Compared with the use of monocultures in the field,cultivation of medicinal herbs in forests is an effective strategy to alleviate disease.Chemical interactions between herbs and trees play an important role in diseas...Compared with the use of monocultures in the field,cultivation of medicinal herbs in forests is an effective strategy to alleviate disease.Chemical interactions between herbs and trees play an important role in disease suppression in forests.We evaluated the ability of leachates from needles of Pinus armandii to induce resistance in Panax notoginseng leaves,identified the components via gas chromatography-mass spectrometry(GC-MS),and then deciphered the mechanism of 2,3-Butanediol as the main component in the leachates responsible for resistance induction via RNA sequencing(RNA-seq).Prespraying leachates and 2,3-Butanediol onto leaves could induce the resistance of P.notoginseng to Alternaria panax.The RNA-seq results showed that prespraying 2,3-Butanediol onto leaves with or without A.panax infection upregulated the expression of large number of genes,many of which are involved in transcription factor activity and the mitogen-activated protein kinase(MAPK) signaling pathway.Specifically,2,3-Butanediol spraying resulted in jasmonic acid(JA)-mediated induced systemic resistance(ISR) by activating MYC2 and ERF1.Moreover,2,3-Butanediol induced systemic acquired resistance(SAR) by upregulating pattern-triggered immunity(PTI)-and effector-triggered immunity(ETI)-related genes and activated camalexin biosynthesis through activation of WRKY33.Overall,2,3-Butanediol from the leachates of pine needles could activate the resistance of P.notoginseng to leaf disease infection through ISR,SAR and camalexin biosynthesis.Thus,2,3-Butanediol is worth developing as a chemical inducer for agricultural production.展开更多
Vitamin D co-regulates cell proliferation, differentiation and apoptosis in numerous tissues, including cancers. The known anti-proliferative and pro-apoptotic actions of the active metabolite of vitamin D, 1,25-dihyd...Vitamin D co-regulates cell proliferation, differentiation and apoptosis in numerous tissues, including cancers. The known anti-proliferative and pro-apoptotic actions of the active metabolite of vitamin D, 1,25-dihydroxy-vitamin D [1,25(OH)2D] are mediated through binding to the vitamin D receptor (VDR). Here, we report on the unexpected finding that stable knockdown of VDR expression in the human breast and prostate cancer cell lines, MDA-MB-231 and PC3, strongly induces cell apoptosis and inhibits cell proliferation in vitro. Implantation of these VDR knockdown cells into the mammary fat pad (MDA-MB-231), subcutaneously (PC3) or intra-tibially (both cell lines) in immune-incompetent nude mice resulted in reduced tumor growth associated with increased apoptosis and reduced cell proliferation compared with controls. These growth-retarding effects of VDR knockdown occur in the presence and absence of vitamin D and are independent of whether cells were grown in bone or soft tissues. Transcriptome analysis of VDR knockdown and non-target control cell lines demonstrated that loss of the VDR was associated with significant attenuation in the Wnt/0-catenin signaling pathway. In particular, cytoplasmic and nuclear β-catenin protein levels were reduced with a corresponding downregulation of downstream genes such as Axin2, Cyclin D1, interleukin-6 (IL-6), and IL-8. Stabilization of 0-catenin using the GSK-3β inhibitor BIO partly reversed the growth-retarding effects of VDR knockdown. Our results indicate that the unliganded VDR possesses hitherto unknown functions to promote breast and prostate cancer growth, which appear to be operational not only within but also outside the bone environment. These novel functions contrast with the known anti-proliferative nuclear actions of the liganded VDR and may represent targets for new diagnostic and therapeutic approaches in breast and prostate cancer.展开更多
The mortality of cancer patients has considerably improved due to progress in surgery, chemotherapy and radiotherapy. However, some types of cancers, such as melanoma, remain refractory to conventional strategies. Alt...The mortality of cancer patients has considerably improved due to progress in surgery, chemotherapy and radiotherapy. However, some types of cancers, such as melanoma, remain refractory to conventional strategies. Although melanoma accounts for only 4% of all dermatological malignancies, it is responsible for 80% of mortalities from skin tumors[11. The reported survival rate of melanoma over 5 years is not yet encouraging due to its chemo-resistance and rapid metastasis. Therefore, it is necessary to develop new drugs with potent activity and weak side-effect against melanoma.展开更多
Toll-like receptor (TLR)-mediated inflammatory response could negatively affect bone metabolism. In this study, we determined how osteogenesis is regulated during inflammatory responses that are downstream of TLR si...Toll-like receptor (TLR)-mediated inflammatory response could negatively affect bone metabolism. In this study, we determined how osteogenesis is regulated during inflammatory responses that are downstream of TLR signaling. Human primary osteoblasts were cultured in collagen gels. Pam3CSK4 (P3C) and Escherichia coli lipopolysaccharide (EcLPS) were used as TLR2 and TLR4 ligand respectively. Porphyromonas gingivalis LPS having TLR2 activity with either TLR4 agonism (Pg1690) or TLR4 antagonism (Pg1449) and mutant E. coli LPS (LPxE/LPxF/WSK) were used. IL-lp, SH2-containing inositol phosphatase-1 (SHIP1) that has regulatory roles in osteogenesis, alkaline phosphatase and mineralization were analyzed. 3α-Aminocholestane (3AC) was used to inhibit SHIP1. Our results suggest that osteoblasts stimulated by P3C, poorly induced IL-1β but strongly upregulated SHIP1 and enhanced osteogenic mediators. On the contrary, EcLPS significantly induced IL-1β and osteogenic mediators were not induced. While Pg1690 downmodulated osteogenic mediators, Pg1449 enhanced osteogenic responses, suggesting that TLR4 signaling annuls osteogenesis even with TLR2 activity. Interestingly, mutant E. coli LPS that induces weak inflammation upregulated osteogenesis, but SHIP1 was not induced. Moreover, inhibiting SHIP1 significantly upregulated TLR2-mediated inflammatory response and downmodulated osteogenesis. In conclusion, these results suggest that induction of weak inflammatory response through TLR2 (with SHIP1 activity) and mutant TLR4 ligands could enhance osteogenesis.展开更多
