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Objective:To discuss the repairment effect of intra-articular injection of adipose derived stem cells(ADSCs)on articular cartilage destruction in the temporomandibular joint osteoarthritis(TMJOA)model rabbits,and to clarify the possible mechanism.Methods:Twenty-seven rabbits were randomly divided into control group,model group,and ADSCs group.The ADSCs of the rabbits were extracted and cultured.The rabbit TMJOA model was prepared by monosodium-iodoacetate(MIA)injection technique.The temporomandibular joint cavity of the TMJOA model rabbits in ADSCs group was given two continuous intra-articular injections of 1.0×106 mL-1 ADSCs,while the rabbits in control and model group were given sequivalent volume of saline into the temporomandibular joint cavity.After 8 weeks,Micro-CT scan was performed on the temporomandibular joints of the rabbits in various groups;the bone volume fraction(BV/TV),bone surface area/bone volume(BS/BV),trabecular thickness(Tb.Th),trabecular separation(Tb.Sp),and trabecular number(Tb.N)of condyles tissue of the rabbits in various groups were analyzed;HE staining was used to observe the pathomorphology of condyles tissue of the rabbits in various groups;immunohistochemistry was used to detect the localization and expression levels of SRY-related high mobility group box gene 9(SOX9),matrix metalloproteinase-13(MMP-13),and vascular endothelial growth factor(VEGF)proteins in condyles tissue of the rabbits in various groups;Western blotting method was used to detect the expression levels of SOX9,MMP-13,and VEGF proteins in condyles tissue of the rabbits in various groups.Results:The micro-CT scan results showed that compared with control group,the BV/TV,Tb.Th,and Tb.N of condyles tissue of the rabbits in model group were significantly decreased(P<0.05),while the BS/BV and Tb.Sp were significantly increased(P<0.05);compared with model group,the BV/TV,Tb.Th,and Tb.N in condyles tissue of the rabbits in ADSCs group were significantly increased(P<0.05),and the BS/BV and Tb.Sp were significantly decreased(P<0.05).The HE staining results showed that the condylar cartilage surface of the rabbits in control group was smooth with clear layers and intact structure;compared with control group,the surface of condyles tissue of the rabbits in model group was irregular with thickened hypertrophic layer and areas of cell depletion and clustering;compared with model group,the pathological damage of condyles tissue of the rabbits in ADSCs group was significantly decreased.The immunohistochemical staining results showed that compared with control group and ADSCs group,the number of brown granule in condyles tissue of the rabbits in model group was increased,mainly concentrated in the hypertrophic layer,especially in the bone cartilage junction site and the expression levels of SOX9,MMP-13,and VEGF proteins in condyles tissue of the rabbits in model group were significantly increased(P<0.05);compared with model group,the number of brown granule in condyles tissue of the rabbits in ADSCs group was significantly decreased,and the expression levels of SOX9,MMP-13,and VEGF proteins were significantly decreased(P<0.05).The Western blotting results showed that compared with control group,the expression levels of SOX9,MMP-13,and VEGF proteins in condyles tissue of the rabbits in model group were significantly increased(P<0.05);compared with model group,the expression levels of SOX9,MMP-13,and VEGF proteins in condyles tissue of the rabbits in ADSCs group were significantly decreased(P<0.05).Conclusion:Intra-articular injection of ADSCs can effectively repair the cartilage destruction in TMJOA,alleviate the cartilage injury,and mitigate the progression of osteoarthritis.
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BACKGROUND:Immunotherapy enhances the anti-cancer immune response in many ways,so combined immunotherapy is a better choice.Ultrasound-targeted microbubble destruction technique delivers drugs,genes,antibodies and cytokines directly to the cytoplasm of immune cells and enhances the immune response.However,the application of ultrasound-targeted microbubble destruction technique in the treatment of ovarian cancer with both CXC chemokine receptor 4 antibody and programmed death-ligand 1 antibody has not been reported. OBJECTIVE:To investigate the effect of ultrasound irradiation on the proliferation and migration of ovarian cancer cells with CXC chemokine receptor 4 antibody and programmed death-ligand 1 antibody double targeted nanobubbles. METHODS:IOSE-80 normal ovarian epithelial cells,SKOV3 and CAOV3 ovarian cancer cells were cultured and expanded.Double labeling fluorescence immunoassay was used to co-locate CXC chemokine receptor 4 and programmed death-ligand 1 protein.Western blot assay was used to detect the relative expression of CXC chemokine receptor 4 and programmed death-ligand 1 protein in three kinds of cells and screen out the experimental cells,i.e.,pure nanobubbles,nanobubbles carrying CXC chemokine receptor 4 antibody,nanobubbles carrying CXC chemokine receptor 4 and programmed death-ligand 1 antibody.SKOV3 ovarian cancer cells in the logarithmic growth phase were taken and divided into six groups for treatment.Group A was added with McCoy's 5A medium.Group B was added with McCoy's 5A medium containing stromal cell-derived factor-1.Group C was added with pure nanobubble solution and McCoy's 5A medium containing stromal cell-derived factor-1.Group D was added with nanobubble solution containing CXC chemokine receptor 4 antibody and McCoy's 5A medium containing stromal cell-derived factor-1.Group E was added with nanobubble solution containing CXC chemokine receptor 4 and programmed death-ligand 1 antibody and McCoy's 5A medium containing stromal cell-derived factor-1.Pure nanobubble solution was added in group F.After ultrasonic irradiation for 120 seconds and incubation for 48 hours,the survival rate of cells was measured by CCK-8 assay,and the healing and migration ability of cells in groups B-E were measured by wound healing test. RESULTS AND CONCLUSION:(1)Immunofluorescence staining showed that CXC chemokine receptor 4 and programmed death-ligand 1 protein could be expressed in all three kinds of cells.Western blot assay showed that the expression levels of CXC chemokine receptor 4 and programmed death-ligand 1 in SKOV3 and CAOV3 ovarian cancer cells were significantly higher than those in IOSE-80 normal ovarian epithelial cells(P<0.05).(2)CCK-8 assay results exhibited that the cell survival rate of group B was higher than that of group A(P<0.05).The cell survival rate of group F was lower than that of group A(P<0.05).The cell survival rate of groups B-E decreased gradually,and there were significant differences between the two groups(P<0.05).(3)Wound healing test demonstrated that the cell healing rate of groups B-E decreased gradually,and there were significant differences between the two groups(P<0.05).(4)The results show that the use of CXC chemokine receptor 4 antibody and programmed death-ligand 1 antibody double targeted nanobubbles under ultrasound-targeted microbubble destruction can significantly inhibit the proliferation and migration of ovarian cancer cells.
