The neuroprotection of electro-acupuncture via the PGC-1α/TFAM pathway in transient focal cerebral ischemia rats

ATP depletion is one of the pathological bases in cerebral ischemia. Electro-acupuncture (EA) is widely used in clinical practice for ischemia. However, the mechanism of EA remains unclear. The purpose of this study was to investigate whether EA could activate the AMPK/PGC-1α/TFAM signaling pathway and, consequently, increase the preservation of ATP in rats with ischemia. In this study, 48 rats were randomly divided into four groups as a sham-operation control group (sham group), a middle cerebral artery occlusion group (MCAO group), an EA group, and an EA group blocked by the AMPK inhibitor compound C (EA + CC group) (N = 12/group). The rats of the EA group and EA + CC group received the EA treatment for 7 days. The rats that belonged in the two remaining groups were only grasped in the same condition. Then, their brain tissues were collected for further detection. When compared with other groups, EA significantly reduced neurological deficits score and increased motor function. The cerebral infarction volume was significantly reduced in the EA group according to TTC staining. With western blot, we found that EA improved the ratio of p-AMPKα/AMPKα (P < 0.05), however, there is no difference between the MCAO group and sham group (P > 0.05). In addition, EA also increased the expression of PGC-1α and TFAM (all P < 0.05). By Elisa, we observed that EA increased the preservation of ATP (P < 0.05) and mitochondrial respiratory enzymes, including Complex I (P < 0.05), Complex IV (P < 0.05), but not Complex III (P > 0.05). In summary, we conclude that EA may protect against ischemic damage in MCAO rats, improve the preservation of ATP and mitochondrial respiratory enzymes. This effect may be positively regulated by the activation of the PGC-1α/TFAM signaling pathway.     

Butyrate inhibits the bovine rumen epithelial cell proliferation via downregulation of positive regulators at G0/G1 phase checkpoint

Short-chain fatty acids (SCFAs) butyrate promote the postnatal rumen epithelial development and maturation in ruminants. However, molecular mechanisms of effects of butyrate on the bovine rumen epithelial cells (BRECs) proliferation remain elusive. Therefore, purpose of this study was to investigate the effects of butyrate on the expression of genes and proteins at G0/G1 and S phase of BRECs cycle. Our results showed that BRECs treated with butyrate inhibited (P < 0.05) the proliferation of BRECs, relatively to control. Flow cytometric assays revealed that butyrate triggers the BRECs cycle arrest at the G0/G1 phase. qRT-PCR analyses of mRNA level of genes involved in the G0/G1 phase of cell cycle showed that butyrate significantly upregulated (P < 0.001) the expression of mRNA encoding p21^Cip1 compared with control group, but it decreased (P < 0.05) the mRNA levels of cyclin D1 and CDK4 genes at G0/G1 phase checkpoint compared with control. Moreover, Western blot also revealed that butyrate downregulated the expression of cyclin D3, CDK6, p-Rb, and E2F1 proteins involved in the modulation of G0/G1 phase of cell cycle. In conclusion, our results demonstrated that butyrate inhibits the proliferation of BRECs via downregulation of positive regulators at G0/G1 phase checkpoint.     

Dexmedetomidine alleviates oxygen and glucose deprivation-induced apoptosis in mesenchymal stem cell via downregulation of MKP-1

Bone marrow mesenchymal stem cell (MSC)-based therapy is a novel candidate for heart repair. But ischemia-reperfusion injury leads to low viability of MSC. Dexmedetomidine (Dex) has been found to protect neurons against ischemia-reperfusion injury. It remains unknown if Dex could increase the viability of MSCs under ischemia. The present study is to observe the potential protective effect of Dex on MSCs under ischemia and its underlying mechanisms. Specific mRNAs related to myocardial ischemia in the GEO database were selected from the mRNA profiles assessed in a previous study using microarray. The most dysregulated mRNAs of the specific ones from the above study were subject to bioinformatics analysis at our laboratory. These dysregulated mRNAs possibly regulated apoptosis of cardiomyocytes and were validated in vitro for their protective effect on MSCs under ischemia. MSCs were pre-treated with Dex at 10 μM concentration for 24 h under oxygen-glucose deprivation (OGD). Flow cytometry and TUNEL assay were carried out to detect apoptosis in Dex-pretreated MSCs under OGD. The relative expressions of mitogen-activated protein kinase phosphatase 1 (MKP-1) and related genes were detected by quantitative polymerase chain reaction and western blotting. Microarray data analysis revealed that Dex regulates MAPK phosphatase activity. Dex significantly reduced in vitro apoptosis of MSCs under OGD, which suppressed the synthesis level of Beclin1 and light chain 3 proteins. Dex down-regulated MKP-1 expression and attenuated an OGD-induced change in the mitogen activated protein kinase 3 (MAPK3) signaling pathway. Dex increases the viability of MSC and improves its tolerance to OGD in association with the MKP-1 signaling pathway, thus suggesting the potential of Dex as a novel strategy for promoting MSCs efficacy under ischemia.     

