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BACKGROUND: Acupuncture has been used for the treatment of chronic migraine, but high-quality evidence is scarce. We aimed to evaluate acupuncture's efficacy and safety compared to topiramate for chronic migraine. METHODS: This double-dummy randomized controlled trial included participants aged 18-65 years diagnosed with chronic migraine. They were randomly assigned (1:1) to receive acupuncture (three sessions/week) plus topiramate placebo (acupuncture group) or topiramate (50-100â mg/day) plus sham acupuncture (topiramate group) over 12 weeks, with the primary outcome being the mean change in monthly migraine days during weeks 1-12. RESULTS: Of 123 screened patients, 60 (mean age 45.8, 81.7% female) were randomly assigned to acupuncture or topiramate groups. Acupuncture demonstrated significantly greater reductions in monthly migraine days than topiramate (weeks 1-12: -2.79 [95% CI: -4.65 to -0.94, p = 0.004]; weeks 13-24: -3.25 [95% CI: -5.57 to -0.92, p = 0.007]). No severe adverse events were reported. CONCLUSIONS: Acupuncture may be safe and effective for treating chronic migraine. The efficacy of 12 weeks of acupuncture was sustained for 24 weeks and superior to that of topiramate. Acupuncture can be used as an optional preventive therapy for chronic migraine. TRIAL REGISTRATION: ISRCTN.org Identifier 13563102.
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Terapia por Acupuntura , Trastornos Migrañosos , Topiramato , Humanos , Topiramato/uso terapéutico , Topiramato/administración & dosificación , Trastornos Migrañosos/prevención & control , Trastornos Migrañosos/terapia , Femenino , Masculino , Persona de Mediana Edad , Adulto , Terapia por Acupuntura/métodos , Enfermedad Crónica , Resultado del Tratamiento , Método Simple Ciego , Adulto Joven , Terapia Combinada/métodos , Adolescente , AncianoRESUMEN
Advanced oxidation processes (AOPs) demonstrate great micropollutant degradation efficiency. In this study, CuFe2O4 was successfully used to activate peracetic acid (PAA) to remove Rhodamine B. Acetyl(per)oxyl radicals were the dominant species in this novel system. The addition of 2,4-hexadiene (2,4-HD) and Methanol (MeOH) significantly inhibited the degradation efficiency of Rhodamine B. The ≡Cu2+/≡Cu+ redox cycle dominated PAA activation, thereby producing organic radicals (R-OË) including CH3C(O)OË and CH3C(O)OOË, which accounted for the degradation of Rhodamine B. Increasing either the concentration of CuFe2O4 (0-100 mg/L) or PAA (10-100 mg/L) promoted the removal efficiency of this potent system. In addition, weakly acid to weakly alkali pH conditions (6-8) were suitable for pollutant removal. The addition of Humid acid (HA), HCO3-, and a small amount of Cl- (10-100 mmol·L-1) slightly inhibited the degradation of Rhodamine B. However, degradation was accelerated by the inclusion of high concentrations (200 mmol·L-1) of Cl-. After four iterations of catalyst recycling, the degradation efficiency remained stable and no additional functional group characteristic peaks were observed. Taking into consideration the reaction conditions, interfering substances, system stability, and pollutant-removal efficiency, the CuFe2O4/PAA system demonstrated great potential for the degradation of Rhodamine B.
