OBJECTIVE: To explore the effects of hydroxychloroquine (HCQ) on immune mediators dysregulation in severe infection after chemotherapy in acute myeloid leukemia (AML) and its molecular mechanism. METHODS: Bone marrow or peripheral blood samples of 36 AML patients with severe infection (AML-SI) and 29 AML patients without infection (AML-NI) after chemotherapy were collected from the First Affiliated Hospital of Gannan Medical University from August 2022 to June 2023. In addition, the peripheral blood of 21 healthy subjects from the same period in our hospital was selected as the control group. The mRNA expressions of CXCL12, CXCR4 and CXCR7 were detected by RT-qPCR technology, and the levels of IL-6, IL-8 and TNF-α were detected by ELISA. Leukemia-derived THP-1 cells were selected and constructed as AML disease model. At the same time, bone marrow mesenchymal stem cells (BM-MSCs) from AML-SI patients were co-cultured with THP-1 cells and divided into Mono group and Co-culture group. THP-1 cells were treated with different concentration gradients of HCQ. The cell proliferation activity was subsequently detected by CCK-8 method and apoptosis was detected by Annexin V/PI double staining flow cytometry. ELISA was used to detect the changes of IL-6, IL-8 and TNF-α levels in the supernatant of the cell co-culture system, RT-qPCR was used to detect the mRNA expression changes of the core members of the CXCL12-CXCR4/7 regulatory axis, and Western blot was used to detect the expressions of apoptosis regulatory molecules and related signaling pathway proteins. RESULTS: CXCL12, CXCR4, CXCR7, as well as IL-6, IL-8, and TNF-α were all abnormally increased in AML patients, and the increases were more significant in AML-SI patients (P <0.01). Furthermore, there were statistically significant differences between AML-NI patients and AML-SI patients (all P <0.05). HCQ could inhibit the proliferation and induce the apoptosis of THP-1 cells, but the low concentration of HCQ had no significant effect on the killing of THP-1 cells. When THP-1 cells were co-cultured with BM-MSCs of AML patients, the levels of IL-6, IL-8 and TNF-α in the supernatance of Co-culture group were significantly higher than those of Mono group (all P <0.01). After HCQ intervention, the levels of IL-6, IL-8 and TNF-α in cell culture supernatant of Mono group were significantly decreased compared with those before intervention (all P <0.01). Similarly, those of Co-culture group were also significantly decreased (all P <0.001). However, the expression of the core members of the CXCL12-CXCR4/7 regulatory axis was weakly affected by HCQ. HCQ could up-regulate the expression of pro-apoptotic protein Bax, down-regulate the expression of anti-apoptotic protein Bcl-2, as well as simultaneously promote the hydrolytic activation of Caspase-3 when inhibiting the activation level of TLR4/NF-κB pathway, then induce the programmed death of THP-1 cells after intervention. CONCLUSION The core members of CXCL12-CXCR4/7 axis and related cytokines may be important mediators of severe infectious immune disorders in AML patients. HCQ can inhibit cytokine levels to reverse immune mediators dysregulation and suppress malignant biological characteristics of leukemia cells. The mechanisms may be related to regulating the expression of Bcl-2 family proteins, hydrolytically activating Caspase-3 and inhibiting the activation of TLR4/NF-κB signaling pathway.
