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BACKGROUND: The diagnosis of tuberculous pleurisy (TP) presents a significant challenge due to the low bacterial load in pleural effusion (PE) samples. Cell-free Mycobacterium tuberculosis DNA (cf-TB) in PE samples is considered an optimal biomarker for diagnosing TP. This study aimed to evaluate the applicability of cf-TB testing across diverse research sites with a relatively large sample size. METHODS: Patients suspected of TP and presenting with clinical symptoms and radiological evidence of PE were consecutively enrolled by treating physicians from 11 research sites across 6 provinces in China between April 2020 and August 2022. Following centrifugation, sediments obtained from PE were used for Xpert MTB/RIF (Xpert) and mycobacterial culture, while the supernatants were subjected to cf-TB testing. This study employed a composite reference standard to definite TP, which was characterized by any positive result for Mycobacterium tuberculosis (MTB) through either PE culture, PE Xpert, or pleural biopsy. RESULTS: A total of 1412 participants underwent screening, and 1344 (95.2%) were subsequently enrolled in this study. Data from 1241 (92.3%) participants were included, comprising 284 with definite TP, 677 with clinically diagnosed TP, and 280 without TP. The sensitivity of cf-TB testing in definite TP was 73.6% (95% CI 68.2-78.4), significantly higher than both Xpert (40.8%, 95% CI 35.3-46.7, P < 0.001) and mycobacterial culture (54.2%, 95% CI 48.4-59.9, P < 0.001). When clinically diagnosed TP was incorporated into the composite reference standard for sensitivity analysis, cf-TB testing showed a sensitivity of 46.8% (450/961, 95% CI 43.7-50.0), significantly higher than both Xpert (116/961, 12.1%, 95% CI 10.2-14.3, P < 0.001) and mycobacterial culture (154/961, 16.0%, 95% CI 13.8-18.5, P < 0.001). The specificities of cf-TB testing, Xpert, and mycobacterial culture were all 100.0%. CONCLUSIONS: The performance of cf-TB testing is significantly superior to that of Xpert and mycobacterial culture methods, indicating that it can be considered as the primary diagnostic approach for improving TP detection. Trial registration The trial was registered on Chictr.org.cn (ChiCTR2000031680, https://www.chictr.org.cn/showproj.html?proj=49316 ).
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ADN Bacteriano , Mycobacterium tuberculosis , Derrame Pleural , Tuberculosis Pleural , Humanos , Tuberculosis Pleural/diagnóstico , Femenino , Mycobacterium tuberculosis/genética , Estudios Transversales , Masculino , Persona de Mediana Edad , Adulto , Derrame Pleural/microbiología , Derrame Pleural/diagnóstico , China , ADN Bacteriano/análisis , Ácidos Nucleicos Libres de Células/análisis , Anciano , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Inflammatory bowel disease (IBD) is an idiopathic intestinal disease with various levels and trends in different countries and regions. Understanding the current burden and trends of IBD in various geographical locations is essential to establish effective strategies for prevention and treatment. We report the average annual percentage change (AAPC) and estimated annual percentage change (EAPC) in age-standardized rates (ASR) of IBD in different regions based on the Global Burden of Disease (GBD) study from 1990-2019, and the relationships between IBD and the human development index (HDI) and socio-demographic index (SDI). The prevalence trends of IBD were predicted by gender from 2019-2039. AIM: To comprehensively investigate IBD data, providing further insights into the management of this chronic disease. METHODS: We collected the information on the incidence of IBD from the GBD study from 1990-2019 to calculate the AAPC and EAPC in ASR of IBD in different regions. The relationships between IBD, HDI, and SDI were analyzed. The Nordpred and Bayesian age-period-cohort models were used to predict the prevalence trends of IBD by gender from 2019-2039, and the reliability of the results was validated. Statistics of all the data in this study were performed using R software (version 4.2.1). RESULTS: North America consistently had the highest IBD ASR, while Oceania consistently had the lowest. East Asia had the fastest average annual growth in ASR (2.54%), whereas Central Europe had the fastest decline (1.38%). Countries with a low age-standardized incidence rates in 1990 showed faster growth in IBD while there was no significant correlation in 2019. Additionally, IBD increased faster in countries with a low age-standardized death rates in 1990, whereas the opposite was true in 2019. Analysis of SDI and IBD ASR showed that countries with a high SDI generally had a higher IBD ASR. Finally, the projections showed a declining trend in the incidence of IBD from 2019-2039, but a gradual increase in the number of cases. CONCLUSION: As the global population increases and ages, early monitoring and prevention of IBD is important to reduce the disease burden, especially in countries with a high incidence of IBD.
