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1.
Rev. bras. cir. cardiovasc ; 37(4): 447-453, Jul.-Aug. 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1394729

ABSTRACT

Abstract Introduction: This study's objective is to investigate the effect of downregulation of micro ribonucleic acid (miR)-124a on myocardial injury after ischemia reperfusion (I/R) in rats. Methods: Sprague Dawley (SD) rats (n=20) were divided into four groups - sham, I/R, I/R+miR-124a antagomir (I/R+ant-miR-124a), and I/R+ant-normal control (NC). The pathomorphological and infarct size variance of injured myocardial tissues with IR were conducted with hematoxylin (HE) and triphenyltetrazolium chloride (TTC) staining. The expression levels of miR-124a, BAX, nuclear factor kappa B (NF-KB), Notch1, and Hes1 were examined by quantitative real-time polymerase chain reaction or Western blot in myocardium. The inflammatory cytokines interleukin (IL)-6, IL-1β, and tumor necrosis factor alpha (TNF-α) were detected by the enzyme-linked immunosorbent assay, as well as the activity of lactate dehydrogenase (LDH) and creatine kinase (CK) in serum by colorimetry. Results: The expression of miR-124a was increased in the I/R group. Compared with I/R and I/R+ant-NC groups, after downregulating miR-124a, the expression of IL-6, IL-1β, TNF-α, BAX, NF-KB, LDH, and CK were decreased, but the expression of Notch1 and Hes1 were increased. In HE staining, myocardial tissue edema, red blood cell exudation, and myocardial fiber arrangement disorder were accompanied by inflammatory cell infiltration and local necrosis in the I/R group. However, the pathological injury of myocardial tissue was alleviated after downregulating miR-124a. Additionally, TTC results showed that the myocardial infarction area was decreased in the I/R+ant-miR-124a group. Conclusion: Downregulation of miR-124a expression through Notch pathway can significantly reduce myocardial damage after 24 hours of I/R in SD rats. Therefore, miR-124a may become a potential therapeutic target for I/R injury.

2.
Dement. neuropsychol ; 16(2): 228-236, Apr.-June 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1384665

ABSTRACT

ABSTRACT. Alzheimer's dementia (AD) is a neurodegenerative disease. The mechanism of oxidative stress in AD is due to amyloid beta (Aβ) protein that aggregates to form plaques, which further triggers chronic inflammation and neuronal apoptosis. Purple sweet potato extract with the main content of anthocyanins is a potential antioxidant with a direct target on the amyloid cascade hypothesis. Objective: The research objective was to determine the role of purple sweet potato water extract as an antioxidant and anti-inflammatory in preventing apoptosis in order to provide a neuroprotective effect in d-galactose-induced rats. Methods: A total of 100 male Wistar rats with randomized posttest-only control group design that met the eligibility criteria were included in this study. The treatment group was given 200 mg/kg BW/day of purple sweet potato water extract on days 1-70. d-galactose induction was administered in the treatment and control groups on days 15-70. Results: The independent t-test showed that the mean tumor necrosis factor-α (TNF-α) levels in the treatment group (735.36±139.74) was significantly lower than that in the control group (896.77±152.52). The p53 and glial fibrillary acidic protein (GFAP) expressions of astrocyte cells in the treatment group were significantly lower than that in the control group. The brain-derived neurotrophic factor (BDNF) levels in the treatment group (498.13±121.47) were higher than that in the control (391.93±140.28), and there was a significant increase in spatial working memory in the treatment group (72.01±10.22) than the control (59.77±11.87). Conclusions: The neuroprotective effect of purple sweet potato extract is due to d-galactose induction resulting from decrease in TNF-α levels, p53 expression, and GFAP expression and increase in BDNF levels and spatial working memory.


RESUMO. A doença de Alzheimer (DA) é uma doença neurodegenerativa. O mecanismo de estresse oxidativo na DA ocorre devido à proteína beta amilóide que se agrega para formar placas que desencadeiam inflamação crônica e apoptose neuronal. O extrato de batata-doce roxa composto principalmente por antocianinas é um potencial antioxidante com efeito direto sobre a hipótese da cascata amilóide. Objetivo: O objetivo da pesquisa foi determinar o papel do extrato aquoso de batata-doce roxa como antioxidante e anti-inflamatório na prevenção da apoptose, para proporcionar um efeito neuroprotetor em ratos induzidos por D-galactose. Métodos: Grupo controle randomizado pós-teste com 100 ratos Wistar machos que preencheram os critérios de elegibilidade. O grupo de tratamento recebeu 200mg/kg de peso corporal/dia de extrato aquoso de batata-doce roxa nos dias 1-70. A indução de D-galactose foi testada nos grupos de tratamento e controle nos dias 15-70. Resultados: O teste t independente mostrou que a média dos níveis de TNF-α no grupo de tratamento (735,36±139,74) foi significativamente menor do que no grupo controle (896,77±152,52). A expressão de p53 e a expressão de GFAP de células de astrócitos foram significativamente menores no grupo de tratamento do que no grupo controle. Os níveis de BDNF no grupo de tratamento (498,13±121,47) foram maiores que no grupo controle (391,93±140,28) e houve um aumento significativo da memória de trabalho espacial no grupo de tratamento (72,01±10,22) em relação ao controle (59,77±11,87). Conclusões: O efeito neuroprotetor do extrato de batata-doce roxa é devido à indução de D-galactose pela diminuição dos níveis de TNF-α, expressão de p53 e expressão de GFAP, aumentando assim os níveis de BDNF e memória espacial.

