Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 151.347
Filtrar
1.
J Cataract Refract Surg ; 46(3): 331-332, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32142037
2.
Chirurgia (Bucur) ; 115(1): 39-49, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32155398

RESUMEN

Introduction: The inflammatory response plays a critical role in carcinogenesis. There are recent scores based on the systemic inflammatory response, such as neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), which have been shown to have prognostic value in cancer patients. These scores allow the identification of patients who will have poor response to treatment and poor survival. The aim of this study is to evaluate the prognostic role of NLR, PLR, LMR and PNI in terms of long-term survival in patients with colorectal cancer, operated in emergency. Material and Methods: We included 391 patients admitted and operated for complicated colorectal cancer in the Surgery II clinic of the Clinical Emergency County Hospital Sf. Ap. Andrei - from Galati, between 2008-2017. We analyzed the paraclinical factors of systemic inflammation NLR, PLR, MRL and PNI. As prognostic factors, survival curves were analyzed. Results: The high values of NLR and PLR increased the risk of death (HR = 7.581, 95% CI = (6.358,9.039), p value = 0.000000, respectively HR = 1.043, 95% CI = (1.039, 1.047), p value = 0.000000), and the increased values of LMR and PNI led to the decrease of this risk (HR = 0.069, 95% CI = (0.054.0.090), p value = 0.000000, respectively HR = 0.758, 95 % CI = (0.730.0.788), p value = 0.000000). In the multivariate regression analysis, the increase of PLR resulted in an increase in the risk of death (HR = 1.024, 95% CI = (1.019.1.029), p value = 0.000000), and for the LMR and PNI, a reduction of the risk of death (HR = 0.353, 95% CI = (0.248.0.504), p value = 0.000000, respectively HR = 0.852, 95% CI = (0.822.0.883), p value = 0.000000). Conclusions: The univariate analysis showed that NLR and PLR are risk factors, and LMR and PNI are protective factors in terms of survival. The multivariate analysis revealed that PLR is an independent risk factor, and LMR and PNI were independent protection factors.


Asunto(s)
Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/mortalidad , Inflamación/sangre , Recuento de Leucocitos , Recuento de Plaquetas , Biomarcadores/sangre , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Urgencias Médicas , Humanos , Pronóstico
3.
Bratisl Lek Listy ; 121(2): 143-150, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32115968

RESUMEN

OBJECTIVES: This study was aimed to explore the effects of follistatin on cisplatin-induced renal dysfunction, histopathological changes, apoptosis, inflammation and oxidative damage in rats. BACKGROUND: Follistatin plays an important role in the developmental and regeneration processes of kidney by blocking the actions of activin, which is a member of transforming growth factor-ß superfamily. METHODS: Twenty seven rats were separated into 4 equal groups: Control, Cp (cisplatin, 6 mg/kg, intrapertoneally (ip)), F1 (cisplatin + 1 µg/day follistatin ip for 4 consecutive days) and F4 (cisplatin + 4 µg/day follistatin ip single dose) groups. Renal health was monitored by blood urea nitrogen, serum creatinine and histological analysis. Apoptosis, inflammation and oxidative stress was investigated in kidney tissue. Activin A levels in serum and kidney were evaluated as well. RESULTS: Follistatin administration showed a considerable nephroprotective effect against cisplatin-induced nephrotoxicity by preventing renal functional and structural abnormalities, apoptosis and inflammation. The activin A levels in both serum and kidney were also suppressed by follistatin administration. CONCLUSION: Exogenous follistatin ameliorates acute kidney injury, by blocking activin A. The renoprotective effect of follistatin against cisplatin-induced nephrotoxicity appears to be associated with its anti-inflammatory, antiapoptotic and direct nephroprotective actions (Tab. 1, Fig. 7, Ref. 23).


Asunto(s)
Lesión Renal Aguda , Cisplatino , Folistatina , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Cisplatino/efectos adversos , Folistatina/farmacología , Folistatina/uso terapéutico , Inflamación , Riñón , Estrés Oxidativo , Ratas
4.
Bratisl Lek Listy ; 121(2): 154-158, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32115970