Association of hypoxia-inducible factor-1α (HIF1α) 1772C/T gene polymorphism with susceptibility to renal cell carcinoma/prostate cancer

In this study, we used a meta-analysis method to evaluate the relationship between hypoxia-inducible factor-1α (HIF1α) 1772C/T gene polymorphism (rs 11549465) and renal cell carcinoma (RCC)/prostate cancer risk. We searched for relevant studies (before March 1, 2019) on Cochrane Library, Embase, and PubMed. Studies meeting the inclusion criteria were recruited into this meta-analysis. The outcome of dichotomous data was showed in the way of odds ratios (OR), and 95% confidence intervals (CI) were also counted. In this investigation, there was no association between HIF1α 1772C/T gene polymorphism and susceptibility to RCC in Caucasians, Asians as well as overall populations. In addition, HIF1α 1772C/T gene polymorphism was not found to be relevant to the survival in RCC. Interestingly, the T allele was relevant to prostate cancer risk in all populations, but not in Caucasians and Asians. However, the TT genotype and the CC genotype were not related to prostate cancer susceptibility in Asian, Caucasian, and all populations. In conclusion, the T allele of the HIF1α 1772C/T gene polymorphism was related to prostate cancer risk in the overall populations.     

LncRNA <i>ZFAS1</i> regulates cardiomyocyte differentiation of human embryonic stem cells

Background: Cardiomyocytes derived from human embryonic stem cells (hESCs) are regulated by complex and stringent gene networks during differentiation. Long non-coding RNAs (lncRNAs) exert critical epigenetic regulatory functions in multiple differentiation processes. However, the involvement of lncRNAs in the differentiation of hESCs into cardiomyocytes has not yet been fully elucidated. Here, we identified the key roles of ZFAS1 (lncRNA zinc finger antisense 1) in the differentiation of cardiomyocytes from hESCs. Methods: A model of cardiomyocyte differentiation from stem cells was established using the monolayer differentiation method, and the number of beating hESCs-derived cardiomyocytes was calculated. Gene expression was analyzed by quantitative real-time PCR (qRT-PCR). Immunofluorescence assays were performed to assess the expression of cardiac troponin T (cTnT) and α-actinin protein in cardiomyocytes. Results: qRT-PCR showed that ZFAS1 expression in the mesoderm was significantly higher than that in embryonic stem cells, cardiac progenitor cells, and cardiomyocytes. Knockdown of ZFAS1 inhibited cardiomyocyte differentiation from hESCs, which was characterized by reduced expression of the cardiac-specific markers cTnT, α-actinin, myosin heavy chain 6 (MYH6), and myosin heavy chain 7 (MYH7). In contrast, ZFAS1 overexpression remarkably increased the percentage of spontaneously beating cardiomyocytes. In terms of the mechanism, we found that ZFAS1 is an antisense lncRNA at the 5′ end of the protein-coding gene ZNFX1. Knockdown of ZFAS1 could increase the mRNA expression level of ZNFX1. Furthermore, qRT-PCR demonstrated that the silencing of ZNFX1 led to an increase in cardiac-specific markers that predicted the promotion of cardiomyocyte differentiation. Conclusion: Altogether, these data suggest that lncRNA-ZFAS1 is required for cardiac differentiation by functionally inhibiting the expression of ZNFX1, which may provide a reference for the treatment of heart disease to a certain extent.     

