Résumé
Objective @#To investigate the value of methyltransferase-like protein 16 (METTL16) in the clinical di- agnosis and prognostic prediction of multiple myeloma (MM) patients . @*Methods @#The expression level and prog- nostic potential of each gene involved in N6 -methyladenosine ( m6A) modification in MM were respectively ana- lyzed in the databases of the Multiple Myeloma Research Foundation (MMRF) and the Genotype-Tissue Expression Proj ect (GTEx ) . Bone marrow specimens from 26 patients with initial diagnosis of MM and 19 patients with MM af- ter treatment with standard regimens and peripheral blood specimens from 24 normal subjects were collected respec- tively , and the expression levels of m6A genes were determined by qRT-PCR. The correlation between METTL16 expression and various laboratory and clinical indexes was analyzed: hemoglobin ( Hb) , white blood cell count ( WBC) , platelet count (PLT) , blood creatinine (Scr ) , serum calcium (Ca2 + ) , β-microglobulin ( β-MG) , bone destruction , ISS stage , type , and overall survival (OS) in the patients with primary diagnosis . The expression lev- els of interleukin (IL) -4 , IL-6 , IL-10 , IL-18 and chemokine ligand 2 ( CCL2) , CCL3 , CCL4 in the specimens were further examined and their correlation with the expression of METTL16 was investigated . @*Results @#Database analysis suggested that METTL16 expression was significantly higher in MM patient samples compared with normal controls , which was associated with poor prognosis and had certain diagnostic value . qRT-PCR results showed that the expression level of METTL16 in the bone marrow of patients with initial diagnosis of MM was significantly higher than that of treated patients and normal controls . Its expression was positively correlated with hemoglobin , leuko- cytes and stage , and its expression was positively correlated with CCL4 expression .@*Conclusion @#METTL16 expres- sion was significantly elevated in patients with MM , and its expression level was correlated with anemia , more bone destruction and worse stage , which might indicate a poor prognosis . The significant correlation between the expres- sion of METTL16 and CCL4 suggests that METTL16 may play a corresponding pathogenic role through the relevant pathway. METTL16 will have significant clinical value in the management of MM .
Résumé
BACKGROUND Leprosy is a highly neglected disease that is considered a serious public health problem in many countries. This illness is characterised by a variety of clinical and histopathological manifestations that are related to the patient immune response. OBJECTIVES This work aimed evaluate the profile of circulating immune mediators in the plasma from patients classified clinically as paucibacillary (PB), multibacillary (MB), households contacts (HHC), type1 leprosy reaction (T1R), type2 leprosy reaction (T2R) and control individuals without medical history of leprosy (CTL). METHODS To assessment of the plasma immune mediators was used multiplex microbeads immunoassay "Luminex". FINDINGS The results showed that patients (PB) had a regulatory-biased profile, while MB revealed a pro-inflammatory trend of highly expressed biomarkers. HHC display conspicuously increased levels in the plasma of the chemokines (CCL2, CCL3, CCL4, CCL5 and CXCL8), pro-inflammatory cytokines (IFN-γ,TNF and IL-1β), modulating cytokines (IL-9 and IL-1Ra) and growth factors (PDGF, G-CSF and IL-2). Interestingly, HHC displayed superior production of IFN-γ as compared to other leprosy groups, indicating a putative protective role for this cytokine during chronic Mycobacterium leprae exposure. MAIN CONCLUSION Further investigations are currently underway to elucidate the potential of these mediators as biomarkers applicable to the diagnosis/prognosis of leprosy and also T1R and T2R leprosy reactions.
Résumé
Abstract Background Vitiligo is the most common pigmentary disorder and is considered a chronic, cumulative, multifactorial disease. The crucial role of cytotoxic CD8+ T lymphocytes and the IFNγ/CXCL10 axis has been demonstrated in its pathogenesis. Objective To evaluate the clinical profile and immuno-inflammatory markers in patients with vitiligo in a reference medical center. Methods Cross-sectional study in which all patients with vitiligo seen at the medical center the from 2019 to 2022 were evaluated, to outline the clinical profile. Moreover, cardiovascular risk biomarkers (neutrophil/lymphocyte ratio and C-reactive protein levels) were measured, as well as cytokines and chemokines (TNFα, IFNγ, IL10, IL15 and CXCL10) in the serum of a subgroup of 30 patients. Results There was a predominance of females, with a mean age of 43 years. Most were phototypes IV or V (71.3%), without comorbidities (77.55%), and without a family history of vitiligo (70.41%). Higher levels of neutrophil/lymphocyte ratio, C-reactive protein, and inflammatory cytokines/chemokines were documented in vitiligo patients when compared to the control group (non-significant). As relevant data, the highest values of CXCL10 were detected in patients with vitiligo versus controls, as well as in patients with disease of shorter duration (p < 0.05). Study limitations The number of assessed patients was small due to recruitment difficulties caused by the COVID-19 pandemic. Conclusion The present data contribute to confirming the relevant role of the IFNγ/CXCL10 axis in the pathogenesis of vitiligo, highlighting CXCL10 as a possible activity marker.