Humans ; Leukemia, Myeloid, Acute/immunology* ; Hydroxychloroquine/pharmacology* ; Receptors, CXCR4/metabolism* ; Apoptosis/drug effects* ; Tumor Necrosis Factor-alpha/metabolism* ; Chemokine CXCL12/metabolism* ; Interleukin-8/metabolism* ; Interleukin-6/metabolism* ; Receptors, CXCR/metabolism* ; Mesenchymal Stem Cells ; THP-1 Cells

OBJECTIVE: To illustrate the role of dehydrocorydaline (DHC) in chronic constriction injury (CCI)-induced neuropathic pain and the underlying mechanism. METHODS: C57BL/6J mice were randomly divided into 3 groups by using a random number table, including sham group (sham operation), CCI group [intrathecal injection of 10% dimethyl sulfoxide (DMSO)], and CCI+DHC group (intrathecal injection of DHC), 8 mice in each group. A CCI mouse model was conducted to induce neuropathic pain through ligating the right common sciatic nerve. On day 14 after CCI modeling or sham operation, mice were intrathecal injected with 5 µL of 10% DMSO or 10 mg/kg DHC (5 µL) into the 5th to 6th lumbar intervertebral space (L5-L6). Pregnant ICR mice were sacrificed for isolating primary spinal neurons on day 14 of embryo development for in vitro experiment. Pain behaviors were evaluated by measuring the paw withdrawal mechanical threshold (PWMT) of mice. Immunofluorescence was used to observe the activation of astrocytes and microglia in mouse spinal cord. Protein expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), phosphorylation of N-methyl-D-aspartate receptor subunit 2B (p-NR2B), and NR2B in the spinal cord or primary spinal neurons were detected by Western blot. RESULTS: In CCI-induced neuropathic pain model, mice presented significantly decreased PWMT, activation of glial cells, overexpressions of iNOS, TNF-α, IL-6, and higher p-NR2B/NR2B ratio in the spinal cord (P<0.05 or P<0.01), which were all reversed by a single intrathecal injection of DHC (P<0.05 or P<0.01). The p-NR2B/NR2B ratio in primary spinal neurons were also inhibited after DHC treatment (P<0.05). CONCLUSION An intrathecal injection of DHC relieved CCI-induced neuropathic pain in mice by inhibiting the neuroinflammation and neuron hyperactivity.
Animals ; Neuralgia/etiology* ; Mice, Inbred C57BL ; Analgesics/pharmacology* ; Neuroinflammatory Diseases/pathology* ; Constriction ; Male ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Nitric Oxide Synthase Type II/metabolism* ; Mice, Inbred ICR ; Microglia/pathology* ; Spinal Cord/drug effects* ; Female ; Mice ; Tumor Necrosis Factor-alpha/metabolism* ; Disease Models, Animal ; Constriction, Pathologic/complications* ; Interleukin-6/metabolism* ; Astrocytes/metabolism* ; Chronic Disease ; Neurons/metabolism*

OBJECTIVE: To investigate the effect of pachymic acid (PA) against TNBS-induced Crohn's disease (CD)-like colitis in mice and explore the possible mechanism. METHODS: Twenty-four C57BL/6J mice were randomized equally into control group, TNBS-induced colitis model group and PA treatment group. PA treatment was administered via intraperitoneal injection at the daily dose of 5 mg/kg for 7 days, and the mice in the control and model groups were treated with saline. After the treatments, the mice were euthanized for examination of the disease activity index (DAI) of colitis, body weight changes, colon length, intestinal inflammation, intestinal barrier function and apoptosis of intestinal epithelial cells, and the expressions of TNF-α, IL-6 and IL-1β in the colonic mucosa were detected using ELISA. The possible treatment targets of PA in CD were predicted by network pharmacology. String platform and Cytoscape 3.7.2 software were used to construct the protein-protein interaction (PPI) network. David database was used to analyze the GO function and KEGG pathway; The phosphorylation of PI3K/AKT in the colonic mucosal was detected with Western blotting. RESULTS: PA significantly alleviated colitis in TNBS-treated mice as shown by improvements in the DAI, body weight loss, colon length, and histological inflammation score and lowered levels of TNF-α, IL-6 and IL-1β. PA treatment also significantly improved FITC-dextran permeability, serum I-FABP level and colonic transepithelial electrical resistance, and inhibited apoptosis of the intestinal epithelial cells in TNBS-treated mice. A total of 248 intersection targets were identified between PA and CD, and the core targets included EGFR, HRAS, SRC, MMP9, STAT3, AKT1, CASP3, ALB, HSP90AA1 and HIF1A. GO and KEGG analysis showed that PA negatively regulated apoptosis in close relation with PI3K/AKT signaling. Molecular docking showed that PA had a strong binding ability with AKT1, ALB, EGFR, HSP90AA1, SRC and STAT3. In TNBS-treated mice, PA significantly decreased p-PI3K and p-AKT expressions in the colonic mucosa. CONCLUSION PA ameliorates TNBS-induced intestinal barrier injury in mice by antagonizing apoptosis of intestinal epithelial cells possibly by inhibiting PI3K/AKT signaling.
