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Introduction: With the continued prevalence of COVID-19, repeated infection caused by SARS-CoV-2 has become common. However, studies on immune persistence post Omicron XBB reinfection are limited. Methods: We prospectively studied the durability and cross-reactivity of neutralizing antibodies (NAbs) and T cell responses among 20 subjects who suffered Omicron BA.5 infection with or without Omicron XBB reinfection over 6-month through the pseudovirus neutralization test and the fluorospot assay. Results: NAbs against EG.5.1, BA.2.86, and JN.1 subvariants were decreased and undetectable at 6-month post Omicron BA.5 infection, while those elicited by Omicron XBB reinfection were significant increased and remained detectable against all detected variants within 6-month. Furthermore, in subjects with Omicron XBB reinfection, memory T cell responses could cross-recognized wild-type and Omicron spike peptides and reached peak at 3-month. Interestingly, comparable robust T cell responses were observed among non-seroconverted subjects post Omicron XBB exposure. Conclusion: Though the NAbs against various emerging Omicron subvariants elicited by Omicron XBB reinfection can persist for at least 6-month, the HCWs should strengthen personal protection and timely be immunized with updated vaccines upon current circulating variants or conserved T epitope.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , Células T de Memoria , Reinfección , SARS-CoV-2 , Humanos , Anticuerpos Neutralizantes/inmunología , COVID-19/inmunología , SARS-CoV-2/inmunología , Masculino , Femenino , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Reinfección/inmunología , Adulto , Persona de Mediana Edad , Células T de Memoria/inmunología , Reacciones Cruzadas/inmunología , Estudios Prospectivos , Vacunas contra la COVID-19/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunologíaRESUMEN
OBJECTIVE: Given the lack of global consensus on anesthesia selection for peritoneal dialysis catheter (PDC) placement via open surgery, this study investigates the safety and efficacy of combining local infiltration anesthesia (LIA) with monitored anesthesia care (MAC) in patients with end-stage renal disease (ESRD). METHODS: This retrospective analysis of ESRD patients who underwent open surgical placement of PDC in the Department of Nephrology, the First Affiliated Hospital of the Army Medical University from 1 August 2020 to 31 May 2022. Patients were categorized into two groups based on anesthesia method: LIA group and LIA + MA group. MA was defined as preoperative sedation (0.2-0.7 µg/kg/h) with dexmedetomidine injection (Huidrican trade name, DEX), and intraoperative analgesia with dexrazoxane injection (Garonin trade name, DEZ) as appropriate according to the patients' pain scores. We compared the general clinical data of the two groups of patients, the changes in blood pressure and heart rate during the whole operation, the intraoperative and postoperative pain, the total duration of the operation and the immediate postoperative complications. RESULTS: The study included 123 patients (59 in the LIA + MAC group and 64 in the LIA group). The LIA + MA group exhibited lower pain scores measured by Visual Analogue Scale(VAS) during surgery (skin incision, subcutaneous adipose tissue dissection, anterior fascia, muscle traction, posterior fascia, peritoneum, and catheterization) compared to the LIA group(p<0.05). In terms of surgical incisions, to intraoperative pain scores (VRS), the LIA + MA group showed higher score level I and lower score level II compared to the LIA group (p = 0.002, 0.004, respectively). The LIA + MA group experienced lower postoperative resting pain (NRS) and VAS than the LIA group (p = 0.001,0.003, respectively). The surgical duration for the LIA + MA group was shorter than that of the LIA group (p<0.001). Preoperative systolic and diastolic blood pressures (SBP and DBP) were higher in the LIA + MA group compared to the LIA group (p<0.001,<0.001, respectively). Postoperative heart rate and DBP were lower in the LIA + MA group (p<0.001, 0.004, respectively). The LIA + MA group exhibited greater changes in heart rate, SBP, and DBP during and after surgery compared to the LIA group (p = 0.009, <0.001,<0.001, respectively). In terms of immediate postoperative complications, the proportion of patients requiring analgesics within 24 h post-surgery was significantly lower in the LIA + MA group (p = 0.031). CONCLUSION: Open surgery for PDC placement under LIA + MAC is both safe and effective.
