Therapeutic effect of Panax notoginseng saponins combined with cyclophosphamide in mice bearing hepatocellular carcinoma H22 cell xenograft / 南方医科大学学报

OBJECTIVE@#To investigate the therapeutic effects of total saponins from Panax notognseng (PNS) combined with cyclophosphamide (CTX) in mice bearing hepatocellular carcinoma H22 cell xenograft.@*METHODS@#We examined the effects of treatment with different concentrations of PNS on H22 cell proliferation for 24 to 72 h in vitro using CCK8 colorimetric assay. Annexin V/PI double fluorescence staining was used to detect the effect of PNS on apoptosis of H22 cells. Mouse models bearing H22 cell xenograft were established and treated with CTX (25 mg/kg), PNS (120, 240 or 480 mg/kg), alone or in combinations. After treatments for consecutive 10 days, the mice were euthanized for examinations of carbon clearance ability of the monocytes and macrophages, splenic lymphocyte proliferation, tumor necrosis factor (TNF-α), interleukin-2 (IL-2), serum hemolysin antibody level, blood indicators, and the tumor inhibition rate.@*RESULTS@#Treatment with PNS concentration-dependently inhibited the proliferation and significantly promoted apoptosis of cultured H22 cells (P < 0.01). In the tumor-bearing mouse models, PNS alone and its combination with CTX both resulted in obvious enhancement of phagocytosis of the monocyte-macrophages, stimulated the proliferation of splenic lymphocytes, promoted the release of TNF-α and IL-2 and the production of serum hemolysin antibody, and increased the number of white blood cells, red blood cells and lymphocytes in the peripheral blood. Treatment with 480 mg/kg PNS combined with CTX resulted in a tumor inhibition rate of 83.28% (P < 0.01) and a life prolonging rate of 131.25% in the mouse models (P < 0.05).@*CONCLUSION@#PNS alone or in combination with CTX can improve the immunity and tumor inhibition rate and prolong the survival time of H22 tumor-bearing mice.

Protective effects of Wuwei Xiaodu Drink against chronic osteomyelitis through Foxp3+CD25+CD4+ Treg cells via the IL-2/STAT5 signaling pathway / 中国天然药物

To explore the effectiveness and safety of a Chinese medicinal decoction Wuwei Xiaodu Drink (WWXDD) in inhibiting chronic osteomyelitis via regulatory T cells signaling. The effective constitutes of WWXDD and osteomyelitis related genes were screened. Target proteins were cross-validated using the Venny database. GO function and KEGG pathway analysis were performed for target proteins, while pharmacological network was constructed. The bone properties were analyzed by HE staining and the concentrations of immune factors were measured by ELISA. The expression of CTLA-4 and Foxp3 mRNA and STAT5, p-STAT5, CTLA-4 and Foxp3 protein were detected using Real-time PCR and Western blot, respectively. FACS was used to analyze the percentages of cells. A total of 117 genes overlapped between 785 target genes of the active compounds of WWXDD and 912 osteomyelitis related genes. Inflammation-related genes, including IL-6, TNFα, IL-1β and IL-2 showed high connection degree in the drug-compound-disease-target network. GO function and KEGG pathway analysis revealed that 117 intersection genes mainly enriched in virus infection related pathways, immune related pathways and chemokine signaling pathway. Furthermore, the development of chronic osteomyelitis was suppressed in model rats after treatment with WWXDD. Meanwhile, the concentrations of IL-2 and CD4+CD25+Foxp3 Treg percentages together with the levels of p-STAT5, CTLA-4 and Foxp3 were also down-regulated. Furthermore, IL-2 and WWXDD drug-containing serum exhibited opposite effects on regulating IL-2, IL-10, TGF-β1, Foxp3, CTLA4 and STAT5. In addition, a STAT5 phosphorylation inhibitor suppressed the expression of Foxp3 and CTLA-4. WWXDD can treat chronic osteomyelitis through suppressing the main regulating factors of Tregs and interfere its immunodepression. Our results bring a new solution for chronic osteomyelitis.