Animals ; Mice ; Mice, Inbred C57BL ; Crohn Disease ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Interleukin-6 ; Molecular Docking Simulation ; Tumor Necrosis Factor-alpha ; Colitis/chemically induced* ; Inflammation ; Apoptosis ; ErbB Receptors

The goal of this study was to investigate the regulatory effect of angiotensin converting enzyme 2 (ACE2) on cellular inflammation caused by avian infectious bronchitis virus (IBV) and the underlying mechanism of such effect. Vero and DF-1 cells were used as test target to be exposed to recombinant IBV virus (IBV-3ab-Luc). Four different groups were tested: the control group, the infection group[IBV-3ab-Luc, MOI (multiplicity of infection)=1], the ACE2 overexpression group[IBV-3ab Luc+pcDNA3.1(+)-ACE2], and the ACE2-depleted group (IBV-3ab-Luc+siRNA-ACE2). After the cells in the infection group started to show cytopathic indicators, the overall protein and RNA in cell of each group were extracted. real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine the mRNA expression level of the IBV nucleoprotein (IBV-N), glycoprotein 130 (gp130) and cellular interleukin-6 (IL-6). Enzyme linked immunosorbent assay (ELISA) was used to determine the level of IL-6 in cell supernatant. Western blotting was performed to determine the level of ACE2 phosphorylation of janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3). We found that ACE2 was successfully overexpressed and depleted in both Vero and DF-1 cells. Secondly, cytopathic indicators were observed in infected Vero cells including rounding, detaching, clumping, and formation of syncytia. These indicators were alleviated in ACE2 overexpression group but exacerbated when ACE2 was depleted. Thirdly, in the infection group, capering with the control group, the expression level of IBV-N, gp130, IL-6 mRNA and increased significantly (P < 0.05), the IL-6 level was significant or extremely significant elevated in cell supernatant (P < 0.05 or P < 0.01); the expression of ACE2 decreased significantly (P < 0.05); protein phosphorylation level of JAK2 and STAT3 increased significantly (P < 0.05). Fourthly, comparing with the infected group, the level of IBV-N mRNA expression in the ACE2 overexpression group had no notable change (P > 0.05), but the expression of gp130 mRNA, IL-6 level and expression of mRNA were elevated (P < 0.05) and the protein phosphorylation level of JAK2 and STAT3 decreased significantly (P < 0.05). In the ACE2-depleted group, there was no notable change in IBV-N (P > 0.05), but the IL-6 level and expression of mRNA increased significantly (P < 0.05) and the phosphorylation level of JAK2 and STAT3 protein decreased slightly (P > 0.05). The results demonstrated for the first time that ACE2 did not affect the replication of IBV in DF-1 cell, but it did contribute to the prevention of the activation of the IL-6/JAK2/STAT3 signaling pathway, resulting in an alleviation of IBV-induced cellular inflammation in Vero and DF-1 cells.
