Evaluación de la disfunción del endotelio para el pronóstico de riesgo cardiovascular / Evaluation of endothelial dysfunction for cardiovascular risk prediction i: en

Introducción: Las enfermedades cardiovasculares constituyen la primera causa de muerte en el mundo, por lo que la identificación y modificación de los factores de riesgo asociados a ellas constituyen estrategias priorizadas por la Organización Mundial de la Salud. Contar con un modelo de predicción del riesgo cardiovascular enriquecido con la evaluación de la disfunción endotelial influiría positivamente en estas metas. Objetivos: Identificar la presencia de disfunción endotelial en pacientes con enfermedades cardiovasculares o sin estas y determinar la asociación entre ambas. Métodos: Se realizó un estudio observacional y descriptivo, de serie de casos, en el Centro de Cardiología y Cirugía Cardiovascular del Hospital Provincial Docente Clínico-Quirúrgico Saturnino Lora de Santiago de Cuba, desde enero del 2022 hasta igual mes del 2023, donde se analizaron como variables los factores de riesgo cardiovascular tradicionales y los biomarcadores de disfunción endotelial. Secundariamente, se llevó a cabo un estudio analítico de casos y controles en el cual se aplicó la regresión logística binaria multivariada. Resultados: Se confirmó la presencia de disfunción endotelial asociada a la aparición de las enfermedades cardiovasculares, lo que se evaluó a través del índice de vasodilatación, mediado por el flujo de la arteria braquial y las concentraciones plasmáticas de fibrinógeno. Conclusiones: Las características epidemiológicas y clínicas de los pacientes con enfermedades cardiovasculares o sin estas no difirieron de lo registrado en la literatura especializada acerca de la base de identificación de los factores de riesgo tradicionales.

Introduction: Cardiovascular diseases constitute the first death cause worldwide, reason why the identification and modification of associated risk factors constitute prioritized strategies by the World Health Organization. To have a prediction model of cardiovascular risk enriched with the evaluation of the endothelial dysfunction would influence positively in these goals. Objectives: To identify the presence of endothelial dysfunction in patients with or without cardiovascular diseases and to determine the association between them. Methods: An observational and descriptive cases series study was carried out in the Cardiology and Cardiovascular Surgery Center at Saturnino Lora Teaching Clinical Surgical Provincial Hospital in Santiago de Cuba, from January, 2022 to the same month, 2023, where the traditional cardiovascular risk factors and endothelial dysfunction biomarkers were analyzed as variables. Secondarily, an analytic case-control study was carried out in which multivariate binary logistic regression was applied. Results: The presence of endothelial dysfunction associated with the onset of cardiovascular diseases was confirmed, what was evaluated through the vasodilatation index, mediated by the brachial artery flow and the fibrinogen plasmatic concentrations. Conclusions: The clinical and epidemiological pattern of patients with or without cardiovascular diseases did not differ from that reported in the specialized literature on the base of the identification of traditional risk factors.

Stable Angina Pectoris with Sleep Disorders Treated by Modified Tongmai Anshen Formula （通脉安神方加减）： An Clinical Observation of 74 Cases / 中医杂志

ObjectiveTo observe the clinical efficacy of the Modified Tongmai Anshen Formula （通脉安神方加减， MTAF） in the treatment of stable angina pectoris （SAP） with sleep disorders. MethodsA total of 148 patients suffering from SAP with sleep disorder were included and randomly divided into control group and treatment group， with 74 patients in each group. The control group received conventional western medicine， and the treatment group additionally received MTAF （1 dose per day）， both for 4 weeks. The changes in angina pectoris symptoms， traditional Chinese medicine （TCM） syndromes， sleep quality， quality of life， serological indicators including serum intercellular adhesion molecule-1 （ICAM-1） and vascular cell adhesion molecule-1 （VCAM-1）， brain-derived nerve growth factor （BDNF） and tyrosine kinase receptor B （TrkB） were compared between groups before and after treatment， and the safety was evaluated. ResultsIn the treatment group and the control group， the total effective rates of TCM syndromes（82.43% vs 52.70%）， angina pectoris （79.73% vs 64.86%） and sleep （89.19% vs 68.92%） showing significant difference （P＜0.001）. After treatment， the total TCM syndrome score， primary symptom score， secondary symptom score， and secondary symptoms sleeplessness， restlessness， tiredness and fatigue individual score， angina pectoris score， PSQI total score and each item score were all significantly reduced in both groups， while the SF-36 single item score significantly increased （P＜0.05）. The total TCM syndromes and primary symptom scores， secon-dary symptoms sleeplessness， restlessness， tiredness and fatigue individual score， angina pectoris score， time to fall asleep， sleep quality， hypnotic medication， sleep disturbance， daytime dysfunction score and PSQI total score were significantly lower in the treatment group than those in the control group after treatment （P＜0.05）， while the somatic pain， general health status， social functioning， emotional functioning， mental health， and health change were significantly higher in the treatment group （P＜0.05）. After treatment， ICAM-1 and VCAM-1 level significantly decreased （P＜0.05）， and BDNF and TrkB levels increased （P＜0.05） in the treatment group， while BDNF level significantly decreased in the control group （P＜0.05）. The TrkB level was significantly higher in the treatment group compared to the control group after treatment （P＜0.05）. A total of four adverse events occurred during the treatment， none of which were considered to be related to this study. ConclusionMTAF can significantly improve angina pectoris symptoms， TCM syndromes， sleep quality and quality of life in patients suffering from SAP with sleep disorders， the mechanism of which may be related to the protection of vascular endothelial function and central neurons.

