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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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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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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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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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Leptin signaling and leptin resistance

null

《医学前沿（英文）》 2013年 第7卷 第2期   页码 207-222 doi: 10.1007/s11684-013-0263-5

摘要：

Leptin is secreted into the bloodstream by adipocytes and is required for the maintenance of energy homeostasis and body weight. Leptin deficiency or genetic defects in the components of the leptin signaling pathways cause obesity. Leptin controls energy balance and body weight mainly through leptin receptor b (LEPRb)-expressing neurons in the brain, particularly in the hypothalamus. These LEPRb-expressing neurons function as the first-order neurons that project to the second-order neurons located within and outside the hypothalamus, forming a neural network that controls the energy homeostasis and body weight. Multiple factors, including inflammation and endoplasmic reticulum (ER) stress, contribute to leptin resistance. Leptin resistance is the key risk factor for obesity. This review is focused on recent advance about leptin action, leptin signaling, and leptin resistance.

关键词： leptin signaling     leptin receptor     energy balance     leptin resistance     obesity    

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Autophagy and the nutritional signaling pathway

Long HE,Shabnam ESLAMFAM,Xi MA,Defa LI

《农业科学与工程前沿（英文）》 2016年 第3卷 第3期   页码 222-230 doi: 10.15302/J-FASE-2016106

摘要： During their growth and development, animals adapt to tremendous changes in order to survive. These include responses to both environmental and physiological changes and autophagy is one of most important adaptive and regulatory mechanisms. Autophagy is defined as an autolytic process to clear damaged cellular organelles and recycle the nutrients via lysosomic degradation. The process of autophagy responds to special conditions such as nutrient withdrawal. Once autophagy is induced, phagophores form and then elongate and curve to form autophagosomes. Autophagosomes then engulf cargo, fuse with endosomes, and finally fuse with lysosomes for maturation. During the initiation process, the ATG1/ULK1 (unc-51-like kinase 1) and VPS34 (which encodes a class III phosphatidylinositol (PtdIns) 3-kinase) complexes are critical in recruitment and assembly of other complexes required for autophagy. The process of autophagy is regulated by autophagy related genes (ATGs). Amino acid and energy starvation mediate autophagy by activating mTORC1 (mammalian target of rapamycin) and AMP-activated protein kinase (AMPK). AMPK is the energy status sensor, the core nutrient signaling component and the metabolic kinase of cells. This review mainly focuses on the mechanism of autophagy regulated by nutrient signaling especially for the two important complexes, ULK1 and VPS34.

关键词： Autophagy     ULK1 complex     VPS34 complex     AMPK     mTOR     nutrient signaling    

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Low-temperature caproate production, microbial diversity, and metabolic pathway in xylose anaerobic fermentation

《环境科学与工程前沿（英文）》 2023年 第17卷 第3期 doi: 10.1007/s11783-023-1637-9

摘要：

● Converting xylose to caproate under a low temperature of 20 °C by MCF was verified.

关键词： Xylose fermentation     Caproate     Low temperature     Bifidobacterium     FAB pathway     RBO pathway    

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Role of Wnt and Notch signaling in regulating hair cell regeneration in the cochlea

null

《医学前沿（英文）》 2016年 第10卷 第3期   页码 237-249 doi: 10.1007/s11684-016-0464-9

摘要：

Sensory hair cells in the inner ear are responsible for sound recognition. Damage to hair cells in adult mammals causes permanent hearing impairment because these cells cannot regenerate. By contrast, newborn mammals possess limited regenerative capacity because of the active participation of various signaling pathways, including Wnt and Notch signaling. The Wnt and Notch pathways are highly sophisticated and conserved signaling pathways that control multiple cellular events necessary for the formation of sensory hair cells. Both signaling pathways allow resident supporting cells to regenerate hair cells in the neonatal cochlea. In this regard, Wnt and Notch signaling has gained increased research attention in hair cell regeneration. This review presents the current understanding of the Wnt and Notch signaling pathways in the auditory portion of the inner ear and discusses the possibilities of controlling these pathways with the hair cell fate determiner Atoh1 to regulate hair cell regeneration in the mammalian cochlea.

关键词： inner ear     cochlea     hair cell     regeneration     Wnt     Notch     signaling pathways    

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NADPH oxidase and reactive oxygen species as signaling molecules in carcinogenesis

Gang WANG

《医学前沿（英文）》 2009年 第3卷 第1期   页码 1-7 doi: 10.1007/s11684-009-0018-5

摘要： Reactive oxygen species (ROS) are small molecule metabolites of oxygen that are prone to participate in redox reactions their high reactivity. Intracellular ROS could be generated in reduced nicotinamide-adenine dinucleotidephosphate (NADPH) oxidase-dependent and/or NADPH oxidase-independent manners. Physiologically, ROS are involved in many signaling cascades that contribute to normal processes. One classical example is that ROS derived from the NADPH oxidase and released in neurotrophils are able to digest invading bacteria. Excessive ROS, however, contribute to pathogenesis of various human diseases including cancer, aging, dimentia and hypertension. As signaling messengers, ROS are able to oxidize many targets such as DNA, proteins and lipids, which may be linked with tumor growth, invasion or metastasis. The present review summarizes recent advances in our comprehensive understanding of ROS-linked signaling pathways in regulation of tumor growth, invasion and metastasis, and focuses on the role of the NADPH oxidase-derived ROS in cancer pathogenesis.

关键词： free radicals     tumor     phox     cell proliferation     cancer therapy    

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Exploring the methodology and application of clinical pathway in evidence-based Chinese medicine

Sicheng Wang, He Yu, Jianping Liu, Baoyan Liu

《医学前沿（英文）》 2011年 第5卷 第2期   页码 157-162 doi: 10.1007/s11684-011-0128-8

摘要： At present, clinical pathway has become one of the most important health care reform measures in many countries. In this study, the authors introduced basic concepts and explored the application of the clinical pathway of evidence-based Chinese medicine incorporated with the methodology from the concepts of management, evidence-based medicine, operational research and health economics. Such concepts provide examples and experiences, on which the application of clinical pathway in Chinese medicine practice in China can be based.

关键词： evidence-based medicine     clinical pathway     methodology     concept     technical difficulty    

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标题 作者 时间 类型 操作

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

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

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

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

Leptin signaling and leptin resistance

null

期刊论文

Autophagy and the nutritional signaling pathway

Long HE,Shabnam ESLAMFAM,Xi MA,Defa LI

期刊论文

Low-temperature caproate production, microbial diversity, and metabolic pathway in xylose anaerobic fermentation

期刊论文

Role of Wnt and Notch signaling in regulating hair cell regeneration in the cochlea

null

期刊论文

NADPH oxidase and reactive oxygen species as signaling molecules in carcinogenesis

Gang WANG

期刊论文

Exploring the methodology and application of clinical pathway in evidence-based Chinese medicine

Sicheng Wang, He Yu, Jianping Liu, Baoyan Liu

期刊论文