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NETO2 promotes melanoma progression via activation of the Ca/CaMKII signaling pathway

《医学前沿（英文）》 2023年 第17卷 第2期   页码 263-274 doi: 10.1007/s11684-022-0935-0

摘要： Melanoma is the most aggressive cutaneous tumor. Neuropilin and tolloid-like 2 (NETO2) is closely related to tumorigenesis. However, the functional significance of NETO2 in melanoma progression remains unclear. Herein, we found that NETO2 expression was augmented in melanoma clinical tissues and associated with poor prognosis in melanoma patients. Disrupting NETO2 expression markedly inhibited melanoma proliferation, malignant growth, migration, and invasion by downregulating the levels of calcium ions (Ca2+) and the expression of key genes involved in the calcium signaling pathway. By contrast, NETO2 overexpression had the opposite effects. Importantly, pharmacological inhibition of CaMKII/CREB activity with the CaMKII inhibitor KN93 suppressed NETO2-induced proliferation and melanoma metastasis. Overall, this study uncovered the crucial role of NETO2-mediated regulation in melanoma progression, indicating that targeting NETO2 may effectively improve melanoma treatment.

关键词： melanoma     neuropilin and tolloid-like 2     Ca2+/CaMKII signaling pathway    

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Apigenin alleviates neomycin-induced oxidative damage via the Nrf2 signaling pathway in cochlear hair

《医学前沿（英文）》 2022年 第16卷 第4期   页码 637-650 doi: 10.1007/s11684-021-0864-3

摘要： Oxidative stress plays an important role in the pathogenesis of aminoglycoside-induced hearing loss and represents a promising target for treatment. We tested the potential effect of apigenin, a natural flavonoid with anticancer, anti-inflammatory, and antioxidant activities, on neomycin-induced ototoxicity in cochlear hair cells in vitro. Results showed that apigenin significantly ameliorated the loss of hair cells and the accumulation of reactive oxygen species upon neomycin injury. Further evidence suggested that the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway was activated by apigenin treatment. Disruption of the Nrf2 axis abolished the effects of apigenin on the alleviation of oxidative stress and subsequent apoptosis of hair cells. This study provided evidence of the protective effect of apigenin on cochlear hair cells and its underlying mechanism.

关键词： apigenin     aminoglycosides     ototoxicity     oxidative stress     Nrf2 signaling pathway    

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FERM domain-containing protein FRMD6 activates the mTOR signaling pathway and promotes lung cancer progression

《医学前沿（英文）》 2023年 第17卷 第4期   页码 714-728 doi: 10.1007/s11684-022-0959-5

摘要： FRMD6, a member of the 4.1 ezrin–radixin–moesin domain-containing protein family, has been reported to inhibit tumor progression in multiple cancers. Here, we demonstrate the involvement of FRMD6 in lung cancer progression. We find that FRMD6 is overexpressed in lung cancer tissues relative to in normal lung tissues. In addition, the enhanced expression of FRMD6 is associated with poor outcomes in patients with lung squamous cell carcinoma (n = 75, P = 0.0054) and lung adenocarcinoma (n = 94, P = 0.0330). Cell migration and proliferation in vitro and tumor formation in vivo are promoted by FRMD6 but are suppressed by the depletion of FRMD6. Mechanistically, FRMD6 interacts and colocalizes with mTOR and S6K, which are the key molecules of the mTOR signaling pathway. FRMD6 markedly enhances the interaction between mTOR and S6K, subsequently increasing the levels of endogenous pS6K and downstream pS6 in lung cancer cells. Furthermore, knocking out FRMD6 inhibits the activation of the mTOR signaling pathway in Frmd6−/− gene KO MEFs and mice. Altogether, our results show that FRMD6 contributes to lung cancer progression by activating the mTOR signaling pathway.