Present study deals with the straight impact of hypobaric hypoxia on the quantity and composition of some predominant fecal microflora and its functional aspects. For that, isolated fecal contents of rat were exposed ...Present study deals with the straight impact of hypobaric hypoxia on the quantity and composition of some predominant fecal microflora and its functional aspects. For that, isolated fecal contents of rat were exposed to two different simulated air pressures (70 kPa and 40 kPa) for different time durations (1, 3, and 5 h) and the bacterial community composition was compared with normobaric groups (101.3 kPa). It was found that the total anaerobes, Escherichio coli, Enterbocters spp., Bi^idobocterium spp., CIostridium spp. were increased whereas total aerobes were decreased at both hypobaric treatments. The increased number of amplicon was detected in the pressure-treated groups than the control that clearly mentioned the disruption of microbiota structure at different simulated hypobaric-hypoxia. The amylase, protease, tannase, 13-glucuronidase, and alkaline phosphatase activities were increased at these atmospheric pressures. Thus, the present investigation demonstrates that the hypobaric hypoxia is an important environmental factor which can strongly modulate the composition of intestinal flora as well as microfiora-derived functional aspects.展开更多
Trichloroethylene (TCE) is a major pollutant that affects both occupational and general environments. The liver is an important target organ of TCEE. Substantial efforts and remarkable progress into understanding TC...Trichloroethylene (TCE) is a major pollutant that affects both occupational and general environments. The liver is an important target organ of TCEE. Substantial efforts and remarkable progress into understanding TCE cytotoxicity have been made in cultured liver cells. However, the molecular mechanisms by which TCE induces hepatotoxicity are not well understood. SET (also known as protein phosphatase 2A inhibitor, 12PP2A, or template-activating factor-I, TAF-D is a nuclear protein that regulates histone modification, gene transcription, DNA replication, nucleosome assembly,展开更多
Perfluorooctane sulfonate (PFOS) is a class of stable organic compounds with wide industrial,commercial, and consumer applications, such as in textiles, paper, pesticides, and shampoos;. It is readily absorbed, but ...Perfluorooctane sulfonate (PFOS) is a class of stable organic compounds with wide industrial,commercial, and consumer applications, such as in textiles, paper, pesticides, and shampoos;. It is readily absorbed, but poorly eliminated, with the elimination half-life of approximately 5 years;.Hence, there have been concerns regarding its potential damage to human health. Some studies展开更多
To evaluate the long-term consequence of repetitive mild traumatic brain injury (mTBI) on bone, mTBI was induced in 10-week-old female C57BL/6J mice using a weight drop model, once per day for 4 consecutive days at ...To evaluate the long-term consequence of repetitive mild traumatic brain injury (mTBI) on bone, mTBI was induced in 10-week-old female C57BL/6J mice using a weight drop model, once per day for 4 consecutive days at different drop heights (0.5, 1 and 1.5 m) and the skeletal phenotype was evaluated at different time points after the impact. In vivo micro-CT (μ-CT) analysis of the tibial metaphysis at 2, 8 and 12 weeks after the impact revealed a 5%-32% reduction in trabecular bone mass. Histomorphometric analyses showed a reduced bone formation rate in the secondary spongiosa ofl.5 m impacted mice at 12 weeks post impact. Apparent modulus (bone strength), was reduced by 30% (P 〈 0.05) at the proximal tibial metaphysis in the 1.5 m drop height group at 2 and 8 weeks post impact. Ex vivo μ-CT analysis of the fifth lumbar vertebra revealed a significant reduction in trabecular bone mass at 12 weeks of age in all three drop height groups. Serum levels of osteocalcin were decreased by 22%, 15%, and 19% in the 0.5, 1.0 and 1.5 m drop height groups, respectively, at 2 weeks post impact. Serum IGF-I levels were reduced by 18%-32% in mTBI mice compared to control mice at 2 weeks post impact. Serum osteocalcin and IGF-I levels correlated with trabecular BV/TV (r2 = 0.14 and 0.16, P 〈 0.05). In conclusion, repetitive mTBI exerts significant negative effects on the trabecular bone microarchitecture and bone mechanical properties by influencing osteoblast function via reduced endocrine IGF-I actions.展开更多
We report the cloning and functional characterization of human cyclin L2, a novel member of the cyclin family. Human cyclin L2 shares significant homology to cyclin L1, K, T1, T2, and C, which are involved in transcri...We report the cloning and functional characterization of human cyclin L2, a novel member of the cyclin family. Human cyclin L2 shares significant homology to cyclin L1, K, T1, T2, and C, which are involved in transcriptional regulation via phosphorylation of the C-terminal domain of RNA polymerase Ⅱ. The cyclin L2 protein contains an N-terminal "cyclin box" and C-terminal dipeptide repeats of alternating arginines and serines, a hallmark of the SR family of splicing factors. A new isoform and the mouse homologue of human cyclin L2 have also been cloned in this study. Human cyclin L2 is expressed ubiquitously in normal human tissues and tumor cells. We show here that cyclin L2 co-localizes with splicing factors SC-35 and 9G8 within nuclear speckles and that it associates with hyperphosphorylated, but not hypophosphorylated, RNA polymerase Ⅱ and CDK p110 PITSLRE kinase via its N-terminal cyclin domains. It can also associate with the SC-35 and 9G8 through its RS repeat region. Recombinant cyclin L2 protein can stimulate in vitro mRNA splicing. Overexpression of human cyclin L2 suppresses the growth of human hepatocellular carcinoma SMMC 7721 cells both in vitro and in vivo, inducing cellular apoptosis. This process involves up-regulation of p53 and Bax and decreased expression of Bcl-2. The data suggest that cyclin L2 represents a new member of the cyclin family, which might regulate the transcription and RNA processing of certain apoptosis-related factors, resulting in tumor cell growth inhibition and apoptosis.展开更多
