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1.
Medicine (Baltimore) ; 99(9): e19058, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32118713

RESUMEN

Sepsis can cause septic shock, multiple organ dysfunction and even death. The combination of different blood purification would be the certain trend in the treatment of sepsis.This study was to evaluate the clinical effects of hemoperfusion (HP) combined with pulse high volume hemofiltration (PHVHF) on septic shock.Thirty cases were involved in this study and were randomly divided into two groups: HP and PHVHF group (n = 15) and CVVH (continuous veno-venous hemofiltration) group (n = 15). Acute physiology and chronic health evaluation (APACHE) II scores, sequential organ failure assessment (SOFA) scores as well as biochemical changes were measured before and after the treatment. The levels of IL-6, IL-10, and TNF-α in plasma were assessed by ELISA before and after treatment for 2 and 24 h. The norepinephrine doses were also analyzed. The 28-day mortalities in both groups were also compared.In both groups, body temperature (BT), respiratory rate (RR), white blood cells (WBC), C-reactive protein (CRP), Procalcitonin (PCT), lactic acid, serum creatinine, APACHE II scores and SOFA scores decreased after hemofiltration (P < .05). The HP&PHVHF group was superior to the CVVH group in CRP, APACHE II score (P < .01), and heart rate (HR), WBC, PCT, SOFA (P < .05). The doses of norepinephrine were also decreased after treatment (P < .01), with more reduction in the HP&PHVHF group (P < .05). After 24 h of treatment, the levels of IL-6, IL-10, and TNF-α decreased in both groups (P < .05), and the decrease was more significant in HP&PHVHF group (P < .05). In combined group, after 2 h of hemoperfison, there was a significant reduction in these inflammatory factors (P < .01). Combined therapy group's mortality was 26.7%, while CVVH group's was 40%.HP combined with PHVHF has a significant effect on septic shock and can be an important therapy for septic shock.


Asunto(s)
Hemofiltración , Hemoperfusión , Choque Séptico/terapia , Adulto , Anciano , Citocinas/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Choque Séptico/sangre
2.
Orv Hetil ; 161(13): 483-490, 2020 Mar.
Artículo en Húngaro | MEDLINE | ID: mdl-32202149

RESUMEN

Inflammation contributes to the pathogenesis of low back pain and sciatica. Growing evidence suggests that elevated levels of some inflammatory biomarkers are associated with these conditions. Much of the research evaluating the association between pro- and anti-inflammatory cytokines, chemokines, other regulatory molecules, and low back pain and sciatica, focused on patients with chronic low back pain, while fewer studies addressed the issue of detectable biomarkers in the acute phase. Previous studies suggest that pro-inflammatory cytokines such as TNF-α, IL-6, and IL-8 and anti-inflammatory IL-4 and IL-10 play an important role in the inflammatory response following intervertebral disc herniation. According to the approach of personalized medicine it is important to identify subsets of patients within the acute patient group regarding etiology, prognosis and treatment. In addition, if we can identify subgroups based on levels of pro-inflammatory biomarkers, where inflammation may be the leading cause of pain, we assume that this subgroup would likely be effectively treated with anti-inflammatory medication. The efficacy of TNF-α inhibitors and IL-6 inhibitors in treating low back pain and sciatica has already been tested in clinical trials, but further studies are required. Overall, identification of circulating biomarkers of acute low back pain and sciatica may assist in refining personalized diagnosis and treatment. Further research is needed to evaluate the role of inflammation in acute low back pain and sciatica, to identify what methods are appropriate for evaluation in clinical practice, and whether there are biomarkers of prognostic value in these patients. Orv Hetil. 2020; 161(13): 483-490.


Asunto(s)
Citocinas/sangre , Desplazamiento del Disco Intervertebral/sangre , Dolor de la Región Lumbar/sangre , Ciática/sangre , Biomarcadores/sangre , Humanos , Degeneración del Disco Intervertebral/sangre , Desplazamiento del Disco Intervertebral/inmunología , Dolor de la Región Lumbar/etiología , Ciática/inmunología
3.
Zhonghua Jie He He Hu Xi Za Zhi ; 43(3): 203-208, 2020 Mar 12.
Artículo en Chino | MEDLINE | ID: mdl-32164089

RESUMEN

Objective: To analyze the clinical characteristics of 2019 novel coronavirus (2019-nCoV) pneumonia and to investigate the correlation between serum inflammatory cytokines and severity of the disease. Methods: 29 patients with 2019-ncov admitted to the isolation ward of Tongji hospital affiliated to Tongji medical college of Huazhong University of Science and Technology in January 2020 were selected as the study subjects. Clinical data were collected and the general information, clinical symptoms, blood test and CT imaging characteristics were analyzed. According to the relevant diagnostic criteria, the patients were divided into three groups: mild (15 cases), severe (9 cases) and critical (5 cases). The expression levels of inflammatory cytokines and other markers in the serum of each group were detected, and the changes of these indicators of the three groups were compared and analyzed, as well as their relationship with the clinical classification of the disease. Results: (1) The main symptoms of 2019-nCoV pneumonia was fever (28/29) with or without respiratory and other systemic symptoms. Two patients died with underlying disease and co-bacterial infection, respectively. (2) The blood test of the patients showed normal or decreased white blood cell count (23/29), decreased lymphocyte count (20/29), increased hypersensitive C reactive protein (hs-CRP) (27/29), and normal procalcitonin. In most patients, serum lactate dehydrogenase (LDH) was significantly increased (20/29), while albumin was decreased (15/29). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Tbil), serum creatinine (Scr) and other items showed no significant changes. (3) CT findings of typical cases were single or multiple patchy ground glass shadows accompanied by septal thickening. When the disease progresses, the lesion increases and the scope expands, and the ground glass shadow coexists with the solid shadow or the stripe shadow. (4) There were statistically significant differences in the expression levels of interleukin-2 receptor (IL-2R) and IL-6 in the serum of the three groups (P<0.05), among which the critical group was higher than the severe group and the severe group was higher than the mild group. However, there were no statistically significant differences in serum levels of tumor necrosis factor-alpha (TNF-α), IL-1, IL-8, IL-10, hs-CRP, lymphocyte count and LDH among the three groups (P>0.05). Conclusion: The clinical characteristics of 2019-nCoV pneumonia are similar to those of common viral pneumonia. High resolution CT is of great value in the differential diagnosis of this disease. The increased expression of IL-2R and IL-6 in serum is expected to predict the severity of the 2019-nCoV pneumonia and the prognosis of patients.