Résumé
Objective To investigate the effects of methionine restriction(MR)on macrophages in lipopolysaccharide(LPS)-induced acute lung injury(ALI)and to explore the underlying mechanism.Methods According to the random number table method,36 male C57BL/6J mice(6～8 weeks old,23±2 g)were divided into 3 groups with 12 mice in each group:the sham group,the LPS group and the LPS+MR group.HE staining and pathological scoring of lung injury were performed in lung tissues.The expression of LPS-binding protein(LBP)and Toll-like receptor-4(TLR4)was detected by RT-qPCR and Western blotting.Macrophage-colony stimulating factor(M-CSF),granulocyte-macrophage-colony stimulating factor(GM-CSF)and chemokine C-C motif ligand 3(CCL3)which are all macrophage-associated chemokines were analyzed by immunohistochemistry.Results Compared with the sham group,the pathological score of lung injury in the LPS group was significantly increased(P＜0.01);The mRNA and protein expression levels of LBP and TLR4 were significantly increased;The number of positive cells of CD11b,F4/80,M-CSF,GM-CSF and CCL3 were significantly increased(P＜0.01).MR significantly improved LPS-induced ALI,and decreased the pathological score of lung injury(P＜0.01);The mRNA and protein expression levels of LBP and TLR4 were decreased;Compared with the LPS group,the number of positive cells of CD11 b,F4/80,M-CSF,GM-CSF and CCL3 were reduced in the LPS+MR group(P＜0.01).Conclusion MR could attenuate LPS-induced ALI by inhibiting the expression of macrophage chemokines and preventing infiltration and activation of macrophage to lungs.
Résumé
Diabetic nephropathy (DN) is a common microvascular complication of diabetes mellitus. Cardiovascular disease often occurs in patients with DN. Patients with DN often experience changes in cardiac structure and function as proteinuria increases, glomerular filtration rate decreases, and blood creatinine levels increase, leading to the occurrence of cardiovascular disease. Additionally, inflammatory factors play a crucial role in cardiac structure and function. Understanding the pathological and physiological effects of inflammation on diabetic nephropathy-related cardiovascular disease and clarifying the relationship between cardiac structure and function in patients with DN are crucial for effective prevention and treatment of DN.
Résumé
Objective:To investigate the efficacy of recombinant human interferon α-2b spray, administered under medication guidance, in the clinical treatment of herpangina.Methods:A total of 76 children with herpangina who were treated at The First People's Hospital of Yongkang between October 2020 and October 2022 were included in this study. Using the random number table method, these patients were randomly assigned to an observation group ( n = 42) and a control group ( n = 34). The control group received conventional treatment, whereas the observation group was administered recombinant human interferon α-2b spray under medication guidance. A comparative analysis was conducted between the two groups, evaluating clinical efficacy, inflammatory factor levels, treatment compliance, and the negative conversion rate of throat swab virology. Results:After treatment, the overall response rate of the observation group [95.24% (40/42)] and treatment compliance [97.62% (41/42)] were significantly higher than those of the control group [76.47% (26/34), 79.41% (27/34), χ2 = 4.27, 4.82, P = 0.040, 0.030]. The levels of C-reactive protein [(6.28 ± 1.64) mg/L], white blood cell count [(6.11 ± 1.10) × 10 9], and serum amyloid A [(3.47 ± 0.89) mg/L] in the observation group were significantly lower than those in the control group [(7.51 ± 1.16) mg/L, (7.51 ± 1.16) × 10 9, (7.82 ± 1.30) mg/L, t = 3.69, 6.46, 17.27, all P < 0.001]. The positive conversion rate of throat swab virology in the observation group [4.76% (2/42)] was lower than that in the control group [26.47% (9/34), χ2 = 5.51, P = 0.190]. Conclusion:The use of recombinant human interferon α-2b spray under medication guidance in the treatment of herpangina can improve treatment compliance, rapidly alleviate clinical symptoms, and significantly improve the prognosis.
Résumé
Objective To investigate the correlation between brain injury and spleen damage in a rat model of acute ischemic stroke and stasis interaction,and its effect on the MCP-1/CCR2 axis,and to provide an experimental basis for the mechanism of brain-spleen inflammatory coupling in spleen lesions caused by acute ischemic stroke.Methods Forty male SD rats were randomly divided into a sham group,carrageenan/yeast stasis syndrome group(carrageenan/yeast,CA/Y),middle cerebral artery occlusion group(MCAO),and middle cerebral artery stasis syndrome group(MCAO CA/Y)with 10 rats in each group.CA/Y and MCAO CA/Y groups were injected with 10 mg/kg carrageenan and 10 mg/kg intraperitoneally on the first day of modeling.2 mg/kg of dry yeast suspension were injected subcutaneously on the second day.MCAO and MCAO CA/Y groups were established by wire embolism on the second day.At 24 h after cerebral infarction modeling,the neurological deficit score was calculated in each group,the percentage of the cerebral infarction area was determined by TTC staining,the spleen weight was measured,and the correlation between the percentage of the cerebral infarction area and spleen weight was analyzed by the Spearman correlation coefficient.Furthermore,the pathological morphology of brain and spleen tissues was observed by hematoxylin-eosin(HE)staining,and chemotactic protein 1(MCP-1)and interferon-γ(IFN-γ)contents were measured in rat plasma by enzyme-linked immunosorbent assays.Western blot was used to detect chemokine C-C-motif receptor 2(CCR2)protein expression in the ischemic side of brain tissue.Results Compared with the sham group,the neurological deficit score,cerebral infarction area,and MCP-1 and IFN-γ contents in plasma were significantly increased(P＜0.01),spleen weight was decreased significantly(P＜0.01),and CCR2 protein expression in brain tissue was significantly upregulated(P＜0.05)in MCAO and MCAO CA/Y groups.Moreover,the area of cerebral infarction was increased significantly(P＜0.01),the spleen weight was decreased significantly(P＜0.01),and CCR2 protein expression in brain and spleen tissues was significantly upregulated(P＜0.05)Compared with the MCAO group,the area of cerebral infarction in the MCAO CA/Y group was significantly increased(P＜0.01)and the spleen weight was decreased significantly(P＜0.05).Spearman correlation analysis showed that the spleen weight was negatively correlated to the percentage of the cerebral infarction area(P＜0.01,r=-0.9711).Pathological morphology observation revealed that the pathological changes in the MCAO CA/Y group were the most serious,cerebral liquefaction necrosis foci were seen in the brain tissue cortex,arrangement of neuronal cells in the lesions was sparse and disordered with volume atrophy and a small number of vacuoles and nuclear solidification,most neuronal cells were degenerated and necrotic,microglia hyperplasia was obvious,small blood vessels were significantly increased,and interstitial lipid degeneration was severe.The density of periarterial lymph sheath cells in some of the spleen tissue was reduced and the marginal area is widened.Conclusions A correlation between brain and spleen injury was found after acute ischemic stroke with stasis and toxin syndrome,and the chemokine signaling axis of MCP-1/CCR2 might be involved in the mechanism of brain-spleen inflammation coupling.
