Effects of the combination of tanshinone IIA and puerarin on cardiac function and inflammatory response in myocardial ischemia mice.

Liver fibrosis resulting from continuous long-term hepatic damage represents a heavy burden worldwide. Liver fibrosis is recognized as a complicated pathogenic mechanism with extracellular matrix (ECM) accumulation and hepatic stellate cell (HSC) activation. A series of drugs demonstrate significant antifibrotic activity in vitro and in vivo. No specific agents with ideally clinical efficacy for liver fibrosis treatment have been developed. In this review, we summarized the antifibrotic effects and molecular mechanisms of 29 kinds of common natural products. The mechanism of these compounds is correlated with anti-inflammatory, antiapoptotic, and antifibrotic activities. Moreover, parenchymal hepatic cell survival, HSC deactivation, and ECM degradation by interfering with multiple targets and signaling pathways are also involved in the antifibrotic effects of these compounds. However, there remain two bottlenecks for clinical breakthroughs. The low bioavailability of natural products should be improved, and the combined application of two or more compounds should be investigated for more prominent pharmacological effects. In summary, exploration on natural products against liver fibrosis is becoming increasingly extensive. Therefore, natural products are potential resources for the development of agents to treat liver fibrosis.

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A Comprehensive Review of Natural Products against Liver Fibrosis: Flavonoids, Quinones, Lignans, Phenols, and Acids.

Thioacetamide potentiates high cholesterol and high fat diet induced steato-hepatitic changes in livers of C57BL/6J mice: A novel eight weeks model of fibrosing NASH.

Efficient therapy of idiopathic pulmonary fibrosis (IPF) is still a major challenge. The current studies with single-target drug therapy are the pessimistic approaches due to the complex characteristics of IPF. Here, a combination therapy of Tanshinone IIA and Puerarin for IPF was proposed to alleviate IPF due to their antiinflammatory and anti-fibrotic effects. In vivo, the combination therapy could significantly attenuate the area of ground glass opacification that was presented by 85% percentile density score of the micro-CT images when compared to single conditions. In addition, the combination therapy enormously improved the survival rate and alleviated pathological changes in bleomycin (BLM)-induced IPF mice. By using a wide spectrum of infiltration biomarkers in immunofluorescence assay in pathological sections, we demonstrate that fewer IL6 related macrophage infiltration and fibrosis area after this combination therapy, and further proved that IL6-JAK2-STAT3/STAT1 is the key mechanism of the combination therapy. In vitro, combination therapy markedly inhibited the fibroblasts activation and migration which was induced by TGF-β1 or/and IL6 through JAK2-STAT3/STAT1 signaling pathway. This study demonstrated that combination therapeutic effect of TanIIA and Pue on IPF may be related to the reduced inflammatory response targeting IL6, which could be an optimistic and effective approach for IPF.

Combination therapy of tanshinone IIA and puerarin for pulmonary fibrosis via targeting IL6-JAK2-STAT3/STAT1 signaling pathways.

Molecular mechanisms of protective roles of isoflavones against chemicals-induced liver injuries

Liver fibrosis is a complex pathological process and an early step in the progression of liver cirrhosis, which can eventually develop into hepatocellular carcinoma. Currently, there is no effective treatment for liver fibrosis. Puerarin is a traditional Chinese herb, which is commonly used in the treatment of various diseases. In addition, it is also believed to have a therapeutic effect in liver fibrosis. However, whether puerarin reduces liver fibrosis via the ERK1/2 signaling pathway to inhibit the activation of hepatic stellate cell (HSC) and excessive collagen deposition in liver fibrosis remains unknown. The aim of the current study was to establish a liver fibrosis in vivo model by intraperitoneal injection of thioacetamide (TAA) and investigate the effect of puerarin in the treatment of liver fibrosis. Hematoxylin and eosin and Van Gieson's staining were used to examine histopathological changes associated with liver fibrosis. Liver hydroxyproline content was examined to determine the total amount of collagen in the liver. The relative protein expression levels of transforming growth factor β1 (TGFβ1), α-smooth muscle actin (α-SMA), collagen type I, fibronectin, ERK1/2 and p-ERK1/2 were determined by western blot analysis. In the TAA group, histopathological changes and collagen fiber content in rat liver tissue samples were significantly increased compared with the control group (P<0.05). In addition, treatment with puerarin significantly decreased histopathological changes and collagen fiber content in rat liver tissue samples (P<0.05). The relative protein expression levels of TGFβ1, α-SMA, collagen type I, fibronectin and p-ERK1/2 were significantly upregulated in the TAA group compared with the control group (P<0.05), whereas puerarin treatment reversed these changes. These findings suggest that treatment with puerarin may reduce HSC activation and alleviate extracellular matrix protein expression levels by inhibiting the TGF-β/ERK1/2 pathway in liver fibrosis.

/pdf/puerarin-alleviates-liver-fibrosis-via-inhibition-of-the-10dat7os53.pdf

Puerarin alleviates liver fibrosis via inhibition of the ERK1/2 signaling pathway in thioacetamide‑induced hepatic fibrosis in rats

Circular RNAs (circRNAs) are essential regulators in human cancers, including gastric cancer, by the miRNA/mRNA axis. A previous study identified the upregulation of circ_0110940 in human gastric cancer tissues. The present study performed in vitro assays to reveal the functions of circ_0110940 and its downstream miRNA/mRNA axis in gastric cancer cells. Traditional proliferation and apoptosis assays including colony formation, EdU staining, and Annexin V-PI staining assays were conducted. A luciferase reporter assay was performed to assess the binding between miR-1178-3p and circ_0110940 or SLC38A. We found the significant upregulation of circ_0110940 in human gastric cancer cells AGS and MKN45. Circ_0110940 was a stable circRNA and exerted an antiproliferative and proapoptotic effect in AGS and MKN45. Circ_0110940 binded with miR-1178-3p, which further targeted SLC38A6 3′UTR. Circ_0110940 degraded miR-1178-3p, and miR-1178-3p degraded SLC38A6. Thus, circ_0110940 has a positive effect on SLC38A6 expression. Furthermore, SLC38A6 rescued the effects of circ_0110940 knockdown on gastric cancer cell proliferation and apoptosis. In conclusion, circ_0110940 exerted an antiapoptotic and pro-proliferative effect in gastric cancer cells via the miR-1178-3p/SLC38A6 axis, which may provide basis for the targeted therapy of gastric cancer.

