Zika virus (ZIKV), a mosquito-borne flavivirus, has been associated with benign infections for decades. However, it has become a public health concern due to its association with severe fetal and neurological complica...Zika virus (ZIKV), a mosquito-borne flavivirus, has been associated with benign infections for decades. However, it has become a public health concern due to its association with severe fetal and neurological complications. Although many efforts have been made to control ZIKV infection, approved vaccines or antiviral drugs are still lacking. Consequently, the development of new effective anti-ZIKV agents is urgently needed. In this context, we investigated the antiviral potential of pyrazolone derivatives against ZIKV replication using in silico and in vitro methods. The four pyrazolone derivatives evaluated (1a, 1b, 1c, and 1d) inhibited over 50% of ZIKV replication with low cytotoxicity. Among them, compound 1b exhibited the most potent activity (EC50 = 4.3 μM) and the highest selectivity (SI = 342). Mechanism of action studies indicated that these compounds act at early stages of virus replication, and compound 1b can also directly inactivate ZIKV particles. Molecular docking studies suggested that these compounds can bind to and block the activity of ZIKV NS5 methyltransferase. Finally, pharmacokinetic and toxicological predictions have reinforced the safety and drug-like profiles of these derivatives. In conclusion, the pyrazolone scaffold proved to be valuable for anti-ZIKV drug development, and the derivatives studied deserve further investigation.展开更多
Our ability to learn and remember depends on the active formation,remodeling,and elimination of synapses.Thus,the development and growth of synapses as well as their weakening and elimination are essential for neurona...Our ability to learn and remember depends on the active formation,remodeling,and elimination of synapses.Thus,the development and growth of synapses as well as their weakening and elimination are essential for neuronal rewiring.The structural reorganization of synaptic complexes,changes in actin cytos keleton and organelle dynamics,as well as modulation of gene expression,determine synaptic plasticity.It has been proposed that dys regulation of these key synaptic homeostatic processes underlies the synaptic dysfunction observed in many neurodegenerative diseases.Much is known about downstream signaling of activated N-methyl-D-aspartate andα-amino-3-hydroxy-5-methyl-4-isoazolepro pionate receptors;howeve r,other signaling pathways can also contribute to synaptic plasticity and long-lasting changes in learning and memory.The non-receptor tyrosine kinase c-Abl(ABL1)is a key signal transducer of intra and extracellular signals,and it shuttles between the cyto plasm and the nucleus.This review focuses on c-Abl and its synaptic and neuronal functions.Here,we discuss the evidence showing that the activation of c-Abl can be detrimental to neurons,promoting the development of neurodegenerative diseases.Nevertheless,c-Abl activity seems to be in a pivotal balance between healthy synaptic plasticity,regulating dendritic spines remodeling and gene expression after cognitive training,and synaptic dysfunction and loss in neurodegenerative diseases.Thus,c-Abl genetic ablation not only improves learning and memory and modulates the brain genetic program of trained mice,but its absence provides dendritic spines resiliency against damage.Therefo re,the present review has been designed to elu cidate the common links between c-Abl regulation of structural changes that involve the actin cytos keleton and organelles dynamics,and the transc riptional program activated during synaptic plasticity.By summarizing the recent discove ries on c-Abl functions,we aim to provide an overview of how its inhibition co uld be a potentially fruitful treatment to improve degenerative outcomes and delay memory loss.展开更多
AIM: To study the effectiveness and mechanisms of anti-human vascular endothelial growth factor (hVEGF) hairpin ribozyme on angiogenesis,oncogenicity and tumor growth in a hepatocarcinoma cell line and a xenografted m...AIM: To study the effectiveness and mechanisms of anti-human vascular endothelial growth factor (hVEGF) hairpin ribozyme on angiogenesis,oncogenicity and tumor growth in a hepatocarcinoma cell line and a xenografted model. METHODS: The artificial anti-hVEGF hairpin ribozyme was transfected into hepatocarcinoma cell line SMMC-7721 and,subsequently,polymerase chain reaction (PCR) and reverse transcription polymerase chain reaction (RT-PCR) were performed to confirm the ribozyme gene integration and transcription. To determine the effects of ribozyme ,VEGF expression was detected by semiquantitative RT-PCR and enzyme liked immunosorbent assay (ELISA). MTT assay was carried out to measure the cell proliferation. Furthermore,the transfected and control cells were inoculated into nude mice respectively,the growth of cells in nude mice and angiogenesis were observed. RESULTS: VEGF expression was down-regulated sharply by ribozyme in transfected SMMC-7721 cells and xenografted tumor. Compared to the control group,the transfected cells grew slower in cell cultures and xenografts,and the xenograft formation was delayed as well. In addition,the microvessel density of the xenografted tumor was obviously declined in the transfected group. As demonstratedby microscopy,reduction of VEGF production induced by ribozyme resulted in a significantly higher cell differentiation and less proliferation vigor in xenografted tumor. CONCLUSION: Anti-hVEGF hairpin ribozyme can effectively inhibit VEGF expression and growth of hepatocarcinoma in vitro and in vivo. VEGF is functionally related to cell proliferation,differentiation and tumori-genesis in hepatocarcinoma.展开更多
Background:Rubiadin is a type of anthraquinone compound that can be found in Rubiaceae plants,such as Ronas.Nonetheless,only limited research has been done to explore the potential anticancer properties of rubiadin on...Background:Rubiadin is a type of anthraquinone compound that can be found in Rubiaceae plants,such as Ronas.Nonetheless,only limited research has been done to explore the potential anticancer properties of rubiadin on liver cancer cells.Thus,the objective of the present study is to examine how rubiadin affects the viability of liver cancer cells as well as normal cells.Methods:HepG2 and AGO cell lines were assigned into controls(not exposed to rubiadin)and groups with exposure to rubiadin with 12.5,6.25,3.125,1.56,0.78,and 0.39μg/mL concentrations.3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide and reverse transcription-polymerase chain reaction were used to measure cell viability,and one-way analysis of variance was used for data analysis.Results:The viability of liver cancer cells was significantly reduced when exposed to 12.5,6.25,3.125,and 1.56μg/mL concentrations(P<0.01).An IC50 of 44.73μg/mL was reported.Furthermore,the BAX gene’s relative expression(P<0.05)was significantly increased and the BCL2 gene expression(P<0.05)was significantly reduced.The average ratio of BAX gene expression to BCL2 increased significantly(P<0.01).Conclusion:This research showed that rubiadin decreases cell viability by increasing the ratio of BAX gene expression to BCL2.In addition rubiadin has no cytotoxic effect on normal cells.展开更多
Introduction: Canine mammary gland tumor is the most common type of neoplasia in non-ovariectomized bitches. Approximately 50% of tumors are malignant. Neoplasms originating from the mammary gland represent the most c...Introduction: Canine mammary gland tumor is the most common type of neoplasia in non-ovariectomized bitches. Approximately 50% of tumors are malignant. Neoplasms originating from the mammary gland represent the most common neoplastic disease in canines in Veterinary Medicine. Aim: Relate the expression of the receptor to progesterone (PR) with the tumor stage of canine mammary carcinoma. Material and Methods: Analytical-cross-sectional study, samples of paraffinized tumor tissue obtained from 30 canine patients with breast cancer were used. The expression of PR was performed by immunohistochemical labeling, using murine anti-PR (anti-PR Biocare brand). A descriptive analysis was carried out with the results using the SPSS program. Results: The predominant histological subtype of breast cancer was tubular carcinoma with 12 patients, followed by papillary cystic carcinoma with 6 patients, solid carcinoma 5, carcinosarcoma 4 and comedocarcinoma 3. There was a significant trend between breast cancer subtypes, histological grade G1. Among the histopathological findings, the degree of invasion is related to the presence of tumor cells in adjacent lymph nodes, which is why it is a prognostic indicator. The expression of PR in the tumor tissue samples it was 42.8% positive versus 57.14% negative, of which 75% correspond to G1, 8.3% to G2 and 16.6% to G3. With respect to the relationship of the expression of PR vs type of tumor, it was found that 50% correspond to tubular carcinoma, 33.3% to papillary cystic carcinoma, 8.3% to solid carcinoma and 8.3% to comedocarcinoma. Conclusion: The hormone receptor was negative in more than half of the patients and histological grade is significantly associated with tumor subtypes, this study emphasizes the need to introduce receptor testing into our routine clinical practice to offer the best treatment for breast cancer.展开更多
