ABSTRACT
Cryptosporidium spp. are protozoan parasites that mainly inhabit intestinal epithelial cells, causing diarrheal diseases in humans and a great number of animals. Cryptosporidium parvum is the most common zoonotic species, responsible for nearly 45% of human cryptosporidiosis worldwide. Understanding the interaction mechanisms between C. parvum and host gastrointestinal epithelial cells has significant implications to control cryptosporidiosis. One up-regulated circRNA ciRS-7 was found previously by our group to promote in vitro propagation of C. parvum in HCT-8 cells. In the present study, miR-135a-5p, was found to be a miRNA target of ciRS-7. Cryptosporidium parvum infection induced significantly down-regulation of miR-135a-5p and dramatic up-regulation of its potential target stat1 gene at mRNA and protein levels. Dual luciferase reporter assays validated the physical interactions between miR-135a-5p and stat1, and between ciRS-7 and miR-135a-5p. Further study revealed that ciRS-7 could sponge miR-135a-5p to positively regulate the protein levels of STAT1 and phosphorylated STAT1 (p-STAT1) and thus promote C. parvum propagation in HCT-8 cells. Our findings further reveal the mystery of regulatory roles of host circRNAs during Cryptosporidium infection, and provide a novel insight to develop strategies to control cryptosporidiosis.
Subject(s)
Cryptosporidiosis , Cryptosporidium parvum , Cryptosporidium , MicroRNAs , Animals , Humans , Cell Line, Tumor , Cryptosporidiosis/genetics , Cryptosporidium/genetics , Cryptosporidium parvum/genetics , MicroRNAs/genetics , RNA, Circular/genetics , STAT1 Transcription Factor/genetics , STAT1 Transcription Factor/metabolismABSTRACT
Aim: This study investigated the current status and related risk factors of 48-hour unplanned return to the intensive care unit (ICU) to reduce the return rate and improve the quality of critical care management. Methods: Data were collected from 2365 patients discharged from the comprehensive ICU. Multivariate and 1:1 propensity score matching analyses were performed. Results: Forty patients (1.69%) had unplanned readmission to the ICU within 48 hours after transfer. The primary reason for return was respiratory failure (16 patients, 40%). Furthermore, respiratory failure (odds ratio [OR] = 5.994, p = 0.02) and the number of organ failures (OR = 5.679, p = 0.006) were independent risk factors for unplanned ICU readmission. Receiver operating characteristic curves were drawn for the predictive value of the number of organ injuries during a patient's unplanned transfer to the ICU (area under the curve [AUC] = 0.744, sensitivity = 60%, specificity = 77.5%). Conclusion: The reason for patient transfer and the number of organ injuries during the process were independent risk factors for patients who were critically ill. The number of organs damaged had a predictive value on whether the patient would return to the ICU within 48 hours.
ABSTRACT
Cryptosporidium parvum is an important apicomplexan parasite causing severe diarrhea in both humans and animals. Calmodulin (CaM), a multifunctional and universal calcium-binding protein, contributes to the growth and development of apicomplexan parasites, but the role of CaM in C. parvum remains unknown. In this study, the CaM of C. parvum encoded by the cgd2_810 gene was expressed in Escherichia coli, and the biological functions of CpCaM were preliminarily investigated. The transcriptional level of the cgd2_810 gene peaked at 36 h post infection (pi), and the CpCaM protein was mainly located around the nucleus of the whole oocysts, in the middle of sporozoites and around the nucleus of merozoites. Anti-CpCaM antibody reduced the invasion of C. parvum sporozoites by 30.69%. The present study indicates that CpCaM is potentially involved in the growth of C. parvum. Results of the study expand our knowledge on the interaction between host and Cryptosporidium.