Asunto(s)
Betacoronavirus/aislamiento & purificación , Biomarcadores , Infecciones por Coronavirus/diagnóstico , Interleucina-6/metabolismo , Neumonía Viral/diagnóstico , Receptores de Interleucina-2/metabolismo , Biomarcadores/sangre , Infecciones por Coronavirus/metabolismo , Citocinas/sangre , Humanos , Pulmón/diagnóstico por imagen , Neumonía Viral/metabolismo , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X
4.
Exp Parasitol ; 210: 107846, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32001303

RESUMEN

Leishmaniasis is a neglected disease caused by an intracellular protozoan parasite of the genus Leishmania. Infection starts when this protozoan replicates in a phagolysosomal compartment in macrophages, after evading host immune responses. The balance of Th1 and Th2 immune responses is crucial in leishmaniasis because it will determine whether the infection will be under control or if clinical complications will occur. The inflammasome, which is activated during Leishmania infection, involves the action of caspase-1 and release of the proinflammatory cytokines interleukin-1ß and interleukin-18. Together, they contribute to the maintenance of an inflammatory response and pyroptosis. Here, we evaluated the serum levels of cytokines and the expression of circulating microRNAs related to inflammasome regulation in twenty-seven patients with cutaneous leishmaniasis in comparison to nine healthy individuals, in the context of the inflammasome activation. Evaluation of serum cytokines activation (IL-1ß, IL-2, IL-4, IL-6, IL-10, and IL-17) was performed by flow cytometry using CBA kits (cytometric beads array) while the expression of circulating microRNAs (miR-7, miR-133a, miR-146b, miR-155, miR-223, miR-328, and miR-342) in plasma was measured by quantitative polymerase chain reaction. Our results showed an increase of the expression of miR-7-5p (p < 10-5), miR-133a (p = 0.034), miR-146b (p = 0.003), miR-223-3p (p = 10-5), and miR-328-3p (p = 0.002), and cytokine levels for IL-1ß (p = 0.0005), IL-6 (p = 0.001), and IL-17 (p = 0.001) in patients with cutaneous leishmaniasis compared to the controls. These results suggest that microRNAs and cytokines can play an important role in regulating the human immune responses to Leishmania infection. Our findings may contribute to the understanding of the mechanisms of the gene regulation during the cutaneous leishmaniasis and to the identification of possible biomarkers of the infection.


Asunto(s)
Citocinas/sangre , Inflamasomas/genética , Leishmaniasis Cutánea/genética , MicroARNs/fisiología , Adulto , Anciano , Brasil , Estudios de Casos y Controles , Biología Computacional , Femenino , Humanos , Inflamasomas/inmunología , Interleucina-17/sangre , Interleucina-1beta/sangre , Interleucina-6/sangre , Leishmaniasis Cutánea/sangre , Leishmaniasis Cutánea/inmunología , Masculino , MicroARNs/sangre , MicroARNs/genética , Persona de Mediana Edad , Población Rural , Población Urbana , Adulto Joven
5.
Life Sci ; 245: 117353, 2020 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-31987873

RESUMEN

AIMS: Present study was conducted to optimize the processing parameters for galactooligosaccharides (GOS) synthesis from whey powder followed by exploring its prebiotic efficiency. MAIN METHODS: All factors (initial lactose concentration, pH, reaction time, temperature and enzyme to substrate ratio; E/S) were analyzed by single factor analysis and optimization for GOS yield was done following the orthogonal experimental design. For in vivo analysis, 60 mice were equally divided into four groups (normal control, NC; low, medium, and high dose of GOS, LG, MG and HG) and fed varying levels (0, 0.25, 0.5 and 1.0 g/kg bw per day) of GOS, for 30 days and sampling was done at the end of experiment regarding gut health, immunity, cecal microbiota and metabolites. KEY FINDINGS: Optimum yield of GOS (25.1%) was obtained at reaction time 25 min, temperature 50 °C, pH 4.5 and the enzyme to substrate ratio (E/S) of 20 U/g. In vivo experiment, shallower crypt and greater villus to crypt ratio (V/C) were found in the duodenum of LG treatment compared to NC mice (P < .05). The GOS promotes thymus development and improve immunity. Intervention with GOS increased the population of bifidobacterium and lactobacillus in MG and bifidobacterium in LG mice (P < .05), and was accompanied by decreased proliferation of desulfovibrio. Correlation analysis also supported the above findings. SIGNIFICANCE: This study optimized the processing parameters for GOS preparation and provided data encouraging to suggest that GOS can be a potential option to improve the gut health and immunity.


