Number Of Cells In Peripheral Blood Research Articles

Correlation Analysis of the Number of Hemophagocytes and Peripheral Blood Cells in Bone Marrow

To study the correlation between the number of hemophagocytes and peripheral blood cells in bone marrow of patients with fever of unknown origin. A total of 465 patients with fever of unknown origin in our hospital from January 2019 to December 2021 were selected as the research objects, which was to reviewed retrospectively the correlation between the number of hemophagocytes and peripheral blood cells in bone marrow. The positive rates of hemophagocytes detected in the three lines decreased group, the two lines decreased group, the one line decreased group, normal group of the three lines and at least one of the three lines increased group were 86.4%, 62.1%, 38.3%, 34.6% and 33.3%, respectively. The number of hemophagocytes per unit area in the three lines decreased group was significantly higher than that in the other four groups ( P < 0.001). The number of hemophagocytes per unit area in the two lines decreased group was higher than that in the one line decreased group, normal group of three lines and at least one of the three lines increased group ( P < 0.01). There was no significant difference in the number of hemophagocytes per unit area between the group with a decreased number of one line and the other two groups with a normal number of three lines and the group with at least one increased number of three lines (P >0.05). The missed rates of hemophagocytes in the five groups were 15.78%, 22.03%, 62.22%, 77.78% and 53.84%, respectively. For patients with fever of unknown origin, especially those with obvious decrease in the number of three lines and two lines in peripheral blood cells, which should pay attention to the detection of hemophagocytes in bone marrow. Meanwhile, if the number of three lines was normal even at least one of the three lines increased, the presence of hemophagocytes in the bone marrow slice should be also carefully observed.

Coexpression of Tim-3 and PD-1 of T Lymphocytes Prevents Acute Graft-Versus-Host Disease

