RESUMEN
BACKGROUND: The dysregulation of tissue inhibitor of metalloproteinase-3 (TIMP3) was positively correlated with the progression of hepatocellular carcinoma (HCC). However, it is not clear whether TIMP3 expression is associated with the clinicopathological features and prognosis of aflatoxin B1 (AFB1)-related HCC (AHCC). AIM: To assess the effects of TIMP3 expression on the clinicopathological features and prognosis of AHCC. METHODS: A retrospective study, including 182 patients with AHCC, was conducted to explore the link between TIMP3 expression in cancerous tissues and the clinicopathological characteristics and prognosis of AHCC. TIMP3 expression was detected by immunohistochemistry and its effects on the clinicopathological features and prognosis of AHCC were evaluated by Kaplan-Meier survival analysis and Cox regression survival analysis. Odds ratio, hazard ratio (HR), median overall survival time (MST), median tumor recurrence-free survival time (MRT), and corresponding 95% confidential interval (CI) was calculated to evaluate the potential of TIMP3 expression in predicting AHCC prognosis. RESULTS: Kaplan-Meier survival analysis showed that compared with high TIMP3 expression, low TIMP3 expression in tumor tissues significantly decreased the MST (36.00 mo vs 18.00 mo) and MRT (32.00 mo vs 16 mo) of patients with AHCC. Multivariate Cox regression survival analysis further proved that decreased expression of TIMP3 increased the risk of death (HR = 2.85, 95%CI: 2.04-4.00) and tumor recurrence (HR = 2.26, 95%CI: 1.57-3.26). Furthermore, decreased expression of TIMP3 protein in tissues with AHCC was significantly correlated with tumor clinicopathological features, such as tumor size, tumor grade and stage, tumor microvessel density, and tumor blood invasion. Additionally, TIMP3 protein expression was also negatively associated with amount of AFB1-DNA adducts in tumor tissues. CONCLUSION: These findings indicate that the dysregulation of TIMP3 expression is related to AHCC biological behaviors and affects tumor outcome, suggesting that TIMP3 may act as a prognostic biomarker for AHCC.
RESUMEN
Objectives: Obstructive sleep apnea (OSA) and osteoarthritis (OA) are common comorbidities that significantly impact individuals' quality of life. However, the relationship between OSA and OA remains unclear. This study aims to explore the connection between OSA and OA and evaluate causality using Mendelian randomization (MR). Methods: A total of 12,454 participants from the National Health and Nutrition Examination Survey (2009-2012) were included. OSA participants were identified based on self-reported interviews. The association between OA and OSA was assessed through multivariable logistic regression analysis. A two-sample MR was employed to investigate the relationship between OSA and OA, specifically hip OA and knee OA, utilizing the inverse variance-weighted (IVW) approach. Results: Based on the observational study, individuals with OSA exhibited a higher risk of OA (OR = 1.67, 95% CI = 1.40-1.98). IVW demonstrated that the risk of OA (OR = 1.13, 95% CI: 1.05-1.21, p = 0.001), hip OA (OR = 1.11, 95% CI: 1.04-1.18, p = 0.002), and knee OA (OR = 1.08, 95% CI: 1.02-1.14, p = 0.005) was significantly associated with OSA. Reverse MR analyses indicated no effect of OA on OSA. Additionally, body mass index (BMI) was found to mediate 36.9% (95% CI, 4.64-73.2%, p = 0.026) of the OSA effects on OA risk. Conclusion: The cross-sectional observational analysis unveiled noteworthy associations between OSA and OA. Meanwhile, findings from the MR study provide support for a causal role.
RESUMEN
Lumbar sympathetic blocks (LSBs) are used to treat sympathetically mediated pain in the lower extremities, kidneys, ureters, and genitals. LSBs use local anesthetic to block the sympathetic system to modulate pain response. In this case report, an avid runner was diagnosed with synovial plica syndrome. His pain was refractory to arthroscopic plica excision, physical therapy, nonsteroidal anti-inflammatory drugs, and intraarticular steroid injections. He received 3 rounds of LSB resulting in significant and sustained pain relief. This case suggests that LSB successfully treated knee pain from synovial plica syndrome and there may be a sympathetic component to this disease state.