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Costo de Enfermedad , Enfermedades Inflamatorias del Intestino , Humanos , Teorema de Bayes , Reproducibilidad de los Resultados , Enfermedades Inflamatorias del Intestino/epidemiología , Carga Global de Enfermedades , Salud Global , Años de Vida Ajustados por Calidad de Vida , IncidenciaRESUMEN
Osteosarcoma (OS) is the most common malignant tumor of the bone that affects children and adolescents, and its treatment usually involves doxorubicin hydrochloride (DOX). However, the drug resistance and side effects caused by high-dose DOX infusion greatly hinder its therapeutic effects. To achieve efficient OS treatment with low toxicity, an injectable rhein (RH)-assisted crosslinked hydrogel (PVA@RH@DOX hydrogel, PRDH) was designed, which was prepared by loading DOX and RH into a polyvinyl alcohol (PVA) solution. The cytotoxicity assay and live/dead staining results showed that the combination of RH and DOX more effectively killed OS cells, producing excellent effects at low concentrations of DOX. The wound healing and transwell test results proved that PRDH could significantly inhibit the metastasis and invasion of OS cells. PRDH showed a long-lasting antitumor effect after injection of a single dose, significantly suppressing the proliferation and metastasis of OS and achieving the strategy of a single administration for long-term treatment. Excitingly, RH facilitated hydrogel formation by assisting with PVA crosslinking. This system provides an alternative regimen and broadens the horizon for the clinical treatment of OS.
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Neoplasias Óseas , Osteosarcoma , Niño , Humanos , Adolescente , Hidrogeles/uso terapéutico , Osteosarcoma/tratamiento farmacológico , Doxorrubicina/farmacología , Neoplasias Óseas/tratamiento farmacológico , Línea Celular TumoralRESUMEN
Treatment with metformin can lead to the recovery of pleiotropic biological activities after spinal cord injury. However, its effect on spinal cord injury in aged mice remains unclear. Considering the essential role of angiogenesis during the regeneration process, we hypothesized that metformin activates the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway in endothelial cells, thereby promoting microvascular regeneration in aged mice after spinal cord injury. In this study, we established young and aged mouse models of contusive spinal cord injury using a modified Allen method. We found that aging hindered the recovery of neurological function and the formation of blood vessels in the spinal cord. Treatment with metformin promoted spinal cord microvascular endothelial cell migration and blood vessel formation in vitro. Furthermore, intraperitoneal injection of metformin in an in vivo model promoted endothelial cell proliferation and increased the density of new blood vessels in the spinal cord, thereby improving neurological function. The role of metformin was reversed by compound C, an adenosine monophosphate-activated protein kinase inhibitor, both in vivo and in vitro, suggesting that the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway likely regulates metformin-mediated angiogenesis after spinal cord injury. These findings suggest that metformin promotes vascular regeneration in the injured spinal cord by activating the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway, thereby improving the neurological function of aged mice after spinal cord injury.