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Ácido Peracético , Contaminantes Químicos del Agua , Álcalis , Peróxido de Hidrógeno , Metanol , Oxidación-Reducción , RodaminasRESUMEN
Objective: To investigate the regulatory effect and mechanism of vitamin D on the local renin-angiotensin system at maternal-fetal interface in the pathological process of preeclampsia (PE). Methods: The mRNA and protein expression of renin in decidua of normal pregnancy and PE placentas was determined by RT-PCR and Western blot. Normal decidual tissues were treated with active and inactive vitamin D for 48 h in vitro and the expressions of renin and vitamin D deactivating enzyme CYP24A1 were determined by RT-PCR and Western blot. Normal decidual stromal cells and glandular epithelial cells were isolated and purified, and identified by immunocytochemical staining. RT-PCR was used to examine the mRNA of vdr, cyp27 b1, cyp24 a1, and renin in the two types of cells and in decidual tissue, and the mRNA products were subjected to gel electrophoresis. These two cell types were treated with active and inactive vitamin D in vitro and the expressions of renin and vitamin D deactivating enzyme CYP24A1 were determined by RT-PCR and Western blot. Decidual gland epithelial cells were treated with protein kinase A (PKA) activator forskolin or inhibitor H89 to explore the interaction between PKA pathway and vitamin D in the regulation of renin expression. Results: The expression of renin in PE decidua was significantly higher than that of normal control at transcriptional and translational levels ( P<0.05). Vitamin D treatment could significantly down-regulate the expression of renin in normal decidua tissues ( P<0.05), while it significantly up-regulated CYP24A1 expression ( P<0.001). Decidual stromal cells and gland epithelial cells were successfully isolated from decidual tissue. Compared with that in decidual stromal cells, the mRNA level of vitamin D-related molecules in gland epithelial cells was more similar to that in decidual tissue. Active or inactive vitamin D treatment significantly inhibited the expression of renin in glandular epithelial cells ( P<0.05), but the expression of renin in decidual stromal cells was not affected. However, the treatment of active or inactive vitamin D in these two kinds of cells significantly increased the expression of CYP24A1 ( P<0.001). Active vitamin D could significantly inhibit the upregulation of renin by PKA agonist forskolin, and could inhibit the expression of renin through synergy with PKA inhibitor H89. Conclusion: The expression of renin in placental decidua is up-regulated in patients with PE, and the activation of local renin-angiotensin system at the maternal-fetal interface may be involved in the pathogenesis of PE. Vitamin D can specifically down-regulate renin expression in human decidual gland epithelial cells by competing with the PKA pathway. Vitamin D supplementation may have potential value for clinical intervention of PE.
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Preeclampsia , Vitamina D , Embarazo , Humanos , Femenino , Vitamina D/farmacología , Renina , Vitamina D3 24-Hidroxilasa/genética , Colforsina , Placenta , ARN MensajeroRESUMEN
This study investigated the potential efficacy of pirarubicin (THP) in modulating rabbit conjunctival fibrosis both in vitro and in vivo and characterized the underlying mechanisms. Primary rabbit conjunctival fibroblasts (RCF) were cultured and treated with THP or mitomycin C (MMC) for 5 min, followed by assaying for cell viability, cell cycle distribution, apoptotic and autophagic pathways. The production of reactive oxygen species (ROS) and chemotaxis of macrophages by RCF were evaluated using 2',7'-dichlorofluorescein diacetate (DCFH-DA) labeling and transwell migration assay, respectively. Limbal stem cell excision in combination with alkali burn was performed on the rabbits to establish a model of limbal deficiency and conjunctival fibro-vascular invasion. After three months, the modeled fibro-vascular tissue was excised combined with topical subconjunctival 5-min exposure to THP compared with MMC intraoperatively. The recurrence of postoperative fibrosis and the expression of apoptosis, autophagy, and inflammation markers were evaluated by immunohistochemistry. All modeled rabbits developed conjunctival fibro-vascular lesions, which were similar to human recurrent pterygium (HRP). Both THP and MMC inhibited RCF proliferation and arrested cell cycle at the G0/G1 phase. In particular, 7.5 µmol/L THP remarkably promoted RCF autophagy by upregulating the levels of Beclin 1, Atg 5/12 conjugate, and LC3B, whereas, 15 µmol/L THP significantly triggered a cascade of mitochondrial-associated RCF apoptosis. THP induced the production of ROS and enhanced the chemoattraction of macrophages by RCF. Similar to 600 µmol/L MMC, both 7.5 µmol/L and 15 µmol/L THP attenuated postoperative conjunctival fibrosis in the models; 7.5 µmol/L THP preferentially enhanced autophagy while causing fewer side effects. THP exerted its antifibrotic action by modulating autophagy in RCF, inducing cell cycle arrest, and mitochondrial-mediated apoptosis. THP at the dose of 7.5 µmol/L prevented postoperative conjunctival fibrosis in an animal model.
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Apoptosis/efectos de los fármacos , Muerte Celular Autofágica/efectos de los fármacos , Doxorrubicina/análogos & derivados , Fibroblastos/patología , Pterigion/tratamiento farmacológico , Animales , Supervivencia Celular , Modelos Animales de Enfermedad , Doxorrubicina/farmacología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibrosis/patología , Fibrosis/prevención & control , Humanos , Pterigion/patología , Conejos , Especies Reactivas de Oxígeno/metabolismoRESUMEN
A large number of viruses have been found to be associated with ocular diseases, including human adenovirus, human herpesvirus (HHV), human T lymphotropic virus type-1 (HTLV-1), and newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This group of diseases is prone to be misdiagnosed or missed diagnosis, resulting in serious tissue and visual damage. Etiological diagnosis is a powerful auxiliary mean to diagnose the ocular diseases associated with human adenovirus, herpes simplex virus 1 and varicella-zoster virus, and it provides the leading diagnosis evidence of infections with herpes simplex virus 2, Epstein-Barr virus, cytomegalovirus, HHV-6/7, HHV-8, HTLV-1 and SARS-CoV-2. Virus isolation, immunoassay and genetic diagnosis are usually used for etiologic diagnosis. For genetic diagnosis, the PCR technique is the most important approach because of its advantages of rapid detection, convenient operation, high sensitivity and high specificity.