Asunto(s)
Bloqueo Nervioso Autónomo , Humanos , Masculino , Bloqueo Nervioso Autónomo/métodos , Articulación de la Rodilla/cirugía , SíndromeRESUMEN
Urban stray cats are cats without owners that survive in the wild for extended periods of time. They are one of the most common stray animals in cities, and as such, monitoring the pathogens carried by urban stray cats is an important component of urban epidemiological surveillance. In order to understand the prevalence of respiratory diseases in urban stray cats in Shanghai and provide scientific evidence for the development of targeted prevention and control strategies for respiratory diseases in stray cats, we collected 374 ocular, nasal, and oropharyngeal swabs from urban stray cats in Shanghai from January 2022 to December 2022. After RNA extraction, we used real-time PCR to detect six respiratory pathogens, including influenza A virus, feline calicivirus, feline herpesvirus type 1, Mycoplasma, Chlamydia, and Bordetella bronchiseptica. The results showed that among the 374 samples, 146 tested positive, with a positivity rate of 39.04%. The highest positivity rate was observed for Mycoplasma felis at 18.72% (70/374), followed by Chlamydia felis at 11.76% (44/374), feline calicivirus at 3.74% (14/374), feline herpesvirus 1 at 3.48% (13/374), Bordetella bronchiseptica at 1.34% (5/374), and influenza A virus was not detected. The highest positivity rate for Mycoplasma felis was in Minhang District at 31.94% (23/72), while Chlamydia felis and Bordetella bronchiseptica had the highest positivity rates in Jiading District at 23.53% (8/34) and 5.88% (2/34), respectively. The highest positivity rates for feline calicivirus and feline herpesvirus 1 were both observed in Qingpu District, at 14.46% (12/83) and 9.64% (8/83), respectively. A total of 36 samples showed mixed infections with two or more pathogens, with Mycoplasma felis being involved in 32 of these mixed infections, with the highest number of mixed infections being with Chlamydia felis at 25 samples. Respiratory pathogen positivity was detected throughout the year, with peak detection rates in summer and winter. The positivity rates of cat respiratory pathogens in different seasons showed statistical differences (χ2 = 27.73, p < 0.01). There was no statistical difference in the positivity rates of respiratory pathogens between cats of different genders (χ2 = 0.92, p > 0.05). The positivity rates of respiratory pathogens in cats of different age groups showed statistical differences (χ2 = 44.41, p < 0.01). Mycoplasma felis and Chlamydia felis were the main pathogens causing respiratory infections in stray cats, with Mycoplasma felis showing a much higher positivity rate than other respiratory pathogens and often co-infecting with Chlamydia felis and feline calicivirus. The positivity rate of Mycoplasma felis was high in summer, autumn, and winter, with no statistical difference between seasons. These results indicate a serious overall prevalence of respiratory pathogens in urban stray cats in the Shanghai area, showing seasonal trends and mixed infections with other pathogens. These findings suggest the need for comprehensive prevention and control measures to address respiratory pathogen infections in urban stray cats in the Shanghai area.
RESUMEN
OBJECTIVE: A notable research gap exists in the systematic review and meta-analysis concerning the efficacy, immunogenicity, and safety of the respiratory syncytial virus (RSV) prefusion F vaccine. METHODS: We conducted a comprehensive search across PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov to retrieve articles related to the efficacy, immunogenicity, and safety of RSV prefusion F vaccines, published through September 8, 2023. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: A total of 22 randomized controlled trials involving 78,990 participants were included in this systematic review and meta-analysis. The RSV prefusion F vaccine exhibited a vaccine effectiveness of 68% (95% CI: 59-75%) against RSV-associated acute respiratory illness, 70% (95% CI: 60-77%) against medically attended RSV-associated lower respiratory tract illness, and 87% (95% CI: 71-94%) against medically attended severe RSV-associated lower respiratory tract illness. Common reported local adverse reactions following RSV prefusion F vaccination include pain, redness, and swelling at the injection site, and systemic reactions such as fatigue, headache, myalgia, arthralgia, nausea, and chills. CONCLUSIONS: Our meta-analysis suggests that vaccines using the RSV prefusion F protein as antigen exhibit appears broadly acceptable efficacy, immunogenicity, and safety in the population. In particular, it provides high protective efficiency against severe RSV-associated lower respiratory tract disease.
Asunto(s)
Infecciones por Virus Sincitial Respiratorio , Vacunas contra Virus Sincitial Respiratorio , Humanos , Infecciones por Virus Sincitial Respiratorio/prevención & control , Vacunas contra Virus Sincitial Respiratorio/inmunología , Eficacia de las Vacunas , Virus Sincitial Respiratorio Humano/inmunología , Inmunogenicidad Vacunal , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
In May 2022, mpox began to spread worldwide, posing a serious threat to human public health. Modified Vaccinia Ankara-Bavaria Nordic (MVA-BN) is a live attenuated orthopoxvirus vaccine that has been authorized by the U.S. Food and Drug Administration as the vaccine of choice for the prevention of mpox. In this study, we conducted a meta-analysis of all currently published literature on the efficacy and safety of the MVA-BN vaccine in the real world, showing that the MVA-BN vaccine is effective and safe, with efficacy of up to 75% with a single dose and up to 80% with a two-dose vaccine. Meanwhile, we found that subcutaneous injection has lower local and systemic adverse events than intradermal injection, regardless of single- or two-dose vaccination, and subcutaneous injection is better tolerated in children, the elderly, or people with underlying medical conditions. These results have important reference value for clinical practice.
