RESUMEN
As a "cold tumor", triple-negative breast cancer (TNBC) exhibits limited responsiveness to current immunotherapy. How to enhance the immunogenicity and reverse the immunosuppressive microenvironment of TNBC remain a formidable challenge. Herein, an "in situ nanovaccine" Au/CuNDs-R848 was designed for imaging-guided photothermal therapy (PTT)/chemodynamic therapy (CDT) synergistic therapy to trigger dual immunoregulatory effects on TNBC. On the one hand, Au/CuNDs-R848 served as a promising photothermal agent and nanozyme, achieving PTT and photothermal-enhanced CDT against the primary tumor of TNBC. Meanwhile, the released antigens and damage-associated molecular patterns (DAMPs) promoted the maturation of dendritic cells (DCs) and facilitated the infiltration of T lymphocytes. Thus, Au/CuNDs-R848 played a role as an "in situ nanovaccine" to enhance the immunogenicity of TNBC by inducing immunogenic cell death (ICD). On the other hand, the nanovaccine suppressed the myeloid-derived suppressor cells (MDSCs), thereby reversing the immunosuppressive microenvironment. Through the dual immunoregulation, "cold tumor" was transformed into a "hot tumor", not only implementing a "turning foes to friends" therapeutic strategy but also enhancing immunotherapy against metastatic TNBC. Furthermore, Au/CuNDs-R848 acted as an excellent nanoprobe, enabling high-resolution near-infrared fluorescence and computed tomography imaging for precise visualization of TNBC. This feature offers potential applications in clinical cancer detection and surgical guidance. Collectively, this work provides an effective strategy for enhancing immune response and offers novel insights into the potential clinical applications for tumor immunotherapy.
RESUMEN
The clustered regularly interspaced short palindromic repeats (CRISPR) systems have been demonstrated to be the foremost compelling genetic tools for manipulating prokaryotic and eukaryotic genomes. Despite the robustness and versatility of Cas9 and Cas12a/b nucleases in mammalian cells and plants, their large protein sizes may hinder downstream applications. Therefore, investigating compact CRISPR nucleases will unlock numerous genome editing and delivery challenges that constrain genetic engineering and crop development. In this study, we assessed the archaeal miniature Un1Cas12f1 type-V CRISPR nuclease for genome editing in rice and tomato protoplasts. By adopting the reengineered guide RNA modifications ge4.1 and comparing polymerase II (Pol II) and polymerase III (Pol III) promoters, we demonstrated uncultured archaeon Cas12f1 (Un1Cas12f1) genome editing efficacy in rice and tomato protoplasts. We characterized the protospacer adjacent motif (PAM) requirements and mutation profiles of Un1Cas12f1 in both plant species. Interestingly, we found that Pol III promoters, not Pol II promoters, led to higher genome editing efficiency when they were used to drive guide RNA expression. Unlike in mammalian cells, the engineered Un1Cas12f1-RRA variant did not perform better than the wild-type Un1Cas12f1 nuclease, suggesting continued protein engineering and other innovative approaches are needed to further improve Un1Cas12f1 genome editing in plants.
Asunto(s)
Edición Génica , Oryza , Solanum lycopersicum , Oryza/genética , Solanum lycopersicum/genética , Sistemas CRISPR-Cas , Protoplastos/metabolismo , Genoma de PlantaRESUMEN
High levels of reactive oxygen species (ROS) are known to play a critical role in the secondary cascade of spinal cord injury (SCI). The scavenging of ROS has emerged as a promising approach for alleviating acute SCI. Moreover, identifying the precise location of the SCI site remains challenging. Enhancing the visualization of the spinal cord and improving the ability to distinguish the lesion site are crucial for accurate and safe treatment. Therefore, there is an urgent clinical need to develop a biomaterial that integrates diagnosis and treatment for SCI. Herein, ultra-small-sized gold nanodots (AuNDs) were designed for dual-mode imaging-guided precision treatment of SCI. The designed AuNDs demonstrate two important functions. First, they effectively scavenge ROS, inhibit oxidative stress, reduce the infiltration of inflammatory cells, and prevent apoptosis. This leads to a significant improvement in SCI repair and promotes a functional recovery after injury. Second, leveraging their excellent dual-mode imaging capabilities, the AuNDs enable rapid and accurate identification of SCI sites. The high contrast observed between the injured and adjacent uninjured areas highlights the tremendous potential of AuNDs for SCI detection. Overall, by integrating ROS scavenging and dual-mode imaging in a single biomaterial, our work on functionalized AuNDs provides a promising strategy for the clinical diagnosis and treatment of SCI.