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Oftalmopatías , Investigación , Virosis , COVID-19 , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/virología , ADN Viral/genética , Oftalmopatías/diagnóstico , Oftalmopatías/virología , Humanos , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/virología , Investigación/tendencias , Virosis/diagnóstico , Virosis/virologíaRESUMEN
PURPOSE: To evaluate the effect of different graft fixation sequences in one-stage anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) reconstruction on (1) knee biomechanics and (2) tibiofemoral alignment. METHODS: Twelve porcine knees were used in this study. Five fixation sequences were performed (angle indicating knee flexion): (a) PCL at 30° and ACL at 30°, (b) PCL at 90° and ACL at 30°, (c) ACL at 30° and PCL at 30°, (d) ACL at 30° and PCL at 90°, and (e) ACL and PCL simultaneous fixation at 30°. Anterior and posterior tibial translation was measured under an 89 N load. A 3-D digitizer was used to measure the change in anteroposterior (AP) tibiofemoral position. RESULTS: None of the graft fixation sequences restored the AP laxity of the intact knee, and there are minimal differences in the in situ tissue forces in the ACL and PCL grafts. The reconstructions with fixation of the PCL graft first resulted in a significantly larger change in AP tibiofemoral position from the intact knee at 60° and 90° of knee flexion than the reconstructions with fixation of the ACL graft first (p < 0.05). CONCLUSION: Fixation of the ACL graft at 30° of knee flexion followed by fixation of the PCL graft can best restore the tibiofemoral position of the intact knee. This study has clinical relevance in regard to the effect of graft fixation sequence on the position of the tibia relative to the femur in one-stage ACL and PCL reconstruction.
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Reconstrucción del Ligamento Cruzado Anterior/métodos , Ligamento Cruzado Anterior/cirugía , Desviación Ósea/prevención & control , Traumatismos de la Rodilla/cirugía , Articulación de la Rodilla/fisiopatología , Reconstrucción del Ligamento Cruzado Posterior/métodos , Ligamento Cruzado Posterior/cirugía , Animales , Reconstrucción del Ligamento Cruzado Anterior/efectos adversos , Fenómenos Biomecánicos , Desviación Ósea/etiología , Modelos Animales de Enfermedad , Traumatismos de la Rodilla/fisiopatología , Articulación de la Rodilla/cirugía , Reconstrucción del Ligamento Cruzado Posterior/efectos adversos , Procedimientos de Cirugía Plástica/efectos adversos , Procedimientos de Cirugía Plástica/métodos , Porcinos , Tendones/trasplanteRESUMEN
OBJECTIVE: To explore the clinical features and mutation of TGFBI gene in a Chinese pedigree affected with lattice corneal dystrophy (LCD). METHODS: Genomic DNA was extracted from 35 members including 11 patients from the pedigree. The 17 exons and splicing region of introns of the TGFBI gene were amplified by PCR. The products were directly sequenced and compared with GenBank database to identify potential mutation. Bioinformatic analysis was carried out to predict the effect of mutation on proteins. RESULTS: A heterozygous mutation (p.R124C) was found in exon 4 of the TGFBI gene in all patients from the pedigree but not among unaffected members. The mode of inheritance of corneal dystrophy in this pedigree was identified as autosomal dominant. Bioinformatics analysis predicted that the p.R124C mutation may be functionally deleterious. The phenotype of corneal dystrophy in the pedigree was determined to be LCD I type. CONCLUSION: The p.R124C mutation of the TGFBI gene probably underlies the pathogenesis of LCD in this Chinese pedigree. Genetic testing can facilitate proper diagnosis of this type of corneal dystrophy.