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Anestesia Local , Fallo Renal Crónico , Diálisis Peritoneal , Humanos , Estudios Retrospectivos , Masculino , Femenino , Anestesia Local/métodos , Persona de Mediana Edad , Diálisis Peritoneal/métodos , Fallo Renal Crónico/terapia , Dolor Postoperatorio/prevención & control , Adulto , Anciano , Monitoreo Intraoperatorio/métodosRESUMEN
A great number of COVID-19 patients was caused by Omicron BA.5 subvariant between December 2022 and January 2023 after the end of the zero-COVID-19 policy in China. In this study, we clarified the epidemiological and immunological characteristics of 457 enrolled middle-aged and elderly population in two housing estates after Omicron BA.5 wave. A total of 89.9 % (411/457) individuals have suffered Omicron BA.5 infection, among which 78.1 % (321/411) were symptomatic. The elderly patients were more likely to show fatigue and had longer symptomatic period than that of middle-aged patients post Omicron BA.5 infection. Omicron XBB and BA.2.86 subvariants extensively escaped the immunity elicited by Omicron BA.5 infection. The level of neutralizing antibody was mostly affected by vaccination doses rather than underlying disease status in these participants. It is very important to strengthen the epidemiological investigation and immune resistance assessment among elderly population for control of emerging SARS-CoV-2 variants.
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The impact of Borrelia miyamotoi on human health, facilitated by the expanding geographical distribution and increasing population of Ixodes ticks, remains obscure in the context of global climate change. We employed multiple models to evaluate the effect of global climate change on the risk of B. miyamotoi worldwide across various scenarios. The habitat suitability index of four primary vector tick species for B. miyamotoi, including Ixodes persulcatus, Ixodes ricinus, Ixodes pacificus and Ixodes scapularis, was projected using a boosted regression tree model, considering multiple shared socio-economic pathway scenarios over various time periods. The modelling analysis reveals that, apart from I. scapularis, future global warming will result in a northward shift in the other three vector tick species and a gradual reduction in suitable habitats. Random forest models indicate consistent changes in B. miyamotoi and its primary tick species, with potential risk areas shrinking and shifting northward, particularly in the eastern USA, northeastern and northern Europe and northeast Asia. These findings highlight the urgent need for enhanced active surveillance of B. miyamotoi infection in primary vector tick species across projected potential risk areas. The effect of climate change on B. miyamotoi distribution might have significant implications for public health decision-making regarding tick-borne pathogens.
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Borrelia , Cambio Climático , Ecosistema , Ixodes , Animales , Ixodes/microbiología , Humanos , Infecciones por Borrelia/epidemiología , Infecciones por Borrelia/microbiología , Vectores Arácnidos/microbiologíaRESUMEN
Gouty arthritis (GA) is an inflammatory disorder characterized by deposition of monosodium urate (MSU) crystal in joints. Phillyrin, a natural compound with anti-inflammatory properties, shows promise in mitigating inflammatory responses. This study investigates the therapeutic potential of phillyrin in GA and explores its mechanisms of action. GA was induced in mice via intraarticular MSU injection, and joint inflammation, inflammatory cell infiltration, and their level in serum/tissue were assessed. Key proteins in the NF-κB and NLRP3 pathways were examined using western blot analysis. The impact of phillyrin on oxidative stress, neutrophil extracellular trap (NET) formation, and neutrophil accumulation was evaluated by measuring CD11b + Ly6G + cells, MPO, CitH3, extracellular DNA ratio, and oxidative stress markers. In vitro studies assessed the effects of phillyrin on oxidative stress, cell viability, cytokine production, and NET formation in MSU-treated neutrophils. The KEAP1/NRF2 pathway's role was analyzed using ML385, an NRF2 inhibitor. Phillyrin significantly reversed MSU-induced ankle swelling and inflammatory cell infiltration in joint tissues. It suppressed pro-inflammatory cytokines and proteins in the NF-κB and NLRP3 pathways. Phillyrin reduced neutrophil infiltration, evidenced by lower MPO activity and NET formation, marked by reduced CitH3 expression. In vitro, phillyrin inhibited inflammatory marker expression and NET formation without affecting cell viability. It also restored antioxidant enzyme levels and reduced ROS production, regulating the KEAP1/NRF2 pathway, enhancing NRF2 expression and stability. These effects were reversed by NRF2 inhibition with ML385. Phillyrin alleviates GA by reducing joint inflammation, inhibiting NET formation, and suppressing oxidative stress through NRF2 modulation.