Asunto(s)
Galactosa/metabolismo , Mucosa Intestinal/metabolismo , Oligosacáridos/metabolismo , Animales , Ciego/metabolismo , Ciego/microbiología , Cromatografía Líquida de Alta Presión , Citocinas/sangre , Microbioma Gastrointestinal , Concentración de Iones de Hidrógeno , Mucosa Intestinal/anatomía & histología , Mucosa Intestinal/inmunología , Lactosa/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Oligosacáridos/análisis , Reacción en Cadena en Tiempo Real de la Polimerasa , Temperatura Ambiental
6.
mSphere ; 5(1)2020 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-31996423

RESUMEN

Acute liver failure is a severe liver disorder that poses considerable global challenges. Previous studies on Bifidobacterium longum R0175 have mainly focused on its psychotropic functions. The current research focused on the protective efficacy of B. longum R0175 against acute liver failure caused by d-galactosamine (d-GalN) in rats and further tested the hypothesis that B. longum R0175 exerted liver-protective effects by affecting the intestinal microbiota and fecal metabolites and by inhibiting inflammation. We found that oral gavage of B. longum R0175 markedly reduced the severity of liver injury in d-GalN-treated rats, as evidenced by decreased serum levels of aspartate aminotransferase (AST) and total bile acids (TBAs) (P < 0.05). Moreover, the plasma concentrations of proinflammatory cytokines (interleukin 1ß [IL-1ß] and tumor necrosis factor-α [TNF-α]) and chemokines (granulocyte-macrophage colony-stimulating factor [GM-CSF], macrophage chemoattractant protein 1 [MCP-1], chemokine [C-X-C motif] ligand 1 [CXCL1], chemokine [C-C motif] ligand 5 [CCL5], and macrophage inflammatory protein-1α [MIP-1α]) were also markedly reduced (P < 0.05). Pretreatment with B. longum R0175 partially reversed the gut microbiota dysbiosis in rats with liver injury by increasing the relative abundances of potentially beneficial bacteria, such as Alloprevotella spp., and decreasing the relative abundances of potentially harmful bacteria, such as Acetatifactor muris, Butyricimonas spp., and Oscillibacter spp. Furthermore, B. longum R0175 administration partially improved the metabolic function of the intestinal microbes, as indicated by the decreased level of lithocholic acid found in the feces.IMPORTANCE Our research investigated the protective and preventive roles of B. longum R0175 in a rat model of acute liver failure. The results illustrated that this probiotic strain exhibited protective effects in rats with acute liver failure. Thus, B. longum R0175 showed clinical application prospects that required further exploration.


Asunto(s)
Bifidobacterium longum , Enfermedad Hepática Inducida por Sustancias y Drogas/terapia , Probióticos/uso terapéutico , Animales , Aspartato Aminotransferasas/sangre , Ácidos y Sales Biliares/sangre , Quimiocinas/sangre , Citocinas/sangre , Disbiosis , Galactosamina , Microbioma Gastrointestinal , Masculino , Ratas , Ratas Sprague-Dawley
7.
Nat Commun ; 11(1): 557, 2020 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-31992699

RESUMEN

Hydrogen sulfide (H2S) is involved in numerous pathophysiological processes and shares overlapping functions with CO and •NO. However, the importance of host-derived H2S in microbial pathogenesis is unknown. Here we show that Mtb-infected mice deficient in the H2S-producing enzyme cystathionine ß-synthase (CBS) survive longer with reduced organ burden, and that pharmacological inhibition of CBS reduces Mtb bacillary load in mice. High-resolution respirometry, transcriptomics and mass spectrometry establish that H2S stimulates Mtb respiration and bioenergetics predominantly via cytochrome bd oxidase, and that H2S reverses •NO-mediated inhibition of Mtb respiration. Further, exposure of Mtb to H2S regulates genes involved in sulfur and copper metabolism and the Dos regulon. Our results indicate that Mtb exploits host-derived H2S to promote growth and disease, and suggest that host-directed therapies targeting H2S production may be potentially useful for the management of tuberculosis and other microbial infections.


Asunto(s)
Sulfuro de Hidrógeno/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/metabolismo , Mycobacterium tuberculosis/patogenicidad , Animales , Cobre/metabolismo , Cistationina betasintasa/genética , Cistationina betasintasa/metabolismo , Citocinas/sangre , Modelos Animales de Enfermedad , Complejo IV de Transporte de Electrones/metabolismo , Metabolismo Energético , Femenino , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Homeostasis , Pulmón/patología , Macrófagos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mycobacterium tuberculosis/genética , Células RAW 264.7 , Regulón , Azufre/metabolismo , Transcriptoma , Tuberculosis
8.
Food Chem Toxicol ; 135: 110922, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31669599

