OBJECTIVE: To observe the effects of probiotics supplementation on the natural killer T cell (NKT cell) and inflammatory factors in children with sepsis and its protective effect on long-term lung function. METHODS: A total of 100 children with sepsis admitted to the department of pediatric intensive care unit (PICU) of Henan Provincial People's Hospital from March 2021 to May 2022 were selected as the research objects. The children were randomly divided into placebo group and probiotic group, 50 cases in each group. In addition to the conventional treatment, the probiotic group was given oral or nasal administration of 0.5 g probiotics, three times a day for 30 days, and the placebo group received oral placebo. 40 healthy children were selected as the healthy control group. The levels of interleukins (IL-4, IL-10), interferon-γ (IFN-γ) and immunoglobulin E (IgE), percentages of NKT cell in blood and induced sputum, lung function of the two groups of children with sepsis were measured before treatment, 7 days after treatment, and during follow-up. All these data were compared with those of healthy children. Kaplan-Meier analysis was used to compare the incidence of cough varied cough (CVA) between the two septic groups. Multiple linear regression analysis was used to explore the influence of various factors on the proportion of NKT cells in induced sputum. RESULTS: In the placebo group, 2 cases died and 4 cases were lost to follow-up. In the probiotics group, 3 cases died and 5 cases were lost to follow-up. All the inflammatory factors of two groups decreased slowly after 7 day after treatment. There was no significance in the parameters of the two groups, but the levels of probiotic group declined more evidently. During the follow-up, a further decrease of inflammatory factors in probiotic group could be found, the levels of IL-4 and IL-10 were significantly different from those in the placebo group [IL-4 (ng/L): 20.3±9.3 vs. 27.6±11.9, IL-10 (ng/L): 23.1±6.8 vs. 14.4±4.4, both P < 0.05], with a significant decrease in IgE level (μg/L: 53.0±15.6 vs. 64.2±16.9, P < 0.05]. The results of flow cytometry showed that the percentage of NKT cell in peripheral blood in two septic groups decreased gradually, and the proportion of peripheral blood NKT cells in the probiotics group was significantly lower than that in the placebo group after 7 days of treatment [(4.2±0.9)% vs. (5.3±1.2)%, P < 0.05]. In the follow-up, the level of NKT cell in peripheral blood and induced sputum in probiotic group were lower than the placebo group [peripheral blood: (0.024±0.009)% vs. (0.029±0.008)%, induced sputum: (0.025±0.008)% vs. (0.035±0.01)%, both P < 0.05], which were similar to those in the healthy control group. Meanwhile, the percentage of predicted peak expiratory (PEF%) and ratio of forced expiratory volume in one second/forced vital capacity (FEV1/FVC) of probiotic group were higher than those in the placebo group [PEF%: (91.3±4.8)% vs. (85.8±8.6)%, FEV1/FVC ratio: (91.8±4.7)% vs. (87.2±7.4)%, both P < 0.05]. Although there was no significance in the incidence of CVA between two septic groups according to the Kaplan-Meier curve analysis, multiple linear regression analysis showed mechanical ventilation and allergic history were the risk factors for the increase of NKT cells [β values were 0.584, 0.601, 95% confidence interval (95%CI) were 0.069 to 1.099, 0.011 to 1.192, P = 0.027, 0.046], and probiotics was an independent protective factor for the relieve of increase in NKT cells (β value was -0.984,95%CI was -1.378 to -0.591, P = 0.001). CONCLUSIONS Application of probiotics to septic children early could promote the recovery of NKT cell and inflammatory factors, and alleviate the lung function injury induced by them during follow-up, which is helpful to improve the long-term prognosis of the patients.
Child ; Humans ; Interleukin-10 ; Interleukin-4 ; Sepsis ; Probiotics/therapeutic use* ; Lung ; Cough ; Immunoglobulin E

OBJECTIVETo observe the intervention effect of acupuncture on early onset of selec- tive serotonin reuptake inhibitors (SSRIs) in treating depressive disorder, and to study its effect on ser- um 5-HT and unbalanced inflammatory cytokines secreted by TH1/TH2.

METHODSTotally 90 patients with depressive disorder were randomly assigned to the drug control group (as the control group, 45 cases) and the acupuncture combined drug treatment group (as the treatment group, 45 cases). All patients were treated for 4 consecutive weeks. Another 45 healthy subjects were recruited as a healthy control group. The effect of acupuncture on early onset of SSRls in treating acute phase depressive disorder pa- tients was evaluated by HAMD score in the control group and the treatment group before treatment,and at weekends of the 1st, 2nd, and 4th week after treatment. Besides, their serum levels of 5-HT, IL-1β and IL-6 (secreted by TH1), and IL-4 and IL-10 (secreted by TH2) were detected before treatment and after treatment at the weekend of the 4th week.