Asunto(s)
Eficacia de las Vacunas , Vacunas Atenuadas , Humanos , Vacunas Atenuadas/inmunología , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/efectos adversos , Infecciones por Poxviridae/prevención & control , Infecciones por Poxviridae/inmunología , Virus Vaccinia/inmunología , Virus Vaccinia/genética , Vacunación , Inyecciones Subcutáneas , Inyecciones Intradérmicas , Vacunas Virales/efectos adversos , Vacunas Virales/inmunología , Vacunas Virales/administración & dosificación , Orthopoxvirus/inmunología , Orthopoxvirus/genética , NiñoRESUMEN
Objective: Anti-dipeptidyl-peptidase-like protein-6 (DPPX) encephalitis is a rare autoimmune encephalitis, and clinical and experimental information regarding this disease is limited. We conducted this study to comprehensively describe the clinical characteristics, ancillary test results, neuroimaging results, and treatment response in a group of Chinese patients with anti-DPPX encephalitis for better understanding this disease. Methods: We recruited 14 patients who tested positive for anti-DPPX antibodies in the serum and/or cerebrospinal fluid from 11 medical centers between March 2021 and June 2023. This retrospective study evaluated data on symptoms, autoantibody test, auxiliary examinations, treatments, and outcomes. Results: The average age at diagnosis was 45.93 ± 4.62 years (range: 11-72 years), and 9 of the 14 patients were males. The main symptoms included cognitive impairment (50.0%, 7/14), central nervous system hyperexcitability (42.9%, 6/14), gastrointestinal dysfunction (35.7%, 5/14), and psychiatric disorders (35.7%, 5/14). Notably, we discovered specific findings on 18F-fluorodeoxyglucose positron-emission tomography (PET)/magnetic resonance imaging in two patients. Co-existing autoantibodies were identified in two patients. Parainfection was identified in four patients. One patient had other autoimmune diseases, and one had tumor. Eleven patients received immunotherapy and most patients improved at discharge. Surprisingly, three male patients but no female patients relapsed during the 6 months of follow-up. Conclusion: The development and outcome of anti-DPPX encephalitis are variable. Male patients were predominant in our cohort. The most common symptoms were the classical triad of prodromal gastrointestinal dysfunction, cognitive and mental disorders, and central nervous system hyperexcitability. Infections, immune dysregulation, and tumors may be important etiologies. Long-term monitoring of disease development should be done in male patients. Overall, our results highlight novel clinical characteristics of anti-DPPX encephalitis.
RESUMEN
BACKGROUND: Establishing effective pharmacovigilance systems globally is challenging due to the need for comprehensive epidemiological data on pharmacovigilance-related events, particularly in countries at different stages of development. AIM: This study aimed to determine magnitude and drivers of change in the global and regional burden of pharmacovigilance-related events from 1990 to 2019, analyzing variations between age groups and sex, providing data support for policymakers to adjust their pharmacovigilance policies. METHOD: Pharmacovigilance-related events were defined as Adverse Effects of Medical Treatment (AEMT) and Drug Use Disorders (DUD) in the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Time trend analysis utilized joinpoint regression, age-period-cohort model, and decomposition method. Disease burden was measured in incidence, deaths, and disability-adjusted life years (DALYs). RESULTS: The global burden of pharmacovigilance-related events remained high, driven predominantly by population growth. Children and older adults were identified as particularly susceptible groups. Across various regions and periods of the socio-demographic index (SDI), the risk of death from AEMT showed a decreasing trend. In contrast, the incidence of AEMT and both the incidence and death rates from DUD showed a stable or worsening trend. Significant regional disparities in the burden of these diseases were noted between different SDI levels. CONCLUSION: The study underscores the critical need for robust pharmacovigilance systems worldwide. The observed trends in the burden of pharmacovigilance-related events offer a clear direction for countries to refine and strengthen their pharmacovigilance policies and practices.