RESUMEN

Anthocyanins are natural bioactive compounds that have several health benefits. This systematic review and meta-analysis assessed the impact of dietary anthocyanins on markers of systemic and vascular inflammation. Meta-analysis of 32 randomised controlled trials indicated that dietary anthocyanins significantly decreased levels of C-reactive protein (CRP; -0.33 mg/l, 95% CI: -0.55 to -0.11, P = 0.003), interleukin-6 (IL-6; -0.41 ρg/ml, 95% CI: -0.70 to -0.13, P = 0.004), tumor necrosis factor-alpha (TNF-α; -0.64 ρg/ml, 95% CI: -1.18 to -0.09, P = 0.023), intercellular adhesion molecule-1 (-52.4 ng/ml, 95% CI: -85.7 to -19.1, P = 0.002), and vascular adhesion molecule-1 (VCAM-1; -49.6 ng/ml, 95% CI: -72.7 to -26.5, P < 0.001) while adiponectin level was significantly increased (0.75 µg/ml, 95% CI: 0.23 to 1.26, P = 0.004). The levels of interleukin-1ß (IL-1ß; -0.45 ρg/ml, 95% CI: -3.77 to 2.88, P = 0.793) and P-selectin (-6.98 ng/ml, 95% CI: -18.1 to 4.15, P = 0.219) did not significantly change. Subgroup analyses showed that administration of higher doses of anthocyanins (>300 mg/day) significantly decreased levels of CRP, IL-6, TNF-α, and VCAM-1. The results indicate that dietary anthocyanins reduce the levels of systemic and vascular inflammation in the subjects.


Asunto(s)
Antocianinas/farmacología , Ensayos Clínicos como Asunto/estadística & datos numéricos , Inflamación/dietoterapia , Adiponectina/sangre , Adiponectina/metabolismo , Animales , Biomarcadores/sangre , Biomarcadores/metabolismo , Citocinas/sangre , Citocinas/metabolismo , Humanos , Inflamación/metabolismo
9.
Int J Infect Dis ; 90: 104-110, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31678190

RESUMEN

OBJECTIVE: To evaluate the clinical, laboratory, and immune characteristics of Zika virus (ZIKV)-associated encephalitis in pediatric patients after the epidemic in Huila, southern Colombia. METHODS: A pediatric neuro-surveillance hospital study was conducted in a referral health center in southern Colombia, from October 2016 to October 2017. Cases of encephalitis were confirmed by nucleic acid amplification tests and serological methods in cerebrospinal fluid (CSF), plasma, and/or urine. Levels of six cytokines were evaluated by flow cytometry. Patients underwent daily clinical and laboratory follow-up. RESULTS: Twenty children with probable encephalitis were included for further studies and 16 of them were confirmed. Four cases of bacterial meningoencephalitis (Streptococcus pneumoniae, group B Streptococcus, Staphylococcus epidermidis, and Escherichia coli) and 12 cases of viral encephalitis were identified, six of them associated with ZIKV infection. Other viral encephalitis cases were caused by herpes viruses (n=3), enterovirus (n=2), and dengue virus type 2 (DENV-2; n=1) infections. ZIKV-associated encephalitis symptoms subsided faster than those of patients with encephalitis caused by other agents. CSF analysis revealed lymphocytic pleocytosis. Compared to healthy controls, children with ZIKV-associated encephalitis presented modest plasma interleukin (IL)-10 but not IL-2, IL-4, IL-6, interferon gamma (IFN-γ), or tumor necrosis factor alpha (TNF-α). Cytokine expression was differentially regulated, as dramatically elevated IL-6, IL-10, and IFN-γ levels were observed in CSF but not in paired plasma samples in one of the patients with ZIKV detectable in CSF. CONCLUSIONS: This study provides evidence that ZIKV is responsible for pediatric encephalitis in endemic areas, and the local presence of the virus may induce cephalic but not systemic expression of cytokines.


Asunto(s)
Encefalitis Viral/virología , Infección por el Virus Zika/virología , Adolescente , Niño , Preescolar , Colombia , Citocinas/sangre , Citocinas/líquido cefalorraquídeo , Encefalitis Viral/diagnóstico , Encefalitis Viral/inmunología , Femenino , Humanos , Lactante , Interferón gamma/sangre , Interferón gamma/líquido cefalorraquídeo , Masculino , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/líquido cefalorraquídeo , Virus Zika/aislamiento & purificación , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/inmunología
10.
Int J Radiat Oncol Biol Phys ; 106(2): 349-357, 2020 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-31678224

RESUMEN

PURPOSE: NCT01725165 was a phase II prospective trial in which patients with non-small cell lung cancer were randomized to local consolidative therapy (LCT) versus maintenance therapy or observation (MT/O). METHODS AND MATERIALS: Peripheral blood from patients enrolled on NCT01725165 were labeled as (1) baseline, (2) early follow-up (FU) if obtained in the first or second FU evaluation (6-18 weeks), and (3) late FU if obtained in the third to sixth FU evaluations (22-50 weeks). All patients who underwent LCT and were included in this analysis received radiation. Among 49 randomized patients, 21 patients underwent T cell CDR3 variable region sequencing using immunoSEQ, 31 patients underwent circulating tumor DNA (ctDNA) analysis using next-generation sequencing with a 1021 cancer gene panel, and cytokine concentration was assayed in 19 patients using enzyme-linked immunosorbent assay. All analyses were exploratory and not corrected for multiple testing. RESULTS: No associations were identified between baseline T cell repertoire and ctDNA metrics with patient outcomes. Among baseline cytokines, interleukin 1α was the only cytokine associated with both overall survival (hazard ratio, 0.02; 95% confidence interval, 0.1-0.5; P = .0006) and progression-free survival (hazard ratio, 0.5; 95% confidence interval, 0.2-0.9; P = .03). At early FU, LCT was associated with decreased ctDNA burden, including lower number of detected mutations (median, 2 [interquartile range {IQR}, 1-6] vs 6 [IQR, 4-18]) and decreased average variable allele frequency (VAF; median, 0.006 [IQR, 0.003-0.010] vs 0.011 [IQR, 0.007-0.014]) compared with MT/O. Among 6 patients with serial ctDNA analysis, a rise in ctDNA detected mutation burden preceded clinical progression by 6.7 months. At early FU, LCT was associated with changes in T cell clonality that suggested oligoclonal expansion specifically increased T cell clonality (median, 0.15 [IQR, 0.12-0.24] vs 0.10 [IQR, 0.05-0.13]) and frequency of top 10 clones (median, 0.14 [IQR, 0.06-0.18] vs 0.21[IQR, 0.19-0.28]). CONCLUSION: LCT was associated with decreased ctDNA burden and oligoclonal expansion at early FU timepoints. Baseline interleukin 1α was associated with improved patient outcomes.


Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , ADN Tumoral Circulante/sangre , Citocinas/sangre , Neoplasias Pulmonares/radioterapia , Alelos , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/inmunología , ADN Tumoral Circulante/genética , Dermatoglifia del ADN , Ensayo de Inmunoadsorción Enzimática , Estudios de Seguimiento , Perfilación de la Expresión Génica/métodos , Reordenamiento Génico de la Cadena beta de los Receptores de Antígenos de los Linfocitos T/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Mutación , Supervivencia sin Progresión , Estudios Prospectivos , Linfocitos T/citología , Linfocitos T/inmunología , Linfocitos T/efectos de la radiación , Factores de Tiempo , Investigación en Medicina Traslacional , Espera Vigilante
11.
Int Arch Allergy Immunol ; 181(1): 71-80, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31722337

RESUMEN

BACKGROUND: Few studies have directly compared the immunologic responses to specific subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). OBJECTIVE: We aimed to directly compare clinical efficacy and immunological responses between SLIT and SCIT in allergic rhinitis (AR) sensitized to house dust mites. METHODS: Sixty-seven patients (age 5-55 years) with moderate-severe Dermatophagoides pteronyssinus (Der-p) and Dermatophagoides farinae AR with or without asthma were randomized (2:2:1) into SLIT (n = 27), SCIT (n = 26) and placebo (n = 14) groups. Symptom and medication scores, visual analogue score, serum Der-p specific immunoglobulin G4 (Der-p-sIgG4), CD4+CD25+FoxP3+ regulatory T cells (Tregs) and serum cytokines were measured. RESULTS: After 1-year treatment, a significant improvement of total rhinitis score (TRS), total rhinitis medication score (TRMS) and visual analogue score occurred in both SLIT and SCIT. There were no differences in clinical efficacy except for TRMS (p = 0.026) when SLIT and SCIT were directly compared. CD4+CD25+FoxP3+ Tregs had a trend towards upregulation in the 2 modes and inversely correlated with TRS (p = 0.024) only in SLIT. Der-p-sIgG4 significantly increased in SLIT and SCIT (p < 0.05), and it was 30 times higher in SCIT than SLIT after the treatment (p < 0.05). Serum interferon-γ significantly increased only in SCIT after 1 (p = 0.008), 6 (p = 0.007) and 12 (p = 0.008) months of treatment and inversely correlated with TRS (p = 0.032). CONCLUSION: While SCIT and SLIT have similar rates of clinical improvement, the 2 modes reveal heterogeneous changes of CD4+CD25+Foxp3+ Tregs, sIgG4 and cytokines.


Asunto(s)
Asma/terapia , Citocinas/sangre , Rinitis Alérgica/terapia , Inmunoterapia Sublingual/métodos , Linfocitos T Reguladores/inmunología , Adolescente , Adulto , Antígenos Dermatofagoides/inmunología , Asma/complicaciones , Asma/inmunología , Antígenos CD4/metabolismo , Niño , Preescolar , Estudios Controlados Antes y Después , Femenino , Factores de Transcripción Forkhead/metabolismo , Humanos , Infusiones Subcutáneas , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Masculino , Persona de Mediana Edad , Rinitis Alérgica/complicaciones , Rinitis Alérgica/inmunología , Adulto Joven
12.
Life Sci ; 241: 117115, 2020 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-31790685

RESUMEN

AIMS: Psoriasis is a cutaneous disease mainly characterized by keratinocyte hyperproliferation, abnormal epidermal differentiation, inflammation and angiogenesis. In this study, we aimed to report the therapeutic potential of Diosgenin on psoriasis-like models and explore the underlying mechanisms. MAIN METHODS: For in vitro studies, we initially evaluated the bioeffects of Diosgenin on keratinocytes by detecting the cell viability, cell cycle and apoptosis in HaCaT cells. To mimic psoriatic conditions, we established hyperproliferative model by stimulating HaCaT cells with LPS/IL-22 and inflammatory model by LPS/TNF-α stimulation. Meanwhile, differentiation in HaCaT cells and angiogenesis in HUVECs/HMEC-1 were observed. The influence of Diosgenin on above-mentioned conditions was examined. For in vivo studies, we dosed imiquimod (IMQ) -induced mice with Diosgenin and conducted hematoxylin-eosin (HE), TUNEL assay and immunohistochemistry (IHC) to evaluate histological changes, apoptosis and the status of keratinocyte proliferation, epidermal differentiation, vascularity and cutaneous inflammatory cell infiltration respectively. KEY FINDINGS: Results showed that Diosgenin inhibited HaCaT cell growth through cell cycle arrest and NFκB inhibition while induced apoptosis by regulating Caspase3, Bax and Bcl-2 protein expression. After Diosgenin treatment, NFκB nuclear translocation and IL-22 receptor dependent pathways were suppressed in LPS/IL-22 induced HaCaT cells respectively. Furthermore, Diosgenin downregulated proinflammatory cytokines through TLR4/Myd88 inhibition and upregulated several differentiation markers' expression in HaCaT cells. Additionally, Diosgenin inhibited vascular formation partially by reducing the VEGF-α expression in keratinocytes. In animal studies, Diosgenin attenuated psoriatic lesions on mice accordingly. SIGNIFICANCE: This study suggests that Diosgenin might be a promising candidate for developing anti-psoriatic agents.