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Background: At present, it is known that there is a possibility of pleural cavity and needle tract implantation metastasis after lung cancer puncture biopsy, but clinicians have not paid attention to this phenomenon, and the probability of occurrence is unknown. In this study, we aimed to study the probability of implantation metastasis after peripheral lung cancer biopsy. Methods: The intraoperative isolated completely collapsed fresh intact human lung lobes of 30 patients with peripheral lung cancer were taken, and the tumor body was punctured. The pleural pinholes and puncture needle tips were repeatedly rinsed with normal saline respectively. The flushing solution was prepared as inoculum, and then the inoculum was smeared for microscopic examination to find cancer cells. The inoculum was inoculated subcutaneously into nude mice, and then the probability of pleural cavity and needle tract implantation metastasis after lung biopsy was indirectly obtained by obtaining the nude mice tumorigenesis rate. Results: The tumorigenesis rate of nude mice in the pleural pinholes group was 3.3%, and the tumorigenesis rate of nude mice in the puncture needle tip group was 3.3%. Conclusions: Patients with lung nodules suspected of being early stage cancer and who are fit for surgical resection may benefit from forgoing lung biopsies to avoid pleural cavity or needle tract seeding with tumor cells.
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Background: Personal protective equipment has important environmental impacts, assessing these impacts is therefore an important element of personal protective equipment design. We applied carbon footprinting methodology to Bubble-PAPR™, a novel, part-reusable and part-recyclable powered air-purifying respirator, designed at our institution. Current guidance states that disposable respirator masks can be worn for 1-h in the United Kingdom, whilst the Bubble-PAPR™ allows prolonged use. Methods: Following a detailed use-case analysis, the carbon footprint of each component was estimated using a bottom-up (attributional) cradle-to-grave process-based analysis. Modelling considered the use of virgin or closed loop recycled polyvinyl chloride for the disposable hood element, and disposal via infectious or recycling waste streams to estimate a per-use carbon footprint. Results: The per-use carbon footprint with manufacture from virgin polyvinyl chloride and disposal via incineration is 0.805 kgCO2e. With nine cycles of closed loop recycling and manufacture of the polyvinyl chloride hood (10 uses), the carbon footprint falls to an average of 0.570 kgCO2e per use. Conclusion: Carbon footprinting may contribute to the value proposition of this novel technology. We estimate that a single Bubble-PAPR™ use has a higher carbon footprint than disposable respirator mask-based PPE. However, this is mitigated in circumstances when multiple disposable mask changes are required (e.g. prolonged use) and use may be justifiable when user comfort, visualisation and communication with patients and colleagues are essential.
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This study examines effects of mixing municipal solid waste incineration bottom ash (MSWI-BA) with reddish laterite clay (RLC), evaluating factors such as vertical stress, mixing ratio, curing period, and the addition of lime. A total of 153 direct shear tests were conducted to thoroughly assess the mixture's strength characteristics. Vertical stress levels of 85.5 kPa, 172.4 kPa, and 259.3 kPa were used to simulate varying stress conditions, while mixing ratios of 40 %, 80 %, 100 %, and 120 % were applied to explore potential applications of recycled MSWI-BA with clayey soils. A fast-curing approach was employed, with curing periods of 24, 48, and 72 h, to investigate the time-dependent strength development under controlled conditions. A three-way ANOVA analysis confirmed that mixing ratio, curing period, and vertical stress significantly impacted both peak and residual shear strength. The 100 % MSWI-BA mixture, with or without 1 % lime, exhibited optimal performance, providing the pronounced shear strengths and dilative behavior. The study found that MSWI-BA significantly improved shear strength ratios compared to the RLC, with improvement ratios ranging from 1.439 to 2.460 across stress levels. Additionally, upper and lower bound equations for peak and residual strength ratios were developed, providing predictive tools for mixture design. Cohesion values in the range of 8.3-128.9 kPa and friction angles from 40.6° to 44.1° were achieved, surpassing or matching those reported in similar research. The study employed Bolton's (1986) dilatancy model, finding α values between 0.61 and 0.71, comparable to those in studies of granular materials. These results highlight the effectiveness of adding MSWI-BA and lime in enhancing reddish laterite soil stabilization through both chemical and mechanical means, making it a sustainable and cost-effective approach for civil engineering projects by improving material strength, reusing local soils, recycling waste, and reducing carbon footprints.