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Distrofias Hereditarias de la Córnea/genética , Factor de Crecimiento Transformador beta1/genética , Pueblo Asiatico , China , Análisis Mutacional de ADN , Exones , Proteínas de la Matriz Extracelular , Humanos , Mutación , LinajeRESUMEN
BACKGROUND: Lipoprotein lipase (LPL) deficiency is an autosomal recessive genetic disorder characterized by extreme hypertriglyceridemia, with no cure presently available. The purpose of this study was to test the possibility of using cell therapy to alleviate LPL deficiency. METHODS: The LPL coding sequence was cloned into the MSCV retrovirus vector, after which MSCV-hLPL and MSCV (empty construct without LPL coding sequence) virion suspensions were made using the calcium chloride method. A muscle cell line (C2C12), kidney cell line (HEK293T) and pre-adipocyte cell line (3 T3-L1) were transfected with the virus in order to express recombinant LPL in vitro. Finally, each transfected cell line was injected subcutaneously into nude mice to identify the cell type which could secret recombinant LPL in vivo. Control cells were transfected with the MSCV empty vector. LPL activity was analyzed using a radioimmunoassay. RESULTS: After virus infection, the LPL activity at the cell surface of each cell type was significantly higher than in the control cells, which indicates that all three cell types can be used to generate functional LPL. The transfected cells were injected subcutaneously into nude mice, and the LPL activity of the nearby muscle tissue at the injection site in mice injected with 3 T3-L1 cells was more than 5 times higher at the injection sites than at non-injected control sites. The other two types of cells did not show this trend. CONCLUSION: The subcutaneous injection of adipocytes overexpressing LPL can improve the LPL activity of the adjacent tissue of nude mice. This is a ground-breaking preliminary study for the treatment of LPL deficiency, and lays a good foundation for using cell therapy to correct LPL deficiency.
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Adipocitos/trasplante , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Hiperlipoproteinemia Tipo I/terapia , Hipertrigliceridemia/terapia , Lipoproteína Lipasa/genética , Células Musculares/trasplante , Adipocitos/citología , Adipocitos/metabolismo , Adipocitos/virología , Animales , Línea Celular , Modelos Animales de Enfermedad , Expresión Génica , Vectores Genéticos/química , Vectores Genéticos/metabolismo , Células HEK293 , Humanos , Hiperlipoproteinemia Tipo I/genética , Hiperlipoproteinemia Tipo I/metabolismo , Hiperlipoproteinemia Tipo I/patología , Hipertrigliceridemia/genética , Hipertrigliceridemia/metabolismo , Hipertrigliceridemia/patología , Inyecciones Subcutáneas , Lipoproteína Lipasa/metabolismo , Ratones , Ratones Desnudos , Células Musculares/citología , Células Musculares/metabolismo , Células Musculares/virología , Células 3T3 NIH , Retroviridae/genética , Retroviridae/metabolismo , Transfección , Triglicéridos/metabolismoRESUMEN
BACKGROUND: Keratoconus normally presents as a sporadic disease. Although different studies have found sequence variants of the visual system homeobox 1 (VSX1) gene associated with keratoconus in humans, no research has detected such variants in sporadic keratoconus patients from China. To investigate the possibility of VSX1 being a candidate susceptibility gene for Chinese patients with sporadic keratoconus, we performed sequence screening of this gene in such patients. METHODS: Whole DNA was obtained from the leukocytes in the peripheral venous blood of 50 patients with sporadic keratoconus and 50 control subjects without this ocular disorder. Polymerase chain reaction single-strand conformation polymorphism analysis and direct DNA sequencing technology were used to detect sequence variation in the five exons and splicing regions of the introns of the VSX1 gene. The sequencing results were analyzed using DNAstar software. RESULTS: One novel missense heterozygous sequence variant (p.Arg131Pro) was found in the first exon of the VSX1 gene in one keratoconus patient. Another heterozygous sequence variant (p.Gly160Val) in the second exon was found in two keratoconus patients. These variants were not detected in the control subjects. In the third intron of the VSX1 gene, c.8326G > A nucleotide substitution (including heterozygous and homozygous change) was also discovered. The frequency of this variation did not differ significantly between patients and controls, it should belong to single-nucleotide polymorphism of the VSX1 gene. Bioinformatic analysis also predicted that one missense sequence variation (p.Arg131Pro) may not cause a pathogenic change. CONCLUSIONS: In this study, we added one novel missense sequence variation (p.Arg131Pro) in the coding region of the VSX1 gene to the range of VSX1 coding region variations observed in patients with sporadic keratoconus from China. Our work suggests that VSX1 sequence variants might be involved in the pathogenesis of sporadic keratoconus, but their precise role in disease causation requires further investigation.
