源抑制细胞（MDSC）分化的作用机制。方法: 4~5周龄BALB/c雌性小鼠48只，其中6只为正常对照组，其他42只采用小鼠左侧第二对乳腺皮下脂肪垫接种4T1细胞构建乳腺癌荷瘤小鼠模型，分为粒细胞集落刺激因子（G-CSF）对照组、G-CSF敲减组、模型对照组、玄胡索散小剂量组、玄胡索散中剂量组、玄胡索散大剂量组和环磷酰胺组，每组6只。其中G-CSF对照组和G-CSF敲减组分别采用shRNA慢病毒转染联合嘌呤霉素构建相应4T1稳转细胞模型。各组造模48 h后，玄胡索散小剂量组、玄胡索散中剂量组、玄胡索散大剂量组分别按2、4、8 g·kg－1·d－1玄胡索散灌胃，每天一次；环磷酰胺组按30 mg/kg腹腔注射环磷酰胺，隔天一次；其他组给予等体积0.5%羟甲基纤维素纳。各组连续给药25 d。苏木精-伊红染色观察脾脏组织病理学改变，流式细胞术测定脾脏MDSC亚群比例，免疫荧光法检测脾脏CD11b、Ly6G共表达，酶联免疫吸附测定外周血G-CSF浓度。在体外，建立荷瘤小鼠脾脏与4T1稳转株共培养体系，玄胡索散（30 μg/mL）处理24 h，免疫荧光检测脾脏CD11b、Ly6G共表达；不同浓度的玄胡索散（10、30、100 μg/mL）处理4T1细胞12 h，实时逆转录PCR检测G-CSF mRNA水平。结果: 与正常对照组比较，模型鼠脾脏红髓增宽伴巨核细胞浸润，脾脏多形核细胞样MDSC（PMN-MDSC）比例增加（P<0.01），脾脏CD11b、Ly6G共表达增多，外周血G-CSF浓度上升（P<0.01）。玄胡索散干预后脾脏PMN-MDSC比例减小（P<0.05），脾脏CD11b、Ly6G共表达减少，4T1细胞G-CSF mRNA水平下调（P<0.01），模型鼠外周血G-CSF浓度减少（P<0.05），肿瘤体积缩小，脾脏增大情况改善（均P<0.05）。结论: 玄胡索散可能通过下调G-CSF，阻碍MDSC向PMN-MDSC分化，重建脾脏髓系微环境，从而发挥抗乳腺癌作用。.

OBJECTIVE: This animal model aimed to compare the rat group that received brain irradiation and did not receive additional treatment (only saline) and the rat group that underwent brain irradiation and received Granulocyte colony stimulating factor (G-CSF) treatment. In addition, the effects of G-CSF on brain functions were examined by magnetic resonance (MR) imaging and histopathologically.
METHODS: This study used 24 female Wistar albino rats. Drug administration (saline or G-CSF) was started at the beginning of the study and continued for 15 days after whole-brain radiotherapy (WBRT). WBRT was given on day 7 of the start of the study. At the end of 15 days, the behavioral tests, including the three-chamber sociability test, open field test, and passive avoidance learning test, were done. After the behavioral test, the animals performed the MR spectroscopy procedure. At the end of the study, cervical dislocation was applied to all animals.
RESULTS: G-CSF treatment positively affected the results of the three-chamber sociability test, open-space test and passive avoidance learning test, cornu Ammonis (CA) 1, CA3, and Purkinje neuron counts, and the brain levels of brain-derived neurotrophic factor and postsynaptic density protein-95. However, G-CSF treatment reduced the glial fibrillary acidic protein immunostaining index and brain levels of malondialdehyde, tumor necrosis factor-alpha, nuclear factor kappa-B, and lactate. In addition, on MR spectroscopy, G-CSF had a reversible effect on brain lactate levels.
CONCLUSIONS: In this first designed brain irradiation animal model, which evaluated G-CSF effects, we observed that G-CSF had reparative, neuroprotective and anti-neurodegenerative effects and had increased neurotrophic factor expression, neuronal counts, and morphology changes. In addition, G-CSF had a proven lactate-lowering effect in MR spectroscopy and brain materials.