Asunto(s)
Oro , Traumatismos de la Médula Espinal , Humanos , Especies Reactivas de Oxígeno , Oro/uso terapéutico , Traumatismos de la Médula Espinal/tratamiento farmacológico , Estrés Oxidativo , Materiales Biocompatibles/uso terapéuticoRESUMEN
Insufficient reactive oxygen species (ROS) production and radioresistance have consistently contributed to the failure of radiotherapy (RT). The development of a biomaterial capable of activating ROS-induced apoptosis and ferroptosis is a potential strategy to enhance RT sensitivity. To achieve precision and high-efficiency RT, the theranostic nanoplatform Au/Cu nanodots (Au/CuNDs) were designed for dual-mode imaging, amplifying ROS generation, and inducing apoptosis-ferroptosis to sensitize RT. A large amount of ROS is derived from three aspects: (1) When exposed to ionizing radiation, Au/CuNDs effectively absorb photons and emit various electrons, which can interact with water to produce ROS. (2) Au/CuNDs act as a catalase-like to produce abundant ROS through Fenton reaction with hydrogen peroxide overexpressed of tumor cells. (3) Au/CuNDs deplete overexpressed glutathione, which causes the accumulation of ROS. Large amounts of ROS and ionizing radiation further lead to apoptosis by increasing DNA damage, and ferroptosis by enhancing lipid peroxidation, significantly improving the therapeutic efficiency of RT. Furthermore, Au/CuNDs serve as an excellent nanoprobe for high-resolution near-infrared fluorescence imaging and computed tomography of tumors. The promising dual-mode imaging performance shows their potential application in clinical cancer detection and imaging-guided precision RT, minimizing damage to adjacent normal tissues during RT. In summary, our developed theranostic nanoplatform integrates dual-mode imaging and sensitizes RT via ROS-activated apoptosis-ferroptosis, offering a promising prospect for clinical cancer diagnosis and treatment.
Asunto(s)
Ferroptosis , Neoplasias , Radioterapia Guiada por Imagen , Humanos , Especies Reactivas de Oxígeno , Neoplasias/diagnóstico por imagen , Neoplasias/radioterapia , Apoptosis , Peróxido de Hidrógeno , Línea Celular TumoralRESUMEN
Surgery, radiotherapy (RT), and brachytherapy are crucial treatments for localized deep tumors. However, imprecise tumor location often leads to issues such as positive surgical margins, extended radiotherapy target volumes, and radiation damage to healthy tissues. Reducing side effects in healthy tissue and enhancing RT efficacy are critical challenges. To address these issues, we developed a multifunctional theranostic platform using Au/Ag nanodots (Au/AgNDs) that act as a "pilot light" for real-time guided surgery, high-efficiency RT, and brachytherapy, achieving a strategy of killing three birds with one stone. First, dual-mode imaging of Au/AgNDs enabled precision RT, minimizing damage to adjacent normal tissue during X-ray irradiation. Au/AgNDs enhanced ionizing radiation energy deposition, increased intracellular reactive oxygen species (ROS) generation, regulated the cell cycle, promoted DNA damage formation, and inhibited DNA repair in tumor cells, significantly improving RT efficacy. Second, in brachytherapy, precise guidance provided by dual-mode imaging addressed challenges related to non-visualization of existing interstitial brachytherapy and multiple adjustments of insertion needle positions. Meanwhile, the effect of brachytherapy was improved. Third, the excellent fluorescence imaging of Au/AgNDs accurately distinguished tumors from normal tissue, facilitating their use as a powerful tool for assisting surgeons during tumor resection. Taken together, our multifunctional theranostic platform offers real-time guidance for surgery and high-efficiency RT, and improves brachytherapy precision, providing a novel strategy and vision for the clinical diagnosis and treatment of cancer.