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Organic photoelectrochemical transistor (OPECT) bioanalytics has recently appeared as a promising route for biological measurements, which has major implications in both next-generation photoelectrochemical (PEC) bioanalysis and futuristic biorelated implementations. Via biological dissociation of materials, bioetching is a useful technique for bio-manufacturing and bioanalysis. The intersection of these two domains is expected to be a possible way to achieve innovative OPECT bioanalytics. Herein, we validate such a possibility, which is exemplified by alkaline phosphatase (ALP)-mediated bioetching of a CoOOH/BiVO4 gate for a signal-on OPECT immunoassay of human immunoglobulin G (HIgG) as the model target. Specifically, target-dependent bioetching of the upper CoOOH layer could result into an enhanced electrolyte contact and light accessibility to BiVO4, leading to the modulated response of the polymeric poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) channel that could be monitored by the channel current. The introduced biosensor achieves sensitive detection of HIgG with high selectivity and sensitivity. This work features bioetching-enabled high-efficacy OPECT bioanalysis and is anticipated to serve as a generic protocol, considering the diverse bioetching routes.
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Fosfatasa Alcalina , Técnicas Biosensibles , Humanos , Fosfatasa Alcalina/química , Técnicas Biosensibles/métodos , Técnicas Electroquímicas/métodos , Inmunoensayo/métodos , ÓxidosRESUMEN
Semiconductor metal-organic frameworks (MOFs) and heterojunctions have gained increasing attention in many fields, yet their full potential remains largely unexplored. Advanced optobioelectronics are envisioned to create more opportunities for innovative biomedical applications. This study reports a UiO-66-NH2 (U6N)/CdS quantum dots (QDs)-gated organic photoelectrochemical transistor (OPECT) and its application toward energy-transfer-based sensitive microRNA-166a (miRNA-166a) detection assisted by duplex-specific nuclease (DSN)-enabled target recycling. Specifically, a U6N/CdS QDs photoanode was fabricated and shown to be efficiently gating a poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonate) (PEDOT/PSS) channel, while the DSN-enabled release of Au-reporters and hybridization upon the U6N/CdS QDs photoanode could significantly inhibit the photoanode response via an energy transfer process and thus modulate the device response, permitting novel dual-amplified optobioelectronic miRNA-166a detection with a low detection limit of 1.0 fM. This work not only features the DSN-amplified miRNA detection via an OPECT route but also unveils the potential of semiconductor MOF heterojunctions for futuristic optobioelectronics.
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Técnicas Biosensibles , Nanopartículas del Metal , Estructuras Metalorgánicas , MicroARNs , Puntos Cuánticos , MicroARNs/genética , Transferencia de Energía , Endonucleasas , Límite de Detección , Técnicas ElectroquímicasRESUMEN
Innovative optoelectronics are expected to play more important role in clinical diagnosis. In this study, on the basis of sensitive gating effect by in situ enzymatic functionalization of semiconductors, a novel organic photoelectrochemical transistor (OPECT) detection of serum alkaline phosphatase (ALP) level was demonstrated. Specifically, the OPECT detection operates upon the ALP-catalyzed hydrolysis of sodium thiophosphate to yield hydrogen sulfide (H2S), which could in situ generate CdS on the TiO2 electrode in the presence of Cd2+ cations. Correlated to the ALP level, the CdS directly formed on and interfacing with the TiO2 could sensitively gating the poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) channel, allowing unique optoelectronic detection of serum ALP level with a linear range from 0.005 to 15 U L-1 and a detection limit corresponding to 0.0012 U L-1 (S/N = 3). This study offers not only an optoelectronic method for detection of serum ALP level, but also a perspective for unique OPECT gating and application. Moreover, the general catalytic abilities of enzymes to produce functional species and their rich interactions with various gate substrates further provide great space for futuristic OPECT detection in enzyme-associated diseases.