T lymphocytes are critical players in acute graft-versus-host disease (aGVHD). TIM3expression on the T cell surface was identified to induce immune tolerance in a mouse GVHD model; in addition, PD1 +TIM3 + double-positive T cells displayed more potent immunosuppression compared to PD1 + T cells. However, their clinical potential is greatly limited by their low cell number in peripheral blood (PB). We already introduced a novel method to obtain a high number of PD1 +TIM3 + lymphocytes that culturing CD3 + cells isolated from G-CSF mobilized peripheral blood stem cells (CD3 +G-PBSC) with human serum albumin (HSA). We also confirmed that cultured PD1 +TIM3 + lymphocytes are the most potent subset of the CD3 + cells that inhibit T cell proliferation. In this study, we investigate the immunosuppressive effects of PD1 +TIM3 + lymphocytes after a 2-day culture with HSA (D2-CD3 +G-PBSC) or after a 4-day culture with HSA (D4-CD3 +G-PBSC). Also, we evaluate the treatment efficacy of PD1 +TIM3 + lymphocytes in the xenograft mouse aGVHD model. Methods. The healthy donors were subcutaneously injected with G-CSF (10μg/kg) for five days. G-PBSCs were collected from the donors using a COBE spectra cell separator, and CD3 + cells were isolated by positive selection by magnetic-activated cell sorting (MACS) using CD3 Dynabeads™. CD3 + G-PBSC were cultured with 5% HSA for 2 days or 4 days (1x10 5 cells/mL). PD1 and TIM3 expressions were analyzed using flow cytometry (FACS). Sorted T lymphocytes were cultured with irradiated allo-MNCs for 3 days (Mixed Lymphocyte Reaction; MLR). 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) was used as an intracellular fluorescent dye in MLR (CFSE-MLR) to measure T cell proliferation. aGVHD was induced by intraperitoneal injection of human PB MNCs to the NOD-SCID IL-2Rγ null mouse after exposure of 3Gy irradiation. The treatment efficacy of PD1 +TIM3 + lymphocytes was analyzed by determining the survival rate after tail vein injection of PD1 +TIM3 + lymphocytes (1x10 7/kg). Results. Normally, very few cells (0.2±0.2%) were PD1 +TIM3 + lymphocytesin PB. The numbers of PD1 +TIM3 + lymphocytes markedly increased by 74-fold in D2-CD3 +G-PBSC and 370-fold in D4-CD3 +G-PBSC, respectively. CD3 + G-PBSC were composed of three types of cells such as PD1 -TIM3 -, PD1 +TIM3 -, and PD1 +TIM3 + lymphocytes. To check the origin of PD1 +TIM3 + lymphocytes after HSA treatment, PD1 -Tim3 - and PD1 +Tim3 - lymphocytes from CD3 +G-PBSC were sorted and cultured with HSA. It was confirmed that PD1 +TIM3 + lymphocytes originated from PD1 -TIM3 - lymphocytes. To assess the immunosuppressive effects of cultured T lymphocytes, we used CSFE-MLR. D2-CD3 +G-PBSC significantly increased the levels of unstimulated T cells compared to D4-CD3 +G-PBSC (% of unstimulated T cells in D2-CD3 +G-PBSC vs. in D4-CD3 +G-PBSC; 38.9±3.0% vs. 13.9±6.6%). Also, both PD1 +TIM3 + lymphocytes from D2-CD3 +G-PBSC and D4-CD3 +G-PBSC demonstrated significantly enhanced levels of immunosuppression (% of unstimulated T cells PD1 +TIM3 + lymphocytes from D2-CD3 +G-PBSC and D4-CD3 +G-PBSC; 31.6±5.5 and 36.6±13.3, respectively). Lastly, we tested the effects of anti-PD1 or anti-TIM3 blocking mAb on the PD1 +TIM3 + lymphocytes. The immunosuppressive effects of PD1 +TIM3 + lymphocytes from D2-CD3 +G-PBSC and D4-CD3 +G-PBSC were significantly decreased by anti-PD1 mAb (% of unstimulated T cells in PD1 +TIM3 + lymphocytes from D2-CD3 +G-PBSC and D4-CD3 +G-PBSC; 21.1±4.5 from 31.6±5.5 and 18.4±7.8 from 36.6±13.3, respectively). However, the immunosuppression of PD1 +TIM3 + lymphocytes from D2-CD3 +G-PBSC was not decrease by anti-TIM3 mAb (% of unstimulated T cells in PD1 +TIM3 + lymphocytes from D2-CD3 +G-PBSC and D4-CD3 +G-PBSC; 28.7±3.3 from 31.6±5.5 and 22.7±5.6 from 36.6±13.3, respectively). These data indicated that PD1 +TIM3 + lymphocytes from D2-CD3 +G-PBSC have the same phenotype as PD1 +TIM3 + lymphocytes from D4-CD3 +G-PBSC, however, their functions are different. Next, we used the xenograft mouse aGVHD model to evaluate the treatment efficacy of PD1 +TIM3 + lymphocytes for preventing aGVHD. In the control group, 14% of the mice survived at 100 days. Mice that were treated with PD1 +TIM3 + lymphocytes from D2-CD3 +G-PBSC and D4-CD3 +G-PBSC demonstrated 100% and 71% survival rate at 100 days, respectively. Conclusion. Ex vivo HSA treatment of CD3 + G-PBSCs for 2 days shows promising therapeutic potential for the treating patients with aGVHD.

Immunomodulatory Nanoparticles for Modulating Arthritis Flares.

Disease-modifying drugs have improved the treatment for autoimmune joint disorders, such as rheumatoid arthritis, but inflammatory flares are a common experience. This work reports the development and application of flare-modulating poly(lactic-co-glycolic acid)-poly(ethylene glycol)-maleimide (PLGA-PEG-MAL)-based nanoparticles conjugated with joint-relevant peptide antigens, aggrecan70-84 and type 2 bovine collagen256-270. Peptide-conjugated PLGA-PEG-MAL nanoparticles encapsulated calcitriol, which acted as an immunoregulatory agent, and were termed calcitriol-loaded nanoparticles (CLNP). CLNP had a ∼200 nm hydrodynamic diameter with a low polydispersity index. In vitro, CLNP induced phenotypic changes in bone marrow derived dendritic cells (DC), reducing the expression of costimulatory and major histocompatibility complex class II molecules, and proinflammatory cytokines. Bulk RNA sequencing of DC showed that CLNP enhanced expression of Ctla4, a gene associated with downregulation of immune responses. In vivo, CLNP accumulated in the proximal lymph nodes after intramuscular injection. Administration of CLNP was not associated with changes in peripheral blood cell numbers or cytokine levels. In the collagen-induced arthritis and SKG mouse models of autoimmune joint disorders, CLNP reduced clinical scores, prevented bone erosion, and preserved cartilage proteoglycan, as assessed by high-resolution microcomputed tomography and histomorphometry analysis. The disease protective effects were associated with increased CTLA-4 expression in joint-localized DC and CD4+ T cells but without generalized suppression of T cell-dependent immune response. The results support the potential of CLNP as modulators of disease flares in autoimmune arthropathies.