Asunto(s)
Diosgenina/farmacología , Queratinocitos/efectos de los fármacos , Psoriasis/tratamiento farmacológico , Inhibidores de la Angiogénesis/farmacología , Animales , Apoptosis/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Citocinas/sangre , Diosgenina/efectos adversos , Modelos Animales de Enfermedad , Femenino , Células Endoteliales de la Vena Umbilical Humana , Humanos , Imiquimod/toxicidad , Queratinocitos/metabolismo , Queratinocitos/patología , Ratones Endogámicos BALB C , FN-kappa B/metabolismo , Psoriasis/inducido químicamente , Psoriasis/patología , Receptores de Interleucina/metabolismo
13.
Scand J Immunol ; 91(1): e12839, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31630416

RESUMEN

The humanized IgG1κ monoclonal antibody siplizumab and its rat parent monoclonal IgG2b antibody BTI-322 are directed against the CD2 antigen. Siplizumab is species-specific, reacting with human and chimpanzee cells but not with cells from any other species, including other non-human primates. Because siplizumab treatment has recently shown great potential in clinical transplantation, we now present the results of our previous pharmacokinetic, pharmacodynamic and safety studies of both antibodies. Fourteen chimpanzees received 1-3 doses of 0.143 to 5.0 mg/kg iv The effects were followed with flow cytometry on peripheral lymphocytes and staining of lymph nodes. Side effects were recorded. Serum antibody concentrations were followed. Across the doses, a rapid, transient depletion of CD2, CD3, CD4 and CD8 lymphocytes and NK cells was observed for both antibodies. Immune reconstitution was more rapid for BTI-322 compared to siplizumab. Paracortical lymph node T cell depletion was moderate, estimated at 45% with doses of >0.6 mg/kg. Restoration of lymph node architecture was seen after two weeks to two months for all animals. All four subjects receiving BTI-322 experienced AEs on the first dosing day, while the eight subjects dosed with siplizumab experienced few mild, transient AEs. Infusion with siplizumab and BTI-322 resulted in rapid depletion of CD2+ cells in circulation and tissue. Siplizumab had a longer t1/2 and fewer AEs compared to BTI-322.


Asunto(s)
Anticuerpos Monoclonales/farmacocinética , Antígenos CD2/antagonistas & inhibidores , Animales , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/farmacocinética , Anticuerpos Monoclonales Humanizados/uso terapéutico , Biomarcadores , Biopsia , Citocinas/sangre , Femenino , Inmunoglobulina G/administración & dosificación , Inmunoglobulina G/farmacología , Inmunofenotipificación , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Depleción Linfocítica , Linfocitos/inmunología , Linfocitos/metabolismo , Masculino , Pan troglodytes , Ratas
14.
J Biochem Mol Toxicol ; 34(2): e22431, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31833131

RESUMEN

Cisplatin-induced nephrotoxicity persists as a clinical problem despite several supportive measures to alleviate renal damage. Daidzein (DZ), a dietary isoflavone having antioxidant and anti-inflammatory activity, is investigated in this study for protective effects against cisplatin-induced renal injury in rats. DZ (25, 50, or 100 mg/kg; intraperitoneally; 10 days) was administered along with Cisplatin, single dose, on the 7th day of the experiment. On the 11th day, the rats were euthanized, and different samples were collected for analysis. Biochemical, histopathological, and molecular parameters were assessed to evaluate the effect of daidzein. Cisplatin injection resulted in renal dysfunction, lipid peroxidation that led to consumption of antioxidants, exaggerated apoptosis, and inflammation. These changes were associated with increase in the signaling proteins. DZ attenuated the toxic effects of cisplatin on the kidney at 100 mg/kg dose. The study concludes with the finding that daidzein imparts protection against the nephrotoxic effect of Cisplatin and can be considered as a novel, potential therapy.


Asunto(s)
Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/dietoterapia , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Apoptosis/efectos de los fármacos , Cisplatino/farmacología , Isoflavonas/uso terapéutico , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Nefritis/dietoterapia , Estrés Oxidativo/efectos de los fármacos , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Antioxidantes/administración & dosificación , Antioxidantes/farmacología , Cisplatino/efectos adversos , Citocinas/sangre , Isoflavonas/administración & dosificación , Isoflavonas/farmacología , Riñón/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Masculino , Ratas , Resultado del Tratamiento
15.
Aquat Toxicol ; 218: 105362, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31783303