Hypoxia induced apoptosis of rat gastric mucosal cells by activating autophagy through HIF-1α/TERT/mTORC1 pathway

The pathogenesis of high altitude-related gastric mucosal injury remains poorly understood, this study aimed to investigate the role of autophagy in hypoxia-induced apoptosis of rat gastric mucosal cells. Rats were randomized into four groups which were maintained at an altitude of 400 m (P) or received no treatment (H), autophagy inducer rapamycin (H+AI) or autophagy inhibitor 3-MA (H+AB) at an altitude of 4,300 m for 1, 7, 14 and 21 days, respectively, and the morphology, ultrastructure, autophagy, and apoptosis of gastric mucosal tissues were examined. Gastric mucosal epithelial cells CC-R039 were cultured under conditions of normoxia, 2% O2 (hypoxia), or 2% O2+anti-mTORC1 for 0, 24, 48, and 72 h, respectively, and the autophagy and apoptosis were analyzed. CC-R039 cells were transfected with siHIF-1α, siTERT, or siRNA and the autophagy was examined. The results showed that the exposure to hypoxia increased the autophagy and apoptosis of gastric mucosal cells in rats, and apoptosis was aggravated by rapamycin treatment but alleviated by 3-MA treatment. Increased duration of hypoxia from 0 to 72 h could increase the autophagy and apoptosis but decrease the proliferation of gastric mucosal cells. Inhibition of mTORC1 with rapamycin led to further increase in apoptosis and even substantial cell death, and inhibition of HIF- 1α and TERT increased mTORC1 expression and reduced autophagy. Moreover, the inhibition of HIF-1α reduced TERT expression. In conclusion, hypoxia could induce apoptosis of rat gastric mucosal cells by activating autophagy through HIF-1α/TERT/mTORC1 pathway     

Effect of Peroxiredoxin 1 on the biological function of airway epithelial cells and epithelial-mesenchymal transition

Peroxiredoxin 1 (PRDX1) participates in tumor cell proliferation, apoptosis, migration, invasion, and the epithelial-to-mesenchymal transition (EMT). This study aimed to investigate the effect of PRDX1 on the EMT of airway epithelial cells stimulated with lipopolysaccharide (LPS) and transforming growth factor-beta 1 (TGF-β1). PRDX1 overexpression significantly increased the proliferation and migration of human bronchial epithelial (BEAS-2B) cells, reduced cell apoptosis (p < 0.01), and induced EMT and collagen deposition by upregulating the expression of the matrix metallopeptidase (MMP)2, MMP9, α-smooth muscle actin (α-SMA), N-cadherin, vimentin and twist proteins and inhibiting E-cadherin expression (p < 0.05). PRDX1 overexpression promoted TGF-β1-mediated inhibition of cell proliferation and migration and significantly enhanced the TGF-β1-induced EMT and collagen synthesis (p < 0.05). Knockdown of PRDX1 inhibited cell proliferation, migration, EMT, and collagen synthesis (p < 0.01), reversed LPS-mediated inhibition of cell proliferation and migration, and significantly suppressed LPS-induced EMT and collagen synthesis (p < 0.01). The result indicating that PRDX1 may be involved in LPS/TGF-1-induced EMT and collagen synthesis in human bronchial epithelial cells.     

Bushen Yizhi Formula regulates the IRE1α pathway to alleviate endoplasmic reticulum stress in an Alzheimer’s disease rat model