Evaluation of the level of serum Interleukins (IL-2, IL-4, IL-15 andIL-17) and its relationship with disease severity in patients with alopecia areata

Abstract Background: Alopecia areata (AA) is a hair disease that causes hair loss without scarring. The etiopathogenesis of AA has not been fully understood yet. Objective: To determine serum interleukin levels (IL-2, IL-4, IL-15, and IL-17) in patients diagnosed with alopecia areata and to investigate the relationship of IL levels with the duration and severity of alopecia areata and the response to tofacitinib therapy. Methods: Patients (≥16 years old) diagnosed with alopecia areata and healthy individuals as a control group was enrolled. Baseline serum interleukin levels of the patients and controls were measured. In the patient group receiving tofacitinib therapy, serum interleukin levels were measured again after 6 months. Disease severity for alopecia areata was assessed using the Severity of Alopecia Tool. Results: Sixty-one AA patients and 30 healthy individuals were included; they were comparable regarding age and sex. The mean disease duration for AA was 7 ± 6 years and the baseline mean Severity of Alopecia Tool score was 71 ± 30 (range, 20-100). Baseline IL-2, IL-4 and IL-15 levels were significantly higher in the patient group than those in the control group (p < 0.001 for each). No significant correlation was found between the baseline interleukin levels and either disease duration or disease severity (baseline Severity of Alopecia Tool score). Among the patients receiving tofacitinib (n = 22), all interleukin levels significantly decreased after treatment. However, no significant relationship between the change in interleukin levels and the change in the Severity of Alopecia Tool scores was observed after tofacitinib treatment. Study limitations: This is a monocentric study conducted in a single university hospital. Conclusion: High interleukin levels in alopecia areata patients and the significant decrease with treatment support the idea that interleukins have a role in pathogenesis. Nevertheless, no relationship could be demonstrated between IL levels and disease duration or severity.

Synergistic Mechanism of Interferon alpha-1b, Interleukin-2 and Thalidomide for Immune Regulation in Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the synergistic immunomodulatory mechanism of interferon alpha-1b, interleukin-2 and thalidomide (ITI) regimen on patients with acute myeloid leukemia (AML).@*METHODS@#Sixty eight untreated de novo or relapsed or refractory or maintenance therapy patients with AML admitted in the Affiliated Cancer Hospital of Zhengzhou University and the other 11 medical units from March 2016 to May 2019 were treated with ITI regimen. Peripheral blood specimen per patient was collected into EDTA-K3 anticoagulation vacuum tube before the administration of ITI and 3 months after the treatment; peripheral blood lymphocyte subsets and perforin and Granzyme B expression were analyzed by using flow cytometry; the levels of VEGF, IFN-γ, TNF-α and IL-6 in the plasma were detected by using a cytometric bead array. Thirty-five healthy subjects from the hospital physical examination centre were selected as normal controls.@*RESULTS@#The ratio of CD4@*CONCLUSION@#The ITI regimen can raise the ratio of CD4

IL-10 Cytokine as Potential Biomarkers in Women with Fibromyalgia Who Underwent to a Short Balneotherapy Treatment

Abstract Fibromyalgia (FM) is a nonarticular rheumatic syndrome that leads to diffuse myalgia, sleep disturbances and morning stiffness. Balneotherapy has been shown an effective strategy to improve the health conditions of patients; however, the treatment follow-up is based on patient report due to the lack of biomarkers. Thus, this study evaluated the application of cytokines and phosphoglycerate mutase I (PGAM-I) to monitoring FM patient underwent to balneotherapy treatment. Eleven healthy and eleven women with FM were submitted to daily sessions of balneotherapy during 10 days. Clinical and quality of life parameters were assessed through a FIQ questionnaire. Blood levels of TNF-(, interleukins (IL-1, IL-2 and IL-10) and PGAM-I expression in patients' saliva were also evaluated. Patients with FM showed significant improvements in their clinical status after treatment. Also, FM patients has IL-10 levels lower than healthy women and the balneotherapy increased the expression of this cytokine in both groups, concomitantly to pain relief. Although inflammatory cytokines (IL-1, IL-2 and TNF-() were more expressed in FM patients than healthy patients their levels did not reduce after treatment. A slight increase of PGAM-I expression was observed. In conclusion, IL-10 levels could be a useful biomarker to balneotherapy follow-up of FM patients. However, these findings must be analyzed in a larger number of patients in order to validate IL-10 as an effective biomarker.