RESUMEN
BACKGROUND: Among the numerous studies on physical activity and sleep disorders, few have focused on physical activity and sleep disorders in middle-aged people who are particularly stressed. A restricted cubic web (RCS) technique was applied to determine whether physical activity and the self-rated prevalence of sleep disorders exhibit a dose-response relationship in middle-aged adults. METHODS: This study analyzed 8880 middle-aged adults aged 40-65 years who participated in the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Logistic regression was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) between physical activity and sleep disorders in middle-aged adults. Thereafter, the dose-response connection was examined using RCS. RESULTS: After adjusting for potential confounders, subjects with MET values in the first quartile (Q1) had odds ratios (OR) for sleep disturbance of 0.851 (95% CI = 0.745-0.973), 0.800 (95% CI = 0.698-0.917), and 0.780 (95% CI = 0.680-0.895) compared to subjects with MET values in the second, third, and fourth quartiles respectively. RCS regression showed a non-linear association between physical activity and sleep disorders in middle-aged adults (non-linearity P = 0.0382). Furthermore, the prevalence of sleep disorders in middle-aged adults decreased with increasing physical activity, reaching a minimum when weekly physical activity was around 166.27MET*h (OR = 0.885, 95% CI = 0.799-0.981). CONCLUSION: Our research demonstrates that physical activity was negatively associated with sleep disorders.
Asunto(s)
Ejercicio Físico , Encuestas Nutricionales , Trastornos del Sueño-Vigilia , Humanos , Persona de Mediana Edad , Masculino , Estudios Transversales , Femenino , Trastornos del Sueño-Vigilia/epidemiología , Adulto , Estados Unidos/epidemiología , Anciano , PrevalenciaRESUMEN
F-box protein is a subunit of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex, which plays a critical role in regulating different pathways in plant immunity. In this study, we identified the rice (Oryza sativa) F-box protein OsFBX156, which targets the heat shock protein 70 (OsHSP71.1) to regulate resistance to the rice blast fungus Magnaporthe oryzae. Overexpression of OsFBX156 or knockout of OsHSP71.1 in rice resulted in the elevation of pathogenesis-related (PR) genes and an induction burst of reactive oxygen species (ROS) after flg22 and chitin treatments, thereby enhancing resistance to M. oryzae. Furthermore, OsFBX156 can promote the degradation of OsHSP71.1 through the 26S proteasome pathway. This study sheds lights on a novel mechanism wherein the F-box protein OsFBX156 targets OsHSP71.1 for degradation to promote ROS production and PR gene expression, thereby positively regulating rice innate immunity.
Asunto(s)
Resistencia a la Enfermedad , Proteínas F-Box , Oryza , Enfermedades de las Plantas , Proteínas de Plantas , Ubiquitinación , Oryza/microbiología , Oryza/metabolismo , Oryza/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Resistencia a la Enfermedad/genética , Proteínas F-Box/metabolismo , Proteínas F-Box/genética , Especies Reactivas de Oxígeno/metabolismo , Regulación de la Expresión Génica de las Plantas , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteolisis , Inmunidad de la Planta/genética , Ascomicetos/patogenicidadRESUMEN
Plants typically activate distinct defense pathways against various pathogens. Heightened resistance to one pathogen often coincides with increased susceptibility to another pathogen. However, the underlying molecular basis of this antagonistic response remains unclear. Here, we demonstrate that mutants defective in the transcription factor ETHYLENE-INSENSITIVE 3-LIKE 2 (OsEIL2) exhibited enhanced resistance to the biotrophic bacterial pathogen Xanthomonas oryzae pv oryzae and to the hemibiotrophic fungal pathogen Magnaporthe oryzae, but enhanced susceptibility to the necrotrophic fungal pathogen Rhizoctonia solani. Furthermore, necrotroph-induced OsEIL2 binds to the promoter of OsWRKY67 with high affinity, leading to the upregulation of salicylic acid (SA)/jasmonic acid (JA) pathway genes and increased SA/JA levels, ultimately resulting in enhanced resistance. However, biotroph- and hemibiotroph-induced OsEIL2 targets OsERF083, resulting in the inhibition of SA/JA pathway genes and decreased SA/JA levels, ultimately leading to reduced resistance. Our findings unveil a previously uncharacterized defense mechanism wherein two distinct transcriptional regulatory modules differentially mediate immunity against pathogens with different lifestyles through the transcriptional reprogramming of phytohormone pathway genes.