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BACKGROUND:In chronic gout patients,sodium urate is deposited in bone joints and around synovial membranes,eroding and destroying bone,leading to serious complications such as gouty arthritis and deformity.Research on the mechanisms by which sodium urate crystals erode and destroy bone can help early clinical intervention in gouty diseases and prevent and delay the complications caused by bone destruction. OBJECTIVE:To explore the destructive effects of gout crystals on bone through clinical imaging studies and experimental basic research,review the current progress and development prospects of research on the phenomenon and mechanism of bone destruction caused by gout,guide the clinical early intervention of gouty bone destruction,and guide the direction of research on the role of bone destruction. METHODS:The Chinese search terms were"gout,bone destruction,bone erosion"and the English search terms were"tophi,gout,RANKL,bone destruction,bone erosion,"which were used in the computer search of WanFang and PubMed databases.Finally,64 articles were selected for review according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:The specific manifestations of clinical studies(imaging,histopathology)to some extent elaborate the osteolytic process of gout,and in basic studies,the mechanism of gout-causing bone destruction can be divided into the five aspects:(1)Sodium acid crystals have an important role in bone destruction,directly affecting osteocytes,chondrocytes,osteoblasts and proresorptive factors that promote bone destruction;(2)Receptor activator of nuclear factor-κB ligand and other proresorptive factors are involved in bone destruction;(3)T cell-mediated cellular immunity functions as a bridge in bone destruction,and activated T cells induce osteoclast differentiation;(4)Monocytes/macrophages are not only precursors of osteoclast-like cells,but also induce the expression of proresorptive factors such as Receptor activator of nuclear factor-κB ligand;(5)Neutrophils affect the morphology of osteoclast arrangement,and neutrophil extracellular trap networks promote osteolysis by promoting osteoclast differentiation.
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Based on the previous publications， it is believed that damp-heat syndrome is the core syndrome of rheumatoid arthritis （RA）， and Qingre Huoxue Formula （清热活血方） is an effective formula for the treatment of damp-heat syndrome of RA. “Inflammation-bone destruction” is a key pathological link of RA， and it is also the advantage of the effectiveness of Qingre Huoxue Formula. Leucine rich α-2-glycoprotein 1 （LRG1） can mediate the transforming growth factor-β （TGF-β） signalling pathway to participate in the pathogenic process of “inflammation-bone destruction” of RA， and it can be used as a target protein in the treatment of damp-heat syndrome of RA by Qingre Huoxue Formula. Accordingly， a scientific hypothesis was proposed that Qingre Huoxue Formula may regulate TGF-β signalling pathway mediated by LRG1 to improve “inflammation-bone destruction” of RA， and it was envisioned that the clinical effect of Qingre Huoxue Formula on LRG1 could be confirmed through clinical studies， and the mechanism of action of Qingre Huoxue Formula on the LRG1/TGF-β signalling axis as well as the influence of the expression or non-expression of the LRG1/TGF-β signalling axis on the therapeutic effectiveness of Qingre Huoxue Formula could be clarified through animal experiments.
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In the past few decades, microbubbles were widely used as ultrasound contrast agents in the field of tumor imaging. With the development of research, ultrasound targeted microbubble destruction technology combined with drug-loaded microbubbles can achieve precise drug release and play a therapeutic role. As a micron-scale carrier, microbubbles are difficult to penetrate the endothelial cell space of tumors, and nano-scale drug delivery system—nanobubbles came into being. The structure of the two is similar, but the difference in size highlights the unique advantages of nanobubbles in drug delivery. Based on the classification principle of shell materials, this review summarized micro/nanobubbles used for ultrasound diagnosis or treatment and discussed the possible development directions, providing references for the subsequent development.
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Abstract Mining is vital for human sustenance and a crucial sector in the state economy. However, its impacts on the environment and biodiversity cannot be underestimated. Which are potent to the attract governments attention. Environment and wildlife are subject to the harmful impacts of mining and its related activities. In this study, districts, namely Mardan and Mohmand have been targeted with respect to mining impacts. The assessment was carried out on wildlife adversely affected by the mining sector. The fauna has been keenly observed to bring the calculated risks and threat perception of the regional wildlife. Total 9 species of mammals, 21 species of birds, were recorded in District Mardan. While in District Mohmand 2 species of mammals, 9 species of birds, and 4 species of reptiles were studied. The Study explored that mining primarily responsible for land degradation. Which lead to food and agriculture losses. Several other factors like blasting, pollution, hunting, deforestation, habitat loss was also observed. Deforestation surfaced one of the major causes for extinction of fauna in the said region. preemptive measures are needed to seize the man-made catastrophe.