关键词： FRMD6     lung cancer     mTOR pathway    

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Genetic evidence in planar cell polarity signaling pathway in human neural tube defects

null

《医学前沿（英文）》 2014年 第8卷 第1期   页码 68-78 doi: 10.1007/s11684-014-0308-4

摘要：

Neural tube defects (NTDs) are a group of birth anomalies having a profound physical, emotional, and financial effects on families and communities. Their etiology is complex, involving environmental and genetic factors that interact to modulate the incidence and severity of the developing phenotype. The planar cell polarity (PCP) pathway controls the process of convergent extension (CE) during gastrulation and neural tube closure and has been implicated in the pathogenesis of NTDs in animal models and human cohorts. This review summarizes the cumulative results of recent studies on PCP signaling pathway and human NTDs. These results demonstrate that PCP gene alterations contribute to the etiology of human NTDs.

关键词： planar cell polarity     neural tube defects     rare mutations    

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Wnt/β-catenin signaling pathway and its role in hepatocellular carcinoma

ZHANG Xufeng, YU Liang, LU Yi

《医学前沿（英文）》 2008年 第2卷 第3期   页码 216-228 doi: 10.1007/s11684-008-0042-x

摘要： Wnt/?-catenin signaling pathway has been identified as a key cellular pathway in embryogenesis and disease, including cancers. In recent years, more and more interacting components have been observed and their exact functions approached, thus ensuring the most complicated understanding of this pathway in normal organism development and disorders. In hepatocellular carcinoma (HCC), with a deeply understanding of this pathway, more and more genes which contribute to aberrant activation of Wnt/?-catenin signaling pathway has recently been identified and their exact roles in HCC pursued. In this review, we will focus on a mostly updated understanding of this pathway and its observed role in HCC by emphasizing the gene defects identified to promote tumorigenesis and development.

关键词： interacting     complicated understanding     embryogenesis     activation     organism development    

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Human menstrual blood-derived stem cells alleviate autoimmune hepatitis via JNK/MAPK signaling pathway

《医学前沿（英文）》 2023年 第17卷 第3期   页码 534-548 doi: 10.1007/s11684-022-0953-y

摘要： Autoimmune hepatitis (AIH) is a severe globally distributed liver disease that could occur at any age. Human menstrual blood-derived stem cells (MenSCs) have shown therapeutic effect in acute lung injury and liver failure. However, their role in the curative effect of AIH remains unclear. Here, a classic AIH mouse model was constructed through intravenous injection with concanavalin A (Con A). MenSCs were intravenously injected while Con A injection in the treatment groups. The results showed that the mortality by Con A injection was significantly decreased by MenSCs treatment and liver function tests and histological analysis were also ameliorated. The results of phosphoproteomic analysis and RNA-seq revealed that MenSCs improved AIH, mainly by apoptosis and c-Jun N-terminal kinase/mitogen-activated protein signaling pathways. Apoptosis analysis demonstrated that the protein expression of cleaved caspase 3 was increased by Con A injection and reduced by MenSCs transplantation, consistent with the TUNEL staining results. An AML12 co-culture system and JNK inhibitor (SP600125) were used to verify the JNK/MAPK and apoptosis signaling pathways. These findings suggested that MenSCs could be a promising strategy for AIH.

关键词： autoimmune hepatitis (AIH)     concanavalin A (Con A)     human menstrual blood-derived stem cells (MenSCs)     apoptosis     mitogen-activated protein kinase (MAPK)    

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Caveolin proteins: a molecular insight into disease

null

《医学前沿（英文）》 2016年 第10卷 第4期   页码 397-404 doi: 10.1007/s11684-016-0483-6

摘要：

Caveolae are a kind of specific cystic structures of lipid rafts in the cytoplasmic membrane and are rich in cholesterol and sphingolipids. In recent years, many researchers have found that both caveolins and caveolae play a role in the development of various human diseases, including coronary heart disease, hypertension, and nervous system disorders. The specific mechanisms by which caveolins induce diseases have been a topic of interest. However, a number of detailed molecular mechanisms remain poorly understood. This article focuses on the relationship between caveolin proteins and human diseases and reviews the molecular mechanisms of caveolins in disease networks.