RESULTSCompared with the healthy control group,serum lev- els of 5-HT, IL-4, and IL-10 decreased in the two drug-treated groups before treatment (P < 0.01); serum levels of IL-1β and IL-6 increased (P <0.01). Compared with before treatment in the same group, HAMD score decreased in the control group at weekends of the 2nd and the 4th week after treatment (P < 0.01); HAMD scores decreased in the treatment group at weekends of the 1st, 2nd, 3rd,and 4th week after treatment (P < 0.01); serum levels of 5-HT, IL-4, and IL-10 increased,serum levels of IL-1β and IL- 6 decreased in the two drug-treated groups after treatment (all P < 0.01). Compared with the control group at the same time point,HAMD scores decreased in the treatment group at weekends of the 1st, 2nd,3rd,and 4th week after treatment (P < 0.01),serum levels of 5-HT, IL-4, and IL-10 increased (P < 0.05, P < 0.01), serum levels of IL-6 decreased (P < 0. 01).

CONCLUSIONAcupuncture could accelerate early onset of SSRIs in treating acute phase depressive disorder, and effectively regulate serum 5-HT levels and inflammatory cytokines secreted by TH1/TH2.

Acupuncture Therapy ; Cytokines ; Depressive Disorder ; drug therapy ; Drugs, Chinese Herbal ; Humans ; Interleukin-10 ; Interleukin-1beta ; Interleukin-4 ; Interleukin-6 ; Serotonin Uptake Inhibitors ; therapeutic use

OBJECTIVETo investigate whether oxymatrine (OM) could promote mesenchymal stem cell (MSC) therapy in CCl4-induced hepatic fibrosis (HF) in rats and to initially explore its mechanisms.

METHODSTotally 50 male SD rats were randomly divided into five groups,i.e., the normal control group, the model group, the MSC therapy group, the OM therapy group, and the MSC combined OM therapy group, 10 in each group. Except the normal control group, the HF model was duplicated by CCl4 induction. After successful modeling, rats in the MSC therapy group received 5 x10(6) MSCs by intravenous injection via caudal vein, once a week. Rats in the OM therapy group received 50 mg/kg OM by intramuscular injection, three times a week. Rats in MSC combined OM therapy group received 5 x 10(6) MSCs by intravenous injection via caudal vein, once a week and 50 mg/kg OM by intramuscular injection three times a week. Equal volume of normal saline was given to those in the normal control group and the model group. All medication lasted for 8 weeks. Serum levels of ALT and AST were detected 8 weeks later. The hepatic histopathological injury and extracellular matrix deposit were assessed using HE and Masson staining. Expressions of serum interleukin-4 (IL-4) and interleukin-10 (IL-10) were detected using enzyme linked immunosorbent assay (ELISA).

RESULTS(1) Compared with the normal control group, serum levels of ALT and AST significantly increased in the model group (P < 0.05). Compared with the model group, serum levels of ALT and AST significantly decreased in the OM therapy group, the MSC therapy group, and the MSC combined OM therapy group at the end of 8 weeks of treatment (P < 0.05). But serum levels of ALT and AST were significantly lower in the MSC combined OM therapy group than in the OM therapy group and the MSC therapy group (P < 0.05). (2) Compared with the model group, the hepatic injury was significantly lessened and the area of extracellular matrix deposit was significantly reduced in the OM therapy group, the MSC therapy group, and the MSC combined OM therapy group (P < 0.05). Besides, they wer more significant in the MSC combined OM therapy group (P < 0.05). (3) Compared with the model group, the serum IL-4 level was significantly higher in the MSC therapy group and the MSC combined MO group (P < 0.05). It was higher in the MSC combined MO group (P < 0.05). Although the serum IL-4 level also increased in the OM therapy group, but with no statistical difference (P > 0.05). (4) The serum IL-10 level significantly increased in the OM therapy group, the MSC therapy group, and the MSC combined OM therapy group (P < 0.05), and it was the highest in the MSC combined OM therapy group among the three groups (P < 0.05). (5) Two-photon fluorescence imaging showed no signals of MSCs in liver with or without OM injection.

CONCLUSIONOM could promote mesenchymal stem cell therapy in hepatic fibrosis rats, which might be involved in increasing serum levels of IL-4 and IL-10.