Resumo A mineração é vital para o sustento humano e um setor crucial na economia do Estado. No entanto, seus impactos sobre o meio ambiente e a biodiversidade não podem ser subestimados, visto serem potentes para atrair a atenção do governo. O meio ambiente e a vida selvagem estão sujeitos aos impactos prejudiciais da mineração e de suas atividades relacionadas. Neste estudo, os distritos, nomeadamente Mardan e Mohmand, foram selecionados no que diz respeito aos impactos da mineração. A avaliação foi realizada em animais selvagens afetados negativamente pelo setor de mineração. A fauna tem sido observada atentamente para trazer os riscos calculados e a percepção de ameaça à vida selvagem regional. Um total de nove espécies de mamíferos, 21 espécies de pássaros, foi registrado no Distrito Mardan. Enquanto no Distrito Mohmand, duas espécies de mamíferos, nove espécies de pássaros e quatro espécies de répteis foram estudadas. O estudo explorou essa mineração que é principalmente responsável pela degradação do solo, acarretando perdas de alimentos e na agricultura. Vários outros fatores como explosões, poluição, caça, desmatamento, perda de habitat também foram observados. O desmatamento veio à tona como uma das principais causas de extinção da fauna da região, e tem-se que medidas preventivas são necessárias para dimensionar a catástrofe provocada pelo homem.
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En 2006, el Gobierno mexicano desplegó las Fuerzas Armadas para combatir el crimen organizado en la llamada guerra contra el narcotráfico. Desde entonces, la sociedad civil ha sido víctima de asesinatos, desapariciones y torturas cometidos tanto por los grupos del crimen organizado como por las fuerzas federales y estatales que supuestamente se encuentran combatiendo a estos primeros. En este artículo se muestra el análisis del testimonio de una madre que se enfrentó a la destrucción parcial de los restos de su hijo; para ello, se utilizan tres aspectos fundamentales para guiar el estudio: la relación entre las somatizaciones y la reelaboración de la experiencia traumática de la destrucción parcial de los restos de un ser querido, la creación de zonas de silencio en torno a escenas brutales, y la función que cumple el testimonio en el proceso de simbolización de huellas traumáticas.
Resumos In 2006, the Mexican government deployed the armed forces to combat organized crime in the so-called "war against narcotrafficking". Since then, civilians have been victims o of murders, disappearances, and torture carried out both by cartels and by the federal and state forces who are supposedly fighting the former. This article presents the analysis of the narrative of a mother who faced the partial destruction of her son's remains, focusing on three fundamental aspects: the relationship between somatizations and the working trough of the traumatic experience of the destruction of a beloved's remains, the creation of zones of silence around brutal events, and the role that accounts play in the process of symbolization of traumatic traces.
En 2006, le gouvernement mexicain a déployé les forces armées pour combattre le crime organisé dans le cadre de la soi-disant guerre contre la drogue. Depuis lors, la société civile est victime d'assassinats, de disparitions et de tortures commis tant par les groupes du crime organisés que par les forces gouvernementales censées les combattre. Cet article analyse le témoignage d'une mère confrontée à la destruction partielle de la dépouille de son fils. Trois aspects fondamentaux guident l'étude: la relation entre les somatisations et la réélaboration de l'expérience traumatique, la création des zones de silence autour des scènes brutales et le rôle du témoignage dans le processus de symbolisation des traces traumatiques.
Em 2006, o governo mexicano mobilizou as forças armadas para combater o crime organizado na chamada guerra contra o narcotráfico. Desde então, a sociedade civil tem sido vítima de assassinatos, desaparecimentos e torturas cometidos tanto por grupos do crime organizado quanto por forças federais e estaduais que supostamente lutam contra eles. São três os aspetos fundamentais que orientam o estudo: a relação entre as somatizações e a reelaboração da experiência traumática da destruição dos restos mortais de uma pessoa amada, a criação de zonas de silêncio em torno das cenas brutais e o papel que o testemunho desempenha no processo de simbolização dos vestígios traumáticos.
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Abstract Mining is vital for human sustenance and a crucial sector in the state economy. However, its impacts on the environment and biodiversity cannot be underestimated. Which are potent to the attract government's attention. Environment and wildlife are subject to the harmful impacts of mining and its related activities. In this study, districts, namely Mardan and Mohmand have been targeted with respect to mining impacts. The assessment was carried out on wildlife adversely affected by the mining sector. The fauna has been keenly observed to bring the calculated risks and threat perception of the regional wildlife. Total 9 species of mammals, 21 species of birds, were recorded in District Mardan. While in District Mohmand 2 species of mammals, 9 species of birds, and 4 species of reptiles were studied. The Study explored that mining primarily responsible for land degradation. Which lead to food and agriculture losses. Several other factors like blasting, pollution, hunting, deforestation, habitat loss was also observed. Deforestation surfaced one of the major causes for extinction of fauna in the said region. preemptive measures are needed to seize the man-made catastrophe.