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Técnicas Biosensibles , Sulfuro de Hidrógeno , Fosfatasa Alcalina , Cadmio , Estirenos , Límite de DetecciónRESUMEN
Metal-organic framework (MOF) derivatives with unique physicochemical and electronic properties have seen a tremendous growth in diverse applications. Organic optobioelectronics have long been pursued in modern electronics for next-generation bio-relevant implementations. The intersection of these two disciplines could be an appealing way to pursue better performance of materials and devices. Herein this work reports the exploration of MOF derivatives and its ionic modulation for gating organic photoelectrochemical transistor (OPECT) biosensing. In the representative system of poly(ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) gated by zeolitic-imidazolate-framework (ZIF)-8-derived CdxZn1-xS, a high current gain could be achieved at zero gate bias. In connection to a CuO nanoparticle-labeled sandwich immunoassay, acidolysis-triggered Cu2+-induced ionic modulation of the system results into a good performance toward human IgG with a low limit of detection of 0.003 pg/mL. This work features the MOF derivative-gated organic electronics and is expected to inspire more interest to explore various MOF derivative electronics with unknown possibilities, considering the diversity of MOF derivatives.
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Técnicas Biosensibles , Estructuras Metalorgánicas , Técnicas Biosensibles/métodos , Cadmio , Humanos , Inmunoensayo , Inmunoglobulina G , Iones , Estructuras Metalorgánicas/química , EstirenosRESUMEN
Nature makes use of molecular charges to operate specific biological synthesis and reactions. Targeting advanced opto-bioelectronic sensors, organic photoelectrochemical transistors (OPECTs), taking advantage of the light fuel substituting an external gate potential, is now debuting and expected to serve as a universal platform for studying the rich light-biomatter interplay for new bioanalytics. Given the ubiquity of charged biomolecules in nature, molecular charge manipulation should underpin a generic route for innovative OPECT regulation and operation, which nevertheless has remained unachieved. Herein, this work manifests the biological tuning of surface charge toward the OPECT biosensor, which was exemplified by a light-sensitive CdS quantum dot (QD) gate electrode interfaced by a smart DNA superstructure with adenosine triphosphate (ATP) responsiveness. Highly negative-charged supramolecular DNA concatemers were self-assembled via sequential hybridization, and the ATP-triggered disassembly of the DNA concatemers would cause a tandem change of the effective gate voltage and transfer characteristics with significantly improved resolution. The present opto-bioelectronic device translates the events of charged molecules into amplified electrical signals and outlines a generic format for the future exploitation of rich biological tunability and light-biomatter interplay for innovative bioanalytics and beyond.
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Técnicas Biosensibles , Puntos Cuánticos , Adenosina Trifosfato , ADN/análisis , Hibridación de Ácido Nucleico , Puntos Cuánticos/químicaRESUMEN
INTRODUCTION: Estrogen receptors (ESRs) and progesterone receptors (PGRs) are associated with the development and progression of various tumors. The feasibility of ESRs and PGRs as prognostic markers and therapeutic targets for multiple cancers was evaluated via pan-cancer analysis. METHODS: The pan-cancer mRNA expression levels, genetic variations, and prognostic values of ESR1, ESR2, and PGR were analyzed using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and cBioPortal. The expression levels of ERa, ERb, and PGR proteins were detected by immunohistochemical staining using paraffin-embedded tissue specimens of ovarian serous cystadenocarcinoma (OV) and uterine endometrioid adenocarcinoma (UTEA). Correlation between immunomodulators and immune cells was determined based on the Tumor and Immune System Interaction Database (TISIDB). RESULTS: ESR1, ESR2, and PGR mRNAs were found to be differentially expressed in different cancer types, and were associated with tumor progression and clinical prognosis. ERa, ERb, and PGR proteins were further determined to be significantly differentially expressed in OV and UTEA via immunohistochemical staining. The expression of ERa protein was positively correlated with a high tumor stage, whereas the expression of PGR protein was conversely associated with a high tumor stage in patients with OV. In patients with UTEA, the expression levels of both ERa and PGR proteins were conversely associated with tumor grade and stage. In addition, the expression levels of ESR1, ESR2, and PGR mRNAs were significantly associated with the expression of immunomodulators and immune cells. CONCLUSION: ESR1, ESR2, and PGR are potential prognostic markers and therapeutic targets, as well as important factors for the prediction, evaluation, and individualized treatment in several cancer types.