3.
Rev. bras. cir. cardiovasc ; 37(1): 35-47, Jan.-Feb. 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1365526

ABSTRACT

Abstract Introduction: Severe coronavirus disease 2019 (COVID-19) is characterised by hyperinflammatory state, systemic coagulopathies, and multiorgan involvement, especially acute respiratory distress syndrome (ARDS). We here describe our preliminary clinical experience with COVID-19 patients treated via an early initiation of extracorporeal blood purification combined with systemic heparinisation and respiratory support. Methods: Fifteen patients were included; several biomarkers associated with COVID-19 severity were monitored. Personalised treatment was tailored according to the levels of interleukin (IL)-6, IL-8, tumour necrosis factor alpha, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio, thrombocyte counts, D-dimers, and fibrinogen. Treatment consisted of respiratory support, extracorporeal blood purification using the AN69ST (oXiris®) hemofilter, and 300 U/kg heparin to maintain activation clotting time ≥ 180 seconds. Results: Ten patients presented with severe to critical disease (dyspnoea, hypoxia, respiratory rate > 30/min, peripheral oxygen saturation < 90%, or > 50% lung involvement on X-ray imaging). The median intensive care unit length of stay was 9.3 days (interquartile range 5.3-10.1); two patients developed ARDS and died after 5 and 26 days. Clinical improvement was associated with normalisation (increase) of thrombocytes and white blood cells, stable levels of IL-6 (< 50 ng/mL), and a decrease of CRP and fibrinogen. Conclusion: Continuous monitoring of COVID-19 severity biomarkers and radiological imaging is crucial to assess disease progression, uncontrolled inflammation, and to avert irreversible multiorgan failure. The combination of systemic heparin anticoagulation regimens and extracorporeal blood purification using cytokine-adsorbing hemofilters may reduce hyperinflammation, prevent coagulopathy, and support clinical recovery.

4.
Arq. bras. cardiol ; 118(1): 52-58, jan. 2022. tab, graf
Article in Portuguese | LILACS | ID: biblio-1360111

ABSTRACT

Resumo Fundamento Os níveis de Proteína 3 relacionada ao fator de necrose tumoral/complemento sérico C1q (CTRP3) e a relação com a fibrilação atrial (FA) na doença arterial coronária estável (DAC) não estão claros atualmente. Objetivos O objetivo deste estudo foi investigar a mudança nos níveis séricos de CTRP3 e sua relação com a FA paroxística em DAC estável. Método O estudo incluiu 252 pacientes com DAC e 50 controles saudáveis com idade/sexo compatíveis. Os níveis séricos de CTRP3 foram medidos, além da anamnese de rotina, exame físico, exames laboratoriais e ecocardiograma. Os pacientes foram divididos em grupos com e sem DAC e indivíduos com DAC com e sem FA paroxística. Os valores eram estatisticamente significativos quando p<0,05. Resultados Os níveis séricos de CTRP3 foram significativamente menores em pacientes com DAC do que no grupo controle (p<0,001). A FA foi detectada em 28 pacientes (15,08%) no grupo DAC. A frequência de hipertensão e do sexo feminino, a proteína C reativa de alta sensibilidade (PCR-as), o nitrogênio ureico no sangue, os níveis de creatinina e o diâmetro diastólico do átrio esquerdo foram maiores (p<0,05 para cada um), e os níveis de CTRP3 foram mais baixos em pacientes com FA (p<0,001). Na análise de regressão logística, os níveis séricos de CTRP3 e os diâmetros diastólicos do átrio esquerdo foram independentemente determinados pelos pacientes com FA (p<0,01 para cada um). Nesta análise, observamos que cada 1 ng/mL de redução nos níveis de CTRP3 aumentou o risco de FA em 10,7%. Na análise ROC dos valores de CTRP3 para detectar pacientes com FA, a área da curva ROC para CTRP3 foi 0,971 (0,951-991) e considerada estatisticamente significativa (p<0,001). Quando o ponto de corte de CTRP3 foi considerado em 300 ng/mL, demonstrava a presença de FA com 87,9% de sensibilidade e 86,8% de especificidade. Conclusão Os níveis séricos de CTRP3 caíram significativamente em pacientes com DAC estável, e níveis reduzidos de CTRP3 estiveram relacionados à presença de FA paroxística nesses pacientes.


Abstract Background Serum Complement C1q/tumor necrosis factor-related protein-3 (CTRP3) levels and the relationship with atrial fibrillation (AF) in stable coronary artery disease (CAD) are not clearly known. Objective The aim of this study was to investigate the change in serum CTRP3 levels and its relationship with paroxysmal AF in stable CAD. Method The study included 252 patients with CAD and 50 age-sex matched healthy control subjects. Serum CTRP3 levels were measured in addition to routine anamnesis, physical examination, laboratory and echocardiography examinations. The patients were divided into groups with and without CAD and CAD patients with and without paroxysmal AF. Statistical significance was accepted as p<0.05. Results Serum CTRP3 levels were found to be significantly lower in patients with CAD than in the control group (p<0.001). AF was detected in 38 patients (15.08%) in the CAD group. The frequency of hypertension and female gender, hs-CRP, blood urea nitrogen, creatinine levels and left atrial end-diastolic (LAd) diameter were higher (p<0.05 for each one), and CTRP3 levels were lower in patients with AF (p <0.001). In the logistic regression analysis, serum CTRP3 levels and LAd diameters were independently determined the patients with AF (p<0.01 for each one). In this analysis, we found that every 1 ng/mL reduction in CTRP3 levels increased the risk of AF by 10.7%. In the ROC analysis of CTRP3 values for detecting patients with AF, the area under the ROC curve for CTRP3 was 0.971 (0.951-991) and was statistically significant (p<0.001). When the CTRP3 cut-off value was taken as 300 ng/mL, it was found to predict the presence of AF with 87.9% sensitivity and 86.8% specificity. Conclusion Serum CTRP3 levels were significantly reduced in patients with stable CAD and decreased CTRP3 levels were closely related to the presence of paroxysmal AF in these patients.