The coexistence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) in a single individual, also known as overlap syndrome (OVS), is associated with higher cardiovascular risk and mortality than either OSA or COPD alone. However, the underlying mechanisms remain unclear. We hypothesized that patients with OVS have elevated systemic inflammatory biomarkers relative to patients with either disease alone, which could explain greater cardiovascular risk observed in OVS.
We included 255 participants in the study, 55 with COPD alone, 100 with OSA alone, 50 with OVS, and 50 healthy controls. All participants underwent a home sleep study, spirometry, and a blood draw for high-sensitivity C-reactive protein and total blood count analysis. In a randomly selected subset of 186 participants, inflammatory protein profiling was performed using Bio-Rad Bio-Plex Pro Human Cytokine 27-Plex Assays. Biomarker level differences across groups were identified using a mixed linear model.
Levels of interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and granulocyte colony stimulating factor (G-CSF) were higher in participants with OVS and COPD compared with healthy controls and participants with OSA. Furthermore, participants with OVS had higher circulating levels of leukocytes and neutrophils than those with COPD, OSA, and controls.
COPD and OVS are associated with higher systemic inflammation relative to OSA and healthy controls. This work proposes the potential utilization of interleukin 6, granulocyte colony stimulating factor, and high-sensitivity C-reactive protein as screening biomarkers for COPD in patients with OSA. Inflammatory pathways may not fully explain the higher cardiovascular risk observed in OVS, indicating the need for further investigation.
Sanchez-Azofra A, Gu W, Masso-Silva JA, et al. Inflammation biomarkers in OSA, chronic obstructive pulmonary disease, and chronic obstructive pulmonary disease/OSA overlap syndrome. J Clin Sleep Med. 2023;19(8):1447-1456.

Cell-based therapy and tissue engineering are promising substitutes for liver transplantation to cure end-stage liver disorders. However, the limited sources for healthy and functional cells and poor engraftment rate are main challenges to the cell-based therapy approach. On the other hand, feasibility of production and size of bioengineered tissues are primary bottlenecks in tissue engineering. Here, we induce regeneration in a rat fibrotic liver model by transplanting a natural bioengineered scaffold with a native microenvironment repopulated with autologous stem/progenitor cells. In the main experimental group, a 1 mm3 stromal derived factor-1α (SDF-1α; S) loaded scaffold from decellularized liver extracellular matrix (LEM) was transplanted (Tx) into a fibrotic liver and the endogenous stem/progenitor cells were mobilized via granulocyte colony stimulating factor (G-CSF; G) therapy. Four weeks after transplantation, changes in liver fibrosis and necrosis, efficacy of cell engraftment and differentiation, vasculogenesis, and liver function recovery were assessed in this (LEM-TxSG) group and compared to the other groups. We found significant reduction in liver fibrosis stage in the LEM-TxSG, LEM-TxS and LEM-TxG groups compared to the control (fibrotic) group. Liver necrosis grade, and alanine transaminase (ALT) and aspartate transaminase (AST) levels dramatically reduced in all experimental groups compared to the control group. However, the number of engrafted cells into the transplanted scaffold and ratio of albumin (Alb) positive cells per total incorporated cells were considerably higher in the LEM-TxSG group compared to the LEM-Tx, LEM-TxS and LEM-TxG groups. Serum Alb levels increased in the LEM-Tx, LEM-TxS, and LEM-TxG groups, and was highest in the LEM-TxSG group, which was significantly more than the fibrotic group. Small vessel formation in the LEM-TxSG group was significantly higher than the LEM-Tx and LEM-TxS groups. Totally, these findings support application of the in vivo tissue engineering approach as a possible novel therapeutic strategy for liver fibrosis.