Increased platelet distribution width and reduced IL-2 and IL-12 are associated with thrombocytopenia in Plasmodium vivax malaria

BACKGROUND Thrombocytopenia in malaria involves platelet destruction and consumption; however, the cellular response underlying this phenomenon has still not been elucidated. OBJECTIVE To find associations between platelet indices and unbalanced Th1/Th2/Th17 cytokines as a response to thrombocytopenia in Plasmodium vivax infected (Pv-MAL) patients. METHODS Platelet counts and quantification of Th1/Th2/Th17 cytokine levels were compared in 77 patients with uncomplicated P. vivax malaria and 37 healthy donors from the same area (endemic control group - ENCG). FINDINGS Thrombocytopenia was the main manifestation in 55 patients, but was not associated with parasitaemia. The Pv-MAL patients showed increases in the mean platelet volume (MPV), which may be consistent with larger or megaplatelets. Contrary to the findings regarding the endemic control group, MPV and platelet distribution width (PDW) did not show an inverse correlation, due the increase in the heterogeneity of platelet width. In addition, the Pv-MAL patients presented increased IL-1β and reduced IL-12p70 and IL-2 serum concentrations. Furthermore, the reduction of these cytokines was associated with PDW values. MAIN CONCLUSIONS Our data demonstrate that an increase in MPV and the association between reductions of IL-2 and IL-12 and PDW values may be an immune response to thrombocytopenia in uncomplicated P. vivax malaria.

Effects of astragaloside IV on inflammation and immunity in rats with experimental periodontitis

Abstract: This study aimed to investigate the effects of astragaloside IV (AsIV) on inflammation and immunity in rats with experimental periodontitis. Periodontitis was established in 48 Wistar rats, which were then randomly divided into model and 10, 20 and 40 mg/kg AsIV groups, with 12 rats in each group. The latter 3 groups were treated with AsIV at doses of 10, 20 and 40 mg/kg, respectively. The control group (12 rats, without periodontitis) and model group were given the same amount of 5% sodium carboxymethyl cellulose. The treatment was performed once per day for 8 weeks. Before and after treatment, the tooth mobility scores of the rats were determined. After treatment, the salivary occult blood index (SOBI), plaque index (PLI), peripheral blood T lymphocyte subsets, and serum inflammatory factor and immunoglobulin levels were determined. The results showed that, after treatment, compared with that in model group, in 40 mg/kg AsIV group, the general state of rats was improved, while the tooth mobility score, SOBI and PLI were significantly decreased (p < 0.05); the peripheral blood CD4+ T cell percentage and CD4+/CD8+ ratio were significantly increased (p < 0.05), while the CD8+ T cell percentage was significantly decreased (p < 0.05); the serum tumor necrosis factor-α, interleukin-1β and interleukin-2 levels were significantly decreased (p < 0.05); the serum immunoglobulin A and immunoglobulin G levels were significantly decreased (p < 0.05). In conclusion, AsIV can alleviate inflammation and enhance immunity in rats with experimental periodontitis.

Tumor infiltrating T lymphocyte components in malignant pleural effusion of lung adenocarcinoma and their killing activities to autologous tumor cells / 中南大学学报(医学版)