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Background: In recent years, China has actively promoted the publicity and promotion of breastfeeding, because breastfeeding is conducive to the healthy growth of babies and conducive to the recovery of maternal health. Behavioral nursing theory holds that individual behavior change is a complex and continuous process, and personalized care is given at different stages of individual behavior change to promote individual behavior change. Objective: To explore the impact of behavioral nursing intervention on the breastfeeding maintenance rate of hospitalized newborns. Design: This was a prospective cohort study based on the description provided. Setting: This study was conducted in the Department of Pediatrics, Shanghai Six People's Hospital/Shanghai Six People's Hospital Affiliated with Shanghai Jiaotong University School of Medicine, because the author worked in the hospital. Participants: A total of 120 cases of parturients in our hospital from January 2021 to December 2022 were chosen and separated into a control group and an observation group through the random number table method. Inclusion criteria: Parturients were full-term single pregnancies, examined in our hospital, and there were no abnormalities in prenatal examination. Exclusion criteria: Parturients with a history of mental illness, accompanied by hepatitis B, three Yang, acquired immune deficiency syndrome and other infectious diseases, and combined with visual and hearing disorders. Interventions: The control group adopted routine breastfeeding nursing intervention, including training in the prenatal maternity school, instruction in breastfeeding methods during hospital delivery and follow-up after discharge. The observation group adopted behavioral nursing intervention, the corresponding health guidance and nursing methods were formulated and implemented in the second trimester, the third trimester, the hospitalization period of childbirth, and the discharge, and at each stage. Primary Outcome Measures: (1) Degree of knowledge about breastfeeding, (2) Efficiency of breastfeeding, (3) Rate of exclusive breastfeeding, (4) Nutritional index, (5) Cognitive ability of newborns, (6) Satisfaction of family members with nursing. Results: After the intervention, the score of feeding knowledge in the observation group was elevated relative to the control group (P < .05). The self-efficacy scores and rates of exclusive breastfeeding in the observation group at 1, 6 weeks, and 6 months after delivery were higher relative to the control group (P < .05). After the intervention, the levels of albumin, albumin, and transferrin in the observation group were higher relative to the control group (P < .05). After the intervention, the scores of the mental development index and psychomotor development index in the observation group were elevated relative to the control group (P < .05). Conclusion: Behavioral nursing can effectively improve the effectiveness of breastfeeding and facilitate the health and growth of mothers and newborns, aligning with the broader goals of promoting breastfeeding in healthcare settings.
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BACKGROUND: Scrub typhus is underdiagnosed and underreported but emerging as a global public health problem. To inform future burden and prediction studies we examined through a systematic review the potential effect of environmental covariates on scrub typhus occurrence and the methods which have been used for its prediction. METHODS: In this systematic review, we searched PubMed, Scopus, Web of Science, China National Knowledge Infrastructure and other databases, with no language and publication time restrictions, for studies that investigated environmental covariates or utilized methods to predict the spatial or temporal human. Data were manually extracted following a set of queries and systematic analysis was conducted. RESULTS: We included 68 articles published in 1978-2024 with relevant data from 7 countries/regions. Significant environmental risk factors for scrub typhus include temperature (showing positive or inverted-U relationships), precipitation (with positive or inverted-U patterns), humidity (exhibiting complex positive, inverted-U, or W-shaped associations), sunshine duration (with positive, inverted-U associations), elevation, the normalized difference vegetation index (NDVI), and the proportion of cropland. Socioeconomic and biological factors were rarely explored. Autoregressive Integrated Moving Average (ARIMA) (n = 8) and ecological niche modelling (ENM) approach (n = 11) were the most popular methods for predicting temporal trends and spatial distribution of scrub typhus, respectively. CONCLUSIONS: Our findings summarized the evidence on environmental covariates affecting scrub typhus occurrence and the methodologies used for predictive modelling. We review the existing knowledge gaps and outline recommendations for future studies modelling disease prediction and burden. TRIAL REGISTRATION: PROSPERO CRD42022315209.