Effect and Mechanism of Specnuezhenide on Chemotherapy-induced Myelosuppression.

This study aimed to investigate the therapeutic effect of Specnuezhenide on myelosuppression induced by chemotherapy and clarify its mechanism. In this study, we measured peripheral blood cells, thymus index, spleen index, bone marrow nucleated cells (BMNCs), and the number of cell colonies counted in vitro by hematopoietic progenitor cells (HPCs) to determine the effect of SPN on cyclophosphamide (CTX)-induced myelosuppression. The alterations in the expression of relevant proteins, the cell cycle, and cytokines associated with hematopoietic cells were examined to better understand how it works. In the cyclophosphamide-induced mouse model, our study discovered that SPN can increase the number of peripheral blood cells and BMNCs after treatment, increase the thymus index and decrease the spleen index, and promote the proliferation and differentiation of HPCs. SPN can improve the production of cultured colonies in vitro, reduce the level of hematopoietic factors in vivo, regulate the proportion of G0/G1 phase cells, and promote the normal growth and development of cells. SPN can increase the expression levels of key proteins MEK and p-ERK in the MAPK signaling pathway, which may be one of the important mechanisms for improving myelosuppression. SPN can enhance the hematological and immunological functions of myelosuppressionmice, and it is hypothesized that SPN is extremely helpful to the hematopoietic and immune functions of tumor patients following chemotherapy. SPN might be used to treat myelosuppression. Additionally, high doses of SPN have a stronger therapeutic effect than low levels of SPN.

Thymalfasin therapy accelerates COVID-19 pneumonia rehabilitation through anti-inflammatory mechanisms

IntroductionThymosin drugs are commonly used for the treatment of viral infections due to their immunomodulatory effects. The comprehensive clinical efficacy of Thymalfasin therapy for COVID-19 associated pneumonia is not yet fully researched, another issue, whether the use of thymosin drugs can reduce the rate of COVID-19 progression to severe pneumonia has not been well documented. The aim of the present study was to multi-angle evaluate the clinical efficacy of Thymalfasin therapy for COVID-19 pneumonia by retrospective review of the clinical data of 338 inpatients with common COVID-19 infection who received treatment in our hospital.MethodsThe primary index of observation was whether progression to severe pneumonia occurred within a week after admission, and the secondary indexes were the length of hospital stay, time of negative conversion of COVID-19 antigen, the number of peripheral lymphocytes and white blood cells (WBC), and C-reactive protein (CRP) and procalcitonin (PCT) levels,and the control of pneumonia related symptoms, for example, fever, listlessness, inflammatory exudate area shown on lung CT (%).ResultsThe length of hospital stay of patients in Thymalfasin group was significantly shorter than that of patients in the control group (p < 0.01). The proportion of relief of pneumonia related symptoms (fever, fatigue) in the Thymalfasin therapy group was significantly higher than that in the control group, and the inflammatory exudate area shown on CT was significantly lower than that in the control group (p < 0.05). Multivariate logistic regression analysis showed that the use of Thymalfasin was an independent protective factor affecting the progression to severe pneumonia. Multifactorial Cox model analysis indicated that negative conversion of COVID-19 antigen was significantly faster in patients using Thymalfasin and younger patients.ConclusionThymalfasin therapy has shown excellent clinical efficacy in the treatment of COVID-19 pneumonia, it can reduce inflammatory reactions, promote the relief of COVID-19 pneumonia related symptoms such as fever and fatigue, facilitate effusion absorption, and accelerate COVID-19 pneumonia recovery. Thymalfasin can prevent progression of common COVID-19 infection to severe pneumonia via multiple immunity-enhancing and anti-inflammatory protective mechanisms.

Number of natural killer cells and cytokine levels in peripheral blood at various degrees of severity

This study aims to investigate NK cell number and cytokines level in various degrees of severity in COVID-19 cases. A total of 63 COVID-19 patient aged &gt;18 y were divided into mild-moderate and severe-critical groups. Patient characteristics and peripheral blood count were obtained from medical records. NK cells number, levels of IFN-?, IL-10, and IL-12 in peripheral blood were examined by means of flow cytometry. The severe-critical group had leukocytosis, neutrophilia, lymphopenia, higher Neutrophil Lymphocyte Ratio, lower NK cell number and higher level of IL-10. In severe-critical group, those aged &gt;60 years had higher IL-10. In both groups, patients with diabetes comorbidities had a higher number of NK cells (p&lt;0.05). NK cell number and IL-10 in peripheral blood have potential as a predictor of severe COVID-19 patients.