Resumo A mineração é vital para o sustento humano e um setor crucial na economia do Estado. No entanto, seus impactos sobre o meio ambiente e a biodiversidade não podem ser subestimados, visto serem potentes para atrair a atenção do governo. O meio ambiente e a vida selvagem estão sujeitos aos impactos prejudiciais da mineração e de suas atividades relacionadas. Neste estudo, os distritos, nomeadamente Mardan e Mohmand, foram selecionados no que diz respeito aos impactos da mineração. A avaliação foi realizada em animais selvagens afetados negativamente pelo setor de mineração. A fauna tem sido observada atentamente para trazer os riscos calculados e a percepção de ameaça à vida selvagem regional. Um total de nove espécies de mamíferos, 21 espécies de pássaros, foi registrado no Distrito Mardan. Enquanto no Distrito Mohmand, duas espécies de mamíferos, nove espécies de pássaros e quatro espécies de répteis foram estudadas. O estudo explorou essa mineração que é principalmente responsável pela degradação do solo, acarretando perdas de alimentos e na agricultura. Vários outros fatores como explosões, poluição, caça, desmatamento, perda de habitat também foram observados. O desmatamento veio à tona como uma das principais causas de extinção da fauna da região, e tem-se que medidas preventivas são necessárias para dimensionar a catástrofe provocada pelo homem.
Subject(s)
Humans , Animals , Biodiversity , Animals, Wild , Mining , PakistanABSTRACT
Esta investigación aborda la protesta, los sujetos y sus características, así como las formas de acción colectiva disruptivas en el levantamiento popular de octubre de 2019 en Santiago de Chile. El objetivo es analizar y reflexionar, a partir de la constatación de la ausencia de un sujeto de la convocatoria de las protestas, el uso de las prácticas disruptivas en estas, tratando de problematizar su supuesta "espontaneidad". La metodología se basa en una perspectiva cualitativa y entrevistas en profundidad a intelectuales y actores de la protesta. A modo de conclusión, la protesta, lejos de ser "espontánea", debe interpretarse como resultado de los repertorios de acción conocidos e innovaciones, así como de redes informales de cooperación, en que la acción colectiva disruptiva fue dominante.
This research addresses the protest, the subjects and their characteristics, as well as the forms of disruptive collective action in the popular uprising of October 2019 in Santiago de Chile. The objective is to analyze and reflect about the absence of a predetermined subject calling for the protests, the use of disruptive practices in them, and discussing their presumed "spontaneity". The methodology is based on a qualitative perspective and indepth interviews with academics and participants in the protest. My argument is that the protest, far from being "spontaneous", should be interpreted as the result of known repertoires of action and innovations, as well as informal networks of cooperation in which disruptive collective action was dominant.
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Objective@#To analyze and evaluate the clinical application effect of bioceramic material mineral trioxide aggregate and iRoot BP plus on the formation of apical barrier in adult teeth with incomplete apical foramen.@*Methods@#A total of 200 permanent teeth with apical periodontitis whose apical foramen were not closed were randomly divided into two groups, and the apical barrier was prepared with MTA and iRoot BP plus, respectively. The operation time of MTA and iRoot BP plus and effects of different types of apical foramen destruction, lesion range of apical area, the filling of apical area and patients' age on the treatment success rate was analyzed and compared. @*Results@#The operation time of preparing apical barrier in iRoot BP plus group was shorter than that in MTA group, and the difference was statistically significant (P<0.05). However, different types of apical foramen destruction, lesion scope of apical area, filling of apical area and patients' age had no effect on the treatment success rate of the two groups (P>0.05). @*Conclusion@#The clinical effects of MTA and iRoot BP plus in the treatment of apical periodontitis of permanent teeth with unclosed apical foramen are similar, but the operation performance of iRoot BP plus is better.
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The present study investigated the mechanism of artesunate in the treatment of bone destruction in experimental rheumatoid arthritis(RA) based on transcriptomics and network pharmacology. The transcriptome sequencing data of artesunate in the inhibition of osteoclast differentiation were analyzed to obtain differentially expressed genes(DEGs). GraphPad Prism 8 software was used to plot volcano maps and heat maps were plotted through the website of bioinformatics. GeneCards and OMIM were used to collect information on key targets of bone destruction in RA. The DEGs of artesunate in inhibiting osteoclast differentiation and key target genes of bone destruction in RA were intersected by the Venny 2.1.0 platform, and the intersection target genes were analyzed by Gene Ontology(GO)/Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment. Finally, the receptor activator of nuclear factor-κB(RANKL)-induced osteoclast differentiation model and collagen-induced arthritis(CIA) model were established. Quantitative real time polymerase chain reaction(q-PCR), immunofluorescence, and immunohistochemistry were used to verify the pharmacological effect and molecular mechanism of artesunate in the treatment of bone destruction in RA. In this study, the RANKL-induced osteoclast differentiation model in vitro was established and intervened with artesunate, and transcriptome sequencing data were analyzed to obtain 744 DEGs of artesunate in inhibiting osteoclast differentiation. A total of 1 291 major target genes of bone destruction in RA were obtained from GeneCards and OMIM. The target genes of artesunate in inhibiting osteoclast differentiation and the target genes of bone destruction in RA were intersected to obtain 61 target genes of artesunate against bone destruction in RA. The intersected target genes were analyzed by GO/KEGG enrichment. According to the results previously reported, the cytokine-cytokine receptor interaction signaling pathway was selected for experimental verification. Artesunate intervention in the RANKL-induced osteoclast differentiation model showed that artesunate inhibited CC chemokine receptor 3(CCR3), CC chemokine receptor 1(CCR1) and leukemia inhibitory factor(LIF) mRNA expression in osteoclasts in a dose-dependent manner compared with the RANKL-induced group. Meanwhile, the results of immunofluorescence and immunohistochemistry showed that artesunate could dose-dependently reduce the expression of CCR3 in osteoclasts and joint tissues of the CIA rat model in vitro. This study indicated that artesunate regulated the CCR3 in the cytokine-cytokine receptor interaction signaling pathway in the treatment of bone destruction in RA and provided a new target gene for the treatment of bone destruction in RA.