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There is a growing concern about the effects of nanoplastics on biological safety and human health because of their global ubiquity in the environment. Methodologies for quantitative analysis of nanoplastics are important for the critical evaluation of their possible risks. Herein, a sensitive yet simple and environmentally friendly extraction approach mediated by protein corona is developed and coupled to pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) for nanoplastic determination in environmental waters. The developed methodology involved the formation of protein corona by addition of bovine serum albumin (BSA) to samples and protein precipitation via salting out. Then, the resulting extract was directly introduced to Py-GC/MS for nanoplastic mass quantification. Taking 50 nm polystyrene (PS) particles as a model, the highest extraction efficiency for nanoplastics was achieved under the extraction conditions of BSA concentration of 20 mg/L, equilibration time of 5 min, pH 3.0, 10% (w/v) NaCl, incubation temperature of 80 °C, and incubation period of 15 min. The extraction was confirmed to be mediated by the protein corona by transmission electron microscopy (TEM) analysis of the extracted nanoplastics. In total, 1.92 and 2.82 µg/L PS nanoplastics were detected in river water and the influent of wastewater treatment plant (WWTP), respectively. Furthermore, the feasibility of the present methodology was demonstrated by applying to extract PS and poly(methyl methacrylate) (PMMA) nanoplastics from real waters with recoveries of 72.1-98.9% at 14.2-50.4 µg/L spiked levels. Consequently, our method has provided new insights and possibilities for the investigation of nanoplastic pollution and its risk assessment in the environment.
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Corona de Proteínas , Contaminantes Químicos del Agua , Cromatografía de Gases y Espectrometría de Masas , Humanos , Microplásticos , Poliestirenos/análisis , Pirólisis , Contaminantes Químicos del Agua/análisisRESUMEN
Neural stem cells (NSCs) play vital roles in the homeostasis of neurological function. Ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX) is an important regulator of stem cell phenotypes. In our current study, we aimed to investigate whether the conditional knockout of UTX on neural stem cells alters macrophage assembly in response to spinal cord injury (SCI). Conditional knockout Utx of NSC (Utx-KO) mice was used to generate SCI models by the modified Allen method. We reported that neurological function and scar hyperplasia significantly improved in Utx-KO mice after SCI, accompanied by significantly reduced assembly of macrophages. With a 45-fold pathway array and Western blot, we found that Utx-KO could significantly inhibit NF-κB signaling activation and promote the synthesis and secretion of macrophage migration inhibitory factor (MIF) in NSCs. Administration of the selective NF-κB p65 activator betulinic acid and the selective MIF inhibitor ISO-1 confirmed that the activation of NF-κB p65 phosphorylation or inhibition of MIF could eliminate the benefits of Utx-KO in SCI, such as inhibition of macrophage aggregation and reduction in scar proliferation. This study confirmed that UTX in NSCs could alter macrophage migration and improve neurological function recovery after SCI in mice.
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Histona Demetilasas/fisiología , Macrófagos/fisiología , FN-kappa B/fisiología , Células-Madre Neurales/metabolismo , Transducción de Señal/fisiología , Traumatismos de la Médula Espinal/patología , Animales , Movimiento Celular , Modelos Animales de Enfermedad , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Traumatismos de la Médula Espinal/etiología , Traumatismos de la Médula Espinal/metabolismoRESUMEN
Long non-coding RNAs (lncRNAs) are poorly understood in insects. In this study, we performed genome-wide analysis of lncRNAs in Tribolium castaneum by RNA-seq. In total, 4516 lncRNA transcripts corresponding to 3917 genes were identified from late embryos, early larvae, late larvae, early pupae, late pupae and early adults of T. castaneum, including 3152 novel lncRNAs and 1364 known lncRNAs. These lncRNAs have few exons and transcripts, and are short in length. During development, they exhibited nine different expression patterns. Functionally, they can act either by targeting messenger RNAs (1813 lncRNAs) and lncRNAs (45 lncRNAs) or as micro RNA (miRNA) precursors (46 lncRNAs). LncRNAs were observed to target the metabolic enzymes of glycolysis, TCA cycle and amino acids, demonstrating that lncRNAs control metabolism by regulating metabolic enzymes. Moreover, lncRNAs were shown to participate in cell differentiation and development via their targets. As miRNA precursors, lncRNAs could participate in the ecdysone signaling pathway. This study provides comprehensive information for lncRNAs of T. castaneum, and will promote functional analysis and target identification of lncRNAs in the insect.