To analyze the components of tumor infiltrating T lymphocyte (TIL) cells in malignant pleural effusion of lung adenocarcinoma, and evaluate their killing activities to autologous tumor cells. 
 Methods: Malignant pleural effusions were collected from 17 patients with lung adenocarcinoma. Mononuclear cells were isolated by Ficoll density gradient centrifugation and flow cytometer was used to analyze TIL cell components. TIL and tumor cells were separated through adherent culture. The tumor cells were identified via intramuscular injection of adherent cells into nude mice and the killing effect of cultured lymphocytes on autologous tumor cells was studied.
 Results: Of the TIL in malignant pleural effusions, T cells accounted for 60.6%-79.3%, while T helper cells were significantly higher than T killer cells (36.63%±1.90% vs 24.64%±2.32%, P<0.001). There were also natural killer (NK) cells and NK T cells in the effusions. Tumor cells were successfully isolated and cultured. The killing activity of cultured TIL to autologous tumor cells was 39.14%±12.04%, and the killing activity of TIL with high proliferation rate to autologous tumor cells was higher than that of low proliferation group (50.51%±3.80% vs 29.04%±5.77%, P<0.001).
 Conclusion: T lymphocytes are the major components of TIL in malignant pleural effusions derived from lung adenocarcinoma, and T helper cells are more than T killer cells. The killing activity of TIL with strong proliferation ability to autologous tumor cells is higher than that of TIL with weak proliferation ability. Therefore, cells from malignant pleural effusions could be used for cellular immunotherapy against tumor.

N-acetyl-l-cysteine controls osteoclastogenesis through regulating Th17 differentiation and RANKL in rheumatoid arthritis

BACKGROUND/AIMS: This study aimed to determine the regulatory role of N-acetyl-l-cysteine (NAC), an antioxidant, in interleukin 17 (IL-17)-induced osteoclast differentiation in rheumatoid arthritis (RA). METHODS: After RA synovial fibroblasts were stimulated by IL-17, the expression and production of receptor activator of nuclear factor κ-B ligand (RANKL) was determined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). Osteoclastogenesis was also determined after co-cultures of IL-17-stimulated RA synovial fibroblasts, Th17 cells and various concentrations of NAC with monocytes. After human peripheral CD4⁺ T cells were cultured with NAC under Th17 condition, IL-17, interferon γ, IL-4, Foxp3, RANKL, and IL-2 expression and production was determined by flow cytometry or ELISA. RESULTS: When RA synovial fibroblasts were stimulated by IL-17, IL-17 stimulated the production of RANKL, and NAC reduced the IL-17-induced RANKL production in a dose-dependent manner. NAC decreased IL-17-activated phosphorylation of mammalian target of rapamycin, c-Jun N-terminal kinase, and inhibitor of κB. When human peripheral blood CD14⁺ monocytes were cultured with macrophage colony-stimulating factor and IL-17 or RANKL, osteoclasts were differentiated, and NAC reduced the osteoclastogenesis. After human peripheral CD4⁺ T cells were co-cultured with IL-17-pretreated RA synovial fibroblasts or Th17 cells, NAC reduced their osteoclastogenesis. Under Th17 polarizing condition, NAC decreased Th17 cell differentiation and IL-17 and RANKL production. CONCLUSIONS: NAC inhibits the IL-17-induced RANKL production in RA synovial fibroblasts and IL-17-induced osteoclast differentiation. NAC also reduced Th17 polarization. NAC could be a supplementary therapeutic option for inflammatory and bony destructive processes in RA.

Extrinsic Acquisition of CD80 by Antigen-Specific CD8⁺ T Cells Regulates Their Recall Immune Responses to Acute Viral Infection

CD80 is mainly expressed on Ag-presenting cells (APCs) as a costimulatory molecule but is also detected on T cells. However, the origin and physiological role of CD80 on CD8⁺ T cells remain unclear. In the present study, we demonstrated that effector and memory CD8⁺ T cells, but not naïve CD8⁺ T cells, displayed CD80 molecules on their surfaces after acute lymphocytic choriomeningitis virus infection. Using adoptive transfer of CD80-knockout (KO) CD8⁺ T cells into a wild type or CD80-KO recipient, we demonstrated that the effector CD8⁺ T cells displayed CD80 by both intrinsic expression and extrinsic acquisition, while memory CD8⁺ T cells displayed CD80 only by extrinsic acquisition. Interestingly, the extrinsic acquisition of CD80 by CD8⁺ T cells was observed only in the lymphoid organs but not in the periphery, indicating the trogocytosis of CD80 molecules via interaction between CD8⁺ T cells and APCs. We compared the recall immune responses by memory CD8⁺ T cells that either extrinsically acquired CD80 or were deficient in CD80, and found that CD80, presented by memory CD8⁺ T cells, played a role in limiting their expansion and IL-2 production upon exposure to secondary challenge. Our study presents the in vivo dynamics of the extrinsic acquisition of CD80 by Ag-specific CD8⁺ T cells and its role in the regulation of recall immune responses in memory CD8+ T cells.