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Proteínas del Ojo/genética , Proteínas de Homeodominio/genética , Queratocono/genética , Mutación Missense , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Pueblo Asiatico/genética , China , Exones/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-Simple , Análisis de Secuencia de ADN , Adulto JovenRESUMEN
OBJECTIVE: To analyze the clinical features and TGFBI gene mutation in a Chinese family affected with Reis-Bucklers corneal dystrophy. METHODS: Genomic DNA was extracted from 53 members including 9 patients from the family. The 17 exons and splice region of introns of the TGFBI gene were amplified by PCR and directly sequenced. All family members were subjected to ophthalmologic examination. RESULTS: A heterozygous mutation (R124L) was found in exon 4 of the TGFBI gene among all patients from the family. The same mutation was not found among unaffected family members. The inheritance pattern of the family was identified as autosomal dominant, and the Reis-Bucklers corneal dystrophy in the family was diagnosed as the geographic type. CONCLUSION: The R124L mutation of the TGFBI gene probably underlies the pathogenesis of Reis-Bucklers corneal dystrophy in this Chinese family. Molecular genetic approach is useful for the proper diagnosis of this type of corneal dystrophy.
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Distrofias Hereditarias de la Córnea/genética , Mutación , Factor de Crecimiento Transformador beta1/genética , Distrofias Hereditarias de la Córnea/etiología , Femenino , Humanos , Masculino , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: Reis-Bücklers corneal dystrophy (RBCD) was consistently reported as a corneal dystrophy only affected Bowman's layer and superficial corneal stroma, and superficial keratectomy was a recommendation surgery for treatment in literatures. The study reported new histopathological and ultrastructural findings in RBCD caused by the Arg124Leu mutation of transforming growth factor induced (TGFBI) gene in a four-generation Chinese pedigree. METHODS: Subjects including eight patients and seven unaffected family members received slit-lamp biomicroscopy and photography. DNA was obtained from all subjects, and exons 4 and 11 to 14 of TGFBI gene were analyzed by polymerase chain reaction and the products were sequenced. Anterior segment optical coherence tomography (AS OCT) and in vivo confocal microscopy were conducted for ten eyes of five patients. Based on the results of AS OCT and in vivo confocal microscopy, deep anterior lamellar keratoplasty (DLKP) using cryopreserved donor cornea was applied for four eyes of four patients. Four lamellar dystrophic corneal buttons were studied by light and transmission electron microscopy, and TGFBI immunohistochemistry. RESULTS: Eight patients had typical clinical manifestations of RBCD presenting recurrent painful corneal erosion starting in their early first decades, along with age-dependent progressive geographic corneal opacities. TGFBI sequencing revealed a heterozygous mutation, Arg124Leu in all eight patients. Anterior segment optical coherence tomography and in vivo confocal microscopy showed the dystrophic deposits involved not only in subepithelial and superficial stroma, but also in mid- or posterior stroma in four examined advanced eyes. Light microscopy showed Bowman's layer was absent, replaced by abnormal deposits stain bright red with Masson's trichrome. In superficial cornea, the deposits stacked and produced three to five continuous bands parallel to the corneal collagen lamellae. In mid- to posterior stroma, numerous granular or dot- like aggregates were heavily scattered, and most of them presented around the nuclei of stromal keratocytes. Transmission electron microscopy revealed the multiple electron-dense rod-shaped deposits aggregated and formed a characteristic pattern of three to five continuous bands in superficial cornea, which were similar to those seen under light microscopy. In mid- to posterior stroma, clusters of rod-shaped bodies were scattered extracellular or intracellular of the stromal keratocytes between the stromal lamellae suggesting the close relationship between mutated proteins and keratocyte. CONCLUSIONS: The study offer evidences indicating DLKP is a viable treatment option for advanced RBCD to avoid recurrence, and the mutated TGFBIp in dystrophic corneas are of keratocytes origin.
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Distrofias Hereditarias de la Córnea/genética , Distrofias Hereditarias de la Córnea/patología , Factor de Crecimiento Transformador beta/genética , Adolescente , Adulto , Anciano , Pueblo Asiatico , Lámina Limitante Anterior/patología , Lámina Limitante Anterior/ultraestructura , Niño , Preescolar , Córnea/patología , Córnea/ultraestructura , Distrofias Hereditarias de la Córnea/cirugía , Queratocitos de la Córnea/patología , Sustancia Propia/patología , Sustancia Propia/ultraestructura , Exones , Proteínas de la Matriz Extracelular/genética , Femenino , Humanos , Inmunohistoquímica , Queratoplastia Penetrante , Masculino , Microscopía Confocal , Microscopía Electrónica de Transmisión , Persona de Mediana Edad , Mutación , Linaje , Reacción en Cadena de la Polimerasa , Tomografía de Coherencia Óptica , Adulto JovenRESUMEN
Auxin plays a pivotal role in many facets of plant development. It acts by inducing the interaction between auxin-responsive [auxin (AUX)/indole-3-acetic acid (IAA)] proteins and the ubiquitin protein ligase SCF(TIR) to promote the degradation of the AUX/IAA proteins. Other cofactors and chaperones that participate in auxin signaling remain to be identified. Here, we characterized rice (Oryza sativa) plants with mutations in a cyclophilin gene (OsCYP2). cyp2 mutants showed defects in auxin responses and exhibited a variety of auxin-related growth defects in the root. In cyp2 mutants, lateral root initiation was blocked after nuclear migration but before the first anticlinal division of the pericycle cell. Yeast two-hybrid and in vitro pull-down results revealed an association between OsCYP2 and the co-chaperone Suppressor of G2 allele of skp1 (OsSGT1). Luciferase complementation imaging assays further supported this interaction. Similar to previous findings in an Arabidopsis thaliana SGT1 mutant (atsgt1b), degradation of AUX/IAA proteins was retarded in cyp2 mutants treated with exogenous 1-naphthylacetic acid. Our results suggest that OsCYP2 participates in auxin signal transduction by interacting with OsSGT1.