Subject(s)
Humans , Female , Atrial Fibrillation , Coronary Artery Disease/diagnostic imaging , Echocardiography , ROC Curve , Heart Atria
5.
Acta cir. bras ; 37(1): e370105, 2022. tab, graf
Article in English | LILACS-Express | LILACS, VETINDEX | ID: biblio-1364250

ABSTRACT

ABSTRACT Purpose: To evaluate how the induction of liver damage by ischemia and reperfusion affects the adipose tissue of lean and obese mice. Methods: Lean and diet-induced obese mice were subjected to liver ischemia (30 min) followed by 6 h of reperfusion. The vascular stromal fraction of visceral adipose tissue was analyzed by cytometry, and gene expression was evaluated by an Array assay and by RT-qPCR. Intestinal permeability was assessed by oral administration of fluorescein isothiocyanate (FITC)-dextran and endotoxemia by serum endotoxin measurements using a limulus amebocyte lysate assay. Results: It was found that, after liver ischemia and reperfusion, there is an infiltration of neutrophils, monocytes, and lymphocytes, as well as an increase in the gene expression that encode cytokines, chemokines and their receptors in the visceral adipose tissue of lean mice. This inflammatory response was associated with the presence of endotoxemia in lean mice. However, these changes were not observed in the visceral adipose tissue of obese mice. Conclusions: Liver ischemia and reperfusion induce an acute inflammatory response in adipose tissue of lean mice characterized by an intense chemokine induction and leukocyte infiltration; however, inflammatory alterations are already present at baseline in the obese adipose tissue and liver ischemia and reperfusion do not injure further.

6.
Rev. bras. oftalmol ; 81: e0003, 2022. tab, graf
Article in English | LILACS | ID: biblio-1357125

ABSTRACT

ABSTRACT Objective To describe the use of subconjuctival administration of the anti-tumor necrosis factor agent adalimumab for treatment of dry eye in patients with Sjögren's syndrome, and to investigate conjunctival healing. Methods Prospective, nonrandomized, noncomparative interventional case series including consecutive patients with Sjögren's syndrome and dry eye disease treated with subconjunctival adalimumab, who were refractory to conventional treatment. Patients with infectious ocular surface involvement or structural changes in the tear pathway or eyelids were excluded. Data recorded included age, sex, lissamine green staining pattern, Schirmer test results, intraocular pressure, conjunctival mobility, tear break up time and findings of biomicroscopic evaluation, following fluorescein dye instillation. The Ocular Surface Disease Index questionnaire validated for the Portuguese language was used for subjective assessment of patients. Results Eleven eyes of eight patients were studied. Mean patient age was 53±13.4 years. Patients were treated with subconjunctival injection of 0.03 mL of adalimumab and followed for 90 days thereafter. There were no statistically significant objective improvement (objective tests results; p>0.05) and no statistically significant changes in intraocular pressure (p=0.11). Questionnaire responses revealed a significant improvement in ocular symptoms (p=0.002). Conclusion Based on the Ocular Surface Disease Index questionnaire, subconjunctival administration of adalimumab improved dry eye symptoms. However, objective assessments failed to reveal statistically significant improvements.


RESUMO Objetivo Descrever o uso subconjuntival do antifator de necrose tumoral adalimumabe para o tratamento do olho seco em pacientes com síndrome de Sjögren e avaliar a cicatrização conjuntival. Métodos Série de casos intervencionista com desenho prospectivo, não randomizado, não comparativo. O medicamento adalimumabe foi aplicado em região subconjuntival em pacientes com síndrome de Sjögren e olho seco que eram resistentes a outras terapias convencionais. Pacientes com patologias oculares de origem infecciosa ou com alterações estruturais nas vias lacrimais e pálpebras foram excluídos do estudo. Os dados coletados incluíram idade, sexo, teste com lisamina verde, teste de Schirmer, pressão intraocular, mobilidade conjuntival, teste de ruptura do filme lacrimal, e avaliação biomicroscópica com colírio de fluoresceína. Além disso, o questionário Ocular Surface Disease Index validado para a língua portuguesa foi aplicado com objetivo de avaliar subjetivamente a resposta dos pacientes ao tratamento. Resultados Onze olhos de oito pacientes foram estudados. A idade média dos pacientes foi de 53±13,4 anos. A dose aplicada de adalimumabe subconjuntival foi de 0,03mL, e a duração do seguimento foi de 90 dias após a injeção. Não houve melhora estatisticamente significativa nos testes objetivos (todos apresentaram p>0,05). A pressão intraocular também não sofreu variações estatisticamente significativas (p=0,11). Entretanto, por meio do questionário, foi registrada melhora significativa dos sintomas oculares (p=0,002). Conclusão O uso do adalimumabe subconjuntival melhorou os sintomas de olho seco, avaliados por meio do questionário Ocular Surface Disease Index, mas não houve melhora estatisticamente significativa na avaliação objetiva.


Subject(s)
Humans , Female , Adult , Middle Aged , Aged , Dry Eye Syndromes/drug therapy , Sjogren's Syndrome/drug therapy , Adalimumab/administration & dosage , Dry Eye Syndromes/etiology , Sjogren's Syndrome/complications , Prospective Studies , Conjunctiva , Injections, Intraocular/methods , Adalimumab/therapeutic use
7.
Article in Chinese | WPRIM | ID: wpr-936401

ABSTRACT

Objective @# The purpose of this study was to clarify the regulatory effect and mechanism of Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) on human periodontal ligament stem cell (hPDLSC) proliferation and osteogenic differentiation under inflammatory environment and to provide a new target for the treatment of periodontitis. @*Methods@#SHP2 was knocked down in hPDLSCs, and the transfection efficiency of SHP2 was detected by RT-qPCR and Western blot. An in vitro inflammatory environment was created using tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). The effect of SHP2 knockdown on hPDLSC viability under normal and inflammatory conditions was detected by CCK-8, and the osteogenic capacity of hPDLSCs under normal and inflammatory conditions was detected by ALP staining, ALP activity, ARS staining, RT-qPCR and Western blot. The mechanism by which SHP2 knockdown affected the MAPK pathway and its downstream NF-κB pathway under inflammatory conditions was assessed by Western blot. @*Results@# Green fluorescence was observed after transfection for 72 h, and the titer of SHP2 shRNA recombinant lentivirus was 2.9×108 TU/mL. SHP2 expression was significantly downregulated in lentivirus-transfected cells, as demonstrated by Western blot and RT-qPCR (P<0.001). SHP2 knockdown inhibited hPDLSC proliferation to a certain extent and increased the expression of early osteogenic markers under normal conditions, including increased ALP activity and increased ALP and COL-1 expression (P<0.05). However, SHP2 knockdown exerted no effect on mineralized nodule formation. In the TNF-α- and IL-1β-induced inflammatory environment, SHP2 knockdown exerted no effect on hPDLSC proliferation (P>0.05). Osteogenic markers were upregulated (P<0.05), and mineralized nodules were significantly increased (P<0.05) after SHP2 knockdown. Western blot analysis showed that p65 phosphorylation and IκB-α degradation were reduced in SHP2-knockdown hPDLSCs in the inflammatory environment. Moreover, SHP2 knockdown significantly inhibited the expression of p-p38 and p-JNK MAPK, which represent pathways upstream of the NF-κB pathway (P<0.05). @*Conclusion @# SHP2 knockdown did not affect cell viability but promoted the osteogenic potential of hPDLSCs by inhibiting the MAPK/NF-κB-mediated signaling pathway under inflammatory environment.