RESUMEN
Objectives: This systematic review aimed to comprehensively understand the comorbidity of cerebral palsy (CP) in China. Methods: We searched through databases in both Chinese and English until December 2022 to gather cross-sectional studies on the comorbidity of CP in China. After two reviewers independently screened the articles, collected the data, and assessed the bias risk, a meta-analysis was conducted using the Stata 17.0 software. Results: A total of 73 articles were included. Of these, 16 articles reported total comorbidity, with a prevalence of 79.7% (95% CI: 73.8-85.7%); 56 articles reported epilepsy, with a prevalence of 17.9% (95% CI: 15.4-20.4%); 48 articles reported intellectual disability, with a prevalence of 58.0% (95% CI: 51.8-64.3%); 32 articles reported speech disorders, with a prevalence of 48.0% (95% CI: 41.6-54.4%); 41 articles reported hearing disorders, with a prevalence of 17.2% (95% CI: 13.0-21.4%); and 35 articles reported vision disorders, with a prevalence of 23.1% (95% CI: 16.3-29.8%). The topographical type of CP was the primary source of heterogeneity in the prevalence of epilepsy. Diagnostic criteria for CP, clinical type of CP, GMFCS, publishing time, and topographical type of CP were the primary sources of heterogeneity in the prevalence of intellectual disability. Clinical type of CP and topographical type were the primary sources of heterogeneity in the prevalence of speech disorders. Finally, the region was the primary source of heterogeneity in the prevalence of hearing disorders. Conclusion: The prevalence of comorbidities in CP is high in China. Comorbidities are related to the characteristics, severity, and risk factors of brain insult and have a particular relationship with regional economic development and medical and health levels.
RESUMEN
HYPOTHESIS: The use of tumor cell membrane-camouflaged nanoparticles, specifically the multifunctional biomimetic core-shell nanosystem MPCONPs, can enhance the targeting ability and immune escape functionality of traditional chemotherapy, leading to more precise drug delivery and improved treatment outcomes. EXPERIMENTS: Preparation of MPCONPs: Autologous tumor cell membrane (CM) fragments are collected and used to create a shell for the nanoparticles. A trypsin-sensitive cationic polylysine framework is synthesized and embedded with oxaliplatin (l-OHP) and Ce6-AuNDs (a singlet oxygen generator). The MPCONPs are formed by assembling these components. FINDINGS: MPCONPs, as nanoparticles camouflaged with tumor CM, have enhanced cellular uptake in cancer cells and improved the efficacy of photodynamic therapy (PDT) and chemotherapy (CT). This offers great potential for their use as individualized therapeutic agents for clinical oncology treatment.
