ObjectiveTo investigate the expression of catechol O-methyltransferase (COMT) mRNA and its protein in colorectal adenoma tissues and corresponding adjacent tissues, colorectal cancer tissues and corresponding adjacent tissues. MethodsExpressions of COMT mRNA and its protein were evaluated by real-time PCR and immunohistochemistry method in colorectal adenoma tissues and corresponding adjacent tissues, colorectal cancer tissues and corresponding adjacent tissues. Meanwhile, the relationship between the expression of COMT and clinic-pathological features of colorectal adenoma and colorectal cancer were analyzed. Results①The expression of COMT mRNA in colorectal adenoma tissue/colorectal cancer tissue group was higher than that of corresponding adjacent tissue group (0.109 0 vs. 0.000 5, t=3.02, P=0.01; 0.041 8 vs. 0.013 5, t=2.71, P=0.02).②The rate of high-expression of COMT in colorectal adenoma tissue/colorectal cancer tissue group was higher than that of corresponding adjacent tissue group [72.34% (34/47) vs. 25.53% (12/47), χ2=28.72, P < 0.01; 66.67% (28/42) vs. 28.57% (12/42), χ2=4.97, P < 0.05].③High-expression of COMT was not related to age, gender, location of tumor, and pathological type in colorectal adenoma patients (P > 0.05). High-expression of COMT was not related to age, gender, location of tumor, and differentiation degree (P > 0.05), but was related to TNM staging, T staging, and N staging in colorectal cancer patients (P < 0.05), the patients of TNMⅠ+Ⅱstaging, T1+T2 staging, and N0 staging had higher rate of high-expression of COMT. ConclusionCompared with corresponding adjacent tissues, COMT expresses highly in colorectal adenoma tissues and colorectal cancer tissues, so it may play a partial role in the emergence and development of colorectal cancer.
Acute respiratory distress syndrome (ARDS) is the most common cause of acute respiratory failure. Extensive researches have been conducted for the pathophysiology of this disease, but the mortality rate remains high. Previous studies have found that catecholamines play an important role in acute lung injury, and newly discover prompted that upregulation of phagocyte-derived catecholamines augmented the acute inflammatory response in acute lung injury which provides a new way of thinking. In the current review, we describe the mechanism of the phagocyte-derived catecholamines augmenting the acute lung injury.
The hemodynamic management of adult patients with distributed shock often includes the use of catecholamines vasoconstrictor drugs. It was unclear whether adding vasopressin or vasopressin analogs to catecholamine therapy was beneficial for the treatment of patients with distributed shock. The Canadian Society of Intensive Care recently updated its clinical practice guideline to provide recommendations for the addition of vasopressin to catecholamine boosters in adults with distributed shock. This paper interprets it to assist domestic doctors for better understanding of the latest progress.
Catecholamine-induced cardiomyopathy in pheochromocytoma/paraganglioma (PPGL) is a potential fatal cardiovascular complication caused by excessive secretion of catecholamines by PPGL, leading to structural changes and functional abnormalities in the heart. According to the morphology and function of the heart, it is clinically divided into three types: dilated cardiomyopathy, Takotsubo cardiomyopathy, and hypertrophic cardiomyopathy. The treatment of catecholamine-induced cardiomyopathy in PPGL requires attention to drug selection, application of life support equipment, and perioperative management. Most patients with cardiac dysfunction can effectively improve after tumor resection. This article mainly reviews the diagnosis and treatment of catecholamine-induced cardiomyopathy in PPGL.