8.
Article in Chinese | WPRIM | ID: wpr-934586

ABSTRACT

Objective: To observe the effects of electroacupuncture (EA) pretreatment on M1 polarization of alveolar macrophages (AMs) in rats with acute lung injury (ALI) induced by lipopolysaccharide (LPS), and to explore the potential protective mechanism of EA.Methods: Forty Sprague-Dawley rats were randomly divided into a normal group, a model group, and three groups of EA pretreatment [including a Chize (LU5) group, a Zusanli (ST36) group and a Chize (LU5) plus Zusanli (ST36) group], with eight rats in each group. The model rats of ALI were established by instilling LPS [2 mg/(kg·bw)] into the trachea of rats for 3 h. The rats in each EA pretreatment group were pretreated with EA for 30 min per day at the corresponding bilateral acupoints 6 d before instilling LPS. Three hours after modeling, the pulmonary function of the rats was tested, and the lung tissue was taken to calculate the ratio of lung wet weight to dry weight (W/D). The pathological lung changes and the injury score were observed by hematoxylin-eosin staining. The contents of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and myeloperoxidase (MPO) in rat's bronchoalveolar lavage fluid (BALF) were detected by enzyme-linked immunosorbent assay. The mRNA and protein expression levels of M1 macrophage markers clusters of differentiation 86 (CD86), inducible nitric oxide synthase (iNOS), and its signaling pathway factor Toll-like receptor (TLR) 4, and nuclear factor-κB (NF-κB) p65 in the alveoli were detected by fluorescence quantitative polymerase chain reaction and Western blot, respectively. Results: After being induced by LPS, the pulmonary function of the model rats showed that the forced expiratory volume in 0.1 s (FEV0.1), forced expiratory volume in 0.3 s (FEV0.3), and their respective ratios of FEV to forced vital capacity (FVC) (including FEV0.1/FVC and FEV0.3/FVC) were significantly decreased (P<0.01), while the W/D of lung tissue was increased (P<0.01). The score of lung injury was significantly higher (P<0.01). The contents of TNF-α, IL-1β, and MPO in the BALF and the mRNA and protein expression levels of CD86, iNOS, TLR4, and NF-κB p65 in the lung tissue were significantly increased (P<0.01). After EA pretreatment, the FEV0.1, FEV0.3, FEV0.1/FVC, and FEV0.3/FVC were significantly increased, the lung injury score decreased significantly, and the contents of TNF-α, IL-1β, and MPO in the BALF and the expression levels of CD86, iNOS, TLR4, and NF-κB p65 mRNAs and proteins in the alveoli decreased significantly (P<0.05 or P<0.01). Compared with the other two single acupoint groups, the contents of TNF-α, IL-1β, and MPO in the BALF and the expression levels of CD86, iNOS, TLR4, and NF-κB p65 mRNAs in the alveoli in the Chize (LU5) plus Zusanli (ST36) group were significantly lower (P<0.01). Conclusion: EA pretreatment at Chize (LU5) and Zusanli (ST36) can inhibit inflammation and reduce pulmonary injury in ALI rats induced by LPS. The effect of the combination of Chize (LU5) and Zusanli (ST36) is better than that of using these two acupoints separately, and its mechanism may be related to the inhibition of AMs' M1 polarization by down-regulation TLR4/NF-κB signaling pathway.

9.
Article in Chinese | WPRIM | ID: wpr-933501

ABSTRACT

Psoriasis is an immune-mediated chronic recurrent inflammatory disease, and biological agents targeting cytokines and their receptors involved in its pathogenesis have become an increasingly important option for its treatment in recent years. With the successive appearance of biological agents such as secukinumab and ustekinumab on the market in China, the use of biologics will become increasingly common in the treatment of psoriasis. This review summarizes the efficacy of different biological agents and individualized drug selection in the treatment of moderate to severe plaque psoriasis and psoriatic arthritis, with a view to providing a reference for physicians in clinical practice.

10.
Journal of Chinese Physician ; (12): 270-274, 2022.
Article in Chinese | WPRIM | ID: wpr-932057

ABSTRACT

Objective:To investigate the mechanism of urokinase on inflammatory substances and thrombomodulin (TM) in deep vein thrombosis (DVT) rats.Methods:A rat model of deep vein thrombosis was established. Thirty rats were randomly divided into sham group, DVT group and UK (urokinase) group. The rat model of deep venous thrombosis was established in DVT group and UK group. One day after operation, urokinase (20 000 U/kg) was injected into caudal vein in UK group once a day for 14 days; Sham group and DVT group were given the same volume of normal saline. The wet weight and the ratio of wet weight/length of thrombus were compared among the three groups; HE staining was used to detect the pathological changes of thrombus in the three groups; The plasma inflammatory factors interleukin-8 (IL-8) and tumor necrosis factor α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA expression of TM in the three groups was detected by real-time fluorescence quantitativepolymerase chain reaction (qRT-PCR).Results:Compared with sham group, thrombosis was found in DVT group. The wet weight and wet weight/length ratio of thrombus in DVT group were significantly higher than those in sham group ( P<0.05); After urokinase intervention, the wet weight of thrombus in UK group was significantly lower than that in DVT group, and the wet weight/length ratio of thrombus was also significantly lower than that in DVT group ( P<0.05). Compared with sham group, DVT group had obvious thrombosis, granulation tissue covered around the tissue, obvious adhesion between blood vessels and tube wall, a large number of inflammatory cell infiltration around venous tissue and obvious destruction of valve structure; After urokinase intervention, the thrombus tissue of UK group was significantly improved. Compared with sham group, the concentration of IL-8 , TNF-α and sTM in DVT group were significantly increased ( P<0.05). After urokinase intervention, the IL-8, TNF-α and sTM concentration in UK group were significantly lower than those in DVT group ( P<0.05). qRT-PCR results showed that TM mRNA expression in DVT group was significantly higher than that in sham group ( P<0.05). The TM mRNA expression in UK group was significantly lower than that in DVT group ( P<0.05). Conclusions:Urokinase can inhibit the inflammatory factors and the expression of thrombomodulin in DVT.