Acute-on-chronic liver failure (ACLF) has a high mortality rate. The role of granulocyte colony-stimulating factor (G-CSF) in ACLF remains controversial. Monocytes/macrophages are core immune cells, which are involved in the initiation and progression of liver failure; however, the effect of G-CSF on monocytes/macrophages is unclear. The study aimed to verify the clinical efficacy of G-CSF and explore the effect of it on monocytes in hepatitis B virus (HBV)-related ACLF (HBV-ACLF) paitents.
We performed a large randomized controlled clinical trial for the treatment of HBV-ACLF using G-CSF. A total of 111 patients with HBV-ACLF were prospectively randomized into the G-CSF group (5 μg/kg G-CSF every day for 6 days, then every other day until day 18) or the control group (standard therapy). All participants were followed up for at least 180 days. The relationship between monocyte count and mortality risk was analyzed. The effect of G-CSF on the phenotype and function of monocytes from patients with HBV-ACLF was evaluated using flow cytometry in vivo and in vitro experiments.
The survival probability of the G-CSF group at 180 days was higher than that of the control group (72.2% vs. 53.8%, P = 0.0142). In the G-CSF-treated group, the monocyte counts on days 0 and 7 were independently associated with an evaluated mortality risk in the fully adjusted model (Model 3) [at day 0: hazard ratio (HR) 95% confidence interval (CI): 15.48 (3.60, 66.66), P = 0.0002; at day 7: HR (95% CI): 1.10 (0.50, 2.43), P=0.8080]. Further analysis showed that after treatment with G-CSF in HBV-ACLF patients, the expression of M1-like markers (HLA-DR and CD86) in monocytes decreased (HLA-DR: P = 0.0148; CD86: P = 0.0764). The expression of MerTK (M2-like marker) increased (P = 0.0002). The secretion of TNF-α, IL-6, and IL-10 from monocytes decreased without lipopolysaccharide (LPS) stimulation (TNF-α: P < 0.0001; IL-6: P= 0.0025; IL-10: P = 0.0004) or with LPS stimulation (TNF-α: P = 0.0439; P = 0.0611; IL-10: P = 0.0099). Similar effects were observed in vitro experiments.
G-CSF therapy confers a survival benefit to patients with HBV-ACLF. G-CSF can promote the anti-inflammatory/pro-restorative phenotype (M2-like) transition of monocytes, which may contribute to the recovery of ACLF.Clinical Trial Registration Number: ClinicalTrials.gov, identifier (NCT02331745).

OBJECTIVE: Cirrhosis patients exhibit cytopenia, and, at times refractory neutropenia to granulocyte colony-stimulating factor (G-CSF), which acts through the CSF3-receptor (CSF3R), and changes in CSF3R can affect the response. We conducted this study to assess the CSF3R status and its relevance in cirrhotic patients.
METHODS: Cirrhotic patients (n=127) and controls (n=26) with clinically indicated bone marrow (BM) examination were studied. BM assessment was done by qRT-PCR and immunohistochemistry (IHC) for CSF3R. Circulating G-CSF, CSF3R, and carcinoembryonic antigen cell adhesion molecule-1 (CEACAM1) were measured. BM hematopoietic precursor cells and their alterations were examined by flow cytometry. The findings were validated in liver cirrhosis patients who received G-CSF for severe neutropenia.
RESULTS: The mean age was 48.6±13.4 years, and 80.3% were men. Circulatory CSF3R reduction was noted with the advancement of cirrhosis, and confirmed by qRT-PCR and IHC in BM. CSF3R decline was related to decreased hematopoietic stem cells (HSCs) and downregulation of CSF3R in the remaining HSCs. Cocultures confirmed that CEACAM1 led to CSF3R downregulation in BM cells by possible lysosomal degradation. Baseline low peripheral blood-(PB)-CSF3R also predisposed development of infections on follow-up. Decreased CSF3R was also associated with nonresponse to exogenous G-CSF treatment of neutropenia.
CONCLUSIONS: Advanced liver cirrhosis was associated with low CSF3R and high CEACAM1 levels in the BM and circulation, making patients prone to infection and inadequate response to exogenous G-CSF.