Factors Predicting the Response to Cyclosporin Treatment in Patients With Chronic Spontaneous Urticaria: A Systematic Review

PURPOSE: This study aimed to systemically review literature relating to factors that could potentially predict a favorable response to cyclosporine A (CsA) treatment for chronic spontaneous urticaria (CSU). METHODS: A systematic literature review was done according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations. RESULTS: A total of 13 studies (404 patients with CSU and 200 healthy patients) were included. There were only 1 randomized controlled trial (RCT) and 12 non-RCTs. Our systematic review showed that positive autologous serum skin test results, positive baseline basophil histamine release assays, positive baseline basophil activation test responses, elevated baseline plasma D-dimer levels, elevated baseline serum interleukin (IL)-2, IL-5, and tumor necrosis factor-alpha (TNF-α) levels, and low baseline serum IgE levels might assist in predicting favorable CsA responses in CSU patients. Decreased plasma D-dimer levels; and decreased serum IL-2, IL-5, and TNF-α levels were reported to be correlated with clinical improvement after CsA treatment. CONCLUSIONS: Since most positive results were from non-RCT articles and some data were still inconsistent, this systematic review identified no reliable practical biomarker for predicting CsA treatment response in patients with CSU. There were no positive predictors with good consistency and mechanical plausibility.

MiR-218-5p Suppresses the Killing Effect of Natural Killer Cell to Lung Adenocarcinoma by Targeting SHMT1

PURPOSE: Lung adenocarcinoma (LA) is one of the major types of lung cancer. MicroRNAs (miRNAs) play an essential role in regulating responses of natural killer (NK) cells to cancer malignancy. However, the mechanism of miR-218-5p involved in the killing effect of NK cells to LA cells remains poorly understood. MATERIALS AND METHODS: The expression of miR-218-5p was examined by quantitative real-time polymerase chain reaction (qRT-PCR). Serine hydroxymethyl transferase 1 (SHMT1) level was detected by qRT-PCR or western blots. Cytokines production of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were detected by ELISA. The killing effect of NK cells to LA cells was investigated using lactate dehydrogenase cytotoxicity assay kit. The interaction of miR-218-5p and SHMT1 was probed by luciferase activity assay. Xenograft model was established to investigate the killing effect of NK cells in vivo. RESULTS: miR-218-5p was enhanced and SHMT1 was inhibited in NK cells of LA patients, whereas stimulation of interleukin-2 (IL-2) reversed their abundances. Addition of miR-218-5p reduced IL-2-induced cytokines expression and cytotoxicity in NK-92 against LA cells. Moreover, SHMT1 was negatively regulated by miR-218-5p and attenuated miR-218-5p-mediated effect on cytotoxicity, IFN-γ and TNF-α secretion in IL-2-activated NK cells. In addition, miR-218-5p exhaustion inhibited tumor growth by promoting killing effect of NK cells. CONCLUSION: miR-218-5p suppresses the killing effect of NK cells to LA cells by targeting SHMT1, providing a potential target for LA treatment by ameliorating NK cells function.

Inhibition of miRNA-222-3p Relieves Staphylococcal Enterotoxin B-Induced Liver Inflammatory Injury by Upregulating Suppressors of Cytokine Signaling 1

