In this research, we aimed to observe the changes in myocardial fibrosis indices in patients with chronic heart failure before and after treatment and to evaluate the anti-chronic heart failure and ventricular remodelling effects of Trichosanthis peel (TP) injection. This study was a single-center, open, single-blind, randomized controlled study with an optimal efficacy design. Patients were consecutively and randomly divided into two groups, with 36 patients in the TP injection group and 36 patients in the conventional treatment group. ELISA was used to measure changes in myocardial fibrosis indices before and after discharge, including transforming growth factor β (TGF-β), serum hyaluronic acid (HA), type I procollagen (PCI), laminin (LN) and type III procollagen (PCIII). There was no significant difference between the two groups in clinical data or baseline level of myocardial fibrosis before treatment. After treatment, compared with the conventional treatment group, the myocardial fibrosis index was significantly decreased following TP injection. Our findings indicate that TP injection combined with conventional medicine can attenuate myocardial fibrosis by reducing angiotensin II, aldosterone, TGFβ, HA, PCI, metallomatrix proteinase 2, connective tissue growth factor and LN and promote ventricular remodelling in patients with chronic heart failure.

Pulmonary fibrosis is the end-stage pathological change of lung diseases, which seriously affects the respiratory function of human body. A large number of studies at home and abroad have confirmed that epithelial-mesenchymal transition (EMT) is an important intermediate stage in the development of pulmonary fibrosis. Inhibition of multiple pathways upstream and downstream of EMT, such as the classical Smads pathway and non-Smads pathway of TGF-1 can effectively inhibit the process of EMT and alleviate pulmonary fibrosis. This article will review the main conclusions of the mechanism of action of EMT as a target to improve the pathology of pulmonary fibrosis so far, and provide a theoretical basis and research direction for further research and development of anti-pulmonary fibrosis drugs.
肺纤维化为肺部疾病的终末期病理性改变，严重影响人体的呼吸功能。国内外研究表明，上皮间质转化（EMT）是肺纤维化发展过程中重要的中间阶段，定向调控EMT上下游多条作用路径，如转化生长因子-1的经典Smads通路、非Smads通路等，可有效遏制EMT进程，缓解肺纤维化病变。本文对以EMT为作用靶点，改善肺纤维化病理作用机制的主要研究成果进行综述，为进一步研发抗肺纤维化药物提供理论基础和研究方向。.

The N-methyl-d-aspartate receptor (NMDAR) antagonist (R,S)-ketamine causes rapid onset and sustained antidepressant actions in treatment-resistant patients with major depressive disorder (MDD) and other psychiatric disorders, such as bipolar disorder and post-traumatic stress disorder. (R,S)-ketamine is a racemic mixture consisting of (R)-ketamine (or arketamine) and (S)-ketamine (or esketamine), with (S)-enantiomer having greater affinity for the NMDAR. In 2019, an esketamine nasal spray by Johnson & Johnson was approved in the USA and Europe for treatment-resistant depression. In contrast, an increasing number of preclinical studies show that arketamine has greater potency and longer-lasting antidepressant-like effects than esketamine in rodents, despite the lower binding affinity of arketamine for the NMDAR. Importantly, the side effects, i.e., psychotomimetic and dissociative effects and abuse liability, of arketamine are less than those of (R,S)-ketamine and esketamine in animals and humans. An open-label study demonstrated the rapid and sustained antidepressant effects of arketamine in treatment-resistant patients with MDD. A phase 2 clinical trial of arketamine in treatment-resistant patients with MDD is underway. This study was designed to review the brief history of the novel antidepressant arketamine, the molecular mechanisms underlying its antidepressant actions, and future directions.