ОСОБЕННОСТИ ДИНАМИКИ ЛИМФОЦИТОВ ПЕРИФЕРИЧЕСКОЙ КРОВИ В ТЕЧЕНИЕ ПЕРВОЙ НЕДЕЛИ ПРИ КОМБИНИРОВАННЫХ РАДИАЦИОННО-МЕХАНИЧЕСКИХ ПОРАЖЕНИЯХ

For a long time, the attention of researchers studying combined radiation-mechanical injuries (CRMI) has been focused on the study of individual syndromes: mechanical trauma and acute radiation syndrome. To diagnose and assess the severity of each syndrome, tests used for isolated injuries are recommended. However, the results of tests based on counting the number of different peripheral blood cells in an initially healthy person and in an injured patient who has experienced severe bleeding will be different. Accordingly, the assessment of the severity of developing acute radiation disease these patients will differ. The possibility of predicting the severity of developing radiation injury in CRMI using a lymphatic test during the first week after exposure is also being evaluated. In this report, based on the literature data, the dynamics of the absolute number of lymphocytes in patients with multiple mechanical injuries is considered. The results of numerous clinical and experimental studies indicate that severe and multiple injuries, starting from the first hours and during the first week of observation, are characterized by instability of the number of lymphocytes in peripheral blood with significant absolute lymphopenia on the first day. It is shown that the depth of lymphopenia and the rate of recovery of the number of lymphocytes to normal values depends on the severity of the mechanical injury. In addition, the deepening of lymphopenia is also caused by urgent medical measures that are standard in the provision of medical care for severe trauma with blood loss: massive infusion therapy and the appointment of corticosteroids. Thus, the use of a lymphocytic test in CRMI to assess the radiation dose without taking into account the significance of the trauma suffered will lead to a false prognosis of the degree of developing acute radiation damage, as well as to the lack of differentiation between the effects of radiation and non-radiation factors, and, consequently, to errors in patient management tactics.

Animal Model Establishment and Its Mechanism of Cytarabine-Iduced Myelosuppression

To establish an optimized model of bone marrow suppression induced by cytarabine (Ara-C) in C57BL/6 mice and preliminarily explore the mechanism of myelosuppression based on the cycle and apoptosis of BMNC. C57BL/6 mice were intraperitoneally injected with Ara-C 50, 100 and 200 mg/kg for 7 days, respectively. The survival rate and body weight of C57BL/6 mice were monitored. The number of peripheral blood cells and bone marrow nucleated cells (BMNC) was detected, and the morphology of bone marrow, thymus and spleen were measured on the 7th, 14th and 21st day of the experiment. The cycle and apoptosis of BMNC were also detected by flow cytometry. Ara-C 200 mg/kg caused 46.7% mortality in mice, and other doses had no significant effect on mortality. All doses of Ara-C induced bone marrow suppression in mice, as shown by a decrease in the number of peripheral blood cells (WBC, Neu, RBC, PLT) and BMNC (P<0.05), decrease in bone marrow hyperplasia, accompanied by immunosuppression and compensatory hematopoiesis of the spleen, and the above manifestations and duration were dose-dependent. Among them, the myelosuppression caused by Ara-C 50 mg/kg recovered quickly, and caused by Ara-C 200 mg/kg was too severe. The result of flow cytometry showed that Ara-C could cause S and G2/m arrest and increased apoptosis in BMNC. Ara-C can induce myelosuppression in mice with a dose-dependent severity and duration, and the model of myelosuppression with Ara-C 100 mg/kg is more optimized. The mechanism is related to the inhibition of BMNC proliferation and the promotion of apoptosis.