PURPOSE: Staphylococcal enterotoxin B (SEB) has been well-documented to induce liver injury. miRNA-222-3p (miR-222-3p) was implicated in SEB-induced lung injury and several liver injuries. This study aimed to explore the role of miR-222-3p in SEB-induced liver injury. MATERIALS AND METHODS: Expression of miR-222-3p and suppressors of cytokine signaling 1 (SOCS1) was detected using real-time quantitative PCR and western blot. Liver injury was determined by levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and inflammatory cytokines, numbers of infiltrating mononuclear cells using AST/ALT assay kit, enzyme-linked immunosorbent assay (ELISA), and hematoxylin-eosin staining, respectively. Target binding between miR-222-3p and SOCS1 was predicted on targetScan software, and confirmed by luciferase reporter assay. RESULTS: SEB induced liver injury in D-galactosamine (D-gal)-sensitized mice, as demonstrated by increased serum levels of AST and ALT, elevated release of interferon-gamma (INF-γ), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-2, and promoted infiltrating immune cells into liver. Expression of miR-222-3p was dramatically upregulated, and SOCS1 was downregulated in SEB-induced liver injury both in mice and splenocytes. Moreover, miR-222-3p knockout (KO) mice exhibited alleviated liver injury accompanied with SOCS1 upregulation. Besides, splenocytes under SEB challenge released less INF-γ, TNF-α, IL-6, and IL-2 during miR-222-3p knockdown. Mechanically, SOCS1 was targeted and downregulated by miR-222-3p. Upregulation of SOCS1 attenuated INF-γ, TNF-α, IL-6, and IL-2 release in SEB-induced splenocytes; downregulation of SOCS1 could block the suppressive role of miR-222-3p knockdown in SEB-induced splenocytes. CONCLUSION: Inhibition of miR-222-3p relieves SEB-induced liver inflammatory injury by upregulating SOCS1, thereby providing the first evidence of miR-222-3p in SEB-induced liver injury.

Anti-inflammatory and Immunosuppressive Effects of Panax notoginseng

Here, we designed to examine the anti-inflammatory effects on RAW264.7 cells and the immunosuppressive effects by evaluating interleukin-2 (IL-2) production in Jurkat T cells using a MeOH extract of Panax notoginseng roots. The results showed that the MeOH extract inhibited the synthesis of nitric oxide (NO) in a dose-dependent manner (IC₅₀ value of 7.08 µg/mL) and displayed effects on T cell activation at a concentration of 400 µg/mL. In efforts to identify the potent compounds, bioactivity-guided fractionation of the MeOH extract and chemical investigation of its active CH₂Cl₂-, EtOAc-, and butanol-soluble fractions led to the successful isolation and identification of eleven compounds, including two polyacetylenes (1, 2), a steroid saponin (3), seven dammarane-type ginsenosides (4 – 10), and an oleanane-type ginsenoside (11). Among them, compound 11 was isolated from this plant for the first time. Compound 2 exhibited potent inhibitory effects on NO synthesis and an immunosuppressive effect with IC₅₀ values of 2.28 and 65.57 µM, respectively.

Níveis séricos de citocinas IL-2, IL-10 e IL-12 em pacientes com adenocarcinoma do estômago / Serum cytokine of il-2, il-10 and il-12 levels in patients with stomach adenocarcinoma

ABSTRACT BACKGROUND: Gastric adenocarcinoma is the fourth most common cause of cancer-associated death worldwide. OBJECTIVE: We evaluated the immunological status of patients with gastric cancer before surgery and circulating cytokines as potential diagnostic biomarkers for gastric cancer. METHODS: We included 90 healthy controls and 95 patients with distal Gastric adenocarcinoma in Mazandaran, Sari, Iran. We measured serum IL-2, IL-10 and IL-12 Levels by a sandwich enzyme-linked immunosorbent assay using the IBL international GMBH kit. RESULTS: The serum IL-10 levels in the patients with Gastric adenocarcinoma were significantly higher than those of the healthy controls (P=0.02). There were no significant differences in serum IL-2 and IL-12 levels between patients with gastric cancer and healthy controls. CONCLUSION: Increased levels of IL-10 might be useful as diagnostic biomarkers for Gastric adenocarcinoma; however, this needs to be confirmed with larger number of patients and with control groups other than blood donors, properly age paired. These results suggest that positive expression of IL-10 may be useful as a molecular marker to distinguish stage of gastric cancers which can be more readily controlled.

RESUMO CONTEXTO: O adenocarcinoma gástrico é a quarta causa mais comum de morte relacionada ao câncer em todo o mundo. OBJETIVO: Avaliar o status imunológico dos pacientes com câncer gástrico antes da cirurgia e as citocinas circulantes como potenciais biomarcadores diagnósticos para câncer gástrico. MÉTODOS: Incluímos 90 indivíduos controles saudáveis e 95 pacientes com adenocarcinoma gástrico distal em Mazandaran, Sari, Iran. Os níveis de soro Il-2, IL-10 e Il-12 foram medidos por um ensaio de imunoabsorção enzimática pela técnica de sanduíche usando o kit IBL International GmbH. RESULTADOS: Os níveis séricos IL-10 nos pacientes com adenocarcinoma gástrico foram significativamente superiores aos dos controles saudáveis (P=0,2). Não houve diferenças significativas nos níveis de soro IL-2 e IL-12 entre pacientes com câncer gástrico e controles saudáveis. CONCLUSÃO: Níveis aumentados de IL-10 podem ser úteis como biomarcadores diagnósticos para adenocarcinoma gástrico; no entanto, isso precisa ser confirmado com maior número de pacientes e com grupos de controle que não sejam doadores de sangue, adequadamente emparelhado por idade. Estes resultados sugerem que a expressão positiva do IL-10 pode ser útil como um marcador molecular para distinguir a fase de câncer gástrico que pode ser mais facilmente controlada.

Wound healing of diabetic rats treated with Moringa oleifera extract

Abstract Purpose: To evaluate if Moringa oleifera leaf aqueous extract (ME) influences the healing of skin wounds of diabetic rats. Methods: Wistar rats were used (6 rats/group). Group 1 received normal saline (NS) v.o. Group 2 received moringa extract (100mg/kg v.o) for 3 weeks. Groups 3 and 4: Streptozotocin (STZ) induced diabetes. Group 3 received NS; Group 4 received aqueous ME (100mg/kg) v.o.The wounds of groups 1 and 3 rats were topically treated with NS; wounds of groups 2 and 4 treated with 200µL of 10% ME. After anesthesia, all rats had skin square excision wounds 1.5cm2. Wound percent contractions were measured. On 10th day, blood glucose and serum cytokines were measured. Histometry of wounds was studied using ImagePro6.0 software. Results: Glycemia was significantly reduced in ME treated rats. These rats had higher percent contraction of the wounds on 2nd, 5th and 10th days, then controls (p<0.05). Diabetic rats treated with NS had TNF-α, IL-1β and IL-6 expression higher than in rats receiving ME. The histopathological score of ME treated diabetic rats (198±13.7) was significantly higher than treatment with NS (145±10.5). Conclusion: ME extract positively influenced healing of wounds in diabetic rats after systemic and topical treatment.

Pro-inflammatory Cytokines, Biomarkers, Genetics and the Immune System: A Mechanistic Approach of Depression and Psoriasis / Citocinas proinflamatorias, biomarcadores, genética y sistema inmunológico: un enfoque mecanicista de la depresión y la psoriasis

ABSTRACT Objective: To highlight the inflammatory and immunological mechanisms involved in depression and psoriasis. Methods: A comprehensive literature search was performed in various databases, in total 145 studies were selected. Results: Depression and psoriasis have an association. Immune mechanisms -the actions of tumor necrosis factor-a, interleukin 1 (IL-1), IL-2, IL-10, IL-22, IL-17, interferon-7, IL-1ß, prostaglandin E2, C-reactive protein, IL-6, and IL-8 etc.-, and some genetic changes are involved. Conclusions: A possible bidirectional relationship of psoriasis and major depression exists; i.e. the depression leads to psoriasis, and psoriasis leads to depression. We recommend more studies in the future to get a deeper and better understanding about this relationship.

RESUMEN Objetivo: Poner de relieve los mecanismos inflamatorios e inmunológicos involucrados en la depresión y la psoriasis. Métodos: Se realizó en varias bases de datos una búsqueda bibliográfica completa; en total se incluyeron 145 estudios. Resultados: Hay asociación entre depresión y psoriasis y están involucrados mecanismos inmunitarios -las acciones del factor de necrosis tumoral alfa, las interleucinas (IL) 1, 2, 10, 22 y 17, el interferón gamma, la IL-1ß, la prostaglandina E2, la proteína C reactiva, la IL-6 y la IL-8, etc. - y algunos cambios genéticos. Conclusiones: Hay una posible relación bidireccional entre psoriasis y depresión, es decir, la depresión lleva a psoriasis y la psoriasis lleva a depresión. Se recomiendan más estudios en el futuro para obtener una comprensión más profunda y mejor sobre esta relación.