Lead exposure is a known potential risk factor for neurodegenerative diseases such as Alzheimer’s disease (AD). Exposure to lead during the critical phase of brain development has been linked with mental retardatio...Lead exposure is a known potential risk factor for neurodegenerative diseases such as Alzheimer’s disease (AD). Exposure to lead during the critical phase of brain development has been linked with mental retardation and hypophrenia in later life.展开更多
Modern technology has witnessed milestone achievements in the telecommunication industry.However,the widespread application of telecommunication technology is believed to heighten electromagnetic field(EMF)‘pollution...Modern technology has witnessed milestone achievements in the telecommunication industry.However,the widespread application of telecommunication technology is believed to heighten electromagnetic field(EMF)‘pollution’in our environment[1]and subject living organisms to various sources of electromagnetic emissions.These emissions include;microwaves.展开更多
Microtubules are involved in a variety of cellular functions such as cell division, intracellular transport, maintenance of cell polarity and flagella and ciliary motility. The heterogeneity of tubulin and microtubule...Microtubules are involved in a variety of cellular functions such as cell division, intracellular transport, maintenance of cell polarity and flagella and ciliary motility. The heterogeneity of tubulin and microtubule-associated proteins is responsible for these different microtubule functions. Many studies have confirmed that the structure and function of the different α-tubulin and β-tubulin subunits can affect the microtubule. The sperm axoneme microtubule has linear fiber filaments which are polymerized by heterodimeric a and β-tubulin, each with a molecular mass of approximately 50 kD[1].展开更多
Traumatic cerebral or spinal cord injury induced by military,traffic,and sports accidents,falls or environmental and anthropogenic catastrophes are among main causes of people mortality and disability,especially in yo...Traumatic cerebral or spinal cord injury induced by military,traffic,and sports accidents,falls or environmental and anthropogenic catastrophes are among main causes of people mortality and disability,especially in young and middle age men(Kobeissy,2015).Axon transection,or axotomy,occurs in wounds and during surgery.展开更多
In the process of oxidative phosphorylation, protons are pumped into the intermembrane space to establish the mitochondrial membrane potential (MMP). Relying on the electrochemical gradient, protons can return to the ...In the process of oxidative phosphorylation, protons are pumped into the intermembrane space to establish the mitochondrial membrane potential (MMP). Relying on the electrochemical gradient, protons can return to the matrix through the ATP synthase complex with ATP generation. MitoQ, a lipophilic cation drug, can be bsorbed to the inner mitochondrial membrane with the cationic moiety staying at the intermembrane space[1].展开更多
The effects of chitosan treatment and inoculation on dry rot in tubers and slices of potato were studied. The results showed that chitosan treatment significantly reduced the lesion diameter of potato inoculated with ...The effects of chitosan treatment and inoculation on dry rot in tubers and slices of potato were studied. The results showed that chitosan treatment significantly reduced the lesion diameter of potato inoculated with Fusarium sulphureum. The treatment at 0.25% showed the best effect. Chitosan at 0.25% increased the activities of peroxidase and polyphenoloxidase, and the contents of flavonoid compounds and lignin in tissues. Increased activities of 13-1,3-glucanase, and phenylalanine ammonialyase were observed, but there were no significant differences between the treated and the control. These findings suggested that the effects of chitosan could be associated with the induced resistance against Fusarium dry rot in potato.展开更多
The effectiveness ofpostharvest β-aminobutyric acid (BABA) treatment was studied for inducing resistance against dry rot caused by Fusarium sulphureum in tubers and slices of two potato cultivars (resistant cultiv...The effectiveness ofpostharvest β-aminobutyric acid (BABA) treatment was studied for inducing resistance against dry rot caused by Fusarium sulphureum in tubers and slices of two potato cultivars (resistant cultivar Shepody and susceptible cultivar Xindaping). The results showed that BABA at 100 mmol L-1 significantly reduced lesion diameter in inoculated both tubers and slices. The chemical at 100 mmol L-1 showed an effective reduction in infection ability ofF. sulphureum inoculated 48 and 72 h after treatment in slices of resistant cultivar, and 72 and 96 h in susceptible ones. BABA increased the activitives of peroxidase (POD), polyphenoloxidase (PPO) and phenylalanine ammonialyase (PAL), and accumulated the contents of lignin, flavonoids and phenolics in slices. The resistant cultivar had a stronger resistant response than the susceptible one. These findings suggest that the BABA treatment can induce the resistance in potato tubers, however, the inducing degree depends on the original level of resistance present in each cultivar.展开更多
Acibenzolar-S-methyl (ASM) is a chemical activator of systematic resistance in many plants. The effect of preharvest and postharvest application of ASM was evaluated for its ability to induce resistance in muskmelon...Acibenzolar-S-methyl (ASM) is a chemical activator of systematic resistance in many plants. The effect of preharvest and postharvest application of ASM was evaluated for its ability to induce resistance in muskmelon fruit. The results indicated that 50 and 100 mg L^-1 ASM or 1 mL L^-1 imazalil at 1 week or 1 day before harvest were effective in reducing the lesion area with 100 mg L^-1 ASM the most effective. No treatment inhibited the infection rate. The postharvest results showed that 50 and 100 mg L^-1 ASM, and 0.1 mL L^-1 imazalil were effective in reducing the lesion area with 100 mg L^-1 ASM the most effective. No treatment inhibited the infection rate. There was a clear time-dependent response of the fruit to postharvest ASM treatment, in which treatments applied 1, 3, and 5 day before inoculation provided the best results. ASM did not demonstrate any fungicide effect in vitro and suppressed lesion area in treated muskmelons, indicating that disease resistance was induced. The protection of ASM was associated with the activation of peroxidase (POD) in treated muskmelons.展开更多