11.
Article in Chinese | WPRIM | ID: wpr-931708

ABSTRACT

Objective:To investigate the effects of massive blood transfusion on serum electrolyte balance and serum levels of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in patients with severe trauma.Methods:A total of 83 patients with severe trauma who received treatment in Eastern District of LiHuili Hospital, Ningbo Medical Center between July 2019 and December 2020 were included in this study. All of them underwent blood transfusion. They were divided into massive blood transfusion group ( n = 29) and general blood transfusion group ( n = 54) according to the volume of blood transfused. Changes in coagulation function, electrolyte, liver-kidney function and inflammatory factor levels pre- and post-blood transfusion were compared between massive blood transfusion and general blood transfusion groups. Results:At 1 day after blood transfusion, activated partial thromboplastin time (APTT) and prothrombin time (PT) in the massive blood transfusion group were (45.64 ± 2.78) seconds and (17.71 ± 2.08) seconds, respectively, which were significantly longer than those in the general blood transfusion group [(41.02 ± 2.80) seconds, (15.35 ± 1.72) seconds, t = 5.53, 7.18, P < 0.05). At 1 day after blood transfusion, levels of tumor necrosis factor-α, interleukin-6 and C-reaction protein in the massive blood transfusion group were (1.84 ± 0.32) μg/L, (113.72 ± 13.34) ng/L, (28.94 ± 4.22) mg/L, respectively, which were significantly increased compared with those measured before blood transfusion [(1.28 ± 0.29) μg/L, (95.18 ± 10.64) ng/L, (16.48 ± 3.37) mg/L, t = 6.98, 5.85, 12.42, all P < 0.05]. Levels of tumor necrosis factor-α, interleukin-6 and C-reaction protein in the general blood transfusion group were (1.34 ± 0.27) μg/L, (98.54 ± 9.62) ng/L, (20.05 ± 3.30) mg/L, respectively at 1 day after blood transfusion, which were significantly increased compared with those measured before blood transfusion [(1.23 ± 0.26) μg/L, (94.22 ± 8.82) ng/L, (16.16 ± 3.39) mg/L, t = 2.15, 2.43, 6.04, all P < 0.05]. At 1 day after blood transfusion, serum levels of tumor necrosis factor-α and C-reaction protein in the massive blood transfusion group were significantly higher than those in the general blood transfusion group ( t = 7.53, 10.59, both P < 0.05). At 1 day after blood transfusion, serum levels of K + and Ca 2+ in the massive blood transfusion group were (3.56 ± 0.54) mmol/L and (1.87 ± 0.28) mmol/L, respectively, which were significantly lower than those in the general blood transfusion group [(4.27 ± 0.34) mmol/L, (2.26 ± 0.24) mmol/L, t = 7.34, 6.65, both P < 0.05]. Serum levels of alanine aminotransferase and aspartate aminotransferase in the massive blood transfusion group were (52.46 ± 20.27) U/L, (82.37 ± 31.15) U/L, respectively, which were significantly higher than those in the general blood transfusion group [(37.57 ± 10.31) U/L, (49.35 ± 10.14) U/L, t = 4.44, 7.14, both P < 0.05)]. The incidence of abnormal liver function in the massive blood transfusion group was significantly higher than that in the general blood transfusion group [62.07% (18/29) vs. 29.63% (16/54), χ2 = 10.13, P < 0.05)]. Conclusion:The internal environment of patients with severe trauma will change after massive blood transfusion. Their coagulation function, inflammatory factors, liver function and electrolyte balance should be monitored in time.

12.
Article in Chinese | WPRIM | ID: wpr-931703

ABSTRACT

Objective:To investigate the relationship between tumor necrosis factor α (TNF-α) and pulmonary vascular remodeling in rats with chronic thromboembolic pulmonary hypertension (CTEPH).Methods:A total of 104 Wister rats were provided by Laboratory Animal Center, Harbin Medical University between January 2020 and June 2020 and included in this study. They were randomly divided into CTEPH group ( n = 52) and sham-operation group ( n = 52). Rats in the CTEPH group were injected with an embolus via the left external jugular vein to establish rat models of CTEPH. Rats in the sham-operation group were injected with the same amount of 0.9% sodium chloride injection. Relevant indicators were measured after 7 days and 1 month of embolization. Results:After embolization for 7 days and 1 month, plasma TNF-α level in the sham-operation group was (45.62 ± 1.65) ng/L and (46.24 ± 2.82) ng/L, respectively, which were significantly lower than those in the CTEPH group [(47.15 ± 1.58) ng/L, (48.85 ± 2.96) ng/L, t = 3.48, 3.31, both P < 0.05). Mean pulmonary artery pressure in the sham-operation group was significantly lower than that in the CTEPH group ( t = 1.89, 3.11, both P < 0.05). TNF-α mRNA expression in the sham-operation group was significantly lower than that in the CTEPH group ( t = 3.06, 3.36, both P < 0.05). The area/total area of pulmonary artery wall in the sham-operation group was significantly lower than that in the CTEPH group ( t = 1.73, 4.17, both P < 0.05). Plasma TNF-α level was positively correlated with pulmonary artery TNF-α mRNA expression ( r = 0.82, P < 0.05). Plasma TNF-α level and pulmonary artery TNF-α mRNA expression were positively correlated with mean pulmonary artery pressure ( r = 0.62, 0.73, both P < 0.05) and area/total area of pulmonary artery wall ( r = 0.61, 0.63, both P < 0.05). Conclusion:TNF-α may be involved in the pathogenesis of CTEPH by increasing pulmonary artery pressure and vascular remodeling.

