ABSTRACT
Experimental models that consider host-pathogen interactions are relevant for improving knowledge about oral candidiasis. The aim of this study was to assess the epithelial immune responses, Candida penetration of cell monolayers, and virulence during mixed species culture infections. Single species cultures of Candida albicans and mixed cultures (C. albicans, Streptococcus mutans, and Streptococcus sanguinis) were used to infect monolayers of HaCaT and FaDu ATCC HTB-43 cells for 12 h. After infection, IL-18 and IL-34 gene expression was measured to assess epithelial cell immune responses, and lactate dehydrogenase (LDH) activity was measured as an indicator of cell damage. Microscopy determined C. albicans morphology and penetration of fungal cells through the keratinocyte monolayer. Monolayers devoid of infection served as controls. Data were analyzed by an ANOVA one-way test followed by Tukey's post-hoc test (α = 0.05). The results found that IL-18 and IL-34 gene expression and LDH activity were significantly (p < 0.05) upregulated for both cell lines exposed to mixed species cultures compared with C. albicans alone. Candida albicans yeast and hyphae were evident in C. albicans only infections. In contrast, monolayers infected by C. albicans, S. mutans, and S. sanguinis exhibited higher microbial invasion with several hyphal aggregates detected. The presence of streptococci in C. albicans infection enhances the virulence and pathogenicity of the fungus with associated increased immune responses and tissue damage. Extrapolation of these findings to oral infection would indicate the added potential benefit of managing bacterial components of biofilms during treatment.
Subject(s)
Candida albicans , Interleukin-18 , Virulence , Interleukin-18/metabolism , Streptococcus , Streptococcus mutans/physiology , BiofilmsABSTRACT
Abstract Experimental models that consider host-pathogen interactions are relevant for improving knowledge about oral candidiasis. The aim of this study was to assess the epithelial immune responses, Candida penetration of cell monolayers, and virulence during mixed species culture infections. Single species cultures of Candida albicans and mixed cultures (C. albicans, Streptococcus mutans, and Streptococcus sanguinis) were used to infect monolayers of HaCaT and FaDu ATCC HTB-43 cells for 12 h. After infection, IL-18 and IL-34 gene expression was measured to assess epithelial cell immune responses, and lactate dehydrogenase (LDH) activity was measured as an indicator of cell damage. Microscopy determined C. albicans morphology and penetration of fungal cells through the keratinocyte monolayer. Monolayers devoid of infection served as controls. Data were analyzed by an ANOVA one-way test followed by Tukey's post-hoc test (α = 0.05). The results found that IL-18 and IL-34 gene expression and LDH activity were significantly (p < 0.05) upregulated for both cell lines exposed to mixed species cultures compared with C. albicans alone. Candida albicans yeast and hyphae were evident in C. albicans only infections. In contrast, monolayers infected by C. albicans, S. mutans, and S. sanguinis exhibited higher microbial invasion with several hyphal aggregates detected. The presence of streptococci in C. albicans infection enhances the virulence and pathogenicity of the fungus with associated increased immune responses and tissue damage. Extrapolation of these findings to oral infection would indicate the added potential benefit of managing bacterial components of biofilms during treatment.