Pharmacodynamic Material Basis of Astragali Radix and Angelicae Sinensis Radix Drug Pair in Supplementing Qi and Activating Blood Circulation / 中国实验方剂学杂志

ObjectiveTo evaluate the effect of Astragali Radix （AR）-Angelicae Sinensis Radix （ASR） drug pair on supplementing Qi and activating blood circulation in rats with Qi deficiency and blood stasis and provide a theoretical basis for clinical rational medication and identification and quality control of compound pharmacodynamic substances from the three aspects of characteristic map， identification of pharmacodynamic substances， and comparison of blood components. MethodHigh-performance liquid chromatography （HPLC） was employed to establish the fingerprint of AR∶ASR （3∶1）， and ultra-high performance liquid chromatography-Q-Exactive Orbitrap-mass spectrometry （UPLC-Q-Exactive Orbitrap-MS） was employed to analyze the ingredients of the decoction. Adult male Wistar rats with SPF grades were selected and randomly divided into a blank group， a model group， a 3∶1 group， and a 5∶1 group. The rat model of Qi deficiency and blood stasis syndrome was prepared by controlling food intake and swimming in cold water every day. In parallel， each group was given medicine （or water） once a day. The dose of drug groups was 10.2 g∙kg-1， and the model group and blank group were given the same amount of distilled water for 15 d. Animal behavior， body weight， whole blood and plasma viscosity， thymus index， spleen index， the levels of adenosine triphosphate （ATP）， adenosine diphosphate（ADP）， von willebrand factor （vWF）， and ATP/ADP value in serum of rats were recorded. The morphology of vascular endothelium was observed by hematoxylin-eosin （HE） staining and scanning electron microscopy. UPLC-Q-Exactive Orbitrap-MS was used to analyze prototype and metabolic components in serum. ResultThe fingerprint of AR-ASR drug pair （AR-ASR 3∶1） was established. UPLC-Q-Exactive Orbitrap MS identified 49 chemical components in vitro and preliminarily identified 11 prototype components absorbed into blood in vivo. As compared with the blank group， the body mass decreased significantly （P<0.01）， the whole blood （high shear， middle shear， and low shear） viscosity and plasma viscosity were significantly increased （P<0.05， P<0.01）， the thymus index and spleen index decreased significantly （P<0.05， P<0.01）， serum ATP content decreased significantly （P<0.01）， ADP content increased significantly （P<0.01）， ATP/ADP value decreased significantly （P<0.01）， and vWF content increased significantly （P<0.01）. The results of HE staining and scanning electron microscopy showed that the vessels were partially damaged， showing the structural disorder of the intima， the bulge， defect， and roughness of the endothelium， and the obvious cell adhesion and migration in the model group. As compared with the model group， the body mass also increased significantly （P<0.01）. The results of whole blood and plasma viscosity showed that the whole blood low shear viscosity was significantly decreased in the 3∶1 group （P<0.05）. The results of thymus index and spleen index showed that 5∶1 group significantly increased the thymus index of rats （P<0.05）. The results of serum ATP and ADP levels showed that the 5∶1 group had more significant effects on ATP and ADP levels （P<0.05）， and both groups significantly reduced ATP/ADP values （P<0.01）. The results of serum vWF level showed that the vWF content in the 3∶1 group decreased significantly （P<0.05）. The results of HE staining and scanning electronic microscopy showed that the damage of vascular endothelium was improved in the treatment group and the structure of intima was neat. ConclusionAR-ASR drug pair can improve the macro and micro indexes of rats with qi deficiency and blood stasis in the 3∶1 and 5∶1 groups. Overall， the 5∶1 ratio has a better effect on supplementing Qi but 3∶1 ratio has a better effect on promoting blood circulation.

Effects of therapeutic ultrasound on the endothelial function of patients with type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is characterized by endothelial dysfunction that causes micro- and macrovascular complications. Low intensity therapeutic ultrasound (LITUS) may improve endothelial function, but its effects have not been investigated in these patients. The aim of our study was to compare the effects of pulsed (PUT) and continuous (CUT) waveforms of LITUS on the endothelium-dependent vasodilation of T2DM patients. The present randomized crossover trial had a sample of twenty-three patients (7 men) diagnosed with T2DM, 55.6 (±9.1) years old, with a body mass index of 28.6 (±3.3) kg/m2. All patients were randomized and submitted to different waveforms (Placebo, CUT, and PUT) of LITUS and the arterial endothelial function was evaluated. The LITUS of 1 MHz was applied in pulsed (PUT: 20% duty cycle, 0.08 W/cm2 SATA), continuous (CUT: 0.4 W/cm2 SPTA), and Placebo (equipment off) types of waves during 5 min on the brachial artery. Endothelial function was evaluated using the flow-mediated dilation (FMD) technique. PUT (mean difference 2.08%, 95% confidence interval 0.65 to 3.51) and CUT (mean difference 2.32%, 95% confidence interval 0.89 to 3.74) increased the %FMD compared to Placebo. In the effect size analysis, PUT (d=0.65) and CUT (d=0.65) waveforms presented moderate effects in the %FMD compared to Placebo. The vasodilator effect was similar in the different types of waves. Pulsed and continuous waveforms of LITUS of 1 MHz improved the arterial endothelial function in T2DM patients.

Anthropometric measurements and their association with endothelial function and arterial stiffness of eutrophic individuals and with overweight

ABSTRACT Objective: The objective of the study was to assess the association of anthropometric measurements with endothelial function and arterial stiffness of eutrophic individuals and with overweight. Subjects and methods: A cross-sectional study was carried out with individuals with body mass index (BMI) between 18.5 kg/m² and < 30 kg/m², low to intermediate global cardiovascular risk scores, and aged ≥ 18 and < 60 years. We assessed the sociodemographic data, anthropometric variables (body weight, height, circumferences of the waist [WC], neck [NC], hip [HC], sagittal abdominal diameter [SAD], [BMI], waist-to-hip ratio [WHR], and waist-to-height ratio [WHtR]), biochemical parameters (lipid profile and nitric oxide), endothelial function (flow-mediated dilation [FMD], by ultrasound), and arterial stiffness (pulse wave velocity [PWV] and the amplification index [AIx@75] by oscillometry). Thirty-six individuals were included, 18 eutrophic and 18 with overweight, with a mean age of 37.5 ± 10.2 years, mostly at low cardiovascular risk (86.1%), female (80.6%), single (52.8%), employed with formal contracts (44.4%), and with over twelve years of education (88.9%). Results: The PWV presented positive and moderate correlation with the WC (r = 0.584; P = 0.001), WHR (r = 0.513; P = 0.001), and WHtR (r = 0.590; P = 0.001), and positive and low correlation with the NC (r = 0.372; P = 0.013) and SAD (r = 0.356; P = 0.033). Moreover, no anthropometric parameter presented a correlation with the AIx@75 or the FMD percentage in the total sample. Conclusion: Our findings show that in eutrophic individuals and with overweight the WC, WHR, WHtR, SAD, and NC were positively correlated with the PWV but not to the endothelial function in the overall sample. These are hypothesis-generating findings and they should be replicated in other studies.