Background: While the Bushen Yizhi Formula can treat Alzheimer’s disease (AD), the yet to be ascertained specific mechanism of action was explored in this work. Methods: Different concentrations of the Bushen Yizhi Formula and amyloid-beta peptide (Aβ) were used to treat rat pheochromocytoma cells (P12) and human neuroblastoma cells (SH-SY5Y). Cell morphological changes were observed to determine the in vitro cell damage. Cell Counting Kit (CCK)-8 assay and flow cytometry were employed to identify cell viability and apoptosis/cell cycle, respectively. Western blotting and immunohistochemistry were employed to measure the expressions of endoplasmic reticulum stress (ERS)-related proteins (GRP78 and CHOP), p-IRE1α, IRE1α, ASK1, p-JNK, JNK, Bax, Bcl-2, XBP-1, and Bim. Fura 2-acetoxymethyl ester (Fura-2/AM) was used to determine the intracellular calcium (Ca²⁺) concentration. Also, an AD model was constructed by injecting Aβ into the CA1 area of the hippocampus in Sprague Dawley rats. AD model rats were gavaged with different concentrations of Bushen Yizhi Formula for 14 consecutive days. The Morris water maze experiment was conducted to test the learning and memory of rats. Hematoxylin & Eosin (H&E) and Terminal-deoxynucleotidyl Transferase (TdT)-mediated dUTP Nick-End Labeling (TUNEL) staining were done to determine histopathological changes in the brain. Results: Bushen Yizhi Formula relieved the Aβ-induced effects including cell injury, decreased viability, increased apoptosis, G0/G1 phase cell cycle arrest, upregulation of GRP78, CHOP, p-IRE1α, p-JNK, Bax, XBP-1 and Bim, as well as down-regulation of Bcl-2. These results were also seen with IRE1α silencing. While Aβ suppressed the learning and memory abilities of rats, the Bushen Yizhi Formula alleviated these effects of Aβ. Brain nerve cell injury induced by Aβ could also be treated with Bushen Yizhi Formula. Conclusion: Bushen Yizhi Formula could influence ERS through the IRE1α signaling pathway to achieve its therapeutic effects on AD.     

Scutellarin alleviates complete freund’s adjuvant-induced rheumatoid arthritis in mice by regulating the Keap1/Nrf2/HO-1 pathway

Scutellarin (SCU) is a herbal flavonoid glucuronide with multiple pharmacological activities, including anti-oxidant, anti-inflammation, vascular relaxation, anti-platelet, and myocardial protection. However, the effect of SCU on complete Freund’s adjuvant (CFA)-induced rheumatoid arthritis (RA) had not been studied. In this study, we investigated the beneficial effects of SCU in the CFA-induced RA mice model and the anti-arthritic activity was evaluated by paw edema. Enzyme-linked immunosorbent assay (ELISA) was carried out to evaluate the plasma levels of immunoglobulin (Ig)G, IgE, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, receptor activator of nuclear factor-κB ligand (RANKL), and osteoprotegerin (OPG). Histological slides were prepared from the harvested paws of mice to determine the pathological changes in the joints. The proportions of T helper type 1 (Th1) and T helper type 2 (Th2) cells of CD4+ T lymphocyte subsets were analyzed by flow cytometry. The expression of Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) was analyzed using real-time quantitative PCR (RT-qPCR) and western blotting assays. The present study demonstrated that SCU prevented CFA-induced RA, and inhibited the expression of inflammation factors, IgG, IgE, TNF-α, IL-1β, and IL-6. While SCU also reduced the RANKL level, it increased OPG expression in RA mice. The Th1/Th2 ratio was significantly lower in mice treated with SCU. Additionally, HO-1 expression was reduced while the expression of Keap1 and Nrf2 was elevated following SCU treatment. Results provide preliminary evidence to employ SCU in arthritis treatment which might be related to the regulation of Th1/Th2 balance and the Keap1/Nrf2/HO-1 pathway.     

AKT regulates IL-1β-induced proliferation and activation of hepatic stellate cells

Background: Activated hepatic stellate cells (HSCs) are closely involved in the initiation, perpetuation, and resolution of liver fibrosis. Pro-inflammatory cytokine levels are positively correlated with the transition from liver injury to fibrogenesis and contribute to HSC pathophysiology in liver fibrosis. Methods: In this study, we investigated the effect of the pro-inflammatory cytokine interleukin (IL)-1β on the proliferation and signaling pathways involved in fibrogenesis in LX-2 cells, an HSC cell line, using western blotting and cell proliferation assays. Results: IL-1β increased the proliferation rate and α-smooth muscle actin (SMA) expression of LX-2 cells in a dose-dependent manner. Within 1 h after IL-1β treatment, c-Jun N-terminal kinase (JNK), p38, and nuclear factor-κB (NF-κB) signaling was activated in LX-2 cells. Subsequently, protein kinase B (AKT) phosphorylation and an increase in α- SMA expression were observed in LX-2 cells. Each inhibitor of JNK, p38, or NF-κB decreased cell proliferation, AKT phosphorylation, and α-SMA expression in IL-1β-treated LX-2 cells. Conclusion: These results indicate that JNK, p38, and NF-κB signals converge at AKT phosphorylation, leading to LX-2 activation by IL-1β. Therefore, the AKT signaling pathway can be used as a target for alleviating liver fibrosis by the inflammatory cytokine IL-1β.     