Inflammatory bowel diseases(IBDs), including Crohn's disease and ulcerative colitis are complex disorders with undetermined etiology. Several hypotheses suggest that IBDs result from an abnormal immune response ag...Inflammatory bowel diseases(IBDs), including Crohn's disease and ulcerative colitis are complex disorders with undetermined etiology. Several hypotheses suggest that IBDs result from an abnormal immune response against endogenous flora and luminal antigens in genetically susceptible individuals. The dysfunction of the mucosal immune response is implicated in the pathogenesis of IBD. The balance between pro-inflammatory cytokines [tumor necrosis factor(TNF)-α, interleukin(IL)-1b, IL-8, and IL-17A], anti-inflammatory cytokines(IL-4 and IL-13), and immunoregulatory cytokines(IL-10 and transforming growth factors b) is disturbed. Moreover, evidence from animal and clinical studies demonstrate a positive correlation between an increased concentration of nitric oxide(NO) and the severity of the disease. Interestingly, proinflammatory cytokines are involved in the up-regulation of inducible oxide synthase(iN OS) expression in IBD. However, anti-inflammatory and immunoregulatory cytokines are responsible for the negative regulation of iN OS. A positive correlation between NO production and increased pro-inflammatory cytokine levels(TNF-α, IL-6, IL-17, IL-12, and interferon-γ) were reported in patients with IBD. This review focuses on the role of cytokines in intestinal inflammation and their relationship with NO in IBD.展开更多
Respiratory diseases,including coronavirus disease 2019 and chronic obstructive pulmonary disease(COPD),are leading causes of global fatality.There are no effective and curative treatments,but supportive care only.Cel...Respiratory diseases,including coronavirus disease 2019 and chronic obstructive pulmonary disease(COPD),are leading causes of global fatality.There are no effective and curative treatments,but supportive care only.Cell therapy is a promising therapeutic strategy for refractory and unmanageable pulmonary illnesses,as proved by accumulating preclinical studies.Stem cells consist of totipotent,pluripotent,multipotent,and unipotent cells with the potential to differentiate into cell types requested for repair.Mesenchymal stromal cells,endothelial progenitor cells,peripheral blood stem cells,and lung progenitor cells have been applied to clinical trials.To date,the safety and feasibility of stem cell and extracellular vesicles administration have been confirmed by numerous phase I/II trials in patients with COPD,acute respiratory distress syndrome,bronchial dysplasia,idiopathic pulmonary fibrosis,pulmonary artery hypertension,and silicosis.Five routes and a series of doses have been tested for tolerance and advantages of different regimes.In this review,we systematically summarize the global trends for the cell therapy of common airway and lung diseases registered for clinical trials.The future directions for both new clinical trials and preclinical studies are discussed.展开更多
Objective: To investigate the protective effects of Aristolochia longa (A. longa) and Aquilaria malaccensis (A. malaccensis) on acute hepatotoxicity induced by lead in female albino rats. Methods: Twenty five (25) app...Objective: To investigate the protective effects of Aristolochia longa (A. longa) and Aquilaria malaccensis (A. malaccensis) on acute hepatotoxicity induced by lead in female albino rats. Methods: Twenty five (25) apparently healthy female Wistar rats were randomly divided into five groups of five rats in each: control, Pb, Pb + A. longa (Ar), Pb+ A. malaccensis (Aq), and Pb+ A. longa (Ar) + A. malaccensis (Aq) lead (100 mg/kg b.w.) as Pb (C2H3O2)2 added in their drinking water for 75 days. A. longa (rhizome powder at a dose of 10 g/kg of diet ) and A. malaccensis (heartwood powder at a dose 10 g/kg of diet) were added to the feed during the last 15 days of lead exposed in the animals. Results: Obtained results revealed that lead treatment caused a significant increase in serum GOT, GPT and ALP activities and in liver of MDA level and CAT activity. In contrast, it led to an decrease in the liver GOT, GPT and GST activities and in GSH level in rats. Also, the results clearly showed that lead causes alterations of hepatic tissue in comparison with controls. Our results showed that treatment with A. malaccensis and A. longa a partial correction of the previous parameters. The histological observations confirmed the hepatoprotection results by the biochemical parameters. Conclusions: Results demonstrated beneficial effects of A. longa and A. malaccensis treatment in Pb-induced oxidative stress and tissue damage in liver.展开更多
Objective:To determine the effects of routine iron supplementation on oxidative stress markers in pregnant women.Methods:This study enrolled 122 pregnant women aged between 20-38 years throughout three stages of pregn...Objective:To determine the effects of routine iron supplementation on oxidative stress markers in pregnant women.Methods:This study enrolled 122 pregnant women aged between 20-38 years throughout three stages of pregnancy:beginning with pregnancy,until the twentieth week and up to the thirtieth week.They were divided into two groups:61 pregnant women not supplemented with iron(the control group),and 61 pregnant women supplemented with iron(the iron group).Blood samples were collected and protein,iron,uric acid,total bilirubin level and oxidative stress status were estimated using molecular spectrophotometric method.Copper levels were estimated by using atomic absorption spectroscopy method.Results:Iron,protein and copper concentrations were significantly increased(P<0.05)at 20 and 30 weeks of pregnancy and hemoglobin level was significantly increased(P<0.05)at the beginning of pregnancy and until 20 weeks in the iron group compared to the control group.In addition,levels of serum uric acid,serum total bilirubin and malondialdehyde in serum and erythrocytes were significantly increased at 20 and 30 weeks of pregnancy whereas the reduced glutathione level was significantly decreased in serum(30 weeks of pregnancy)and erythrocytes(20 and 30 weeks of pregnancy)in the iron group as compared to the control group.Serum oxygen radical absorbance capacity was not significantly changed.There was a significant positive correlation between serum iron level and serum copper,malondialdehyde level in serum and erythrocytes in pregnant women supplemented with iron.Conclusions:Iron supplement at 20 and 30 weeks of pregnancy plays a role in the development of oxidative stress which is the origin of several maternal-fetal complications.展开更多
The aim of this study was to estimate the seroprevalence of immunoglobulin M(IgM)and G(IgG)antibodies against SARS-CoV-2 in asymptomatic people in Wuhan.This was a cross-sectional study,which enrolled 18,712 asymptoma...The aim of this study was to estimate the seroprevalence of immunoglobulin M(IgM)and G(IgG)antibodies against SARS-CoV-2 in asymptomatic people in Wuhan.This was a cross-sectional study,which enrolled 18,712 asymptomatic participants from 154 work units in Wuhan.Pearson Chi-square test,t-test,and Mann-Whitney test were used to compare the standardized seroprevalence of IgG and IgM for age and gender between different groups.展开更多