/pdf/circ-0110940-exerts-an-antiapoptotic-and-pro-proliferative-3jlwb9ep.pdf

Circ_0110940 Exerts an Antiapoptotic and Pro-Proliferative Effect in Gastric Cancer Cells via the miR-1178-3p/SLC38A6 Axis

Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer, and its development, growth, and invasiveness are regulated by the tumor microenvironment (TME). Insulin-like growth factor-binding protein-7 (IGFBP7), which is closely related to various tumors, transforming growth factor-β1 (TGFβ1), which is a key signal mediator in oncogenesis, α-smooth muscle actin (α-SMA), and collagen I are important components of the TME. IGFBP7 can upregulate the expression of TGFβ1 and activate the TGFβ1/SMAD signaling pathway, which leads to an increase in collagen I in hepatic stellate cells (HSCs). However, the contribution of IGFBP7 to TGFβ1 and the TME in the progression of ESCC remains unknown. In the present study, we investigated IGFBP7 expression and its effects on TGFβ1 and the TME in ESCC. A total of 45 patients were divided into three groups: early-tumor group (n=15), advanced-tumor group (n=15), and paracancer control group (n=15). The EC109 cell line was cultured and treated with AdIGFBP7 and LvshTGFβ1, and the expression levels of IGFBP7, TGFβ1, α-SMA, collagen I, and p-SMAD2/3 were determined by immunohistochemical staining and western blotting analysis. IGFBP7, TGFβ1, α-SMA, and collagen I were upregulated in the ESCC samples compared with the control samples (P<0.05), and the values peaked in the advanced-tumor group (P<0.05). Compared with the control group, the TGFβ1, α-SMA, p-SMAD2/3, and collagen I proteins were gradually increased from 24 to 72 h in the EC109 cells treated with AdIGFBP7 (P<0.05). Inhibition of TGFβ1 expression in the EC109 cells treated with AdIGFBP7 gradually reduced the expression of α-SMA, collagen I, and p-SMAD2/3 from 24 to 72 h (P<0.05). These findings suggest that increased IGFBP7 may accelerate the progression of ESCC by upregulating TGFβ1, α-SMA, and collagen I via activating the TGFβ1/SMAD signaling pathway, which could remodel the TME.

/pdf/igfbp7-remodels-the-tumor-microenvironment-of-esophageal-21cwaxkr.pdf

IGFBP7 remodels the tumor microenvironment of esophageal squamous cell carcinoma by activating the TGFβ1/SMAD signaling pathway

[This corrects the article DOI: 10.3892/ol.2022.13371.].

Objective Gastrointestinal cancer is the leading cause of cancer-related death in China, and its early screening is largely recommended by healthcare workers. This study investigated the knowledge, attitudes, and practice (KAP) of healthcare workers on early gastrointestinal cancer (EGC). Methods This cross-sectional study was conducted on healthcare workers who volunteered to participate from 30 hospitals in China between September and December 2022. A self-administered questionnaire including 37 questions was developed. Results A total of 545 completed questionnaires were finally obtained. Healthcare workers had moderate knowledge level [9.22 ± 1.80 (65.88±12.89%), total score: 14], positive attitude [21.84 ± 2.67 (91.01 ± 11.14%), total score: 24], and excellent practice level [19.07 ± 4.43 (79.47 ± 18.44%), total score: 24] on EGC. Pearson's correlation analysis suggested that knowledge score was positively correlated with attitude (r = 0.264, P < 0.001) and practice score (r = 0.140, P = 0.001), and higher attitude score was significantly correlated with higher practice score (r = 0.380, P < 0.001), which were supported and reinforced by structural equation modeling. In addition, subgroup analysis showed that knowledge scores might be influenced by sex, age, education, type of hospital, type of occupation, professional title, and years of working (all P < 0.05); attitude scores might be influenced by years of working (P < 0.05); and practice scores were statistically distinct among groups of different sex, department, and years of working (all P < 0.05). Conclusion Healthcare workers have moderate knowledge level, positive attitude, and excellent practice levels on EGC. Good knowledge and positive attitude might be correlated with excellent practice. KAP level might be influenced by sociodemographic characteristics.

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Youshan Wu

Papers

Puerarin alleviates liver fibrosis via inhibition of the ERK1/2 signaling pathway in thioacetamide‑induced hepatic fibrosis in rats

Circ_0110940 Exerts an Antiapoptotic and Pro-Proliferative Effect in Gastric Cancer Cells via the miR-1178-3p/SLC38A6 Axis

IGFBP7 remodels the tumor microenvironment of esophageal squamous cell carcinoma by activating the TGFβ1/SMAD signaling pathway

IGFBP7 remodels the tumor microenvironment of esophageal squamous cell carcinoma by activating the TGFβ1/SMAD signaling pathway

Knowledge, attitude, and practice of healthcare workers on early gastrointestinal cancer in China