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1.
BMC Med ; 19(1): 37, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33568158

RESUMO

BACKGROUND: Chronic inflammation, which can be modulated by diet, is linked to high white blood cell counts and correlates with higher cardiometabolic risk and risk of more severe infections, as in the case of COVID-19. METHODS: Here, we assessed the association between white blood cell profile (lymphocytes, basophils, eosinophils, neutrophils, monocytes and total white blood cells) as markers of chronic inflammation, habitual diet and gut microbiome composition (determined by sequencing of the 16S RNA) in 986 healthy individuals from the PREDICT-1 nutritional intervention study. We then investigated whether the gut microbiome mediates part of the benefits of vegetable intake on lymphocyte counts. RESULTS: Higher levels of white blood cells, lymphocytes and basophils were all significantly correlated with lower habitual intake of vegetables, with vegetable intake explaining between 3.59 and 6.58% of variation in white blood cells after adjusting for covariates and multiple testing using false discovery rate (q < 0.1). No such association was seen with fruit intake. A mediation analysis found that 20.00% of the effect of vegetable intake on lymphocyte counts was mediated by one bacterial genus, Collinsella, known to increase with the intake of processed foods and previously associated with fatty liver disease. We further correlated white blood cells to other inflammatory markers including IL6 and GlycA, fasting and post-prandial glucose levels and found a significant relationship between inflammation and diet. CONCLUSION: A habitual diet high in vegetables, but not fruits, is linked to a lower inflammatory profile for white blood cells, and a fifth of the effect is mediated by the genus Collinsella. TRIAL REGISTRATION: The ClinicalTrials.gov registration identifier is NCT03479866 .


Assuntos
Dieta , Frutas , Microbioma Gastrointestinal/genética , Leucócitos , Verduras , Actinobacteria , Adulto , Biomarcadores/sangue , Clostridiales , Clostridium , Jejum , Feminino , Humanos , Interleucina-6/sangue , Contagem de Leucócitos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Ruminococcus
2.
Eur Rev Med Pharmacol Sci ; 25(2): 1097-1100, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33577066

RESUMO

OBJECTIVE: The aim of the present study was to assess the value of inflammatory factors procalcitonin (PCT), interleukin 6 (IL-6), and C-reactive protein (CRP) in the early diagnosis and evaluation of novel coronavirus pneumonia (COVID-19). MATERIALS AND METHODS: The data of 140 patients with pneumonia in our hospital, including 70 who had COVID-19 and 70 who had community-acquired pneumonia (CAP), were statistically analyzed. The levels of PCT, IL-6, and CRP were measured and statistically analyzed to determine the differences between the two groups. The differences in the COVID-19 group were analyzed after subgrouping into the ordinary type, severe type, and critical type. RESULTS: The PCT and CRP levels in the COVID-19 group were statistically lower than those in the CAP group (p < 0.05), but IL-6 was not statistically different between the two groups (p > 0.05). Statistically significant differences existed in IL-6 and CRP when comparing the COVID-19 subgroups of the critical type, severe type, and ordinary type (p < 0.05). However, there was no clinical meaning in the evaluation of the difference in PCT levels among the three subgroups with COVID-19. CONCLUSIONS: PCT and CRP could be used as indicators in the differentiation between COVID-19 and CAP, but IL-6 was of little significance in the differentiation. The higher the IL-6 and CRP, the more severe the condition of COVID-19 might be.


Assuntos
Proteína C-Reativa/metabolismo , /diagnóstico , Interleucina-6/sangue , Pró-Calcitonina/sangue , Biomarcadores/sangue , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/diagnóstico , Diagnóstico Diferencial , Diagnóstico Precoce , Humanos , Pneumonia/sangue , Pneumonia/diagnóstico
3.
Medicine (Baltimore) ; 100(5): e24275, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592871

RESUMO

ABSTRACT: To investigate serum level of high mobility group box protein-1 (HMGB1) and prognosis of patients with end-stage renal disease (ESRD) on hemodialysis (HD) and peritoneal dialysis (PD).This prospective cohort observational study included a total of 253 ESRD patients who came to our hospital for HD or PD from February 2013 to February 2015. Enzyme linked immunosorbent assay (ELISA) method was used to detect the serum level of HMGB1, interleukin (IL-6), IL-8, and tumor necrosis factor-alpha (TNF-α). The kidney disease quality of life short form (KDQOL-SF) and kidney disease targeted area (KDTA) was applied for evaluating the quality of life. Kaplan-Meier (K-M) curve was performed for survival time.Serum level of HMGB1 in patients on HD was higher than PD. HMGB1 levels were gradually decreased with the treatment of HD or PD. Furthermore, HMGB1 was positively correlated with IL-6 and TNF-α. Moreover, patients with higher HMGB1 had more complications than patients with lower HMGB1, but there was no difference for the survival rate. In addition, the quality of life was associated with different dialysis methods.The serum level of HMGB1 and prognosis of ESRD patients was associated with different dialysis methods.