Corneal fibrosis is a complication of severe corneal injury, one of the major causes of vision loss. The formation of myofibroblasts has emerged as a key stimulative factor of corneal fibrosis. In the current study, we focused on the role of LINC00963 in regulating corneal fibrosis. Transforming growth factor β1 (TGF-β1) was used to induce human corneal stromal cells differentiating into corneal myofibroblasts, and the significant increase of α-smooth muscle actin (α-SMA) was verified by quantitative real-time PCR (qRT-PCR), western blot, and immunofluorescence, respectively. LINC00963 was identified to be one-half decreased compared with nonstimulated human corneal stromal cells, indicating that it might play a role in corneal fibrosis. Interestingly, overexpression of LINC00963 resulted in decreased formation of myofibroblasts indicating that it might exhibit an inhibiting effect. Moreover, bioinformatics tool was applied to predict the downstream target of LINC00963. We investigated that LINC00963 suppressed α-SMA induced by TGF-β1 in corneal fibroblasts, at least in part, by downregulating the expression of miR-143-3p. In addition, either LINC00963 promotion or miR-143-3p inhibition could significantly decrease myofibroblast contractility and collagen I and III secretion, which are the key to contribute to corneal fibrosis. Taken together, our study identified LINC00963 as a promising therapeutic target.

Metabolic reprogramming is a hallmark of pulmonary arterial hypertension. Platelet activation has been implicated in pulmonary arterial hypertension (PAH), whereas the role of platelet in the pathogenesis of PAH remains unclear.
First, we explored the platelet function of semaxanib\' a inhibitor of VEGF receptor (SU5416)/hypoxia mice and monocrotaline-injected rats PAH model. Then we investigated pulmonary arterial smooth muscle cell aerobic glycolysis after being treated with platelet supernatant. TGF (transforming growth factor)-βRI, pyruvate kinase muscle 2, and other antagonists were applied to identify the underlying mechanism. In addition, platelet-specific deletion TGF-β1 mice were exposed to chronic hypoxia and SU5416. Cardiopulmonary hemodynamics, vascular remodeling, and aerobic glycolysis of pulmonary arterial smooth muscle cell were determined.
Here, we demonstrate that platelet-released TGF-β1 enhances the aerobic glycolysis of pulmonary arterial smooth muscle cells after platelet activation via increasing pyruvate kinase muscle 2 expression. Mechanistically, platelet-derived TGF-β1 regulate spyruvate kinase muscle 2 expression through mTOR (mammalian target of rapamycin)/c-Myc/PTBP-1(polypyrimidine tract binding protein 1)/hnRNPA-1(heterogeneous nuclear ribonucleoprotein A1) pathway. Platelet TGF-β1 deficiency mice are significantly protected from SU5416 plus chronic hypoxia-induced PAH, including attenuated increases in right ventricular systolic pressure and less pulmonary vascular remodeling. Also, in Pf4cre+ Tgfb1fl/fl mice, pulmonary arterial smooth muscle cells showed lower glycolysis capacity and their pyruvate kinase muscle 2 expression decreased.
Our data demonstrate that TGF-β1 released by platelet contributes to the pathogenesis of PAH and further highlights the role of platelet in PAH.

OBJECTIVE: To investigate the effects of intense pulsed light (IPL) and ablative 2.940 nm erbium-doped yttrium aluminum garnet (Er: YAG) laser on dynamic changes in collagen by quantitative analysis of type I collagen (Col I) and type III collagen (Col III), transforming growth factor (TGF), and matrix metalloproteinases (MMPs) in the dermis of rabbits.
METHODS: Backs of ten rabbits were divided into four treatment areas: IPL normal energy group, IPL high-energy group, erbium laser normal energy group, and erbium laser high-energy group. HE staining was performed immediately after the first treatment and two weeks after the first treatment. Col I, Col III, TGF-β1, and MMP-1 were collected by real-time PCR at baseline, 2 weeks after each session, and three months after the entire treatment monthly.
RESULTS: HE staining showed that collagen fibers in the superficial layer of the dermis in the four treatment groups were increased and thickened to different degrees. Real-time PCR showed that statistically differences were noted in each checkpoint before and after treatments in the four groups, whereas no significant difference in the change in the four biomarkers was found among the four treatment groups.
CONCLUSIONS: Both the IPL and Er: YAG laser can effectively upregulate collagens, but in this experiment, there was no significant difference in the therapeutic effect among the four irradiation groups. Moreover, the high-energy level group tended to bring more serious epidermal injury.