RESUMEN

OBJECTIVE: This study aimed to evaluate the effect of Coenzyme Q10 (CoQ10) administration to patients in the early phase of sepsis to determine its effect on the markers of inflammation and the clinical outcomes of septic patients. BACKGROUND: Previous studies showed that CoQ10 levels were decreased in septic patients and worsening of mitochondrial dysfunction was observed. METHODS: In this randomized controlled trial septic patients (n=40) received 100 mg CoQ10 twice a day for seven days added to standard treatment of sepsis. As a primary endpoint levels of Interleukin 6 (IL-6), Tumor Necrosis Factor-α (TNF-α), Glutathione peroxidase and malondialdehyde (MDA) were assessed at baseline, third and 7th day after the intervention. Secondary endpoints included assessment of clinical scores and     in-hospital mortality. RESULTS: There was no difference in baseline inflammatory and oxidative injury markers between the groups. TNF-α and MDA levels decreased significantly in the CoQ10 group on the 7th day of the study (P:0.003 for both). There was a significant difference in the in-hospital mortality in the CoQ10 group compared to the control group (P:0.01). CONCLUSION: These findings suggest that CoQ10 has a positive effect on clinical parameters as well as mitochondrial dysfunction when administered in the early phase of sepsis (Tab. 2, Fig. 1, Ref. 38).


Asunto(s)
Inflamación , Sepsis , Ubiquinona/análogos & derivados , Biomarcadores , Método Doble Ciego , Humanos , Inflamación/tratamiento farmacológico , Malondialdehído , Sepsis/tratamiento farmacológico , Sepsis/inmunología , Ubiquinona/uso terapéutico
5.
Bratisl Lek Listy ; 121(3): 225-229, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32115981

RESUMEN

AIM: Nicotine at high concentrations induces apoptosis in trophoblastic cells through induction of cell cytotoxicity and Reactive Oxygen Species (ROS). Methamphetamine in low dose has pharmaceutical properties. It seems that this components in low dose can protect the trophoblastic cells from nicotine-induced cell death. METHOD: Trophoblastic (JEG-3) cells grown in DMEM culture medium. MTT assay test detected the cell viability and Lactate Dehydrogenase test measured the cells cytotoxicity. Griess reaction was used for NO production analysis. Cell migration traced by wounding technique. Human Cytokine Array Focused 13-plex was also used for analysis of IL-1α, IL-1ß, IL-6, INFγ, and TNFα pre-inflammatory cytokines. RESULTS: Methamphetamine, in very low dose (pM), increased the cell viability and NO production, and decreased cell cytotoxicity, IL-1α, IL-1ß, IL-6, INFγ, and TNFα pre-inflammatory cytokines of JEG-3 cell which were exposed to high dose of nicotine, respectively. Cell migration was enhanced by low dose of methamphetamine in JEG-3 cells. CONCLUSION: Methamphetamine in very low dose suppressed the JEG-3 cell death induced by high dose of nicotine (Fig. 5, Ref. 48) Keywords: methamphetamine, nicotine, cell death, NO.


Asunto(s)
Dopaminérgicos , Inflamación , Metanfetamina , Trofoblastos , Línea Celular Tumoral , Supervivencia Celular , Dopaminérgicos/farmacología , Humanos , Inflamación/tratamiento farmacológico , Metanfetamina/farmacología , Nicotina/toxicidad , Trofoblastos/efectos de los fármacos
6.
Zhen Ci Yan Jiu ; 45(1): 8-13, 2020 Jan 25.
Artículo en Chino | MEDLINE | ID: mdl-32144902

RESUMEN

OBJECTIVE: To investigate the effect of manual acupuncture (MA) and electroacupuncture (EA) on histopathological changes, and levels of oxidative-stress related cytokines and key proteins of the endoplasmic reticulum stress (ERS) pathway in ulcerative colitis (UC) rats, so as to reveal their mechanisms underlying improvement of UC. METHODS: Twenty-eight male SD rats were randomly divided into control, model, EA and MA groups (n= 7 rats per group). The UC model was established by enema of mixture solution of 5% 2, 4, 6-trinitrobenzene sulfonic acid (TNBS, 100 mg/kg). Rats of the control group received intra-rectal perfusion of normal saline. After modeling, the left "Quchi"(LI11) and "Zusanli"(ST36) were stimulated with EA (2-4 mA,8 Hz/25 Hz) or MA for 20 min, once every other day for consecutive 2 weeks. The rats in the control and model group were just anesthetized and fixed. At the end of experiments, the colon tissue was collected for observing histopathological changes with H.E. staining. The contents of oxidative stress-related factors as superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), reduced glutathione (GSH) and total antioxidant capacity (T-AOC) were detected by ELISA, and the expression levels of key proteins of ERS as phosphorylated inhibitor of nuclear factor kappa B kinase α (p-IκBα), phosphorylated p65 (p-p65), glucose regulated protein 78 (GRP78), phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK) and phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α) by using Western blot. RESULTS: After modeling, the colon tissues showed severe swelling, disordered arrangement of intestinal mucosal cells, hemorrhage with infiltration of inflammatory cell and partial loss of colon villus, which was relatively milder in the EA and MA groups. The colonic lesion score was remarkably increased in the model group in contrast to the control group (P<0.01), and obviously reduced in both EA and MA groups relevant to the model group (P<0.01). The levels of SOD, CAT, GSH and T-AOC were all significantly decreased (P<0.01), and the content of MDA, and expression levels of p-IκBα, p-p65 and GRP78, p-PERK and p-eIF2α proteins were all significantly increased in the model group relevant to the control group (P<0.01). After the treatment, modeling-induced down-regulation of SOD, CAT and GSH in both EA and MA groups, and T-AOC in the EA group, and up-regulation of levels of MDA, p-IκBα, p-p65, GRP78, p-PERK and p-eIF2α in both groups were reversed (P<0.01, P<0.05). CONCLUSION: Both EA and MA treatment can obviously alleviate colonic inflammation in UC rats via inhibiting oxidative stress and ERS.