Assuntos
Proteína HMGB1/sangue , Falência Renal Crônica , Diálise Peritoneal , Qualidade de Vida , Diálise Renal , China/epidemiologia , Correlação de Dados , Feminino , Humanos , Interleucina-6/sangue , Estimativa de Kaplan-Meier , Falência Renal Crônica/sangue , Falência Renal Crônica/mortalidade , Falência Renal Crônica/psicologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/métodos , Diálise Peritoneal/estatística & dados numéricos , Prognóstico , Estudos Prospectivos , Diálise Renal/métodos , Diálise Renal/estatística & dados numéricos , Fator de Necrose Tumoral alfa/sangue
4.
Nat Commun ; 12(1): 1041, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33589633

RESUMO

Growing evidence supports that pharmacological application of growth differentiation factor 15 (GDF15) suppresses appetite but also promotes sickness-like behaviors in rodents via GDNF family receptor α-like (GFRAL)-dependent mechanisms. Conversely, the endogenous regulation of GDF15 and its physiological effects on energy homeostasis and behavior remain elusive. Here we show, in four independent human studies that prolonged endurance exercise increases circulating GDF15 to levels otherwise only observed in pathophysiological conditions. This exercise-induced increase can be recapitulated in mice and is accompanied by increased Gdf15 expression in the liver, skeletal muscle, and heart muscle. However, whereas pharmacological GDF15 inhibits appetite and suppresses voluntary running activity via GFRAL, the physiological induction of GDF15 by exercise does not. In summary, exercise-induced circulating GDF15 correlates with the duration of endurance exercise. Yet, higher GDF15 levels after exercise are not sufficient to evoke canonical pharmacological GDF15 effects on appetite or responsible for diminishing exercise motivation.


Assuntos
Regulação do Apetite/fisiologia , Exercício Físico/fisiologia , Comportamento Alimentar/fisiologia , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Fator 15 de Diferenciação de Crescimento/genética , Resistência Física/fisiologia , Adulto , Animais , Creatina Quinase/sangue , Creatina Quinase/genética , Regulação da Expressão Gênica , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/deficiência , Fator 15 de Diferenciação de Crescimento/sangue , Fator 15 de Diferenciação de Crescimento/metabolismo , Humanos , Interleucina-10/sangue , Interleucina-10/genética , Interleucina-6/administração & dosagem , Leptina/sangue , Leptina/genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Knockout , Motivação/fisiologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Miocárdio/metabolismo , Condicionamento Físico Animal , Fatores de Tempo
5.
Wei Sheng Yan Jiu ; 50(1): 46-50, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33517959

RESUMO

OBJECTIVE: To investigate the roles of extracellular signal-regulated kinase(ERK)/c-Jun amino-terminal kinase(JNK) signaling pathway on the expression of interleukin-6(IL-6) and interleukin-8(IL-8) in human embryonic lung fibroblasts(HELF) induced by carbon black. METHODS: HELFs were cultured in RPMI-1640 medium containing 0, 15, 30, 60, 120 or 240 µg/mL carbon black for 24 h, and the appropriate dose of carbon black was determined by MTT assay result HELFs were divided into three groups: HELFs, HELFs transfected with ERK dominant negative mutant plasmid(DN-ERK) and HELFs transfected with JNK dominant negative mutant plasmid(DN-JNK). 100 µg/mL carbon black was used to treat HELFs(CB), DN-ERK HELFs(CB-DN-ERK), DN-JNK HELFs(CB-DN-JNK), and HELFs without any black carbon treatment were considered as control group. At 16 h after carbon black treatment, scanning electron microscope(SEM) was used to observe HELFs morphology and whether there were carbon black particless. At 0, 1, 2, 4, 8, 12, 24 and 36 h, the enzyme linked immunosorbent assay(ELISA) was used to detect CB and control groups HELFs IL-6 and IL-8 expression levels, whereas CB-DN-ERK and CB-DN-JNK HELFs were detected only at 24 h. RESULTS: SEM result showed no carbon black particles were observed in CB group HELFs, whereas their surface projections were increased. The CB group HELFs IL-6 expression levels at 2 h(44. 86±3. 65 ng/L) and 4 h(76. 52±3. 15 ng/L) were significantly lower than those of the control group(96. 78±2. 82 and 147. 32±3. 26 ng/L)(P<0. 05), whereas the IL-6 expression levels were significantly higher than those of the control group(105. 54±6. 10, 101. 27±5. 84 and 97. 15±5. 12 ng/L) at 16 h(202. 64±7. 20 ng/L), 24 h(200. 38±6. 20 ng/L) and 36 h(183. 54±4. 54 ng/L)(P<0. 001). At 24 h(136. 75±3. 81 ng/L) and 36 h(149. 12±2. 74 ng/L), the CB group IL-8 expression levels were significantly higher than those of the control group(75. 16±2. 84 and 73. 44±2. 15 ng/L)(P<0. 001). Compared with CB group HELFs, CB-DN-ERK and CB-DN-JNK groups HELFs had significantly lower IL-6 and IL-8 expression levels(P<0. 05). CONCLUSION: While carbon black induced HELFs IL-6 and IL-8 expression levels changes, ERK and JNK may upregulate IL-6 and IL-8 expression levels.