关键词： caveolin     caveolae     microRNA     disease     signaling pathway     heart     tumor    

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Regulatory factors of mesenchymal stem cell migration into injured tissues and their signal transduction mechanisms

null

《医学前沿（英文）》 2011年 第5卷 第1期   页码 33-39 doi: 10.1007/s11684-011-0114-1

摘要：

Adult stem cells hold great promise for wound healing and tissue regeneration. Mesenchymal stem cells (MSCs), for example, have been shown to play a role in tissue repair. Research has shown that endogenous bone marrow MSCs or exogenously delivered MSCs migrate to the sites of injury and participate in the repair process. The precise mechanisms underlying migration of MSCs into the injured tissue are still not fully understood, although multiple signaling pathways and molecules were reported, including both chemoattractive factors and endogenous electric fields at wounds. This review will briefly summarize the regulatory facors and signaling transduction pathways involved in migration of MSCs. A better understanding of the molecular mechanisms involved in the migration of MSCs will help us to develop new stem cell-based therapeutic strategies in regenerative medicine.

关键词： mesenchymal stem cells     migration     molecular mechanisms     signaling pathway    

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Triterpenoid inducers of Nrf2 signaling as potential therapeutic agents in sickle cell disease: a review

null

《医学前沿（英文）》 2015年 第9卷 第1期   页码 46-56 doi: 10.1007/s11684-015-0375-1

摘要：

Sickle cell disease (SCD) is an inherited disorder of hemoglobin in which the abnormal hemoglobin S polymerizes when deoxygenated. This polymerization of hemoglobin S not only results in hemolysis and vaso-occlusion but also precipitates inflammation, oxidative stress and chronic organ dysfunction. Oxidative stress is increasingly recognized as an important intermediate in these pathophysiological processes and is therefore an important target for therapeutic intervention. The transcription factor nuclear erythroid derived- 2 related factor 2 (Nrf2) controls the expression of anti-oxidant enzymes and is emerging as a protein whose function can be exploited with therapeutic intent. This review article is focused on triterpenoids that activate Nrf2, and their potential for reducing oxidative stress in SCD as an approach to prevent organ dysfunction associated with this disease. A brief overview of oxidative stress in the clinical context of SCD is accompanied by a discussion of several pathophysiological mechanisms contributing to oxidative stress. Finally, these mechanisms are then related to current management strategies in SCD that are either utilized currently or under evaluation. The article concludes with a perspective on the potential of the various therapeutic interventions to reduce oxidative stress and morbidity associated with SCD.

关键词： oxidative stress     Nrf2     triterpenoids     sickle cell disease     vaso-occlusion     CDDO-Me    

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Proteome comparisons reveal influence of different dietary proteins on the development of rat jejunum

Mengjie LI, Chunbao LI, Shangxin SONG, Xinglian XU, Guanghong ZHOU

《农业科学与工程前沿（英文）》 2018年 第5卷 第3期   页码 362-372 doi: 10.15302/J-FASE-2018206

摘要：

This study compared proteome profiles and morphological changes of rat jejunum in response to different dietary proteins. Fifty male Sprague-Dawley rats were fed with casein (control), and isolated beef, pork, fish and chicken proteins for 14 days. Proteome analysis, histological observation and PEPT1 quantification of the jejunum were performed. The results indicated that rats fed with chicken proteins had higher PEPT1 mRNA and protein levels (P<0.05) but lower villus height and ratio of villus height to crypt depth (V/C ratio, P<0.05) than those fed with casein and pork protein. Label-free LC-MS/MS indicated that, as compared to casein, intake of chicken protein can regulate oligopeptide transport mainly by upregulating PEPT1 protein expression and reducing dipeptidyl-peptidase activity related to biological oxidation, and can reduce oligopeptide absorption capacity by regulating Hippo signaling pathway. Although intake of beef and fish proteins had no significant effect on PEPT1 expression, they altered several signaling pathways.