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Linfoma de Células B Grandes Difuso , Terapia Recuperativa , Trasplante Haploidéntico , Humanos , Linfoma de Células B Grandes Difuso/terapia , Linfoma de Células B Grandes Difuso/patología , Terapia Recuperativa/métodos , Trasplante Haploidéntico/métodos , Terapia Combinada , Niño , Masculino , Trasplante de Células Madre Hematopoyéticas/métodos , Recurrencia Local de Neoplasia/terapia , Recurrencia Local de Neoplasia/patología , Linfocitos B/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , FemeninoRESUMEN
BACKGROUND AND PURPOSE: Elevated levels of 5-HT have been correlated with coronary artery disease and cardiac events, suggesting 5-HT is a potential novel factor in the development of atherosclerotic cardiovascular disease. However, the underlying pathological mechanisms of the 5-HT system in atherosclerosis remain unclear. The 5-HT2B receptor (5-HT2BR), which establishes a positive feedback loop with 5-HT, has been identified as a contributor to pathophysiological processes in various vascular disorders. In this study, we investigated the immunological impact of 5-HT2BR in atherosclerosis-prone apolipoprotein E-deficient (ApoE-/-) mice. EXPERIMENTAL APPROACH: Plasma levels of 5-HT were measured in mice using an ELISA kit. Atherosclerotic plaque formation, macrophage infiltration and inflammatory signalling were assessed in ApoE-/- mice by employing both pharmacological inhibition and genetic deficiency of 5-HT2BR. Inflammasome activation was elucidated using peritoneal macrophages isolated from 5-HT2BR-deficient mice. KEY RESULTS: An upregulation of 5-HT2BR expression was observed in the aortas of ApoE-/- mice, exhibiting a strong correlation with the presence of macrophages in plaques. Atherosclerosis was attenuated in mice through pharmacological inhibition and genetic deficiency of 5-HT2BR. Additionally, a significant reduction in atherosclerotic plaque size was achieved through bone marrow reconstitution with 5-HT2BR-deficient cells. 5-HT2BR-deficient macrophages showed attenuated interferon (IFN) signalling, NLRP3 inflammasome activation, and interleukin-1ß release. Moreover, macrophages primed with 5-HT2BR deficiency displayed an anti-inflammatory phenotype. CONCLUSION AND IMPLICATIONS: These findings support the hypothesis that 5-HT2BR in macrophages plays a causal role in the development of atherosclerosis, revealing a novel perspective for potential therapeutic strategies in atherosclerosis-related diseases.
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To plant crops (especially dry crops such as water spinach) with concomitant electricity recovery, a hanging-submerged-plant-pot system (HSPP) is developed. The HSPP consists of a soil pot (anodic) partially submerged under the water surface of a cathode tank. The microbial communities changed with conditions were also investigated. It was found that with chemical fertilizers the closed-circuit voltage (CCV, with 1 kΩ) was stable (approximately 250 mV) within 28 d; however, without fertilizer, the water spinach could adjust to the environment to obtain a better power output (approximately 3 mW m-2) at day 28. The microbial-community analyses revealed that the Pseudomonas sp. was the only exoeletrogens found in the anode pots. Using a secondary design of HSPP, for a better water-level adjustment, the maximum power output of each plant was found to be approximately 27.1 mW m-2. During operation, high temperature resulted in low oxygen solubility, and low CCV as well. At this time, it is yet to be concluded whether the submerged water level significantly affects electricity generation.