Objective:Currently,only a limited numbers of tumor markers for non small lung cancer(NSCLC) diagnosis,new biomarker,such as serum autoantibodies may improve the early detection of lung cancer.Our objective is constru...Objective:Currently,only a limited numbers of tumor markers for non small lung cancer(NSCLC) diagnosis,new biomarker,such as serum autoantibodies may improve the early detection of lung cancer.Our objective is construction human lung squamous carcinoma and adenocarcinoma T7 phage display cDNA library from the tissues of NSCLC patients.Methods:mRNA was isolated from a pool of total RNA extract from NSCLC tissues obtained from 5 adenocarcinomas and 5 squamous carcinomas,and then mRNA was reverse transcribed into double stranded cDNA.After digestion,the cDNA was inserted into T7Select 10-3 vector.The phage display cDNA library was constructed by package reaction in vitro and plate proliferation.Plaque assay and PCR were used to evaluate the library.Results:Two T7 phage display cDNA library were established.Plaque assay show the titer of lung squamas carcinoma library was 1.8 × 106 pfu,and the adenocarcinoma library was 5 × 106 pfu.The phage titer of the amplified library were 3.2 × 1010 pfu/mL and 2.5 × 1010 pfu/mL.PCR amplifica-tion of random plaque show insert ratio were 100%(24/24) in adenocarcinoma library and 95.8% in human lung squamas carcinoma library(23/24).Insert range from 300 bp to 1 500 bp.Conclusion:Two phage display cDNA library from NSCLC were constructed.展开更多
Echinococcosis is a global and zoonotic helminthic disease caused by Echinococcus sp. A 24-year-old woman, coming from Bolivia two years before, was diagnosed as cystic echinococcosis (CE) by unstained wet mount and c...Echinococcosis is a global and zoonotic helminthic disease caused by Echinococcus sp. A 24-year-old woman, coming from Bolivia two years before, was diagnosed as cystic echinococcosis (CE) by unstained wet mount and cytological findings through aspiration cytology from the liver, suggested as liver abscess by diagnostic images. The patient was classified as CE1, smaller than 5 cm, and was diagnosed as P1N0M0, stage I. The phylogenetic trees of Echinococcus spp., based on cox1 genes showed that the isolates on the patient belonged to E. ortleppi. The patient was conservatively treated with two courses of albendazole therapy. E. ortleppi has been reported to be in regions including Latin America, except with Japan. Although the patient came from Bolivia before two years, this is the first case report of E. ortleppi from liver echinococcosis in Japan.展开更多
Objective: To evaluate the acute toxicity effect of metribuzin at low dose on liver of mother rabbits and its fetus.Methods: Pregnant female rabbitsOryctolagus cuniculus were divided into three groups (n=5). The first...Objective: To evaluate the acute toxicity effect of metribuzin at low dose on liver of mother rabbits and its fetus.Methods: Pregnant female rabbitsOryctolagus cuniculus were divided into three groups (n=5). The first group of non-treated pregnancy rabbits served as control;the second group of pregnancy rabbits were treated with 1/100 LD50 of metribuzin and the third group of pregnancy rabbits were treated with 1/50 LD50 of metribuzin. Metribuzin was added in their drinking water for 60 d before and during pregnancy. Levels of liver malondialdehyde, liver glutathione S transferase, serum glutamic oxaloacetic transaminase and serum glutamic-pyruvic transaminase were determined. Liver reduced glutathione level was also determined by a colorimetric method. And hepatic homogenate was analyzed by HPLC analysis to determine the existence of traces of metribuzin.Results: Results revealed a significant increase in level of liver malondialdehyde, glutathione S transferase, serum glutamic oxalacetic transaminase and serum glutamic-pyruvic transaminase activities in mother and fetuses rabbits of both metribuzin treatment groups as compared to the control group. However the level of reduced glutathione was decreased in mother and fetuses rabbits of both groups treated with metribuzin compared to control group. Also, the results obtained by HPLC technique showed the presence of trace metribuzin in liver cells of mothers and fetuses rabbits of the both metribuzin treated groups.Conclusions: In conclusion, this study shows that exposure to metribuzin at low concentrations causes a acute toxicity in liver of mother rabbits and its fetus, also the trace of the metribuzin detected in the liver is the origin of possible malformation of the fetuses or abortion of the rabbits.展开更多
The sieving and enrichment of rare tumor cells from large-volume pleural effusion(PE)samples is a promising technique for cell-based lung tumor diagnosis and drug tests,which features high throughput and recovery,puri...The sieving and enrichment of rare tumor cells from large-volume pleural effusion(PE)samples is a promising technique for cell-based lung tumor diagnosis and drug tests,which features high throughput and recovery,purification,as well as viability rates of rare target cells as the prerequisites for high sensitivity,specificity,and accuracy of tumor cell analysis.In this paper,we propose a three-dimensional(3 D)sieving method for rare tumor cell enrichment,which effectively eliminates the"dead zones"in traditional two-dimensional(2 D)cell filters with a dimension-raising strategy to satisfy the requirements mentioned above.The prototype device was combined with a funnel-shaped holder,a flexible micropore membrane in the middle,and a3 D spiral fluid channel covered on the membrane as a three-layer ice-creaming cone composite structure.Driven by gravity alone,the device performed as follows:(1)20-fold throughput compared with the 2 D commercial planee hich was up to 20 mL/min for a threefold dilution of whole blood sample;(2)high recovery rates of 84.5%±21%,86%±25%,83%±14%for 100,1000,and 10000 cells/mL,respectively,in 30 mL phosphate buffer saline(PBS)sample,and a 100%positive detection rate in the case of≤5 A549 cells in 1 mL PBS;(3)a typical purification rate of 85.5%±9.1%;and(4)a viability rate of>93%.In the demonstration application,this device effectively enriched rare target cells from large volumes(>25 mL)of clinical pleural effusions.The following results indicated that tumor cells were easy-to-discover in the enriched PE samples,and the proliferation capability of purified cells was(>4.6 times)significantly stronger than that of unprocessed cells in the subsequent 6-day culture.The above evaluation indicates that the proposed easily reproducible method for the effective execution of rare cell enrichments and assays is expected to become a practical technique for clinical cell-based tumor diagnosis.展开更多
Interspecific and intergeneric hybridizations have been widely used in plant genetics and breeding to construct stocks for genetic analysis and to introduce into crops the desirable traits and genes from their relativ...Interspecific and intergeneric hybridizations have been widely used in plant genetics and breeding to construct stocks for genetic analysis and to introduce into crops the desirable traits and genes from their relatives. The intergeneric crosses between Brassica juncea (L.) Czern. & Coss., B. carinata A. Braun and Orychophragmus violaceus (L.) O. E. Schulz were made and the plants produced were subjected to genomic in situ hybridization analysis. The mixoploids from the cross with B. juncea were divided into three groups. The partially fertile mixoploids in the first group (2n = 36—42) mainly contained the somatic cells and pollen mother cells (PMCs) with the 36 chromosomes of B. juncea and additional chromosomes of O. violaceus. The mixoploids (2n = 30—36) in the second and third groups were morphologically quite similar to the mother plants B. juncea and showed nearly normal fertility. The plants in the second group produced the majority of PMCs (2n = 36) with their chromosomes paired and segregated normally, but 1—4 pairs of the O. violaceus chromosomes were included in some PMCs. The plants in the third group produced only PMCs with the 36 B. juncea chromosomes, which were paired and segregated normally. The mixoploids (2n = 29—34) from the cross with B. carinata produced the majority of PMCs (2n = 34) with normal chromosome pairing and segregation, but some plants had some PMCs with 1—3 pairs of chromosomes from O. violaceus and other plants had only PMCs with the B. carinata chromosomes. The Brassica homozygous plants and aneuploids with complete or partial chromo-some complements of Brassica parents and various numbers of O. violaceus chromosomes were derived from these progeny plants. The results in this study provided the molecular cytogenetic evidence for the separation of parental genomes which was previously proposed to occur in the hybridizations of these two genera.展开更多