Alkaloids ; therapeutic use ; Animals ; Interleukin-10 ; blood ; Interleukin-4 ; blood ; Liver Cirrhosis, Experimental ; therapy ; Male ; Mesenchymal Stem Cell Transplantation ; Quinolizines ; therapeutic use ; Rats ; Rats, Sprague-Dawley

In recent decades, the treatment of autoimmune diseases has moved from the use of hormones and conventional immunosuppressive drugs to biological agents. B cell proliferation and maturation play crucial roles in the development of autoimmune diseases. The tumor necrosis factor superfamily ligand B cell activating factor (BAFF) and its receptor mediate B cell survival through regulating signaling pathways. Therefore, BAFF and its receptors are important therapeutic targets for the treatment of autoimmune diseases. This review describes the mechanism of BAFF and its receptor in the human body system and introduces the latest views on how over-activation of BAFF pathway promotes the development of autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, and rheumatoid arthritis. In connection to the treatment of the above three diseases, this review discusses the clinical trials and application status of three BAFF-targeting antibody drugs, including Belimumab, Tabalumab and Atacicept. Finally, this review proposes new strategies that targeting the BAFF pathway to provide a new treatment for autoimmune diseases.
Autoimmune Diseases/drug therapy* ; B-Cell Activating Factor/therapeutic use* ; B-Lymphocytes ; Humans ; Interleukin-4 ; Lupus Erythematosus, Systemic/drug therapy*

Periodontal bone regeneration is a major challenge in the treatment of periodontitis. Currently the main obstacle is the difficulty of restoring the regenerative vitality of periodontal osteoblast lineages suppressed by inflammation, via conventional treatment. CD301b⁺ macrophages were recently identified as a subpopulation that is characteristic of a regenerative environment, but their role in periodontal bone repair has not been reported. The current study indicates that CD301b⁺ macrophages may be a constituent component of periodontal bone repair, and that they are devoted to bone formation in the resolving phase of periodontitis. Transcriptome sequencing suggested that CD301b⁺ macrophages could positively regulate osteogenesis-related processes. In vitro, CD301b⁺ macrophages could be induced by interleukin 4 (IL-4) unless proinflammatory cytokines such as interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) were present. Mechanistically, CD301b⁺ macrophages promoted osteoblast differentiation via insulin-like growth factor 1 (IGF-1)/thymoma viral proto-oncogene 1 (Akt)/mammalian target of rapamycin (mTOR) signaling. An osteogenic inducible nano-capsule (OINC) consisting of a gold nanocage loaded with IL-4 as the "core" and mouse neutrophil membrane as the "shell" was designed. When injected into periodontal tissue, OINCs first absorbed proinflammatory cytokines in inflamed periodontal tissue, then released IL-4 controlled by far-red irradiation. These events collectively promoted CD301b⁺ macrophage enrichment, which further boosted periodontal bone regeneration. The current study highlights the osteoinductive role of CD301b⁺ macrophages, and suggests a CD301b⁺ macrophage-targeted induction strategy based on biomimetic nano-capsules for improved therapeutic efficacy, which may also provide a potential therapeutic target and strategy for other inflammatory bone diseases.
Animals ; Mice ; Bone Regeneration ; Cytokines/metabolism* ; Interleukin-4/therapeutic use* ; Macrophages/physiology* ; Mammals ; Osteogenesis ; Periodontitis/drug therapy*

Antibodies, Anti-Idiotypic ; therapeutic use ; Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Asthma ; drug therapy ; immunology ; Cytokines ; antagonists & inhibitors ; Humans ; Interleukin-5 ; antagonists & inhibitors ; Omalizumab ; Receptors, Interleukin-4 ; therapeutic use ; T-Lymphocytes ; physiology ; Tumor Necrosis Factor-alpha ; antagonists & inhibitors

Panax ginseng roots have long been used as a medicinal herb in oriental countries. We have investigated anti-proliferative effects of lipid soluble Panax ginseng components on human renal cancer cell lines. Petroleum ether extract of Panax ginseng roots (GX-PE) or its partially purified preparation (7:3 GX) was added to cultures of three human renal cell carcinoma (RCC) cell lines, A498, Caki-1, and CURC II. Proliferation of RCC cells was estimated by a [3H]thymidine incorporation assay and cell cycle distribution was analyzed by flow cytometry. GX-PE, 7:3 GX, panaxydol and panaxynol inhibited proliferation of all three RCC cell lines in a dose dependent manner in vitro with an order of potency, 7:3 GX > panaxydol > panaxynol = GX-PE. Additive effect of interleukin 4 was also demonstrated, most prominently in Caki-1 which responded poorly to GX-PE alone. Analysis of cell cycle in CURC II and Caki-1 treated with GX-PE demonstrated increase in G1 phase population and corresponding decrease in S phase population. The present study demonstrated that proliferation of human RCC cell lines were inhibited by lipid soluble components of Panax ginseng roots by blocking cell cycle progression at G1 to S phase transition.
Alkanes ; Alkynes/therapeutic use ; Antineoplastic Agents/therapeutic use ; Antineoplastic Agents, Phytogenic/therapeutic use* ; Carcinoma, Renal Cell/drug therapy* ; Cell Cycle/drug effects ; Fatty Alcohols/therapeutic use ; Ginseng/therapeutic use* ; Ginseng/chemistry ; Human ; Interleukin-4/therapeutic use ; Kidney Neoplasms/drug therapy* ; Plant Extracts/therapeutic use ; Plant Roots/therapeutic use ; Plant Roots/chemistry

OBJECTIVETo observe the effect of Ziyinqingsang decoction on the levels of interleukin-4 (IL-4) and IL-5 in the peripheral blood mononuclear cells (PBMCs) in children with cough variant asthma (CVA) in the acute stage.