Clinical Significance of RAS Gene Mutations in Patients with Acute Myeloid Leukemia

To investigate the clinical characteristics of RAS gene mutations in patients with acute myeloid leukemia (AML). 43 myeloid gene mutations were detected using next-generation sequencing (NGS) in 180 patients with AML who were first diagnosed between May 2011 and February 2021. The molecular and clinical features of RAS gene mutations and their effects on efficacy and survival of patients were retrospectively analyzed. Among 180 AML patients, the proportion of mutations in RAS pathway-related genes were NRAS (14.4%), KRAS (2.2%), FLT3-ITD (13.8%), PTPN11 (7.7%), KIT (5.0%), FLT3-TKD (3.8%) and CBL (2.7%). Seventy-three (40.6%) AML patients had gene mutations associated with the RAS pathway.The number of peripheral blood white blood cells and the proportion of bone marrow primitive juvenile cells in patients with NRAS/KRAS gene mutation were higher than those of patient with RAS wild-type, the difference was statistically significant (P<0.05). NRAS/KRAS gene mutations were significantly associated with the CBL gene mutation(r=0.287). In young AML patients (age <60 years), there were no significant differences in complete response rate (CR), progression-free survival (PFS), and overall survival (OS) between patients with RAS gene mutation and those with wild-type(P>0.05). In elderly AML patients (age≥60 years), PFS and OS in RAS mutants were significantly lower than those in wild-type patients(P<0.05). In AML patients, RAS gene mutation is relatively common, and RAS gene mutation is associated with clinical characteristics and efficacy of patients, and may be a molecular marker of poor prognosis for elderly AML.

Dioscin Regulating Bone Marrow Apoptosis in Aplastic Anemia.

BackgroundAplastic anemia (AA), a disease of bone marrow failure, is caused by CD8+T mediated apoptosis of hematopoietic cells. However, traditional immunosuppressive therapy (IST) has severe liver and kidney toxicity and even cannot achieve the expected therapeutic effect in some patients.PurposeOur study is aimed to investigate the effect and mechanism of dioscin (DNS) for treating AA.MethodsBriefly, we established and evaluated the AA mouse model, DNS and positive control drugs were used for intervention treatment. After 14 days of intervention, femoral bone marrow pathology, bone marrow mononuclear cells (BMMCs) apoptosis rate, bone marrow CD34+ cell surface Fas (CD95) expression and Fas signaling pathway key proteins were detected.ResultsAfter the establishment of the AA mouse model, the number of peripheral blood cells including granulocytes, erythrocytes, hemoglobin, platelets and reticulocytes in the AA group model was significantly decreased compared with the group control (P < 0.01). The degree of bone marrow hyperplasia in the sternum and femur is extremely low. After different drug interventions, compared with the group model, the number of peripheral blood cells in the AA mice rebounded significantly in group DNS (P < 0.01). Not only that the apoptosis rate of BM-MCs decreased (P < 0.01), meanwhile, the CD95 molecule expressed on the CD34+ bone marrow cells had a significant decline (P < 0.01), and the expression level of the key proteins of Fas signaling pathway was also significantly decreased (P < 0.01).ConclusionDNS recovered the peripheral pancytopenia and bone marrow failure in AA mice. DNS reduced the key protein of Fas signaling pathway level to inhibit apoptosis of bone marrow cells to treat AA.

THE INFLUENCE OF LOW-DOSE OCCUPATIONAL RADIATION EXPOSURE ON PERIPHERAL BLOOD CELLS IN A COHORT OF CHINESE MEDICAL RADIATION WORKERS

Abstract Objectives The study aims to assess the change of peripheral blood cell numbers following protracted low-dose radiation exposure among medical radiation workers. Methods A cohort of 375 Chinese medical workers were followed for 5 years (2015–19) and recorded the changes in blood cells and cumulative doses. T-test, least significant difference-T test, variance analysis and correlation analysis were utilized in this study. Results Compared with the control group, the white blood cells, hemoglobin counts and the ratio of eosinophils in the study group showed a downward trend. The differences in blood cells between groups were mainly found in the number of red blood cells. In a short cumulative time, such as 1 or 3 years, a correlation between the cumulative dose and the quantity of blood cells was detected, but not at 5 years. Conclusions There is no significant difference in the blood cell counts between different types of work, and the long-term cumulative dose has not been statistically correlated with the number of blood cells. So that the number of peripheral blood cells can no longer be used as a good indicator of radiation damage.

Comprehensive Metabolomics and Network Pharmacology to Explore the Mechanism of 5-Hydroxymethyl Furfural in the Treatment of Blood Deficiency Syndrome.