Various epidemiological studies have shown an inverse association between the consumption of polyphenols or polyphenol-rich foods and the risk of cardiovascular diseases. The purpose of the study was to emphasize the ...Various epidemiological studies have shown an inverse association between the consumption of polyphenols or polyphenol-rich foods and the risk of cardiovascular diseases. The purpose of the study was to emphasize the effects of the association between the renin inhibitor and the polyphenolic extract on biochemical parameters and systolic and diastolic blood pressure. The polyphenols are extracted from isolated and purified vegetable material represented by the mature fruit of the Aronia melanocarpa. The experiment was performed on the arterial hypertension model. In the arterial hypertensive model the cardioprotective effects of the polyphenolic extract from Aronia melanocarpa are represented by the antioxidant, hypocolesterolemiant intervention. Polyphenolic extract from Aronia melanocarpa reduce systolic and diastolic arterial tension values in rats with drug-induced hypertension, a phenomenon more pronounced when polyphenols are associated with Aliskiren (renin inhibitor). The combination between the Aliskiren and polyphenolic extract produce superior hypolipidemic and antioxidant effects than in the case of separate administration within experimental arterial hypertension induced in the murine model.展开更多
With advancements in gene editing technologies,our ability to make precise and efficient modifications to the genome is increasing at a remarkable rate,paving the way for scientists and clinicians to uniquely treat a ...With advancements in gene editing technologies,our ability to make precise and efficient modifications to the genome is increasing at a remarkable rate,paving the way for scientists and clinicians to uniquely treat a multitude of previously irremediable diseases.CRISPR-Cas9,short for clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9,is a gene editing platform with the ability to alter the nucleotide sequence of the genome in living cells.This technology is increasing the number and pace at which new gene editing treatments for genetic disorders are moving toward the clinic.Theβ-hemoglobinopathies are a group of monogenic diseases,which despite their high prevalence and chronic debilitating nature,continue to have few therapeutic options available.In this review,we will discuss our existing comprehension of the genetics and current state of treatment forβ-hemoglobinopathies,consider potential genome editing therapeutic strategies,and provide an overview of the current state of clinical trials using CRISPR-Cas9 gene editing.展开更多
Objective：To focus on the asthmatic pathogenesis and clinical manifestations related to epithelial sodium channel （ENaC）/chlorine ion channel.Data Sources：The data analyzed in this review were the English articles...Objective：To focus on the asthmatic pathogenesis and clinical manifestations related to epithelial sodium channel （ENaC）/chlorine ion channel.Data Sources：The data analyzed in this review were the English articles from 1980 to 2015 from journal databases,primarily PubMed and Google Scholar.The terms used in the literature search were：（1） ENaCs;cystic fibrosis （CF） transmembrane conductance regulator （CFTR）;asthma/asthmatic,（2） ENaC/sodium salt;CF;asthma/asthmatic,（3） CFTR/chlorine ion channels;asthma/asthmatic,（4） ENaC/sodium channel/scnn1a/scnn1b/scnn1g/scnn1d/amiloride-sensitive/amiloride-inhibtable sodium channels/sodium salt;asthma/asthmatic,lung/pulmonary/respiratory/tracheal/alveolar,and （5） CFTR;CF;asthma/asthmatic （ti）.Study Selection：These studies included randomized controlled trials or studies covering asthma pathogenesis and clinical manifestations related to ENaC/chlorine ion channels within the last 25 years （from 1990 to 2015）.The data involving chronic obstructive pulmonary disease and CF obtained from individual studies were also reviewed by the authors.Results：Airway surface liquid dehydration can cause airway inflammation and obstruction.ENaC and CFTR are closely related to the airway mucociliary clearance.Ion transporters may play a critical role in pathogenesis of asthmatic exacerbations.Conclusions：Ion channels have been the center of many studies aiming to understand asthmatic pathophysiological mechanisms or to identify therapeutic targets for better control of the disease.展开更多
Dear Editor,The DNA-dependent protein kinase catalytic subunit(DNA-PKcs)forms a serine/threonine protein kinase complex with the Ku heterodimer(Ku70/Ku80)and plays an important role in the DNA damage response(DDR)and ...Dear Editor,The DNA-dependent protein kinase catalytic subunit(DNA-PKcs)forms a serine/threonine protein kinase complex with the Ku heterodimer(Ku70/Ku80)and plays an important role in the DNA damage response(DDR)and maintenance of genomic stability through nonhomologous end joining(NHEJ),wherein the Ku heterodimer recognizes and binds broken DNA ends,facilitating the recruitment and activation of DNA-PKcs.1 Activated DNA-PKcs phosphorylates and alters the function of factors that mediate NHEJ,including DNA-PKcs itself.2 In addition,DDR-independent roles of DNA-PKcs have been demonstrated.3 Studies further identified DNA-PKcs as a modulator of cancer-associated pathways distinct from DNA repair,including hypoxia,metabolism,the inflammatory response,and transcriptional regulation.展开更多
Metabolomics is the last frontier of modern molecular biology,and the state-of-the-art technique for studying metabolism.Mass spectrometry and nuclear magnetic resonance spectroscopy are the main analytical approaches...Metabolomics is the last frontier of modern molecular biology,and the state-of-the-art technique for studying metabolism.Mass spectrometry and nuclear magnetic resonance spectroscopy are the main analytical approaches in metabolomics.Cellular metabolism plays a pivotal role during cell resting and activation.Immune cells exhibit remarkable metabolic plasticity,fundamental to support their adaptation to inflammatory environments and functional requirements.Cancer is a metabolic and inflammatory disease.A metabolic shift is crucial for oncogenesis,tumor cell survival,invasion,metastasis,and the associated inflammatory process.The tumor microenvironment is mainly orchestrated by immune-inflammatory cells and essential for the neoplastic process.Inflammatory cells from tumor stroma adapt to different metabolic pathways during tumor progression,and this metabolic reprogramming affects macrophages,neutrophils,T cells,and others.Targeting the metabolism of tumor and immune cells may lead to important therapeutic implications in cancer.Thus,understanding the metabolic changes that drive the interactions between tumor and stromal cells is a promising avenue advances in cancer diagnostics and therapies,leading to more accurate guidance.In this review,we discuss the most recent metabolomics approaches in cancer studies on the tumor-associated inflammatory microenvironment.展开更多
文摘Zika virus (ZIKV), a mosquito-borne flavivirus, has been associated with benign infections for decades. However, it has become a public health concern due to its association with severe fetal and neurological complications. Although many efforts have been made to control ZIKV infection, approved vaccines or antiviral drugs are still lacking. Consequently, the development of new effective anti-ZIKV agents is urgently needed. In this context, we investigated the antiviral potential of pyrazolone derivatives against ZIKV replication using in silico and in vitro methods. The four pyrazolone derivatives evaluated (1a, 1b, 1c, and 1d) inhibited over 50% of ZIKV replication with low cytotoxicity. Among them, compound 1b exhibited the most potent activity (EC50 = 4.3 μM) and the highest selectivity (SI = 342). Mechanism of action studies indicated that these compounds act at early stages of virus replication, and compound 1b can also directly inactivate ZIKV particles. Molecular docking studies suggested that these compounds can bind to and block the activity of ZIKV NS5 methyltransferase. Finally, pharmacokinetic and toxicological predictions have reinforced the safety and drug-like profiles of these derivatives. In conclusion, the pyrazolone scaffold proved to be valuable for anti-ZIKV drug development, and the derivatives studied deserve further investigation.