Asunto(s)
Colitis Ulcerosa , Electroacupuntura , Estrés del Retículo Endoplásmico , Estrés Oxidativo , Puntos de Acupuntura , Animales , Inflamación , Masculino , Ratas , Ratas Sprague-Dawley
7.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(1): 68-73, 2020 Jan 28.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-32132300

RESUMEN

The cholinergic anti-inflammatory pathway (CAP) is a neuro-immunomodulatory pathway,in which acetylcholine (ACh) released by the interaction of vagal nerves with α7 nicotinic acetylcholine receptor (α7nAChR),which prevents the synthesis and release of pro-inflammatory cytokines and ultimately regulates the local or systemic inflammatory response in a feedback manner. It has been shown that there are many possible effective treatments for sepsis, including vagus nerve stimulation by physical therapy, drugs such as acetylcholine receptor agonist and ultrasound therapy.


Asunto(s)
Neuroinmunomodulación , Sepsis , Acetilcolina , Humanos , Inflamación , Estimulación del Nervio Vago , Receptor Nicotínico de Acetilcolina alfa 7
8.
Medicine (Baltimore) ; 99(9): e19326, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32118763

RESUMEN

Complete blood count (CBC)-derived parameters such as neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), eosinophil-to-lymphocyte (ELR) ratio, and platelet-to-lymphocyte ratio (PLR) are sensitive markers of occult inflammation and disease activity for systemic lupus erythematosus, rheumatoid arthritis, psoriasis, esophageal cancer, etc. We assessed NLR, PLR, MLR, and ELR as indicators of inflammation in achalasia patients.This cross-sectional study included 103 achalasia patients and 500 healthy blood donor volunteers (HD). Demographic, clinical and laboratory information was collected. NLR, MLR, ELR and PLR were calculated. Peripheral Th22, Th17, Th2 and Th1 subsets were determined by flow cytometry. Correlation between hematologic indices and clinical questionnaires scores, HRM parameters and CD4+ T-cells were assessed. Hematologic parameters associated with the different achalasia subtypes were evaluated by logistic regression analysis.Hemoglobin, leukocytes, lymphocytes, monocytes, and platelets counts were significantly lower in achalasia patients vs controls. NLR (P = .006) and ELR (P < .05) were higher in achalasia patients vs controls. NLR was significantly associated with achalasia in multivariate analysis (P < .001). Compared to HD, the achalasia group was 1.804 times more likely to have higher NLR (95% CI 1.287-2.59; P < .001). GERD-HRQL score had statistically significant correlations with PLR (Pearson's rho:0.318, P = .003), and ELR (Pearson's rho:0.216; P = .044). No correlation between CD4+ T-cells and hematologic indices were determined. NLR with a cut-off value of ≥2.20 and area under the curve of 0.581 yielded a specificity of 80% and sensitivity of 40%, for the diagnosis of achalasia.NLR is increased in achalasia patients vs HD. Sensitivity and specificity achieved by NLR may contribute to a clinical and manometric evaluation. We suggest these indices as potential indicators of silent inflammation and disease activity.