Subject(s)
Rats , Animals , Arthritis, Experimental/drug therapy , Artesunate/therapeutic use , Arthritis, Rheumatoid/genetics , Transcriptome , Network Pharmacology , Osteoclasts , Receptors, Cytokine/therapeutic useABSTRACT
Rheumatoid arthritis （RA） is a systemic chronic auto-inflammatory disease， characterized by infiltration of inflammatory cells， pannus formation， articular cartilage destruction， and bone matrix destruction. Therefore， improving articular cartilage destruction has an important impact on the treatment of RA. Chinese medicine has a good application effect in improving cartilage destruction of RA due to its characteristics of multiple components， multiple targets， high activity and low side effects. Based on this， the author reviewed relevant literature to summarize the relevant research and mechanism of Chinese medicine and its active components in improving RA cartilage destruction. The results showed that Chinese medicine and its active components can improve RA cartilage destruction by regulating inflammatory factors， phosphatidylinositol 3-kinase/protein kinase B， Wnt/β- catenin， nuclear factor-κB， mitogen-activated protein kinase， Janus kinase 2/signal transduction and activator of transcription 3/ vascular endothelial growth factor， microRNAs， fibroblastic synovial cells.
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Nowadays,the application of ultrasound is not only used in clinical imaging,but also extended in the study of drug delivery.Diagnostic ultrasound combined with microbubbles can effectively open the biological barriers,which can enhance the targeted delivery of drugs and be beneficial to the combination of ultrasound and disease treatment.This review summarizes the biological effects of ultrasound,the characteristics of ultrasound microbubbles and the potential ability that solving the biological barrier problems in cancer therapy by using ultrasound targeted microbubble destruction,hoping to provide some reference for the further development of therapeutic ultrasound as a safe and effective drug targeted delivery strategy.
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ObjectiveTo study the clinical efficacy of Shire Biqing pill in the treatment of rheumatoid arthritis （damp-heat obstruction syndrome） and its effect on the expression of serum osteoprotegerin （OPG）， nuclear factor-κB receptor activating factor ligand （RANKL）， and tumor necrosis factor-α （TNF-α）， and to explore its mechanism from the perspective of bone destruction. MethodPatients with rheumatoid arthritis （damp-heat obstruction syndrome） were randomly divided into two groups， with 36 patients in each group. The control group was treated with methotrexate tablets and celecoxib capsule， while the treatment group was treated with Shire Biqing pill based on the control group. The treatment period was 3 months. The pain visual analogue scale （VAS） score， joint tenderness number， joint swelling number， disease activity score （DAS28-ESR）， traditional Chinese medicine （TCM） symptom quantitative score， and related adverse reactions were recorded before and after treatment， and the peripheral serum OPG， RANKL， TNF-α， erythrocyte sedimentation rate （ESR）， and Creactive protein （CRP） were detected. ResultAfter treatment， the total effective rate was 88.57% （31/35） in the treatment group and 79.41% （27/34） in the control group. The total effective rate of the treatment group was higher than that of the control group （Z=-2.089， P<0.05）. The pain VAS score， joint tenderness number， joint swelling number， and DAS28-ESR of the two groups were significantly lower than those before treatment （P<0.05）， and the pain VAS score， joint tenderness number， joint swelling number， and DAS28-ESR of the treatment group were significantly better than those of the control group after treatment （P<0.05）. Compared with that before treatment， the TCM symptom quantitative score in the two groups decreased significantly （P<0.05）， and the decrease was more obvious in the treatment group than in the control group （P<0.05）. Compared with those before treatment， the levels of RANKL， TNF-α， ESR， and CRP in the two groups decreased and the level of OPG increased （P<0.05）， and the changes in the treatment group were more obvious that in the control group （P<0.05）. There were no serious adverse events or serious adverse reactions during this clinical trial. ConclusionShire Biqing pill can effectively improve the clinical symptoms of rheumatoid arthritis （damp-heat obstruction syndrome） with good safety. Shire Biqing pill effectively regulate the OPG/RANKL/RANK system and reduce the pro-inflammatory factor TNF-α， which may be its mechanism in the intervention in rheumatoid arthritis bone destruction.
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The Indian crested porcupine (Hystrix indica) is a vertebrate pest of agricultural lands and forest. The study was aimed to report the damage to local crops by the Indian crested porcupine (Hystrix indica) in the Muzaffarabad District. A survey was conducted to identify the porcupine-affected areas and assess the crop damage to the local farmers in district Muzaffarabad Azad Jammu and Kashmir (AJK) from May 2017 to October 2017. Around 19 villages were surveyed, and a sum of 191 semi-structured questionnaires was distributed among farmers. Crop damage was found highest in village Dhanni where a porcupine destroyed 175 Kg/Kanal of the crops. Regarding the total magnitude of crop loss, village Danna and Koomi kot were the most affected areas. More than half (51.8%) of the respondents in the study area suffered the economic loss within the range of 101-200$, and (29.8%) of the people suffered losses in the range of 201-300$ annually. Among all crops, maize (Zea mays) was found to be the most damaged crop ranging between 1-300 Kg annually. In the study area, porcupine also inflicted a lot of damages to some important vegetables, including spinach (Spinacia oleracea), potato (Solanum tuberosum) and onion (Allium cepa). It was estimated that, on average, 511Kg of vegetables are destroyed by porcupine every year in the agricultural land of Muzaffarabad. It was concluded that the Indian crested porcupine has a devastating effect on agriculture which is an important source of income and food for the local community. Developing an effective pest control strategy with the help of the local government and the Wildlife department could help the farmers to overcome this problem.