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In this study, a Janus BiTeCl/SnSe2 van der Waals (vdW) heterostructure is constructed and systematically investigated for its potential in solar cell applications using first-principles calculations. The heterostructure introduces distinct contact interfaces (Cl-Se and Te-Se), both exhibiting a type-II band alignment. However, the conduction band minimum (CBM) and valence band maximum (VBM) contributions vary, depending on the interface. The Cl-Se interface demonstrates a significantly higher power conversion efficiency (PCE) of 20.11%, attributed to the suitable bandgap of the SnSe2 donor material and a smaller conduction band offset. Both interfaces exhibit enhanced optical properties compared to those of isolated BiTeCl and SnSe2 monolayers. Additionally, the electronic structure of the heterostructure is tunable via biaxial strain and electric fields, enabling further optimization of the PCE. Moreover, optical absorption can be adjusted by biaxial strain and electric fields. These findings position the Janus BiTeCl/SnSe2 heterostructure, particularly the Cl-Se interface, as a promising candidate for next-generation photovoltaic devices, offering both high efficiency and an external tunability.
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AIM: To investigate whether retinal nerve fiber layer defects (RNFLDs) is a potential risk factor for chronic kidney disease (CKD) in Chinese adults. METHODS: The Kailuan Eye Study was a population-based study that included 14 440 participants. All participants underwent detailed assessments, RNFLDs were diagnosed using color fundus photographs. RESULTS: Overall, 12 507 participants [8533 males (68.23%)] had complete systemic examination data and at least one evaluable fundus photograph. RNFLDs were found in 621 participants [5.0%; 95% confidence interval (CI): 4.6%-5.34%], and 70 cases of multiple RNFLDs were found (11.27%). After adjusting multiple factors, RNFLDs was significantly associated with CKD severity, the ORs of CKD stage 3, stage 4 and stage 5 were 1.698, 4.167, and 9.512, respectively. Multiple RNFLDs were also associated with CKD severity after adjusting multiple factors, the ORs of CKD stage 3 and stage 5 were 4.465 and 11.833 respectively. Furthermore, 2294 participants had CKD (18.34%, 95%CI: 17.68%-18.99%). After adjusting for other factors, CKD presence was significantly correlated with the presence of RNFLDs. CONCLUSION: The strongest risk factors for RNFLDs are CKD and hypertension. Conversely, RNFLDs can be an ocular feature in patients with CKD. Fundoscopy can help detect systemic diseases, and assessment for RNFLDs should be considered in CKD patients.
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Spinal Cord Injury (SCI) is a severe condition that often leads to substantial neurological impairments. This study aimed to explore the role of Aquaporin-4 (AQP4) in regulating astrocyte autophagy and neuroinflammation post-SCI, as well as to evaluate the therapeutic potential of AQP4 inhibition using the specific inhibitor TGN-020. Using Western blot, CCK8 assays, immunofluorescence staining, histopathological assessments, and behavioral analyses, we investigated the effects of TGN-020 on SCI-induced alterations in autophagy, neuroinflammation, astrocyte proliferation, neuronal damage, and motor function recovery in both rat and astrocyte models. Our findings indicate that TGN-020 significantly enhances astrocyte autophagy, reduces neuroinflammation, thereby leading to mitigated astrocyte activation by suppressing AQP4 expression. These beneficial effects are associated with the activation of the peroxisome proliferator-activated receptor-γ/mammalian target of rapamycin (PPAR-γ/mTOR) signaling pathway. Notably, the introduction of the PPAR-γ specific inhibitor GW9662 abrogated the positive regulatory effects of TGN-020 on SCI-induced autophagy and neuroinflammation. Collectively, our in vivo and in vitro experiments demonstrate that TGN-020, by down-regulating AQP4, activates the PPAR-γ/mTOR pathway, ameliorates astrocyte autophagy, diminishes neuroinflammation, and ultimately enhances motor function recovery.
