OBJECTIVEAging is associated with the development of diseases because of immunosuppression and altered functioning of the neuroendocrine system. The medicinal properties of Morinda citrifolia L. have been widely exploited for the treatment of age-associated diseases. This study aims to investigate the in vitro and in vivo effects of noni (M. citrifolia) fruit juice (NFJ) on neuro-immunomodulation in the lymph node lymphocytes of F344 rats.

METHODSLymphocytes isolated from axillary and inguinal lymph nodes of young (3-4 months) and old (18-21 months) rats were treated in vitro with different concentrations (0.0001%, 0.01%, and 1%) of NFJ for a period of 24 h. In the in vivo study, old (16-17 months) male F344 rats were treated with 5 mL/kg body weight of 5%, 10% and 20% of NFJ, twice a day, by oral gavage, and lymph node lymphocytes were isolated after 60 d. Concanavalin A (Con A)-induced lymphocyte proliferation, interleukin-2 (IL-2) and interferon-γ (IFN-γ) production and expression of intracellular markers, such as phospho-extracellular signal-regulated kinase (p-ERK1/2), phospho-cAMP response element-binding protein, phospho-protein kinase B (p-Akt), phospho-tyrosine hydroxylase (p-TH), phospho-nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor-α (p-IκB-α) and phospho-nuclear factor-κB (p-NF-κB p65 and p50) were examined in the lymphocytes of lymph nodes.

RESULTSNFJ increased Con A-induced lymphocyte proliferation, IL-2 and IFN-γ production, and p-ERK1/2 expression both in vitro and in vivo. In in vivo NFJ-treated old rats, lymph node lymphocytes showed increased expression of p-TH and Akt, nitric oxide production and decreased expression of p-NF-κB p65 and p50.

CONCLUSIONThese results suggest that the immunostimulatory properties of NFJ are facilitated through intracellular signaling pathways involving ERK1/2, Akt and NF-κB.

Adjuvants, Immunologic ; metabolism ; Aging ; immunology ; metabolism ; Animals ; Cell Proliferation ; Fruit ; chemistry ; metabolism ; Fruit and Vegetable Juices ; analysis ; Humans ; Interleukin-2 ; immunology ; Lymph Nodes ; cytology ; immunology ; Lymphocytes ; cytology ; immunology ; Male ; Morinda ; chemistry ; metabolism ; NF-kappa B ; immunology ; Plant Preparations ; metabolism ; Rats ; Rats, Inbred F344 ; Transcription Factor RelA ; immunology

OBJECTIVETo investigate the predictive factors of pathological complete response (pCR) in primary human epidermal growth factor receptor 2 (HER2)-positive breast cancer treated with trastuzumab-based neoadjuvant chemotherapy (NAC).

METHODSTotally 101 patients of primary HER2-positive breast cancer treated with trastuzumab-based NAC and subsequent curative surgical therapy in the Breast Disease Center of Peking University First Hospital from September 2007 to December 2014 were retrospectively reviewed. All patients were female with a median age of 53 (range 23 to 70) years.All patients received a taxanes- and carboplatin-containing chemotherapy, and trastuzumab was administered concurrently.A pCR, defined as the absence of invasive tumor cells in the breast and axillary lymph nodes, was achieved in 37.6% of patients (38/101). For analysis of the associations between clinicopathological factors and pCR, the χ(2) test or Fisher's exact test was used for univariate analysis, and multivariate Logistic regression analysis was performed to estimate OR and 95% CI.

RESULTSTumor-infiltrating lymphocytes (χ(2)=14.981, P=0.000), hormone receptor (HR) status (χ(2)=9.513, P=0.002), and tumor grade (χ(2)=4.005, P=0.045) were significantly associated with pCR in univariate analysis. Tumor-infiltrating lymphocytes positive (OR=4.74, 95% CI: 1.87 to 12.01, P=0.001) and HR-negative (OR=3.28, 95% CI: 1.31 to 8.20, P=0.011) were independent predictive factors of pCR in multivariate analysis.