The effect of hot air(HA, 45°C, 3.5 h) treatment on reducing gray mold caused by Botrytis cinerea in strawberry fruit and the possible mechanisms were investigated. The results showed that HA treatment signific...The effect of hot air(HA, 45°C, 3.5 h) treatment on reducing gray mold caused by Botrytis cinerea in strawberry fruit and the possible mechanisms were investigated. The results showed that HA treatment significantly reduced lesion diameter and enhanced activities of chitinase(CHI), β-1,3-glucanase and phenylalanine ammonia-lyase(PAL) in strawberry fruit. Total phenolic contents were also increased by HA treatment. The activities of antioxidant enzymes including superoxide dismutase(SOD), catalase(CAT) and ascorbate peroxidase(APX) were higher in HA treated strawberry fruit than those in control. Expression of three defense related genes such as CAT, CCR-1 allele and PLA6 was greatly induced in HA treated strawberry fruit with or without inoculation by B. cinerea. In addition, the in vitro experiment showed that HA treatment inhibited spore germination and tube growth of B. cinerea. These results suggested that HA treatment directly activated disease resistance against B. cinerea in strawberry fruit without priming response and directly inhibiting growth of B. cinerea.展开更多
Liver fibrosis is an important health problem that can further progress into cirrhosis or liver cancer,and result in significant morbidity and mortality. Inhibiting proliferation and inducing apoptosis of hepatic stel...Liver fibrosis is an important health problem that can further progress into cirrhosis or liver cancer,and result in significant morbidity and mortality. Inhibiting proliferation and inducing apoptosis of hepatic stellate cells(HSCs) may be the key point to reverse liver fibrosis. At present,anti-fibrosis drugs are rare. Kinetin is a type of plant-derived cytokinin which has been reported to control differentiation and induce apoptosis of human cells. In this study,the HSCs were incubated with different concentrations of kinetin. The proliferation of rat HSCs was measured by MTT assay,cell cycle and apoptosis were analyzed by flow cytometry,and the apoptosis was examined by TUNEL method. The expression of Bcl-2 and Bax proteins was detected by immunocytochemistry staining. It was found that kinetin could markedly inhibit proliferation of HSCs. In a concentration range of 2 to 8 μg/m L,the inhibitory effects of kinetin on proliferation of HSCs were increased with the increased concentration and the extension of time(P〈0.01). Flow cytometry indicated that kinetin could inhibit the DNA synthesis from G0/G1 to S phase in a dose-dependent manner(P〈0.01). The apoptosis rates of the HSCs treated with 8,4 and 2 μg/m L kinetin(25.62%±2.21%,15.31%±1.9% and 6.18%±1.23%,respectively) were increased significantly compared with the control group(3.81%±0.93%)(P〈0.01). All the DNA frequency histogram in kinetin-treated groups showed obvious hypodiploid peak(sub-G1 peak),and with the increase of kinetin concentrations,the apoptosis rate of HSCs also showed a trend of increase. It was also found that kinetin could down-regulate the expression of Bcl-2,and up-regulate the expression of Bax,leading to the decreased ratio of Bcl-2/Bax significantly. The kinetin-induced apoptosis of HSCs was positively correlated with the expression of Bax,and negatively with the expression of Bcl-2. It was concluded that kinetin can inhibit activation and proliferation of HSCs by interrupting the cell cycle at G1/S restriction point and inducing apoptosis of HSCs via reducing the ratio of Bcl-2/Bax.展开更多
Potassium(K),an important nutrient element,can improve the stress resistance/tolerance of crops.The application of K in resisting plant-parasitic nematodes shows that the K treatment can reduce the occurrence of nemat...Potassium(K),an important nutrient element,can improve the stress resistance/tolerance of crops.The application of K in resisting plant-parasitic nematodes shows that the K treatment can reduce the occurrence of nematode diseases and increase crop yield.However,data on K_(2)SO_(4)induced rice resistance against the root-knot nematode Meloidogyne graminicola are still lacking.In this work,K_(2)SO_(4)treatment reduced galls and nematodes in rice plants and delayed the development of nematodes.Rather than affecting the attractiveness of roots to nematodes and the morphological phenotype of giant cells at feeding sites,such an effect is achieved by rapidly priming hydrogen peroxide(H_(2)O_(2))accumulation and increasing callose deposition.Meanwhile,galls and nematodes in rice roots were more in the potassium channel OsAKT11 and transporter OsHAK5 gene-deficient plants than in wild-type,while the K_(2)SO_(4)-induced resistance showed weaker in the defective plants.In addition,during the process of nematode infection,the expression of jasmonic acid(JA)/ethylene(ET)/brassinolide(BR)signaling pathway-related genes and pathogenesis-related(PR)genes OsPR1 a/OsPR1 b was up-regulated in rice after K_(2)SO_(4)treatment.In conclusion,K_(2)SO_(4)induced rice resistance against M.graminicola.The mechanism of inducing resistance was to prime the basal defense and required the participation of the K^(+)channel and transporter in rice.These laid a foundation for further study on the mechanism of rice defense against nematodes and the rational use of potassium fertilizer on improving rice resistance against nematodes in the field.展开更多
基金supported by the National Key Research and Development Program of China (2017YFC1702502)the Major Science and Technology Project in Yunnan Province(202102AE090042+2 种基金202102AA310048-2)Science and Technology Project of Kunming (2021JH002)Innovative Research Team of Science and Technology in Yunnan Province (202105AE160016)。