Resumo O objetivo deste estudo foi avaliar a resposta epithelial imune, a colonização da Candida albicans em monocamadas celulares e sua virulência em resposta a infecções de culturas de biofilme multiespécie. Culturas de biofilme monoespécie de C. albicans e culturas mistas (C. albicans, Streptococcus mutans e Streptococcus sanguinis) foram utilizadas para infectar monocamadas de células HaCaT e FaDu por 12 h. Após a infecção, a expressão dos genes IL-18 e IL-34 foi medida para avaliar as respostas imunes das células epiteliais. A atividade da lactato desidrogenase (LDH) foi medida como um indicador de dano celular. A microscopia determinou a morfologia de C. albicans e a penetração das células fúngicas através da monocamada de queratinócitos. Monocamadas em que não houve infecção serviram como controles. Os dados foram analisados por um teste ANOVA one-way seguido pelo teste post-hoc de Tukey (α = 0,05). Os resultados demonstraram que a expressão gênica de IL-18 e IL-34 e a atividade de LDH foram (p < 0,05) reguladas positivamente para ambas as linhagens de células expostas a culturas de espécies mistas em comparação com C. albicans isoladamente. Leveduras de C.albicans e hifas foram evidentes em infecções apenas por C. albicans. Entretanto, monocamadas infectadas por C. albicans, S. mutans e S. sanguinis exibiram maior invasão microbiana com vários agregados de hifas detectados. Dessa maneira, a presença de estreptococos na infecção por C. albicans aumentou a virulência e a patogenicidade do fungo com respostas imunes aumentadas associadas a danos nos tecidos. A extrapolação desses achados para a infecção oral indicaria o potencial benéfico do controle dos componentes bacterianos em biofilmes durante a terapia da candidíase
ABSTRACT
BACKGROUND: In 2017 Tuta absoluta was identified as an invasive species in China. Due to its rapid geographic expansion and the severe crop damage it causes, T. absoluta poses a serious threat to China's tomato production industry. To determine its geographic distribution and host range, intensive surveys and routine monitoring were conducted across the Chinese mainland between 2018 and 2019. The population colonization coefficient (PCC; ratio of colonized sites and prefectures) and population occurrence index (POI; ratio of infested host species and PCCs) were calculated. RESULTS: In northwestern China, T. absoluta populations established in Xinjiang exhibited a medium PCC value (~0.03). In southwestern China, populations in Yunnan and its five neighboring provinces exhibited high (~0.50 in Yunnan and Guizhou), or low (<0.02 in Guangxi, Sichuan, Hunan, and Chongqing) PCC values. In the Chinese mainland, infestations of four crop plant species (tomato, eggplant, potato, and Chinese lantern) and two wild plant species (black nightshade and Dutch eggplant) were identified; tomatoes were infested in every colonized province. Chinese lantern and Dutch eggplant are potentially novel hosts. Yunnan, Guizhou, and Xinjiang experienced the most serious damage (POI). In southwestern China, observed damage significantly decreased with increased distance from the first discovery site of T. absoluta to the farthest county of an infested province increased. CONCLUSION: T. absoluta populations are well-established and could potentially spread to other regions of China. The present study helps to inform the establishment of better pest management guidelines and strategies in China and tomato-producing regions worldwide. © 2021 Society of Chemical Industry.
Subject(s)
Moths , Solanum lycopersicum , Animals , China/epidemiology , Disease Outbreaks , Host Specificity , Larva , South AmericaABSTRACT
Population-based identity by descent (IBD) mapping is a statistical method for detection of genetic loci that share an ancestral segment among "unrelated" pairs of individuals for a disease. As a complementary method to genome-wide association studies, IBD mapping is robust to allelic heterogeneity and may identify rare inherited variants when combined with sequence data. Our objective is to identify the causal genes for diastolic blood pressure (DBP). We applied a population-based IBD mapping method to 105 unrelated individuals selected from the family data provided for the Genetic Analysis Workshop 19. Using the genome-wide association study data (ie, the microarray data), chromosome 3 was scanned for IBD sharing segments among all pairs of these individuals. At the chromosomal region with the most significant relationship between IBD sharing and DBP, the whole genome sequence data were examined to identify the risk variants for DBP. The most significant chromosomal region that was identified to have a relationship between the IBD sharing and DBP was at 3q12.3 (p = 0.0016), although it did not achieve the chromosome-wide significance level (p = 0.00012). This chromosomal region contains 1 gene, ZPLD1, which has been reported to be associated with cerebral cavernous malformations, a disease with enlarged small blood vessels (capillaries) in the brain. Although 24 deleterious variants were identified at this region, no significant association was found between these variants and DBP (p = 0.40). We presented a mapping strategy which combined a population-based IBD mapping method with sequence data analyses. One gene was located at a chromosomal region identified by this method for DBP. However, further study with a large sample size is needed to assess this result.