Subject(s)
Cryptosporidiosis , Cryptosporidium parvum , Cryptosporidium , Animals , Humans , Cryptosporidium parvum/genetics , Cryptosporidium/genetics , Cryptosporidiosis/parasitology , Oocysts/metabolism , Sporozoites/metabolismABSTRACT
Connected ramets of colonal plants often suffer from different environmental conditions such as light, nutrient, and stress. Colonal Bermudagrass (Cynodon dactylon [L.] Pers.) can form interconnected ramets and this connection facilitates the tolerance to abiotic stress, which is a kind of physiological integration. However, how bermudagrass responds to heterogeneously distributed salt stress needs to be further elucidated. Here, we demonstrated that severance of stolons aggravated the damage of salt-stressed ramets, displaying higher relative electrolytic leakage (EL), lower content of chlorophyll, higher accumulation of Na+ , and serious oxidative damages. This finding implied the positive effects of the physiological integration of bermudagrass on salt tolerance. The unstressed ramets connected with the stressed one were mildly injured, implying the supporting and sacrifice function of the unstressed ramets. Physiological integration did not mediate the translocation of Na+ among ramets, but induced a higher expression of salt overly sensitive (SOS) genes in the stressed ramets, consequently reducing the accumulation of Na+ in leaves and roots. In addition, physiological integration upregulated the genes expression and enzymes activity of catalase (CAT) and peroxidase (POD) in both stressed and unstressed ramets. This granted a stronger antioxidant ability of the whole clonal plants under salt stress. Enhanced Na+ transfer and increased reactive oxygen species (ROS) scavenging are mechanisms that likely contribute to the physiological integration leading to the salt tolerance of bermudagrass.
Subject(s)
Cynodon , Salt Stress , Chlorophyll/metabolism , Cynodon/genetics , Cynodon/metabolism , Reactive Oxygen Species/metabolism , Stress, PhysiologicalABSTRACT
This letter responds to comments on our article (Yin YL et al., Parasit Vectors, 10.1186/s13071-021-04739-w) by Yuqing Wang and colleagues, who wrote a letter entitled "Microarray analysis of circular RNAs in HCT-8 cells infected with Cryptosporidium parvum" and discussed statistical procedures for microarray analysis during C. parvum infection. To further confirm our data, in this letter, a common R package for analyses of differentially expressed genes, namely DESeq2, with Benjamini-Hochberg correction, was used to analyze our microarray data and identified 26 significantly differentially expressed circRNAs using adjusted P value < 0.05 and | Log2 (fold change [FC]) | ≥ 1.0, including our circRNA ciRS-7 of interest. Therefore, the protocol for selecting circRNAs of interest for further study in our article is acceptable and did not affect the subsequent scientific findings in our article.
Subject(s)
Cryptosporidiosis/parasitology , Cryptosporidium parvum/genetics , RNA, Circular/genetics , RNA, Protozoan/genetics , Cryptosporidium parvum/metabolism , Gene Expression Profiling , Humans , RNA, Circular/metabolism , RNA, Protozoan/metabolismABSTRACT
BACKGROUND: Cryptosporidium is an important zoonotic pathogen responsible for severe enteric diseases in humans and animals. However, the molecular mechanisms underlying host and Cryptosporidium interactions are still not clear. METHODS: To study the roles of circRNAs in host cells during Cryptosporidium infection, the expression profiles of circRNAs in HCT-8 cells infected with C. parvum were investigated using a microarray assay, and the regulatory role of a significantly upregulated circRNA, ciRS-7, was investigated during C. parvum infection. RESULTS: C. parvum infection caused notable alterations in the expression profiles of circRNAs in HCT-8 cells, and a total of 178 (including 128 up- and 50 downregulated) circRNAs were significantly differentially expressed following C. parvum infection. Among them, ciRS-7 was significantly upregulated and regulated the NF-κB signaling pathway by sponging miR-1270 during C. parvum infection. Furthermore, the ciRS-7/miR-1270/relA axis markedly affected the propagation of C. parvum in HCT-8 cells. CONCLUSIONS: Our results revealed that ciRS-7 would promote C. parvum propagation by regulating the miR-1270/relA axis and affecting the NF-κB pathway. To the best of our knowledge, this is the first study to investigate the role of circRNA during Cryptosporidium infection, and the findings provide a novel view for implementing control strategies against Cryptosporidium infection.