Objective: To investigate the role and probable mechanism of miRNA-181a in nonalcoholic fatty liver disease. Methods: HepG2 cells were treated with palmitic acid to construct a nonalcoholic fatty liver disease cell model, and the expression of miR-181a and lipidosis in the cells were measured. Transforming growth factor-β (TGF-β) was used to examine the effect of miR-181a expression in HepG2 cells. The miR-181a, lipidosis, reduced glutathione and reactive oxygen species (ROS) were determined by controlling and regulating the miR-183 expression levels after transfection with miR-181 mimics and inhibitors in HepG2 cells. The miR-181a target genes were predicted by bioinformatics analysis, and verified by real-time fluorescent quantitative PCR and western blotting. The independent sample t-test was used for the comparison between the two independent samples, and the comparison between multiple groups were accorded with the normal distribution, homogeneity of variance, and one-way analysis of variance. Results: Lipidosis was significantly increased after palmitic acid treatment in HepG2 cells, and the expression level of miR-181a was significantly increased than control group. After HepG2 cells were transfected with miR-181a inhibitors, the expression of miR-181a, triglycerides and reactive oxygen species were down-regulated, and reduced glutathione, predicting the mRNA and protein expression of target gene silencing information regulator 2 related enzyme 1 were up-regulated. However, the results were contrary to the above changes after transfection with miR-181a mimics. Conclusion: miR-181a participates in lipidosis and promotes lipid peroxidation in nonalcoholic fatty liver disease. miR-181a may affect the pathogenesis and progression of nonalcoholic fatty liver disease by inhibiting the expression of silencing information regulator 2 related enzyme 1.
目的： 探讨miRNA-181a（miR-181a）对非酒精性脂肪性肝病的影响及其可能的机制。 方法： 使用棕榈酸处理HepG2细胞构建非酒精性脂肪性肝病细胞模型，检测细胞内miR-181a的表达及脂质沉积。用转化生长因子-β处理细胞检测其对miR-181a表达的影响。通过调控HepG2细胞miR-181a的表达水平，分别检测转染miR-181a模拟物和抑制物后HepG2细胞内miR-181a表达、脂质沉积和还原型谷胱甘肽和活性氧水平。通过实时荧光定量PCR和蛋白质印迹法对生物信息学预测的miR-181a靶基因进行验证。两组独立样本间比较采用独立样本t检验，多组间比较资料特征符合正态分布且方差齐性，采用单因素方差分析。 结果： 棕榈酸处理后HepG2中脂质沉积明显增多，miR-181a表达水平显著高于对照组。HepG2细胞转染miR-181a抑制物后，miR-181a表达下调，甘油三酯和活性氧下降，还原型谷胱甘肽升高，预测靶基因沉默信息调节因子2相关酶1的mRNA和蛋白表达量上调；而转染miR-181a模拟物后，结果与上述改变相反。 结论： miR-181a参与非酒精性脂肪性肝病的脂质沉积并促进脂质过氧化，miR-181a可能是通过抑制沉默信息调节因子2相关酶1的表达来影响非酒精性脂肪性肝病的发病机制及进展。.

Bone morphogenetic protein 15 (BMP15) and follicle-stimulating hormone (FSH) both play important roles in mammalian ovary and follicular development. The aim of the present study is to investigate the effects of BMP15 and FSH in the prepubertal ovary of Rongchang pigs considering a possible signaling mechanism involving TβRII/ SMAD4 and FSHR in granulosa cells. For this purpose, we quantified expression levels of BMP15, SMAD2, SMAD3, SMAD4, SMAD7, TGF-β1, TGF-β2, TGF-β3, TGFβRI, TGFβRII, and FSHR via qRT-PCR at different ages in prepubertal ovaries and cultured biopsy of 90-day-old ovary in Rongchang pig. Additionally, the protein levels of BMP15, FSHR, SMAD2, SMAD4, TGFβRI, TGFβRII, TGF-β1, TGF-β2 were quantified via Western blot and the localizations of BMP15, FSHR and TGFβRII were observed via immunofluorescence confocal microscope. The results showed that expression levels of BMP15, TGF-β1, TGFβRII and FSHR increased significantly at day 60 as compared to day 30 and reached peak value at day 90 in prepubertal ovary of Rongchang pigs. We observed that BMP15, TGFβRII and FSHR was highly presented, which TGFβRII and FSHR displayed co-localization in the follicles of the prepubertal ovaries of 90-day-old Rongchang gilts. Treatment with TGFβRI/II inhibitor LY2109761 significantly decreased the expression of TGFβRI, TGFβRII and SMAD4 and TGFβRI inhibitor LY2157299 decreased TGFβRI, but increased the TGFβRII, SMAD4 and FSHR expression levels. Furthermore, the addition of rBMP15 and rFSH group significantly increased the expression of TGFβRII and FSHR proteins (P < 0.01), but no significant change in the expression of TGFβRI (P > 0.05) was observed by Western blot. In conclusion, BMP15, TGFβRII and FSHR were increased significantly in the prepubertal ovarian follicles of Rongchang pigs and FSHR expression in GCs was regulated by BMP15 and FSH through the TGFβRII.

Pathogenic Th17 cells are critically involved in many autoimmune diseases, while non-pathogenic Th17 cells are more immune regulatory. Understanding the mechanisms of the induction and maintenance of pathogenic Th17 cells will benefit the development of therapeutic treatments of related diseases. We have shown that the transforming growth factor-β (TGFβ) induced SKI degradation and dissociation from Smad4 complex is a prerequisite for TGFβ-induced Th17 cell differentiation. However, it is unclear whether and how SKI regulates pathogenic Th17 differentiation, which does not require TGFβ cytokine. Here we showed that SKI expression was downregulated during pathogenic Th17 cell differentiation and the ectopic expression of SKI abrogated the differentiation of pathogenic Th17 cells. Functionally, using a knock-in mouse model, we found ectopic SKI expression specifically in T cells prevented myelin oligodendrocyte glycoprotein peptide (MOG33-55) induced experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis. We further revealed that induced SKI expression in already differentiated pathogenic Th17 cells reduced the maintenance of Th17 program and ameliorated EAE in an adoptive T cell transfer model. Therefore, our study provides valuable insights of targeting SKI to modulate pathogenic Th17 cell function and treat Th17-related diseases.

Malignant tumors are a serious threat to human health. Surgical resection is the most effective treatment for liver cancer. However, liver cancer is mostly found at an advanced stage, is difficult to remove by surgery, and has a very high recurrence rate after surgery. The current liver cancer treatment drugs have serious side effects, and the treatment effect is not ideal, far from meeting the clinical needs. Based on this, this paper studies the effect of propofol on the proliferation and apoptosis of liver cancer cells through the TGF-B1/Smad2 signaling pathway, and explores the proliferation, adhesion and apoptosis of cancer cells in patients with propofol. This paper uses a comparative experiment. With medical imaging method, 80 rats with liver cancer in the same period were cultured. High-precision microscope and radiolocation method were used to observe and record the whole process of propofol regulating Smad2 signal pathway. The results show that propofol can effectively inhibit the proliferation of cancer cells in patients with liver cancer. Propofol can increase the activity and content of transforming growth factor-β1 by 12% and 20%, respectively, and then inhibit the proliferation rate of liver cancer cells by 10% through the Smad2 signaling pathway, and exponentially increase the apoptotic number of liver cancer cells. This shows that propofol has a significant inhibitory effect on the cycle of liver cancer cells. Under the action of propofol, the life cycle of liver cancer cells is shortened, which provides a certain theoretical basis for the treatment of liver cancer.