Résumé
Abstract Objective To compare the patterns of systemic inflammatory response in women with epithelial ovarian cancer (EOC) or no evidence of malignant disease, as well as to evaluate the profile of systemic inflammatory responses in type-1 and type-2 tumors. This is a non-invasive and indirect way to assess both tumor activity and the role of the inflammatory pattern during pro- and antitumor responses. Materials and Methods We performed a prospective evaluation of 56 patients: 30 women without evidence of malignant disease and 26 women with EOC. The plasma quantification of cytokines, chemokines, and microparticles (MPs) was performed using flow cytometry. Results Plasma levels of proinflammatory cytokines interleukin-12 (IL12), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) interleukin-1 beta (IL-1β), and interleukin-10 (IL-10), and C-X-C motif chemokine ligand 9 (CXCL-9) and C-X-C motif chemokine ligand 10 (CXCL-10) were significantly higher in patients with EOC than in those in the control group. Plasma levels of cytokine interleukin-17A (IL-17A) and MPs derived from endothelial cells were lower in patients with EOC than in the control group. The frequency of leukocytes and MPs derived from endothelial cells was higher in type-2 tumors than in those without malignancy. We observed an expressive number of inflammatory/regulatory cytokines and chemokines in the cases of EOC, as well as negative and positive correlations involving them, which leads to a higher complexity of these networks. Conclusion The present study showed that, through the development of networks consisting of cytokines, chemokines, and MPs, there is a greater systemic inflammatory response in patients with EOC and a more complex correlation of these biomarkers in type-2 tumors.
Resumo Objetivo Comparar os padrões de resposta inflamatória sistêmica em mulheres com câncer epitelial de ovário (CEO) ou sem evidência de doença maligna, bem como avaliar o perfil de respostas inflamatórias sistêmicas em tumores dos tipos 1 e 2. Esta é uma forma não invasiva e indireta de avaliar tanto a atividade tumoral quanto o papel do padrão inflamatório durante as respostas pró- e antitumorais. Métodos Ao todo, 56 pacientes foram avaliados prospectivamente: 30 mulheres sem evidência de doença maligna e 26 mulheres com CEO. A quantificação plasmática de citocinas, quimiocinas e micropartículas (MPs) foi realizada por citometria de fluxo. Resultados Os níveis plasmáticos das citocinas pró-inflamatórias interleucina-12 (IL12), interleucina-6 (IL-6), fator de necrose tumoral alfa (tumor necrosis factor alpha, TNF-α, em inglês), interleucina-1 beta (IL-1β), e interleucina-10 (IL-10), e da quimiocina de motivo C-X-C 9 (CXCL-9) e da quimiocina de motivo C-X-C 10 (CXCL-10) foram significativamente maiores em pacientes com EOC do que nos controles. Os níveis plasmáticos da citocina interleucina-17A (IL17A) e MPs derivados de células endoteliais foram menores em pacientes com CEO do que no grupo de controle. A frequência de leucócitos e de MPs derivadas de células endoteliais foi maior nos tumores de tipo 2 do que naqueles sem malignidade. Observou-se um número expressivo de citocinas e quimiocinas inflamatórias/regulatórias nos casos de CEO, além de correlações negativas e positivas entre elas, o que leva a uma maior complexidade dessas redes. Conclusão Este estudo mostrou que, por meio da construção de redes compostas por citocinas, quimiocinas e MPs, há maior resposta inflamatória sistêmica em pacientes com CEO e correlação mais complexa desses biomarcadores em tumores de tipo 2.