METHODSThirty children with CVA in the acute stage were given Ziyinqingsang decoction for 2 weeks. The IL-4 and IL-5 levels in the PBMCs were determined using ELISA before and after the treatment, and the changes of the clinical symptoms were observed.

RESULTSThe levels of IL-4 and IL-5 in the PBMCs was 89.69∓13.82 ng/l and 12.17∓0.43 ng/ml before the treatment, which were significantly reduced to 72.18∓14.89 ng/l and 5.81∓0.31 ng/ml after the treatment (P<0.05). The symptoms including coughing, pharyngodynia, and pharyngo-itch were all improved obviously (P<0.05).

CONCLUSIONZiyinqingsang decoction ameliorates the symptoms of CVA in the acute stage probably by decreasing the levels of IL-4 and IL-5 in the PBMCs of the children.

Asthma ; blood ; drug therapy ; Child ; Cough ; blood ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Interleukin-4 ; blood ; Interleukin-5 ; blood ; Leukocytes, Mononuclear ; Male ; Phytotherapy

OBJECTIVE: To explore the prophylactic effect of Budesonide on the expression of IL-4,IL-5 in nasal mucosa in model of minimal persistent inflammation of allergic rhinitis in rats. METHOD: Eighty SD rats were randomly divided into allergic rhinitis group (A group), experimental (B group), control group (C group) and negative control group (D group). A group was made for model of allergic rhinitis. B and C group were made for model of the lightest persistent inflammatory response. After the models were established, half of rats in the A group, B group, C group and D group were executed, and EOS infiltration and the expression of IL-4, IL-5, ICAM-1 were observed in nasal mucosa. The remaining rats of B group were given budesonide (64 microg/side/time, twice/day) treatment for 2 weeks. A, C, D group were given nasal spray with normal saline for 2 weeks. After that A, B, and C groups were stimulated with 1% OVA daily for one week, D group were given nasal spray with normal saline. All rats were executed after excitation, EOS infiltration and IL-4, IL-5 expression were observed. RESULT: After the drug treatment, B group only had a small amount of mucous EOS infiltration and had no significant difference with D group, but in A and C group EOS had heavy infiltration. Gray value of the IL-4 positive areas in B group were significantly different compared with A and C group (P < 0.05), A group and C group had no significant difference (P > 0.05). Distribution of IL-5 positive signals was similar with that of IL-4. CONCLUSION Budesonide MPI application could significantly inhibit the allergic.
Animals ; Budesonide ; therapeutic use ; Disease Models, Animal ; Female ; Interleukin-4 ; metabolism ; Interleukin-5 ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Rhinitis, Allergic ; metabolism ; prevention & control

OBJECTIVETo observe the clinical efficacy of Huangqi Fuzheng Decoction (HQFZD) in treating recurrent genital herpes (RGH) and its influence on related cytokines in peripheral blood.

METHODSEighty-four patients with RGH were randomly assigned to 3 groups, the treated group treated with HQFZD (31 cases), the control group A (25 cases) treated with Aciclovir, and the control group B (28 cases) treated with Aciclovir plus interferon. The course of treatment was 3 weeks for all. The relapse rate was estimated at 6 months after treatment, and levels of IL-4, IL-10, IL-12 and IL-18 in all patients were detected before and after treatment using double-sandwich ELISA.

RESULTSAll patients were cured after treatment. The relapse rate in the treated group and the control group B was lower than that in the control group A (P < 0.01) but insignificant difference was shown between the former two groups. Before treatment, patients' serum levels of IL-4 and IL-10 were significantly higher while those of IL-12 and IL-18 were lower than the normal range (P < 0.01). The abnormal change aforementioned reversed after treatment in the treated group and the control group B (P < 0.05 or P < 0.01), showing a superior effect to that in the control group A (P < 0.01).

CONCLUSIONHQFZD can reduce the relapse rate of RGH without obvious adverse reaction, and it could also enhance the immunity of the patients.

Adolescent ; Adult ; Cytokines ; blood ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Herpes Genitalis ; blood ; drug therapy ; pathology ; Humans ; Interleukin-10 ; blood ; Interleukin-12 ; blood ; Interleukin-18 ; blood ; Interleukin-4 ; blood ; Male ; Middle Aged ; Phytotherapy ; Recurrence ; Young Adult