文摘Compared with the use of monocultures in the field,cultivation of medicinal herbs in forests is an effective strategy to alleviate disease.Chemical interactions between herbs and trees play an important role in disease suppression in forests.We evaluated the ability of leachates from needles of Pinus armandii to induce resistance in Panax notoginseng leaves,identified the components via gas chromatography-mass spectrometry(GC-MS),and then deciphered the mechanism of 2,3-Butanediol as the main component in the leachates responsible for resistance induction via RNA sequencing(RNA-seq).Prespraying leachates and 2,3-Butanediol onto leaves could induce the resistance of P.notoginseng to Alternaria panax.The RNA-seq results showed that prespraying 2,3-Butanediol onto leaves with or without A.panax infection upregulated the expression of large number of genes,many of which are involved in transcription factor activity and the mitogen-activated protein kinase(MAPK) signaling pathway.Specifically,2,3-Butanediol spraying resulted in jasmonic acid(JA)-mediated induced systemic resistance(ISR) by activating MYC2 and ERF1.Moreover,2,3-Butanediol induced systemic acquired resistance(SAR) by upregulating pattern-triggered immunity(PTI)-and effector-triggered immunity(ETI)-related genes and activated camalexin biosynthesis through activation of WRKY33.Overall,2,3-Butanediol from the leachates of pine needles could activate the resistance of P.notoginseng to leaf disease infection through ISR,SAR and camalexin biosynthesis.Thus,2,3-Butanediol is worth developing as a chemical inducer for agricultural production.
基金supported by Cancer Institute NSW CDF fellowship (YZ)Cure Cancer Foundation of Australia (YZ)+3 种基金Cancer Council New South Wales (MJS, YZ, HZ, and CRD)Prostate Cancer Foundation of Australia (MJS, YZ, HZ, and CRD)NH and MRC Early Career Fellowship 596870 (YZ)German Research Foundation HO 5109/2-1 and HO 5109/2-2 (KH)
文摘Vitamin D co-regulates cell proliferation, differentiation and apoptosis in numerous tissues, including cancers. The known anti-proliferative and pro-apoptotic actions of the active metabolite of vitamin D, 1,25-dihydroxy-vitamin D [1,25(OH)2D] are mediated through binding to the vitamin D receptor (VDR). Here, we report on the unexpected finding that stable knockdown of VDR expression in the human breast and prostate cancer cell lines, MDA-MB-231 and PC3, strongly induces cell apoptosis and inhibits cell proliferation in vitro. Implantation of these VDR knockdown cells into the mammary fat pad (MDA-MB-231), subcutaneously (PC3) or intra-tibially (both cell lines) in immune-incompetent nude mice resulted in reduced tumor growth associated with increased apoptosis and reduced cell proliferation compared with controls. These growth-retarding effects of VDR knockdown occur in the presence and absence of vitamin D and are independent of whether cells were grown in bone or soft tissues. Transcriptome analysis of VDR knockdown and non-target control cell lines demonstrated that loss of the VDR was associated with significant attenuation in the Wnt/0-catenin signaling pathway. In particular, cytoplasmic and nuclear β-catenin protein levels were reduced with a corresponding downregulation of downstream genes such as Axin2, Cyclin D1, interleukin-6 (IL-6), and IL-8. Stabilization of 0-catenin using the GSK-3β inhibitor BIO partly reversed the growth-retarding effects of VDR knockdown. Our results indicate that the unliganded VDR possesses hitherto unknown functions to promote breast and prostate cancer growth, which appear to be operational not only within but also outside the bone environment. These novel functions contrast with the known anti-proliferative nuclear actions of the liganded VDR and may represent targets for new diagnostic and therapeutic approaches in breast and prostate cancer.
基金supported by Natural Science Foundation of Jiangsu Province(BK2011049)Jiangsu"333"Projects in Jiangsu Province(BK201140032)Innovation Fund ofYangzhou University(2012CXJ085)
文摘The mortality of cancer patients has considerably improved due to progress in surgery, chemotherapy and radiotherapy. However, some types of cancers, such as melanoma, remain refractory to conventional strategies. Although melanoma accounts for only 4% of all dermatological malignancies, it is responsible for 80% of mortalities from skin tumors[11. The reported survival rate of melanoma over 5 years is not yet encouraging due to its chemo-resistance and rapid metastasis. Therefore, it is necessary to develop new drugs with potent activity and weak side-effect against melanoma.
基金supported by Elam M. and Georgina E.Hack Memorial Research Funds,Department of Periodontics,University of Washington,Seattle,WA,USAsupported by WVCTSI funds,West Virginia University,Morgantown,WV,USA
文摘Toll-like receptor (TLR)-mediated inflammatory response could negatively affect bone metabolism. In this study, we determined how osteogenesis is regulated during inflammatory responses that are downstream of TLR signaling. Human primary osteoblasts were cultured in collagen gels. Pam3CSK4 (P3C) and Escherichia coli lipopolysaccharide (EcLPS) were used as TLR2 and TLR4 ligand respectively. Porphyromonas gingivalis LPS having TLR2 activity with either TLR4 agonism (Pg1690) or TLR4 antagonism (Pg1449) and mutant E. coli LPS (LPxE/LPxF/WSK) were used. IL-lp, SH2-containing inositol phosphatase-1 (SHIP1) that has regulatory roles in osteogenesis, alkaline phosphatase and mineralization were analyzed. 3α-Aminocholestane (3AC) was used to inhibit SHIP1. Our results suggest that osteoblasts stimulated by P3C, poorly induced IL-1β but strongly upregulated SHIP1 and enhanced osteogenic mediators. On the contrary, EcLPS significantly induced IL-1β and osteogenic mediators were not induced. While Pg1690 downmodulated osteogenic mediators, Pg1449 enhanced osteogenic responses, suggesting that TLR4 signaling annuls osteogenesis even with TLR2 activity. Interestingly, mutant E. coli LPS that induces weak inflammation upregulated osteogenesis, but SHIP1 was not induced. Moreover, inhibiting SHIP1 significantly upregulated TLR2-mediated inflammatory response and downmodulated osteogenesis. In conclusion, these results suggest that induction of weak inflammatory response through TLR2 (with SHIP1 activity) and mutant TLR4 ligands could enhance osteogenesis.