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MicroARNs , ARN Largo no Codificante , Tribolium , Animales , Genoma de los Insectos , MicroARNs/genética , ARN Largo no Codificante/genética , ARN Mensajero , Tribolium/genéticaRESUMEN
Toxicity and transport of metal-based nanoparticles (M-NPs) in environmental waters strongly depend on their speciation. A detailed understanding of the composition and speciation of M-NPs is necessary in order to move this field forward. Unfortunately, there is a shortage of analytical methods for metal-sulfide nanoparticles (MS-NPs) in the environment. In this work, a cloud point extraction (CPE) method combined with liquid chromatography hyphenated to inductively coupled plasma mass spectrometry (LC-ICPMS) is developed for sensitive determination of Ag2S- and ZnS-NPs. Under the condition of 0.15% (w/v) of Triton X-114 (TX-114), pH 5, 20 mM NaNO3, incubation temperature of 45 °C, and time of 15 min, MS-NPs and non-MS-NPs were extracted into the surfactant-rich phase. With the sequent addition of 10 mM bis(p-sulfonatophenyl)phenylphosphane dehydrate dipotassium (BSPP) aqueous solution (100 µL) into the CPE-obtained extract, the non-MS-NPs were selectively dissociated into their ionic counterparts while maintaining the original size and shape of Ag2S- and ZnS-NPs. Interestingly, the micelle-mediated behavior suddenly disappeared with the addition of BSPP. Thus, the extract can be injected to LC-ICPMS for speciation analysis of trace Ag2S- and ZnS-NPs. This method exhibited excellent reproducibility (relative standard deviations < 4.9%), high sensitivity with the respective detection limits of 8 ng/L for Ag2S-NPs and 15 ng/L for ZnS-NPs, enabling recoveries of 81.3-96.6% for Ag2S-NPs and 83.9-93.5% for ZnS-NPs when they were spiked into three environmental water samples. Due to its potential applicability to low concentrations of Ag2S- and ZnS-NPs, this method is particularly convenient for monitoring the transformations of AgNPs and ZnO-NPs in the environment.