Asunto(s)
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Biomimética , Fotoquimioterapia/métodos , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Membrana Celular , Línea Celular Tumoral , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéuticoRESUMEN
Objective: To study the worldwide prevalence and associated factors of epilepsy in children and adolescents with Cerebral Palsy (CP) and to analyze the differences between various subgroups. Method: We identified all potential studies on the prevalence of epilepsy in children and adolescents with CP from PubMed, Web of Science, and Embase. The search time was from the establishment of the database to November 2022. Randomized effects meta-analysis models were used to calculate the prevalence of epilepsy in CP. Subgroup analysis and meta-regression were utilized to further explore heterogeneity between articles and prevalence disparities between subgroups. The funnel plot and Egger's test were used to investigate potential publication bias. Results: Seventy-two articles, comprising 53,969 children and adolescents with CP, were included in this study. The results indicated a total epilepsy prevalence of 38.0% (95% CI: 34.8%-41.2%) in CP. The prevalence of epilepsy was 46.4% (95% CI: 41.4%-51.5%) in clinical sample-based studies and 31.6% (95% CI: 28.7%-34.5%) in population-based studies. Meta-regression demonstrated that the sample source, neonatal seizure, family history of epilepsy, EEG or cranial imaging abnormalities, intellectual/cognitive impairment, and topographical types of CP were heterogeneous contributors to the epilepsy prevalence in CP. Conclusion: Approximately one-third of children and adolescents with CP have epilepsy, and the sample source can significantly impact the total prevalence of epilepsy. Neonatal seizures, family history of epilepsy, EEG abnormalities, cranial imaging abnormalities, severe intellectual disability, and quadriplegia may be contributing factors to epilepsy comorbid in CP. Further study is required to verify the strength of these associations with epilepsy. This study aids in identifying the clinical characteristics of young people with CP at risk of developing epilepsy, which may assist clinicians in the early prevention and diagnosis of epilepsy within this population.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=367766, identifier CRD42022367766.
RESUMEN
Objective: To comprehensively evaluate the efficacy of non-invasive brain stimulation (NIBS) in patients with autism spectrum disorder (ASD) in randomized controlled trials (RCT), providing a reference for future research on the same topic. Methods: Five databases were searched (Pubmed, Web of Science, Medline, Embase, and Cochrane library) and tracked relevant references, Meta-analysis was performed using RevMan 5.3 software. Results: Twenty-two references (829 participants) were included. The results of the meta-analysis showed that NIBS had positive effects on repetitive and stereotypical behaviors, cognitive function, and executive function in autistic patients. Most of the included studies had a moderate to high risk of bias, Mainly because of the lack of blinding of subjects and assessors to treatment assignment, as well as the lack of continuous observation of treatment effects. Conclusion: Available evidence supports an improvement in some aspects of NIBS in patients with ASD. However, due to the quality of the original studies and significant publication bias, this evidence must be treated with caution. Further large multicenter randomized double-blind controlled trials and appropriate follow-up observations are needed to further evaluate the specific efficacy of NIBS in patients with ASD.
RESUMEN
TiAlN-coated carbide tools have been used to machine Ti-6Al-4V alloys in aviation workshops. However, the effect of TiAlN coating on surface morphology and tool wear in the processing of Ti-6Al-4V alloys under various cooling conditions has not been reported in the public published literature. In our current research, turning experiments of Ti-6Al-4V with uncoated and TiAlN tools under dry, MQL, flood cooling, and cryogenic spray jet cooling conditions were carried out. The machined surface roughness and tool life were selected as the two main quantitative indexes for estimating the effects of TiAlN coating on the cutting performance of Ti-6Al-4V under various cooling conditions. The results showed that TiAlN coating makes it hard to improve the machined surface roughness and tool wear of a cutting titanium alloy at a low speed of 75 m/min compared to that achieved by uncoated tools. The TiAlN tools presented excellent tool life in turning Ti-6Al-4V at a high speed of 150 m/min compared to that achieved by uncoated tools. From the perspective of obtaining finished surface roughness and superior tool life in high-speed turning Ti-6Al-4V, the selection of TiAlN tools is feasible and reasonable under the cryogenic spray jet cooling condition. The dedicative results and conclusions of this research could guide the optimized selection of cutting tools in machining Ti-6Al-4V for the aviation industry.