Overexpression of inhibin α (1-32) fusion protein promotes apoptosis and cell cycle arrest in a cervical cancer cell model (Hela cells)

Inhibins play important roles in the reproductive system. To evaluate whether inhibin α (1-32) fusion protein plays a role in cervical cancer growth, the plasmid pVAX-inhα was constructed and its effect on proliferation and apoptosis of the human cervical cancer cell line (Hela) was checked by flow cytometry and real-time PCR. The expression and localization of inhibin α protein were detected by RT-PCR and confocal microscopy which showed that inhibin α protein was expressed and localized in the nucleus of Hela cells. Over expression of inhibin α gene significantly induced cell apoptosis and ceased S phase of cell cycle. Furthermore, cell proliferation was significantly suppressed 96 h post-transfection and mRNA level of anti-apoptosis genes (Bcl-2, NFκB) were decreased but pro-apoptosis genes (Bax, wild type p53) and inhibin co receptor (TGFβR3) were increased, indicating that inhibin, through its co-receptor, might activate apoptotic and cell growth cascades which regulate proliferation and apoptosis in Hela cells. These results suggest that inhibin α (1-32) fusion protein, located in the cell nucleus, can regulate Hela cells growth and apoptosis by induction of apoptotic pathways such as NFκB, Bcl-2 and p53 families. These findings may have a significant impact on future research regarding cervical cancer cell lines     

STMN1 promotes the proliferation and inhibits the apoptosis of acute myeloid leukemiacells by activating the PI3K/Akt pathway

Recent studies have shown that the microtubule disrupting protein Stathmin 1 (STMN1) is differentially expressed in AML patients and healthy control. The aim of this study was to explore the effects and molecular mechanism of STMN1 in AML. Here, the expression of STMN1 in peripheral blood cells (PBMCs) and bone marrow of AML patients and healthy volunteers was detected by RT-PCR and Western blot. STMN1 expression was regulated by transfected with STMN1 overexpressed plasmid or shRNA in two human leukemia cell lines K562 and HL60. Cell proliferation was examined by CCK8 and Edu staining. Annexin V and TUNEL assays were applied to test cell apoptosis. Flow cytometry was used to test the cell cycle distribution. The activation of the PI3K signaling pathway and the expression levels of cell cycle and cell apoptosis-related protein were determined by Western blot. In this study, we found that STMN1 was overexpressed in PBMCs and bone marrow of AML patients. STMN1 expression was closely related to FAB subtypes, risk stratification, disease-free survival, and overall survival of AML. Functional assays showed that overexpression of STMN1 in HL60 and K562 cells enhanced cell proliferation, decreased cell apoptosis, and caused G₁ phase arrest. In contrast, suppression of STMN1reduced cell proliferation and enhanced cell apoptosis in both HL60 and K562 cells. Moreover, the PI3K/Akt pathway was activated by STMN1, while suppression of STMN1 dysregulated the PI3K/Akt pathway and upregulating the levels of caspases3 and Bax expression. In conclusion, STMN1 was confirmed to promote the proliferation and inhibit the apoptosis of HL60 and K562 cells by modulating the PI3K/Akt pathway. STMN1 might be a novel molecular target for treating AML.     

P53-Rb signaling pathway is involved in tubular cell senescence in renal ischemia/reperfusion injury.