Sujets)
Humains , Femelle , Tumeurs de l'ovaire , Cytokines , Chimiokines , InflammationRésumé
Introduction: Oral Submucous Fibrosis (OSF) is a chronic fibrosis condition of oral cavity. It is a multifactorial condition, are- canut chewing being the prime etiologic factors. Objectives: Arecanut alkaloids stimulate the oral tissue initiating the inflammatory response. As an inflammatory response, cells release cytokines activating the cascade of different fibrinogenic pathways leading to fibrosis. Conclusion: This review briefs about the various cytokines studied in Oral Submucous Fibrosis.
Résumé
Resumen Introducción: Los anticuerpos anti-Ro52/TRIM21 son marcadores de varias enfermedades reumáticas autoinmunes sistémicas (ERAS). Objetivo: Evaluar si los anticuerpos anti-Ro52/TRIM21 están relacionados con anomalías en los circuitos inflamatorios. Métodos: Estudio transversal de pacientes consecutivos y ambulatorios con ERAS. Los anticuerpos anti-Ro52/TRIM21 y la proteína amiloide sérica se midieron mediante ELISA; los paneles para 18 citocinas y nueve quimiocinas se analizaron en una plataforma de lectura Luminex; la proteína C reactiva (hs-CRP) y el complemento se midieron mediante nefelometría. Resultados: Se incluyeron 167 pacientes, 143 con lupus eritematoso sistémico (LES), 16 con síndrome de Sjögren primario y ocho con esclerosis sistémica; 41 fueron positivos para anticuerpos anti-Ro52/TRIM21 (24 %). Los pacientes con anticuerpos anti-Ro52/TRIM21 tuvieron niveles séricos más altos de IL-2, IL-4, IL-6, GM-CSF, IL-21, IL-22, hs-CRP y quimiocinas CCL4, CXCL8, CXCL10 y CXCL12; y más bajos de complemento C4. Los títulos de anticuerpos anti-Ro52/TRIM21 correlacionaron positivamente con IL-2, IL-4, IL-6, IL-10, IL-21, IL-22, CXCL10 y hs-CRP; y negativamente con complemento C3 y C4. Al incluir solo LES, no se identificó asociación entre los anticuerpos anti-Ro52/TRIM21 y la actividad de la enfermedad o la afectación específica de órganos. Conclusiones: Los anticuerpos anti-Ro52/TRIM21 se asocian a circuitos aberrantes de citocinas y niveles elevados de moléculas angiogénicas y quimioatrayentes de neutrófilos y monocitos, lo que sugiere un papel activo de esos anticuerpos en las ERAS.
Abstract Introduction: Anti-Ro52/TRIM21 antibodies are markers for several systemic autoimmune rheumatic diseases (SARD). Objective: To assess whether anti-Ro52/TRIM21 antibodies are related to abnormalities in inflammatory circuits. Methods: Cross-sectional study of consecutive outpatients with SARD. Anti-Ro52/TRIM21 antibodies and serum amyloid A protein were measured by ELISA; panels for 18 cytokines and nine chemokines were analyzed on a Luminex reading platform, while high-sensitivity C-reactive protein (hs-CRP) and complement were measured by nephelometry. Results: Among 167 included patients, 143 had systemic lupus erythematosus (SLE), 16 had primary Sjögren's syndrome and eight had systemic sclerosis; 41 (24%) were positive for anti-Ro52/TRIM21 antibodies. Patients with anti-Ro52/TRIM21 antibodies had higher serum levels of IL-2, IL-4, IL-6, GM-CSF, IL-21, IL-22, hs-CRP and chemokines CCL4, CXCL8, CXCL10 and CXCL12, but lower levels of complement C4. Anti-Ro52/TRIM21 antibody titers were positively correlated with IL-2, IL-4, IL-6, IL-10, IL-21, IL-22, CXCL10, and hs-CRP, and negatively with complement C3 and C4. When only SLE patients were included, no association was identified between anti-Ro52/TRIM21 antibodies and disease activity or organ-specific involvement. Conclusions: Anti-Ro52/TRIM21 antibodies are associated with aberrant cytokine circuits and elevated levels of angiogenic molecules and neutrophil and monocyte chemoattractants, which suggests an active role for these antibodies in SARD.
Résumé
Objective:To investigate the clinical efficacy and mechanism of Ganoderma lucidum hypoglycemic formula in the treatment of insulin resistance in patients with type 2 diabetes mellitus (T2DM) with liver and kidney yin deficiency. Methods:A total of 86 patients with T2DM with liver and kidney yin deficiency who were diagnosed and treated at Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine from January 2021 to February 2022 were included in this study. These patients were divided into a control group and a treatment group, with 43 patients in each group using a 1:1 ratio using the sealed envelope method. Both groups were treated with standardized Western medicine. The treatment group was also treated with the Ganoderma lucidum hypoglycemic formula. All patients were followed up for 12 weeks. The clinical symptoms, curative effect, glucose and lipid metabolism, inflammatory factors, oxidative stress change, and safety were compared between the two groups. Results:The total response rate in the treatment group was 88.4% (38/43), which was significantly higher than 53.5% (23/43) in the control group ( χ2 = 12.69, P < 0.001). After treatment, the traditional Chinese medicine syndrome score, fasting blood glucose, 2-hour postprandial blood glucose, glycosylated hemoglobin, insulin resistance index, total cholesterol, triglyceride, tumor necrosis factor α, and interleukin-6 decreased in each group. The amplitudes of decrease of the above indexes were greater in the treatment group compared with the control group (all P < 0.05). C-peptide in the fasting state, C-peptide at 2 hours after a diet, and superoxide dismutase increased in each group. The amplitudes of increase of the three indexes were greater in the treatment group compared with the control group (all P < 0.05). Conclusion:Ganoderma lucidum hypoglycemic formula can greatly improve insulin resistance and glucose and lipid metabolism in T2DM patients with liver and kidney yin deficiency. The underlying mechanism may be to further reduce the inflammatory response and anti-oxidative stress by down-regulating tumor necrosis factor α and interleukin-6 levels and up-regulating superoxide dismutase level, thereby effectively alleviating insulin resistance in T2DM.