RESUMEN
Diabetic wounds are chronically hard-healing wounds. Bacterial infection, persistent inflammation and impaired angiogenesis are key factors affecting diabetic wound healing. Herein, inspired by pomegranate, Au/Ag nanodots (Au/AgNDs) with fluorescent and photothermal properties were adopted as the pomegranate-like core, and the polyvinyl alcohol hydrogel as the pomegranate-like shell to obtain the multifunctional nanocomposite wound dressing for promoting diabetic wounds healing and real-time self-monitoring the dressing state. On the one hand, the antibacterial and photothermal therapy synergistic strategy based on the nanocomposite has an excellent treatment effect on diabetic wounds by highly antibacterial, anti-inflammation, accelerating collagen deposition and angiogenesis. On the other hand, the nanocomposite can be used as "smart messenger" to determine the appropriate time for dressing replacement. With the release of Au/AgNDs from the nanocomposite, the photothermal performance and antibacterial activity of the wound dressing were reduced, and the fluorescence intensity decreased. The change of fluorescence intensity can be visualized by the naked eye, which guides the appropriate time for dressing replacement, and avoids secondary wound damage caused by frequent and blind dressing replacement. This work provides an effective strategy for the treatment of diabetic wounds and intelligent self-monitoring of the state of dressings in clinical practice.
Asunto(s)
Técnicas Biosensibles , Diabetes Mellitus , Nanocompuestos , Vendajes , Cicatrización de Heridas , Antibacterianos , Diabetes Mellitus/terapiaRESUMEN
Background: In recent years, there has been a growing body of research suggesting that ASD and ADHD are two disorders that often co-exist. Despite the rapid development of research, little is known about their etiology, diagnostic markers, and interventions, which has led us to review and summarise the development of the field in the hope that this will provide an opportunity to look for future directions. Methods: A bibliometric approach was used to analyse papers in the field of ASD co-morbidities in ADHD on Web of Science from 1991-2022, using CiteSpace and VOSview to map the country/institution, journal, author, co-citation, and keyword networks in the field and to visualise the results. Results: A total of 3284 papers were included, showing an increasing trend in terms of posting trends. Research on co-morbidities of ASD has proven to be mainly focused on universities. The USA (1662) published the most relevant literature in this area, followed by the UK (651) and Sweden (388). Lichtenstein P is the most published author (84), and research into the pathogenesis of ASD co-occurring ADHD and related clinical diagnostics is currently at the forefront of the field. Conclusion: This analysis identifies the most influential institutions and countries, cited journals, and authors in the field of ASD co-morbid ADHD research. The future direction of ASD co-occurring ADHD should be based on improving case identification, discovering the etiological and diagnostic markers of ASD and ADHD, and finding more effective clinical interventions.
RESUMEN
Prostate cancer (PCa) routinely employs magnetic resonance (MR) imaging, while metastatic PCa needs more complicated detection methods for precise localization. The inconvenience of using different methods to detect PCa and its metastases in patients and the limitations of single-mode imaging have brought great challenges to clinicians. Meanwhile, clinical treatments for metastatic PCa are still limited. Herein, we report a targeted theranostic platform of Au/Mn nanodots-luteinising hormone releasing hormone (AMNDs-LHRH) nano-system for multi-mode imaging guided photothermal therapy of PCa. The nano-system not only can simultaneously target Gonadotropin-Releasing Hormone Receptor (GnRH-R) positive PCa and its metastases for accurate preoperative CT/MR diagnosis, but also possesses fluorescence (FL) visualization navigated surgery, demonstrating its potential application in clinical cancer detection and surgery guidance. Meanwhile, the AMNDs-LHRH with promising targeting and photothermal conversion ability significantly improve the photothermal therapy effect of metastatic PCa. The AMNDs-LHRH nano-system guarantees the diagnostic accuracy and enhanced therapeutic effect, which provides a promising platform for clinical diagnosis and treatment of metastatic PCa. STATEMENT OF SIGNIFICANCE: Accurate clinical diagnosis and treatment of prostate cancer and its metastases is challenging. A targeted theranostic platform of AMNDs-LHRH nano-system for multi-mode imaging (FL/CT/MR) guided photothermal therapy of metastatic prostate cancer has been reported. The nano-system not only can simultaneously target prostate cancer and its metastases for accurate preoperative CT/MR diagnosis, but also possesses fluorescence visualization navigated surgery, demonstrating its potential application in clinical cancer detection and surgery guidance. The nano-system with great targeting and photothermal conversion ability significantly improve the photothermal therapy effect of metastatic prostate cancer. Overall, the AMNDs-LHRH nano-system integrates tumor targeting, multi-mode imaging and enhanced therapeutic effect, which can provide an effective strategy for the clinical diagnosis and treatment of metastatic PCa.