OBJECTIVE: To investigate the course of tubular cell senescence and expressions of p53, p21, and Rb during the late phase of ischemia/reperfusion (IRI) in the kidney, and assess the effects of the p53-Rb pathway on tubular cell senescence. METHODS: Experimental models of unilateral renal IRI were used in p53 (+/+) and p53 (-/-) mice. Histological changes at the tubular level, progress of cell senescence, and the expression of Rb, p21, and/or p53 proteins in tubular cells were studied at different moments in time after IRI. RESULTS: Chronic tubulointerstitial fibrosis was much more severe and widely distributed in IRI kidneys of p53 (+/+) mice in later stages than in earlier stages. Senescent tubular cells were significantly increased at 3 and 6 months after IRI. In contrast, in contralateral kidneys of p53 (+/+) mice and in both kidneys of p53 (-/-) mice, almost no senescent cells were observed at 1 and 3 months after IRI, and only a few senescent cells were detected in IRI kidneys of p53 (-/-) mice at 6 months. In mice of both genotypes, cell senescence was correlated with the expression levels of p53, p21, and Rb proteins. CONCLUSION: The IRI accelerated tubular cell senescence is presumed to be one of the mechanisms of the "long-term effect" of IRI. Furthermore, the activation of p53-Rb signaling pathway may play a vital role in tubular cell senescence induced by IRI.     

Arsenic trioxide inhibits the activity of SphK1 by decreasing the level of phosphatidylserine and phosphatidic acid in the human gastric cancer cell line MGC-803

Sphingosine kinase 1 (SphK1) is an important synthetase during the synthesis of sphingosine-1-phosphate (S1P) from sphingosine (Sph). Previous studies demonstrated that arsenic trioxide (As₂O₃) could reduce the level of S1P in human gastric cancer cell line MGC-803, indicating that As₂O₃ may inhibit the activity of SphK1. In this study, the effect of As₂O₃ on the SphK1 activation pathway was investigated. Western blot and quantitative real-time PCR analysis were used to evaluate the changes in protein and mRNA levels. The multi-dimensional mass spectrometry-based shotgun lipidomics method (MDMS-SL) was used for the quantitative detection of phosphatidylserine (PS) and phosphatidic acid (PA). The results revealed that As₂O₃ did not affect the protein and mRNA expression of SphK1 in the MGC-803 cells. However, As₂O₃ increased the levels of p-ERK1/2 and CIB1 in the SphK1 activation pathway and decreased the levels of PS and PA in the MGC-803 cells. The outcomes suggested that As₂O₃ may enhance the activity of SphK1 by increasing the levels of p-ERK1/2 and CIB1 and decrease the activity of SphK1 by decreasing the levels of PS and PA. It was suggested that the inhibition effect is stronger and resulting in an overall decrease in the activity of SphK1.     

20(R)-ginsenoside Rg3, a product of high-efficiency thermal deglycosylation of ginsenoside Rd,exerts protective effects against scrotal heat-induced spermatogenic damage in mice

Heat stress (HS) reaction can lead to serious physiological dysfunction associated with cardiovascular and various organ diseases. Ginsenoside Rg3 (G-Rg3) is a representative component of ginseng rare saponin and can protect against multiple organs, also used as functional food to adjust the balance of the human body, but the therapeutic effect and molecular mechanism of G-Rg3 on male diseases under HS are underexplored. The aim of the present study, G-Rg3 was prepared through the efficient conversion of ginsenoside Rd and investigate the contribution of G-Rg3 to testicular injury induced exposure to HS. All mice were divided into four groups as follows: normal group, HS group, and HS+G-Rg3 (5 and 10 mg/kg) groups. G-Rg3 was administered orally for 14 days, then exposed to a single scrotal heat treatment (43°C, 18min) on the 7th day. After HS treatment, the morphology of testis and epididymis changes, and caused a significant loss of multinucleated giant cells, desquamation of germ cells in destructive seminiferous tubules, and degenerative Leydig cells, further destroying the production of sperm. After administration G-Rg3 (5 and 10 mg/kg/day) for 2 weeks, the spermatogenic-related indexes of testosterone levels and superoxide dismutase (SOD) activity, glutathione (GSH) content significantly (p < 0.01) increase compared with the HS group. Moreover, G-Rg3 treatment effectively ameliorated the production of malondialdehyde (MDA) (p < 0.05 or p < 0.01). Importantly, G-Rg3 exhibited the protective potential against HS-induced injury not only suppressing the protein levels of heme oxygenase-1 (HO-1), hypoxia-inducible factor-1α (HIF-1α), and heat shock protein 70 (HSP70) but also modulating the Bcl-2 family (p < 0.01 or p < 0.001) and activation of mitogen-activated protein kinase (MAPK) signaling pathways (p < 0.01). For most of the parameters tested, the HS+G-Rg3 (10 mg/kg) group exhibited potent effects compared with those exhibited by the low dose (5 mg/kg) group. In conclusion, the present study demonstrated that G-Rg3 exerted protective effects against HS-induced testicular dysfunction via inhibiting the MAPK-mediated oxidative stress and apoptosis in mice.     