INOCA: Evaluación no invasiva de los mecanismos fisiopatológicos mediante CZT-SPECT / INOCA: Non-Invasive Assessment of the Pathophysological Mechanisms Using CZT-SPECT

RESUMEN Introducción: Una de las causas propuestas del síndrome INOCA (por sus siglas en inglés: Ischemia with Non-Obstructive Coronary Arteries) es la disfunción microvascular (DMV), la cual puede evaluarse en forma no invasiva, mediante la cuantificación del flujo sanguíneo miocárdico (FSM) y la reserva de flujo miocárdica (RFM). Las imágenes de perfusión miocárdica (IPM) y dinámicas con CZT-SPECT en reposo - dipiridamol - y prueba de frio (PF), permiten establecer la presencia de DMV evaluando diferentes mecanismos fisiopatológicos: endotelio independiente o dependiente, respectivamente. Objetivos: Evaluar la utilidad de CZT-SPECT en el diagnóstico de DMV y los diferentes mecanismos patológicos involucrados, en pacientes con diagnóstico de INOCA. Material y métodos: Se incluyeron en forma prospectiva 93 pacientes consecutivos con diagnóstico de INOCA, a los que se les realizó IPM e imágenes dinámicas con CZT-SPECT en reposo-dipiridamol-PF. El FSM se cuantificó con el software 4DM. Se consideró respuesta anormal al dipiridamol una RFM menor a 2 y a la variación del FSM (∆FSM) menor a 1,5 con PF. Se definió DMV a la presencia de una o ambas respuestas anormales. Resultados: El CZT-SPECT detectó DMV en un 85% (n=79) de los pacientes con INOCA. El 42% tuvo respuesta anormal con ambos apremios mientras que el 43% restante, mostró una respuesta alterada del FSM sólo con PF. Conclusiones: El uso de CZT-SPECT empleando ambos apremios, permitió evaluar diferentes mecanismos fisiopatológicos que causan DMV presente en la mayoría de los pacientes con INOCA.

ABSTRACT Background: One of the causes of INOCA (Ischemia with Non- Obstructive Coronary Arteries) is microvascular dysfunction (MVD), which can be noninvasively assessed through the quantification of myocardial blood flow (MBF) and myocardial flow reserve (MFR). Dynamic myocardial perfusion imaging (MPI) by CZT-SPECT at rest, with dipyridamole stress test and cold pressor test (CPT) can establish the presence of two different pathophysiological mechanisms of MVD: endothelium-independent or endothelium-dependent, respectively. Objectives: The aim of this study was to evaluate the usefulness of CZT-SPECT for the diagnosis of MVD and the different mechanisms involved in patients with INOCA. Materials and Methods : A total of 93 consecutive INOCA patients were prospectively included and underwent dynamic MPI with CZT-SPECT at rest and with dipyridamole stress test and CPT. THe MBF was quantified using 4DM® software. A MFR response to dipyridamole <2, and changes in MBF (∆MBF) <1.5 with CPT were considered abnormal responses. MVD was defined in the presence of one abnormal response or both. Results: CZT-SPECT detected MVD in 85% (n=79) of the patients with INOCA. Forty-two percent had an abnormal response to both stressors while 43% presented an abnormal response of MBF only with CPT. Conclusion: The use of CZT-SPECT with both stress tests allowed the evaluation of different possible pathophysiological mechanisms of MVD present in most patients with INOCA.

Paeoniflorin improves myocardial injury via inhibition of Src/VE-cadherin pathway in septic rats / 中华内科杂志

Objective:To study the protective effect and mechanism of paeoniflorin (pae) on myocardial injury in septic rats.Methods:Sprague-Dawley (SD) rats were randomly divided into 4 groups with 10 rats in each group. Rats were intraperitoneally injected with 1.4 ml normal saline and 1.4 ml 5% dimethyl sulfoxide (DMSO)solution independently in control group and DMSO group. Rats were intraperitoneally injected with 1.4 ml normal saline and 1.4 ml pae independently, then with 0.1 ml lipopolysaccharide (LPS) 1 hour later in sepsis group and pae group. Enzyme linked immunosorbent assay (ELISA) was used to detect serum cardiac troponin I (cTnI) levels and myocardial tissue tumor necrosis factor alpha (TNFα), interleukin(IL)-6, IL-1β, chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C-X-C motif) ligand 2 (CXCL2), vascular cell adhesion molecule 1 (VCAM-1) levels. Evans blue (EB) method was used to detect the EB content of myocardial tissue. HE staining method was used to observe the pathological changes, real-time quantitative polymerase chain reaction (RT-qPCR) to detect mRNA expression levels of the above molecules, and Western-blot to detect vascular endothelium-cadherin (VE-cadherin), phosphorylated p38 mitogen-activated protein kinase (P-p38MAPK), phosphorylated Src protein (P-Src), Ras-Related C3 Botulinum Toxin Substrate 1 (Rac1) levels.Results:Compared with control group, cTnI level and the EB content in sepsis group increased significantly, and the myocardial inflammatory cell infiltration was obvious. The cTnI level and EB content in pae group were significantly reduced, and myocardial inflammatory cell infiltration was reduced [cTnI: (227.7±15.9)pg/ml vs. (312.9±17.9)pg/ml;EB: (13.2±2.3)μg/g vs. (23.8±2.9)μg/g; P<0.05]. Compared with control group, the levels of TNFα, IL-6, IL-1β, CXCL1, CXCL2, and VCAM-1 in sepsis group were increased. Compared with sepsis group, the above-mentioned molecular levels of pae group were significantly decreased [TNFα: (63.39±9.55)pg/ml vs. (126.54±19.17)pg/ml ;IL-6: (64.03±8.82)pg/ml vs. (85.60±9.52)pg/ml;IL-1β: (69.52±9.23)pg/ml vs. (130.45±15.10)pg/ml;CXCL1: (2 600.19±379.54)pg/ml vs. (4 903.89±533.42)pg/ml;CXCL2: (93.71±10.83)pg/ml vs. (127.24±13.92)pg/ml;VCAM-1: (112.22±13.49)pg/ml vs. (149.32±15.65)pg/ml, both P<0.05]. RT-qPCR results showed that the mRNA expressions of TNFα, IL-6, IL-1β, CXCL1, CXCL2 and VCAM-1 in the sepsis group were increased compared with the control group; Compared with sepsis group, the IL-6 mRNA (1.271±0.139 vs. 1.920±0.191, P<0.05), IL-1βmRNA (1.180±0.130 vs. 1.817±0.191, P<0.05), VCAM-1 mRNA (1.088±0.144 vs. 1.460±0.166, P<0.05) expression decreased significantly in the pae group. Compared with control group, the levels of P-p38MAPK and P-Src in sepsis group increased, and the level of VE-cadherin decreased. Compared with sepsis group, the levels of p38MAPK and P-p38MAPK in pae group were significantly decreased, and the level of VE-cadherin was increased (p38MAPK/β-actin: 1.125±0.078 vs. 1.520±0.164; P-p38MAPK protein: 1.639±0.133 vs. 2.112±0.222; both P<0.05). Conclusion:Paeoniflorin could improve the permeability of cardiac microvascular endothelium in sepsis rats and inhibit the secretion and expression of inflammation-related proteins and genes, which might be related to the inhibition of Src/VE-cadherin pathway by paeoniflorin.

Efeito do tratamento com antileucotrieno em contratura capsular: estudo experimental / Effect of antileukotriene treatment on capsular contracture: an experimental study

RESUMO Introdução: 40% dos pacientes submetidos à radioterapia após reconstrução de mama por implante de prótese de silicone podem desenvolver encapsulamento da prótese. Diversas estratégias já foram testadas para prevenir a contratura da cápsula com resultados insatisfatórios. Este estudo analisou o efeito do antileucotrieno (AL) tópico na formação de contratura capsular em ratos com implantes de silicone associados à irradiação. Métodos: Foram implantados blocos de silicone na região dorsal em 20 ratas fêmeas, espécie Wistar com peso variando de 200-250g. Os animais foram divididos em dois grupos: controle (injeção de solução fisiológica 0,9% no tecido ao redor do implante) e grupo intervenção (injeção de 10mg de AL no tecido ao redor do implante). Imediatamente após a cirurgia os animais foram irradiados com dose única de 10Gy. Após dois meses, coletamos amostras de cápsulas para análise histológica e análise da expressão gênica dos seguintes biomarcadores: iNOS, VEGF-a e MMP-9. Resultados: A densidade vascular foi menor no grupo AL quando comparado ao grupo controle (55,4±30,0 vs. 81,8±26,7, p=0,05, respectivamente). Da mesma forma, o VEGF-a teve o mesmo comportamento (grupo controle - 0,34±0,1 vs. grupo Al - 0,02±0,001, p=0,04). Conclusão: Este estudo sugeriu que o tratamento com AL diminui a angiogênese em animais submetidos a implantes de silicone e submetidos à radioterapia

ABSTRACT Introduction: 40% of patients undergoing radiotherapy after breast reconstruction by silicone prosthesis implant may develop prosthesis encapsulation. Several strategies have already been tested to prevent capsule contracture with unsatisfactory results. This study analyzed the effect of topical antileukotriene (AL) on capsular contracture formation in rats with silicone implants associated with irradiation. Methods: Silicone blocks were implanted in the dorsal region in 20 female rats Wistar with weights ranging from 200-250g. The animals were divided into two groups: control (injection of 0.9% saline solution into the tissue around the implant) and intervention group (injection of 10mg of AL into the tissue around the implant). Immediately after surgery, the animals were irradiated with a single dose of 10Gy. After two months, we collected capsule samples for histological analysis and gene expression analysis of the following biomarkers: iNOS, VEGF-a and MMP-9. Results: Vascular density was lower in the AL group when compared to the control group (55.4±30.0 vs. 81.8±26.7, p=0.05, respectively). Similarly, VEGF-a had the same behavior (control group - 0.34±0.1 vs. group Al - 0.02±0.001, p=0.04). Conclusion: This study suggested that treatment with AL decreases angiogenesis in animals submitted to silicone implants and underwent radiotherapy.

Immunolocalización de s100a4 y α-sma en tejidos gingivales de pacientes con hipertrofia gingival por tratamiento ortodóntico: estudio preliminar / Immunolocalization of s100a4 and α-sma in gingival tissues of patients with gingival hypertrophy due to orthodontic treatment: preliminary study

Objective: to determine the presence and distribution of markers of the epithelialmesenchymal transition (EMT) (S-100A4 and alpha-smooth muscle actin-α-SMA) in gingival tissues of patients affected by Gingival hypertrophy (GH) due to orthodontics.GH is an exaggerated increase in gingival tissue whose pathogenesis is unknown. However, it has been reported that the epithelial-mesenchymal transition as a process involved in other types of GH. Materials and methods: descriptive study that included the analysis of gingival tissues of healthy individuals (n = 6) and patients with GH by orthodontic treatment (n = 6). Before gingival surgery, the patients underwent a periodontal hygiene phase. The gingival tissue samples obtained were processed and embedded in paraffin. The cuts were made with a microtome and deposited on polysine adhesion slides. Histological hematoxylin-eosin staining was performed.The identification and location of S-100A4 and α-SMA markers was determined by immunohistochemistry with monoclonal antibodies. The reading of the findings was carried out by oral pathologists. Results: in healthy individuals, an S100A4 label was observed in Langerhans cells, while α-SMA was identified in the vascular endothelium of all samples analysed. However, in patients with GH due to orthodontics, they registered an intense staining of S100A4 in gingival fibroblasts, Langerhans cells, vascular endothelium, and areas adjacent to the rupture of blood vessel. α-SMA expression in GO was detected in the vascular endothelium and gingival fibroblasts. Conclusion: the differential immunostaining of EMT markers in gingival tissues of patients with orthodontic GH suggests an eventual role of EMT in the pathogenesis of this pathology..Au