Asunto(s)
Biomarcadores/análisis , Recuento de Células Sanguíneas/métodos , Acalasia del Esófago/complicaciones , Inflamación/diagnóstico , Adulto , Biomarcadores/sangre , Recuento de Células Sanguíneas/tendencias , Estudios Transversales , Acalasia del Esófago/sangre , Femenino , Voluntarios Sanos , Humanos , Inflamación/sangre , Inflamación/fisiopatología , Masculino , México , Persona de Mediana Edad
10.
Chem Biol Interact ; 321: 109031, 2020 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-32142722

RESUMEN

Reactive oxygen species (ROS) is mainly produced as a by-product from electron transport chain (ETC) of mitochondria and effectively eliminated by cellular antioxidants. However, 2-chloroethyl ethyl sulfide (CEES) exposure to keratinocytes declined antioxidant capacity and increased accumulation of ROS triggered alteration of mitochondrial activity and apoptosis is lacking. Our findings demonstrated that the electron leakage from the impaired ETC, leading to the accumulation of ROS was gradually elevating with increasing concentration of CEES exposure, which decline the activity of superoxide dismutase (SOD), manganese SOD (MnSOD) and copper-zinc SOD (Cu-ZnSOD) in keratinocytes. Further, excess accumulation of ROS, decreased the mitochondrial membrane potential (ΔΨm) and increased the mitochondrial mass with increasing dose of CEES. CEES exposure provoked the decrease in expression of transcription factor A mitochondrial (TFAM), augmented mitochondrial DNA (mtDNA) damage and altered the mtDNA-encoded oxidative phosphorylation (OXPHOS) subunits. Moreover, fragmented mtDNA translocated into cytosol, where it activated cGAS-STING and interferon regulatory factor3 (IRF3), coinciding with the increased expression of inflammatory mediators and alteration of cell-to-cell communication markers. Pre-treatment of N-acetyl-l-cysteine (NAC) or L-Nω-nitroarginine methyl ester (NAME), hydralazine hydrochloride (Hyd·HCl) or ERK1/2 or phosphoinositide3-kinase (PI3-K)/Akt inhibitors in keratinocyte cells significantly restored the CEES effect. Our findings suggest that CEES-induced mitochondrial ROS production and accumulation leads to mitochondrial dysfunction and inflammatory response in keratinocytes. However, treatment of antioxidants or ERK1/2 or PI3-K/Akt inhibitors is a novel therapeutic option for the keratinocytes complication.


Asunto(s)
Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Gas Mostaza/análogos & derivados , Especies Reactivas de Oxígeno/metabolismo , Animales , Línea Celular , Sustancias para la Guerra Química/toxicidad , Daño del ADN , ADN Mitocondrial/metabolismo , Humanos , Inflamación/inducido químicamente , Inflamación/metabolismo , Inflamación/patología , Irritantes/toxicidad , Queratinocitos/patología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Ratones Pelados , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/patología , Gas Mostaza/toxicidad , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos
11.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 42(1): 30-36, 2020 Feb 28.
Artículo en Chino | MEDLINE | ID: mdl-32131937

RESUMEN

Objective To investigate the protective effect of salvianolic acid B(SAB)on the intestinal tract of rats after intestinal ischemia-reperfusion injury(IIRI). Methods Forty-eight healthy male SD rats were equally randomized into IIRI group,SAB+IIRI group,sham control group,and SAB+sham control group. The malonyldialdehyde(MDA)level and superoxide dismutase(SOD)activity in the ileum were measured in each group according to the kit instructions,the transcription levels of inflammatory factors in the ileum of rats were detected by real-time fluorescence quantitative RT-PCR,the secretion level of inflammatory factors was detected by ELISA,and the effects of intestinal ischemia-reperfusion on intestinal permeability and histological lesions were measured by histopathology. Results The MDA level in IIRI group was significantly higher than those in negative control group(P=0.005)and SAB+IIRI group(P=0.012). SOD activity of IIRI group was significantly lower than those of negative control group(P=0.006)and SAB+IIRI group(P=0.017). The optical densities of tumor necrosis factor-α(TNF-α)(P=0.003,P=0.009),interleukin(IL)-1ß(P=0.026,P=0.005),IL-6(P=0.015,P=0.003),and nuclear factor kappa-B(NF-κB)(P=0.007,P=0.015)in IIRI group were significantly higher than those in sham control group and SAB+IIRI group. The TNF-α(P=0.002,P=0.006),IL-1ß(P=0.002,P=0.006),IL-6(P=0.008,P=0.002),and NF-κB(P=0.026,P=0.005)levels in IIRI group were significantly higher than those in sham control group and SAB+IIRI group. The inulin level in IIRI group was significantly lower than that in negative control group(P=0.015)and significantly higher than that in SAB+IIRI group(P=0.011). The dextran level in IIRI group was significantly lower than those in sham control group(P=0.011)and SAB+IIRI group(P=0.012). The dextran gel level in IIRI group was significantly higher than those in sham control group(P=0.031)and SAB+IIRI group(P=0.020). SAB pretreatment remarkably improved the edema,necrosis,and villus stripping of the intestinal mucosa in the ileum of rats. The Chiu score was significantly higher in SAB+sham control group than in sham control group(P=0.001)and was significantly lower in SAB+IIRI group than in IIRI group(P=0.001). Conclusion SAB pretreatment can alleviate IIRI in rat models,and this protective effect may be achieved by alleviating oxidative stress and inflammation in the intestinal tract.