ABSTRACT
BACKGROUND AND OBJECTIVES: Postoperative analgesia is crucial for early functional excise after total knee arthroplasty. To investigate the clinical efficacy of ultrasound and nerve stimulator guided continuous femoral nerve block analgesia after total knee arthroplasty. METHODS: 46 patients with ASA grade I-III who underwent total knee arthroplasty received postoperative analgesia from October 2012 to January 2013. In 22 patients, ultrasound and nerve stimulator guided continuous femoral nerve block were performed for analgesia (CFNB group); in 24 patients, epidural analgesia was done (PCEA group). The analgesic effects, side effects, articular recovery and complications were compared between two groups. RESULTS: At 6 h and 12 h after surgery, the knee pain score (VAS score) during functional tests after active exercise and after passive excise in CFNB were significantly reduced when compared with PCEA group. The amount of parecoxib used in CFNB patients was significantly reduced when compared with PCEA group. At 48 h after surgery, the muscle strength grade in CFNB group was significantly higher, and the time to ambulatory activity was shorter than those in PCEA group. The incidence of nausea and vomiting in CFNB patients was significantly reduced when compared with PCEA group. CONCLUSION: Ultrasound and nerve stimulator guided continuous femoral nerve block provide better analgesia at 6 h and 12 h, demonstrated by RVAS and PVAS. The amount of parecoxib also reduces, the incidence of nausea and vomiting decreased, the influence on muscle strength is compromised and patients can perform ambulatory activity under this condition. .
JUSTIFICATIVA E OBJETIVOS: Analgesia pós-operatória é fundamental para o exercício funcional precoce logo após a artroplastia total de joelho. O objetivo foi investigar a eficácia clínica do bloqueio contínuo do nervo femoral guiado por ultrassom e estimulador de nervo em analgesia após artroplastia total do joelho. MÉTODOS: Receberam analgesia pós-operatória, de outubro de 2012 a janeiro de 2013, 46 pacientes, estado físico ASA I-III, submetidos à artroplastia total de joelho. Em 22 pacientes, o bloqueio femoral contínuo foi guiado por ultrassom e estimulador de nervo para analgesia (grupo BFC); em 24 pacientes, analgesia foi administrada por via epidural (grupo ACP). Os efeitos analgésicos, efeitos colaterais, a recuperação articular e as complicações foram comparados entre os dois grupos. RESULTADOS: Às seis e 12 horas após a cirurgia, os escores de dor no joelho (escore EVA) durante os testes funcionais após exercício ativo e passivo foram significativamente menores no grupo BFC do que no grupo ACP. A quantidade usada de parecoxib nos pacientes do grupo BFC foi significativamente menor em comparação com o grupo ACP. Quarenta e oito horas após a cirurgia, o grau de força muscular no grupo BFC foi significativamente maior e o tempo de atividade ambulatória foi menor do que no grupo ACP. A incidência de náusea e vômito em pacientes do grupo BFC foi significativamente menor em comparação com o grupo ACP. CONCLUSÃO: O bloqueio femoral contínuo guiado por ultrassom e estimulador do nervo proporcionou melhor analgesia às seis e 12 horas, demonstrada por EVA-R e EVA-P. A quantidade de parecoxib também foi menor, a incidência de náusea e vômito diminuiu, a influência sobre a força muscular é comprometida e os pacientes podem fazer atividade ambulatorial sob essa condição. .
JUSTIFICACIÓN Y OBJETIVOS: La analgesia postoperatoria es fundamental para el ejercicio funcional precoz posteriormente a la artroplastia total de rodilla. El objetivo fue investigar la eficacia clínica del bloqueo continuo del nervio femoral guiado por ultrasonido y estimulador de nervio en analgesia después de la artroplastia total de la rodilla. MÉTODOS: Cuarenta y seis pacientes, con estado físico ASA I-III, sometidos a artroplastia total de rodilla recibieron analgesia postoperatoria de octubre de 2012 a enero de 2013. En 22 pacientes, el bloqueo femoral continuo fue guiado por ultrasonido y estimulador de nervio para analgesia (grupo BFC); en 24 pacientes, la analgesia fue administrada por vía epidural (grupo ACP). Los efectos analgésicos, efectos colaterales, recuperación articular y las complicaciones fueron comparados entre los 2 grupos. RESULTADOS: A las 6 y 12 h después de la operación, las puntuaciones de dolor en la rodilla (puntuación EVA) durante los test funcionales después del ejercicio activo y pasivo fueron significativamente menores en el grupo BFC que en el grupo ACP. La cantidad usada de parecoxib en los pacientes del grupo BFC fue significativamente menor en comparación con el grupo ACP. Cuarenta y ocho horas después de la operación, el grado de fuerza muscular en el grupo BFC fue significativamente mayor y el tiempo de actividad ambulatoria fue menor que en el grupo ACP. La incidencia de náuseas y vómitos en pacientes del grupo BFC fue significativamente menor en comparación con el grupo ACP. CONCLUSIÓN: El bloqueo femoral continuo guiado por ultrasonido y estimulador del nervio proporcionaron una mejor analgesia a las 6 y 12 horas, lo que quedó demostrado por EVA-R y EVA-P. La cantidad de parecoxib también fue menor, la incidencia de náuseas y vómito disminuyó, la influencia sobre la fuerza muscular está comprometida y los pacientes pueden realizar una actividad ambulatoria bajo esa condición. .