Radix Rehmanniae (RR, from Radix Rehmanniae (Gaertn.) DC.) is a natural medicine used in traditional Chinese medicine (TCM) since ancient times for the treatment of blood disorders. RR is steamed to get Rehmanniae Radix Praeparata (RP), which has a tonic effect on blood; the content of 5-hydromethylfurfural (5-HMF) increases more than four times after steaming. Studies have shown that 5-HMF has positive pharmacological effects on cardiovascular and hematological disorders. This study aimed to explore and verify the impact of 5-HMF on rats with chemotherapy-induced blood deficiency syndrome (BDS). Rats were given cyclophosphamide (CP) and acetophenhydrazine (APH) to induce BDS, the coefficients of some organs (liver, spleen, and kidney) were measured, and a routine blood test examined the coefficients of several peripheral blood cells. Metabolomics and network pharmacology were combined to find important biomarkers, targets, and pathways. Western blot was used to detect the expression of CYP17A1 and HSD3B1 proteins in the spleen. All these findings suggested that the 5-HMF significantly increased the number of peripheral blood cells and reversed splenomegaly in rats. In addition, 5-HMF upregulated CYP17A1 and HSD3B1 protein expression in splenic tissues. Also, 5-HMF ameliorated chemotherapy-induced BDS in rats, and its therapeutic mechanism might depend on steroid hormone biosynthesis and other pathways. It acts on blood deficiency via multiple targets and pathways, which is unique to Chinese medicine.

Establishment of a Mouse Model of Acquired Aplastic Anemia Mediated by Cyclophosphamide Combined with Cyclosporine

To establish a stable mouse model of acquired aplastic anemia. Female BALB/C mice aged 6 months were intraperitoneally injected with cyclophosphamide and cyclosporine for 14 days. The number of peripheral blood cells, the concentration of hemoglobin, the number of bone marrow nucleated cells, bone marrow smear, bone marrow pathological sections and other indexes were observed. In BALB/C mice injected intraperitoneally with cyclophosphamide and cyclosporine, the number of peripheral blood cells and the concentration of hemoglobin were significantly decreased, especially the white blood cells and platelets. Bone marrow smear showed a significant decrease in the number of nucleated cells and bone marrow hyperplasia. Bone marrow pathology showed decreased hematopoietic cells and increased non-hematopoietic cells such as adipocytes. The mouse model with intraperitoneal injection of cyclophosphamide and cyclosporine can meet the diagnostic criteria of acquired aplastic anemia, which can be used as a mouse model for the study of the pathogenesis and treatment of acquired aplastic anemia.

No association of natural killer cell number and function in peripheral blood with overweight/obesity and metabolic syndrome in a cohort of young women.

AimTo reexamine the associations of NK cell number and function in the peripheral blood with overweight/obesity and the metabolic syndrome in a large, well‐phenotyped human cohort.MethodsCross‐sectional analysis of 273 women in the PPSDiab Study; measurement of absolute and relative number of NK cells in peripheral blood, and of functional parameters CD69 positivity and cytotoxicity against K562 cells; group comparison of NK cell characteristics between lean, overweight, and obese participants, as well as metabolic syndrome scores of 0, 1, 2, and ≥3; Spearman correlation analyses to clinical parameters related to the metabolic syndrome.ResultsWe found no differences in NK cell number and function between lean, overweight, and obese women (relative NK cell number (median (Q1–Q3), [%]) 5.1(2.6–9.4) vs. 4.8 (2.9–8.4) vs. 3.8 (1.7–7.8), p = 0.187; absolute NK cell number [106/L]: 86.9 (44.6–188.8) vs. 92.6 (52.5–154.6) vs. 85.9 (44–153.8), p = 0.632; CD69+ [%]: 27.2 (12.9–44.3) vs. 37.6 (13.2–52.8) vs. 33.6 (16.3–45), p = 0.136; cytotoxicity [%]: 11.0 (7.1–14.5) vs. 8.5 (6.4–13.2) vs. 11.3 (8.7–14.2), p = 0.094), as well as between different metabolic syndrome scores. Nonesterified fatty acids correlated with absolute and relative NK cell number and cytotoxicity (ρ [p‐value]: 0.142 [0.021], 0.119 [0.049], and 0.131 [0.035], respectively). Relative NK cell number further correlated with high‐density lipoprotein cholesterol (0.144 [0.018]) and cytotoxicity with 2 h glucose in oral glucose tolerance testing (0.132 [0.034]). CD69 positivity correlated with body fat (0.141 [0.021]), triglycerides (0.129 [0.033]), and plasma leptin (0.155 [0.010]). After correction for multiple testing, none of the associations remained significant.ConclusionIn the present study, we observed no associations of NK cell number and function in the peripheral blood with overweight/obesity and the metabolic syndrome. Extreme phenotypes of obesity and the metabolic syndrome might have caused differing results in previous studies. Further analyses with a focus on compartments other than peripheral blood may help to clarify the relation between NK cells and metabolic diseases.

