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1.
Sci Total Environ ; 933: 172875, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38703839

RESUMEN

Dry direct-seeded rice cultivation has gained popularity and expanded its cultivated area due to reduced labor requirements and water consumption. However, the impact of this cultivation method on cadmium (Cd) bioavailability in soil and the accumulation levels in grains remains uncertain. Field experiments were conducted in acidic soils at two locations in southern China to compare rice varieties and evaluate the dry direct-seeding method alongside the wet direct-seeding and traditional transplanting methods. Dry direct-seeded rice reached significantly higher Cd concentrations in its tissues starting from the heading stage than transplanted rice. Cd accumulation levels by the maturation stage in the brown rice of dry direct-seeded rice were 18.33 %-150.69 % higher than those of wet direct-seeded and transplanted rice, with a considerable ability to translocate Cd into brown rice. Furthermore, dry direct seeding decreased iron plaque formation, particularly in the amorphous Fe form; it resulted in high soil temperature and low moisture content during tillering, elevating Cd availability in the soil. Additionally, the proportion of ions and more labile forms of Cd in the soil solution was high. Moreover, the soil under dry direct seeding had high urease and acid phosphatase enzyme activities. However, low richness and diversity in the bacterial community were characterized by a significant increase in the relative abundance of Actinobacteria and Gammaproteobacteria at the class level, while exhibiting decreased relative abundances of Alphaproteobacteria, Bacilli, and KD4-96, along with fewer biomarkers. Nonetheless, these differences are gradually reduced during the maturation stage. Overall, although dry direct seeding offers several advantages, it is crucial to implement additional measures to mitigate the increased health risks linked to rice cultivation through this approach in Cd-contaminated areas.

2.
Appl Opt ; 63(8): 2065-2069, 2024 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-38568648

RESUMEN

Laser interference lithography is an effective approach for grating fabrication. As a key parameter of the grating profile, the duty cycle determines the diffraction characteristics and is associated with the irradiance of the exposure beam. In this study, we developed a fabrication technique amplitude-splitting flat-top beam interference lithography to improve duty cycle uniformity. The relationship between the duty cycle uniformity and irradiance of the exposure beam is analyzed, and the results indicate that when the beam irradiance nonuniformity is less than 20%, the grating duty cycle nonuniformity is maintained below ±2%. Moreover, an experimental amplitude-splitting flat-top beam interference lithography system is developed to realize an incident beam irradiance nonuniformity of 21%. The full-aperture duty cycle nonuniformity of the fabricated grating is less than ±3%. Amplitude-splitting flat-top beam interference lithography improves duty cycle uniformity, greatly reduces energy loss compared to conventional apodization, and is more suitable for manufacturing highly uniform gratings over large areas.

3.
Heliyon ; 10(8): e29147, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38681549

RESUMEN

Although studies have explored the relationship between temperature and CO poisoning, the results are not consistent, and there is still a lack of early warning criteria of temperature related to CO poisoning. In order to comprehensively study the exposure-response relationship between daily average temperature and CO poisoning, and to further explore the early warning criteria of temperature related to CO poisoning, we used daily cases of CO poisoning in 31 National Injury Surveillance System (NISS) surveillance sites in seven administrative geographical regions of China and daily meteorological data obtained from the China Meteorological Science Data Sharing Service Platform from 2009 to 2019 to do the analysis. Daily meteorological data of 698 weather stations across China were interpolated at a 0.01° × 0.01°spatial resolution, which were then applied to extract the daily meteorological data of all included NISS sites. The Distributed Lag Non-linear Model (DLNM) model was applied to estimate the exposure-response associations (relative risk, RR) of daily mean temperature with CO poisoning, which was then further used to identify early warning criteria of temperature related to CO poisoning. A total of 10,618 CO poisoning cases were included in this study, with an average of 0.4 cases per day. There was generally a reverse J-shaped association between temperature and CO poisoning risk, indicating that both low and high temperature may increase the risk of CO poisoning, but low temperature usually has a longer lagged effects than high temperature. Spatialy, the exposure-response associations between temperatue and CO poisoning largely varied among regions, with greater effects of low temperatures in Southern China than in Northern China. The cumulative effects (RR, lag0-6 days) of 10 % percentile temperature ranged from 1.13 (95%CI: 1.01,1.26) in East China to 1.73 (95%CI:1.63,1.83) in South China. We also observed significant spatial variations in the early warning criteria of temperature related to CO poisoning across China. However, the patterns of high temperature effects on CO poisoning and the warning criteria of high temperature were mixed across China. In conclusions, both low temperature and high temperature may increase the risk of CO poisoning in China, and the effect of low temperature is more obvious, especially in South China, Northeast China, and North China. In addition, there is an urgent need to establish air temperature early warning and grading criteria for CO poisoning in different areas of China.