Subject(s)
Humans , Analgesia, Epidural , Ultrasonography/instrumentation , Arthroplasty, Replacement, Knee/instrumentation , Cyclooxygenase 2 Inhibitors/administration & dosageABSTRACT
BACKGROUND AND OBJECTIVES: Postoperative analgesia is crucial for early functional excise after total knee arthroplasty. To investigate the clinical efficacy of ultrasound and nerve stimulator guided continuous femoral nerve block analgesia after total knee arthroplasty. METHODS: 46 patients with ASA grade I-III who underwent total knee arthroplasty received postoperative analgesia from October 2012 to January 2013. In 22 patients, ultrasound and nerve stimulator guided continuous femoral nerve block were performed for analgesia (CFNB group); in 24 patients, epidural analgesia was done (PCEA group). The analgesic effects, side effects, articular recovery and complications were compared between two groups. RESULTS: At 6h and 12h after surgery, the knee pain score (VAS score) during functional tests after active exercise and after passive excise in CFNB were significantly reduced when compared with PCEA group. The amount of parecoxib used in CFNB patients was significantly reduced when compared with PCEA group. At 48h after surgery, the muscle strength grade in CFNB group was significantly higher, and the time to ambulatory activity was shorter than those in PCEA group. The incidence of nausea and vomiting in CFNB patients was significantly reduced when compared with PCEA group. CONCLUSION: Ultrasound and nerve stimulator guided continuous femoral nerve block provide better analgesia at 6h and 12h, demonstrated by RVAS and PVAS. The amount of parecoxib also reduces, the incidence of nausea and vomiting decreased, the influence on muscle strength is compromised and patients can perform ambulatory activity under this condition.
ABSTRACT
The reaction of 2,6-pyridinedimethanol (pdmH(2)), CoCl(2)·6H(2)O, Ln(NO(3))(3)·6H(2)O and pivalic acid (pivH) in the presence of triethylamine in MeCN and CH(2)Cl(2) under ambient conditions results in the tetranuclear heterobimetallic compounds [Co(II)(2)Ln(2)(pdmH)(4)(Piv)(6)]·4CH(3)CN (Ln = Y (1), Gd (2), Tb (3), Ho (4)) and [Co(II)(2)Dy(2)(pdmH)(4)(Piv)(6)]·2CH(3)CN (5). The molecular structures of 1-5 were determined by single-crystal X-ray diffraction and reveal that they are isostructural. However, compounds 1-4 crystallize in the monoclinic space group P2(1)/n, while compound 5 crystallizes in the orthorhombic space group Pnna. In all of these compounds, the four metal ions are held together by four alkoxide mu(3)-RCH(2)O(-) bridges to form novel Co(2)Ln(2)O(4)-heterocubanes. Magnetic properties of 1-5 have been investigated using dc and ac susceptibility measurements. Of these compounds, only compound 5 displays an out-of-phase signal in the ac susceptibility and exhibits slow relaxation of the magnetization, which is attributed to the presence of the anisotropic Dy(III) ions.
ABSTRACT
Interleukin-18 deficient mice on a BALB/c background display increased resistance to cutaneous infection with Leishmania mexicana, with reduced lesion progression and reduced parasite burdens compared with wild-type mice. Infected IL-18-/- mice had lower antigen specific IgG1 levels and total IgE levels and conversely higher antigen specific IgG2a levels than similarly infected wild-type mice. Splenocytes isolated from infected IL-18-/- mice produced significantly lower levels of antigen induced IL-4 and higher levels of IFN-gamma than wild-type animals. Consequently IL-18 during L. mexicana infection of BALB/c mice promotes a Th2 biased response and thereby has a disease exacerbating role.