Asunto(s)
Ciclopentanos , Regulación de la Expresión Génica de las Plantas , Oryza , Oxilipinas , Enfermedades de las Plantas , Inmunidad de la Planta , Proteínas de Plantas , Rhizoctonia , Ácido Salicílico , Xanthomonas , Oxilipinas/metabolismo , Ácido Salicílico/metabolismo , Ciclopentanos/metabolismo , Oryza/microbiología , Oryza/genética , Oryza/inmunología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Xanthomonas/fisiología , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Rhizoctonia/fisiología , Inmunidad de la Planta/efectos de los fármacos , Mutación/genética , Resistencia a la Enfermedad/genética , Regiones Promotoras Genéticas/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Unión Proteica/efectos de los fármacosRESUMEN
OBJECTIVES: This study aimed to systematically assess global economic evaluation studies on COVID-19 vaccination, offer valuable insights for future economic evaluations, and assist policymakers in making evidence-based decisions regarding the implementation of COVID-19 vaccination. METHODS: Searches were performed from January 2020 to September 2023 across seven English databases (PubMed, Web of Science, MEDLINE, EBSCO, KCL-Korean Journal Dataset, SciELO Citation Index, and Derwent Innovations Index) and three Chinese databases (Wanfang Data, China Science and Technology Journal, and CNKI). Rigorous inclusion and exclusion criteria were applied. Data were extracted from eligible studies using a standardized data collection form, with the reporting quality of these studies assessed using the Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022). RESULTS: Of the 40 studies included in the final review, the overall reporting quality was good, evidenced by a mean score of 22.6 (ranging from 10.5 to 28). Given the significant heterogeneity in fundamental aspects among the studies reviewed, a narrative synthesis was conducted. Most of these studies adopted a health system or societal perspective. They predominantly utilized a composite model, merging dynamic and static methods, within short to medium-term time horizons to simulate various vaccination strategies. The research strategies varied among studies, investigating different doses, dosages, brands, mechanisms, efficacies, vaccination coverage rates, deployment speeds, and priority target groups. Three pivotal parameters notably influenced the evaluation results: the vaccine's effectiveness, its cost, and the basic reproductive number (R0). Despite variations in model structures, baseline parameters, and assumptions utilized, all studies identified a general trend that COVID-19 vaccination is cost-effective compared to no vaccination or intervention. CONCLUSIONS: The current review confirmed that COVID-19 vaccination is a cost-effective alternative in preventing and controlling COVID-19. In addition, it highlights the profound impact of variables such as dose size, target population, vaccine efficacy, speed of vaccination, and diversity of vaccine brands and mechanisms on cost effectiveness, and also proposes practical and effective strategies for improving COVID-19 vaccination campaigns from the perspective of economic evaluation.
Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Análisis Costo-Beneficio , SARS-CoV-2 , Humanos , COVID-19/prevención & control , COVID-19/economía , Vacunas contra la COVID-19/economía , Vacunas contra la COVID-19/administración & dosificación , Programas de Inmunización/economía , Vacunación/economíaRESUMEN
Although the antagonistic effects of host resistance against biotrophic and necrotrophic pathogens have been documented in various plants, the underlying mechanisms are unknown. Here, we investigated the antagonistic resistance mediated by the transcription factor ETHYLENE-INSENSITIVE3-LIKE 3 (OsEIL3) in rice. The Oseil3 mutant confers enhanced resistance to the necrotroph Rhizoctonia solani but greater susceptibility to the hemibiotroph Magnaporthe oryzae and biotroph Xanthomonas oryzae pv. oryzae. OsEIL3 directly activates OsERF040 transcription while repressing OsWRKY28 transcription. The infection of R. solani and M. oryzae or Xoo influences the extent of binding of OsEIL3 to OsWRKY28 and OsERF040 promoters, resulting in the repression or activation of both salicylic acid (SA)- and jasmonic acid (JA)-dependent pathways and enhanced susceptibility or resistance, respectively. These results demonstrate that the distinct effects of plant immunity to different pathogen types are determined by two transcription factor modules that control transcriptional reprogramming and the SA and JA pathways.