Asunto(s)
Benzofuranos/farmacología , Intestinos/lesiones , Daño por Reperfusión/tratamiento farmacológico , Animales , Citocinas/metabolismo , Inflamación , Masculino , Estrés Oxidativo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley
12.
Anticancer Res ; 40(3): 1503-1512, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32132050

RESUMEN

AIM: We examined whether the perioperative systemic inflammation score (SIS), which describes systemic inflammation and/or malnutrition, affected the tumor recurrence and survival in advanced gastric cancer patients. PATIENTS AND METHODS: The study retrospectively analyzed 160 patients with stage II/III gastric cancer who underwent curative resection at the Kanagawa Cancer Center. The SIS was evaluated before surgery, one week after surgery and one month after surgery, as determined by the serum albumin level (cut-off value=4.0 g/dl) and lymphocyte-to-monocyte ratio (cut-off value=4.44). RESULTS: A high SIS at one month after surgery was identified as an independent predictor for overall survival [hazard ratio (HR)=2.143, p=0.020] and showed a marginal significance for the relapse-free survival (HR=1.814, p=0.053) in multivariate analyses. CONCLUSION: The SIS at one month after surgery is a useful biomarker for predicting the long-term outcome in patients with advanced gastric cancer.


Asunto(s)
Inflamación/patología , Recurrencia Local de Neoplasia/patología , Neoplasias Gástricas/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Capecitabina/administración & dosificación , Quimioterapia Adyuvante , Humanos , Inflamación/sangre , Linfocitos/patología , Persona de Mediana Edad , Monocitos/patología , Estadificación de Neoplasias , Oxaloacetatos/administración & dosificación , Periodo Perioperatorio , Pronóstico , Estudios Retrospectivos , Neoplasias Gástricas/sangre , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Análisis de Supervivencia , Adulto Joven
13.
Med Sci Monit ; 26: e920442, 2020 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-32198879

RESUMEN

BACKGROUND Notoginsenoside R1 (NR) is a major dynamic constituent of Panax notoginseng found to possess anti-inflammatory activity against various inflammatory diseases. However, its protective effects against renal ischemia-reperfusion (I/R) injury have not been elucidated. In male Wistar rats, we induced I/R under general anesthesia by occluding the renal artery for 60 min, followed by reperfusion and right nephrectomy. MATERIAL AND METHODS Rats were randomized to 4 groups: a sham group, an I/R group, an NR-pretreated (50 mg/kg) before I/R induction group, and an NR control group. All animals were killed at 72 h after I/R induction. Blood and renal tissues were collected, and histological and basic renal function parameters were assessed. In addition, levels of various kidney markers and proinflammatory cytokines were measured using RT-PCR, ELISA, and immunohistochemistry analysis. RESULTS After I/R induction, the onset of renal dysfunction was shown by the elevated levels of serum urea, creatinine levels, and histological evaluation, showing a 2-fold increase in the renal failure markers kim-1 and NGAL compared to control rats. Rats pretreated with NR before I/R induction had significantly better renal functions, with attenuated levels of oxidative markers, restored levels of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), tumor growth factor-ß1 (TGF-ß1), INF-γ, and IL-6, and increased anti-inflammatory cytokine levels (IL-10) compared to I/R-induced rats. CONCLUSIONS NR suppressed I/R-induced inflammatory cytokines production by suppressing oxidative stress and kidney markers, suggesting that NR is a promising drug candidate for prevention, progression, and treatment of renal dysfunction.