Assuntos
Interleucina-6 , Interleucina-8 , Citocinas , Humanos , Interleucina-6/genética , Interleucina-8/genética , Proteínas Quinases JNK Ativadas por Mitógeno , Transdução de Sinais , Fuligem/toxicidade
6.
Int J Mol Sci ; 22(3)2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33530554

RESUMO

The aim of this review is to highlight the influence of the Mediterranean Diet (MedDiet) on Gestational Diabetes Mellitus (GDM) and Gestational Weight Gain (GWG) during the COVID-19 pandemic era and the specific role of interleukin (IL)-6 in diabesity. It is known that diabetes, high body mass index, high glycated hemoglobin and raised serum IL-6 levels are predictive of poor outcomes in coronavirus disease 2019 (COVID-19). The immunopathological mechanisms of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection include rising levels of several cytokines and in particular IL-6. The latter is associated with hyperglycemia and insulin resistance and could be useful for predicting the development of GDM. Rich in omega-3 polyunsaturated fatty acids, vitamins, and minerals, MedDiet improves the immune system and could modulate IL-6, C reactive protein and Nuclear Factor (NF)-κB. Moreover, polyphenols could modulate microbiota composition, inhibit the NF-κB pathway, lower IL-6, and upregulate antioxidant enzymes. Finally, adhering to the MedDiet prior to and during pregnancy could have a protective effect, reducing GWG and the risk of GDM, as well as improving the immune response to viral infections such as COVID-19.


Assuntos
/sangue , Diabetes Gestacional/prevenção & controle , Dieta Mediterrânea , Interleucina-6/sangue , Animais , Diabetes Gestacional/sangue , Diabetes Gestacional/epidemiologia , Feminino , Ganho de Peso na Gestação , Humanos , Estilo de Vida , Obesidade/sangue , Obesidade/epidemiologia , Obesidade/prevenção & controle , Gravidez
7.
Adv Exp Med Biol ; 1290: 1-8, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33559852

RESUMO

Interleukin-6 (IL-6) is a proinflammatory cytokine, which is involved in pathogenesis of several cancers. Its expression and function in prostate cancer have been extensively studied in cellular models and clinical specimens. High levels of IL-6 were detected in conditioned media from cells which do not respond to androgens. Increased phosphorylation of signal transducer and activator of transcription (STAT)3 factor which is induced in response to IL-6 is one of the typical features of prostate cancer. However, reports in the literature show regulation of neuroendocrine phenotype by IL-6. Effects of IL-6 on stimulation of proliferation, migration, and invasion lead to the establishment of experimental and clinical approaches to target IL-6. In prostate cancer, anti-IL-6 antibodies were demonstrated to inhibit growth in vitro and in vivo. Clinically, application of anti-IL-6 therapies did not improve survival of patients with metastatic prostate cancer. However, clinical trial design in the future may include different treatment schedule and combinations with experimental and clinical therapies. Endogenous inhibitors of IL-6 such as suppressors of cytokine signaling and protein inhibitors of activated STAT have variable effects on prostate cells, depending on presence or absence of the androgen receptor.


Assuntos
Interleucina-6 , Neoplasias da Próstata , Humanos , Interleucina-6/metabolismo , Masculino , Fosforilação , Neoplasias da Próstata/tratamento farmacológico , Fator de Transcrição STAT3/genética
8.
Blood Adv ; 5(3): 662-673, 2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33560382

RESUMO

This study examined the association between dynamic angiopoietin-2 assessment and COVID-19 short- and long-term clinical course. We included consecutive hospitalized patients from 1 February to 31 May 2020 with laboratory-confirmed COVID-19 from 2 Italian tertiary referral centers (derivation cohort, n = 187 patients; validation cohort, n = 62 patients). Serum biomarker levels were measured by sandwich enzyme-linked immunosorbent assay. Lung tissue from 9 patients was stained for angiopoietin-2, Tie2, CD68, and CD34. Cox model was used to identify risk factors for mortality and nonresolving pulmonary condition. Area under the receiver operating characteristic curve (AUROC) was used to assess the accuracy of 3- and 10-day angiopoietin-2 for in-hospital mortality and nonresolving pulmonary condition, respectively. Three-day angiopoietin-2 increase of at least twofold from baseline was significantly associated with in-hospital mortality by multivariate analysis (hazard ratio [HR], 6.69; 95% confidence interval [CI], 1.85-24.19; P = .004) with AUROC = 0.845 (95% CI, 0.725-0.940). Ten-day angiopoietin-2 of at least twofold from baseline was instead significantly associated with nonresolving pulmonary condition by multivariate analysis (HR, 5.33; 95% CI, 1.34-11.77; P ≤ .0001) with AUROC = 0.969 (95% CI, 0.919-1.000). Patients with persistent elevation of 10-day angiopoietin-2 levels showed severe reticular interstitial thickening and fibrous changes on follow-up computed tomography scans. Angiopoietin-2 and Tie2 were diffusely colocalized in small-vessel endothelia and alveolar new vessels and macrophages. Angiopoietin-2 course is strongly associated with COVID-19 in-hospital mortality and nonresolving pulmonary condition. Angiopoietin-2 may be an early and useful predictor of COVID-19 clinical course, and it could be a relevant part of disease pathogenesis. Angiopoietin-2 blockade may be a COVID-19 treatment option.


Assuntos
Angiopoietina-2/sangue , /patologia , Antivirais/uso terapêutico , Área Sob a Curva , Biomarcadores/sangue , /mortalidade , Mortalidade Hospitalar , Hospitalização , Humanos , Interleucina-6/sangue , Modelos de Riscos Proporcionais , Curva ROC , Fatores de Risco , Taxa de Sobrevida
9.
Int J Mol Sci ; 22(3)2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33572938

RESUMO

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a global public health emergency. Periodontitis, the most prevalent disease that leads to tooth loss, is caused by infection by periodontopathic bacteria. Periodontitis is also a risk factor for pneumonia and the exacerbation of chronic obstructive pulmonary disease, presumably because of the aspiration of saliva contaminated with periodontopathic bacteria into the lower respiratory tract. Patients with these diseases have increased rates of COVID-19 aggravation and mortality. Because periodontopathic bacteria have been isolated from the bronchoalveolar lavage fluid of patients with COVID-19, periodontitis may be a risk factor for COVID-19 aggravation. However, the molecular links between periodontitis and COVID-19 have not been clarified. In this study, we found that the culture supernatant of the periodontopathic bacterium Fusobacterium nucleatum (CSF) upregulated the SARS-CoV-2 receptor angiotensin-converting enzyme 2 in A549 alveolar epithelial cells. In addition, CSF induced interleukin (IL)-6 and IL-8 production by both A549 and primary alveolar epithelial cells. CSF also strongly induced IL-6 and IL-8 expression by BEAS-2B bronchial epithelial cells and Detroit 562 pharyngeal epithelial cells. These results suggest that when patients with mild COVID-19 frequently aspirate periodontopathic bacteria, SARS-CoV-2 infection is promoted, and inflammation in the lower respiratory tract may become severe in the presence of viral pneumonia.


Assuntos
/metabolismo , Meios de Cultivo Condicionados/química , Citocinas/metabolismo , Fusobacterium nucleatum/metabolismo , /genética , /virologia , Linhagem Celular , Meios de Cultivo Condicionados/farmacologia , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Células Epiteliais/microbiologia , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Regulação para Cima/efeitos dos fármacos
10.
Trials ; 22(1): 130, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33573696

RESUMO

OBJECTIVES: The primary objectives of the study are to determine the effectiveness of the Kaba Sura Kudineer (KSK) & Nilavembu Kudineer (NVK) along with standard Allopathy Treatment to compared with Placebo (Decaffeinated Tea) with standard Allopathy Treatment in the management of Symptomatic COVID 19 patients and also in reduction of Hospital Stay Time & Changes in Immunological (IL6) and Bio Chemical Markers (Ferritin, CRP, D-Dimer and LDH). The secondary objectives are to evaluate the safety of the trial medicines and their effects in the reduce the risks of the disease. In addition, to document the profile of Symptomatic COVID 19 patients as per Siddha Principles. TRIAL DESIGN: A Double Blinded, Three arm, Single Centre, Placebo Controlled, Exploratory and comparative Randomized Controlled Trial PARTICIPANTS: Patients who were admitted to the COVID Care Centre at Govt. Institute of Medical Sciences. Noida in India will be recruited. These will be patients with Mild and Moderate symptoms with laboratory confirmed COVID 19 (RT - PCR Tested Positive) aged 18-65, willing and consenting to participate. INTERVENTION AND COMPARATOR: Arm I: Decaffeinated Tea (Placebo - similar in taste and appearance to the other Two Decoctions), 60 Ml Morning and Night after Food, along with standard Allopathy Treatment for 10 days. Arm II: Nilavembu Kudineer (The Siddha Medicines which is used as a standard Anti-Viral drug for the past Pandemics by Siddha Physicians) 60 Ml Morning and Night after Food, along with standard Allopathy Treatment for 10 days. Arm III: Kaba Sura Kudineer (The Siddha Medicine which is proposed to be used as a Treatment for COVID 19 based on Siddha Literature) 60 Ml Morning and Night after Food, along with standard Allopathy Treatment for 10 days. The investigational drugs are registered products under the Govt.of India and bought from GMP Certified Manufacturing Units. MAIN OUTCOMES: Primary outcomes: 1. Reduction in Viral load of SARS-CoV-2 at the end of treatment (10 days). 2. Time taken to convert Patient from symptomatic to Asymptomatic based on Reduction in clinical symptoms (10 days). 3. Effect of drugs inflammatory markers (IL6,) at the end of treatment (10 days). 4. Reduction in hospital stay time (20 days follow up). (Based on RT PCR CT Value 3rd, 6th if needed 10th day). (Based on IL 6 Value needed 10th day or IL6 value on turning negative. (entry level/exit level). Secondary outcomes (10 days): 1. Reduction in use of Intensive Supportive Care. 2. Reduction in incidence of complications (Acute Respiratory Distress Syndrome, other systemic complications). 3. MuLBSTA score for viral pneumonia (multinodular infiltration, hypo-lymphocytosis, bacterial co infection, Total Leucocyte Count (TLC ≤ 0.8 x 109/L), smoking history, hyper-tension and age) score. 4. Laboratory markers (Haematological & Biochemical Markers). 5. Adverse events/effects Siddha-based measurements. 6. Siddha Udaliyal assessment by using Yakkai Ilakkanam (YI) Tool to diagnose body condition for covid-19 patients. RANDOMISATION: The assignment of the participants into 3 Groups will be allocated in 1:1:1 Ratio through randomization Blocks in Microsoft Excel by a Statistician who is not involved in the study. The allocation scheme will be made by another statistician by using a closed envelope after the assessment of eligibility and Informed consent procedures. The groups will be balanced for age and sex with 3:1 Ratio in each group for mild: severe COVID-19 symptoms. BLINDING: The Study is Double Blinded. Participants and Investigators were blinded. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Sample size could not be calculated, Since there are no prior trials on KSK and NVK as a comparative trial. In addition, there are no prior trials on KSK and NVK in this region. A total Number of 120 Patients, 40 each in 3 groups will be recruited in 1:1:1 Ratio. TRIAL STATUS: Protocol Number : SCRUND GIMS Noida Study 1,Version: 2.0 Protocol Date : 20.08.2020 The recruitment period is completed for the trial. The Trial started its recruitment on 22.8.2020. We anticipate study including data analysis will finish in January 2021. This is to state that it was a late submission from authors for publication of the protocol to the BMC, after enrolment in the study was over. TRIAL REGISTRATION: The trial protocol was registered with CTRI (Clinical Trial Registry of India) and number is CTRI/2020/08/027286 on 21.08.2020 FULL PROTOCOL: The full Protocol is attached as an additional file, Accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated. This letter serves as a summary of the key elements of the full protocol. The Study protocol has been reported in accordance with the SPIRIT guidelines.


Assuntos
/tratamento farmacológico , Medicina Ayurvédica , Preparações de Plantas/uso terapêutico , Proteína C-Reativa/metabolismo , /fisiopatologia , Método Duplo-Cego , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Hospitalização , Humanos , Interleucina-6/sangue , L-Lactato Desidrogenase/sangue , Tempo de Internação/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
J Ovarian Res ; 14(1): 28, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33550983

RESUMO

Improving early diagnosis along with timely and effective treatment of COVID-19 are urgently needed. However, at present, the mechanisms underlying disease spread and development, defined prognosis, and immune status of patients with COVID-19 remain to be determined. Patients with severe disease state exhibit a hyperinflammatory response associated with cytokine storm syndrome, hypercoagulability, and depressed cell-mediated immunity. These clinical manifestations, sharing similar pathogenesis, have been well-studied in patients with advanced ovarian cancer. The present review suggests treatment approaches for COVID-19 based on strategies used against ovarian cancer, which shares similar immunopathology and associated coagulation disorders.The chronicization of the hyperinflammatory cytokine storm in patients with severe COVID-19 highlights a defective resistance phase that leads to aspecific chronic inflammation, associated with oxidative stress, which impairs specific T-cell response, induces tissue and endothelial damage, and thrombosis associated with systemic effects that lead to severe multi-organ failure and death. These events are similar to those observed in advanced ovarian cancer which share similar pathogenesis mediated primarily by Interleukin-6, which is, as well demonstrated in ovarian cancer, the key cytokine driving the immunopathology, related systemic symptoms, and patient prognosis.Consistent with findings in other disease models with similar immunopathology, such as advanced ovarian cancer, treatment of severe COVID-19 infection should target inflammation, oxidative stress, coagulation disorders, and immunodepression to improve patient outcome. Correctly identifying disease stages, based on available laboratory data, and developing a specific protocol for each phase is essential for effective treatment.


Assuntos
/complicações , Síndrome da Liberação de Citocina/etiologia , Interleucina-6/metabolismo , Neoplasias Ovarianas/metabolismo , Corticosteroides/uso terapêutico , Aspirina/uso terapêutico , /metabolismo , /terapia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/prevenção & controle , Feminino , Humanos , Imunização Passiva , Inflamação/tratamento farmacológico , Inflamação/virologia , Interleucina-6/imunologia , Necrose , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/imunologia , Estresse Oxidativo
12.
Medicine (Baltimore) ; 100(6): e24647, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578591

RESUMO

PURPOSE: Presently, whether interleukin-6 (IL-6) gene-174 G/C promoter polymorphism is correlated to the susceptibility of multiple myeloma (MM) remains controversial. For this reason, the method of meta-analysis was applied to exploring the association between IL-6 gene-174 G/C promoter polymorphism and MM. METHOD: Two independent researchers systematically searched PubMed, EMBASE, Google academic, Cochrane Library and Chinese literature databases to screen case-control studies on IL-6 gene-174 G/C promoter polymorphism and MM susceptibility. The retrieval period was limited from the formation of the database to January 2020, and data analysis was conducted by employing Stata 11.0 software. RESULT: Seven articles were ultimately included in the present study, including 594 MM patients and 681 controls. Integration analysis exhibited that compared with GC or CC genotype, GG genotype did not increase MM susceptibility (OR = 0.95, 95% CI 0.75-1.22; OR = 0.79, 95% CI 0.52-1.19, respectively). Further, in comparison with CC genotype, GC genotype also presented no effect on increasing MM susceptibility (OR = 0.79, 95% CI 0.53-1.16), while compared with GC+CC genotype, GG genotype had no significant relationship with MM susceptibility (OR = 0.94, 95% CI 0.75-1.19). In subsequent analysis, an observation was made that allele G or C was not related to MM susceptibility (OR = 0.92, 95% CI 0.76-1.12). Funnel chart and Begg test did not reveal publication bias in the included articles. CONCLUSION: The results of the present study advocate that there is no testimony to support the relationship between IL-6 gene-174 G/C promoter polymorphism and MM susceptibility.


Assuntos
Interleucina-6/genética , Mieloma Múltiplo/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Alelos , Estudos de Casos e Controles , China/epidemiologia , Gerenciamento de Dados , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Genótipo , Humanos , Fatores de Risco
13.
Curr Med Sci ; 41(1): 14-23, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33582900

RESUMO

Last December 2019, a cluster of viral pneumonia cases identified as coronavirus disease 2019 (COVID-19) was reported in Wuhan, China. We aimed to explore the frequencies of nasal symptoms in patients with COVID-19, including loss of smell and taste, as well as their presentation as the first symptom of the disease and their association with the severity of COVID-19. In this retrospective study, 1206 laboratory-confirmed COVID-19 patients were included and followed up by telephone one month after discharged from Tongji Hospital, Wuhan. Demographic data, laboratory values, comorbidities, symptoms, and numerical rating scale scores (0-10) of nasal symptoms were extracted from the hospital medical records, and confirmed or reevaluated by the telephone follow-up. From patients (n=1172) completing follow-up, 199 (17%) subjects had severe COVID-19 and 342 (29.2%) reported nasal symptoms. 20.6% COVID-19 patients had loss of taste (median score=6), while 11.4% had loss of smell (median score=5). Loss of taste scores, but not loss of smell scores, were significantly increased in severe vs. non-severe COVID-19 patients. Interleukin (IL)-6 and lactose dehydrogenase (LDH) serum levels were positively correlated with loss of taste scores. About 80% of COVID-19 patients recovered from smell and taste dysfunction in 2 weeks. In this cohort, only 1 out of 10 hospital admitted patients had loss of smell while 1 out of 5 reported loss of taste which was associated to severity of COVID-19. Most patients recovered smell and taste dysfunctions in 2 weeks.


Assuntos
/epidemiologia , Interleucina-6/sangue , L-Lactato Desidrogenase/sangue , Transtornos do Olfato/epidemiologia , Distúrbios do Paladar/virologia , Idoso , /complicações , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/sangue , Transtornos do Olfato/virologia , Recuperação de Função Fisiológica , Estudos Retrospectivos , Autorrelato , Índice de Gravidade de Doença , Distúrbios do Paladar/sangue
14.
Curr Med Sci ; 41(1): 58-61, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33582906

RESUMO

Over 85 590 000 individuals have been infected with severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Although there have been an increasing number of reports on coronavirus disease 2019 (COVID-19), it is unclear why infected children show milder symptoms than adults. A retrospective case study was performed at two designated hospitals for COVID-19. Patients (56 children and 63 adults) with confirmed SARS-CoV-2 infection and mild pneumonia were randomly enrolled in this study. The median age of the children was 7.0 years, and 51.79% of them were boys. The median age of the adults was 57 years, and 47.62% were men. The most common symptoms were fever, cough, sputum and diarrhoea. There were no significant differences in symptoms between children and adult patients. In terms of immunological indices on admission, adult patients displayed typical leukopenia and markedly higher levels of IL-2, IL-4, and IL-6 than child patients. The elevation of IL-2, IL-4 and IL-6 in adults induced more extensive lung injury. The effective and non-aggressive immune response successfully resisted SARS-CoV-2 invasion and maintained mild symptoms in child patients. The correlation of higher IL-2, IL-4, and IL-6 with the lung injury might be evidence that preventing excessive cytokine production can avoid further lung damage in these patients.


Assuntos
/imunologia , Imunidade , Leucopenia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Interleucina-2/sangue , Interleucina-4/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença
15.
Aging (Albany NY) ; 13(2): 1620-1632, 2021 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-33429366

RESUMO

Both lung adenocarcinoma and coronavirus disease 2019 would cause pulmonary inflammation. Angiotensin-converting enzyme 2, the functional receptor of SARS-CoV-2, also plays a key role in lung adenocarcinoma. To study the risk of SARS-CoV-2 infection in lung adenocarcinoma patients, mRNA and microRNA profiles were obtained from The Cancer Genome Atlas and Gene Expression Omnibus followed by bioinformatics analysis. A network which regards angiotensin-converting enzyme 2 as the center was structured. In addition, via immunological analysis to explore the essential mechanism of SARS-CoV-2 susceptibility in lung adenocarcinoma. Compared with normal tissue, angiotensin-converting enzyme 2 was increased in lung adenocarcinoma patients. Furthermore, a total of 7 correlated differently expressed mRNAs (ACE2, CXCL9, MMP12, IL6, AZU1, FCN3, HYAL1 and IRAK3) and 5 correlated differently expressed microRNAs (miR-125b-5p, miR-9-5p, miR-130b-5p, miR-381-3p and miR-421) were screened. Interestingly, the most frequent toll-like receptor signaling pathway was enriched by mRNA (interlukin 6) and miRNA (miR-125b-5p) sets simultaneously. In conclusion, it was assumed that miR-125b-5p-ACE2-IL6 axis could alter the risk of SARS-CoV-2 infection in lung adenocarcinoma patients.


Assuntos
Adenocarcinoma de Pulmão/virologia , /complicações , Neoplasias Pulmonares/virologia , Transcriptoma , Adenocarcinoma de Pulmão/metabolismo , Biologia Computacional , Humanos , Interleucina-6/metabolismo , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , Fatores de Risco
16.
Aging (Albany NY) ; 13(2): 1571-1590, 2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33465050

RESUMO

The main aspects of severe COVID-19 disease pathogenesis include hyper-induction of proinflammatory cytokines, also known as 'cytokine storm', that precedes acute respiratory distress syndrome (ARDS) and often leads to death. COVID-19 patients often suffer from lung fibrosis, a serious and untreatable condition. There remains no effective treatment for these complications. Out of all cytokines, TNFα and IL-6 play crucial roles in cytokine storm pathogenesis and are likely responsible for the escalation in disease severity. These cytokines also partake in the molecular pathogenesis of fibrosis. Therefore, new approaches are urgently needed, that can efficiently and swiftly downregulate TNFα, IL-6, and the inflammatory cytokine cascade, in order to curb inflammation and prevent fibrosis, and lead to disease remission. Cannabis sativa has been proposed to modulate gene expression and inflammation and is under investigation for several potential therapeutic applications against autoinflammatory diseases and cancer. Here, we hypothesized that the extracts of novel C. sativa cultivars may be used to downregulate the expression of pro-inflammatory cytokines and pathways involved in inflammation and fibrosis. Initially, to analyze the anti-inflammatory effects of novel C. sativa cultivars, we used a well-established full thickness human 3D skin artificial EpiDermFTTM tissue model, whereby tissues were exposed to UV to induce inflammation and then treated with extracts of seven new cannabis cultivars. We noted that out of seven studied extracts of novel C. sativa cultivars, three (#4, #8 and #14) were the most effective, causing profound and concerted down-regulation of COX2, TNFα, IL-6, CCL2, and other cytokines and pathways related to inflammation and fibrosis. These data were further confirmed in the WI-38 lung fibroblast cell line model. Most importantly, one of the tested extracts had no effect at all, and one exerted effect that may be deleterious, signifying that careful cannabis cultivar selection must be based on thorough pre-clinical studies. The observed pronounced inhibition of TNFα and IL-6 is the most important finding, because these molecules are currently considered to be the main targets in COVID-19 cytokine storm and ARDS pathogenesis. Novel anti-TNFα and anti-IL-6 cannabis extracts can be useful additions to the current anti-inflammatory regimens to treat COVID-19, as well as various rheumatological diseases and conditions, and 'inflammaging' - the inflammatory underpinning of aging and frailty.


Assuntos
Cannabis , Síndrome da Liberação de Citocina , Interleucina-6/antagonistas & inibidores , Extratos Vegetais/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Anti-Inflamatórios/farmacologia , Canabinoides/farmacologia , Linhagem Celular , Fibroblastos/efeitos dos fármacos , Humanos , Inflamação/virologia , Pele/efeitos dos fármacos , Técnicas de Cultura de Tecidos
17.
Cytokine ; 140: 155438, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33493861

RESUMO

BACKGROUND: Patients infected by SARS-CoV-2 can develop interstitial pneumonia, requiring hospitalisation or mechanical ventilation. Increased levels of inflammatory biomarkers are associated with development of acute respiratory distress syndrome (ARDS). The aim of the present study was to determine which cytokines are associated with respiratory insufficiency in patients hospitalised for COVID-19. PATIENTS AND METHODS: Data on 67 consecutive patients were collected between March 8 and March 30, 2020. PaO2/FiO2 ratio (P/F) was calculated at hospital admission. The following cytokines were analysed: interleukin (IL)-6, IL-1α, IL-18, tumour necrosis factor (TNF)-ß, macrophage colony-stimulating factor (M-CSF), macrophage migration inhibitory factor (MIF), soluble IL-2 receptor alpha (sIL-2Rα; CD25), IL-12ß, IL-3, interferon (IFN) α2a, monokine induced by gamma interferon (MIG), monocyte-chemotactic protein 3 (MCP3) and hepatocyte growth factor (HGF). RESULTS: P/F lower than 300 was recorded in 22 out of 67 patients (32.8%). P/F strongly correlated with IL-6 (r = -0.62, P < 0.0001), M-CSF (r = -0.63, P < 0.0001), sIL-2Rα (r = -0.54, P < 0.0001), and HGF (r = -0.53, P < 0.0001). ROC curve analyses for IL-6 (AUC 0.83, 95% CI 0.73-0.93, P < 0.0001), M-CSF (AUC 0.87, 95% CI 0.79-0.96, P < 0.0001), HGF (AUC 0.81, 95% CI 0.70-0.93, P < 0.0001), and sIL-2Rα (AUC 0.80, 95% CI, 0.69-0.90, P < 0.0001) showed that these four soluble factors were highly significant. All four soluble factors correlated with LDH, white blood cell count, neutrophil count, lymphocyte count, and CRP. CONCLUSION: IL-6, M-CSF, sIL-2Rα, and HGF are possibly involved in the main biological processes of severe COVID-19, mirroring the level of systemic hyperinflammatory state, the level of lung inflammation, and the severity of organ damage.


Assuntos
/sangue , Citocinas/sangue , Imunidade Inata/imunologia , Inflamação/sangue , Subunidade alfa de Receptor de Interleucina-2/sangue , Insuficiência de Múltiplos Órgãos/sangue , Pneumonia/sangue , Idoso , /virologia , Feminino , Fator de Crescimento de Hepatócito/sangue , Interações Hospedeiro-Patógeno , Humanos , Inflamação/complicações , Interleucina-6/sangue , Fator Estimulador de Colônias de Macrófagos/sangue , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/complicações , Pneumonia/complicações , Pneumonia/virologia , Estudos Retrospectivos , /fisiologia
18.
Nat Commun ; 12(1): 213, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431899

RESUMO

High-fat diet (HFD) decreases insulin sensitivity. How high-fat diet causes insulin resistance is largely unknown. Here, we show that lean mice become insulin resistant after being administered exosomes isolated from the feces of obese mice fed a HFD or from patients with type II diabetes. HFD altered the lipid composition of exosomes from predominantly phosphatidylethanolamine (PE) in exosomes from lean animals (L-Exo) to phosphatidylcholine (PC) in exosomes from obese animals (H-Exo). Mechanistically, we show that intestinal H-Exo is taken up by macrophages and hepatocytes, leading to inhibition of the insulin signaling pathway. Moreover, exosome-derived PC binds to and activates AhR, leading to inhibition of the expression of genes essential for activation of the insulin signaling pathway, including IRS-2, and its downstream genes PI3K and Akt. Together, our results reveal HFD-induced exosomes as potential contributors to the development of insulin resistance. Intestinal exosomes thus have potential as broad therapeutic targets.


Assuntos
Dieta Hiperlipídica , Exossomos/metabolismo , Resistência à Insulina/genética , Fosfatidilcolinas/metabolismo , Regulação para Cima/genética , Tecido Adiposo/metabolismo , Animais , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Dislipidemias/complicações , Dislipidemias/genética , Dislipidemias/patologia , Células Epiteliais/metabolismo , Fígado Gorduroso/complicações , Fígado Gorduroso/genética , Fígado Gorduroso/patologia , Fezes , Regulação da Expressão Gênica , Intolerância à Glucose , Proteínas de Fluorescência Verde/metabolismo , Humanos , Insulina/metabolismo , Interleucina-6/sangue , Intestinos/citologia , Lipídeos/química , Fígado/metabolismo , Fígado/patologia , Ativação de Macrófagos , Camundongos Endogâmicos C57BL , Receptores de Hidrocarboneto Arílico/metabolismo , Transdução de Sinais , Tetraspanina 30/metabolismo , Fator de Necrose Tumoral alfa/sangue
19.
Nat Commun ; 12(1): 301, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436596

RESUMO

Macrophages are innate immune cells that contribute to fighting infections, tissue repair, and maintaining tissue homeostasis. To enable such functional diversity, macrophages resolve potentially conflicting cues in the microenvironment via mechanisms that are unclear. Here, we use single-cell RNA sequencing to explore how individual macrophages respond when co-stimulated with inflammatory stimuli LPS and IFN-γ and the resolving cytokine IL-4. These co-stimulated macrophages display a distinct global transcriptional program. However, variable negative cross-regulation between some LPS + IFN-γ-specific and IL-4-specific genes results in cell-to-cell heterogeneity in transcription. Interestingly, negative cross-regulation leads to mutually exclusive expression of the T-cell-polarizing cytokine genes Il6 and Il12b versus the IL-4-associated factors Arg1 and Chil3 in single co-stimulated macrophages, and single-cell secretion measurements show that these specialized functions are maintained for at least 48 h. This study suggests that increasing functional diversity in the population is one strategy macrophages use to respond to conflicting environmental cues.


Assuntos
Polaridade Celular , Macrófagos/citologia , Animais , Arginase/metabolismo , Polaridade Celular/efeitos dos fármacos , Polaridade Celular/genética , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Interferon gama/farmacologia , Interleucina-12/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Aprendizado de Máquina , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Redes Neurais de Computação , Razão de Chances , Análise de Célula Única , Fatores de Transcrição/metabolismo , Transcrição Genética/efeitos dos fármacos
20.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(2): 158-163, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33504422

RESUMO

Objective To investigate the regulatory effect of interleukin-6 (IL-6) on the expression of indoleamine 2, 3-dioxygenase (IDO) in the early pregnant chorionic villi and decidua tissues. Methods The chorionic villi and decidua tissues of women who received induced abortion at early pregnancy were collected. The expression of IL-6 and IDO in the chorionic villi and decidua tissues was detected by Western blotting. Subsequently, 10, 50 and 100 ng/mL IL-6 was added into the chorionic villi and decidua tissues to culture for 48 hours. In addition, changes in the IDO mRNA and protein expression levels in chorionic villi and decidua tissues were detected by real-time quantitative reverse PCR (qRT-PCR) and Western blotting. Results Both IDO and IL-6 were expressed in human early pregnant chorionic villi and decidua tissues. Besides, the expression of these two proteins were positively correlated (r=0.72, 0.91). After being cultured with 10, 50 and 100 ng/mL IL-6 for 48 hours, IDO protein expression significantly increased in the cultured early pregnant chorionic villi and decidua tissues in an IL-6 concentration-dependent manner. Conclusion The expression of IL-6 and IDO proteins at the maternal-fetal interface show a positive correlation in normal physiological pregnancy, and IL-6 may up-regulate the expression of IDO.


Assuntos
Vilosidades Coriônicas , Interleucina-6 , Decídua , Feminino , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Interleucina-6/genética , Gravidez , RNA Mensageiro
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