ObjectiveTo understand the research status of phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) signaling pathway in the thyroid cancer (TC), as well as its role in the occurrence, cell differentiation, invasion, and metastasis of the TC, so as to find potential targets for treatment of TC. MethodThe literature about the research of PI3K/AKT signaling pathway in the TC was searched and summarized. ResultsThe PI3K/AKT signaling pathway was abnormally activated directly or indirectly in the TC, resulting in inhibition of cell apoptosis, malignant proliferation, accelerated cycle progression, invasion, and metastasis, etc., which promoted the occurrence and development of the TC. There were also some tumor suppressor genes, microRNAs, long chain non-coding RNAs, etc., which indirectly inhibited the activation of PI3K/AKT signaling pathway, or directly acted on it inhibiting its activity to inhibit the occurrence and development of the TC. ConclusionsFor the TC, some proteins, genes, microRNAs, and long chain non-coding RNAs directly or indirectly activate the PI3K/AKT signaling pathway through different targets to promote the occurrence and development of TC. At the same time, many targets inhibit the activation of the PI3K/AKT signaling pathway, which inhibits the malignant proliferation, invasion, and metastasis of TC. At present, there have been studies trying to use PI3K/AKT signaling pathway as a breakthrough for the treatment of TC. In-depth exploration of the role of PI3K/AKT signaling pathway in different TC is of great significance to find new targets for the treatment of TC.
ObjectiveTo explore the phenotypic changes of epidermal stem cells (ESCs) differentiating into sweat glands cells (SGCs) in vitro and its mechanisms. MethodsESCs and SGCs were isolated and cultured in vitro, which were identified using immunofluorescence staining. ESCs at passage 2 were divided into 4 groups: ESCs and SGCs co-cultured by Transwell plates in group A, ESCs cultured by simply adding sweat supernatant in group B, ESCs and SGCs co-cultured on Transwell plate adding epidermal growth factor (EGF) (60 ng/mL) in group C, and ESCs and SGCs co-cultured on transwell plate adding PD98059 (10 mmol/L) in group D. The inverted microscope was used for observing the morphology of ESCs, flow cytometry for detecting ESCs positive phenotype, and Western blot for exploring mitogen-activated protein kinase/extracellular signal regulated kinase (MAPK/ERK) pathway. ResultsThe morphology observation and immunofluorescence staining suggested that cultured cells were ESCs and SGCs. The inverted phase contrast microscope observation showed that cells had similar morphological changes, with flat polygonal shape at 9 days in groups A, C, and D; cells had slow morphological change in group B, and had similar change to that of other groups at 12 days. Significant decreasing of β1-integrin expression and increasing of carcino-embryonic antigen (CEA) expression of ESCs were observed in group A when compared with group B, which was inhibited by EGF (group C) and enhanced by PD98059 (group D), and there were significant differences among groups A, C, and D (P<0.05). High level of ERK expression was displayed in 4 groups, but it was significantly lower in group B than the other 3 groups (P<0.05). The expression of phosphorylation ERK was the highest in group A and was the lowest in group C, showing significant difference among 4 groups (P<0.05). ConclusionESCs can be induced to differentiate into SGCs with the phenotypic changes under the condition of co-cultured by Transwell plates. The MAPK/ERK pathway plays a key role in the differentiation of ESCs into SGCs.
Acute lung injury (ALI), in which various factors inside and outside the lung lead to hypoxemic respiratory insufficiency and even the development of acute respiratory distress syndrome, has a high morbidity and mortality rate, and its pathogenesis is characterized by complex signaling pathways and limited therapeutic options. A large number of studies have reported that nuclear factor kappa B (NF-κB), phosphatidylinositol 3-kinase (PI3K)/Akt, mitogen-activated protein kinase (MAPK), AMP-activated protein kinase (AMPK), vascular endothelial growth factors (VEGF) and JAK/signal transducer and activator of transcription (STAT) signaling pathways are all related to the inflammatory response of ALI, and they are involved in regulating the inflammatory response process of ALI individually or cooperatively. Therefore, this article reviews the research progress on the pathogenesis-related signaling pathways and the drug interventions, aiming to provide a reference for early intervention in lung injury, optimizing the donor pool to increase the proportion of donation after cardiac death and providing quality donor protection conditions.