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Ciclofilinas/metabolismo , Ácidos Indolacéticos/farmacología , Oryza/genética , Proteínas de Plantas/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Clonación Molecular , Ciclofilinas/genética , Regulación de la Expresión Génica de las Plantas , Datos de Secuencia Molecular , Mutación , Oryza/crecimiento & desarrollo , Reguladores del Crecimiento de las Plantas/farmacología , Proteínas de Plantas/genética , Transducción de Señal , Técnicas del Sistema de Dos HíbridosRESUMEN
BACKGROUND: There is an association between migraine and dementia, however, their causal relationship remains unclear. This study employed bidirectional two-sample Mendelian randomization (MR) to investigate the potential causal relationship between migraine and dementia and its subtypes: Alzheimer's disease (AD), vascular dementia (VaD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). METHODS: Summary-level statistics data were obtained from publicly available genome-wide association studies (GWAS) for both migraine and five types of dementia. Single nucleotide polymorphisms (SNPs) associated with migraine and each dementia subtype were selected. MR analysis was conducted using inverse variance weighting (IVW) and weighted median (WM) methods. Sensitivity analyses included Cochran's Q test, MR pleiotropy residual sum and outlier (MR-PRESSO) analysis, the intercept of MR-Egger, and leave-one-out analysis. RESULTS: Migraine showed a significant causal relationship with AD and VaD, whereas no causal relationship was observed with all-cause dementia, FTD, or DLB. Migraine may be a potential risk factor for AD (odds ratio [OR]: 1.09; 95% confidence interval [CI]: 0.02-0.14; P = 0.007), while VaD may be a potential risk factor for migraine (OR: 1.04; 95% CI: 0.02-0.06; P = 7.760E-5). Sensitivity analyses demonstrated the robustness of our findings. CONCLUSION: Our study suggest that migraine may have potential causal relationships with AD and VaD. Migraine may be a risk factor for AD, and VaD may be a risk factor for migraine. Our study contributes to unraveling the comprehensive genetic associations between migraine and various types of dementia, and our findings will enhance the academic understanding of the comorbidity between migraine and dementia.
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Demencia , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Trastornos Migrañosos , Polimorfismo de Nucleótido Simple , Humanos , Trastornos Migrañosos/genética , Trastornos Migrañosos/complicaciones , Demencia/genética , Predisposición Genética a la EnfermedadRESUMEN
Covalent organic frameworks (COFs) constitute a class of highly functional porous materials composed of lightweight elements interconnected by covalent bonds, characterized by structural order, high crystallinity, and large specific surface area. The integration of naturally occurring porphyrin molecules, renowned for their inherent rigidity and conjugate planarity, as building blocks in COFs has garnered significant attention. This strategic incorporation addresses the limitations associated with free-standing porphyrins, resulting in the creation of well-organized porous crystal structures with molecular-level directional arrangements. The unique optical, electrical, and biochemical properties inherent to porphyrin molecules endow these COFs with diversified applications, particularly in the realm of biology. This review comprehensively explores the synthesis and modulation strategies employed in the development of porphyrin-based COFs and delves into their multifaceted applications in biological contexts. A chronological depiction of the evolution from design to application is presented, accompanied by an analysis of the existing challenges. Furthermore, this review offers directional guidance for the structural design of porphyrin-based COFs and underscores their promising prospects in the field of biology.