Résumé
Objective:To investigate the role of serum CX3CR1 in the diagnosis of coronary artery stenosis and in the evaluation of prognosis after percutaneous coronary intervention.Methods:A total of 101 patients with coronary artery stenosis (≥ 50% stenosis) confirmed with coronary angiography (CAG) in Haiyang People's Hospital from January 2018 to May 2019 who were followed up till May 2021 were included in the observation group. Thirty-four healthy individuals who underwent physical examination during the same period were included in the control group. Patients in the observation group were divided into an in-stent restenosis group (ISR group, n = 28) and a non-ISR group ( n = 73). The expression of CX3CR1 was detected. The incidence of adverse cardiac events was calculated. The sensitivity, specificity, and area under the curve (AUC) plotted for the use of CX3CR1 to diagnose coronary artery stenosis and predict adverse cardiac events were evaluated. Results:The expression of CX3CR1 in the observation group was (3.95 ± 1.05) μg/L, which was significantly higher than (2.30 ± 0.65) μg/L in the control group ( t = 2.87, P < 0.05). The receiver operating characteristic curve analysis showed that the AUC, sensitivity, and specificity of the use of CX3CR1 in diagnosing coronary artery stenosis were 0.892, 75.2%, and 88.2%. The incidence of non-fatal myocardial infarction, angina pectoris, heart failure, and cardiac death in the ISR group was significantly higher compared with the non-ISR group ( χ2 = 8.06, 7.17, 8.06, 7.17, all P < 0.05). The receiver operating characteristic curve analysis results showed that the AUC value of CX3CR1 in predicting non-fatal myocardial infarction, angina pectoris, heart failure, and cardiac death were 0.786, 0.895, 0.997, and 0.887, respectively. Conclusion:CX3CR1 is highly expressed in coronary artery stenosis, which can provide a reference for the diagnosis and prognostic evaluation of coronary artery stenosis.
Résumé
Despite exciting achievements with some malignancies, immunotherapy for hypoimmunogenic cancers, especially glioblastoma (GBM), remains a formidable clinical challenge. Poor immunogenicity and deficient immune infiltrates are two major limitations to an effective cancer-specific immune response. Herein, we propose that an injectable signal-amplifying nanocomposite/hydrogel system consisting of granulocyte-macrophage colony-stimulating factor and imiquimod-loaded antigen-capturing nanoparticles can simultaneously amplify the chemotactic signal of antigen-presenting cells and the "danger" signal of GBM. We demonstrated the feasibility of this strategy in two scenarios of GBM. In the first scenario, we showed that this simultaneous amplification system, in conjunction with local chemotherapy, enhanced both the immunogenicity and immune infiltrates in a recurrent GBM model; thus, ultimately making a cold GBM hot and suppressing postoperative relapse. Encouraged by excellent efficacy, we further exploited this signal-amplifying system to improve the efficiency of vaccine lysate in the treatment of refractory multiple GBM, a disease with limited clinical treatment options. In general, this biomaterial-based immune signal amplification system represents a unique approach to restore GBM-specific immunity and may provide a beneficial preliminary treatment for other clinically refractory malignancies.
Résumé
Objective:To investigate the clinical efficacy of liraglutide in the treatment of type 2 diabetes mellitus complicated by osteoporosis and its effects on serum chemokines and bone mineral density.Methods:This is a case-control study. The clinical data of 78 patients with type 2 diabetes mellitus complicated by osteoporosis who received treatment in the Siming Branch of The First Affiliated Hospital of Xiamen University from May 2019 to September 2021 were retrospectively analyzed. These patients were divided into an observation group and a control group ( n = 39 per group) according to different treatment methods. The control group was treated with adjuvant therapy with afacalcitol, while the observation group was given liraglutide in addition to adjuvant therapy with afacalcitol. Both groups were treated for 16 weeks. Clinical efficacy was compared between the two groups. Before and after treatment, serum chemokines and bone mineral density were determined in each group. Adverse reactions were evaluated in each group. Results:The total effective rate in the observation group was 92.3% (36/39), which was significantly higher than 71.8% (28/39) in the control group ( χ2 = 5.57, P < 0.05). After treatment, the serum chemokine level in the observation group was (60.11±10.25) μg/L, which was significantly lower than (63.15 ± 10.24) μg/L in the control group ( t = -2.01, P < 0.05). Bone mineral density in the observation group was (1.77 ± 1.05) g/cm 2, which was significantly higher than (1.01 ± 0.06) g/cm 2 in the control group ( t = 4.51, P < 0.05). The incidence of adverse reactions in the observation group was 7.7% (3/39), which was not significantly different from 12.8% (5/39) in the control group ( χ2 = 0.56, P > 0.05). Conclusion:Liraglutide is highly effective on type 2 diabetes mellitus complicated by osteoporosis. Liraglutide can effectively decrease serum chemokine levels, increase bone mineral density, and thereby is worthy of clinical application.