Animals ; Chlorocebus aethiops ; Humans ; Interleukin-6/genetics* ; Janus Kinase 2/pharmacology* ; Infectious bronchitis virus/metabolism* ; STAT3 Transcription Factor/metabolism* ; Angiotensin-Converting Enzyme 2/pharmacology* ; Cytokine Receptor gp130/metabolism* ; Vero Cells ; Signal Transduction ; Inflammation ; RNA, Messenger

To explore the application of IL-6, PCT, T lymphocyte subsets and TIGIT expression on T lymphocytes in the evaluation of Crohn's disease status. Using a cross-sectional study, total of 119 confirmed patients with Crohn's disease who were treated in the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine from June 2020 to December 2022 were selected. The age range was 18-59 years old, and the median age (interquartile range) was 37 (29, 45) years old, including 57 cases in active disease group (30 males, 27 females), 62 cases in disease remission group (33 males, 29 females); 50 healthy control groups (27 males, 23 females), the age range was 19-60 years old, and the median age (interquartile range) was 38 (31, 46) years old. The level of IL-6 was detected by flow fluorescence microsphere method, the concentration of PCT was detected by immunochromatography, and the levels of T lymphocyte subsets and TIGIT were detected by flow cytometry. The differences and correlations between the detection indicators in each group were compared, logistic regression was used to analyze the factors influencing the progression of Crosne's disease and the clinical value of each detection indicator was analyzed by ROC curve. The results showed that there were no statistically significant differences in age and gender among the control group, the remission group, and the active group (H=1.422,χ²=0.020;P=0.491, P=0.990); in the active group, IL-6 was 17.55(9.67, 21.72)pg/ml, PCT was 0.38(0.14, 0.43)ng/ml, CD3⁺CD4⁺ was 35.47%±6.01%, CD3⁺CD8⁺ was 30.50%±5.20%, TIGIT was 25.08%±6.30%; in the remission group, IL-6 was 8.46(5.21, 10.04) pg/ml, PCT was 0.26(0.11, 0.35) ng/ml, CD3⁺CD4⁺ was 37.62%±4.86%, CD3⁺CD8⁺ was 28.30%±5.28%, TIGIT was 34.22%±5.45%; in the control group, IL-6 was 6.13(3.57, 8.12)pg/ml, PCT was 0.17(0.10, 0.21)ng/m, CD3⁺CD4⁺ was 39.74%±3.94%, CD3⁺CD8⁺ was 26.59%±4.50%, and TIGIT was 37.64%±6.22%.There were significant differences in IL-6, PCT, CD3⁺CD4⁺%, CD3⁺CD8⁺%, and TIGIT among the three groups(H=58.688, H=18.003, F=9.600, F=8.124, F=65.059;P<0.001, P<0.001, P<0.001, P<0.001, P<0.001), Among them, IL-6 and TIGIT in the active group were significantly different from those in the remission group (P<0.001, P<0.001), and only TIGIT was significantly different between the remission group and the control group (P=0.007);Spearman correlation analysis showed that the expression of TIGIT on T lymphocytes was negatively correlated with the levels of IL-6; the results of Logistic regression analysis showed that IL-6, PCT and TIGIT were independent factors affecting the progression of Crohn's disease;Comparing the ROC curves of the active group and the remission group, found that TIGIT was significantly different from PCT, CD3⁺CD4⁺, CD3⁺CD8⁺(Z=4.011, Z=4.091, Z=4.157; P<0.001, P<0.001, P<0.001), no statistical difference with IL-6 (Z=1.193, P=0.233). Selected the combined detection of IL-6 and TIGIT with the best AUC area and Youden index, which shows that the clinical value is improved, the AUC area of IL-6+TIGIT was significantly different from that of IL-6 (Z=2.674, P=0.008). In summary, TIGIT of T lymphocytes and IL-6 detection may be valuable in the diagnosis and treatment of Crohn's disease, and the combined detection of TIGIT and IL-6 may be meaningful for evaluating the status of Crohn's disease.
Male ; Female ; Humans ; Adult ; Adolescent ; Young Adult ; Middle Aged ; Interleukin-6 ; Crohn Disease/diagnosis* ; Cross-Sectional Studies ; T-Lymphocyte Subsets ; Receptors, Immunologic

To explore the application of IL-6, PCT, T lymphocyte subsets and TIGIT expression on T lymphocytes in the evaluation of Crohn's disease status. Using a cross-sectional study, total of 119 confirmed patients with Crohn's disease who were treated in the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine from June 2020 to December 2022 were selected. The age range was 18-59 years old, and the median age (interquartile range) was 37 (29, 45) years old, including 57 cases in active disease group (30 males, 27 females), 62 cases in disease remission group (33 males, 29 females); 50 healthy control groups (27 males, 23 females), the age range was 19-60 years old, and the median age (interquartile range) was 38 (31, 46) years old. The level of IL-6 was detected by flow fluorescence microsphere method, the concentration of PCT was detected by immunochromatography, and the levels of T lymphocyte subsets and TIGIT were detected by flow cytometry. The differences and correlations between the detection indicators in each group were compared, logistic regression was used to analyze the factors influencing the progression of Crosne's disease and the clinical value of each detection indicator was analyzed by ROC curve. The results showed that there were no statistically significant differences in age and gender among the control group, the remission group, and the active group (H=1.422,χ²=0.020;P=0.491, P=0.990); in the active group, IL-6 was 17.55(9.67, 21.72)pg/ml, PCT was 0.38(0.14, 0.43)ng/ml, CD3⁺CD4⁺ was 35.47%±6.01%, CD3⁺CD8⁺ was 30.50%±5.20%, TIGIT was 25.08%±6.30%; in the remission group, IL-6 was 8.46(5.21, 10.04) pg/ml, PCT was 0.26(0.11, 0.35) ng/ml, CD3⁺CD4⁺ was 37.62%±4.86%, CD3⁺CD8⁺ was 28.30%±5.28%, TIGIT was 34.22%±5.45%; in the control group, IL-6 was 6.13(3.57, 8.12)pg/ml, PCT was 0.17(0.10, 0.21)ng/m, CD3⁺CD4⁺ was 39.74%±3.94%, CD3⁺CD8⁺ was 26.59%±4.50%, and TIGIT was 37.64%±6.22%.There were significant differences in IL-6, PCT, CD3⁺CD4⁺%, CD3⁺CD8⁺%, and TIGIT among the three groups(H=58.688, H=18.003, F=9.600, F=8.124, F=65.059;P<0.001, P<0.001, P<0.001, P<0.001, P<0.001), Among them, IL-6 and TIGIT in the active group were significantly different from those in the remission group (P<0.001, P<0.001), and only TIGIT was significantly different between the remission group and the control group (P=0.007);Spearman correlation analysis showed that the expression of TIGIT on T lymphocytes was negatively correlated with the levels of IL-6; the results of Logistic regression analysis showed that IL-6, PCT and TIGIT were independent factors affecting the progression of Crohn's disease;Comparing the ROC curves of the active group and the remission group, found that TIGIT was significantly different from PCT, CD3⁺CD4⁺, CD3⁺CD8⁺(Z=4.011, Z=4.091, Z=4.157; P<0.001, P<0.001, P<0.001), no statistical difference with IL-6 (Z=1.193, P=0.233). Selected the combined detection of IL-6 and TIGIT with the best AUC area and Youden index, which shows that the clinical value is improved, the AUC area of IL-6+TIGIT was significantly different from that of IL-6 (Z=2.674, P=0.008). In summary, TIGIT of T lymphocytes and IL-6 detection may be valuable in the diagnosis and treatment of Crohn's disease, and the combined detection of TIGIT and IL-6 may be meaningful for evaluating the status of Crohn's disease.
Male ; Female ; Humans ; Adult ; Adolescent ; Young Adult ; Middle Aged ; Interleukin-6 ; Crohn Disease/diagnosis* ; Cross-Sectional Studies ; T-Lymphocyte Subsets ; Receptors, Immunologic

This project was aimed to investigate the role and the underlying mechanism of microglia polarization on blood-brain barrier (BBB) during cerebral ischemia-reperfusion. After construction of the mouse model of cerebral ischemia-reperfusion, upregulated IL-6 and TNF-α in peripheral blood and increased IL-6 and iNOS in ischemia tissues were confirmed. The supernatant expression of TNF-α and IL-6, as well as IL-6, iNOS and CD86 mRNA, was significantly increased in the of Bv-2 cells after oxygen-glucose deprivation/reoxygenation (OGD/R) model was constructed in vitro. For further understanding the expression pattern of RNAs, the next-generation RNA sequencing was performed and upregulation of Robo4 (roundabout guidance receptor 4) was found both in M1-polarized and OGD/R treated Bv-2 cells, which was also confirmed by RT-qPCR. Extracellular soluble Robo4 (sRobo4) protein also increased in the supernatant of M1-polarized and OGD/R treated Bv-2 cells. Treating bEND3 cells with the Robo4 recombinant protein, M1-polarized Bv-2 cell supernatant or OGD/R Bv-2 cell supernatant decreased trans-endothelial electrical resistance (TEER), suggesting the injury of BBB. In addition, Robo4 was also highly expressed in the serum of patients who experienced acute ischemia stroke and mechanical thrombectomy operation. All the results suggest that increased secretion of Robo4 by M1-polarized-microglia during cerebral ischemia-reperfusion is most likely one of the causes of BBB injury, and Robo4 may be one of the therapeutic targets for BBB functional protection.