RESUMEN

Nitrite is a major environmental pollutant in aquatic environments that negatively affects aquatic species. In this study, we investigated the impact of nitrite exposure on plasma biochemical parameters and immune responses in Takifugu rubripes. Fish were exposed to various concentrations of nitrite (0, 0.5, 1, 3, and 6 mM) for 96 h. After 0, 12, 24, 48, and 96 h of exposure, fish blood samples were collected to assay the levels of total protein (TP), albumin (Alb), glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (ALT), complement C3 (C3), complement C4 (C4), immunoglobulin (IgM), and lysozyme activity (LZM). The gills were sampled to analyze the mRNA levels of heat shock protein 70 (hsp70), heat shock protein 90 (hsp90), tumor necrosis factor α (tnf-α), B-cell activating factor (baff), interleukin-6 (il-6), and interleukin-12 (il-12). Levels of GOT, ALT, C3, and C4 were significantly enhanced in the high nitrite concentration group (3 and 6 mM), whereas those of TP, Alb, LZM, and IgM decreased significantly with the same treatments. Nitrite significantly upregulated hsp70, hsp90, tnf-α, il-6, il-12, and baff mRNA levels after 96 h of exposure. These results indicated that nitrite exposure altered the blood physiological status and immune system response, resulting in dysfunction and immunotoxicity in T. rubripes. Furthermore, our results reveal the possible mechanism of aquatic-nitrite-induced toxicity in fish.


Asunto(s)
Citocinas/sangre , Proteínas de Peces/sangre , Inmunidad Humoral/efectos de los fármacos , Nitritos/toxicidad , Takifugu , Contaminantes Químicos del Agua/toxicidad , Animales , Citocinas/genética , Proteínas de Peces/genética , Branquias/efectos de los fármacos , Branquias/metabolismo , Takifugu/sangre , Takifugu/inmunología , Transcripción Genética/efectos de los fármacos
16.
Parasitol Int ; 74: 101918, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31004803

RESUMEN

The relationship between the cellular immune response during Trichuris trichiura infection and asthma has not yet been established. In this study, the cytokines interleukin (IL)-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL-17A were evaluated in asthmatic children harboring T. trichiura. For this assessment, asthmatic and non-asthmatic children (ISAAC questionnaire) were submitted to parasitological tests and blood samples were cultured (mitogen stimulation) for cytokine measurements in the supernatant. Asthma frequencies were similar in infected and uninfected children, but IL-4, IL-6, TNF-α and IL-10 levels were high in the infected asthmatic children. Additionally, infected non-asthmatic children exhibited high levels of these cytokines in relation to uninfected non-asthmatic children; however, cytokine levels were lower when compared with infected and asthmatic children. Therefore, T. trichiura infection positively modulated the pro- and anti-inflammatory cytokines in asthmatic children, but a background of asthma seemed to narrow the production of cytokines induced by this helminth.


Asunto(s)
Asma/parasitología , Citocinas/sangre , Tricuriasis/inmunología , Animales , Asma/inmunología , Brasil , Niño , Preescolar , Citocinas/inmunología , Femenino , Humanos , Hipersensibilidad/inmunología , Hipersensibilidad/parasitología , Inmunidad Celular , Masculino , Trichuris
17.
J Surg Res ; 245: 441-452, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31445496

RESUMEN

BACKGROUND: Whitmania pigra Whitman (W pigra), a traditional Chinese medicine, has functions of breaking stagnant and eliminating blood stasis. The aim of this study was to investigate the underlying mechanism of W pigra against deep vein thrombosis (DVT). METHODS: A rat model of DVT induced by inferior vena cava stenosis was successfully established. Rats were administered vehicle (saline solution, p.o.), three doses of W pigra aqueous extract (34.7, 104.2, or 312.5 mg crude W pigra/kg, p.o.), heparin (200 U/kg, i.v.), or clopidogrel (25 mg/kg, p.o.) once daily for 2 d. Thrombus weight and histopathological changes were examined. Blood samples were collected to determine blood cell counts, blood viscosity, blood coagulation, blood fibrinolysis, serum levels of interleukin-1ß, and tumor necrosis factor-α. Protein expressions of Sirtuin1 (SIRT1), acetylated p65 (Ace-p65), and phosphorylated p65 (p-p65) were determined by Western blot. Furthermore, SIRT1-specific inhibitor EX527 was applied to confirm the role of SIRT1 in the antithrombotic effect of W pigra. RESULTS: W pigra significantly decreased thrombus weight. W pigra had no effects on blood cell counts, whole blood viscosity, blood coagulation, blood fibrinolysis. However, it reduced tissue factor protein expression in the vein wall and thrombus. Moreover, it sharply increased SIRT1 protein expression and decreased leukocytes recruitment in the thrombus and vein wall, serum levels of interleukin-1ß and tumor necrosis factor-α, and protein expressions of Ace-p65 and p-p65. Furthermore, the antithrombotic effect of W pigra was significantly abolished by EX527. CONCLUSIONS: Aqueous extract of W pigra effectively reduced DVT burden by inhibiting inflammation via SIRT1/nuclear factor-kappa B signaling pathway.