Asunto(s)
Terapia Fototérmica , Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/terapia , Neoplasias de la Próstata/patología , Fototerapia , Imagen por Resonancia Magnética/métodos , Hormona Liberadora de Gonadotropina , Línea Celular TumoralRESUMEN
The high incidence and complex subtypes of prostate cancer put forward higher requirements for accurate diagnosis. Furthermore, advanced prostate cancer is prone to metastasis. Single biological imaging mode faces a challenge of sensitive and fast bioimaging of metastasic prostate cancer. Thus, exploring a nanoprobe with multi-mode imaging function has an important impact on preoperative imaging and intraoperative visualization guide of metastatic prostate cancer. Herein, based on the optical properties and X-ray attenuation capability of Au nanodots as well as the slow electronic relaxation of Gd3+, we designed and fabricated the multifunctional nanoprobe Au/Gd nanodots for multi-mode imaging and accurate diagnosis of bone metastatic prostate cancer. The results showed that multiple imaging modes complement each other to achieve high-precision of metastasic prostate cancer detection and accurately guide treatment. In addition, in vitro/vivo experiments showed that Au/Gd nanodots had good biocompatibility and biosafety. Therefore, the prepared multifunctional nanoprobe may provide new strategies and insights for precise diagnosis of metastatic prostate cancer in clinical practice.
Asunto(s)
Neoplasias de la Próstata , Tomografía Computarizada por Rayos X , Masculino , Humanos , Tomografía Computarizada por Rayos X/métodos , Imagen por Resonancia Magnética/métodos , Neoplasias de la Próstata/diagnóstico por imagenRESUMEN
Radiotherapy (RT) is one of the most effective and commonly used cancer treatments for malignant tumors. However, the existing radiosensitizers have a lot of side effects and poor efficacy, which limits the curative effect and further application of radiotherapy. In recent years, emerging nanomaterials have shown unique advantages in enhancing radiosensitization. In particular, gold-based nanomaterials, with high X-ray attenuation capacity, good biocompatibility, and promising chemical, electronic and optical properties, have become a new type of radiotherapy sensitizer. In addition, gold-based nanomaterials can be used as a carrier to load a variety of drugs and immunosuppressants; in particular, its photothermal therapy, photodynamic therapy and multi-mode imaging functions aid in providing excellent therapeutic effect in coordination with RT. Recently, many novel strategies of radiosensitization mediated by multifunctional gold-based nanomaterials have been reported, which provides a new idea for improving the efficacy and reducing the side effects of RT. In this review, we systematically summarize the recent progress of various new gold-based nanomaterials that mediate radiosensitization and describe the mechanism. We further discuss the challenges and prospects in the field. It is hoped that this review will help researchers understand the latest progress of gold-based nanomaterials for radiosensitization, and encourage people to optimize the existing methods or explore novel approaches for radiotherapy.
Asunto(s)
Nanopartículas del Metal , Nanoestructuras , Neoplasias , Fármacos Sensibilizantes a Radiaciones , Humanos , Oro/química , Nanopartículas del Metal/química , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , Fármacos Sensibilizantes a Radiaciones/químicaRESUMEN
Obesity is a significant risk factor for atrial fibrillation (AF), which is the most common sustained arrhythmia with increased mortality and morbidity. High-fat diet (HFD)-induced obesity is associated with the activation of endoplasmic reticulum stress (ERS). However, the role of ERS in HFD-induced AF remains elusive. Human atrium samples were examined for the ERS activation test. C57BL/6J mice were divided into four groups, including the control group, the HFD group, the 4-phenylbutyric acid (4-PBA) group, and the HFD + 4-PBA group. At the age of 4 weeks, the HFD group and the HFD + 4-PBA group were given HFD to construct the obesity model, while the other two groups were given a normal diet (ND). Transesophageal programmed electrical stimulation was conducted to evaluate the AF inducibility and duration. Atrial fibrosis and ERS activation were also investigated.We found that CHOP and GRP-78 protein were significantly higher in overweight patients than the controls (both P < 0.05). AF inducibility and duration of the HFD group were significantly higher than the other groups (both P < 0.05), while there was no difference between those groups (P > 0.05). The mice of the HFD group had significantly higher collagen volume fraction (CVF%) than the other groups (P < 0.05). ERS marker protein of GRP78, p-PERK, ATF6 and CHOP protein expression level was increased in the HFD group, which were significantly mitigated in the HFD + 4-PBA group. In summary, HFD-induced ERS activation facilitates atrial fibrosis and AF. The inhibition of ERS might alleviate atrial fibrosis and reduce the incidence of AF-associated obesity.