Asunto(s)
Antiinflamatorios/uso terapéutico , Ginsenósidos/uso terapéutico , Inflamación/prevención & control , Daño por Reperfusión/prevención & control , Transducción de Señal/efectos de los fármacos , Animales , Riñón/irrigación sanguínea , Riñón/efectos de los fármacos , Masculino , Nefrectomía , Distribución Aleatoria , Ratas , Ratas Wistar
14.
Biomed Khim ; 66(1): 77-82, 2020 Jan.
Artículo en Ruso | MEDLINE | ID: mdl-32116229

RESUMEN

Cyanopyrrolidine derivatives benzyloxycarbonyl-methionyl-cyanopyrrolidine (ZMetPrdN), benzyloxycarbonylphenylalanyl- cyanopyrrolidine (ZPhePrdN), tert-butyl-hydroxycarbonyl-glycyl-cyanopyrrolidine (BocGlyPrdN), tert-butyl-hydroxycarbonyl-methionyl-cyanopyrrolidine (BocMetPrdN) are inhibitors of prolylendopeptidase (PREP; EC 3.4.21.26) with an IC50 of 2 nM to 12 nM. ZMetPrdN, ZPhePrdN and BocMetPrdN additionally inhibited dipeptidyl peptidase IV (DPP-4; EC 3.4.14.5) with an IC50 of 1100 nM to 3200 nM. All the compounds have antinociceptive properties in the acetic acid writhing test in mice. But only cyanopyrrolidine derivatives with aromatic substituents decrease exudative inflammation. The cyanopyrrolidine derivatives also increase PREP activity and compensatorily reduce DPP-4 activity in the serum of mice three hours after the induction of inflammation. Thus, cyanopyrrolidine derivatives exhibit antinociceptive and antiexudative properties in part via their effect on PREP.


Asunto(s)
Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Inflamación/tratamiento farmacológico , Metionina/análogos & derivados , Pirrolidinas/farmacología , Inhibidores de Serina Proteinasa/farmacología , Dolor Visceral/tratamiento farmacológico , Animales , Dipeptidil Peptidasa 4 , Metionina/farmacología , Ratones , Serina Endopeptidasas
15.
Exerc Immunol Rev ; 26: 42-55, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32139348

RESUMEN

Chronic low-grade inflammation is increasingly recognized in the aetiology of a range of chronic diseases, including type 2 diabetes mellitus and cardiovascular disease, and may therefore serve as a promising target in their prevention or treatment. An acute inflammatory response can be induced by exercise; this is characterised by the acute increase in proinflammatory markers that subsequently stimulate the production of anti-inflammatory proteins. This may help explain the reduction in basal concentrations of pro-inflammatory markers following chronic exercise training. For sedentary populations, such as people with a disability, wheelchair users, or the elderly, the prevalence of chronic low-grade inflammation- related disease is further increased above that of individuals with a greater capacity to be physically active. Performing regular exercise with its proposed anti-inflammatory potential may not be feasible for these individuals due to a low physical capacity or other barriers to exercise. Therefore, alternatives to exercise that induce a transient acute inflammatory response may benefit their health. Manipulating body temperature may be such an alternative. Indeed, exercising in the heat results in a larger acute increase in inflammatory markers such as interleukin-6 and heat shock protein 72 when compared with exercising in thermoneutral conditions. Moreover, similar to exercise, passive elevation of body temperature can induce acute increases and chronic reductions in inflammatory markers and positively affect markers of glycaemic control. Here we discuss the potential benefits and mechanisms of active (i.e., exercise) and passive heating methods (e.g., hot water immersion, sauna therapy) to reduce chronic low-grade inflammation and improve metabolic health, with a focus on people who are restricted from being physically active.


Asunto(s)
Temperatura Corporal , Terapia por Ejercicio , Hipertermia Inducida , Inflamación/terapia , Proteínas del Choque Térmico HSP72/metabolismo , Humanos , Interleucina-6/metabolismo
16.
Exerc Immunol Rev ; 26: 10-22, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32139355