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Estructuras Metalorgánicas , Porfirinas , Porfirinas/química , Porfirinas/síntesis química , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/síntesis química , Humanos , Porosidad , AnimalesRESUMEN
BACKGROUND: Diabetic patients have a high prevalence of shoulder pain and stiffness. Interleukin (IL) 1ß was reportedly correlated with shoulder stiffness and decreased shoulder function. We retrospectively compared the expression of IL-1ß in the subacromial synovial fluid between diabetic and nondiabetic patients with rotator cuff tearing. MATERIALS AND METHODS: We enrolled 68 patients with rotator cuff tearing (23 diabetic patients and 45 nondiabetic patients). The preoperative sum of range-of-motion deficit (SROMD), Constant score, and visual analog scale (VAS) score were obtained. Intraoperatively, subacromial synovial fluid was collected for the IL-1ß level measurement. Comparisons of IL-1ß levels, Constant scores, SROMD, and VAS scores between diabetic and nondiabetic patients were analyzed with the Mann-Whitney U test. RESULT: Diabetic patients with rotator cuff tearing had significantly increased subacromial IL-1ß levels (P = .048), SROMD (P < .001) and VAS scores (P = .022) and lower Constant scores (P < .001) than nondiabetic patients. The IL-1ß levels in the subacromial fluid were significantly correlated with the Constant score (r = -0.477, P < .001), VAS score (r = 0.698, P < .001), and SROMD (r = 0.293, P = .015) in all patients. CONCLUSION: The elevated IL-1ß levels in the subacromial fluid of patients with diabetes may explain the likelihood of pain and shoulder stiffness developing in these patients. We suggest more aggressive treatment for rotator cuff lesions in diabetic patients.
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Diabetes Mellitus/inmunología , Interleucina-1beta/análisis , Artropatías/inmunología , Lesiones del Manguito de los Rotadores , Articulación del Hombro/inmunología , Líquido Sinovial/química , Adulto , Anciano , Diabetes Mellitus/fisiopatología , Femenino , Humanos , Interleucina-1beta/biosíntesis , Artropatías/fisiopatología , Masculino , Persona de Mediana Edad , Rango del Movimiento Articular , Estudios Retrospectivos , Manguito de los Rotadores/inmunología , Manguito de los Rotadores/fisiopatología , Articulación del Hombro/fisiopatología , Dolor de Hombro/inmunología , Dolor de Hombro/fisiopatología , Líquido Sinovial/inmunologíaRESUMEN
Herpes simplex virus type 1 (HSV-1) Keratitis (HSK) is a highly prevalent eye disease worldwide, characterized by lifelong recurrent episodes and a major risk of leading to blindness. Detecting HSV-1 promptly and accurately can initiate a timely and appropriate therapeutic regimen, minimizing tissue damage and preventing vision impairment. Currently, PCR is the most reliable method for identifying HSV-1, but its utilization for point-of-care (POC) HSV-1 detection is limited due to the need for sophisticated equipment, particularly in areas with limited resources. Here, we propose a new method for on-site HSV detection by using LAMP-Cas12 diagnostic technology and gold nanoparticles. This technique possesses comparable sensitivity to qPCR, and its detection results could be easily read and interpreted without the need for complex equipment. In detecting HSV in clinical tear specimens, this strategy achieved a 93.9 % consistency in positive detection and a 100 % consistency in negative detection compared to qPCR. Our strategy innovates the technique of current HSV-1 detections and is expected to play a crucial role in POC diagnosis of HSK in the future.
RESUMEN
⢠A rice mutant, Oryza sativa short postembryonic roots 1 (Osspr1), has been characterized. It has short postembryonic roots, including adventitious and lateral roots, and a lower iron content in its leaves. ⢠OsSPR1 was identified by map-based cloning. It encodes a novel mitochondrial protein with the Armadillo-like repeat domain. ⢠Osspr1 mutants exhibited decreased root cell elongation. The iron content of the mutant shoots was significantly altered compared with that of wild-type shoots. A similar pattern of alteration of manganese and zinc concentrations in shoots was also observed. Complementation of the mutant confirmed that OsSPR1 is involved in post-embryonic root elongation and iron homeostasis in rice. OsSPR1 was found to be ubiquitously expressed in various tissues throughout the plant. The transcript abundance of various genes involved in iron uptake and signaling via both strategies I and II was similar in roots of wild-type and mutant plants, but was higher in the leaves of mutant plants. ⢠Thus, a novel mitochondrial protein that is involved in root elongation and plays a role in metal ion homeostasis has been identified.