RETRACTED: Two new luminescent coordination polymers: Therapeutic effects on angina pectoris

Via tuning the central metal ions from Zn(II) to Cd(II), two new coordination polymers was acquired in success, namely {(H 3 O)[Zn 4 (bptc) 3 (3-bpmh)]} n ·6n(H 2 O) ( 1 ) and [Cd 3 (bptc)(3-bpmh)(H 2 O) 3 ] n ·4n(H 2 O) ( 2 ) (H 3 bptc = biphenyl-3,4′,5-tricarboxylic acid, 3-bpmh = N,N-bis-pyridin-3-ylmethylene-hydrazine), under hydrothermal conditions. The luminescent properties investigations showed that 1 – 2 emit intense luminescence with different maximum emission peaks. Their therapeutic and nursing protective effects on angina pectoris were assessed and we also discussed the corresponding mechanism simultaneously. The content of Interleukin-6 (IL-6) and soluble vascular cell adhesive molecule (SVCAM-1) released by endothelial cells (EC) was discovered through enzyme linked immunosorbent assay (ELISA) detection kit. Besides, the activation of Notch signaling pathway was also evaluated by the real time reverse transcription-polymerase chain reaction (RT-PCR). Influence of compounds on the peripheral blood white blood cell (WBC) numbers was measured with flow cytometry. We utilized optical coherence tomography (OCT) to measure the thickness of the fibrous cap of atherosclerotic plaque in patients with angina pectoris.

Targeting pancreatic cancer by TAK-981: a SUMOylation inhibitor that activates the immune system and blocks cancer cell cycle progression in a preclinical model

ObjectivePancreatic ductal adenocarcinoma (PDAC) has the characteristics of high-density desmoplastic stroma, a distinctive immunosuppressive microenvironment and is profoundly resistant to all forms of chemotherapy and immunotherapy, leading to a 5-year...

Steamed Panax notoginseng attenuates renal anemia in an adenine-induced mouse model of chronic kidney disease

Ethnopharmacological relevancePanax notoginseng (PN) (Burk.) F. H. Chen is a medicinal herb used to treat blood disorders since ancient times, of which the steamed form exhibits the anti-anemia effect and acts with a “blood-tonifying” function according to the traditional use. However, its pharmacological effect and mechanism on alleviating renal anemia (RA) are still unclear. Aims of the studyThe study aims to investigate the effect of steamed Panax notoginseng (SPN) to attenuate RA and its underlying mechanism based on the model of adenine-induced RA mice. Materials and methodsSeventy mice were randomly divided into seven groups of ten: the control group, model group, the erythropoietin (EPO) group, the Fufang E'jiao Jiang (FEJ) group, the high-dose steamed PN (H-SPN) group, the middle-dose steamed PN (M-SPN) group, and the low-dose steamed PN (L-SPN) group. The adenine induction RA model was applied to assess the “blood enriching” function of SPN. The blood routine indexes, erythrocyte fragility, pathologic morphology of kidney tissue and the expression levels of related cytokines and proteins in the mice were detected after 3-week administration with SPN and positive drugs. ResultsOur study provided evidences that SPN could ameliorate RA. Compared with the control group, SPN could attenuate RA by significantly increasing the numbers of peripheral blood cells (p < 0.01), improving the erythrocyte fragility (p < 0.01), and restoring the expression of EPO mRNA in the kidneys and EPO receptor mRNA in bone marrow nucleated cells. The expression of TGF-β1 mRNA was declined and the expression of HGF mRNA was significantly increased in a dose-dependent way after the treatment of SPN. Additionally, the expression of Bcl-2 and Bcl-2/Bax ratio in the kidneys were significantly increased. In contrast, there was a highly significant decrease in the expression of Bax (p < 0.01), following SPN treatment. ConclusionSPN could alleviate RA by promoting the overall hematopoiesis and inhibiting the progress of renal injury in mice.

Preparation of icariside I and icariside II, an exploration of their protective mechanism against cyclophosphamide-induced bone marrow suppression in mice, and their regulatory effects on immune function.