RESUMEN

Moderate aerobic training may be therapeutic for chronic low-grade inflammatory diseases due to the associated anti-inflammatory response that is mediated by immune cells. The peroxisome proliferator-activated receptor gamma (PPARγ) regulates the M1 (pro-inflammatory) and M2 (anti-inflammatory) polarization, as well as the immunometabolic response of macrophages. Against this background, the present study seeks to clarify whether the conditional deletion of PPARγ in macrophages would have any effect on the anti-inflammatory role of moderate aerobic training. To test this hypothesis, two mice strains were used: PPARγ LyzCre+/+ (KO) and littermates control animals (WT). Each genotype was divided into 1) sedentary high-fat diet (HF) and 2) high-fat diet and moderate aerobic training (HFT) (n = 5-8 per group). The experimental protocol lasted for 12 weeks, comprising 4 weeks of HF diet only and 8 weeks of HF diet and aerobic training (5 times/week, 50-60 minutes/day at 60% of maximum speed). Metabolic analyses were carried out on the serum glucose homeostase, adipose tissue morphology and cytokine content, and macrophage cytokine production.Immunophenotyping and gene expression were also performed. KO male mice were more prone to hypertrophy in the subcutaneous adipose tissue, though only the IL-1ß (p = 0.0049) was higher compared to the values observed in WT animals. Peritoneal macrophages from KO animals exhibited a marked inflammatory environment with an increase in TNF-α (p = 0.0008), IL- 1ß (p = 0.0017), and IL-6 (p < 0.0001) after lipopolysaccharide stimulation. The moderate aerobic training protected both genotypes from weight gain and reduced the caloric intake in the KO animals. Despite the attenuation of the M2 marker CD206 (p < 0.001) in the absence of PPAR-γ, the aerobic training modulated cytokine production in LPS stimulated peritoneal macrophages from both genotypes, reducing proinflammatory cytokines such as TNF-α (p = 0.0002) and IL-6 (p < 0.0001). Overall, our findings demonstrate the essential role of PPARγ in macrophage immunophenotypes. However, the deletion of PPARγ did not inhibit the exercise-mediated anti-inflammatory effect, underscoring the important role of exercise in modulating inflammation.


Asunto(s)
Inflamación/inmunología , Macrófagos Peritoneales/inmunología , PPAR gamma/inmunología , Condicionamiento Físico Animal , Animales , Dieta Alta en Grasa , Inmunofenotipificación , Interleucina-1beta/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Obesos , Factor de Necrosis Tumoral alfa/inmunología
17.
Adv Exp Med Biol ; 1204: 57-73, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32152943

RESUMEN

CLEC5A is a spleen tyrosine kinase (Syk)-coupled C-type lectin that is highly expressed by monocytes, macrophages, neutrophils, and dendritic cells and interacts with virions directly, via terminal fucose and mannose moieties of viral glycans. CLEC5A also binds to N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) disaccharides of bacterial cell walls. Compared to other C-type lectins (DC-SIGN and DC-SIGNR) and TLRs, CLEC5A binds its ligands with relatively low affinities. However, CLEC5A forms a multivalent hetero-complex with DC-SIGN and other C-type lectins upon engagement with ligands, and thereby mediates microbe-induced inflammatory responses via activation of Syk. For example, in vivo studies in mouse models have demonstrated that CLEC5A is responsible for flaviviruses-induced hemorrhagic shock and neuroinflammation, and a CLEC5A polymorphism in humans is associated with disease severity following infection with dengue virus. In addition, CLEC5A is co-activated with TLR2 by Listeria and Staphylococcus. Furthermore, CLEC5A-postive myeloid cells are responsible for Concanavilin A-induced aseptic inflammatory reactions. Thus, CLEC5A is a promiscuous pattern recognition receptor in myeloid cells and is a potential therapeutic target for attenuation of both septic and aseptic inflammatory reactions.


Asunto(s)
Lectinas Tipo C/inmunología , Receptores de Superficie Celular/inmunología , Receptores de Reconocimiento de Patrones/inmunología , Animales , Virus del Dengue/inmunología , Flavivirus/inmunología , Humanos , Inflamación/inmunología , Macrófagos/inmunología , Monocitos/inmunología , Neutrófilos/inmunología
18.
J Korean Med Sci ; 35(10): e63, 2020 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-32174062