ObjectiveTo explore the genetic mutation characteristics, clinical manifestations, and treatment outcomes of catecholaminergic polymorphic ventricular tachycardia (CPVT), and to construct a quantitative scoring system for the severity of CPVT. The correlation between the mutations in different structural domains of the RyR2 gene and clinical manifestations and prognosis was analyzed. MethodsBy searching the PubMed and Web of Science databases for CPVT-related case reports published up to December 2024, data such as patient age, clinical manifestations, gene mutation sites, and treatment responses were collected. The quality of the literature was assessed using the CARE guidelines. The χ2 test was used to compare the severity and treatment response differences among different RyR2 structural domain mutation groups, and an innovative quantitative scoring system based on symptoms and efficacy was established. ResultsA total of 81 articles were included, with 102 patients in total. The quality of the literature was reliable. The age of the patients ranged from 1 to 84 years, with a higher proportion of children under 10 years old (25.5%). Female patients (55%) outnumbered males (45%). For CPVT patients, a quantitative scoring system was developed, with a total score of 2 to 10 points. Among them, 2 to 4 points were classified as mild, 5 to 7 points as moderate, and 8 to 10 points as severe. The results showed that severe patients often had a history of cardiac arrest and were resistant to treatment. Out of the 102 CPVT patients, RyR2 gene mutations accounted for 53.9% (55/81) of patients. Among them, the proportion of severe patients with N-terminal structural domain mutations was significantly higher than other regions, indicating that the RyR2 gene mutation structural domain has a significant impact on the severity of CPVT (χ2=17.530, P=0.008). The proportion of patients with mutations in the central hinge region who were ineffective with β-blockers reached 42.9% (3/7), which was significantly higher than other regions. Left cardiac sympathectomy was performed in 24 cases, and postoperative symptoms were almost completely controlled, significantly better than the drug treatment group. ConclusionMutations in the N-terminal structural domain of the RyR2 gene are significantly correlated with the severity of CPVT. Left cardiac sympathectomy has gradually become an effective intervention for refractory cases. The scoring system proposed in this study can provide a basis for clinical stratified treatment. In the future, there is a need to expand the sample size to verify mutation-specific treatment strategies.
Objective To investigate the effects of 4-methylcatechol (4MC) on the migration and inflammatory response in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS), as well as its underlying mechanisms of action. Methods RA-FLS was isolated from synovial tissue donated by RA patients, and the optimal concentration of 4MC was determined by cell counting kit 8 method for subsequent experiments, and the effect of 4MC on the migratory ability of RA-FLS was evaluated via a cell scratch assay. An inflammation model of RA-FLS was induced by tumor necrosis factor α (TNF-α). Real-time fluorescence quantitative PCR and ELISA were employed to detect the gene and protein expression levels of interleukin-1β (IL-1β) and IL-6 in RA-FLS and their culture supernatants, respectively, thereby investigating the anti-inflammatory effects of 4MC. Western blot was used to examine the expression of nuclear factor κB (NF-κB) signaling pathway-related proteins, including inhibitor of NF-κB-α (IKBα), phosphorylated (P)-IκBα, NF-κB-inducing kinase α (IKKα), P-IKKαβ, P-p65, and p65. Cellular immunofluorescence was utilized to detect the expression and localization of p65 in RA-FLS, exploring whether 4MC exerts its anti-inflammatory effects by regulating the NF-κB signaling pathway. Finally, a collagen-induced arthritis (CIA) mouse model was established. The anti-RA effect of 4MC in vivo was evaluated by gross observation and histological examination. Results 4MC inhibited RA-FLS migration in a concentration-dependent manner. In the TNF-α-induced RA-FLS inflammation model, 4MC significantly decreased the gene and protein expression levels of IL-1β and IL-6. Furthermore, 4MC markedly reduced the ratios of P-IΚBα/IΚBα, P-IKKαβ/IKKα, and P-p65/p65, thereby blocking the transcriptional activity of p65 by inhibiting its nuclear translocation. This mechanism effectively suppressed the activation of the TNF-α-mediated NF-κB signaling pathway. Animal studies demonstrated that 4MC [10 mg/(kg·day)] significantly lowered serum levels of IL-1β, IL-6, and TNF-α, and alleviated arthritis severity and bone destruction in CIA mice. Conclusion 4MC not only inhibits the migration of RA-FLS but also mitigates their inflammatory response by suppressing the NF-κB signaling pathway, thereby effectively exerting its anti-RA effects.