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Monitoreo del Ambiente , Nanopartículas/análisis , Compuestos de Plata/análisis , Sulfuros/análisis , Contaminantes Químicos del Agua/química , Compuestos de Zinc/análisis , Fraccionamiento Químico , Cromatografía Liquida , Espectrometría de Masas , Tamaño de la Partícula , Propiedades de SuperficieAsunto(s)
Exosomas/metabolismo , Neovascularización Fisiológica , Células-Madre Neurales/metabolismo , Recuperación de la Función , Traumatismos de la Médula Espinal/fisiopatología , Médula Espinal/fisiopatología , Animales , Células Cultivadas , Células Endoteliales/metabolismo , Femenino , Ratones Endogámicos C57BL , Microvasos/patología , Regeneración , Médula Espinal/patología , Traumatismos de la Médula Espinal/patología , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
OBJECTIVE: To compare the effects of intravenous and subcutaneous injection of bortezomib on incidence and relative risk of peripheral neuropathy in patients with multiple myeloma(MM). METHODS: The electronic database of PubMed, Embase, Cochrance library, CNKI and related meeting records were searched by computers. The data were derived all from a matched randomized controlled studies. The incidence, relative risk(RR) and 95% confidence interval of peripheral neuropathy caused by intravenous and subcustaneous injections were calculated by the statistical methods. RESULTS: Four RCT studies were selected for meta-analysis, with a total of 911 patients (479 cases and 432 cases in the subcutaneous injection and intravenous injection groups, respectively). The incidence of peripheral neuropathy in the intravenous injection group was 41.4% (95% CI=0.137-0.692, P=0.003), and the incidence of >2 grade of peripheral neuropathy was 15.6% (95% CI=0.005-0.308, P=0.043). The corresponding incidence rates of the subcutaneous injection group were 16% (95% CI=0.021-0.299, P=0.024) and 3.4% (95% CI=-0.011-0.080, P=0.141) respectively. Compared with the intravenous injection group, the RR of peripheral neuropathy and the relative risk of peripheral neuropathy above grade 2 were 0.525, 95% CI=0.297-0.928 (P=0.027) and 0.376, 95% CI=0.196-0.722 (P=0.003) respectively. CONCLUSION: Subcutaneous injection of bortezomib at therapeutic doses significantly reduces the incidence of peripheral neuropathy compared with intravenous injection.
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Bortezomib/efectos adversos , Mieloma Múltiple , Enfermedades del Sistema Nervioso Periférico , Antineoplásicos , Humanos , Incidencia , Inyecciones Subcutáneas , Enfermedades del Sistema Nervioso Periférico/inducido químicamenteRESUMEN
OBJECTIVE: To investigate the significance of detecting serum complement C3 and C4 in patients with multiple myeloma (MM) and to explore its correlation with myeloma bone disease (MBD). METHODS: The levels of serum complement C3 and C4 in 69 MM patients and 30 healthy people were examined by scatter nephelometry. The bone density of L1-4 vertebral body, bilateral femoral neck and bilateral hip joints were measured by dual energy bone density meter (DXA). RESULTS: The levels of serum complement C3 and C4 in MM patients significantly increased in comparison with that in healthy people (Pï¼0.01). The patients in advanced clinical stage exhibited a higher levels of C3 and C4 than those in stable stage (Pï¼0.01). In addition, the patients with grade C of MBD had a higher levels of serum complement C3 and C4 than those in patients with grade A and B of MBD (Pï¼0.01). The levels of serum complement C3 and C4 in MM patients negatively correlated with bone density in L1-4 vertebral body, bilateral femoral necks and hip joints. The correlation coefficients were r=-0.938, r=-0.659, r=-0.745, r=-0.748, r=-0.596 in complement C3 and r=-0.908, r=-0.623, r=-0.710, r=-0.714, r=-0.595 in complement C4, respectively. CONCLUSION: The levels of complement C3 and C4 positively correlate with the severity of bone disease and bone density in MM patients, which suggests that complement C3 and C4 plays important roles in the development of MBD. The levels of serum C3 and C4 may be the sensitive biomarkers of MBD.
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Complemento C3/metabolismo , Complemento C4/metabolismo , Mieloma Múltiple , Biomarcadores , Cuello Femoral , HumanosRESUMEN
Pilocarpine-induced acute seizures strongly induce aberrant hippocampal neurogenesis, characterized by increased proliferation of neural progenitors and abnormal integrations of newly generated granule cells - hilar ectopic granule cells (EGCs), mossy fibre sprouting (MFS), and hilar basal dendrites (HBDs), which may disturb hippocampal neuronal circuits and thus contribute to cognitive impairment in temporal lobe epilepsy (TLE) patients and animal models. Previous studies via ablating hippocampal neurogenesis after acute seizures produced inconsistent results regarding the development of long-term cognitive impairment. Furthermore, a sufficient decrease of subsequent abnormal integrations in chronically epileptic hippocampus was not well-established in these studies. Therefore, the link between seizure-induced aberrant hippocampal neurogenesis and cognitive decline associated with epilepsy is still in need to be clarified. In this study, the mice were injected with methylazoxymethanol acetate (MAM) both before and after pilocarpine-induced status epilepticus (SE) to achieve an overall ablation of newborn cells contributing to the pathological recruitment. In addition, a protracted time point was chosen for behavioral testing considering it takes a fairly long time for newborn granule cells to adequately develop abnormal integrations, especially MFS. Although an overall reduction of abnormal integrations, including EGCs, MFS and HBDs was confirmed following the ablation regime, the performance of ablated and non-ablated mice in the Morris Water Maze (MWM) task did not differ. The current findings therefore provide novel evidences that ablation of neurogenesis with an overall decrease of abnormal integrations cannot attenuate subsequent cognitive impairment at least in the model used in this study.