Asunto(s)
Fibrilación Atrial/etiología , Fibrilación Atrial/metabolismo , Dieta Alta en Grasa/efectos adversos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Atrios Cardíacos/patología , Atrios Cardíacos/fisiopatología , Anciano , Animales , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/prevención & control , Biomarcadores , Comorbilidad , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Ecocardiografía , Chaperón BiP del Retículo Endoplásmico , Femenino , Fibrosis , Atrios Cardíacos/efectos de los fármacos , Humanos , Inmunohistoquímica , Incidencia , Masculino , Ratones , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/metabolismo , Sobrepeso/complicaciones , Sobrepeso/metabolismoRESUMEN
The aim of this study was to assess the prevalence of metabolic syndrome (MetS) in non-obese adults (body mass index (BMI) < 25 kg/m2) and the prevalence of obese adults (body mass index (BMI) ≥ 25 kg/m2) without MetS in Chinese Beijing urban subjects. A cross-sectional study was conducted and the subjects who came to the hospital to receive a health examination were enrolled randomly. Regardless of age stratification, men have a higher prevalence of MetS than women. Among the urban Beijing population, prevalence of metabolically obese but normal weight (MONW) is lower than metabolically healthy but obese (MHO) regardless of gender. Except for the underweight group, participants exhibit significant differences between MetS and non-MetS subgroups in all tested variables in normal weight and overweight groups, whereas MONW and MHO participants exhibit significant differences in all variables except for creatinine (CR), aspartate aminotransferase (AST), uric acid (UAC) and high-density lipoprotein cholesterol (HDL-C). Women tend to have a higher MONW prevalence but lower MHO prevalence than men. Accordingly, MetS happens more frequently among those 40-59 yr. Besides, sex, age, WC, SBP, DBP, ALT, FG, UAC, TG, HDL-C and LDL-C are risk factors for MetS after multivariate adjustment. In conclusion, the prevalence of MONW is lower than MHO regardless of gender. Women tend to have a higher MONW prevalence but lower MHO prevalence than men.