基金Council for Scientific and Industrial Research (CSIR),New Delhi for providing the fellowshipthe Defence Institute of Physiology & Allied Sciences (DIPAS),the Defence Research & Development Organisation (DRDO),Government of India,for their consecutive financial support
文摘Present study deals with the straight impact of hypobaric hypoxia on the quantity and composition of some predominant fecal microflora and its functional aspects. For that, isolated fecal contents of rat were exposed to two different simulated air pressures (70 kPa and 40 kPa) for different time durations (1, 3, and 5 h) and the bacterial community composition was compared with normobaric groups (101.3 kPa). It was found that the total anaerobes, Escherichio coli, Enterbocters spp., Bi^idobocterium spp., CIostridium spp. were increased whereas total aerobes were decreased at both hypobaric treatments. The increased number of amplicon was detected in the pressure-treated groups than the control that clearly mentioned the disruption of microbiota structure at different simulated hypobaric-hypoxia. The amylase, protease, tannase, 13-glucuronidase, and alkaline phosphatase activities were increased at these atmospheric pressures. Thus, the present investigation demonstrates that the hypobaric hypoxia is an important environmental factor which can strongly modulate the composition of intestinal flora as well as microfiora-derived functional aspects.
基金supported by NSFC (the National Natural Science Foundation of China) [81273126, 30972454]the Key Project of Guangdong Natural Science Foundation [S2012020010903]+2 种基金the Project of Shenzhen Basic Research Plan [JCYJ20120616 154222545]the Upgrade Scheme of Shenzhen Municipal Key Laboratory [CXB201005260068A]Medical Scientific Research Foundation of Guangdong Province (A2012577)
文摘Trichloroethylene (TCE) is a major pollutant that affects both occupational and general environments. The liver is an important target organ of TCEE. Substantial efforts and remarkable progress into understanding TCE cytotoxicity have been made in cultured liver cells. However, the molecular mechanisms by which TCE induces hepatotoxicity are not well understood. SET (also known as protein phosphatase 2A inhibitor, 12PP2A, or template-activating factor-I, TAF-D is a nuclear protein that regulates histone modification, gene transcription, DNA replication, nucleosome assembly,
基金supported by awards from National Natural Science Foundation of China [No.81703260]the Education Department of Jiangsu Province [No.16KJB330010]+2 种基金the Science and Technology Department of Jiangsu Province [No.BK20160227]the China Postdoctoral Science Foundation funded project [No.2016M601892]the Priority Academic Program for the Development of Jiangsu Higher Education Institutions(PAPD)
文摘Perfluorooctane sulfonate (PFOS) is a class of stable organic compounds with wide industrial,commercial, and consumer applications, such as in textiles, paper, pesticides, and shampoos;. It is readily absorbed, but poorly eliminated, with the elimination half-life of approximately 5 years;.Hence, there have been concerns regarding its potential damage to human health. Some studies
基金supported by funding from a Veterans Administration BLR&D merit review grant 1–101-BX-002717 to Dr Subburaman Mohan
文摘To evaluate the long-term consequence of repetitive mild traumatic brain injury (mTBI) on bone, mTBI was induced in 10-week-old female C57BL/6J mice using a weight drop model, once per day for 4 consecutive days at different drop heights (0.5, 1 and 1.5 m) and the skeletal phenotype was evaluated at different time points after the impact. In vivo micro-CT (μ-CT) analysis of the tibial metaphysis at 2, 8 and 12 weeks after the impact revealed a 5%-32% reduction in trabecular bone mass. Histomorphometric analyses showed a reduced bone formation rate in the secondary spongiosa ofl.5 m impacted mice at 12 weeks post impact. Apparent modulus (bone strength), was reduced by 30% (P 〈 0.05) at the proximal tibial metaphysis in the 1.5 m drop height group at 2 and 8 weeks post impact. Ex vivo μ-CT analysis of the fifth lumbar vertebra revealed a significant reduction in trabecular bone mass at 12 weeks of age in all three drop height groups. Serum levels of osteocalcin were decreased by 22%, 15%, and 19% in the 0.5, 1.0 and 1.5 m drop height groups, respectively, at 2 weeks post impact. Serum IGF-I levels were reduced by 18%-32% in mTBI mice compared to control mice at 2 weeks post impact. Serum osteocalcin and IGF-I levels correlated with trabecular BV/TV (r2 = 0.14 and 0.16, P 〈 0.05). In conclusion, repetitive mTBI exerts significant negative effects on the trabecular bone microarchitecture and bone mechanical properties by influencing osteoblast function via reduced endocrine IGF-I actions.