RESUMEN

BACKGROUND: Familial Mediterranean fever (FMF) is an autoinflammatory disease that has self-limiting inflammatory attacks during polyserositis. Hepcidin is a protein, and interleukin-6 stimulation increases hepcidin levels. Calprotectin (CLP) is a recently defined cytokine released from monocytes and neutrophils in response to tissue trauma and inflammation. There are studies in the literature showing that it can be used as a biomarker in rheumatic diseases such as ankylosing spondylitis and rheumatoid arthritis. Here, we compared the levels of hepcidin and CLP in healthy individuals and FMF patients during an attack-free period and show its relation to genetic mutations. METHODS: This is a cross-sectional study. Between July 2017 and December 2017, 60 patients diagnosed with FMF an admitted to the Cumhuriyet University Faculty of Medicine Department of Internal Medicine Rheumatology as well as 60 healthy volunteers without any rheumatic, systemic, or metabolic diseases were enrolled in this study. Blood was collected from a peripheral vein to measure serum CLP and hepcidin levels. Blood tests were examined by ELISA; the study protocol was approved by the local ethics committee. RESULTS: Median serum hepcidin level was 468.1 (210.3-807.8) pg/mL in FMF group and 890.0 (495.0-1,716.9) pg/mL in the healthy control (HC) group. There was a statistically significant difference between the two groups (P < 0.001). The median serum levels of CLP in the FMF group were measured as 1,331.4 (969.3-1,584.6 pg/mL and 73.8(45.0-147.9) pg/mL in the HC group. There was a statistically significant difference between the two groups (P < 0.001). Receiver operating characteristic analysis showed that the sensitivity was 66.7% and the specificity was 71.7% at serum hepcidin < 581.25 pg/mL (P < 0.05); the sensitivity was 96.7% and specificity was 100% at CLP > 238 pg/mL (P < 0.05). There was no significant difference between serum hepcidin and CLP levels in FMF patients with M694V homozygous and M694V heterozygous (P > 0.05). There was no significant difference in serum hepcidin levels between FMF patients with and without arthritis, proteinuria, and amyloidosis (P < 0.05). There was no significant correlation between laboratory findings, gender, age, and serum CLP and hepcidin levels (P > 0.05, r < 0.25). CONCLUSION: Serum CLP levels in FMF patients during an attack-free period are significantly higher than in the HC groups. Serum hepcidin levels in FMF patients are significantly lower than in the HC group. Low levels of hepcidin may be explained by including FMF patients during an attack-free period in the study. CLP may be an important biomarker in FMF. A better understanding of the role of these biomarkers in the diagnosis of FMF is needed to evaluate the results in a more comprehensive way.


Asunto(s)
Fiebre Mediterránea Familiar , Hepcidinas/metabolismo , Inflamación , Complejo de Antígeno L1 de Leucocito/sangre , Estudios de Casos y Controles , Estudios Transversales , Fiebre Mediterránea Familiar/sangre , Fiebre Mediterránea Familiar/diagnóstico , Hepcidinas/sangre , Homocigoto , Humanos , Inflamación/sangre , Mutación , Neutrófilos , Proteinuria , Curva ROC , Sensibilidad y Especificidad
19.
Medicine (Baltimore) ; 99(11): e19071, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32176032

RESUMEN

BACKGROUND: It is important to manage inflammation after craniotomy. It may be prudent to reduce the excessive usage of antibiotics and to add supplementary treatments like acupuncture, which would be effective and safe. However, there are only a few studies available to date on the effects of acupuncture on anti-inflammatory response after craniotomy. The aim of this study was to explore the anti-inflammatory effects of acupuncture in patients after a craniotomy. METHODS: This study was a single-center, prospective, open-label, controlled trial. Forty-four subjects who underwent craniotomy for an unruptured aneurysm, facial spasm, or brain tumor were allocated to either an acupuncture group or a control group. Both groups received postoperative routine care in the Department of Neurosurgery. The subjects in the acupuncture group also received a total of 6 acupuncture treatments sessions within 8 days after craniotomy. Acupuncture treatments included acupuncture, electroacupuncture, and intradermal acupuncture. The serum interleukin (IL)-1ß and IL-6, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and erythrocyte sedimentation rate levels were assessed four times within 7 days after surgery. The presence of fever, use of additional antibiotics, presence of infection including pneumonia or urinary tract infection, and safety were also reviewed. RESULTS: The IL-1ß levels of subjects who underwent aneurysmal clipping were significantly lower in the acupuncture group (P = .02). TNF-α levels of subjects who underwent aneurysmal clipping at the seventh postoperative day were also significantly lower in the acupuncture group (P = .03). Six cases of fever of unknown origin were observed in the control group, while none were seen in the acupuncture group, revealing that the incidence of fever was significantly lower in the acupuncture group (P = .02). No adverse events occurred during the trial. CONCLUSION: Acupuncture showed a possibility of alleviating inflammation by attenuating the levels of proinflammatory cytokines and significantly reduced the incidence of fever of unknown origin in patients after craniotomy. Acupuncture would be suitable as an adjunctive therapy to alleviate inflammation after craniotomy.


Asunto(s)
Terapia por Acupuntura/métodos , Craneotomía/efectos adversos , Inflamación/terapia , Complicaciones Posoperatorias/terapia , Proteína C-Reactiva/análisis , Femenino , Humanos , Inflamación/sangre , Inflamación/etiología , Interleucina-1beta/sangre , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factor de Necrosis Tumoral alfa/sangre
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA