Detoxification and Activating Blood Circulation Decoction Promotes Reendothelialization of Damaged Blood Vessels via VEGF Signaling Pathway Activation by miRNA-126.

The occurrence of in-stent restenosis (ISR) poses a significant challenge for percutaneous coronary intervention (PCI). Thus, the promotion of vascular reendothelialization is essential to inhibit endothelial proliferation. In this study, we clarified the mechanism by which Detoxification and Activating Blood Circulation Decoction (DABCD) promotes vascular reendothelialization to avoid ISR by miRNA-126-mediated modulation of the vascular endothelial growth factor (VEGF) signaling pathway. A rat model of post-PCI restenosis was established by balloon injury. The injured aortic segment was collected 14 and 28 d after model establishment. Our findings indicate that on the 14th and 28th days following balloon injury, DABCD reduced intimal hyperplasia and inflammation and promoted vascular reendothelialization. Additionally, DABCD markedly increased NO expression and significantly decreased ET-1 production in rat serum. DABCD also increased the mRNA level of eNOS and the protein expression of VEGF, p-Akt, and p-ERK1/2 in vascular tissue. Unexpectedly, the expression of miR-126a-5p mRNA was significantly lower in the aortic tissue of balloon-injured rats than in the aortic tissue of control rats, and higher miR-126a-5p levels were observed in the DABCD groups. The results of this study indicated that the vascular reendothelialization effect of DABCD on arterial intimal injury is associated with the inhibition of neointimal formation and the enhancement of vascular endothelial activity. More specifically, the effects of DABCD were mediated, at least in part, through miR-126-mediated VEGF signaling pathway activation.

Diagnostic value of combined detection of IL-1β, IL-6, and TNF-α for sepsis-induced cardiomyopathy / Valor diagnóstico de la detección combinada de IL-1, IL-6, y TNF-α para la cardiomiopatía inducida por sepsis

Introduction:This study aimed to explore the diagnostic value and the correlation of the combined detection of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) with sepsis-induced cardiomyopathy (SIC).Patients and methods:Admitted to our hospital from January 2017 to January 2019, 96 patients with SIC (a study group) and 90 patients with sepsis (a control group) were enrolled. The three cytokines were determined and the diagnostic value of their combined detection for SIC was analyzed.Results:The cytokines were remarkably higher in the study group (p<.001). The combined detection of the three had a better diagnostic value for SIC (p<.001). The three cytokines were independent risk factors for the death of patients with SIC.Conclusion:IL-1β, IL-6, and TNF-α in SIC patients rise markedly. The combined detection of the three has a better predictive value for patients with SIC and is closely related to the patients’ prognoses, so it may be crucial in diagnosing and treating the disease. (AU)

Introducción:El objetivo de este estudio fue explorar el valor diagnóstico y la correlación de la detección combinada de interleucina-1β (IL-1β), interleucina-6 (IL-6), y factor de necrosis tumoral-α (TNF-α) con la miocardiopatía inducida por sepsis (CIS).Pacientes y métodos:Ingresados en nuestro hospital entre enero de 2017 y enero de 2019, se incluyó en el estudio a 96 pacientes con CIS (grupo de estudio) y 90 pacientes con sepsis (grupo control). Se determinaron las tres citocinas y se analizó el valor diagnóstico de su detección combinada para CIS.Resultados:Las citocinas fueron marcadamente superiores en el grupo de estudio (p<0,001). La detección combinada de las tres tuvo un mejor valor diagnóstico para CIS (p<0,001). Las tres citocinas fueron factores de riesgo independientes de la muerte de los pacientes con CIS.Conclusión:IL-1β, IL-6, y TNF-α se incrementaron considerablemente en los pacientes de CIS. La detección combinada de los tres valores tiene un mejor valor predictivo para los pacientes con CIS, y está estrechamente relacionada con los pronósticos de los pacientes, lo cual puede ser esencial para diagnosticar y tratar la enfermedad. (AU)

Diagnostic value of combined detection of IL-1ß, IL-6, and TNF-α for sepsis-induced cardiomyopathy.

INTRODUCTION: This study aimed to explore the diagnostic value and the correlation of the combined detection of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) with sepsis-induced cardiomyopathy (SIC). PATIENTS AND METHODS: Admitted to our hospital from January 2017 to January 2019, 96 patients with SIC (a study group) and 90 patients with sepsis (a control group) were enrolled. The three cytokines were determined and the diagnostic value of their combined detection for SIC was analyzed. RESULTS: The cytokines were remarkably higher in the study group (p<.001). The combined detection of the three had a better diagnostic value for SIC (p<.001). The three cytokines were independent risk factors for the death of patients with SIC. CONCLUSION: IL-1ß, IL-6, and TNF-α in SIC patients rise markedly. The combined detection of the three has a better predictive value for patients with SIC and is closely related to the patients' prognoses, so it may be crucial in diagnosing and treating the disease.

Matrine Suppresses Pancreatic Fibrosis by Regulating TGF-ß/Smad Signaling in Rats.

PURPOSE: This study aimed to elucidate the molecular mechanisms of the anti-pancreatic fibrosis effects of matrine in rats. MATERIALS AND METHODS: Trinitrobenzene sulfonic acid was administrated to rats to establish a pancreatic fibrosis model. Rats were divided into four groups: Control, Sham, Model, and Matrine (n=8). Hematoxylin-eosin staining, Masson staining, and Azan staining were performed to evaluate pancreatic fibrosis. Expression of transforming growth factor-ß1 (TGF-ß1), α-smooth muscle actin (α-SMA), and collagen I in pancreatic tissues was evaluated by immunohistochemical staining. mRNA and protein levels of TGF-ß receptor 1 (TßR1), TßR2, and Smad2 in pancreatic tissues were determined by RT-PCR and Western blot, respectively. RESULTS: In the model group, hyperplasia of glandules around the glandular ducts, mitochondrial swelling of acinous cells, and severe fibrosis were found. Interestingly, in the Matrine group, mitochondrial swelling was only found in a small number of acinous cells, and the fundamental structures of pancreatic tissues were intact. Moreover, pancreatic fibrosis was markedly alleviated. Comparing to the Sham group, expression of α-SMA, TGF-ß1, and collagen I was sharply elevated in the Model group (p<0.05); however, their expressions were much lower in the Matrine group, compared to the Model group (p<0.05). Compared with the Sham group, mRNA and protein levels of Smad2, TßR1, and TßR2 in the Model group were notably raised (p<0.05). However, their high expression was significantly downregulated in the Matrine group (p<0.05). CONCLUSION: Matrine suppressed pancreatic fibrosis by regulating TGF-ß/Smad signaling in rats.

Detoxification and activating blood circulation decoction reduces restenosis involving the TLR4/NF-κB pathway after balloon injury.

Restenosis is a major problem after percutaneous coronary intervention (PCI) treatment. Inflammation is one of the major core mechanisms involved in the occurrence of restenosis, and plays an important role in intimal hyperplasia. Detoxification and activating blood circulation decoction (DABCD) is a traditional Chinese medicine that is used in the treatment and prevention of atherosclerotic and inflammatory diseases. Our previous studies demonstrated that DABCD-mediated cardioprotection involves anti-inflammatory mechanisms and could be developed as a novel drug for the treatment of vascular smooth muscle cell (VSMC) proliferation and aortic restenosis. A rat model of postoperative restenosis after PCI was generated by balloon injury to determine the protective effects and potential mechanisms of DABCD. The injured segments of aortae were collected on days 14 and 28 after the operation to observe the morphological changes in the vascular structure and measure the proportion of inflammatory factors in plasma and vascular tissues, as well as test the proliferative activity of VSMCs. The expression of related proteins, namely, Toll-like receptor (TLR) 4 and nuclear factor (NF)-κB, in the mechanistic study was clarified by western blot analysis. We tested the hypothesis that the cardioprotective effects of DABCD on aortic restenosis are associated with the inhibition of aortic intimal hyperplasia in this model. Our results showed that DABCD has protective effect on rat aortic restenosis and the anti-inflammatory mechanism of DABCD on balloon-induced restenosis in rat may be due to its ability to inhibit TLR4-mediated NF-κB signaling pathways. DABCD may be a potential therapeutic agent against restenosis.

Tetrandrine down-regulates expression of miRNA-155 to inhibit signal-induced NF-κB activation in a rat model of diabetes mellitus.

AIMS: This study is to investigate expression of miRNA-155 and the related signaling pathway in a rat model of diabetes mellitus (DM). METHODS: Thirty-six SD rats were divided into control, DM, and tetrandrine groups. A rat model of DM was constructed by tail vein injection with alloxan. Levels of related cytokines in serum samples were detected. The mRNA levels of IκBα and TNF-α in pancreatic islet tissues were detected by real-time PCR. Protein expression of IκBα and TNF-α was detected by western blotting. Expression of miRNA-155 in pancreatic islet tissues and serum samples was detected by real-time PCR. RESULTS: Compared with those in the control and the tetrandrine groups, activities of methane dicarboxylic aldehyde and reactive oxygen species in serum samples and pancreatic islet mitochondria tissues in the DM group were increased (P < 0.05), while activity of superoxide dismutase in the DM group was decreased (P < 0.05). Activities of haemoglobin A1c and glucose in serum samples in the DM group were increased, while insulin in the DM group was decreased (P < 0.05). The mRNA and protein levels of IκBα in pancreatic islet tissues in the DM group were decreased (P < 0.05), while the mRNA and protein levels of TNF-α in the DM group were increased (P < 0.05). Expression of miRNA-155 in pancreatic islet tissues and serum samples in the DM group was increased (P < 0.05). CONCLUSION: Tetrandrine prevented injury in rat pancreatic islet caused by alloxan, which was related with decreased oxidative stress, down-regulated miRNA-155 and decreased TNF-α in the NF-κB signaling pathway. These results indicate that tetrandrine plays an important role in DM by regulating expression of miRNA-155.