Asunto(s)
Ciclopentanos , Regulación de la Expresión Génica de las Plantas , Oryza , Oxilipinas , Enfermedades de las Plantas , Inmunidad de la Planta , Proteínas de Plantas , Ácido Salicílico , Xanthomonas , Ciclopentanos/metabolismo , Oryza/microbiología , Oryza/genética , Oryza/inmunología , Oryza/metabolismo , Oxilipinas/metabolismo , Ácido Salicílico/metabolismo , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Xanthomonas/patogenicidad , Inmunidad de la Planta/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Rhizoctonia , Transducción de Señal , Resistencia a la Enfermedad/genética , Regiones Promotoras Genéticas/genética , Magnaporthe , Transcripción GenéticaRESUMEN
Understanding interfacial interactions of graphene oxide (GO) is important to evaluate its colloidal behavior and environmental fate. Single-layer GO is the fundamental unit of GO colloids, and its interfacial aqueous layers critically dictate these interfacial interactions. However, conventional techniques like X-ray diffraction are limited to multilayer systems and are inapplicable to single-layer GO. Therefore, our study employed atomic force microscopy to precisely observe the in situ dynamic behaviors of interfacial aqueous layers on single-layer GO. The interfacial aqueous layer height was detected at the subnanometer level. In real-time monitoring, the single-layer height increased from 1.17 to 1.70 nm within 3 h immersion. This sluggish process is different from the rapid equilibration of multilayer GO in previous studies, underscoring a gradual transition in hydration kinetics. Ion strength exhibited negligible influence on the single-layer height, suggesting a resilient response of the interfacial aqueous layer to ion-related perturbations due to intricate ion interactions and electrical double-layer compression. Humic acid led to a substantial increase in the interfacial aqueous layers, improving the colloidal stability of GO and augmenting its potential for migration. These findings hold considerable significance regarding the environmental behaviors of the GO interfacial aqueous layer in ion- and organic-rich water and soil.
Asunto(s)
Grafito , Agua , Microscopía de Fuerza Atómica , ColoidesRESUMEN
Ferroptosis is a newly recognized type of programmed cell death that is implicated in the pathophysiological process of neurological disorders. Our previous studies have revealed that exposure to high concentrations of fluoride for long periods of time induces hippocampal neural injury and cognitive deficits. However, whether ferroptosis is involved in fluoride-induced neuronal death and the underlying mechanism remain unknown. In this study, the results indicated that exposure to high fluoride triggered ferroptosis in SH-SY5Y cells and in the hippocampus of mice. Fluoride exposure accelerated the lysosomal degradation of GPX4 and led to neuronal ferroptosis, while GPX4 overexpression protected SH-SY5Y cells against fluoride-induced neurotoxicity. Intriguingly, the enhanced chaperone-mediated autophagy (CMA) induced by fluoride stimulation was responsible for GPX4 degradation because the inhibition of CMA activity by LAMP2A knockdown effectively prevented fluoride-induced GPX4 loss. Furthermore, mitochondrial ROS (mtROS) accumulation caused by fluoride contributed to CMA activation-mediated GPX4 degradation and subsequent neuronal ferroptosis. Notably, the ferroptosis-specific inhibitor ferrostatin-1 (Fer-1) or the ROS scavenger N-acetyl-L-cysteine (NAC) alleviated fluoride-evoked hippocampal neuronal death and synaptic injury as well as cognitive deficits in mice. The present studies indicates that ferroptosis is a novel mechanism of fluoride-induced neurotoxicity and that chronic fluoride exposure facilitates GPX4 degradation via mtROS chaperone-mediated autophagy, leading to neuronal ferroptosis and cognitive impairment.
Asunto(s)
Autofagia Mediada por Chaperones , Disfunción Cognitiva , Ferroptosis , Fluoruros , Neuronas , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Especies Reactivas de Oxígeno , Animales , Humanos , Ratones , Autofagia/efectos de los fármacos , Autofagia Mediada por Chaperones/fisiología , Autofagia Mediada por Chaperones/efectos de los fármacos , Disfunción Cognitiva/inducido químicamente , Ferroptosis/efectos de los fármacos , Ferroptosis/fisiología , Fluoruros/toxicidad , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Neuronas/efectos de los fármacos , Fosfolípido Hidroperóxido Glutatión Peroxidasa/efectos de los fármacos , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The primary focal point in the fabrication of microfiltration membranes revolves around mitigating issues of low permeability stemming from the initial design as well as countering biofouling tendencies. This work aimed to address these issues by synthesizing an antibacterial capsaicin derivative (CD), which was then grafted to the poly(vinylidene fluoride-co-chlorotrifluoroethylene)-g-polymethacrylic acid (P(VDF-CTFE)-g-PMAA) matrix polymer, resulting in an antibacterial polymer (PD). Notably, both CD and PD demonstrated low cytotoxicities. Utilizing PD, a microfiltration membrane (MA) was successfully prepared through non-solvent-induced phase inversion. The pore sizes of the MA membrane were mainly concentrated at around 436 nm, while the pure water flux of MA reached an impressive value of 62 ± 0.17 Lm-2 h-1 at 0.01 MPa. MA exhibited remarkable efficacy in eradicating both Gram-negative (E. coli) and Gram-positive bacteria (Bacillus subtilis) from its surface. Compared with M1 prepared from P(VDF-CTFE), MA exhibited a lower flux decay rate (41.00% vs. 76.03%) and a higher flux recovery rate (84.95% vs. 46.54%) after three cycles. Overall, this research represents a significant step towards the development of a microfiltration membrane with inherent stable anti-biofouling capability to enhance filtration.