文摘We report the cloning and functional characterization of human cyclin L2, a novel member of the cyclin family. Human cyclin L2 shares significant homology to cyclin L1, K, T1, T2, and C, which are involved in transcriptional regulation via phosphorylation of the C-terminal domain of RNA polymerase Ⅱ. The cyclin L2 protein contains an N-terminal "cyclin box" and C-terminal dipeptide repeats of alternating arginines and serines, a hallmark of the SR family of splicing factors. A new isoform and the mouse homologue of human cyclin L2 have also been cloned in this study. Human cyclin L2 is expressed ubiquitously in normal human tissues and tumor cells. We show here that cyclin L2 co-localizes with splicing factors SC-35 and 9G8 within nuclear speckles and that it associates with hyperphosphorylated, but not hypophosphorylated, RNA polymerase Ⅱ and CDK p110 PITSLRE kinase via its N-terminal cyclin domains. It can also associate with the SC-35 and 9G8 through its RS repeat region. Recombinant cyclin L2 protein can stimulate in vitro mRNA splicing. Overexpression of human cyclin L2 suppresses the growth of human hepatocellular carcinoma SMMC 7721 cells both in vitro and in vivo, inducing cellular apoptosis. This process involves up-regulation of p53 and Bax and decreased expression of Bcl-2. The data suggest that cyclin L2 represents a new member of the cyclin family, which might regulate the transcription and RNA processing of certain apoptosis-related factors, resulting in tumor cell growth inhibition and apoptosis.
基金supported by the National Natural Science Foundation of China(NSFC),No.31201878,81172716,and U1204804Post Doctoral Foundation of China,No.2015M572109Post Doctoral Fund of Henan province,No.2014049
文摘Lead exposure is a known potential risk factor for neurodegenerative diseases such as Alzheimer’s disease (AD). Exposure to lead during the critical phase of brain development has been linked with mental retardation and hypophrenia in later life.
文摘Modern technology has witnessed milestone achievements in the telecommunication industry.However,the widespread application of telecommunication technology is believed to heighten electromagnetic field(EMF)‘pollution’in our environment[1]and subject living organisms to various sources of electromagnetic emissions.These emissions include;microwaves.
基金supported by grants from the National Basic Research Program of China(2010CB834202)The National Natural Science Foundation of China(10835011)the Scientific Technology Research Projects of Gansu Province(0702NKDA045,0806RJYA020)
文摘Microtubules are involved in a variety of cellular functions such as cell division, intracellular transport, maintenance of cell polarity and flagella and ciliary motility. The heterogeneity of tubulin and microtubule-associated proteins is responsible for these different microtubule functions. Many studies have confirmed that the structure and function of the different α-tubulin and β-tubulin subunits can affect the microtubule. The sperm axoneme microtubule has linear fiber filaments which are polymerized by heterodimeric a and β-tubulin, each with a molecular mass of approximately 50 kD[1].
基金Supported by the Ministry of Education and Science of Russia grants 6.4951.2017/6.7 and 6.6З24.2017/8.9
文摘Traumatic cerebral or spinal cord injury induced by military,traffic,and sports accidents,falls or environmental and anthropogenic catastrophes are among main causes of people mortality and disability,especially in young and middle age men(Kobeissy,2015).Axon transection,or axotomy,occurs in wounds and during surgery.
基金Key Program of National Natural Science Foundation of China (U1432248), National Natural Science Foundation of China (11505245), Western Talent Program of Chinese Academy of Sciences (Y460040XB0)
文摘In the process of oxidative phosphorylation, protons are pumped into the intermembrane space to establish the mitochondrial membrane potential (MMP). Relying on the electrochemical gradient, protons can return to the matrix through the ATP synthase complex with ATP generation. MitoQ, a lipophilic cation drug, can be bsorbed to the inner mitochondrial membrane with the cationic moiety staying at the intermembrane space[1].
文摘The effects of chitosan treatment and inoculation on dry rot in tubers and slices of potato were studied. The results showed that chitosan treatment significantly reduced the lesion diameter of potato inoculated with Fusarium sulphureum. The treatment at 0.25% showed the best effect. Chitosan at 0.25% increased the activities of peroxidase and polyphenoloxidase, and the contents of flavonoid compounds and lignin in tissues. Increased activities of 13-1,3-glucanase, and phenylalanine ammonialyase were observed, but there were no significant differences between the treated and the control. These findings suggested that the effects of chitosan could be associated with the induced resistance against Fusarium dry rot in potato.
基金supported by the Gansu Agricultural Bio-Technology Foundation, China (GNSW-2005-08)the R&D Special Funds for Public Welfare Indus-try (Agriculture) of Ministry of Agriculture of China(NYHYZX07-6)
文摘The effectiveness ofpostharvest β-aminobutyric acid (BABA) treatment was studied for inducing resistance against dry rot caused by Fusarium sulphureum in tubers and slices of two potato cultivars (resistant cultivar Shepody and susceptible cultivar Xindaping). The results showed that BABA at 100 mmol L-1 significantly reduced lesion diameter in inoculated both tubers and slices. The chemical at 100 mmol L-1 showed an effective reduction in infection ability ofF. sulphureum inoculated 48 and 72 h after treatment in slices of resistant cultivar, and 72 and 96 h in susceptible ones. BABA increased the activitives of peroxidase (POD), polyphenoloxidase (PPO) and phenylalanine ammonialyase (PAL), and accumulated the contents of lignin, flavonoids and phenolics in slices. The resistant cultivar had a stronger resistant response than the susceptible one. These findings suggest that the BABA treatment can induce the resistance in potato tubers, however, the inducing degree depends on the original level of resistance present in each cultivar.