Asunto(s)
Productos Biológicos/uso terapéutico , Sanguijuelas , FN-kappa B/metabolismo , Sirtuina 1/metabolismo , Trombosis de la Vena/tratamiento farmacológico , Animales , Productos Biológicos/farmacología , Carbazoles , Citocinas/sangre , Evaluación Preclínica de Medicamentos , Femenino , Inflamación/tratamiento farmacológico , Masculino , Medicina China Tradicional , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Sirtuina 1/antagonistas & inhibidores , Tromboplastina/metabolismo , Trombosis de la Vena/metabolismo
18.
Environ Toxicol ; 35(1): 37-46, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31456356

RESUMEN

Phenanthrene (Phe) female rat model was established to explore the effects of Phe on oxidative stress and inflammation. The rats were randomly divided into three groups including control (C), low (L), and high (H) group. Phe was supplied to L and H groups at the dosage of 180 mg/kg and 900 mg/kg orally at first day, and with the dose 90 mg/kg and 450 mg/kg by intraperitoneal injection at the last 2 days. The C group was enriched with the same volume of corn oil. The blood, lung, and liver tissues were collected. The superoxide dismutase (SOD), malonaldehyde (MDA), and 8-hydroxy-2-deoxyguanosine (8-OHdG) were detected to evaluate oxidative stress. The protein and mRNA expressions of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), transforming growth factor-ß (TGF-ß), and interleukin 10 (IL-10) were detected to evaluate inflammation. Further, the forkhead box transcription factor 3 (Foxp3) was analyzed to hint the injury mechanism of inflammation. The results showed SOD and MDA in lung and liver, and serum 8-OHdG elevated significantly in H groups (P < .05). Meanwhile, there were significant increases in the protein and mRNA expression of TNF-α and IL-6 in lung and liver of H groups (P < .05). In addition, the protein and mRNA expressions of TGF-ß and Foxp3 were all decreased significantly in both lung and liver of H groups (P < .05). Results demonstrated that an obvious change of Phe exposure could induce oxidative stress and inflammation in female rats. This is a first pilot study to explore the association between Phe exposure and oxidative stress and inflammation using a female rat model.


Asunto(s)
Contaminantes Atmosféricos/toxicidad , Hígado/efectos de los fármacos , Pulmón/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/inmunología , Fenantrenos/toxicidad , Animales , Citocinas/sangre , Citocinas/inmunología , Relación Dosis-Respuesta a Droga , Femenino , Hígado/inmunología , Hígado/metabolismo , Pulmón/inmunología , Pulmón/metabolismo , Masculino , Proyectos Piloto , Distribución Aleatoria , Ratas , Ratas Wistar
19.
J Appl Microbiol ; 128(1): 74-87, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31574195

RESUMEN

AIMS: Porcine circovirus type 2 (PCV2) can cause postweaning, multisystemic wasting syndrome in pigs, which leads to enormous losses in the swine industry worldwide. Here, a genetically engineered Lactococcus strain expressing the main protective antigen of PCV2, the Cap protein, was developed to act against PCV2 infection as an oral vaccine. METHODS AND RESULTS: Expression of the Cap protein was confirmed via western blot, ELISA and fluorescence microscopy. Over 90% of the recombinant pAMJ399-Cap/MG1363 survived a simulated gastrointestinal transit. It also survived the murine intestinal tract for at least 11 days. Then, the safety and immunogenicity of pAMJ399-Cap/MG1363 in orally immunized mice was evaluated. The levels of the sIgA, IgG and cytokines (IL-4 and IFN-γ) obtained from the mice immunized with pAMJ399-Cap/MG1363 were significantly higher than those in the control groups. CONCLUSIONS: pAMJ399-Cap/MG1363 can survive in the gastrointestinal transit and effectively induce mucosal, cellular and humoral immune response against PCV2 infection via oral administration. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates the potential of the genetically engineered Lactococcus lactis as a candidate for an oral vaccine against PCV2.


Asunto(s)
Proteínas de la Cápside/inmunología , Circovirus/inmunología , Lactococcus lactis/inmunología , Vacunas Virales/inmunología , Animales , Anticuerpos Antivirales/inmunología , Proteínas de la Cápside/genética , Citocinas/sangre , Inmunogenicidad Vacunal , Lactococcus lactis/genética , Ratones , Vacunación , Vacunas Virales/administración & dosificación
20.
Int J Cancer ; 146(1): 223-235, 2020 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-31444972

RESUMEN

Angiogenesis is necessary for tumor growth and has been targeted in breast cancer; however, it is unclear which patients will respond and benefit from antiangiogenic therapy. We report noninvasive monitoring of patient response to neoadjuvant chemotherapy given alone or in combination with anti-vascular endothelial growth factor (bevacizumab) in a randomized clinical trial. At four time points during neoadjuvant chemotherapy ± bevacizumab of receptor tyrosine-protein kinase erbB-2-negative breast cancers, we measured metabolites and inflammation-related markers in patient's serum. We report significant changes in the levels of several molecules induced by bevacizumab, the most prominent being an increase in pentraxin 3 (PTX3) and von Willebrand factor (VWF). Serum levels of AXL, VWF and pulmonary and activation-regulated cytokine (PARC/CCL18) reflected response to chemotherapy alone or in combination with bevacizumab. We further analyzed serum cytokines in relation to tumor characteristics such as gene expression, tumor metabolites and tumor infiltrating leukocytes. We found that VWF and growth-differentiation factor 15 tumor mRNA levels correlated with their respective serum protein levels suggesting that these cytokines may be produced by tumors and outflow to the bloodstream while influencing the tumor microenvironment locally. Finally, we used binomial logistic regression which allowed to predict patient's response using only 10 noninvasive biomarkers. Our study highlights the potential of monitoring circulating levels of cytokines and metabolites during breast cancer therapy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante , Mediadores de Inflamación/sangre , Bevacizumab/administración & dosificación , Biomarcadores/metabolismo , Neoplasias de la Mama/sangre , Citocinas/sangre , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante
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