基金supported by Comisión Nacional de Investigación Cientifica y Tecnologica-Chile Fondecyt 12011668(to ARA)Fondecyt 1190334(to SZ)+6 种基金Fondecyt 11200592(to MJY)Fondef ID21/10347(to ARA andSZ)Fondef D10E1077(to ARA and SZ)CARE-UCAFB 170005(to ARA)MSCA-RISE-2016-Lysomod-734825 European Union's Horizon 2020Research and Innovation Program under the Marie Sklodowska-Curie grant agreement N°953489(to SZ)Millennium Science Initiative Program-ICN09_016/ICN 2021_045(to ARA)。
文摘Our ability to learn and remember depends on the active formation,remodeling,and elimination of synapses.Thus,the development and growth of synapses as well as their weakening and elimination are essential for neuronal rewiring.The structural reorganization of synaptic complexes,changes in actin cytos keleton and organelle dynamics,as well as modulation of gene expression,determine synaptic plasticity.It has been proposed that dys regulation of these key synaptic homeostatic processes underlies the synaptic dysfunction observed in many neurodegenerative diseases.Much is known about downstream signaling of activated N-methyl-D-aspartate andα-amino-3-hydroxy-5-methyl-4-isoazolepro pionate receptors;howeve r,other signaling pathways can also contribute to synaptic plasticity and long-lasting changes in learning and memory.The non-receptor tyrosine kinase c-Abl(ABL1)is a key signal transducer of intra and extracellular signals,and it shuttles between the cyto plasm and the nucleus.This review focuses on c-Abl and its synaptic and neuronal functions.Here,we discuss the evidence showing that the activation of c-Abl can be detrimental to neurons,promoting the development of neurodegenerative diseases.Nevertheless,c-Abl activity seems to be in a pivotal balance between healthy synaptic plasticity,regulating dendritic spines remodeling and gene expression after cognitive training,and synaptic dysfunction and loss in neurodegenerative diseases.Thus,c-Abl genetic ablation not only improves learning and memory and modulates the brain genetic program of trained mice,but its absence provides dendritic spines resiliency against damage.Therefo re,the present review has been designed to elu cidate the common links between c-Abl regulation of structural changes that involve the actin cytos keleton and organelles dynamics,and the transc riptional program activated during synaptic plasticity.By summarizing the recent discove ries on c-Abl functions,we aim to provide an overview of how its inhibition co uld be a potentially fruitful treatment to improve degenerative outcomes and delay memory loss.
基金Supported by the Grant from Calling for Tenders by Key Subject of Jiangsu Province, No. WK200221
文摘AIM: To study the effectiveness and mechanisms of anti-human vascular endothelial growth factor (hVEGF) hairpin ribozyme on angiogenesis,oncogenicity and tumor growth in a hepatocarcinoma cell line and a xenografted model. METHODS: The artificial anti-hVEGF hairpin ribozyme was transfected into hepatocarcinoma cell line SMMC-7721 and,subsequently,polymerase chain reaction (PCR) and reverse transcription polymerase chain reaction (RT-PCR) were performed to confirm the ribozyme gene integration and transcription. To determine the effects of ribozyme ,VEGF expression was detected by semiquantitative RT-PCR and enzyme liked immunosorbent assay (ELISA). MTT assay was carried out to measure the cell proliferation. Furthermore,the transfected and control cells were inoculated into nude mice respectively,the growth of cells in nude mice and angiogenesis were observed. RESULTS: VEGF expression was down-regulated sharply by ribozyme in transfected SMMC-7721 cells and xenografted tumor. Compared to the control group,the transfected cells grew slower in cell cultures and xenografts,and the xenograft formation was delayed as well. In addition,the microvessel density of the xenografted tumor was obviously declined in the transfected group. As demonstratedby microscopy,reduction of VEGF production induced by ribozyme resulted in a significantly higher cell differentiation and less proliferation vigor in xenografted tumor. CONCLUSION: Anti-hVEGF hairpin ribozyme can effectively inhibit VEGF expression and growth of hepatocarcinoma in vitro and in vivo. VEGF is functionally related to cell proliferation,differentiation and tumori-genesis in hepatocarcinoma.
文摘Background:Rubiadin is a type of anthraquinone compound that can be found in Rubiaceae plants,such as Ronas.Nonetheless,only limited research has been done to explore the potential anticancer properties of rubiadin on liver cancer cells.Thus,the objective of the present study is to examine how rubiadin affects the viability of liver cancer cells as well as normal cells.Methods:HepG2 and AGO cell lines were assigned into controls(not exposed to rubiadin)and groups with exposure to rubiadin with 12.5,6.25,3.125,1.56,0.78,and 0.39μg/mL concentrations.3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide and reverse transcription-polymerase chain reaction were used to measure cell viability,and one-way analysis of variance was used for data analysis.Results:The viability of liver cancer cells was significantly reduced when exposed to 12.5,6.25,3.125,and 1.56μg/mL concentrations(P<0.01).An IC50 of 44.73μg/mL was reported.Furthermore,the BAX gene’s relative expression(P<0.05)was significantly increased and the BCL2 gene expression(P<0.05)was significantly reduced.The average ratio of BAX gene expression to BCL2 increased significantly(P<0.01).Conclusion:This research showed that rubiadin decreases cell viability by increasing the ratio of BAX gene expression to BCL2.In addition rubiadin has no cytotoxic effect on normal cells.