13.
Article in Chinese | WPRIM | ID: wpr-931700

ABSTRACT

Objective:To investigate the effects of amoxicillin capsules combined with Fuke Qianjin Tablets on serum inflammatory factors in patients with acute pelvic inflammatory disease. Methods:A total of 240 patients with acute pelvic inflammatory disease who received treatment in Department of Obstetrics and Gynecology, Shizhu Branch of the First People's Hospital of Yongkang from January 2016 to June 2020 were included in this study. They were randomly assigned to receive either treatment with amoxicillin capsules and conventional drugs (control group, n = 120) or amoxicillin capsules, conventional drugs and Fuke Qianjin Tablets in combination (study group, n = 120). Serum inflammatory factors [C-reactive protein (CRP), interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)] were compared between before and after treatment in each group and between two groups after treatment. Results:After treatment, CRP, IL-1, IL-6 and TNF-α levels in the control group were (34.28 ± 7.19) mg/L, (103.52 ± 30.18) mg/L, (103.27 ± 37.18) ng/L, and (64.11 ± 13.28) ng/L, respectively and they were (15.26 ± 6.49) mg/L, (60.44 ± 17.64) mg/L, (62.15 ± 15.33) ng/L, (38.19 ± 9.46) ng/L, respectively in the study group. Before treatment, CRP, IL-1, IL-6 and TNF-α levels in the control group were (89.32 ± 17.36) mg/L, (193.27 ± 52.18) mg/L, (180.48 ± 49.25) ng/L, (81.27 ± 18.16) ng/L , respectively and they were (90.48 ± 19.73) mg/L, (192.55 ± 51.84) mg/L, (178.93 ± 50.11) ng/L, (79.83 ± 17.35) ng/L, respectively in the study group. CRP, IL-1, IL-6 and TNF-α levels post-treatment were significantly lower than the levels pre-treatment in each group (control group: tCRP = 11.28, P < 0.001; tIL-1 = 12.73, P < 0.001; tIL-6 = 9.48, P < 0.001; tTNF-α = 8.94, P < 0.001; study group: tCRP = 12.38, P < 0.001; tIL-1 = 18.44, P < 0.001; tIL-6 = 13.29, P < 0 .001; tTNF-α = 12.43, P < 0.001). CRP, IL-1, IL-6 and TNF-α levels post-treatment in the study group were significantly lower than those in the control group ( tCRP = 9.37, P < 0.001; tIL-1 = 11.84, P < 0.001; tIL-6 = 8.33, P < 0.001; tTNF-α = 7.38, P = 0.002). Response rate in the study group was significantly higher than that in the control group (95.83% vs. 75.00%, χ2 = 27.29, P < 0.001). Before and after treatment, there were no significant differences in safety indicators between the two groups (all P > 0.05). Conclusion:Amoxicillin capsules combined with Fuke Qianjin Tablets is highly effective on acute pelvic inflammatory disease, greatly lower inflammatory factor levels, and is highly safe.

14.
Article in Chinese | WPRIM | ID: wpr-931689

ABSTRACT

Objective:To compare the effects of different doses of ticagrelor on microcirculation, inflammatory factors and cardiac function in older adult patients with coronary heart disease after percutaneous coronary intervention (PCI).Methods:A total of 250 older adult patients with coronary heart disease who received PCI in The First People's Hospital of Wenling, China between March 2019 and March 2020 were included in this study. They were randomly assigned into group A and group B, with 125 patients per group. The group A was subjected to staged exercise and oral ticagrelor (45 mg once, twice a day). The group B was given staged exercise and oral ticagrelor (90 mg once, twice a day). Platelet function (maximum platelet aggregation rate, P2Y12 reaction unit), microcirculation (the index of microcirculatory resistance, circulatory flow reserve), inflammatory factor levels (high-sensitivity C-reactive protein, tumor necrosis factor alpha, interleukin-6), cardiac function recovery (left ventricular ejection fraction, 6-minute walk test, maximal oxygen consumption), cardiovascular adverse events, and bleeding events were compared between the two groups.Results:After treatment, maximum platelet aggregation rate and P2Y12 reaction unit in group B were (28.79 ± 3.52)% and (132.36 ± 12.16) U, respectively, which were significantly lower than those in group A [(33.45 ± 4.60)%, (146.79 ± 13.52) U, t = 8.99, 8.87, both P < 0.001]. After treatment, the index of microcirculatory resistance in group B was significantly lower than that in group A [(26.43 ± 4.51) vs. (29.68 ± 5.14), t = 5.31, P < 0.001]. Circulatory flow reserve in group B was significantly higher than that in group A [(2.16 ± 0.62) vs. (1.61 ± 0.50), t = 7.72, P < 0.001]. After treatment, tumor necrosis factor alpha, interleukin-6 and high-sensitivity C-reactive protein in group B were (39.54 ± 6.74) ng/L, (19.68 ± 4.06) ng/L, (5.98 ± 1.35) mg/L, respectively, which were significantly higher than those in group A [(28.26 ± 6.15) ng/L, (15.33 ± 3.87) ng/L, (4.83 ± 1.28) mg/L, t = 13.82, 8.67, 6.91, all P < 0.001]. After treatment, left ventricular ejection fraction, 6-minute walk test, maximal oxygen consumption in group B were (37.39 ± 5.10)%, (443.28 ± 29.64) m, (19.69 ± 3.57) L/min, respectively, which were significantly higher than those in group A [(34.64 ± 4.86)%, (410.45 ± 25.76) m, (17.33 ± 3.27) L/min, t = 4.36, 9.34, 5.45, all P < 0.001]. There was no significant difference in total incidence of cardiovascular events between the two groups (χ 2 = 0.05, P > 0.05). The incidence of bleeding events in group A was significantly lower than that in group B (4.80% vs. 13.60%, χ 2 = 5.79, P < 0.05). Conclusion:Compared with ticagrelor 90 mg/d, ticagrelor 180 mg/d can more greatly improve platelet function and microcirculation, reduce inflammatory reaction, promote the recovery of cardiac function, and reduce bleeding events in older adult patients with coronary heart disease after percutaneous coronary intervention.