Objective: to determine the presence and distribution of markers of the epithelialmesenchymal transition (EMT) (S-100A4 and alpha-smooth muscle actin-α-SMA) in gingival tissues of patients affected by Gingival hypertrophy (GH) due to orthodontics. GH is an exaggerated increase in gingival tissue whose pathogenesis is unknown. However, it has been reported that the epithelial-mesenchymal transition as a process involved in other types of GH. Materials and methods: descriptive study that included the analysis of gingival tissues of healthy individuals (n = 6) and patients with GH by orthodontic treatment (n = 6). Before gingival surgery, the patients underwent a periodontal hygiene phase. The gingival tissue samples obtained were processed and embedded in paraffin. The cuts were made with a microtome and deposited on polysine adhesion slides. Histological hematoxylin-eosin staining was performed. The identification and location of S-100A4 and α-SMA markers was determined by immunohistochemistry with monoclonal antibodies. The reading of the findings was carried out by oral pathologists. Results: in healthy individuals, an S100A4 label was observed in Langerhans cells, while α-SMA was identified in the vascular endothelium of all samples analysed. However, in patients with GH due to orthodontics, they registered an intense staining of S100A4 in gingival fibroblasts, Langerhans cells, vascular endothelium, and areas adjacent to the rupture of blood vessel. α-SMA expression in GO was detected in the vascular endothelium and gingival fibroblasts. Conclusion: the differential immunostaining of EMT markers in gingival tissues of patients with orthodontic GH suggests an eventual role of EMT in the pathogenesis of this pathology..Au

Acute myocardial infarction associated with cocaine use / Infarto agudo al miocardio asociado al uso de cocaína

Abstract Cocaine abuse is related to a greater risk of cardiovascular events such as myocardial infarction and ischemic cerebrovascular accidents. The pathophysiological mechanisms are not fully understood, although the formation of intravascular thrombi and accelerated atherosclerosis are notable findings. We report the case of a 38-year-old man addicted to cocaine who presented ischemic events in the form of acute myocardial infarction complicated by heart failure. The pathophysiology of cocaine-induced vascular damage and the treatment of complications are discussed.

Resumen El abuso de cocaína se asocia con un mayor riesgo de eventos cardiovasculares, como infarto de miocardio y accidente cerebrovascular isquémico. Los mecanismos fisiopatológicos no se entienden completamente, aunque la formación de trombos intravasculares y la aterosclerosis acelerada son hallazgos destacados. Reportamos el caso de un hombre de 38 años adicto a la cocaína, que presentó eventos isquémicos caracterizados por infarto agudo de miocardio complicado por insuficiencia cardíaca. Se discute la fisiopatología del daño vascular inducido por la cocaína y el manejo de las complicaciones.

Revisión Bibliográfica: Disfunción Eréctil y Enfermedad Periodontal / literature Review: Erectile Dysfunction and Periodontal Disease

La asociación entre Enfermedad Periodontal y Disfunción Eréctil se ha estudiado limitadamente. Sin embargo, hoy en día los estudios disponibles han reportado una posible asociación en base a factores de riesgo compartidos entre ambas patologías, pero fundamentalmente se atribuye la asociación al fenómeno de disfunción endotelial que se vincula con ambas enfermedades. Se ha propuesto que la enfermedad periodontal crónica puede inducir una respuesta inflamatoria sistémica que resulta en el deterioro de las condiciones fisiológicas y bioquímicas del endotelio generando disfunción endotelial. Por otro lado, se reconoce a la disfunción eréctil como una enfermedad de origen multifactorial, en la que prevalece la condición vasculogénica como el factor etiológico más frecuente, esto atribuido a un defecto vascular (disfunción endotelial). Es así como el punto de enlace más fuerte es la alteración de la función vascular, que sin duda demuestra argumento sólido de asociación entre las dos enfermedades. El objetivo de esta revisión bibliográfica es informar sobre los posibles mecanismos de asociación entre enfermedad periodontal y disfunción eréctil, enfocándose en el proceso de disfunción endotelial como el principal vínculo existente.(au)

The association between periodontal disease and erectile dysfunction has not been sufficiently studied. However, recent studies have reported a possible link based on mutually shared risks factors between both pathologies, but the association is fundamentally attributed to endothelial dysfunction, phenomenon that is related to both diseases. It has been suggested that chronic periodontal disease can induce systemic inflammatory response that results in deterioration of the physiological and biochemical conditions of the endothelium causing endothelial dysfunction. On the other hand, erectile dysfunction is a multifactorial disease, but the vasculogenic factor is considered as the most frequent one, attributed to a vascular defect (endothelial dysfunction). So, the strongest link is the vascular function alteration, which undoubtedly demonstrates demonstrates a solid argument of association between both diseases. The objective of this literature review is to report the possible mechanisms of association between periodontal disease and erectile dysfunction, focusing mainly on endothelial dysfunction as the main existing link.(au)

Human umbilical cord mesenchymal stem cells overexpressing interleukin 8 receptor inhibit inflammation and promote vascular repair / 中国组织工程研究