Animals ; Blood-Brain Barrier/metabolism* ; Brain Ischemia/drug therapy* ; Glucose/metabolism* ; Interleukin-6/metabolism* ; Mice ; Microglia/metabolism* ; Oxygen/metabolism* ; Receptors, Cell Surface/metabolism* ; Reperfusion ; Reperfusion Injury/drug therapy* ; Tumor Necrosis Factor-alpha/metabolism*

This study aims to investigate mechanism of "Ephedrae Herba-Descurainiae Semen Lepidii Semen" combination(MT) in the treatment of bronchial asthma based on network pharmacology and in vivo experiment, which is expected to lay a theoretical basis for clinical application of the combination. First, the potential targets of MT in the treatment of bronchial asthma were predicted based on network pharmacology, and the "Chinese medicine-active component-target-pathway-disease" network was constructed, followed by Gene Oncology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the potential targets. Molecular docking was used to determine the binding activity of key candidate active components to hub genes. Ovalbumin(OVA, intraperitoneal injection for sensitization and nebulization for excitation) was used to induce bronchial asthma in rats. Rats were classified into control group(CON), model group(M), dexamethasone group(DEX, 0.075 mg·kg~(-1)), and MT(1∶1.5) group. Hematoxylin and eosin(HE), Masson, and periodic acid-Schiff(PAS) staining were performed to observe the effect of MT on pathological changes of lungs and trachea and goblet cell proliferation in asthma rats. The levels of transforming growth factor(TGF)-β1, interleukin(IL)6, and IL10 in rat serum were detected by enzyme-linked immunosorbent assay(ELISA), and the mRNA and protein levels of mitogen-activated protein kinase 8(MAPK8), cyclin D1(CCND1), IL6, epidermal growth factor receptor(EGFR), phosphatidylinositol 3-kinase(PI3 K), and protein kinase B(Akt) by qRT-PCR and Western blot. Network pharmacology predicted that MAPK8, CCND1, IL6, and EGFR were the potential targets of MT in the treatment of asthma, which may be related to PI3 K/Akt signaling pathway. Quercetin and β-sitosterol in MT acted on a lot of targets related to asthma, and molecular docking results showed that quercetin and β-sitosterol had strong binding activity to MAPK, PI3 K, and Akt. In vivo experiment showed that MT could effectively alleviate the symptoms of OVA-induced asthma rats, improve the pathological changes of lung tissue, reduce the production of goblet cells, inhibit the inflammatory response of asthma rats, suppress the expression of MAPK8, CCND1, IL6, and EGFR, and regulate the PI3 K/Akt signaling pathway. Therefore, MT may relieve the symptoms and inhibit inflammation of asthma rats by regulating the PI3 K/Akt signaling pathway, and quercetin and β-sitosterol are the candidate active components.
Animals ; Asthma/drug therapy* ; Cyclin D1 ; Dexamethasone/adverse effects* ; Drug Combinations ; Drugs, Chinese Herbal/therapeutic use* ; Eosine Yellowish-(YS)/adverse effects* ; Ephedra ; ErbB Receptors ; Hematoxylin/therapeutic use* ; Interleukin-10 ; Interleukin-6 ; Mitogen-Activated Protein Kinase 8/therapeutic use* ; Molecular Docking Simulation ; Network Pharmacology ; Ovalbumin/adverse effects* ; Periodic Acid/adverse effects* ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt/metabolism* ; Quercetin ; RNA, Messenger ; Rats

OBJECTIVE: To observe the therapeutic effect of acupuncture on cancer-related fatigue (CRF) and to explore its possible mechanism. METHODS: A total of 80 patients with CRF were randomized into an observation group and a control group, and finally 67 patients completed the trial (36 patients in the observation group, 31 patients in the control group). Patients in the control group were treated with conventional chemoradiotherapy and symptomatic treatment, while no particular anti-fatigue intervention was adopted. On the basis of treatment in the control group, acupuncture was applied at Baihui (GV 20), Guanyuan (CV 4), Qihai (CV 6), Fengchi (GB 20), Zusanli (ST 36), Sanyinjiao (SP 6) in the observation group, once a day, 5 times as one course, with 2 days interval between