Asunto(s)
Antibacterianos , Bacillus subtilis , Incrustaciones Biológicas , Capsaicina , Escherichia coli , Membranas Artificiales , Incrustaciones Biológicas/prevención & control , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Escherichia coli/efectos de los fármacos , Capsaicina/química , Capsaicina/farmacología , Bacillus subtilis/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Filtración , Propiedades de Superficie , Tamaño de la PartículaRESUMEN
Exposure to environmental cadmium (Cd) is known to cause neuronal death and cognitive decline in humans. Ferroptosis, a novel iron-dependent type of regulated cell death, is involved in various neurological disorders. In the present study, Cd exposure triggered ferroptosis in the mouse hippocampus and in the HT22 murine hippocampal neuronal cell line, as indicated by significant increases in ferroptotic marker expression, intracellular iron levels, and lipid peroxidation. Interestingly, ferroptosis of hippocampal neurons in response to Cd exposure relied on the induction of autophagy since the suppression of autophagy by 3-methyladenine (3-MA) and chloroquine (CQ) substantially ameliorated Cd-induced ferroptosis. Furthermore, nuclear receptor coactivator 4 (NCOA4)-mediated degradation of ferritin was required for the Cd-induced ferroptosis of hippocampal neurons, demonstrating that NCOA4 knockdown decreased intracellular iron levels and lipid peroxidation and increased cell survival, following Cd exposure. Moreover, Cd-induced mitochondrial reactive oxygen species (mtROS) generation was essential for the ferritinophagy-mediated ferroptosis of hippocampal neurons. Importantly, pretreatment with the ferroptosis inhibitor ferrostatin-1 (Fer-1) effectively attenuated Cd-induced hippocampal neuronal death and cognitive impairment in mice. Taken together, these findings indicate that ferroptosis is a novel mechanism underlying Cd-induced neurotoxicity and cognitive impairment and that the mtROS-ferritinophagy axis modulates Cd-induced neuronal ferroptosis.
Asunto(s)
Cadmio , Disfunción Cognitiva , Ferroptosis , Hipocampo , Neuronas , Coactivadores de Receptor Nuclear , Especies Reactivas de Oxígeno , Ferroptosis/efectos de los fármacos , Animales , Ratones , Cadmio/toxicidad , Neuronas/efectos de los fármacos , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Coactivadores de Receptor Nuclear/metabolismo , Coactivadores de Receptor Nuclear/genética , Ferritinas/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Masculino , Autofagia/efectos de los fármacos , Hierro/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Línea Celular , Ratones Endogámicos C57BLRESUMEN
OBJECTIVES: The popularity of contracted family doctor services in China has been growing in recent years, but community-family-doctor-based type 2 diabetes mellitus (T2DM) intervention programs have yet to be adequately studied. This study was to evaluate the short- and long-term effects of community-family-doctor-based self-management interventions for T2DM and to explore strategies for long-term glycemic control. STUDY DESIGN: This was a randomized controlled trial. METHODS: A total of 144 eligible participants were randomly assigned to intervention and control groups. The control group received only routine community diabetes care, and the intervention group received community-family-doctor-based interventions involving the same standard of care. The interventions lasted for 3 months, and the follow-up was continued for 15 months. Intention-to-treat analysis and generalized estimation equations were then used to determine the short- and long-term effects of the interventions on glycated hemoglobin (HbA1c), diabetes self-management, and medication adherence. RESULTS: There were statistically significantly greater improvements in all aspects of the intervention group after 3 months of intervention. Compared with baseline, changes in the attitude (ß = 0.384, 95% confidence interval [CI; 0.194, 0.574], P < 0.001), practice (ß = 1.751, 95% CI [0.762, 2.739], P = 0.001), and knowledge, attitudes, practice total scores (ß = 2.338, 95% CI [0.682, 3.995], P = 0.006) of patients in the intervention group were statistically significant after 15 months, and the HbA1c (8.19 ± 1.73%), knowledge (16.42 ± 3.21), and medication adherence (5.53 ± 1.76) scores were slightly better than those at baseline, although not statistically significant (P > 0.05). CONCLUSIONS: T2DM self-management interventions based on community family doctors improved patients' HbA1c, diabetes self-management, and medication adherence, did not do so significantly in the long term.