This study aimed to prepare icariside I (ICS I) and icariside II (ICS II) from Epimedium koreanum Nakai, explore their protective mechanism against cyclophosphamide-induced bone marrow suppression in mice and determine their regulatory effects on immune function. The results showed that after treatment with ICS I and ICS II, the number of peripheral blood cells in the mice returned to normal. The number of bone marrow nucleated cells (BMNCs) and haematopoietic progenitor cell (HPC) colonies in the ICS I-H and ICS II-H treatment groups increased significantly. The thymus and spleen indices and related cytokine levels in the mice returned to normal. ICS I-H and ICS II-H treatment significantly increased the ratio of Bcl-2/Bax and downregulated the expression of caspase-3 to regulate cell apoptosis. In conclusion, ICS I and ICS II promoted the proliferation and differentiation of bone marrow haematopoietic cells and protected the damaged immune system, and the therapeutic effects of high doses were more significant. Regulating the levels of haematopoietic cytokines, the balance of Bcl-2/Bax, and the inhibition of caspase-3 expression may be the mechanisms of action of ICS I and ICS II against cyclophosphamide-induced bone marrow suppression in mice.

Screening of Translocation Ets-Leukemia-Acute-Myeloid-Leukemia-1 Fusion Gene and Expression Pattern of Multidrug Resistance Protein Protein in Children with Acute Lymphoblastic Leukemia

The study aimed to investigate the positive rate of TEL-AML 1 fusion gene in acute lymphoblastic leukemia (ALL) children and the clinical characteristics of ALL patients with TEL-AML 1 fusion gene positively expressed, as well as the expression level of MRP-1. 40 ALL children were selected, with their medical records collected. The TEL-AML 1 fusion gene was screened by nested RTPCR. Bone marrow specimens were taken for G-banded karyotype analysis and flow cytometry immunophenotyping of the marrow chromosome. A semi-quantitative RT-PCR method was used to study the mRNA expression level of MRP 1. The results showed that the positive rate of TEL-AML 1 fusion gene in ALL patients was 22.5% (9/40). The positive group exhibited lower gene expression level, the hepatosplenomegaly degree, the total number of peripheral white blood cells, the absolute count of naive cells, and the Hb level at the first visit, indicating that the tumor burden of children in the positive group was lower. The complete remission rate of the positive group was higher (P &lt; 0.05). The mRNA expression level of MRP 1 gene positive group was lower. In conclusion, patients with positive TEL-AML 1 fusion gene were more sensitive to chemotherapeutic drugs, and their treatment responses and prognosis were better.

Novel Effects of Combination Therapy Through Inhibition of Caspase-1/Gasdermin D Induced-Pyroptosis in Lupus Nephritis.

ObjectivesCombination therapy with mycophenolate mofetil, tacrolimus and steroids are effective in achieving complete remission in lupus nephritis (LN). Combination therapy uniquely downregulated caspase-1 compared with monotherapies, which can cleave gasdermin D (GSDMD) and was recently identified as the pyroptosis executioner. We therefore investigated whether combination therapy enabled the suppression of caspase-1/GSDMD-mediated pyroptosis in LN.MethodsExpression and activation of GSDMD were detected in kidney specimens of the human and mouse with LN using immunohistochemical staining and immunoblotting. Primary podocytes isolated from MRL/lpr mice were incubated with LPS+ATP, and pretreated with monotherapy or combination therapy. Inhibition of caspase-1/GSDMD-induced pyroptosis by combination therapy were assessed in MRL/lpr mice and human specimens. Pyroptosis was examined using a FAM caspase-1 kit and flow cytometry. The correlation between pyroptosis in peripheral blood and the systemic lupus erythematosus disease activity index (SLEDAI) was analyzed.ResultsKidney tissue specimens from LN patients and mice exhibited greatly increased expression levels and cleavage of GSDMD. In cultured podocytes, combination treatment significantly suppressed the activation of NLRP3 and caspase-1 and reduced GSDMD N-terminal levels. Combination therapy repressed disease progression through inhibition of caspase-1/GSDMD-mediated pyroptosis in both humans and MRL/lpr mice. Caspase-1/PI positive cell numbers in peripheral blood were positively correlated with SLE-DAI. LN patients with complete remission and partial remission had remarkably reduced caspase-1/PI positive cell numbers compared to baseline. Ac-FLTD-CMK, a GSDMD-derived inhibitor, prevented the development of LN.ConclusionCombination therapy suppressed caspase-1/GSDMD-mediated pyroptosis in vitro and in vivo and reduced disease progression.