文摘Introduction: Canine mammary gland tumor is the most common type of neoplasia in non-ovariectomized bitches. Approximately 50% of tumors are malignant. Neoplasms originating from the mammary gland represent the most common neoplastic disease in canines in Veterinary Medicine. Aim: Relate the expression of the receptor to progesterone (PR) with the tumor stage of canine mammary carcinoma. Material and Methods: Analytical-cross-sectional study, samples of paraffinized tumor tissue obtained from 30 canine patients with breast cancer were used. The expression of PR was performed by immunohistochemical labeling, using murine anti-PR (anti-PR Biocare brand). A descriptive analysis was carried out with the results using the SPSS program. Results: The predominant histological subtype of breast cancer was tubular carcinoma with 12 patients, followed by papillary cystic carcinoma with 6 patients, solid carcinoma 5, carcinosarcoma 4 and comedocarcinoma 3. There was a significant trend between breast cancer subtypes, histological grade G1. Among the histopathological findings, the degree of invasion is related to the presence of tumor cells in adjacent lymph nodes, which is why it is a prognostic indicator. The expression of PR in the tumor tissue samples it was 42.8% positive versus 57.14% negative, of which 75% correspond to G1, 8.3% to G2 and 16.6% to G3. With respect to the relationship of the expression of PR vs type of tumor, it was found that 50% correspond to tubular carcinoma, 33.3% to papillary cystic carcinoma, 8.3% to solid carcinoma and 8.3% to comedocarcinoma. Conclusion: The hormone receptor was negative in more than half of the patients and histological grade is significantly associated with tumor subtypes, this study emphasizes the need to introduce receptor testing into our routine clinical practice to offer the best treatment for breast cancer.
文摘Inflammatory bowel diseases(IBDs), including Crohn's disease and ulcerative colitis are complex disorders with undetermined etiology. Several hypotheses suggest that IBDs result from an abnormal immune response against endogenous flora and luminal antigens in genetically susceptible individuals. The dysfunction of the mucosal immune response is implicated in the pathogenesis of IBD. The balance between pro-inflammatory cytokines [tumor necrosis factor(TNF)-α, interleukin(IL)-1b, IL-8, and IL-17A], anti-inflammatory cytokines(IL-4 and IL-13), and immunoregulatory cytokines(IL-10 and transforming growth factors b) is disturbed. Moreover, evidence from animal and clinical studies demonstrate a positive correlation between an increased concentration of nitric oxide(NO) and the severity of the disease. Interestingly, proinflammatory cytokines are involved in the up-regulation of inducible oxide synthase(iN OS) expression in IBD. However, anti-inflammatory and immunoregulatory cytokines are responsible for the negative regulation of iN OS. A positive correlation between NO production and increased pro-inflammatory cytokine levels(TNF-α, IL-6, IL-17, IL-12, and interferon-γ) were reported in patients with IBD. This review focuses on the role of cytokines in intestinal inflammation and their relationship with NO in IBD.
文摘Respiratory diseases,including coronavirus disease 2019 and chronic obstructive pulmonary disease(COPD),are leading causes of global fatality.There are no effective and curative treatments,but supportive care only.Cell therapy is a promising therapeutic strategy for refractory and unmanageable pulmonary illnesses,as proved by accumulating preclinical studies.Stem cells consist of totipotent,pluripotent,multipotent,and unipotent cells with the potential to differentiate into cell types requested for repair.Mesenchymal stromal cells,endothelial progenitor cells,peripheral blood stem cells,and lung progenitor cells have been applied to clinical trials.To date,the safety and feasibility of stem cell and extracellular vesicles administration have been confirmed by numerous phase I/II trials in patients with COPD,acute respiratory distress syndrome,bronchial dysplasia,idiopathic pulmonary fibrosis,pulmonary artery hypertension,and silicosis.Five routes and a series of doses have been tested for tolerance and advantages of different regimes.In this review,we systematically summarize the global trends for the cell therapy of common airway and lung diseases registered for clinical trials.The future directions for both new clinical trials and preclinical studies are discussed.
文摘Objective: To investigate the protective effects of Aristolochia longa (A. longa) and Aquilaria malaccensis (A. malaccensis) on acute hepatotoxicity induced by lead in female albino rats. Methods: Twenty five (25) apparently healthy female Wistar rats were randomly divided into five groups of five rats in each: control, Pb, Pb + A. longa (Ar), Pb+ A. malaccensis (Aq), and Pb+ A. longa (Ar) + A. malaccensis (Aq) lead (100 mg/kg b.w.) as Pb (C2H3O2)2 added in their drinking water for 75 days. A. longa (rhizome powder at a dose of 10 g/kg of diet ) and A. malaccensis (heartwood powder at a dose 10 g/kg of diet) were added to the feed during the last 15 days of lead exposed in the animals. Results: Obtained results revealed that lead treatment caused a significant increase in serum GOT, GPT and ALP activities and in liver of MDA level and CAT activity. In contrast, it led to an decrease in the liver GOT, GPT and GST activities and in GSH level in rats. Also, the results clearly showed that lead causes alterations of hepatic tissue in comparison with controls. Our results showed that treatment with A. malaccensis and A. longa a partial correction of the previous parameters. The histological observations confirmed the hepatoprotection results by the biochemical parameters. Conclusions: Results demonstrated beneficial effects of A. longa and A. malaccensis treatment in Pb-induced oxidative stress and tissue damage in liver.
基金the research project funded by the ministry of higher education,Algeria and by Directorate general for Scientific Research and Technological Development(Grant D01N01UN390120190001).
文摘Objective:To determine the effects of routine iron supplementation on oxidative stress markers in pregnant women.Methods:This study enrolled 122 pregnant women aged between 20-38 years throughout three stages of pregnancy:beginning with pregnancy,until the twentieth week and up to the thirtieth week.They were divided into two groups:61 pregnant women not supplemented with iron(the control group),and 61 pregnant women supplemented with iron(the iron group).Blood samples were collected and protein,iron,uric acid,total bilirubin level and oxidative stress status were estimated using molecular spectrophotometric method.Copper levels were estimated by using atomic absorption spectroscopy method.Results:Iron,protein and copper concentrations were significantly increased(P<0.05)at 20 and 30 weeks of pregnancy and hemoglobin level was significantly increased(P<0.05)at the beginning of pregnancy and until 20 weeks in the iron group compared to the control group.In addition,levels of serum uric acid,serum total bilirubin and malondialdehyde in serum and erythrocytes were significantly increased at 20 and 30 weeks of pregnancy whereas the reduced glutathione level was significantly decreased in serum(30 weeks of pregnancy)and erythrocytes(20 and 30 weeks of pregnancy)in the iron group as compared to the control group.Serum oxygen radical absorbance capacity was not significantly changed.There was a significant positive correlation between serum iron level and serum copper,malondialdehyde level in serum and erythrocytes in pregnant women supplemented with iron.Conclusions:Iron supplement at 20 and 30 weeks of pregnancy plays a role in the development of oxidative stress which is the origin of several maternal-fetal complications.