Asunto(s)
Pueblo Asiatico/estadística & datos numéricos , Peso Corporal , Salud , Síndrome Metabólico/epidemiología , Obesidad/epidemiología , Población Urbana/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Beijing/epidemiología , Índice de Masa Corporal , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Prevalencia , Factores de Riesgo , Adulto JovenRESUMEN
AIMS/INTRODUCTION: There is still a lack of simple methods and instruments for the early assessment of autonomic dysfunction in metabolic syndrome patients. Assessment of sudomotor function has been proposed to explore autonomic function, and could be used as an early biomarker for metabolic syndrome. In the present study, we use a quick and non-invasive method to measure sudomotor function, and aimed to evaluate its efficacy to identify metabolic syndrome in a Chinese population. MATERIALS AND METHODS: Information on the 1,160 Chinese participants involved in the study, such as age, sex, blood pressure, waist circumference, body mass index, fasting plasma glucose and lipid profile, and SUDOSCAN, was recorded. During the sudomotor test, patients were asked to place their bare hands and feet on large electrodes. The test took 2 min to carry out, was painless and no participant preparation was required. RESULTS: A total of 567 participants were diagnosed with metabolic syndrome. The prevalence of metabolic syndrome correlated significantly with increasing SUDOSCAN cardiac risk score (P for trend <0.0001). Furthermore, an increase in cardiac risk score value was associated with an increase in the number of metabolic syndrome components (P for trend <0.0001). Compared with the no-risk group (cardiac risk score <20), participants in the high-risk group (cardiac risk score ≥30) had a 2.83-fold increased risk of prevalent metabolic syndrome (P < 0.0001), and 1.51-fold increased risk (P = 0.01) after adjustments. CONCLUSIONS: Autonomic dysfunction is correlated to components of metabolic syndrome. The role of SUDOSCAN in the screening of at-risk populations for metabolic syndrome has to be confirmed by further studies.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/complicaciones , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/diagnóstico , Síndrome Metabólico/complicaciones , Adulto , Pueblo Asiatico , Enfermedades del Sistema Nervioso Autónomo/epidemiología , Enfermedades Cardiovasculares/epidemiología , China/epidemiología , Femenino , Respuesta Galvánica de la Piel , Humanos , Masculino , Síndrome Metabólico/epidemiología , Persona de Mediana Edad , Factores de RiesgoRESUMEN
The innate immune system plays a crucial role in the rapid recognition and elimination of invading microbes. Detection of microbes relies on germ-line encoded pattern recognition receptors (PRRs) that recognize essential bacterial molecules, so-called pathogen-associated molecular patterns (PAMPs). A subset of PRRs, belonging to the nucleotide binding oligomerization domain (NOD)-like receptor (NLR) families, detects viral and bacterial pathogens in the cytosol of host cells and induces the assembly of a multi-protein signaling platform called the inflammasome. The inflammasome serves as an activation platform for the cysteine protease Caspase-1, a central mediator of innate immunity. Caspase-1 initiates a novel form of cell death called pyroptosis. Inflammasome activation by pathogen-associated signatures results in the autocatalytic cleavage of Caspase-1 and ultimately leads to the processing and thus secretion of pro-inflammatory cytokines, most importantly interleukin (IL)-1ß and IL-18. Here, we review the recent advancements of negative regulatory functions and mechanisms leading to the activation of NLRP1, NLRP3, NLRC4, and AIM2 inflammasomes.
Asunto(s)
Inflamasomas/metabolismo , Inflamación/metabolismo , Proteínas Adaptadoras de Señalización NOD/metabolismo , Apoptosis , Proteínas Portadoras , Caspasa 1 , Humanos , Inmunidad Innata , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Transducción de SeñalRESUMEN
BACKGROUND: The assembled data from a population could provide information on health trends within the population. The aim of this research was to extract and know basic health information from an urban professional population in Beijing. METHODS: Data analysis was carried out in a population who underwent a routine medical check-up and aged > 20 years, including 30 058 individuals. General information, data from physical examinations and blood samples were collected in the same method. The health status was separated into three groups by the criteria generated in this study, i.e., people with common chronic diseases, people in a sub-clinic situation, and healthy people. The proportion of both common diseases suffered and health risk distribution of different age groups were also analyzed. RESULTS: The proportion of people with common chronic diseases, in the sub-clinic group and in the healthy group was 28.6%, 67.8% and 3.6% respectively. There were significant differences in the health situation in different age groups. Hypertension was on the top of list of self-reported diseases. The proportion of chronic diseases increased significantly in people after 35 years of age. Meanwhile, the proportion of sub-clinic conditions was decreasing at the same rate. The complex risk factors to health in this population were metabolic disturbances (61.3%), risk for tumor (2.7%), abnormal results of morphological examination (8.2%) and abnormal results of lab tests of serum (27.8%). CONCLUSIONS: Health information could be extracted from a complex data set from the heath check-ups of the general population. The information should be applied to support prevention and control chronic diseases as well as for directing intervention for patients with risk factors for disease.