Objective To review the current researches about tumor necrosis factor-related apoptosis ligand (TRAIL) and its receptors in gastric carcinoma. Methods Relevant articles of researches on TRAIL and its receptors in gastric carcinoma were searched in electronic databases of PUB-MEDLINE and Chinese Journal Fulltext Database. Results The reported TRAIL expression level of gastric carcinoma was diverse, which was highly correlated to the histological differentiation degree, serosa invasion and lymph node metastasis. Its receptors DR4 and DR5 were both positive in gastric carcinoma tissue, while some researches reported DcR1 and DcR2 were also positive expressed. caspase-3, -8 and survivin were the important factors for regulation of TRAIL signal pathway. 5-Aza-CdR, doxorubicin, 5-fluorouracil, α-TOS and X-ray irradiation might enhance the TRAIL-induced apoptosis of gastric carcinoma cells. Conclusion Gastric carcinoma may be potentially sensitive to TRAIL targeting therapy, but the mechanism of TRAIL-induced apoptosis is quite complex and is regulated by multi-factors. Up to now, there are still many issues to research further, such as how to efficiently enhance and regulate the TRAIL-induced apoptosis of gastric carcinoma, whether any potential toxicities existing, etc.
Objective To observe the protein expression of c-Jun amino-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) in normal skin and keloid and to explore their influences on the formation of kloid. Methods Keloid tissues and normal skin tissues were collected from 16 keloid resection patients (experimental group) and 10 voluntary plastic surgery patients (control group). In the experimental group, the keloid formation time ranged from 8 months to 10 years; the keloid tissues were collected from the chest in 6 cases, the ear lobe in 4 cases, the perineum in 2 cases, the shoulder in 3 cases, and the abdomen in 1 case; and all keloid tissues were confirmed by pathological examination. In the control group, normal skin tissues were collected from the abdomen in 4 cases, the thighs in 3 cases, the shoulder in 2 cases, and the back in 1 case. Two-step l ine of Envision immunohistochemical staining was performed to observe the expressions of nonphosphorylated and phosphorylated JNK and ERK; Image Pro Plus 4.5 image analysis system was used to measure the integrated absorbance (IA) and to observe the positive staining strength. Results The immunohistochemical staining showed that no obvious expressions of phosphorylated and non-phosphorylated ERK, JNK were observed in the fibroblasts of the control group, and the expressions of phosphorylated JNK and ERK proteins were significantly higher in the experimental group than in the control group (P lt; 0.05). There was no significant difference in the expressions of non-phosphorylated JNK and ERK proteins between 2 groups (P gt; 0.05). Conclusion Activation of ERK and JNK pathways might be involved in formation of keloid.
ObjectiveTo investigate the effect of PI3K/Akt/mTOR signaling pathway on liver injury induced by severe acute pancreatitis (SAP). MethodsForty healthy adult male Sprague-Dawley (SD) rats were randomly divided into 4 groups: Sham operation group (SO group), SAP group, PI3K inhibitor LY294002 group (LY294002 group), and mTOR kinase inhibitor rapamycin group (rapamycin group). The rat model with SAP was made by injection with 5% sodium deoxycholate through retrogradely bilio pancreatic duct. Serum levels of amylase (AMY), alanine aminotransferase (ALT), and aspartate transaminase (AST) were detected through the inferior vena at 6 h after modeling. Pathologic change of the liver was observed under the light microscope. TUNEL analysis was used to detect apoptotic index (AI) of the heptocyte. Expressions of Akt, phosphated-Akt (p-Akt), mTOR, phosphated-mTOR (p-mTOR) protein were evaluated by Western blot. Results①Compared with the SO group, the serum levels of AMY, ALT, AST, and the hepatocyte AI were significantly increased among the other three groups (P < 0.05). Compared with the SAP group, the serum levels of AMY, ALT, AST, and the hepatocyte AI were significantly decreased in the LY294002 group and rapamycin group (P < 0.05).②Compared with the SO group, the damages of the liver tissues were aggravated among the other three groups. The pathologies of the liver tissues were ameliorated in the LY294002 group and rapamycin group as compared with the SAP group.③Compared with the SO group, the levels of p-Akt/Akt, p-mTOR/mTOR were significantly increased among the other three groups (P < 0.05). Compared with the SAP group, the levels of p-Akt/Akt, p-mTOR/mTOR were significantly decreased in the LY294002 group (P < 0.05), but in the rapamycin group, only the p-mTOR/mTOR level was significantly decreased (P < 0.05). ConclusionThe activation of PI3K/Akt/mTOR signaling pathway might be one of the reasons for the liver injury induced by SAP and blocking this signaling pathway might be a potential target of preventing progress of SAP and alleviating liver injury induced by SAP.
Objective The biological effects of fibroblast growth factor (FGF) may be different under different intensities and durations. To investigate the impact of sustained increasing FGF signal upon the development of epiphyseal plate. Methods Epiphyseal plates cultured in vitro were obtained from embryonic C57BL/6J mice, and were divided into control group (0.1% DMSO), basic FGF (bFGF) group (100 μg/L bFGF and 0.1% DMSO), and PD98059 group (100 μg/L bFGF and 50 μmol/L PD98059 with 0.1% DMSO). The total length (TL) and ossified tissue length (OSL) of the cultured bones weremeasured with Calcein staining 6 days after culture. The expressions of Indian hedgehog (Ihh), collagen type II (Col II), and Col X genes were detected by real-time fluorescent quantative PCR 7 days after culture. Results The embryonic bones cultured in vitro continued growth. At 6 days after culture, there was no significant difference in increased percentage of TL between bFGF group and control group (P gt; 0.05), the increased percentage of OSL in bFGF group was significantly less than that in control group (P lt; 0.05). There was no significant difference in the increased percentage of TL and OSL between PD98059 group and control group (P gt; 0.05), but they were significantly higher than those of bFGF group (P lt; 0.05). At 7 days after culture, the gene expressions of Ihh, Col II, and Col X in bFGF group significantly decreased when compared with those in control group (P lt; 0.05). There was no significant difference in the gene expressions of Col II and Col X between PD98059 group and control group (P gt; 0.05), but the gene expressions were significantly higher than those of bFGF group (P lt; 0.05); the expression of Ihh in PD98059 group was significantly higher than that in control group and bFGF group (P lt; 0.05). Conclusion Sustained increasing FGF signal may affect the Col II and Col X expressions by down-regulating Ihh, which may lead to the development retardation of epiphyseal plate cultured in vitro. The external signal regulated kinase pathway may play an important role in the process.
ObjectiveTo summarize the research progress of the effects and mechanisms of Hedgehog signaling pathway in regulating bone formation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). MethodsThe related literature concerning the regulations and mechanism of Hedgehog signaling pathway in osteogenic differentiation of BMSCs and bone formation in vivo, in vitro, and ex vivo studies in recent years was analyzed and summarized. ResultsThe in vitro studies indicate that Hedgehog signaling pathway can promote osteogenic differentiation of BMSCs via activation of key molecules Smoothened (Smo) and Gli1 which are downstream of Hedgehog signaling, and Hedgehog signaling can activate mTORC2-Akt signaling by upregulation of insulin-like growth factor which has similar effects. Hedgehog signaling regulates osteoblast differentiation via activation of Hh-Smo-Ptch1-Gli signaling pathway and inhibition of Hh-Gαi-RhoA stress fibre signaling. Hedgehog signaling can regulate key molecules of osteogenesis Runx2 for promoting osteogenic differentiation and matrix mineralization by synergism of bone morphogenetic protein and Wnt signaling, and promotes bone formation and repair and healing for bone defect and bone graft model in vivo. ConclusionHedgehog signaling can regulate bone formation and osteogenic differentiation of BMSCs via activation of Hedgehog signaling and other signaling pathways. Hedgehog signaling pathway may be a potential target for developing treatment for bone related diseases of osteoporosis and fracture healing disorders.
ObjectiveTo investigate the effects of telmisartan on the proliferation, migration and apoptosis of non-small cell lung cancer A549 and the mechanism of regulating Wnt signaling pathway.MethodsNon-small cell lung cancer cell line A549 was cultured in vitro. Cell counting kit-8 (CCK-8) assay was used to detect the effect of telmisartan at different concentrations on the proliferative activity of A549 cells. The survival fraction of A549 treated with different concentrations of telmisartan was determined by colony-formation assay. The effect of telmisartan at different concentrations on the migration ability of A549 cells was examined in the wounding healing assay. Hoechst staining was used to detect the effects of telmisartan at different concentrations on the apoptosis of A549. Western bloting was used to detect the expressions of β-actin, proliferating cell nuclear antigen (PCNA), Bax, Bcl-2, Wnt-3a, Beta-catenin (β-catenin), serine protein kinase 3β (p-GSK-3β), glycogen synthase kinase-3β (GSK-3β) and c-myc.ResultsDifferent concentrations of telmisartan treatment inhibited the proliferation activity, colony-formation rate and migration of A549 cells, and reduced the expression of PCNA in a concentration-dependent manner. Telmisartan treatment promoted the apoptosis of A549 cells, significantly increased the expression of pro-apoptotic protein Bax and decreased the expression of anti-apoptotic protein Bcl-2. The expression levels of Wnt-3a, β-catenin, p-GSK-3β, and c-myc in A549 cells increased after treatment with telmisartan, while the expression levels of GSK-3β decreased.ConclusionTelmisartan may play a role in the proliferation, migration and apoptosis of non-small cell lung cancer A549 cells, and inhibiting the Wnt/β-catenin signaling pathway may be one of the mechanisms.