关键词： Hippo signaling pathway     meat protein     PEPT1     proteome analysis     rat jejunum    

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Kinetics of pozzolanic reaction for preparation of flue gas desulfurizer from fly ash and Ca(OH)2

WANG Jingang, HU Jinbang, WANG Daobin, DUAN Zhenya

《化学科学与工程前沿（英文）》 2007年 第1卷 第3期   页码 266-270 doi: 10.1007/s11705-007-0048-y

摘要： A kinetic model of the pozzolanic reaction for the preparation of flue gas desulfurizers from fly ash and Ca(OH) was deduced on the basis of solid phase reaction kinetic theory. Kinetic expressions and parameters were obtained and verified by experiment. A comparison of calculated results with experimental results showed that precision in kinetic expressions was good. The apparent reaction rate constants of the pozzolanic reaction could be raised by increasing the specific surface area of fly ash and the hydration temperature, and by using a suitable additive.

关键词： comparison     calculated     pozzolanic reaction     precision     preparation    

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Inhibition of protein kinase B by Palmitate in the insulin signaling of HepG2 cells and the preventive

XIA Yanzhi, WAN Xuedong, DUAN Qiuhong, HE Shansu, WANG Ximing

《医学前沿（英文）》 2007年 第1卷 第2期   页码 200-206 doi: 10.1007/s11684-007-0038-y

摘要： Elevated plasma levels of free fatty acids (FFAs) may contribute to insulin resistance (IR) that is characteristic of type 2 diabetes mellitus. In this study, we investigated the effects of two fatty acids, palmitate (PA) and arach

关键词： palmitate     characteristic     study     plasma     resistance    

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Laboratory study on high-temperature adsorption of HCl by dry-injection of Ca(OH)

Junjun TAN,Guohua YANG,Jingqiao MAO,Huichao DAI

《环境科学与工程前沿（英文）》 2014年 第8卷 第6期   页码 863-870 doi: 10.1007/s11783-013-0618-9

摘要： Combustion-generated hydrogen chloride (HCl) is considered to be a very hazardous acid gaseous pollutant. This paper presents a laboratory study on the dry adsorption of HCl. The experiments were conducted in a dual-layer granular bed filter, at gas temperatures of 500°C–700°C and (Ca)/ (Cl)molar ratios of 1.0–5.0 using the silver nitrate titration method by dry adsorbent powders Ca(OH) . Mainly, the adsorption efficiency of HCl and utilization efficiency of Calcium were studied, by varying relevant factors including (Ca)/ (Cl), temperature, feeding method, water vapor and CO . With a relatively higher HCl concentration of 1000 ppm, the experimental results revealed that 600°C may be the optimum temperature for HCl adsorption when optimum (Ca)/ (Cl) was 2.5 in our tests. The results also demonstrated that the feeding at a constant pressure was more effective, and the HCl adsorption efficiency could rapidly reach over 90% with (Ca)/ (Cl) = 2.5 at 600°C. Furthermore, the HCl adsorption efficiency was found to be slightly promoted by water vapor, while could be impeded by CO , and the utilization efficiency of calcium could be up to 74.4% without CO , while was only 36.8% with CO when (Ca)/ (Cl) was 2.5 at 600°C.

关键词： acid gas HCl     Ca(OH)2     dry adsorption     high temperature     dual-layer granular bed filter    

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Pathway of the ozonation of 2,4,6-trichlorophenol in aqueous solution

PI Yunzheng, WANG Jianlong

《环境科学与工程前沿（英文）》 2007年 第1卷 第2期   页码 179-183 doi: 10.1007/s11783-007-0031-3

摘要： The reaction mechanism and pathway of the ozonation of 2,4,6-trichlorophenol (2,4,6-TCP) in aqueous solution were investigated. The removal efficiency and the variation of HO, Cl, formic acid, and oxalic acid were studied during the semi-batch ozonation experiments (continuous for ozone gas supply, fixed volume of water sample). The results showed that when there was no scavenger, the removal efficiency of 0.1 mmol/L 2,4,6-TCP could reach 99% within 6 min by adding 24 mg/L ozone. The reaction of molecular ozone with 2,4,6-TCP resulted in the formation of HO. The maximal concentration of HO detected during the ozonation could reach 22.5% of the original concentration of 2,4,6-TCP. The reaction of ozone with HO resulted in the generation of a lot of OH° radicals. Therefore, 2,4,6-TCP was degraded to formic acid and oxalic acid by ozone and OH° radicals together. With the inhibition of OH°radicals, ozone molecule firstly degraded 2,4,6-TCP to form chlorinated quinone, which was subsequently oxidized to formic acid and oxalic acid. Two reaction pathways of the degradation of 2,4,6-TCP by ozone and O/OH° were proposed in this study.
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GDF15 negatively regulates chemosensitivity via TGFBR2-AKT pathway-dependent metabolism in esophageal