Maternal schistosomiasis: IL-2, IL-10 and regulatory T lymphocytes to unrelated antigen in adult offspring mice

Abstract INTRODUCTION: We evaluated IL-10, IL-2 and regulatory T cells (Treg), in response to ovalbumin (OA), in offspring from schistosomotic mouse mothers. METHODS: We used animals born (BIM) or suckled (SIM) from infected mothers; and mice born/suckled from infected (BSIM) or non-infected mothers (CONTROL). After OA+adjuvant immunization, spleen cells were cultured, with or without OA, and doubly marked for cytometry. RESULTS: BIM showed fewer CD4+/IL-2+ and more B220+/IL-10+ cells, whereas the SIM group showed increased Treg frequency. BSIM had fewer B220+/IL-10+ and Treg cells. CONCLUSIONS: Separately, gestation or nursing induced immunosuppressive cells in infected mothers, but improved anti-OA immunity when combined.

Polymorphisms in the TGFB1 and IL2RA genes are associated with clinical forms of leprosy in Brazilian population

BACKGROUND Leprosy is a chronic infectious disease caused by Mycobacterium leprae, and compromises the skin and peripheral nerves. This disease has been classified as multibacillary (MB) or paucibacillary (PB) depending on the host immune response. Genetic epidemiology studies in leprosy have shown the influence of human genetic components on the disease outcomes. OBJECTIVES We conducted an association study for IL2RA and TGFB1 genes with clinical forms of leprosy based on two case-control samples. These genes encode important molecules for the immunosuppressive activity of Treg cells and present differential expressions according to the clinical forms of leprosy. Furthermore, IL2RA is a positional candidate gene because it is located near the 10p13 chromosome region, presenting a linkage peak for PB leprosy. METHODS A total of 885 leprosy cases were included in the study; 406 cases from Rondonópolis County (start population), a hyperendemic region for leprosy in Brazil, and 479 cases from São Paulo state (replication population), which has lower epidemiological indexes for the disease. We tested 11 polymorphisms in the IL2RA gene and the missense variant rs1800470 in the TGFB1 gene. FINDINGS The AA genotype of rs2386841 in IL2RA was associated with the PB form in the start population. The AA genotype of rs1800470 in TGFB1 was associated with the MB form in the start population, and this association was confirmed for the replication population. MAIN CONCLUSIONS We demonstrated, for the first time, an association data with the PB form for a gene located on chromosome 10. In addition, we reported the association of TGFB1 gene with the MB form. Our results place these genes as candidates for validation and replication studies in leprosy polarisation.

Enhancement of oral bioavailability and immune response of Ginsenoside Rh2 by co-administration with piperine / 中国天然药物

Ginsenoside Rh2 (Rh2) is one of the major bioactive ginsenosides in Panax ginseng. However, the oral bioavailability of Rh2 is low, with P-glycoprotein (P-gp) and CYP3A4 being reported to be the main factors. The purpose of the present study was to determine the enhancing effect of piperine on the oral bioavailability as well as bioactivity of Rh2. The inhibitory effect of piperine on P-gp and CYP3A4 was determined using a Caco-2 monolayer model and a recombinant CYP3A4 metabolic system, respectively. The pharmacokinetics of oral Rh2 (10 mg·kg) administered alone or in combination with piperine (10 and 20 mg·kg) was performed in rats. The immune boosting effect of Rh2 was assessed in rats by measuring IL-12 level after treated by Rh2 alone or co-administered with piperine. The results indicated that piperine significantly increased the permeability of Rh2 and inhibited the metabolism of Rh2. The pharmacokinetic study results showed that the AUC of Rh2 was significantly increased in combination with piperine at high dose (20 mg·kg) when compared to the control group, with relative bioavailability of 196.8%. The increase of Rh2 exposure led to increased serum levels of IL-12. In conclusion, piperine may be used as a bioenhancer to improve pharmacological effect of Rh2 when given orally.