BACKGROUND: Vascular injury is a common complication after balloon dilatation. The development of umbilical cord mesenchymal stem cells (UC-MSCs) provides a new method for treating vascular injury. OBJECTIVE: To investigate the mechanism underlying the repair of damaged blood vessels by human UC-MSCs (hUC-MSCs) transfected with interleukin-8RA/B (IL-8RA/B) adenovirus. METHODS: hUC-MSCs and human umbilical vein endothelial cells (hUVECs) were collected and transfected with adenovirus vectors containing human IL-8RA and/or IL-8RB cDNAs and green fluorescent protein. A rat model of carotid artery injury was established. Sprague-Dawley rats were randomly divided into four groups: IL-8RA/B-hUCMSCs group, Il-8ra/B-hUVECs group, Null-hUCMSCs group, and control group, followed by injection of 0.5×106 corresponding cells (500 μL) and same volume of normal saline via the tail vein respectively at 1, 3, and 5 hours post-surgery. After 30 minutes of injection, the carotid artery was taken and the expression of green fluorescent protein was observed. After 24 hours, the serum levels of inflammatory and anti-inflammatory factors were measured by ELISA; and the infiltration of neutrophil cells and mononuclear macrophages was observed by immunohistochemistry. After 14 days, Evans blue staining was used to observe vascular endothelialization and fibrosis. After 28 days, the neointimal hyperplasia was observed by hematoxylin-eosin staining. RESULTS AND CONCLUSION: (1) After 30 minutes of IL-8RA/B-hUC-MSCs infusion, the expression of green fluorescent protein was observed in the injured vascular intima, and the fluorescence expression was higher than that of the other three groups. (2) After 24 hours of IL-8RA/B-hUC-MSCs infusion, the expression of inflammatory factors in the serum was significantly lower than that of the other three groups, while the expression of anti-inflammatory factor interleukin-10 was higher than that of the other three groups (P < 0.05). In addition, inflammatory cell infiltration in the IL-8RA/B-hUC-MSCs group decreased significantly. (3) hUC-MSCs overexpressing interleukin-8 receptor promoted re-endothelialization of injured vessels and reduced vascular fibrosis after 14 days of infusion. (4) IL-8RA/B-hUC-MSCs reduced vascular neointimal hyperplasia after 28 days of infusion. (5) Interleukin-8 receptor enhances the targeted homing ability of hUC-MSCs, allowing MSCs to migrate to the site of vascular injury, inhibit inflammation, reduce neointimal hyperplasia, and promote vascular repair.

Application progress of recombinant human endostatin in the treatment of head and neck cancer / 口腔疾病防治

@#The main treatment of head and neck cancer is comprehensive sequential treatment, but the 5-year overall survival rate is less than 50%. Strategies to further improve the curative effect of head and neck cancer are urgently needed in the clinic. Recombinant human vascular endostatin is an antiangiogenesis drug targeting vascular endothelial cells, which has a certain inhibitory effect on tumors. The treatment of malignant tumors by drugs alone is not significantly better than chemoradiation, but combined with radiotherapy and chemotherapy, it can increase the effect of radiotherapy and chemotherapy without drug resistance by changing the distribution of blood vessels, reducing oxygen and normalizing blood vessels. Head and neck tumor treatment has certain advantages. New tumor treatments are expected. The results of a literature review showed that the mechanism of action of recombinant human endostatin mainly includes regulating the matrix protein inside and outside the endothelial cells to influence neovascularization, acting on receptors related to the surface of endothelial cells, reversing abnormal neovascularization to achieve vascular normalization, inhibiting hypoxia inducible factor to improve the hypoxic status of the tumor area, and regulating the cell cycle to ensure the tumor cells are sensitive to radiation in the sensitive period, and vascular normalization can increase the effect of radiotherapy. This treatment has a good synergistic effect with radiotherapy and chemotherapy of head and neck tumors and has a good effect on advanced head and neck tumors.

Research progress of circular RNA in regulating vascular endothelial dysfunction / 药学学报

Atherosclerosis refers to vascular pathological changes in which vascular lumen was narrowed or blocked by cholesterol or fat existed in vascular endothelium, which could induce serious cardiovascular events. The pathogenesis of atherosclerosis is complicated extremely. Vascular endothelial dysfunction initiated the plague formation and deterioration, which determined the prognosis of atherosclerosis. Circular RNA (circRNA) is a special endogenous non-coding RNA, which has become a research hotpot in the field of non-coding RNA. This review aims to bring together the recent research on the pathogenesis and pathological process of endothelial dysfunction, and the regulative effect of circRNA on it. Our article will provide new targets and new ideas for the research and development of anti-atherosclerosis drugs.

Interventional Effect and Mechanism of Extract of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma on Vascular Endothelial Cellular Senescence Induced by High Glucose and High Fat / 中国实验方剂学杂志

Objective: To explore the mechanism of extract of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma in delaying the senescence of vascular endothelial cells induced by high glucose and high fat. Method: The 40 mmol·L-1 glucose and 100 μmol·L-1 palmitate were used to induce endothelial cell senescence. The experiment was divided into control group, model group and low, medium and high-dose traditional Chinese medicine groups (50,100,200 mg·L-1). The intervention lasted for 48 h. Cell proliferation was detected by cell counting kit-8(CCK-8); cell senescence was detected by senescence β-galactosidase staining; p16 and p21 protein expression levels were detected by Western blot; p-H2A. X(Ser139) expression, mitochondria ROS(mtROS) production and changes in mitochondrial membrane potential(MMP) were detected by immunofluorescence. Result: Compared with the control group, in model group, the cell proliferation ability and the number of SA-β-gal blue-stained cells decreased(PPPPβ-gal blue-stained cells, the mtROS production, and expression levels of p16, p21 and p-H2A. X(Ser139)(PPConclusion: The above results suggest that extract of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma delay of endothelial cellular senescence induced by high glucose and high fat, and its mechanism may be related to increasing mitochondrial membrane potential and reducing DNA damage accumulation caused by ROS production.