香樟木质部挥发性成分的SPME-GC/MS分析

采用固相微萃取技术（SPME）吸附香樟木质部挥发性成分,结合气相色谱-质谱（GC/MS）进行化学成分的分离和鉴定,同时比较不同色谱柱对分离效果的影响。结果表明：采用弱极性DB-5MS色谱柱共分离出51个组分,解析出43种挥发性成分,占总峰面积的97.04%,分离效果和所得的峰形较好于DB-WAXetr色谱柱。鉴定出含量较高的成分有：左旋-α-蒎烯（4.57%）、莰烯（2.14%）,双环[3.1.0]-4-甲基-1-异丙基-2-己烯（4.16%）、β-蒎烯（2.3%）、邻异丙基甲苯（2.15%）、D-柠檬烯（7.49%）、桉叶油醇（13.85%）、樟脑（38.71%）、(R)-4-萜品醇（1.74%）、α-松油醇（2.40%）、黄樟素（2.96%）、α-荜澄茄油烯（4.36%）、1-石竹烯（1.92%）等。该方法可为香樟材在医药、食品和化学工业等方面的进一步开发和利用提供参考。     

The expressional level of tankyrase-1 gene and its regulation in colorectal cancer in a Saudi population

Tankyrase1 plays an essential role in cancer progression by regulating telomere length. The study aimed to determine expression of TNKS1 and its regulation in colorectal cancer (CRC) in 20 samples from Saudi patients. mRNA expression of TNKS1 in CRC and paired normal tissues was measured by qRT-PCR. Epigenetic modification of TNKS1 promoter was determined by methylation-specific PCR while somatic mutation was analyzed by Sanger sequencing in exon 10 of the gene. All cancerous and normal tissues expressed TNKS1, but level of expression in CRC tissues was significantly associated with tumor stage though no other parameters; age, gender, and tumor location, showed any correlation. Expression of TNKS1 was markedly higher in earlier (I, II) than later (III, IV) stages of CRC development. Both cancerous and healthy tissues had unmethylated promoter. Sanger sequencing of exon 10 masked any somatic mutation in the samples. Our findings suggest that up-regulation of TNKS1 was inversely correlated with cancer progression in CRC, indicating that TNKS1 participates in the initiation of CRC by stabilizing telomere length in the first phase of cancer progression. Mechanisms other than TNKS1 might play a role in malignant tumor progression and telomere maintenance in the late stages of CRC.     

浮动平底推杆-盘形凸轮组合机构的第Ⅰ类机构综合问题

提出“预设凸轮轴心O1+等距/网格/离散化+校核+取舍”的新型求解策略和路线,通过建立“固定、浮动坐标系”并引入“支撑函数法”、“瞬时区域套”、“经济搜索区域”及“等距/网格/离散化”等概念和方法,研究了满足ρ＞0、α≤[α]∩α≤[α]r和ρ＞0、α≤[α]∩α≤[α]r等单纯或组合条件下凸轮轴心O1的求解原理、解析表达、“位置区域Πρ、Π[α]和Πρ∩[α]”及其形态特征,提出了搜索求解的思路和方法,推导出了平底工作段及其长度、总长度的求解确定方法,揭示出“位置区域Π[α]和 Πρ∩[α]”的“类等腰三角形”、“收缩聚敛性”、“脊点O*1/脊线{O*1}存在性”和“最优脊点O**1存在性”等规律特性,得到“凸轮轴心O1优选(非劣)解集”、“最优凸轮轴心O*1opt和O**opt”等重要的关键性结论,较圆满地解决了浮动平底推杆-盘形凸轮组合机构的第Ⅰ类机构综合问题。