Subject(s)
Cryptosporidium parvum , Epithelial Cells/parasitology , MicroRNAs/metabolism , RNA, Circular/metabolism , Animals , Cell Line , Cryptosporidiosis/metabolism , Cryptosporidium parvum/growth & development , Cryptosporidium parvum/pathogenicity , Epithelial Cells/metabolism , Humans , NF-kappa B/metabolism , Signal TransductionABSTRACT
This study was aimed to determine the effect of acute cerebral ischemia on the protein expression level of silent mating type information regulator 2 homolog 3 (Sirt3) in the neurons and clarify the pathological role of Sirt3 in acute cerebral ischemia. The mice with middle cerebral artery occlusion (MCAO) and primary cultured rat hippocampal neurons with oxygen glucose deprivation (OGD) were used as acute cerebral ischemia models in vivo and in vitro, respectively. Sirt3 overexpression was induced in rat hippocampal neurons by lentivirus transfection. Western blot was utilized to measure the changes in Sirt3 protein expression level. CCK8 assay was used to detect cell viability. Immunofluorescent staining was used to detect mitochondrial function. Transmission electron microscope was used to detect mitochondrial autophagy. The results showed that, compared with the normoxia group, hippocampal neurons from OGD1 h/reoxygenation 2 h (R2 h) and OGD1 h/R12 h groups exhibited down-regulated Sirt3 protein expression levels. Compared with contralateral normal brain tissue, the ipsilateral penumbra region from MCAO1 h/reperfusion 24 h (R24 h) and MCAO1 h/R72 h groups exhibited down-regulated Sirt3 protein expression levels, while there was no significant difference between the Sirt3 protein levels on both sides of sham group. OGD1 h/R12 h treatment damaged mitochondrial function, activated mitochondrial autophagy and reduced cell viability in hippocampal neurons, whereas Sirt3 over-expression attenuated the above damage effects of OGD1 h/R12 h treatment. These results suggest that acute cerebral ischemia results in a decrease in Sirt3 protein level. Sirt3 overexpression can alleviate acute cerebral ischemia-induced neural injuries by improving the mitochondrial function. The current study sheds light on a novel strategy against neural injuries caused by acute cerebral ischemia.
Subject(s)
Brain Ischemia , Reperfusion Injury , Sirtuin 3 , Animals , Down-Regulation , Infarction, Middle Cerebral Artery , Mice , Mitochondria , Neurons/metabolism , Rats , Sirtuin 3/genetics , Sirtuin 3/metabolism , SirtuinsABSTRACT
Cryptosporidium is an important intestinal protozoan parasite that causes diarrhoea in humans and animals. To rapidly and specifically detect Cryptosporidium spp., we designed a pair of primers based on the small subunit ribosomal RNA (SSU rRNA) gene of Cryptosporidium spp. to be used in a new nanoparticle-assisted PCR (nano-PCR) assay. The minimum detectable concentration (1.02 pg) of this nano-PCR was 10 times more sensitive than conventional PCR using the same primer pair. The DNA samples of C. parvum, C. baileyi, C. xiaoi, C. ryanae, and C. andersoni were successfully detected by the nano-PCR. No amplifications were evident with DNA samples of some common intestinal pathogens, including Eimeria tenella, Blastocystis sp., Giardia lamblia, Enterocytozoon bieneusi, and Balantidium coli. To validate the clinical usefulness of the novel nano-PCR, a total of 40 faecal samples from goats, camels, calves, and chickens were examined. The positive rate of Cryptosporidium spp. was 27.5% (11/40), which was consistent with that of an established nested PCR. These results indicate that the novel nano-PCR assay enables the rapid, specific, and accurate detection of Cryptosporidium infection in animals. The findings provide a technical basis for the clinical diagnosis, prevention, and control of cryptosporidiosis.