基金supported by Advisory Research Project of the Chinese Academy of Engineering in 2019[2019-XZ-70]。
文摘The aim of this study was to estimate the seroprevalence of immunoglobulin M(IgM)and G(IgG)antibodies against SARS-CoV-2 in asymptomatic people in Wuhan.This was a cross-sectional study,which enrolled 18,712 asymptomatic participants from 154 work units in Wuhan.Pearson Chi-square test,t-test,and Mann-Whitney test were used to compare the standardized seroprevalence of IgG and IgM for age and gender between different groups.
基金Supported by the grants of Beijing Novel Program (No.2006B34)Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry and Beijing Research Foundation for Excellent Talents (No.20061D03)
文摘Objective:Currently,only a limited numbers of tumor markers for non small lung cancer(NSCLC) diagnosis,new biomarker,such as serum autoantibodies may improve the early detection of lung cancer.Our objective is construction human lung squamous carcinoma and adenocarcinoma T7 phage display cDNA library from the tissues of NSCLC patients.Methods:mRNA was isolated from a pool of total RNA extract from NSCLC tissues obtained from 5 adenocarcinomas and 5 squamous carcinomas,and then mRNA was reverse transcribed into double stranded cDNA.After digestion,the cDNA was inserted into T7Select 10-3 vector.The phage display cDNA library was constructed by package reaction in vitro and plate proliferation.Plaque assay and PCR were used to evaluate the library.Results:Two T7 phage display cDNA library were established.Plaque assay show the titer of lung squamas carcinoma library was 1.8 × 106 pfu,and the adenocarcinoma library was 5 × 106 pfu.The phage titer of the amplified library were 3.2 × 1010 pfu/mL and 2.5 × 1010 pfu/mL.PCR amplifica-tion of random plaque show insert ratio were 100%(24/24) in adenocarcinoma library and 95.8% in human lung squamas carcinoma library(23/24).Insert range from 300 bp to 1 500 bp.Conclusion:Two phage display cDNA library from NSCLC were constructed.
文摘Echinococcosis is a global and zoonotic helminthic disease caused by Echinococcus sp. A 24-year-old woman, coming from Bolivia two years before, was diagnosed as cystic echinococcosis (CE) by unstained wet mount and cytological findings through aspiration cytology from the liver, suggested as liver abscess by diagnostic images. The patient was classified as CE1, smaller than 5 cm, and was diagnosed as P1N0M0, stage I. The phylogenetic trees of Echinococcus spp., based on cox1 genes showed that the isolates on the patient belonged to E. ortleppi. The patient was conservatively treated with two courses of albendazole therapy. E. ortleppi has been reported to be in regions including Latin America, except with Japan. Although the patient came from Bolivia before two years, this is the first case report of E. ortleppi from liver echinococcosis in Japan.
文摘Objective: To evaluate the acute toxicity effect of metribuzin at low dose on liver of mother rabbits and its fetus.Methods: Pregnant female rabbitsOryctolagus cuniculus were divided into three groups (n=5). The first group of non-treated pregnancy rabbits served as control;the second group of pregnancy rabbits were treated with 1/100 LD50 of metribuzin and the third group of pregnancy rabbits were treated with 1/50 LD50 of metribuzin. Metribuzin was added in their drinking water for 60 d before and during pregnancy. Levels of liver malondialdehyde, liver glutathione S transferase, serum glutamic oxaloacetic transaminase and serum glutamic-pyruvic transaminase were determined. Liver reduced glutathione level was also determined by a colorimetric method. And hepatic homogenate was analyzed by HPLC analysis to determine the existence of traces of metribuzin.Results: Results revealed a significant increase in level of liver malondialdehyde, glutathione S transferase, serum glutamic oxalacetic transaminase and serum glutamic-pyruvic transaminase activities in mother and fetuses rabbits of both metribuzin treatment groups as compared to the control group. However the level of reduced glutathione was decreased in mother and fetuses rabbits of both groups treated with metribuzin compared to control group. Also, the results obtained by HPLC technique showed the presence of trace metribuzin in liver cells of mothers and fetuses rabbits of the both metribuzin treated groups.Conclusions: In conclusion, this study shows that exposure to metribuzin at low concentrations causes a acute toxicity in liver of mother rabbits and its fetus, also the trace of the metribuzin detected in the liver is the origin of possible malformation of the fetuses or abortion of the rabbits.
基金supported by the National Key Research and Development Program of China(No.2018YFC2001100)the National Natural Science Foundation of China(Nos.61774167 and 61801477)+2 种基金the Instrument Development Program of the Chinese Academy of Sciences,Beijing Municipal Natural Science Foundation(Nos.4192062 and 4182072)Beijing Municipal Administration of Hospitals Incubating Program(No.PX2017050)Youth Innovation Promotion Association of Chinese Academy of Sciences。
文摘The sieving and enrichment of rare tumor cells from large-volume pleural effusion(PE)samples is a promising technique for cell-based lung tumor diagnosis and drug tests,which features high throughput and recovery,purification,as well as viability rates of rare target cells as the prerequisites for high sensitivity,specificity,and accuracy of tumor cell analysis.In this paper,we propose a three-dimensional(3 D)sieving method for rare tumor cell enrichment,which effectively eliminates the"dead zones"in traditional two-dimensional(2 D)cell filters with a dimension-raising strategy to satisfy the requirements mentioned above.The prototype device was combined with a funnel-shaped holder,a flexible micropore membrane in the middle,and a3 D spiral fluid channel covered on the membrane as a three-layer ice-creaming cone composite structure.Driven by gravity alone,the device performed as follows:(1)20-fold throughput compared with the 2 D commercial planee hich was up to 20 mL/min for a threefold dilution of whole blood sample;(2)high recovery rates of 84.5%±21%,86%±25%,83%±14%for 100,1000,and 10000 cells/mL,respectively,in 30 mL phosphate buffer saline(PBS)sample,and a 100%positive detection rate in the case of≤5 A549 cells in 1 mL PBS;(3)a typical purification rate of 85.5%±9.1%;and(4)a viability rate of>93%.In the demonstration application,this device effectively enriched rare target cells from large volumes(>25 mL)of clinical pleural effusions.The following results indicated that tumor cells were easy-to-discover in the enriched PE samples,and the proliferation capability of purified cells was(>4.6 times)significantly stronger than that of unprocessed cells in the subsequent 6-day culture.The above evaluation indicates that the proposed easily reproducible method for the effective execution of rare cell enrichments and assays is expected to become a practical technique for clinical cell-based tumor diagnosis.