O porco-espinho de crista indiano (Hystrix indica) é uma praga vertebrada de terras agrícolas e florestais. No estudo atual, o dano às plantações locais pelo porco-espinho de crista indiano (Hystrix indica) foi relatado pela primeira vez no distrito de Muzaffarabad. O estudo foi projetado para investigar a perda econômica causada pelo porco espinho de crista indiano (Hystrix indica) nos distritos de Muzaffarabad, Azad Jammu e Caxemira (AJK) de maio de 2017 a outubro de 2017. Um estudo baseado em pesquisa foi conduzido para identificar as áreas afetadas por porcos-espinhos e avaliar os danos às colheitas para os agricultores locais. Cerca de 19 aldeias foram pesquisadas e um total de 191 questionários semiestruturados foi distribuído entre os agricultores. Os danos às colheitas foram encontrados mais intensamente na aldeia Dhanni, onde um porco-espinho destruiu 175 kg / Kanal das colheitas. Em relação à magnitude total da perda de safra, as aldeias Danna e Koomi Kot foram as áreas mais afetadas. Mais da metade (51,8%) dos entrevistados na área de estudo sofreu perdas econômicas na faixa de 101-200 $, e 29,8% das pessoas sofreram perdas na faixa de 201-300 $ anualmente. Entre todas as culturas, o milho (Zea mays) foi considerado a cultura mais danificada, variando entre 1-300 kg anualmente. Na área de estudo, o porco-espinho também causou muitos danos a alguns vegetais importantes, incluindo espinafre (Spinacia oleracea), batata (Solanum tuberosum) e cebola (Allium cepa). Estimou-se que, em média, 511 kg de vegetais são destruídos pelo porco-espinho todos os anos nas terras agrícolas de Muzaffarabad. Concluiu-se que o porco-espinho de crista indiano tem um efeito devastador na agricultura, que é importante fonte de renda e alimento para a comunidade local. O desenvolvimento de uma estratégia eficaz de controle de pragas com a ajuda do governo local e do Departamento de Vida Selvagem pode ajudar os agricultores a superar esse problema.
Subject(s)
Pest Control/economics , Porcupines , Agricultural PestsABSTRACT
Abstract The Indian crested porcupine (Hystrix indica) is a vertebrate pest of agricultural lands and forest. The study was aimed to report the damage to local crops by the Indian crested porcupine (Hystrix indica) in the Muzaffarabad District. A survey was conducted to identify the porcupine-affected areas and assess the crop damage to the local farmers in district Muzaffarabad Azad Jammu and Kashmir (AJK) from May 2017 to October 2017. Around 19 villages were surveyed, and a sum of 191 semi-structured questionnaires was distributed among farmers. Crop damage was found highest in village Dhanni where a porcupine destroyed 175 Kg/Kanal of the crops. Regarding the total magnitude of crop loss, village Danna and Koomi kot were the most affected areas. More than half (51.8%) of the respondents in the study area suffered the economic loss within the range of 101-200$, and (29.8%) of the people suffered losses in the range of 201-300$ annually. Among all crops, maize (Zea mays) was found to be the most damaged crop ranging between 1-300 Kg annually. In the study area, porcupine also inflicted a lot of damages to some important vegetables, including spinach (Spinacia oleracea), potato (Solanum tuberosum) and onion (Allium cepa). It was estimated that, on average, 511Kg of vegetables are destroyed by porcupine every year in the agricultural land of Muzaffarabad. It was concluded that the Indian crested porcupine has a devastating effect on agriculture which is an important source of income and food for the local community. Developing an effective pest control strategy with the help of the local government and the Wildlife department could help the farmers to overcome this problem.
Resumo O porco-espinho de crista indiano (Hystrix indica) é uma praga vertebrada de terras agrícolas e florestais. No estudo atual, o dano às plantações locais pelo porco-espinho de crista indiano (Hystrix indica) foi relatado pela primeira vez no distrito de Muzaffarabad. O estudo foi projetado para investigar a perda econômica causada pelo porco-espinho de crista indiano (Hystrix indica) nos distritos de Muzaffarabad, Azad Jammu e Caxemira (AJK) de maio de 2017 a outubro de 2017. Um estudo baseado em pesquisa foi conduzido para identificar as áreas afetadas por porcos-espinhos e avaliar os danos às colheitas para os agricultores locais. Cerca de 19 aldeias foram pesquisadas e um total de 191 questionários semiestruturados foi distribuído entre os agricultores. Os danos às colheitas foram encontrados mais intensamente na aldeia Dhanni, onde um porco-espinho destruiu 175 kg / Kanal das colheitas. Em relação à magnitude total da perda de safra, as aldeias Danna e Koomi Kot foram as áreas mais afetadas. Mais da metade (51,8%) dos entrevistados na área de estudo sofreu perdas econômicas na faixa de 101-200 $, e 29,8% das pessoas sofreram perdas na faixa de 201-300 $ anualmente. Entre todas as culturas, o milho (Zea mays) foi considerado a cultura mais danificada, variando entre 1-300 kg anualmente. Na área de estudo, o porco-espinho também causou muitos danos a alguns vegetais importantes, incluindo espinafre (Spinacia oleracea), batata (Solanum tuberosum) e cebola (Allium cepa). Estimou-se que, em média, 511 kg de vegetais são destruídos pelo porco-espinho todos os anos nas terras agrícolas de Muzaffarabad. Concluiu-se que o porco-espinho de crista indiano tem um efeito devastador na agricultura, que é importante fonte de renda e alimento para a comunidade local. O desenvolvimento de uma estratégia eficaz de controle de pragas com a ajuda do governo local e do Departamento de Vida Selvagem pode ajudar os agricultores a superar esse problema.