Subject(s)
Cryptosporidiosis/diagnosis , Cryptosporidium/isolation & purification , Nanoparticles , Polymerase Chain Reaction/methods , Animals , Camelus , Cattle , Chickens , Cryptosporidiosis/parasitology , Cryptosporidium/genetics , Cryptosporidium parvum/genetics , DNA, Protozoan , Feces/parasitology , Goats , Sequence Analysis, DNAABSTRACT
Retinitis pigmentosa (RP) is characterized by visual acuity decrease and visual field loss. However, the impact of visual field loss on the cognitive performance of RP patients remains unknown. In the present study, in order to understand whether and how RP affects spatial processing and attentional function, one spatial processing task and three attentional tasks were conducted on RP patients and healthy controls. In addition, an EZ-diffusion model was performed for further data analysis with four parameters, mean decision time, non-decision time, drift rate, and boundary separation. It was found that in the spatial processing task, compared with the control group, the RP group exhibited a slower response speed in large and medium visual eccentricities, and slower drift rate for the large stimulus, which is strongly verified by the significant linear correlation between the visual field eccentricity with both reaction time (p = 0.047) and non-decision time (p = 0.043) in RP patients. In the attentional orienting task and the attentional switching task, RP exerted a reduction of speed and an increase of non-decision time on every condition, with a decrease of drift rate in the orienting task and boundary separation in the switching task. In addition, the switching cost for large stimulus was observed in the control group but not in the RP group. The stop-signal task demonstrated similar inhibition function between the two groups. These findings implied that RP exerted the impairment of spatial cognition correlated with the visual field eccentricity, mainly in the peripheral visual field. Moreover, specific to the peripheral visual field, RP patients had deficits in the attentional orienting and flexibility but not in the attentional inhibition.
ABSTRACT
Cryptosporidium parvum is one of the most important enteric protozoan pathogens, responsible for severe diarrhea in immunocompromised human and livestock. However, few effective agents were available for controlling this parasite. Accumulating evidences suggest that long non-coding RNA (lncRNA) played key roles in many diseases through regulating the gene expression. Here, the expression profiles of lncRNAs and mRNAs were analyzed in HCT-8 cells infected with C. parvum IId subtype using microarray assay. A total of 821 lncRNAs and 1,349 mRNAs were differentially expressed in infected cells at 24 h post infection (pi). Of them, all five types of lncRNAs were identified, including 22 sense, 280 antisense, 312 intergenic, 44 divergent, 33 intronic lncRNAs, and 130 lncRNAs that were not found the relationship with mRNAs' location. Additionally, real-time polymerase chain reactions of 10 lncRNAs and 10 mRNAs randomly selected were successfully confirmed the microarray results. The co-expression and target prediction analysis indicated that 27 mRNAs were cis-regulated by 29 lncRNAs and 109 were trans-regulated by 114 lncRNAs. These predicted targets were enriched in several pathways involved in the interaction between host and C. parvum, e.g., hedgehog signaling pathway, Wnt signaling pathway, and tight junction, suggesting that these differentially expressed lncRNAs would play important regulating roles during the infection of C. parvum IId subtype.
ABSTRACT
Giardia duodenalis (syn. Giardia lamblia, Giardia intestinalis) is an important zoonotic parasite that parasitizes the gastro-intestines of humans and animals, with diarrhea as the most common clinical symptom. The goat has been indicated as one of the most important reservoirs of G. duodenalis for humans. In the present study, we investigated the prevalence and genetic diversity of G. duodenalis in goats in Shaanxi province, northwestern China. A total of 1311 faecal specimens were examined, and the overall prevalence was 7.1% (93/1311). Although all the meat, cashmere and dairy goats were positive for infection, the highest prevalence was found in cashmere goats (10.2%), followed by dairy (9.4%) and meat goats (2.0%). Negative correlation between age and prevalence was also observed, and the highest prevalence was detected in 0-2-month goats. Genetic analysis showed the presence of three assemblages, including two zoonotic (A and B) and one animal-adapted assemblage E, with E as the prevalent assemblage found in all breeds of positive goats. The zoonotic assemblage A was found in Guanzhong dairy and Shanbei cashmere goats, but B was only detected in Boar goats. Additionally, mixed assemblages E and A were also identified in two cashmere goats. Multi-locus genotyping (MLST) using the gene loci of the triosephosphate isomerase (tpi), b-giardin (bg) and glutamate dehydrogenase (gdh) identified four novel multi-locus genotypes (MLGs), including two assemblage E MLGs and two assemblage A MLGs. These results suggested that Boar, Guanzhong dairy and Shanbei cashmere goats in Shaanxi province would be potential reservoirs for human infections in this area, and this study also provided basic data for controlling G. duodenalis infection in goats as well as other hosts.