Protective effect of Rhodiola rosea on vascular endothelium in rats with intermittent hypoxia / 中国中西医结合急救杂志

Objective To observe the protective effect of Rhodiola rosea on vascular endothelium in rats with intermittent hypoxia (IH) and to explore its possible mechanism. Methods According to random number table method, 45 male Sprague-Dawley (SD) rats were divided into normal control group, IH group and Rhodiola rosea low, medium and high dose groups, with 9 rats in each group. The IH model was reproduced by putting the rats into IH model chamber, and then feeding them with nitrogen, oxygen and compressed air for 45 days. The feeding bin and feeding time of rats in the normal control group were consistent with those in other groups, and the oxygen concentration in the tank was maintained at 20%-21%. The rats in Rhodiola rosea high, medium and low dose groups were intraperitoneally injected with Rhodiola rosea (0.2, 0.1 and 0.05 mL/100 g), starting from the 15 th day in IH chamber, and the injection continued for 30 days. The levels of malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO) in the coronary arteries of rats in each group were detected by automatic biochemical analyzer. The contents of coronary hypoxia-inducible factor-1α(HIF-1α) and tumor necrosis factor-α(TNF-α) in rats were determined by enzyme linked immunosorbent assay (ELISA). The mRNA expression levels of endothelin-1 (ET-1) and vascular endothelial growth factor (VEGF) in coronary artery tissues of rats in each group were measured by reverse transcription-polymerase chain reaction (RT-PCR). The pathological changes of aorta in each group were observed under light microscope. Results Compared with the normal control group, SOD and NO in the IH group decreased [SOD (U/mg): 4.43±0.22 vs. 8.60±0.34, NO (μmol/g): 3.09±0.07 vs. 4.81±0.41, both P < 0.01], MDA, TNF-α, HIF-1α and mRNA expression of ET-1 and VEGF increased [MDA (nmol/mg): 0.78±0.03 vs. 0.50±0.03, TNF-α(pg/mg): 6.35±0.29 vs. 3.27±0.14, HIF-1α (ng/mg): 14.55±0.70 vs. 7.16±0.17, ET-1 mRNA (2-ΔΔCt): 1.75±0.03 vs. 1.10±0.07, VEGF mRNA (2-ΔΔCt):4.38±0.10 vs. 1.20±0.07, all P < 0.01]. Compared with the IH group, SOD and NO were increased in three Rhodiola rosea groups, MDA, TNF-α, HIF-1α and mRNA expression of ET-1 and VEGF were decreased in three Rhodiola rosea groups, and the changes in the Rhodiola rosea high dose group were more significant than those in the low and medium dose Rhodiola rosea groups [SOD(U/mg): 7.47±0.19 vs. 5.41±0.37, 6.71±0.28, MDA (nmol/mg): 0.57±0.20 vs. 0.74±0.04, 0.70±0.03, NO (μmol/g): 4.00±0.28 vs. 3.27±0.18, 3.47±0.28, TNF-α(pg/mg): 3.90±0.17 vs. 5.08±0.27, 4.39±0.26, HIF-1α(ng/mg): 8.40±0.23 vs. 11.07±0.41, 9.81±0.44, ET-1 mRNA (2-ΔΔCt): 1.12±0.04 vs. 1.71±0.03, 1.63±0.07, VEGF mRNA (2-ΔΔCt): 2.45±0.09 vs. 3.99±0.12, 3.27±0.08, all P < 0.05]. Under light microscope, the inner membrane of the normal control group was intact, and the endothelial cells were loose and slightly stained on the surface of the inner membrane; in the IH group, part of the arterial areas showed endointima edema or even abscission, and interstitial edema in the vascular wall. The pathological changes in three Rhodiola rosea groups were less than that in the IH group, and the changes of Rhodiola rosea high dose group were more significant. Conclusion Rhodiola rosea can protect the vascular endothelium caused by IH exposure through improving the level of anti-hypoxia in tissues and inhibiting oxidative stress and inflammatory response.

Improvement Effects of Fibrinolytic Enzyme from Sipunculus nudus on Hemorheology Disorder and Vascular Endothelium Injury of Naked Acute Blood Stasis Model Rats / 中国药房

OBJECTIVE： To study the improvement effects of fibrinolytic enzyme from Sipunculus nudus （SNFE） on hemorheology disorder and vascular endothelium injury in naked acute blood stasis model rats. METHODS： SD rats were randomly divided into control group， model group， aspirin group （100 mg/kg） and SNFE high-dose and low-dose groups （2 500， 5 000     U/kg）， with 10 rats in each group. They were given relevant medicine intragastrically once a day， for consecutive 7 d. One hour after the 6th day of administration， except for control group， other groups were given adrenaline hydrochloride 0.8 mg/kg subcutaneously， and then the acute blood stasis model was induced by ice-water bath. Blood was collected from abdominal aorta 2 h after the next day. Blood rheological parameters such as whole blood viscosity （high， medium and low shear rate）， plasma viscosity， hematocrit， erythrocyte aggregation index and erythrocyte deformability index were measured by automatic rheometer. The contents of NO and ET-1 in plasma and their ratio were determined by ELISA， and the damaged degree of vascular endothelium were observed by HE staining. RESULTS： Compared with control group， whole blood viscosity of high， medium and low-shear rate， plasma viscosity， erythrocyte aggregation index and ET-1 content were increased significantly in model group， while erythrocyte deformability index， NO content and NO/ET-1 ratio were decreased significantly， with statistical significance （P＜0.05 or P＜0.01）. Compared with model group， whole blood viscosity of high， medium and low-shear rate， plasma viscosity， hematocrit， erythrocyte aggregation index and ET-1 content were decreased significantly in SNFE high-dose groups. Erythrocyte deformability index， NO content and NO/ET-1 ratio were increased significantly， with statistical significance （P＜0.05 or P＜0.01）. In SNFE low-dose group， erythrocyte deformability index and NO/ET-1 ratio were increased significantly， while ET-1 content was decreased significantly， with statistical significance （P＜0.05 or P＜0.01）. Vascular endothelial staining showed that compared with control group， the structure of aorta layers in model group was loose and disordered， the endothelial defect was incomplete， the vacuoles increased， and the endothelial damage was obvious. The endothelium of rats in each administration group was damaged to varying degrees， but the degree of injury was lighter than in model group. CONCLUSIONS： SNFE can improve hemorheological abnormalities and vascular endothelial injury in rats with acute blood stasis.