基金supported by the National Natural Science Foundation of China (Grant No. 30070413) and China Scholarship Council. References
文摘Interspecific and intergeneric hybridizations have been widely used in plant genetics and breeding to construct stocks for genetic analysis and to introduce into crops the desirable traits and genes from their relatives. The intergeneric crosses between Brassica juncea (L.) Czern. & Coss., B. carinata A. Braun and Orychophragmus violaceus (L.) O. E. Schulz were made and the plants produced were subjected to genomic in situ hybridization analysis. The mixoploids from the cross with B. juncea were divided into three groups. The partially fertile mixoploids in the first group (2n = 36—42) mainly contained the somatic cells and pollen mother cells (PMCs) with the 36 chromosomes of B. juncea and additional chromosomes of O. violaceus. The mixoploids (2n = 30—36) in the second and third groups were morphologically quite similar to the mother plants B. juncea and showed nearly normal fertility. The plants in the second group produced the majority of PMCs (2n = 36) with their chromosomes paired and segregated normally, but 1—4 pairs of the O. violaceus chromosomes were included in some PMCs. The plants in the third group produced only PMCs with the 36 B. juncea chromosomes, which were paired and segregated normally. The mixoploids (2n = 29—34) from the cross with B. carinata produced the majority of PMCs (2n = 34) with normal chromosome pairing and segregation, but some plants had some PMCs with 1—3 pairs of chromosomes from O. violaceus and other plants had only PMCs with the B. carinata chromosomes. The Brassica homozygous plants and aneuploids with complete or partial chromo-some complements of Brassica parents and various numbers of O. violaceus chromosomes were derived from these progeny plants. The results in this study provided the molecular cytogenetic evidence for the separation of parental genomes which was previously proposed to occur in the hybridizations of these two genera.
文摘Various epidemiological studies have shown an inverse association between the consumption of polyphenols or polyphenol-rich foods and the risk of cardiovascular diseases. The purpose of the study was to emphasize the effects of the association between the renin inhibitor and the polyphenolic extract on biochemical parameters and systolic and diastolic blood pressure. The polyphenols are extracted from isolated and purified vegetable material represented by the mature fruit of the Aronia melanocarpa. The experiment was performed on the arterial hypertension model. In the arterial hypertensive model the cardioprotective effects of the polyphenolic extract from Aronia melanocarpa are represented by the antioxidant, hypocolesterolemiant intervention. Polyphenolic extract from Aronia melanocarpa reduce systolic and diastolic arterial tension values in rats with drug-induced hypertension, a phenomenon more pronounced when polyphenols are associated with Aliskiren (renin inhibitor). The combination between the Aliskiren and polyphenolic extract produce superior hypolipidemic and antioxidant effects than in the case of separate administration within experimental arterial hypertension induced in the murine model.
文摘With advancements in gene editing technologies,our ability to make precise and efficient modifications to the genome is increasing at a remarkable rate,paving the way for scientists and clinicians to uniquely treat a multitude of previously irremediable diseases.CRISPR-Cas9,short for clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9,is a gene editing platform with the ability to alter the nucleotide sequence of the genome in living cells.This technology is increasing the number and pace at which new gene editing treatments for genetic disorders are moving toward the clinic.Theβ-hemoglobinopathies are a group of monogenic diseases,which despite their high prevalence and chronic debilitating nature,continue to have few therapeutic options available.In this review,we will discuss our existing comprehension of the genetics and current state of treatment forβ-hemoglobinopathies,consider potential genome editing therapeutic strategies,and provide an overview of the current state of clinical trials using CRISPR-Cas9 gene editing.
基金grants from American Heart Association grant （No. 20130034） and National Natural Science Foundation of China （No. 21307158）.
文摘Objective：To focus on the asthmatic pathogenesis and clinical manifestations related to epithelial sodium channel （ENaC）/chlorine ion channel.Data Sources：The data analyzed in this review were the English articles from 1980 to 2015 from journal databases,primarily PubMed and Google Scholar.The terms used in the literature search were：（1） ENaCs;cystic fibrosis （CF） transmembrane conductance regulator （CFTR）;asthma/asthmatic,（2） ENaC/sodium salt;CF;asthma/asthmatic,（3） CFTR/chlorine ion channels;asthma/asthmatic,（4） ENaC/sodium channel/scnn1a/scnn1b/scnn1g/scnn1d/amiloride-sensitive/amiloride-inhibtable sodium channels/sodium salt;asthma/asthmatic,lung/pulmonary/respiratory/tracheal/alveolar,and （5） CFTR;CF;asthma/asthmatic （ti）.Study Selection：These studies included randomized controlled trials or studies covering asthma pathogenesis and clinical manifestations related to ENaC/chlorine ion channels within the last 25 years （from 1990 to 2015）.The data involving chronic obstructive pulmonary disease and CF obtained from individual studies were also reviewed by the authors.Results：Airway surface liquid dehydration can cause airway inflammation and obstruction.ENaC and CFTR are closely related to the airway mucociliary clearance.Ion transporters may play a critical role in pathogenesis of asthmatic exacerbations.Conclusions：Ion channels have been the center of many studies aiming to understand asthmatic pathophysiological mechanisms or to identify therapeutic targets for better control of the disease.
基金This work was supported by grants from the National Key Basic Research Program(973 Program)of MOST,China(Grant No.2015CB910601)the National Natural Science Foundation of China(Grant Nos.31370843 and 31500681)to P.KZhou and the National Natural Science Foundation,China(Grant Nos.31570853 and 81602799)to T.Ma.
文摘Dear Editor,The DNA-dependent protein kinase catalytic subunit(DNA-PKcs)forms a serine/threonine protein kinase complex with the Ku heterodimer(Ku70/Ku80)and plays an important role in the DNA damage response(DDR)and maintenance of genomic stability through nonhomologous end joining(NHEJ),wherein the Ku heterodimer recognizes and binds broken DNA ends,facilitating the recruitment and activation of DNA-PKcs.1 Activated DNA-PKcs phosphorylates and alters the function of factors that mediate NHEJ,including DNA-PKcs itself.2 In addition,DDR-independent roles of DNA-PKcs have been demonstrated.3 Studies further identified DNA-PKcs as a modulator of cancer-associated pathways distinct from DNA repair,including hypoxia,metabolism,the inflammatory response,and transcriptional regulation.
文摘Metabolomics is the last frontier of modern molecular biology,and the state-of-the-art technique for studying metabolism.Mass spectrometry and nuclear magnetic resonance spectroscopy are the main analytical approaches in metabolomics.Cellular metabolism plays a pivotal role during cell resting and activation.Immune cells exhibit remarkable metabolic plasticity,fundamental to support their adaptation to inflammatory environments and functional requirements.Cancer is a metabolic and inflammatory disease.A metabolic shift is crucial for oncogenesis,tumor cell survival,invasion,metastasis,and the associated inflammatory process.The tumor microenvironment is mainly orchestrated by immune-inflammatory cells and essential for the neoplastic process.Inflammatory cells from tumor stroma adapt to different metabolic pathways during tumor progression,and this metabolic reprogramming affects macrophages,neutrophils,T cells,and others.Targeting the metabolism of tumor and immune cells may lead to important therapeutic implications in cancer.Thus,understanding the metabolic changes that drive the interactions between tumor and stromal cells is a promising avenue advances in cancer diagnostics and therapies,leading to more accurate guidance.In this review,we discuss the most recent metabolomics approaches in cancer studies on the tumor-associated inflammatory microenvironment.