Subject(s)
Giardia lamblia/genetics , Goats/parasitology , Multilocus Sequence Typing , Animals , China/epidemiology , Genetic Variation , Genotype , Giardia lamblia/isolation & purification , Giardiasis/epidemiology , Giardiasis/veterinary , Prevalence , Triose-Phosphate Isomerase/geneticsABSTRACT
BACKGROUND: Giardiasis, caused by Giardia duodenalis (syn. Giardia intestinalis, Giardia lamblia), is a significant zoonotic parasitic disease of animals and humans worldwide. Accurate genotyping of G. duodenalis is essential for efficient control and management of giardiasis. The objectives of the present study were to investigate the prevalence and assemblages of giardiasis in pigs in Shaanxi Province, northwestern China, and for the first time study multilocus genotypes (MLGs) in pigs using multilocus genotyping technology in this region. RESULTS: Of 560 faecal samples collected from five farms in Shaanxi Province, 45 were positive for G. duodenalis and significant differences in prevalence were observed among different locations. Differences in prevalence were also detected in pigs of different age groups, with the highest prevalence in sows and the lowest in boars. Two assemblages, A and E, were identified, and a mixed infection of both A and E was identified in one faecal sample. Assemblage E was predominant and widely distributed in all investigated areas and age groups. Genetic viability was detected for both assemblages, and four different multi-locus genotypes (MLGs) within assemblage E were found, MLGE1-MLGE4. CONCLUSIONS: Giardia duodenalis was detected in pigs from Shaanxi Province, northwestern China, and genetic diversity was observed in these infections. Both assemblages A and E were detected, and four distinct MLGs within assemblage E were identified. These findings provide new data for controlling G. duodenalis infection in pigs.
Subject(s)
Genetic Variation , Giardia lamblia/genetics , Giardia lamblia/isolation & purification , Giardiasis/veterinary , Swine Diseases/parasitology , Animals , China/epidemiology , Feces/parasitology , Giardiasis/parasitology , Swine , ZoonosesABSTRACT
Blastocystis is one of the most common parasites inhabiting in small intestines of human and animals. Although its pathogenicity has been remaining controversial, the possibility of zoonotic transmission between human and animals was recognized. The goat was one of the most important economic animals supplying people with cashmere, meat, and dairy products. However, few studies were to investigate Blastocystis infection in goats. A total of 789 faecal specimens of goats (including 362 of dairy, 193 of meat and 234 of cashmere goats) were collected from multiple regions of Shaanxi province in northwestern China to investigate the colonization frequency and subtypes of Blastocystis, and to assess the zoonotic potential of these goats. The respective colonization frequencies of Blastocystis in dairy, meat and cashmere goats were 54.1% (196/362), 40.4% (78/193) and 78.6% (184/234). The prevalence of Blastocystis in pre-weaned (0-2-month) goats was significantly lower than that in goats of other age groups, and the highest colonization was observed in goats of 7-11-month age group. Sequence analysis of Blastocystis positive samples indicated the presence of seven subtypes in these goats, including six known subtypes (STs1, 3, 4, 5, 10, 14) and one possible novel subtype (isolate Sd26), with the subtype 10 as the predominant one. Additionally, zoonotic subtypes were found in dairy (ST1, ST3 and ST5) and cashmere (ST4 and ST5) goats, but not detected in meat goats. These results showed that Blastocystis is highly prevalent, widely distributed and genetically diverse in goats in Shaanxi province, northwestern China, and zoonotic potential of dairy and cashmere goats to transmit Blastocystis.