Subject(s)
Interleukin-18/immunology , Leishmania mexicana/immunology , Th2 Cells/immunology , Animals , Antibodies, Protozoan/blood , Immunoglobulin E/blood , Immunoglobulin G/blood , Interferon-gamma/metabolism , Interleukin-18/deficiency , Interleukin-4/metabolism , Lymphocytes/immunology , Mice , Mice, Inbred BALB C , Mice, Knockout , Severity of Illness Index , Skin/pathology , Spleen/immunologyABSTRACT
IL-15 is closely associated with inflammatory diseases. IL-15 targeting is effective in treating experimental and clinical rheumatoid arthritis (RA). Because hyperalgesia accompanies RA, we investigated the ability of IL-15 to induced nociceptor sensitization (hypernociception). We report here that IL-15 induced time- and dose-dependent mechanical hypernociception in mice. IL-15-induced hypernociception was inhibited by treatment with a dual endothelin receptor type A (ET(A))/endothelin receptor type B (ET(B)) antagonist (bosentan), ET(A) receptor antagonist (BQ123), or cyclooxygenase inhibitor (indomethacin). Moreover, IL-15 failed to induce hypernociception in IFN-gamma(-/-) mice, suggesting that IL-15 mediated hypernociception via an IFN-gamma-, endothelin (ET)-, and prostaglandin-dependent pathway. Consistent with this finding, IFN-gamma and ET-1 induced dose- and time-dependent mechanical hypernociception that was inhibited by BQ123 or indomethacin but not BQ788 (an ET(B) receptor antagonist). IFN-gamma induced the production of ET-1 and the expression of its mRNA precursor (preproET-1, PPET-1). Moreover, IL-15 also induced ET-1 production and PPET-1 mRNA expression in an IFN-gamma-dependent manner. Prostaglandin E(2) (PGE(2)) production was induced by IL-15, IFN-gamma, or ET-1. We also found that hypernociception induced by ovalbumin (OVA) in OVA-immunized mice was significantly diminished by treatment with sIL-15Ralpha (soluble IL-15 receptor alpha-chain), bosentan, BQ123, or indomethacin. Furthermore, OVA challenge induced the expression of PPET-1 mRNA in WT mice but not in IFN-gamma(-/-) mice. The PPET-1 mRNA expression was also inhibited by sIL-15Ralpha pretreatment. Therefore, our results demonstrate the sequential mechanical hypernociceptive effect of IL-15 --> IFN-gamma --> ET-1 --> PGE(2) and suggest that these molecules may be targets of therapeutic intervention in antigen-induced hypernociception.
Subject(s)
Endothelins/metabolism , Interferon-gamma/metabolism , Interleukin-15/pharmacology , Prostaglandins/metabolism , Animals , Endothelins/pharmacology , Gene Expression Regulation , Inflammation/chemically induced , Inflammation/immunology , Inflammation/metabolism , Interferon-gamma/deficiency , Interferon-gamma/genetics , Interferon-gamma/pharmacology , Mice , Ovalbumin/pharmacology , Prostaglandins/genetics , RNA, Messenger/geneticsABSTRACT
The human syncytiotrophoblast (hST) is the most apical epithelial barrier that covers the villous tree of the human placenta. An intricate and highly organized network of cytoskeletal structures supports the hST. Recently, polycystin-2 (PC2), a TRP-type nonselective cation channel, was functionally observed in hST, where it may be an important player to Ca2+ transport. Little is known, however, about channel regulation in hST. In this report, the regulatory role of actin dynamics on PC2 channels reconstituted from hST apical membranes was explored. Acute addition of cytochalasin D (CD, 5 microg ml-1) to reconstituted hST apical membranes transiently increased K+ -permeable channel activity. The actin-binding proteins alpha-actinin and gelsolin, as well as PC2, were observed by Western blot and immunofluorescence analyses in hST vesicles. CD treatment of hST vesicles resulted in a re-distribution of actin filaments, in agreement with the effect of CD on K+ channel activity. In contrast, addition of exogenous monomeric actin, but not prepolymerized actin, induced a rapid inhibition of channel function in hST. This inhibition was obliterated by the presence of CD in the medium. The acute (<15 min) CD stimulation of K+ channel activity was mimicked by addition of the actin-severing protein gelsolin in the presence, but not in the absence, of micromolar Ca2+. Ca2+ transport through PC2 triggers a regulatory feedback mechanism, which is based on the severing and re-formation of filamentous actin near the channels. Cytoskeletal structures may thus be relevant to ion transport regulation in the human placenta.