15.
Article in Chinese | WPRIM | ID: wpr-931668

ABSTRACT

Objective:To investigate the clinical efficacy of quadruple therapy combined with probiotics for helicobacter pylori-positive erosive gastritis.Methods:A total of 350 patients with helicobacter pylori-positive erosive gastritis who received treatment in Jinan Seventh People's Hospital from January 2020 to January 2021 were included in this study. They were randomly assigned to receive a quadruple therapy (clarithromycin, ribavirin, amoxicillin and rabeprazole) alone (control group, n = 175) or in combination with probiotics (observation group, n = 175) for 2 weeks. Clinical efficacy was compared between the two groups. Results:Total response rate was 90.86% (150/175) in the observation group, which was significantly higher than that in the control group [72.57% (127/175), χ 2 = 19.58, P < 0.001]. After treatment, gastrointestinal microbiota were improved in both groups, but the improvements were greater in the observation group than in the control group ( t = 15.14, 14.30, 17.37, all P < 0.001). At 3 and 6 months after treatment, conversion rates from helicobacter pylori-positive to helicobacter pylori-negative in the observation group were 72.57% (127/175) and 95.43% (167/175) respectively, which were significantly higher than 50.29% (88/175) and 79.43% (139/175) in the control group (χ 2 = 18.34, 20.38, both P < 0.001). After treatment, the amplitude of decrease in serum level of gastrin, motilin, tumor necrosis factor-α and interleukin-6 in the observation group were greater than those in the control group ( t = 35.15, 44.91, 16.76, 5.73, all P < 0.001). Conclusion:Quadruple therapy combined with probiotics is highly effective on helicobacter pylori-positive erosive gastritis. The combined therapy can increase conversion rate from helicobacter pylori-positive to helicobacter pylori-negative, improve gastrointestinal function, and greatly inhibit inflammatory reaction.

16.
Article in Chinese | WPRIM | ID: wpr-931622

ABSTRACT

Objective:To investigate the protective effects of overexpression of long-chain noncoding RNA FAM224B on lung tissue of rats with severe pneumonia and the underlying mechanism.Methods:From August 2020 to March 2021, we randomly allocated 20 rats into the pneumonia group (severe pneumonia modeling) and FAM224B group (severe pneumonia modeling + FAM224B plasmid), with 10 rats in each group. We performed a quantitative real-time polymerase chain reaction to detect the level of FAM224B in lung tissue and performed an enzyme-linked immunosorbent assay to detect the levels of tumor necrosis factor-alpha, interleukin-6, and interleukin-1β in lung tissue. We used the software starBase v2.0 to predict the target gene of FAM224B. We performed a quantitative real-time polymerase chain reaction to detect the expression of the target gene in lung tissue and performed a western blot assay to detect the protein expression of the nuclear factor-kappa B signal pathway in lung tissue.Results:FAM224B expression was (1.09 ± 0.23) and (10.12 ± 1.52) in the pneumonia and FAM224B groups, respectively. FAM224B expression was significantly lower in the pneumonia group compared with the FAM224B group ( t = 15.86, P < 0.01). The levels of tumor necrosis factor-alpha, interleukin-6, and interleukin-1β were (41.53 ± 2.46) μg/L, (34.01 ± 2.53) ng/L, (20.92 ± 1.95) μg/L in the pneumonia group and they were (21.71 ± 2.25) μg/L, (17.13 ± 3.01) ng/L, (11.97 ± 1.21) μg/L in the FAM224B group. There were significant differences in the levels of tumor necrosis factor-alpha, interleukin-6, and interleukin-1β between the two groups ( t = 15.94, 14.29, 13.89, all P < 0.01). FAM224B had complementary binding sites with miR-34b-5p. The expression level of miR-34b-5p in lung tissue was significantly lower in the FAM224B group compared with the pneumonia group ( t = 15.55, P < 0.01). The protein expression levels of phosphorylated nuclear factor-κB subunit (p-p65) and phosphorylated inhibitor of kappa B alpha in lung tissue were significantly lower in the FAM224B group compared with the pneumonia group. Conclusion:FAM224B overexpression reduces the inflammatory reaction in lung tissue of rats with severe pneumonia through inhibiting miR-34b-5p expression.

17.
Article in Chinese | WPRIM | ID: wpr-931616

ABSTRACT

Objective:To investigate the efficacy and safety of Xuebijing injection combined with phentolamine and dobutamine for the treatment of severe pneumonia complicated by heart failure. Methods:A total of 200 patients with severe pneumonia complicated by heart failure treated in Hangzhou Ninth People's Hospital from January 2017 to December 2019 were included in this study. They were randomly allocated into the control and observation groups ( n = 100/group). The control group was treated with phentolamine and dobutamine. The observation group was treated with Xuebijing injection combined with phenolamine and dobutamine. Clinical efficacy, changes in C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), left ventricular ejection fraction (LVEF), cardiac troponin I (cTnI), and B-type natriuretic peptide (BNP) post-treatment relative to pre-treatment, and the incidence of adverse reactions were compared. Results:Total response rate was significantly higher in the observation group than in the control group [94.0% (94/100) vs. 85.0% (85/100), χ2 = 4.31, P < 0.05]. There were no significant differences in CRP, IL-6, TNF-α, LVEF, cTnI, and BNP pre-treatment between the two groups (all P > 0.05). CRP, IL-6, TNF-α post-treatment in the observation group were (56.29 ± 10.78) ng/L, (75.60 ± 13.24) ng/L, (130.42 ± 24.79) ng/L respectively, which were significantly lower than those in the control group [(70.52 ± 13.10) ng/L, (87.46 ± 15.68) ng/L, (164.51 ± 28.47) ng/L, t = 8.38, 5.77, 9.03, all P < 0.001]. LVEF post-treatment was significantly higher in the observation group than in the control group [(58.30 ± 8.65)% vs. (54.29 ± 7.9)%, t = -3.42, P < 0.05]. cTnI and BNP post-treatment in the observation group were (1.87 ± 0.52) μg/L and (218.42 ± 24.23) ng/L, respectively, which were significantly lower than those in the control group [(2.40 ± 0.65) μg/L, (325.61 ± 36.97) ng/L, t = 6.36, 24.25, both P < 0.05]. The incidence of adverse reactions in the observation group was slightly, but not significantly, higher than that in the control group [8.0% (8/100) vs. 6.0% (6/100), P > 0.05]. Conclusion:Xuebijing injection combined with phentolamine and dobutamine is effective in the treatment of severe pneumonia complicated by heart failure. The combined therapy inhibits the expression of inflammatory factors, improves cardiac function, has a low incidence of adverse reactions, and is highly safe.