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Trastornos del Conocimiento/tratamiento farmacológico , Trastornos del Conocimiento/etiología , Hipocampo/patología , Acetato de Metilazoximetanol/uso terapéutico , Estado Epiléptico/complicaciones , Animales , Bromodesoxiuridina/metabolismo , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Proteínas de Dominio Doblecortina , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/fisiopatología , Proteínas de Homeodominio/metabolismo , Antígeno Ki-67/metabolismo , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Ratones , Proteínas Asociadas a Microtúbulos/metabolismo , Agonistas Muscarínicos/toxicidad , Neurogénesis/efectos de los fármacos , Neurogénesis/fisiología , Neuropéptidos/metabolismo , Pilocarpina/toxicidad , Proteínas Proto-Oncogénicas c-fos/metabolismo , Estado Epiléptico/inducido químicamente , Estado Epiléptico/patología , Transducción Genética , Proteínas Supresoras de Tumor/metabolismoRESUMEN
Circadian rhythms are endogenous oscillations with a period of about 24 h driven by a circadian clock. So far, variable oscillators have been found in insects. To explore the circadian clock of Tribolium castaneum, we cloned the clock gene timeless (Tctimeless). Its open reading frame is 3240 bp in length and consists of 10 exons. Tctimeless is highly expressed in the late pupal stage. Tissue-specific expression analysis in late adult stages revealed high expression of Tctimeless in the head, epidermis, fat body and accessory glands. Silencing of Tctimeless by RNA interference (RNAi) at the late larval stages caused a failure to initiate eclosion. Tctimeless knockdown in late pupal stages led to a gender-independent decline in egg production and progeny survival. As a core clock gene, Tctimeless exhibited one expression peak in the middle of the circadian day. Knockdown of Tctimeless disrupted daily expression patterns of Tccycle, Tcclock, Tcperiod and itself, while Tctimeless and Tcperiod expression patterns over the circadian day were also perturbed when Tccycle or Tcclock is suppressed by RNAi. This study identified a complex transcriptional relationship among circadian clock genes in T. castaneum.
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Proteínas CLOCK/genética , Relojes Circadianos/genética , Proteínas Circadianas Period/genética , Tribolium/genética , Animales , Proteínas CLOCK/metabolismo , Femenino , Regulación de la Expresión Génica , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Masculino , Proteínas Circadianas Period/metabolismo , Filogenia , Interferencia de ARN , Tribolium/crecimiento & desarrollo , Tribolium/metabolismoRESUMEN
The ethanol extract of the aerial parts of Alstonia yunnanensis Diels afforded five new monoterpenoid indole alkaloids, alstiyunnanenines A-E (1-5), along with one known compound, alstoniascholarine I (6). The structures of the isolated compounds were established based on 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated compounds were tested in vitro for cytotoxic potential using eight tumor cell lines. As a result, alkaloids 4-6 exhibited cytotoxicities against all tested tumor cell lines, especially against osteosarcoma cell lines (SOSP-9607, MG-63, Saos-2, M663) with IC50 values<6µM.