Subject(s)
Blastocystis Infections/genetics , Blastocystis Infections/veterinary , Blastocystis/genetics , Age Factors , Animals , Blastocystis/isolation & purification , China/epidemiology , Dairy Products/parasitology , Feces/parasitology , Female , Genotype , Goats , Humans , Meat/parasitology , Prevalence , VirulenceABSTRACT
OBJECTIVE The objective of this study was to review the literature on the use of flow-diverting devices (FDDs) to treat intracranial aneurysms (IAs) and to investigate the safety and complications related to FDD treatment for IAs by performing a meta-analysis of published studies. METHODS A systematic electronic database search was conducted using the Springer, EBSCO, PubMed, Medline, and Cochrane databases on all accessible articles published up to January 2016, with no restriction on the publication year. Abstracts, full-text manuscripts, and the reference lists of retrieved articles were analyzed. Random-effects meta-analysis was used to pool the complication rates across studies. RESULTS Sixty studies were included, which involved retrospectively collected data on 3125 patients. The use of FDDs was associated with an overall complication rate of 17.0% (95% confidence interval [CI] 13.6%-20.5%) and a low mortality rate of 2.8% (95% CI 1.2%-4.4%). The neurological morbidity rate was 4.5% (95% CI 3.2%-5.8%). No significant difference in the complication or mortality rate was observed between 2 commonly used devices (the Pipeline embolization device and the Silk flow-diverter device). A significantly higher overall complication rate was found in the case of ruptured IAs than in unruptured IA (odds ratio 2.3, 95% CI 1.2-4.3). CONCLUSIONS The use of FDDs in the treatment of IAs yielded satisfactory results with regard to complications and the mortality rate. The risk of complications should be considered when deciding on treatment with FDDs. Further studies on the mechanism underlying the occurrence of adverse events are required.
Subject(s)
Endovascular Procedures/adverse effects , Endovascular Procedures/instrumentation , Intracranial Aneurysm/therapy , Postoperative Complications/etiology , Stents , Databases, Bibliographic/statistics & numerical data , Humans , Treatment OutcomeABSTRACT
Differentiating between sepsis and non-infectious systemic inflammatory response syndrome (SIRS) poses a great challenge. Several potential bloodstream biomarkers including Interleukin 6 (IL-6) have been investigated for their ability to diagnose sepsis. We conducted the present meta-analysis to evaluate the diagnostic quality of IL-6 in differentiating sepsis from non-infectious SIRS in adults. We also compared its accuracy with procalcitonin (PCT) and C-reactive protein (CRP). PubMed and EMBASE were systematically searched for studies published up to January 18, 2016. Twenty articles containing 22 studies and 2680 critically ill patients were included, of which, 21 studies also involved PCT and 14 involved CRP. Quantitative synthesis of studies showed that the pooled sensitivity/specificity of IL-6 and PCT were 0.68/0.73 and 0.78/0.67. The area under the curve (AUC) of IL-6, PCT and CPR for diagnosis of sepsis was 0.80, 0.83, and 0.71, respectively. This meta-analysis provides evidence that the IL-6 test has moderate diagnostic performance in differentiating sepsis from non-infectious SIRS in adults. IL-6 and PCT test has similar diagnostic value but higher than CRP. Considering its relatively high specificity, we recommend the use of IL-6 as a diagnostic aid to confirm infection rather than exclude infection in patients with SIRS.
Subject(s)
C-Reactive Protein/metabolism , Calcitonin/blood , Interleukin-6/blood , Sepsis/blood , Sepsis/diagnosis , Adult , Female , Humans , MaleABSTRACT
The translocator protein 18kDa (TSPO) is closely related to regulation of immune/inflammatory response. However, the putative role and signaling mechanisms of TSPO in regulation of neuroinflammation remain unclear. GV287 lentiviral vectors mediating TSPO over-expression were injected into bilateral hippocampal CA1 areas to test whether TSPO over-expression was neuroprotective in lipopolysaccharide (LPS)-induced mice model. Finasteride, a blocker of allopregnanolone production, was used to test whether the protective effects were related to steroideogenesis. The results demonstrated that TSPO over-expression increased progesterone and allopregnanolone synthesis. TSPO over-expression in CA1 area improved LPS-induced cognitive deficiency in mice and this cognitive improvement was reversed by finasteride administration. These data suggest that up-regulation of TSPO level during neuroinflammation may be an adaptive response mechanism, a way to provide more neurosteroids. We confer that TSPO could be an attractive drug target for controlling neuroinflammation in the future.