each course, totally 4 courses were required. Before and after treatment, scores of functional assessment of cancer therapy-fatigue (FACT-F) in Chinese and McGill quality of life questionnaire (MQOL), serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α) and soluble TNF receptor-1 (sTNF-R1) were observed in the two groups. RESULTS: ①Compared before treatment, the FACT-F score was decreased after treatment in the observation group (<0.05), while there was no significant difference in the control group (<0.05). The change of the FACT-F score in the observation group was larger than that in the control group (<0.05). ②In the observation group, scores of physiological and psychological dimension were decreased (<0.05), score of social support dimension was increased after the treatment (<0.05). The score changes of physiological, psychological and social support dimension in the observation group were larger than those in the control group (all <0.05). ③After treatment, the serum levels of IL-6, TNF-α and sTNF-R1 were decreased in the observation group (<0.05), while the serum levels of CPR and IL-6 were increased in the control group (<0.05). The serum levels of CPR, IL-6 and TNF-α in the observation were lower than those in the control group (<0.05). CONCLUSION ①Acupuncture can improve the related symptoms of depression, weakness and headache in patients with CRF, strengthen their cognition of the support from society and family, and boost the confidence in curing the disease. ②Acupuncture can effectively down-regulate serum levels of the relative inflammatory factors, which may be its possible mechanism on treating CRF.
Acupuncture Points ; Acupuncture Therapy ; Biomarkers ; blood ; C-Reactive Protein ; analysis ; Fatigue ; etiology ; therapy ; Humans ; Interleukin-6 ; blood ; Neoplasms ; complications ; therapy ; Quality of Life ; Receptors, Tumor Necrosis Factor, Type I ; blood ; Tumor Necrosis Factor-alpha ; blood

BACKGROUND AND OBJECTIVES: We sought to investigate an anti-atherosclerotic and anti-inflammatory effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in normoglycemic atherosclerotic rabbit model.METHODS: Male New Zealand white rabbits (n=26) were fed with a 1% high-cholesterol diet for 7 weeks followed by normal diet for 2 weeks. After balloon catheter injury, the rabbits were administered with the Dapagliflozin (1mg/kg/day) or control-medium for 8 weeks (n=13 for each group). All lesions were assessed with angiography, optical coherence tomography (OCT), and histological assessment.RESULTS: Atheroma burden (38.51±3.16% vs. 21.91±1.22%, p<0.01) and lipid accumulation (18.90±3.63% vs. 10.20±2.03%, p=0.047) was significantly decreased by SGLT-2 inhibitor treatment. The SGLT-2 inhibitor group showed lower macrophage infiltration (20.23±1.89% vs. 12.72±1.95%, p=0.01) as well as tumor necrosis factor (TNF)-α expression (31.17±4.40% vs. 19.47±2.10%, p=0.025). Relative area of inducible nitric oxide synthase+ macrophages was tended to be lower in the SGLT-2 inhibitor-treated group (1.00±0.16% vs. 0.71±0.10%, p=0.13), while relative proportion of Arg1⁺ macrophage was markedly increased (1.00±0.27% vs. 2.43±0.64%, p=0.04). As a result, progression of atherosclerosis was markedly attenuated in SGLT-2 inhibitor treated group (OCT area stenosis, 32.13±1.20% vs. 22.77±0.88%, p<0.01). Mechanistically, SGLT-2 treatment mitigated the inflammatory responses in macrophage. Especially, Toll-like receptor 4/nuclear factor-kappa B signaling pathway, and their downstream effectors such as interleukin-6 and TNF-α were markedly suppressed by SGLT-2 inhibitor treatment.CONCLUSIONS: These results together suggest that SGLT-2 inhibitor exerts an anti-atherosclerotic effect through favorable modulation of inflammatory response as well as macrophage characteristics in non-diabetic situation.
Angiography ; Atherosclerosis ; Catheters ; Constriction, Pathologic ; Diet ; Humans ; Interleukin-6 ; Macrophages ; Male ; Nitric Oxide ; Plaque, Atherosclerotic ; Rabbits ; Toll-Like Receptors ; Tomography, Optical Coherence ; Tumor Necrosis Factor-alpha