Effects of captopril on Klotho protein in hypertensive rats / 西安交通大学学报(医学版)

Objective: To evaluate the effects of captopril on Klotho protein and related inflammatory factors in the model of hypertensive SD rats. Methods: Eighteen SD rats were randomly divided into normal group, hypertensive model group and captopril experimental group, respectively. N'-nitro-L-arginine (L-NNA) was used by gavage in SD rats to make the hypertensive model. After successful establishment of the model, the experimental group was given captopril for treatment of hypertension, and the normal group and hypertension group were given an equal volume of normal saline by gavage in the SD rats. Blood pressure changes were measured by tail arteries of the SD rats. Enzyme-linked immunosorbent assay (ELISA) was used to measure plasma levels of Klotho protein, thromboxane (TXA2), and endothelin (ET). The level of nitric oxide (NO) was measured by nitrate reductase method. The content of malondialdehyde (MDA) was measured by TBA method, and the activity of superoxide dismutase (SOD) was measured by WST-1 method. The pathological changes of HE stained vascular wall in thoracic aorta of each group were observed. The vascular endothelial cell injury was evaluated by measuring the expression of CD31 by immunohistochemistry (IHC). Results: Compared with those in the normal group, the contents of TXA2, ET and MDA in the model group were significantly higher (P<0.05), while the content of Klothoprotein and NO and SOD activities were lower (P<0.05). Compared with those in the model group, the contents of TXA2, ET and MDA in the captopril group were significantly decreased (P<0.05), and the Klotho protein content, NO content and SOD activity were higher (P<0.05). The results of HE staining showed that the aortic vascular fibrosis and disorder in the model group and the aorticl wall were thicker than those in the normal group. The vessel wall was significantly thinner in the treatment group than in the model group. The results of IHC showed that the aortic endothelial cells in the model group were damaged and shedding. The vascular endothelial cells in the controlled group were increased and gradually repaired. Conclusion: Captopril can reduce the stress response of endothelial cells and repair the vascular endothelium, which can improve vascular endothelial function and increase Klotho protein level.

Effects of moxibustion at 45 ℃ on blood lipoids and serum level of ox-LDL and NO in rats with hyperlipidemia / 中国针灸

OBJECTIVE@#To observe the effects of moxibustion at different temperatures (38 ℃ and 45 ℃) on blood lipoids and serum level of oxidized low density lipoprotein (ox-LDL) and nitric oxide (NO) in rats with hyperlipidemia, and to explore the correlation between regulating blood fat and anti-oxidative stress and protection of vascular endothelium of moxibustion at 45 ℃.@*METHODS@#According to random number table, 60 SD rats were randomly divided into a normal group, a model group, a moxibustion at 38 ℃ group and a moxibustion at 45 ℃ group, 15 rats in each group. The rats in the normal group received no treatment; the rats in the remaining three groups were fed with high-fat diet for 8 weeks to prepare rat models of hyperlipidemia. After successful modeling, the rats in the model group received no treatment; the rats in the moxibustion at 38 ℃ group and moxibustion at 45 ℃ group were treated with moxibustion at "Shenque" (CV 8) and "Zusanli" (ST 36), and the temperature was controlled at (38±1) ℃ and (45±1) ℃, respectively. The moxibustion was given for 10 min at each acupoint, once every two days, and totally 4-week treatment was given. After treatment, the levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured by using biochemical colorimetric method; the levels of ox-LDL and NO were measured by using ELISA method.@*RESULTS@#① Compared with the normal group, the levels of TC, TG and LDL-C were significantly increased in the model group (all 0.05). ② Compared with the normal group, the level of ox-LDL was increased but that of NO was decreased in the model group (both <0.01); compared with the model group and moxibustion at 38 ℃ group, the level of ox-LDL was decreased but that of NO was increased in the moxibustion at 45 ℃ group (<0.01, <0.05); compared with the model group, the level of ox-LDL was decreased but that of NO was increased in the moxibustion at 38 ℃ group (both <0.05).@*CONCLUSION@#Moxibustion at 45 ℃ has regulating effects on blood lipid in rats with hyperlipidemia, which can regulate blood lipid through various ways, such as anti-oxidative stress and protection of vascular endothelium.

Antihypertensive effect and mechanism of Dendrobium officinale flos on high-blood pressure rats induced by high glucose and high fat compound alcohol / 中国中药杂志

This study aimed to investigate the antihypertensive effect and possible mechanism of Dendrobium officinale flos on hypertensive rats induced by high glucose and high fat compound alcohol. The hypertensive models were successfully made by high-glucose and high-fat diet, with gradient drinking for 4 weeks, and then divided into model control group, valsartan (5.7 mg·kg⁻¹) positive control group and D. officinale flos groups (3，1 g·kg⁻¹). After 6 weeks of treatment, the blood pressure of rats was measured regularly. After the last administration, endothelin-1 (ET-1), thromboxane B₂ (TXB₂), prostacyclin (PGI₂) and nitric oxide (NO) were tested. Endothelial nitric oxide synthase (eNOS) expression and lesion status in thoracic aorta were detected. The vascular endothelium dependent dilation of the thoracic aorta was detected by the isolated vascular loop tension test. The results showed that D. officinale flos could significantly reduce systolic blood pressure and mean arterial pressure in hypertensive rats, inhibit the thickening of thoracic aorta and the loss of endothelial cells, reduce plasma content of ET-1 and TXB₂, and increase the content of PGI₂ and NO. After long-term administration, vascular endothelium dependent dilation of the thoracic aorta was significantly increased, and could be blocked by the eNOS inhibitor (L-NAME) and increase the expression of eNOS. Therefore, D. officinale flos has an obvious antihypertensive effect on high glucose and high fat compound alcohol-induced hypertensive rats. Its mechanism may be correlated with the improvement of vascular diastolic function by protecting vascular endothelial cells, and finally resist hypertension.