Subject(s)
Humans , Animals , Porcupines , Pakistan , Crops, Agricultural , Agriculture , Animals, WildABSTRACT
Abstract The Indian crested porcupine (Hystrix indica) is a vertebrate pest of agricultural lands and forest. The study was aimed to report the damage to local crops by the Indian crested porcupine (Hystrix indica) in the Muzaffarabad District. A survey was conducted to identify the porcupine-affected areas and assess the crop damage to the local farmers in district Muzaffarabad Azad Jammu and Kashmir (AJK) from May 2017 to October 2017. Around 19 villages were surveyed, and a sum of 191 semi-structured questionnaires was distributed among farmers. Crop damage was found highest in village Dhanni where a porcupine destroyed 175 Kg/Kanal of the crops. Regarding the total magnitude of crop loss, village Danna and Koomi kot were the most affected areas. More than half (51.8%) of the respondents in the study area suffered the economic loss within the range of 101-200$, and (29.8%) of the people suffered losses in the range of 201-300$ annually. Among all crops, maize (Zea mays) was found to be the most damaged crop ranging between 1-300 Kg annually. In the study area, porcupine also inflicted a lot of damages to some important vegetables, including spinach (Spinacia oleracea), potato (Solanum tuberosum) and onion (Allium cepa). It was estimated that, on average, 511Kg of vegetables are destroyed by porcupine every year in the agricultural land of Muzaffarabad. It was concluded that the Indian crested porcupine has a devastating effect on agriculture which is an important source of income and food for the local community. Developing an effective pest control strategy with the help of the local government and the Wildlife department could help the farmers to overcome this problem.
Resumo O porco-espinho de crista indiano (Hystrix indica) é uma praga vertebrada de terras agrícolas e florestais. No estudo atual, o dano às plantações locais pelo porco-espinho de crista indiano (Hystrix indica) foi relatado pela primeira vez no distrito de Muzaffarabad. O estudo foi projetado para investigar a perda econômica causada pelo porco-espinho de crista indiano (Hystrix indica) nos distritos de Muzaffarabad, Azad Jammu e Caxemira (AJK) de maio de 2017 a outubro de 2017. Um estudo baseado em pesquisa foi conduzido para identificar as áreas afetadas por porcos-espinhos e avaliar os danos às colheitas para os agricultores locais. Cerca de 19 aldeias foram pesquisadas e um total de 191 questionários semiestruturados foi distribuído entre os agricultores. Os danos às colheitas foram encontrados mais intensamente na aldeia Dhanni, onde um porco-espinho destruiu 175 kg / Kanal das colheitas. Em relação à magnitude total da perda de safra, as aldeias Danna e Koomi Kot foram as áreas mais afetadas. Mais da metade (51,8%) dos entrevistados na área de estudo sofreu perdas econômicas na faixa de 101-200 $, e 29,8% das pessoas sofreram perdas na faixa de 201-300 $ anualmente. Entre todas as culturas, o milho (Zea mays) foi considerado a cultura mais danificada, variando entre 1-300 kg anualmente. Na área de estudo, o porco-espinho também causou muitos danos a alguns vegetais importantes, incluindo espinafre (Spinacia oleracea), batata (Solanum tuberosum) e cebola (Allium cepa). Estimou-se que, em média, 511 kg de vegetais são destruídos pelo porco-espinho todos os anos nas terras agrícolas de Muzaffarabad. Concluiu-se que o porco-espinho de crista indiano tem um efeito devastador na agricultura, que é importante fonte de renda e alimento para a comunidade local. O desenvolvimento de uma estratégia eficaz de controle de pragas com a ajuda do governo local e do Departamento de Vida Selvagem pode ajudar os agricultores a superar esse problema.
ABSTRACT
Pancreatic adenocarcinoma (PAAD) is one of the most lethal malignancies. Although gemcitabine (GEM) is a standard treatment for PAAD, resistance limits its application and therapy. Secoemestrin C (Sec C) is a natural compound from the endophytic fungus Emericella, and its anticancer activity has not been investigated since it was isolated. Our research is the first to indicate that Sec C is a broad-spectrum anticancer agent and could exhibit potently similar anticancer activity both in GEM-resistant and GEM-sensitive PAAD cells. Interestingly, Sec C exerted a rapid growth-inhibiting effect (80% death at 6 h), which might be beneficial for patients who need rapid tumor shrinkage before surgery. Liquid chromatography/mass spectrometry and N-acetyl-l-cysteine (NAC) reverse assays show that Sec C sulfates cysteines to disrupt disulfide-bonds formation in endoplasmic reticulum (ER) proteins to cause protein misfolding, leading to ER stress and disorder of lipid biosynthesis. Microarray data and subsequent assays show that ER stress-mediated ER-associated degradation (ERAD) ubiquitinates and downregulates YAP to enhance ER stress via destruction complex (YAP-Axin-GSK-βTrCP), which also elucidates a unique degrading style for YAP. Potent anticancer activity in GEM-resistant cells and low toxicity make Sec C a promising anti-PAAD candidate.