《医学前沿（英文）》 2023年 第17卷 第1期   页码 119-131 doi: 10.1007/s11684-022-0949-7

摘要： Treating patients with esophageal squamous cell carcinoma (ESCC) is challenging due to the high chemoresistance. Growth differentiation factor 15 (GDF15) is crucial in the development of various types of tumors and negatively related to the prognosis of ESCC patients according to our previous research. In this study, the link between GDF15 and chemotherapy resistance in ESCC was further explored. The relationship between GDF15 and the chemotherapy response was investigated through in vitro and in vivo studies. ESCC patients with high levels of GDF15 expression showed an inferior chemotherapeutic response. GDF15 improved the tolerance of ESCC cell lines to low-dose cisplatin by regulating AKT phosphorylation via TGFBR2. Through an in vivo study, we further validated that the anti-GDF15 antibody improved the tumor inhibition effect of cisplatin. Metabolomics showed that GDF15 could alter cellular metabolism and enhance the expression of UGT1A. AKT and TGFBR2 inhibition resulted in the reversal of the GDF15-induced expression of UGT1A, indicating that TGFBR2-AKT pathway-dependent metabolic pathways were involved in the resistance of ESCC cells to cisplatin. The present investigation suggests that a high level of GDF15 expression leads to ESCC chemoresistance and that GDF15 can be targeted during chemotherapy, resulting in beneficial therapeutic outcomes.

关键词： GDF15     esophageal squamous cell carcinoma     chemoresistance     cellular metabolism     TGFBR2     AKT    

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标题 作者 时间 类型 操作

NETO2 promotes melanoma progression via activation of the Ca/CaMKII signaling pathway

期刊论文

Apigenin alleviates neomycin-induced oxidative damage via the Nrf2 signaling pathway in cochlear hair

期刊论文

FERM domain-containing protein FRMD6 activates the mTOR signaling pathway and promotes lung cancer progression

期刊论文

Genetic evidence in planar cell polarity signaling pathway in human neural tube defects

null

期刊论文

Wnt/β-catenin signaling pathway and its role in hepatocellular carcinoma

ZHANG Xufeng, YU Liang, LU Yi

期刊论文

Human menstrual blood-derived stem cells alleviate autoimmune hepatitis via JNK/MAPK signaling pathway

期刊论文

Caveolin proteins: a molecular insight into disease

null

期刊论文

Regulatory factors of mesenchymal stem cell migration into injured tissues and their signal transduction mechanisms

null

期刊论文

Triterpenoid inducers of Nrf2 signaling as potential therapeutic agents in sickle cell disease: a review

null

期刊论文

Proteome comparisons reveal influence of different dietary proteins on the development of rat jejunum

Mengjie LI, Chunbao LI, Shangxin SONG, Xinglian XU, Guanghong ZHOU

期刊论文

Kinetics of pozzolanic reaction for preparation of flue gas desulfurizer from fly ash and Ca(OH)2

WANG Jingang, HU Jinbang, WANG Daobin, DUAN Zhenya

期刊论文

Inhibition of protein kinase B by Palmitate in the insulin signaling of HepG2 cells and the preventive

XIA Yanzhi, WAN Xuedong, DUAN Qiuhong, HE Shansu, WANG Ximing

期刊论文

Laboratory study on high-temperature adsorption of HCl by dry-injection of Ca(OH)

Junjun TAN,Guohua YANG,Jingqiao MAO,Huichao DAI

期刊论文

Pathway of the ozonation of 2,4,6-trichlorophenol in aqueous solution

PI Yunzheng, WANG Jianlong

期刊论文

GDF15 negatively regulates chemosensitivity via TGFBR2-AKT pathway-dependent metabolism in esophageal

期刊论文