18.
Article in Chinese | WPRIM | ID: wpr-931591

ABSTRACT

Objective:To investigate the clinical efficacy and possible mechanism of bifidobacterium tetralogy combined with escitalopram oxalate in the treatment of patients with depression and to provide evidence for further clinical research.Methods:A total of 100 patients with depression who received treatment in Taizhou Second People's Hospital from September 2019 to March 2021 were included in this study. They were randomly assigned to receive either escitalopram oxalate and placebo (control group, n = 50) or escitalopram oxalate and bifidobacterium tetralogy (observation group, n = 50). All patients received 9 weeks of treatment. Psychological status pre- and post-treatment was evaluated using the Hamilton Rating Scale for Depression and the Hamilton Rating Scale for Anxiety. Serum cortisol, inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels were detected using the enzyme-linked immunosorbent assay. Results:Physiological status scores in each group were significantly lower after treatment compared with before treatment. Scores of the Hamilton Rating Scale for Depression and the Hamilton Rating Scale for Anxiety scores post-treatment in the observation group were (10.78 ± 2.03) points and (6.37 ± 2.58) points, which were significantly lower than those in the control group [(16.78 ± 2.85) points, (13.23 ± 2.95) points, t = 11.40, 13.38, both P < 0.001]. Serum levels of cortisol, inflammatory factors IL-1β and TNF-α in each group were significantly decreased after treatment compared with before treatment. Serum levels of cortisol, inflammatory factors IL-1β and TNF-α post-treatment in the observation group were (137.34 ± 63.29) μg/L, (14.38 ± 6.08)ng/L, (13.95 ± 6.46) ng/L, which were significantly lower than those in the control group [(181.22 ± 59.27) μg/L, (25.94 ± 6.92) ng/L, (20.44 ± 6.24) ng/L, t = 15.29, 6.16, 9.24, all P < 0.001). Conclusion:Bifidobacterium tetralogy combined with escitalopram oxalate is highly effective on depression. The combined therapy can remarkably reduce depression and anxiety symptoms and greatly decrease serum cortisol, IL-1β, and TNF-α levels.

19.
Acta Pharmaceutica Sinica B ; (6): 1041-1053, 2022.
Article in English | WPRIM | ID: wpr-929344

ABSTRACT

The immune checkpoint blockade (ICB) targeting on PD-1/PD-L1 has shown remarkable promise in treating cancers. However, the low response rate and frequently observed severe side effects limit its broad benefits. It is partially due to less understanding of the biological regulation of PD-L1. Here, we systematically and comprehensively summarized the regulation of PD-L1 from nuclear chromatin reorganization to extracellular presentation. In PD-L1 and PD-L2 highly expressed cancer cells, a new TAD (topologically associating domain) (chr9: 5,400,000-5,600,000) around CD274 and CD273 was discovered, which includes a reported super-enhancer to drive synchronous transcription of PD-L1 and PD-L2. The re-shaped TAD allows transcription factors such as STAT3 and IRF1 recruit to PD-L1 locus in order to guide the expression of PD-L1. After transcription, the PD-L1 is tightly regulated by miRNAs and RNA-binding proteins via the long 3'UTR. At translational level, PD-L1 protein and its membrane presentation are tightly regulated by post-translational modification such as glycosylation and ubiquitination. In addition, PD-L1 can be secreted via exosome to systematically inhibit immune response. Therefore, fully dissecting the regulation of PD-L1/PD-L2 and thoroughly detecting PD-L1/PD-L2 as well as their regulatory networks will bring more insights in ICB and ICB-based combinational therapy.

20.
Acta Pharmaceutica Sinica B ; (6): 50-75, 2022.
Article in English | WPRIM | ID: wpr-929281

ABSTRACT

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling exert essential regulatory function in microbial-and onco-immunology through the induction of cytokines, primarily type I interferons. Recently, the aberrant and deranged signaling of the cGAS-STING axis is closely implicated in multiple sterile inflammatory diseases, including heart failure, myocardial infarction, cardiac hypertrophy, nonalcoholic fatty liver diseases, aortic aneurysm and dissection, obesity, etc. This is because of the massive loads of damage-associated molecular patterns (mitochondrial DNA, DNA in extracellular vesicles) liberated from recurrent injury to metabolic cellular organelles and tissues, which are sensed by the pathway. Also, the cGAS-STING pathway crosstalk with essential intracellular homeostasis processes like apoptosis, autophagy, and regulate cellular metabolism. Targeting derailed STING signaling has become necessary for chronic inflammatory diseases. Meanwhile, excessive type I interferons signaling impact on cardiovascular and metabolic health remain entirely elusive. In this review, we summarize the intimate connection between the cGAS-STING pathway and cardiovascular and metabolic disorders. We also discuss some potential small molecule inhibitors for the pathway. This review provides insight to stimulate interest in and support future research into understanding this signaling axis in cardiovascular and metabolic tissues and diseases.

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