Asunto(s)
Diabetes Mellitus Tipo 2 , Médicos , Automanejo , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hemoglobina Glucada , AutocuidadoRESUMEN
BACKGROUND: Depression is a common mental illness characterised by abnormal and depressed emotions. Total paeony glycoside (TPG) is a naturally active saponin extracted from the traditional Chinese medicine Radix Paeoniae rubra. However, the antidepressant and neuroinflammatory effects of TPG have not been thoroughly studied. PURPOSE: To study the therapeutic potential of TGP in depression caused by neuronal injury and neuroinflammation and to explore the mechanism of TGP and the relationship between the NLRP3 inflammasome, pyroptosis, and autophagy. STUDY DESIGN: A chronic unpredictable mild stress (CUMS)-induced depression model and a cell model of corticosterone (CORT)-induced hippocampal neuron injury were established to evaluate the therapeutic effects of TPG. METHODS: The composition of TPG was analysed using high-performance liquid chromatography and mass spectrometry. The effects of TPG and fluoxetine on depression-like behaviour, neuronal injury, neuroinflammation, pyroptosis, and mitochondrial autophagy in the mice models were evaluated. RESULTS: TGP alleviated depression-like behaviours in mice and inhibited hippocampal neuronal apoptosis. The secretion of inflammatory cytokines was significantly reduced in CORT-induced hippocampal neuron cells and in the serum of a mouse model of CUMS-induced depression. In addition, TGP treatment reduced the levels of NLRP3 family pyrin structural domains, including NLRP3, pro-caspase-1, caspase-1, and IL-1ß, and the pyroptosis related proteins such as GSDMD-N. Importantly, TPG attenuated mitochondrial dysfunction, promoted the clearance of damaged mitochondria, and the activation of mitochondrial autophagy, which reduced ROS accumulation and NLRP3 inflammasome activation. An in-depth study observed that the regulatory effect of TPG on autophagy was attenuated by the autophagy inhibitor 3-methyladenine (3-MA) in vitro and in vivo. However, administration of the caspase-1 inhibitor Belnacasan (VX-765) successfully inhibited pyroptosis and showed a synergistic therapeutic effect with TPG. CONCLUSION: These results indicate that TPG can repair neuronal damage by activating autophagy, restoring mitochondrial function, and reducing inflammation-mediated pyroptosis, thereby playing an important role in the alleviation of neuroinflammation and depression. This study suggests new potential drugs and treatment strategies for neuroinflammation-related diseases and depression.
Asunto(s)
Antidepresivos , Autofagia , Depresión , Modelos Animales de Enfermedad , Glicósidos , Hipocampo , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Paeonia , Piroptosis , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Autofagia/efectos de los fármacos , Antidepresivos/farmacología , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Ratones , Masculino , Glicósidos/farmacología , Piroptosis/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Depresión/tratamiento farmacológico , Paeonia/química , Ratones Endogámicos C57BL , Neuronas/efectos de los fármacos , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacologíaRESUMEN
PURPOSE: Laparoscopic isolated caudate lobectomy is still a challenging operation for surgeons. The access route of the operation plays a vital role during laparoscopic caudate lobectomy. There are few references regarding this technique. Here, we introduce a preferred inferior vena cava (IVC) approach in laparoscopic caudate lobectomy. METHODS: Twenty-one consecutive patients with caudate hepatic tumours between June 2016 and December 2021 were included in this study. All of them received laparoscopic caudate lobectomy involving an IVC priority approach. The IVC priority approach refers to prioritizing the dissection of the IVC from the liver parenchyma before proceeding with the conventional left or right approach. It emphasizes the importance of the IVC dissection during process. Clinical data, intraoperative parameters and postoperative results were evaluated. Sixteen patients were performed pure IVC priority approach, while 5 patients underwent a combined approach. We subsequently compared the intraoperative and postoperative between the two groups. RESULTS: All 21 patients were treated with laparoscopic technology. The operative time was 190.95 ± 92.65 min. The average estimated blood loss was 251.43 ± 247.45 ml, and four patients needed blood transfusions during the perioperative period. The average duration of hospital stay was 8.43 ± 2.64 (range from 6.0 to 16.0) days. Patients who underwent the pure inferior vena cava (IVC) approach required a shorter hepatic pedicle clamping time (26 vs. 55 min, respectively; P < 0.001) and operation time (150 vs. 380 min, respectively; P = 0.002) than those who underwent the combined approach. Hospitalization (7.0 vs. 9.0 days, respectively; P = 0.006) was shorter in the pure IVC group than in the combined group. CONCLUSIONS: Laparoscopic caudate lobectomy with an IVC priority approach is safe and feasible for patients with caudate hepatic tumours.