Résumé
La Artritis Reumatoide (AR) es una enfermedad autoinmune frecuente, caracterizada por inflamación crónica en las articulaciones que puede progresar a la destrucción ósea. Aunque la fisiopatología de la AR no es clara, se ha visto que las células T y las células B desempeñan un importante papel en la misma. Estudios con Rituximab (RTX), un fármaco que elimina las células B CD20+, han contribuido a esclarecer y destacar la participación de las células B en la AR. Las células B pueden contribuir a la autoinmunidad de manera dependiente de la producción de los anticuerpos e independiente de esta producción. Esta última función puede ser debida al papel de las células B como presentadoras de antígeno para las células T y productoras de citocinas y quimiocinas. Para contribuir a entender este último mecanismo, se revisaron los artículos donde se evidenciaron los efectos del tratamiento con RTX sobre la citocinas y quimiocinas circulantes en pacientes con AR. Se encontró que la mayoría de las citocinas estudiadas disminuyeron sus niveles en circulación luego del tratamiento con RTX. La IL-10 y la IL-6 se vieron consistentemente disminuidas en los pacientes que respondieron al tratamiento y podrían ser marcadores del tratamiento con Rituximab.
Summary Rheumatoid Arthritis (RA) is a common autoimmune disease characterized by chronic inflammation in the joints that can progress to bone destruction. Although the pathophysiology of RA is unclear, T cells and B cells are though to be involved. Rituximab (RTX), a drug that eliminates CD20 + B cells, has helped to clarify and highlight the role of B cells in RA. B cells can contribute to autoimmunity by mechanisms dependent on the production of antibodies and independent of this production. The latter may depend on the role of B cells as antigen-presenting cells for T cells and their capacity to produce cytokines and chemokines. To contribute to our understanding of this mechanism, studies that evaluated levels of circulating cytokines and chemokines in patients with RA after treatment with RTX were reviewed. Most cytokines studied decreased their levels in circulation after treatment with RTX. IL-10 and IL-6 consistently were decreased in patients responding to treatment and maybe markers of Rituximab treatment.
Sujets)
HumainsRésumé
Objective:To investigate the relationship between Helicobacter pylori(Hp)infections in Parkinson's disease(PD)patients at high altitude and peripheral inflammatory markers.Methods:In this prospective study, 120 PD patients in Qinghai Province(altitude: 2260 m)were enrolled and evaluated using PD motor symptom scales and a non-motor symptom scale.The 13C-Urea breath test was used to detect Hp, and patients were divided into an Hp infection group and a non-Hp infection group based on test results.The levels of high-sensitivity C-reactive protein(hs-CRP), white blood cell counts and ratios, serum interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α)were measured. Results:The incidence of Hp infections in PD patients was 56.67%(68/120).The scores of Unified Parkinson's Disease Rating Scale(UPDRS)-Ⅲ, UPDRS-Ⅳ, total UPDRS, Hoehn-Yahr(H-Y)score, constipation scoring system(CSS)and Leeds dyspepsia questionnaire(LDQ)in the Hp infection group were higher than those in the non-Hp infection group, while the mini-mental state examination(MMSE)score was lower in the non-Hp infection group(all P<0.05).The neutrophil count, neutrophil-to-lymphocyte ratio(NLR), monocyte-to-lymphocyte ratio(MLR), serum IL-6 and TNF-α in the Hp-infection group were elevated compared with the non-Hp infection group(all P<0.05).Multivariate Logistic regression analysis showed that IL-6, TNF-α, NLR and H-Y score were independent risk factors for Hp infections in PD patients( OR=1.103, 1.188, 3.320, 4.593, respectively, all P<0.05).Correlation analysis showed that IL-6, TNF-α and NLR had positive correlations with UPDRS-Ⅲ( r=0.676, 0.644, 0.488, respectively), UPDRS-Ⅳ( r=0.679, 0.660, 0.430, respectively), UPDRS-total score( r=0.391, 0.448, 0.319, respectively), H-Y( r=0.610, 0.750, 0.460, respectively), CSS( r=0.529, 0.366, 0.212, respectively)and LDQ( r=0.581, 0.440, 0.263, respectively), but were negatively correlated with MMSE score( r=-0.617, -0.596, -0.321, respectively)(all P<0.05). Conclusions:Peripheral inflammation caused by Hp infections may be involved in the occurrence and development of Parkinson's disease at high altitude and serum IL-6, TNF-α and NLR could serve as indicators to evaluate PD patients with Hp infections.