Subject(s)
CA1 Region, Hippocampal/metabolism , Cognitive Dysfunction/metabolism , Encephalitis/metabolism , Receptors, GABA/metabolism , Animals , CA1 Region, Hippocampal/drug effects , Cognitive Dysfunction/complications , Encephalitis/chemically induced , Encephalitis/complications , Finasteride/administration & dosage , Genetic Vectors/administration & dosage , Lentivirus/physiology , Lipopolysaccharides , Male , Maze Learning/drug effects , Mice , Mice, Inbred C57BL , Pregnanolone/metabolism , Progesterone/metabolism , Up-Regulation/drug effectsABSTRACT
Nitric oxide (NO) and mitogen-activated protein kinase (MPK) play important roles in brassinosteroid (BR)-induced stress tolerance, however, their functions in BR-induced pesticides metabolism remain unclear. Here, we showed that MPK activity and transcripts of SlMPK1 and SlMPK2 were induced by chlorothalonil (CHT), a widely used fungicide, in tomato leaves. However, cosilencing of SlMPK1/2 compromised the 24-epibrassinolide (EBR)-induced upregulation of detoxification genes and CHT metabolism in tomato leaves. In addition, cosilencing of SlMPK1/2 inhibited the accumulation of S-nitrosothiol (SNO), the reservoir of nitric oxide (NO) in plants, whereas tungstate, the inhibitor of nitrate reductase (NR), blocked EBR-induced SNO accumulation and MPK activity. Inhibiting the accumulation of NO by cPTIO, the specific scavenger and tungstate abolished the EBR-induced upregulation of detoxification genes, glutathione accumulation and CHT metabolism. The results showed that MPK and NR-dependent NO were involved in BR-induced CHT metabolism. Notably, there was a positive crosstalk between the MPK and NO production.
Subject(s)
Gene Expression Regulation, Plant , Mitogen-Activated Protein Kinases/metabolism , Nitrate Reductase/chemistry , Nitric Oxide/chemistry , Pesticides/chemistry , Solanum lycopersicum/metabolism , Aldehyde Oxidoreductases/metabolism , Brassinosteroids/chemistry , Chlorophyll/chemistry , Gene Expression Profiling , Gene Silencing , Glutathione/metabolism , Plant Leaves/metabolismABSTRACT
Tissue-type plasminogen activator (t-PA) and matrix metalloproteinase-9 (MMP-9) have been reported to play important roles in increased permeability of blood-brain barrier (BBB) under many pathological circumstances. We have showed that Ulinastatin, a broad-spectrum serine protease inhibitor, could alleviate inflammation in the hippocampus of aged rats following partial hepatectomy. In this study, we investigate the expression and potential roles of t-PA and MMP-9 in the protective effect of Ulinastatin. We found that partial hepatectomy increased Evans blue leakage in hippocampus at day 1 and 3 postoperatively. Furthermore, surgery decreased the protein levels of claudin-5, ZO-1, and NF-kB p65 while upregulating the mRNA and protein levels of t-PA and MMP-9 in brain capillaries. All these effects caused by surgery were partially reversed by administering Ulinastatin. Our study sheds light on the roles of t-PA and MMP-9 of BBB in post-surgical neuroinflammation and postoperative cognitive dysfunction. Besides, it could also help to understand the mechanism of Ulinastatin alleviating neuroinflammation.