CONCLUSIONTumor-infiltrating lymphocytes-positive and HR-negative were independent predictive factors of pCR in primary HER2-positive breast cancer treated with trastuzumab-based NAC.

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Axilla ; Breast Neoplasms ; drug therapy ; metabolism ; Female ; Humans ; Lymph Nodes ; Lymphocytes, Tumor-Infiltrating ; cytology ; Middle Aged ; Neoadjuvant Therapy ; Receptor, ErbB-2 ; metabolism ; Retrospective Studies ; Trastuzumab ; therapeutic use ; Young Adult

Vertical sleeve gastrectomy (VSG) is becoming more and more popular among the world. Despite its dramatic efficacy, however, the mechanism of VSG remains largely undetermined. This study aimed to test interferon (IFN)-γ secretion n of mesenteric lymph nodes in obese mice (ob/ob mice), a model of VSG, and its relationship with farnesoid X receptor (FXR) expression in the liver and small intestine, and to investigate the weight loss mechanism of VSG. The wild type (WT) mice and ob/ob mice were divided into four groups: A (WT+Sham), B (WT+VSG), C (ob/ob+Sham), and D (ob/ob+VSG). Body weight values were monitored. The IFN-γ expression in mesenteric lymph nodes of ob/ob mice pre- and post-operation was detected by flow cytometry (FCM). The FXR expression in the liver and small intestine was detected by Western blotting. The mouse AML-12 liver cells were stimulated with IFN-γ at different concentrations in vitro. The changes of FXR expression were also examined. The results showed that the body weight of ob/ob mice was significantly declined from (40.6±2.7) g to (27.5±3.8) g on the 30th day after VSG (P<0.05). At the same time, VSG induced a higher level secretion of IFN-γ in mesenteric lymph nodes of ob/ob mice than that pre-operation (P<0.05). The FXR expression levels in the liver and small intestine after VSG were respectively 0.97±0.07 and 0.84±0.07 fold of GAPDH, which were significantly higher than pre-operative levels of 0.50±0.06 and 0.48±0.06 respectively (P<0.05). After the stimulation of AML-12 liver cells in vitro by different concentrations of IFN-γ (0, 10, 25, 50, 100, and 200 ng/mL), the relative FXR expression levels were 0.22±0.04, 0.31±0.04, 0.39±0.05, 0.38±0.05, 0.56±0.06, and 0.35±0.05, respectively, suggesting IFN-γ could distinctly promote the FXR expression in a dose-dependent manner in comparison to those cells without IFN-γ stimulation (P<0.05). It was concluded that VSG induces a weight loss in ob/ob mice by increasing IFN-γ secretion of mesenteric lymph nodes, which then increases the FXR expression of the liver and small intestine.
Animals ; Body Weight ; Cell Line ; Gastrectomy ; methods ; Gene Expression ; Hepatocytes ; cytology ; drug effects ; metabolism ; Interferon-gamma ; biosynthesis ; pharmacology ; secretion ; Intestine, Small ; drug effects ; metabolism ; Liver ; drug effects ; metabolism ; Lymph Nodes ; drug effects ; metabolism ; Mesentery ; drug effects ; metabolism ; Mice ; Mice, Obese ; Obesity ; metabolism ; pathology ; surgery ; Receptors, Cytoplasmic and Nuclear ; agonists ; genetics ; metabolism ; Weight Loss