Asunto(s)
Genes de Plantas , Hierro/metabolismo , Proteínas Mitocondriales/metabolismo , Oryza/fisiología , Proteínas de Plantas/metabolismo , Raíces de Plantas/fisiología , Transporte Biológico/genética , Manganeso/metabolismo , Proteínas Mitocondriales/genética , Mutación , Oryza/genética , Proteínas de Plantas/genética , Estructuras de las Plantas/metabolismo , Zinc/metabolismoRESUMEN
Objective: To investigate the effect of FTY720-P on the differentiation and maturation of MC3T3-E1 cells. Methods: The MC3T3-E1 cells were divided into the experimental group and the control group. In the experimental group, the cells were induced by the medium containing 400 ng/mL FTY720-P (chloroform as solubilizer) in vitro. In the control group, the cells were cultured with the medium only containing chloroform. The cell morphology of 2 groups were observed by inverted phase contrast microscope; the expression of osteoblast related protein (collagen type â and collagen type â ¢) was detected by immunofluorescence staining; the alkaline phosphatase (ALP) staining and alizarin red staining were used to observe the formation of osteoblasts and the formation of mineralized nodules in 2 groups; and the TUNEL fluorescence assay was used to detect the cell apoptosis. Results: After 48 hours of culture, the cells of 2 groups had grown into slender fusiform at the bottom of the bottle, and there was no significant difference in cell morphology between 2 groups. Immunofluorescence staining showed that the expression of collagen type â was positive in the experimental group and weakly positive in the control group; the integrated absorbance ( IA) value of the experimental group was 187 600±7 944, which was significantly higher than that of the control group (14 230±1 070) ( t=43.680, P=0.001). The expression of collagen type â ¢ was weakly positive in the experimental group and the control group, and there was no significant difference in IA value between 2 groups ( t=1.976, P=0.119). ALP staining and alizarin red staining were positive in the experimental group and negative in the control group. TUNEL staining was positive in the experimental group and negative in the control group; the rate of TUNEL staining positive cells in the experimental group was 35.82%±2.99%, which was significantly higher than that in the control group (2.28%±0.51%) ( t=23.420, P=0.002). Conclusion: FTY720-P can promote the osteogenic differentiation of MC3T3-E1 cells with speeding up maturation and mineralization of extracellular matrix and affect the apoptosis of the cells.
Asunto(s)
Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/fisiología , Organofosfatos/farmacología , Osteoblastos/fisiología , Osteogénesis/efectos de los fármacos , Esfingosina/análogos & derivados , Fosfatasa Alcalina , Animales , Recuento de Células , División Celular/efectos de los fármacos , División Celular/fisiología , Línea Celular , Células Cultivadas , Colágeno Tipo I , Ratones , Esfingosina/farmacologíaRESUMEN
Objective: To investigate the effects of FTY720-P on EphA2-EphrinA2 bidirectional signaling in osteoclasts. Methods: Murine RAW264.7 macrophages were induced into osteoclasts by dexamethasone and 1α, 25-dihydroxyvitamin D 3, and identified by tartrate resistant acid phosphatase (TRAP) staining. Then, the osteoclasts were divided into 2 groups. The osteoclasts were treated with 400 ng/mL FTY720-P in experimental group and without FTY720-P in control group, respectively. After 48 hours of culture, the cells in 2 groups were detected by real-time fluorescent quantitative PCR, Western blot, and immunofluorescence staining. The expressions of EphA2, EphrinA2, RhoA, and the bone reconstruction associated proteinsï¼»bone morphogenetic protein 2 (BMP-2) and transform growth factor ß 1 (TGF-ß 1)ï¼½were analyzed and compared. Results: RAW264.7 cells were successfully induced into osteoclasts identified by TRAP staining. Compared with control group, the relative expressions of EphA2 and EphrinA2 mRNAs and proteins in experimental group significantly decreased after 48 hours ( P<0.05), and the relative expression of RhoA protein also significantly decreased ( P<0.05). The relative expressions of BMP-2 and TGF-ß 1 mRNAs were significantly increased ( P<0.05), and those protein expressions were enhanced. Conclusion: FTY720-P can down-regulate the expression of RhoA and promote the expressions of TGF- ß 1 and BMP-2 by affecting the transduction of EphA2-EphrinA2 bidirectional signaling in osteoclasts.
Asunto(s)
Diferenciación Celular , Efrina-A2/metabolismo , Organofosfatos/metabolismo , Osteoclastos/metabolismo , Receptor EphA2/metabolismo , Transducción de Señal , Esfingosina/análogos & derivados , Animales , Proteína Morfogenética Ósea 2 , Macrófagos , Ratones , Esfingosina/metabolismoRESUMEN
Kashgarian loach, Triplophysayarkandensis (Day, 1877), a native species in the Tarim River of Northwest China, has been dramatically declined in population size in recent years. In this article, the mitochondrial genome of Kashgarian loach was first determined. The whole mtDNA sequence was 16,574 bp in length, which is similar to other bony fishes in gene order, including 2rRNA genes, 22tRNA, 13 protein-coding and 1 putative control region.