Résumé
Chemokine signal pathways are important for the regulation of tumour metastasis. Chemokine receptors CXCR4 (C-X-C chemokine receptor type 4) and XCR1 (chemokine XC receptor 1) are involved in the metastasis of breast cancer, while the interaction between them remains unclear. Here we first identified the interaction between CXCR4 and XCR1 based on membrane protein yeast two-hybrid assays. Bioluminescence resonance energy transfer (BRET) showed that XCR1 could competitively bind to CXCR4 to form a heterodimer (P < 0.01). Results of wound healing assays via transient transfection of XCR1 and CXCR4 into HEK293 cells showed that 41.55% of the migration area rate in the co-transformation group was lower than 58.75% in the CXCR4-alone group after adding 30 nmol/L S D F-β. The co-expression of XCR1 inhibited the cellular motility, possibly mediated by the SDF-1β (stromal cell-derived factor 1)/CXCR4 signal pathway (P < 0.05). Furthermore, CXCR4 on the cell surface after co-expression of XCR1 in CXCR4-EGFP transgenic HEK293 cells was detected by flow cytometry. And the result suggested that XCR1 could accelerate the internalization of CXCR4 into the heterodimer induced by 30 nmol/L SDF-1β (P<0.05), which increased the internalization rate from 14.38% to 64.10%. Finally, the phosphorylation of Akt and ERK, which were involved in cell proliferation and migration, respectively, were examined. After 10 minutes of SDF-1β stimulation, ERK phosphorylation in the CXCR4-alone group showed a 3.59-fold increase, whereas the increase of ERK phosphorylation in the co-transfected group was only 2.08-fold. Interestingly, heterodimer formation reduced the phosphorylation level of ERK and shortened the activation time, whereas the phosphorylation level of Akt remained unchanged. Collectively, our findings revealed the hetero-dimerization of CXCR4 and XCR1 and its effects on CXCR4-mediated cellular motility, receptor internalization, and ERK pathway phosphorylation. Therefore, XCR1-targeting drugs could be candidates for cross-desensitization of CXCR4 and might represent a possible option for inhibiting breast cancer metastasis.
Résumé
ABSTRACT Background: The inflammatory response plays a significant role in the outcome of coronavirus disease (COVID-19). Methods: We investigated plasma cytokine and chemokine concentrations in non-infected (NI), asymptomatic severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-infected blood donors (AS), and patients with severe COVID-19 (SC). Results: The SC group showed significantly higher levels of interleukin 6 (IL-6), IL-10, and CCL5 than the AS and NI groups. The SC and AS groups had considerably greater CXCL9 and CXCL10 concentrations than the NI group. Only NI and infected people showed separate clusters in the principal component analysis. Conclusions: SC, as well as AS was characterized by an inflammatory profile.
Résumé
Este estudo busca avaliar quantitativamente a expressão do RNA mensageiro (mRNA) das integrinas alfa1, alfa4, alfa 5, alfa L, citocinas e quimiocinas, a partir de células presentes no líquido intersticial periapical adjacente a dentes com infecção do canal radicular. Foram selecionados 22 indivíduos com necessidade de tratamento endodôntico e encaminhados à Faculdade de Odontologia da Universidade Federal de Minas Gerais (Belo Horizonte, MG, Brasil). As amostras foram coletadas em 11 dentes necróticos e portadores de infecções endodônticas e 11 dentes hígidos que necessitavam de tratamento endodôntico por motivos protéticos. Após a cirurgia de acesso e antes dos procedimentos de limpeza e modelagem do sistema de canais radiculares (T0), imediatamente após a limpeza e formatação do sistema de canais radiculares(T1), em 7 (T2) e 14 dias (T3), um cone de papel esterilizado endodôntico # 20 foi inserido no SCR, mantido por 2 min, e posteriormente armazenado a -70°C. Real-Time PCR analisou microbiologicamente essas amostras para ler a expressão gênica do rRNA microbiano 16S e fragmentos da região ITS do gDNA fúngico da espécie Candida. Após os procedimentos de limpeza e formatação do SCR, três cones de papel absorvente esterilizados foram inseridos. Passivamente, a ponta do papel ultrapassou o ápice radicular em 2 mm e permaneceu por 2 minutos. As amostras foram coletadas imediatamente após a limpeza e modelagem do RCS, 7 e 14 dias após a primeira sessão. As pontas de papel tiveram os 4 mm finais cortados, inseridos em Eppendorf e armazenados a - 70°C. Com este procedimento, o RNA foi extraído do líquido intersticial periapical para caracterizar as expressões dos genes ITGA1, ITGA4, ITGA5, ITGAL, IL-1ß, TNF-α, IL-17A, IL-10, IFN-γ, CCL2/MCP-1, CCL5, CXCR4, e 16S usando PCR em tempo real. O DNA genômico (gDNA) foi extraído para se avaliar a abundância de Candida utilizando-se sequências ITS, por PCR em tempo real. Os resultados demonstraram que os níveis de expressão de mRNA do 16S diminuíram após os procedimentos de limpeza e modelagem e que a abundância de Candida foi insipiente na amostra analisada. As citocinas pro- inflamatórias IL-1ß e IL-17 apresentaram níveis de expressão elevados frente a infecção, reduzindo significativamente após os procedimentos de limpeza e formatação. Os níveis de expressão gênica de TNF-α significantemente aumentaram, em ambos os grupos. Não se observou diferença significativa quanto a expressão gênica das citocinas IFN-γ, IL-10, CCL-2 e CCL-5 e das integrinas ITGAL e ITGA5 nos tempos avaliados. A expressão gênica de CXCR4 reduziu significativamente do tempo T1 para o T2, no grupo experimental. As expressões gênicas de ITGA1 e ITGA4, no grupo experimental, reduziram significativamente de maneira tempo dependente. Finalmente, não houve alteração significativa na expressão de marcadores de macrófagos (CD64), enquanto expressão de marcadores de fibroblastos (S100A4) aumentou significativamente no grupo controle. Concluiu-se que a carga microbiana e a abundância de leveduras correlacionam-se positivamente com a expressão de mediadores pró-inflamatórios e que a que terapia endodôntica negativamente impacta a expressão dos mediadores pró-inflamatórios e das integrinas nos tecidos perirradiculares.