Eupatilin is the main active component of DA-9601, an extract from Artemisia. Recently, eupatilin was reported to have anti-inflammatory properties. We investigated the anti-arthritic effect of eupatilin in a murine arthritis model and human rheumatoid synoviocytes. DA-9601 was injected into collagen-induced arthritis (CIA) mice. Arthritis score was regularly evaluated. Mouse monocytes were differentiated into osteoclasts when eupatilin was added simultaneously. Osteoclasts were stained with tartrate-resistant acid phosphatase and then manually counted. Rheumatoid synoviocytes were stimulated with TNF-alpha and then treated with eupatilin, and the levels of IL-6 and IL-1beta mRNA expression in synoviocytes were measured by RT-PCR. Intraperitoneal injection of DA-9601 reduced arthritis scores in CIA mice. TNF-alpha treatment of synoviocytes increased the expression of IL-6 and IL-1beta mRNAs, which was inhibited by eupatilin. Eupatilin decreased the number of osteoclasts in a concentration dependent manner. These findings, showing that eupatilin and DA-9601 inhibited the expression of inflammatory cytokines and the differentiation of osteoclasts, suggest that eupatilin and DA-9601 is a candidate anti-inflammatory agent.
Animals ; Anti-Inflammatory Agents/pharmacology/*therapeutic use ; Arthritis, Experimental/chemically induced/*drug therapy ; Arthritis, Rheumatoid/drug therapy/pathology ; Cell Differentiation/*drug effects ; Cells, Cultured ; Collagen Type II ; Cytokines/biosynthesis ; Disease Models, Animal ; Drugs, Chinese Herbal/therapeutic use ; Female ; Flavonoids/pharmacology/*therapeutic use ; Humans ; Inflammation/drug therapy/immunology ; Interleukin-1beta/genetics/metabolism ; Interleukin-6/genetics/metabolism ; Lymph Nodes/cytology ; Mice ; Mice, Inbred DBA ; Monocytes/cytology ; Osteoclasts/*cytology ; Plant Extracts/pharmacology ; RNA, Messenger/biosynthesis ; Synovial Membrane/cytology ; T-Lymphocytes, Regulatory/cytology/immunology ; Tumor Necrosis Factor-alpha/pharmacology

OBJECTIVETo investigate the effect of oral administration of Zaocys type II collagen (ZCII) on the percentages of Treg/Th17 cells in mesenteric lymph node lymphocytes (MLNLs) in mice with collagen-induced arthritis (CIA).

METHODSCIA was induced in male C57BL/6 mice by immunization with chicken type II collagen. Three weeks later, ZCII, purified by pepsin digestion, was orally administered in the mice for 7 consecutive days (daily dose of 10, 20, or 40 µg/kg). The severity of arthritis in each limb was evaluated using a macroscopic scoring system, and histopathological changes of the joint were observed microscopically with HE staining. The percentages of Treg and Th17 cells in MLNLs was detected by flow cytometry, and the levels of transforming growth factor-β (TGF-β) and interleukin-17 (IL-17) in the supernatant of MLNLs were measured by enzyme-linked immunosorbent assay.

RESULTSCompared with normal control mice, the mice with CIA had significantly higher scores for arthritis and histopathological changes, with also significantly increased percentages of Treg and Th17 cells in MLNLs and elevated levels of TGF-β and IL-17 in MLNL supernatant (P<0.05). In ZCII peptide-treated mice, the scores for arthritis and histopathological changes were significantly lower than those in CIA model group (P<0.05), and Treg cell percentage in MLNLs was up-regulated while Th17 cell percentage lowered; the level of TGF-β was increased but IL-17 was decreased significantly (P<0.05).

CONCLUSIONOral administration of ZCII improves CIA in mice by regulating the percentages of Treg/Th17 cells and the cytokine levels in MLNLs, suggesting the value of ZCII as a promising candidate agent for treatment of rheumatoid arthritis.

Animals ; Arthritis, Experimental ; immunology ; Arthritis, Rheumatoid ; Collagen Type II ; pharmacology ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Interleukin-17 ; metabolism ; Lymph Nodes ; cytology ; Male ; Mice ; Mice, Inbred C57BL ; T-Lymphocytes, Regulatory ; immunology ; Th17 Cells ; immunology ; Transforming Growth Factor beta ; metabolism

No abstract available.
Acute Disease ; Adult ; Antigens, CD4/metabolism ; Antigens, CD45/metabolism ; Antigens, CD56/metabolism ; Bone Marrow Cells/cytology ; Flow Cytometry ; Hematologic Neoplasms/*diagnosis/pathology ; Humans ; Interleukin-3 Receptor alpha Subunit/metabolism ; Lymph Nodes/metabolism/pathology ; Male ; Tomography, X-Ray Computed

OBJECTIVEParkinson's disease (PD), a neurodegenerative disorder, has been reported to be associated with brain neuroinflammation in its pathogenesis. Herein, changes in peripheral immune system were determined to better understand PD pathogenesis and provide possible target for treatment of PD through improvement of immune disorder.

METHODS1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was intraperitoneally injected into mice to prepare PD model. Expression levels of pro-inflammatory and anti-inflammatory cytokines and transcription factors of CD4+ T lymphocyte subsets in spleen and mesenteric lymph nodes and concentrations of the cytokines in serum were examined on day 7 after MPTP injection. Percentages of CD4+ T lymphocyte subsets were measured by flow cytometry.

RESULTSMPTP induced PD-like changes such as motor and behavioral deficits and nigrostriatal impairment. Expression levels of the pro-inflammatory cytokines including interferon (IFN)-γ, interleukin (IL)-2, IL-17 and IL-22, in spleen and mesenteric lymph nodes were upregulated and their concentrations in serum were elevated in PD progression. But, the concentrations of the anti-inflammatory cytokines including IL-4, IL-10 and transforming growth factor (TGF)-β were not altered in the two lymphoid tissues or serum of PD mice. In addition, expression of T-box in T cells (T-bet), the specific transcription factor of helper T (Th) 1 cells, was downregulated, but expression of transcription factor forkhead box p3 (Foxp3), the transcription factor of regulatory T (Treg) cells, was upregulated. In support of the results, the numbers of IFN-γ-producing CD4+ cells (Th1 cells) were reduced but CD4+CD25+ cells (Treg cells) were elevated in both the lymphoid tissues of PD mice.

CONCLUSIONPD has a dysfunction of peripheral immune system. It manifests enhancement of proinflammatory response and CD4+ T cell differentiation bias towards Treg cells away from Th1 cells.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Animals ; CD4-Positive T-Lymphocytes ; pathology ; Cell Differentiation ; Cytokines ; blood ; Disease Models, Animal ; Flow Cytometry ; Forkhead Transcription Factors ; metabolism ; Interferon-gamma ; blood ; Interleukin-10 ; blood ; Interleukin-17 ; blood ; Interleukin-2 ; blood ; Interleukin-4 ; blood ; Interleukins ; blood ; Lymph Nodes ; cytology ; Lymphocyte Activation ; Mice ; Parkinson Disease ; immunology ; physiopathology ; Spleen ; cytology ; T-Box Domain Proteins ; metabolism ; T-Lymphocytes, Regulatory ; Th1 Cells ; Transforming Growth Factor beta ; blood

Animals ; Graft vs Host Disease ; immunology ; metabolism ; Intestines ; immunology ; pathology ; Lymph Nodes ; cytology ; Lymphocyte Activation ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; T-Lymphocytes ; immunology ; metabolism

OBJECTIVETo observe the effects of qingchang huashi recipe (QHR) on the dendritic cells (DCs) of experimental colitis rats, thus exploring its possible mechanisms for treating ulcerative colitis (UC).

METHODSThe UC rat model was induced by TNBS/anhydrous alcohol. Forty male Wistar rats were randomly divided into 4 groups, i.e., the normal group, the model group, the QHR group, and the Mesalazine group, 10 in each group. Since the 2nd day of modeling, corresponding medication was respectively administered to each treatment group by gastrogavage for 10 successive days. The number of DCs in the colonic mucosa was observed using iMmunohistochemical assay. The DCs ratio in the mesenteric lymph nodes, and the expressions of surface molecules MHC-II and CD86 were detected using flow cytometry.

RESULTSCompared with the model group, the number of DCs in the colonic mucosa significantly decreased, the expression of MHC-II in the mesenteric lymph nodes significantly decreased in the QHR group and the Mesalazine group, showing statistical difference (P < 0.01). There was no statistical difference between the two groups (P > 0.05). There was no statistical difference in the DCs ratios and the CD86 expression among the 4 groups (P > 0.05).

CONCLUSIONQHR could decrease the infiltration of DCs in the colonic mucosa, and suppress the activation of DCs in the mesenteric lymph nodes, which might be one of its mechanisms for treating UC.

Animals ; Colitis, Ulcerative ; drug therapy ; physiopathology ; Dendritic Cells ; cytology ; drug effects ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Intestinal Mucosa ; cytology ; Lymph Nodes ; cytology ; Lymphocyte Count ; Male ; Mesentery ; cytology ; Phytotherapy ; Rats ; Rats, Wistar

OBJECTIVETo observe the effect of burn on cytokines in lymph and T lymphocyte subsets in lymph node of rats.

METHODSEighteen Wistar rats were used in the experiment. One of the hind limbs of each rat was immersed in 70 °C hot water for 30 s to reproduce 4%TBSA deep partial-thickness scald model (burn group), while the other hind limb was immersed in 22 °C warm water for 30 s to simulate scald (sham injury group). On post injury hour (PIH) 6, 24, and 72, 6 rats were chosen according to the random number table. Lymph fluid in the lymph vessel of each animal (two groups) was obtained for determination of levels of tumor necrosis factor α (TNF-α), interferon-γ (IFN-γ) and interleukin-4 (IL-4) by ELISA, and IFN-γ/IL-4 ratio was calculated. Common iliac lymph node of each animal (two groups) was obtained for determination of ratios of CD4(+), CD8(+)T lymphocytes with flow cytometry, and CD4(+)/CD8(+) ratio was calculated. Data were processed with t test.

RESULTS(1) On PIH 6, 24, and 72, TNF-α level in burn group was respectively (51.6 ± 5.4), (27.4 ± 2.6), (23.0 ± 2.7) pg/mL, which were significantly higher than those in sham injury group [(17.8 ± 1.6), (16.4 ± 1.2), (17.2 ± 2.0) pg/mL, with t value respectively 15.346, 11.854, 4.189, P values all below 0.01]. (2) On PIH 6, 24, and 72, there was no significant statistical difference between burn group and sham injury group in IFN-γ level (with t value respectively 2.059, -0.805, -0.415, P values all above 0.05); IL-4 level in burn group was respectively higher than that in sham injury group (with t value respectively 9.141, 11.669, 6.940, P values all below 0.01); IFN-γ/IL-4 ratio in burn group (2.27 ± 0.34, 1.54 ± 0.19, 1.60 ± 0.16) was respectively lower than that in sham injury group (3.33 ± 0.25, 3.34 ± 0.22, 2.52 ± 0.24, with t value respectively -6.298, -11.313, -8.893, P values all below 0.01). (3) On PIH 6 and 24, there was no significant statistical difference between burn group and sham injury group in ratios of CD4(+) and CD8(+)T lymphocytes and also CD4(+)/CD8(+) ratio (with t values from -2.486 to -0.215, P values all above 0.05). On PIH 72, ratio of CD4(+)T lymphocytes and CD4(+)/CD8(+) ratio in burn group was respectively (38.6 ± 2.3)% and 2.13 ± 0.16, which were significantly lower than those in sham injury group [(48.9 ± 2.9)% and 2.68 ± 0.12, with t value respectively -7.551, -5.068, P values below 0.01]; there was no significant statistical difference between burn group and sham injury group in ratio of CD8(+)T lymphocytes (t = 0.845, P > 0.05).

CONCLUSIONSBurn may decrease IFN-γ/IL-4 ratio in locally drained lymph and CD4(+)/CD8(+) ratio in locally drained lymph node of rat, which may indicate lowering of local immune function.

Animals ; Burns ; immunology ; metabolism ; CD4-CD8 Ratio ; Flow Cytometry ; Interferon-gamma ; metabolism ; Interleukin-4 ; metabolism ; Lymph Nodes ; immunology ; metabolism ; Lymphatic Vessels ; immunology ; metabolism ; Male ; Rats ; Rats, Wistar ; T-Lymphocytes ; cytology ; immunology