Subject(s)
Blood-Brain Barrier/drug effects , Glycoproteins/pharmacology , Matrix Metalloproteinase 9/metabolism , Tissue Plasminogen Activator/metabolism , Trypsin Inhibitors/pharmacology , Animals , Blood-Brain Barrier/metabolism , Claudin-5/metabolism , Hepatectomy/adverse effects , Hippocampus/drug effects , Hippocampus/metabolism , Inflammation/etiology , Inflammation/metabolism , Male , NF-kappa B/metabolism , Permeability/drug effects , Rats , Rats, Sprague-Dawley , Zonula Occludens-1 Protein/metabolismABSTRACT
Recent studies showed that pathology of alcoholic encephalopathy was associated with cerebral vascular damage. TMP (tetramethyl- pyrazine) is widely used in the treatment of cerebrovascular diseases, however, it has not been reported whether TMP can relieve alcohol-induced cerebral vascular damages. The study was performed to investigate the learning and memory, cerebrovascular pathological changes and the expressions of vascular endothelial growth factor (VEGF) and serum levelsofendothelin-1 (ET-1) in the rat model of chronic alcoholic encephalopathy, and explore the effects of TMP intervention on alcoholic encephalopathy. In the present study, the rat model of chronic alcoholic encephalopathy was established by the gavage administration of alcohol; the learning and memory ability was tested by Morris water maze; the expression of VEGF was measured by RT-PCR and Western blot; and the serum levels of ET-1 was measured by radioimmunoassay. We found that alcohol intoxication impaired learning and memory, induced VEGF overexpression and increased ET 1 concentrations. TMP intervention improved learning abilities, increased the VEGF expression and reduced ET-1 level. These results indicate that TMP exhibits therapeutic effects on chronic alcoholic encephalopathy.
Subject(s)
Alcohol-Induced Disorders, Nervous System/drug therapy , Cerebrovascular Circulation/drug effects , Pyrazines/therapeutic use , Vasodilator Agents/therapeutic use , Alcohol-Induced Disorders, Nervous System/complications , Alcohol-Induced Disorders, Nervous System/physiopathology , Animals , Disease Models, Animal , Endothelin-1/blood , Learning/drug effects , Male , Memory/drug effects , Pyrazines/pharmacology , Random Allocation , Rats , Rats, Wistar , Vascular Endothelial Growth Factor A/analysis , Vasodilator Agents/pharmacologyABSTRACT
BACKGROUND: Plants attenuate their responses to a variety of bacterial and fungal pathogens, leading to higher incidences of pathogen infection at night. However, little is known about the molecular mechanism responsible for the light-induced defence response; transcriptome data would likely facilitate the elucidation of this mechanism. RESULTS: In this study, we observed diurnal changes in tomato resistance to Pseudomonas syringae pv. tomato DC3000 (Pto DC3000), with the greatest susceptibility before midnight. Nightly light treatment, particularly red light treatment, significantly enhanced the resistance; this effect was correlated with increased salicylic acid (SA) accumulation and defence-related gene transcription. RNA-seq analysis revealed that red light induced a set of circadian rhythm-related genes involved in the phytochrome and SA-regulated resistance response. The biosynthesis and signalling pathways of multiple plant hormones (auxin, SA, jasmonate, and ethylene) were co-ordinately regulated following Pto DC3000 infection and red light, and the SA pathway was most significantly affected by red light and Pto DC3000 infection. This result indicates that SA-mediated signalling pathways are involved in red light-induced resistance to pathogens. Importantly, silencing of nonexpressor of pathogensis-related genes 1 (NPR1) partially compromised red light-induced resistance against Pto DC3000. Furthermore, sets of genes involved in redox homeostasis (respiratory burst oxidase homologue, RBOH; glutathione S-transferases, GSTs; glycosyltransferase, GTs), calcium (calmodulin, CAM; calmodulin-binding protein, CBP), and defence (polyphenol oxidase, PPO; nudix hydrolase1, NUDX1) as well as transcription factors (WRKY18, WRKY53, WRKY60, WRKY70) and cellulose synthase were differentially induced at the transcriptional level by red light in response to pathogen challenge. CONCLUSIONS: Taken together, our results suggest that there is a diurnal change in susceptibility to Pto DC3000 with greatest susceptibility in the evening. The red light induced-resistance to Pto DC3000 at night is associated with enhancement of the SA pathway, cellulose synthase, and reduced redox homeostasis.