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Acuaporina 4 , Astrocitos , Autofagia , PPAR gamma , Transducción de Señal , Traumatismos de la Médula Espinal , Serina-Treonina Quinasas TOR , Animales , Masculino , Ratas , Acuaporina 4/metabolismo , Acuaporina 4/antagonistas & inhibidores , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Autofagia/efectos de los fármacos , Inflamación/metabolismo , Inflamación/tratamiento farmacológico , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/metabolismo , Niacinamida/análogos & derivados , PPAR gamma/metabolismo , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/patología , Tiadiazoles/farmacología , Tiadiazoles/uso terapéutico , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/antagonistas & inhibidoresRESUMEN
The E-twenty-six variant 1 (ETV1)-dependent transcriptome plays an important role in atrial electrical and structural remodelling and the occurrence of atrial fibrillation (AF), but the underlying mechanism of ETV1 in AF is unclear. In this study, cardiomyocyte-specific ETV1 knockout (ETV1f/fMyHCCre/+, ETV1-CKO) mice were constructed to observe the susceptibility to AF and the underlying mechanism in AF associated with ETV1-CKO mice. AF susceptibility was examined by intraesophageal burst pacing, induction of AF was increased obviously in ETV1-CKO mice than WT mice. Electrophysiology experiments indicated shortened APD50 and APD90, increased incidence of DADs, decreased density of ICa,L in ETV1-CKO mice. There was no difference in VINACT,1/2 and VACT,1/2, but a significantly longer duration of the recovery time after inactivation in the ETV1-CKO mice. The recording of intracellular Ca2+ showed that there was significantly increased in the frequency of calcium spark, Ca2+ transient amplitude, and proportion of SCaEs in ETV1-CKO mice. Reduction of Cav1.2 rather than NCX1 and SERCA2a, increase RyR2, p-RyR2 and CaMKII was reflected in ETV1-CKO group. This study demonstrates that the increase in calcium spark and SCaEs corresponding to Ca2+ transient amplitude may trigger DAD in membrane potential in ETV1-CKO mice, thereby increasing the risk of AF.
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Fibrilación Atrial , Calcio , Atrios Cardíacos , Ratones Noqueados , Miocitos Cardíacos , Factores de Transcripción , Animales , Miocitos Cardíacos/metabolismo , Ratones , Fibrilación Atrial/metabolismo , Fibrilación Atrial/genética , Calcio/metabolismo , Atrios Cardíacos/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Señalización del Calcio , Potenciales de Acción , Potenciales de la Membrana , MasculinoRESUMEN
PURPOSE: To investigate the immunomodulatory effects and potential mechanisms of human nasal mucosa-derived mesenchymal stem cells(hNMSCs) on mouse allergic rhinitis, and to compare them with human umbilical cord-derived mesenchymal stem cells (hUCMSCs). METHOD: hNMSCs and hUCMSCs were isolated and cultured for identification from human nasal mucosa and umbilical cord tissues. A co-culture system of LPS-stimulated RAW264.7 cells/mouse peritoneal macrophages and MSCs was employed.Changes in inflammatory factors in RAW264.7 cells and the culture medium as well as the expression of NF-κB signaling pathway in RAW264.7 cells were detected. Forty-eight BALB/c mice were randomly divided into control, OVA, hNMSCs, and hUCMSCs groups. An allergic rhinitis (AR) model was established through ovalbumin (OVA) stimulation and treated with hNMSCs and hUCMSCs. Subsequent assessments included related symptoms, biological changes, and the expression of the NF-κB signaling pathway in the nasal mucosa of mice. RESULTS: MSCs can be successfully isolated from human nasal mucosa. Both hNMSCs and hUCMSCs interventions significantly reverseed the inflammation induced by LPS and suppressed the upregulation of the NF-κB signaling pathway in RAW264.7 cells. Treatment with hNMSCs and hUCMSCs alleviated mouse allergic symptoms, reduced levels of total IgE, OVA-specific IgE and IgG1 in mouse serum, TH2-type cytokines and chemokines in mouse nasal mucosa, and TH2-type cytokines in mouse spleen culture medium, while also inhibiting the expression of the NF-κB signaling pathway in the nasal mucosa of mice. moreover, the hNMSCs group showed a more significant reduction in OVA-specific IgG1 in serum and IL-4 expression levels in mouse spleen culture medium compared to the hUCMSCs group. CONCLUSION: Our findings suggest that hNMSCs can ameliorate allergic rhinitis in mice, with a certain advantage in anti-inflammatory effects compared to hUCMSCs. The NF-κB pathway is likely involved in the anti-inflammatory regulation process by hNMSCs.Therefore, hNMSCs might represent a novel therapeutic approach for allergic rhinitis.