文摘Acibenzolar-S-methyl (ASM) is a chemical activator of systematic resistance in many plants. The effect of preharvest and postharvest application of ASM was evaluated for its ability to induce resistance in muskmelon fruit. The results indicated that 50 and 100 mg L^-1 ASM or 1 mL L^-1 imazalil at 1 week or 1 day before harvest were effective in reducing the lesion area with 100 mg L^-1 ASM the most effective. No treatment inhibited the infection rate. The postharvest results showed that 50 and 100 mg L^-1 ASM, and 0.1 mL L^-1 imazalil were effective in reducing the lesion area with 100 mg L^-1 ASM the most effective. No treatment inhibited the infection rate. There was a clear time-dependent response of the fruit to postharvest ASM treatment, in which treatments applied 1, 3, and 5 day before inoculation provided the best results. ASM did not demonstrate any fungicide effect in vitro and suppressed lesion area in treated muskmelons, indicating that disease resistance was induced. The protection of ASM was associated with the activation of peroxidase (POD) in treated muskmelons.
基金supported by the Special Fund for Agro-scientific Research in the Public Interest of China(201303073)the Fundamental Research Funds for the Central Universities,China(KYZ201420)
文摘The effect of hot air(HA, 45°C, 3.5 h) treatment on reducing gray mold caused by Botrytis cinerea in strawberry fruit and the possible mechanisms were investigated. The results showed that HA treatment significantly reduced lesion diameter and enhanced activities of chitinase(CHI), β-1,3-glucanase and phenylalanine ammonia-lyase(PAL) in strawberry fruit. Total phenolic contents were also increased by HA treatment. The activities of antioxidant enzymes including superoxide dismutase(SOD), catalase(CAT) and ascorbate peroxidase(APX) were higher in HA treated strawberry fruit than those in control. Expression of three defense related genes such as CAT, CCR-1 allele and PLA6 was greatly induced in HA treated strawberry fruit with or without inoculation by B. cinerea. In addition, the in vitro experiment showed that HA treatment inhibited spore germination and tube growth of B. cinerea. These results suggested that HA treatment directly activated disease resistance against B. cinerea in strawberry fruit without priming response and directly inhibiting growth of B. cinerea.
基金supported by a grant from Hubei Natural Science Foundation of China(No.2013CFB135)
文摘Liver fibrosis is an important health problem that can further progress into cirrhosis or liver cancer,and result in significant morbidity and mortality. Inhibiting proliferation and inducing apoptosis of hepatic stellate cells(HSCs) may be the key point to reverse liver fibrosis. At present,anti-fibrosis drugs are rare. Kinetin is a type of plant-derived cytokinin which has been reported to control differentiation and induce apoptosis of human cells. In this study,the HSCs were incubated with different concentrations of kinetin. The proliferation of rat HSCs was measured by MTT assay,cell cycle and apoptosis were analyzed by flow cytometry,and the apoptosis was examined by TUNEL method. The expression of Bcl-2 and Bax proteins was detected by immunocytochemistry staining. It was found that kinetin could markedly inhibit proliferation of HSCs. In a concentration range of 2 to 8 μg/m L,the inhibitory effects of kinetin on proliferation of HSCs were increased with the increased concentration and the extension of time(P〈0.01). Flow cytometry indicated that kinetin could inhibit the DNA synthesis from G0/G1 to S phase in a dose-dependent manner(P〈0.01). The apoptosis rates of the HSCs treated with 8,4 and 2 μg/m L kinetin(25.62%±2.21%,15.31%±1.9% and 6.18%±1.23%,respectively) were increased significantly compared with the control group(3.81%±0.93%)(P〈0.01). All the DNA frequency histogram in kinetin-treated groups showed obvious hypodiploid peak(sub-G1 peak),and with the increase of kinetin concentrations,the apoptosis rate of HSCs also showed a trend of increase. It was also found that kinetin could down-regulate the expression of Bcl-2,and up-regulate the expression of Bax,leading to the decreased ratio of Bcl-2/Bax significantly. The kinetin-induced apoptosis of HSCs was positively correlated with the expression of Bax,and negatively with the expression of Bcl-2. It was concluded that kinetin can inhibit activation and proliferation of HSCs by interrupting the cell cycle at G1/S restriction point and inducing apoptosis of HSCs via reducing the ratio of Bcl-2/Bax.
基金supported by the Natural Science Foundation of China(32172382,31801716,and 31571986)the National Key Research and Development Program of China(2021YFC2600404)the Scientific Research Project of Hunan Provincial Department of Education of China(19B259)。
文摘Potassium(K),an important nutrient element,can improve the stress resistance/tolerance of crops.The application of K in resisting plant-parasitic nematodes shows that the K treatment can reduce the occurrence of nematode diseases and increase crop yield.However,data on K_(2)SO_(4)induced rice resistance against the root-knot nematode Meloidogyne graminicola are still lacking.In this work,K_(2)SO_(4)treatment reduced galls and nematodes in rice plants and delayed the development of nematodes.Rather than affecting the attractiveness of roots to nematodes and the morphological phenotype of giant cells at feeding sites,such an effect is achieved by rapidly priming hydrogen peroxide(H_(2)O_(2))accumulation and increasing callose deposition.Meanwhile,galls and nematodes in rice roots were more in the potassium channel OsAKT11 and transporter OsHAK5 gene-deficient plants than in wild-type,while the K_(2)SO_(4)-induced resistance showed weaker in the defective plants.In addition,during the process of nematode infection,the expression of jasmonic acid(JA)/ethylene(ET)/brassinolide(BR)signaling pathway-related genes and pathogenesis-related(PR)genes OsPR1 a/OsPR1 b was up-regulated in rice after K_(2)SO_(4)treatment.In conclusion,K_(2)SO_(4)induced rice resistance against M.graminicola.The mechanism of inducing resistance was to prime the basal defense and required the participation of the K^(+)channel and transporter in rice.These laid a foundation for further study on the mechanism of rice defense against nematodes and the rational use of potassium fertilizer on improving rice resistance against nematodes in the field.