This study seeks to quantitatively evaluate the expression of messenger RNA (mRNA) of integrins alpha1, alfa4, alpha 5, alpha L, cytokines, and chemokines, from cells present in the periapical interstitial fluid adjacent to teeth with root canal infection. Twenty-two individuals needing endodontic treatment and referred to the School of Dentistry of the Federal University of Minas Gerais (Belo Horizonte, MG, Brazil) were selected. The samples were collected in 11 necrotic teeth and carriers of endodontic infections and 11 healthy teeth needing endodontic treatment for prosthetic reasons. After access surgery and before root canal system (RCS) cleaning and shaping procedures (T0), immediately after cleaning and shaping the root canal system (T1), in 7 (T2) and 14 days (T3) an endodontic sterilized paper point #20 was inserted into the RCS, maintained for 2 min, and subsequently stored at -70°C. Real-Time PCR microbiologically analyzed these samples to read the gene expression of microbial rRNA 16S and fragments of the ITS region of the Fungus Candida species gDNA. After RCS cleaning and shaping procedures, three sterilized absorbent paper cones were inserted. Passively, the paper point exceeded the root apex by 2 mm and remained for 2 minutes. Samples were collected immediately after RCS cleaning and shaping, 7 and 14 days after the first session. The paper points have the 4 mm of their tip cut, inserted in Eppendorf, and stored at - 70°C. This procedure extracted RNA from the periapical interstitial fluid to characterize the expressions of the genes ITGA1, ITGA4, ITGA5, ITGAL, IL-1ß, TNF- α, IL-17A, IL-10, IFN-γ, CCL2/MCP-1, CCL5, CXCR4, ITS using Real-Time PCR. The results showed that 16S mRNA expression levels decreased after cleaning and modeling procedures and that Candida abundance was incipient in the analyzed sample. Pro-inflammatory cytokines IL-1ß and IL-17 showed high expression levels against infection, significantly reduced after cleaning and formatting procedures. TNF-α gene expression levels significantly increased in both experimental and control groups. No significant difference was observed regarding the gene expression of the cytokines IFN-γ, IL-10, CCL-2, and CCL-5 and the integrins ITGAL and ITGA5. The gene expressions of ITGA1 and ITGA4 in the experimental group were significantly reduced time-dependent. Finally, there was no significant change in their macrophage markers (CD64) expression, while fibroblast markers (S100A4) expression significantly increased in the control group. It was concluded that microbial load and yeast abundance are positively correlated with the expression of pro-inflammatory mediators and that endodontic therapy negatively impacts the expression of pro-inflammatory mediators and integrins in periradicular tissues.
Sujets)
Parodontite périapicale , Numération de colonies microbiennes , Intégrines , Cytokines , ChimiokinesRésumé
Objective:To investigate the clinical efficacy of Qianjin Weijing Decoction in the treatment of severe pneumonia with the accumulation of phlegm and heat in the lung. Methods:Eighty patients with severe pneumonia with the accumulation of phlegm and heat in the lung received treatment in Wenzhou Hospital of Traditional Chinese Medicine from December 2018 to December 2020. They were randomly allocated to undergo routine treatments (control group, n = 40) or routine treatments combined with Qianjin Weijing Decoction (observation group, n = 40) for 7 days. Clinical efficacy, blood gas analysis, oxygenation index, inflammatory factors (C-reactive protein and procalcitonin), and sequential organ failure score were compared between the two groups. Results:Total response rate in the observation group was significantly higher than that in the control group [87.50% (35/40) vs. 65.00% (26/40), χ2 = 5.59, P < 0.05]. Partial pressure of carbon dioxide (PaCO 2) post-treatment was significantly lower in the observation group than that in the control group [(30.24 ± 2.68) mmHg vs. (39.95 ± 3.27) mmHg, t = 14.52, P < 0.05]. The partial pressure of blood oxygen (PaO 2) and oxygenation index (PaO 2/FiO 2) in the observation group were (76.85 ± 4.56) mmHg and (326.84 ± 8.49) mmHg, respectively, which were significantly higher than those in the control group [(68.39 ± 4.12) mmHg, (284.16 ± 15.56) mmHg, t = -8.70, -15.22, both P < 0.05). Serum levels of C-reactive protein and procalcitonin post-treatment in the observation group were (23.12 ± 6.56) mg/L and (0.31 ± 0.08) μg/L, respectively, which were significantly lower than those in the control group [(38.92 ± 5.62) mg/L, (0.78 ± 0.20) μg/L, t = 11.56, 13.80, both P < 0.05]. Sequential organ failure score was significantly lower in the observation group than in the control group [(2.31 ± 0.46) points vs. (5.12 ± 1.25) points, t = 13.34, P < 0.05)]. Conclusion:Qianjin Weijing Decoction has a good therapeutic effect on severe pneumonia with the accumulation of phlegm and heat in the lung. The treatment can improve blood gas analysis and decrease inflammatory factor levels with a good prognosis.