ABSTRACT
Objective:To investigate the effect of Duhuo Jisheng Decoction on early cartilage destruction markers in patients with rheumatoid arthritis with kidney-qi deficiency and cold syndrome.Methods:A total of 64 patients with rheumatoid arthritis in our hospital from March 2019 to March 2020 who met the inclusion criteria were divided into 2 groups, according to the random number table method, with 32 in each group. The control group was given conventional western medicine therapy, and the observation group was given Duhuo Jisheng decoction on the basis of the control group. Both groups were treated for 8 weeks. TCM syndrome scores were performed before and after treatment, serum CRP, IL-6, cartilage oligosaccharide protein (COMP) and β-catenin were detected by ELISA method, and adverse eventns during treatment were observed and compared. The clinical efficacy was evaluated.Results:The total effective rate was 87.5% (28/32) in the observation group and 65.6% (21/32) in the control group, and the difference between the two groups was statistically significant ( χ2=4.27, P=0.039). After treatment, the main symptoms, secondary symptoms and tongue and pulse scores of the observation group were significantly lower than those in the control group ( t=7.11, 3.11, 2.41, P<0.01 or P<0.05); serum CRP and IL-6 levels were significantly lower than those in the control group ( t=3.04, 4.56, P<0.01); serum COMP [(12.37±1.68) μg/L vs. (14.24±1.88) μg/L, t=4.20], β-catenin [(1.35±0.24) μg/L vs. (1.68±0.31) μg/L, t=4.76] levels were significantly lower than those in the control group ( P<0.01). During the treatment, the incidence of adverse events was 25.0% (8/32) in the observation group and 18.8% (6/32) in the control group, and there was no significant difference between the two groups ( χ2=0.37, P=0.546). Conclusion:The Duhuo Jisheng Decoction can help to reduce the levels of inflammatory cytokines and early cartilage destruction markers in patients with rheumatoid arthritis, and improve the clinical efficacy safely.
ABSTRACT
Objective:To investigate the effect of vancomycin (Vm)-loaded microbubbles (MBs) combined with ultrasound targeted microbubble destruction (UTMD) technique on the morphological structure, thickness and bacterial viability of methicillin-resistant Staphylococcus aureus (MRSA) biofilms.Methods:Vm-MBs were prepared by thin film hydration. Sterile coverslips in a diameter of 13 mm were placed in 24-well plates to construct in vitro biofilm models using MRSA as the test strain, and the biofilm morphology was observed by naked eye and light microscopy after crystal violet staining. LIVE/DEAD, SYTO59 and DIL were used to stain biofilms and MBs, respectively. After staining, the biofilm morphology and position of the biofilm in relation to MBs were observed using laser confocal scanning microscopy. The biofilms were divided into control group, Vm group, Vm-MBs group, UTMD group and Vm-MBs+UTMD group according to the random number table method, with 9 samples in each group. After biofilms of each group were treated accordingly for 24 hours, the morphological and structural changes of biofilms in each group were observed using laser confocal scanning microscopy and scanning electron microscopy following LIVE/DEAD staining; the difference in biofilm density in each group was measured with the aid of an enzyme marker following crystal violet staining; the difference in biofilm thickness and bacterial viability in each group were observed by laser confocal scanning microscopy. Results:The prepared Vm-MBs met the experimental requirements. The constructed biofilm model observed by naked eye, light microscopy and laser confocal scanning microscopy showed that the biofilm structure was dense with a relatively uniform thickness of (13.8±0.2)nm, a small amount of dead bacteria inside the membrane and the percentage of live bacteria of (94.9±0.3)%. Laser confocal scanning microscopy showed that MBs could penetrate into deeper layers of biofilms. After the respective treatment was given to each group for 24 hours, Laser confocal scanning microscopy and scanning electron microscopy following LIVE/DEAD staining showed that the biofilm morphological structure was most significantly disrupted in Vm-MBs+UTMD group compared to control, Vm, Vm-MBs and UTMD groups. In Vm-MBs+UTMD group, a large number of dead bacteria was observed, with only a few scattered planktonic bacteria and irregular changes in cell membrane morphology. Crystal violet staining showed that the biofilm density was significantly lower in Vm-MBs+UTMD group compared to control group ( P<0.05), while the differences between Vm, Vm-MBs and UTMD groups were not statistically significant (all P>0.05). Laser confocal microscopy showed that the biofilm thickness was thinner in Vm-MBs, UTMD and Vm-MBs+UTMD groups compared to control group (all P<0.05), with no significant difference between Vm group and control group ( P>0.05) and that the biofilm thickness was thinner in Vm-MBs+UTMD group compared to Vm, Vm-MBs and UTMD groups (all P<0.01), with no significant differences between the other groups (all P>0.05). Bacterial activity in Vm, Vm-MBs, UTMD and Vm-MBs+UTMD groups was significantly lower than that in control group (all P<0.01), with lower in Vm-MBs+UTMD group compared to Vm, Vm-MBs and UTMD groups (all P<0.01), but without significant difference between the other groups (all P>0.05). Conclusion:Vm-MBs combined with UTMD technology can effectively destroy the biofilm morphological structure to reduce biofilm thickness. Meanwhile, Vm-MBs combined with UTMD technology can release antibiotics and significantly decrease bacterial viability to improve antibiotic bactericidal efficacy.