4.
Cell Tissue Bank ; 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38489016

RESUMEN

Demineralized bone matrix (DBM) has been regarded as an ideal bone substitute as a native carrier of bone morphogenetic proteins (BMPs) and other growth factors. However, the osteoinductive properties diverse in different DBM products. We speculate that the harvest origin further contributing to variability of BMPs contents in DBM products besides the process technology. In the study, the cortical bone of femur, tibia, humerus, and ulna from a signal donor were prepared and followed demineralizd into DBM products. Proteins in bone martix were extracted using guanidine-HCl and collagenase, respectively, and BMP-2 content was detected by sandwich enzyme-linked immunosorbent assay (ELISA). Variability of BMP-2 content was found in 4 different DBM products. By guanidine-HCl extraction, the average concentration in DBMs harvested from ulna, humerus, tibia, and femur were 0.613 ± 0.053, 0.848 ± 0.051, 3.293 ± 0.268, and 21.763 ± 0.344, respectively (p < 0.05), while using collagenase, the levels were 0.089 ± 0.004, 0.097 ± 0.004, 0.330 ± 0.012, and 1.562 ± 0.008, respectively (p < 0.05). In general, the content of BMP-2 in long bones of Lower limb was higher than that in long bones of upper limb, and GuHCl had remarkably superior extracted efficiency for BMP-2 compared to collagenase. The results suggest that the origin of cortical bones harvested to fabricate DBM products contribute to the variability of native BMP-2 content, while the protein extracted method only changes the measured values of BMP-2.

6.
Environ Pollut ; 348: 123858, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38554834

RESUMEN

During the rice growth cycle, the average available cadmium concentration (CA-Cd) in the soil determines the Cd content in rice plant. Given defined soil properties and rice varieties, the meteorological factors play a crucial role in soil's available cadmium concentration (CCd) during the rice growth cycle. Thus, it is significant to investigate the influence of meteorological factors in CCd during the rice growth cycle and develop a predictive model for CA-Cd. The rice was cultivated under seven different sowing dates in Cd and As-contaminated soil in Hunan Province. Studied the impact of meteorological factors on paddy soil. The results showed that accumulated temperature (AT) and total precipitation (TP) were key factors affecting the soil CCd. The correlation coefficients between AT and TP with soil CA-Cd were 0.98 and -0.94 (p < 0.01), respectively. However, there was no significant correlation with CAs. AT mainly influenced the CCd during the grouting and maturity stages. A straightforward empirical prediction model was developed, capable of accurately forecasting CA-Cd during the rice growth cycle by considering meteorological factors and the initial soil CCd. This study supported a novel foundation for the precise prediction of Cd content in rice.


Asunto(s)
Oryza , Contaminantes del Suelo , Cadmio/análisis , Contaminantes del Suelo/análisis , Suelo , Contaminación Ambiental
7.
Sci Rep ; 14(1): 5867, 2024 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-38467756

RESUMEN

To illustrate the surgical technique and explore clinical outcomes of the reconstruction for the malignant and metastatic bone tumour of proximal femur with metallic modular intercalary prosthesis. Sixteen patients who underwent modular intercalary prosthetic reconstruction after tumour resection were included from April 2012 and October 2020. Prosthesis and screws parameters, resected bone length and residual bone length, clinical outcomes and survivorship were analyzed. All patients were followed up for an average of 19 months (range 1-74). In our series, 12 patients died of the progression of the primary disease at the final follow-up. The cumulative survivorship since the treatment of proximal femoral metastasis was 78.6% (11 patients) at 6 months and 38.5% (5 patients) at 1 year. The mean MSTS score was 22.25 ± 4.55 among all patients. There were no cases of loosening or breakage of the prostheses, plates or screws, despite the various measurements of prostheses and residual bones. Modular intercalary prosthetic reconstruction was an effective method for malignant tumour of the proximal femur, including the advantages of providing early pain relief, quickly restoring postoperative function, required a short operation time, and preserving the adjacent joints.


Asunto(s)
Neoplasias Óseas , Fémur , Humanos , Resultado del Tratamiento , Fémur/patología , Extremidad Inferior , Implantación de Prótesis/métodos , Neoplasias Óseas/patología , Estudios Retrospectivos
8.
Neuropediatrics ; 55(2): 112-116, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38253279

RESUMEN

OBJECTIVE: The risk factors for respiratory insufficiency in children with Guillain-Barré syndrome (GBS) are poorly known. This study aimed to investigate the factors associated with respiratory insufficiency in children with GBS. METHODS: This retrospective study included children diagnosed with GBS by pediatric neurologists and admitted at the Wuhan Children's Hospital and other hospitals from January 2013 to October 2022. The patients were divided into the respiratory insufficiency and nonrespiratory insufficiency groups according to whether they received assist breathing during treatment. RESULTS: The median (interquartile range) age of onset of 103 patients were 5 (3.1-8.5) years, 69 (67%) were male, and 64 (62.1%) had a history of precursor infection. Compared with the nonrespiratory insufficiency group, the respiratory insufficiency group showed more facial and/or bulbar weakness (p = 0.002), a higher Hughes Functional Grading Scale (HFGS) at admission (p < 0.001), and a shorter onset-to-admission interval (p = 0.017). Compared with the acute motor axonal neuropathy (AMAN) subtype, the acute inflammatory demyelinating polyneuropathy (AIDP) subtype showed longer days from onset to lumbar (p = 0.000), lower HFGS at admission (p = 0.04), longer onset-to-admission interval (p = 0.001), and more cranial nerve involvement (p = 0.04). The incidence of respiratory insufficiency between AIDP and AMAN showed no statistical difference (p > 0.05). CONCLUSION: In conclusion, facial and/or bulbar weakness, HFGS at admission, and onset-to-admission interval were associated with respiratory insufficiency and might be useful prognostic markers in children with GBS.


Asunto(s)
Síndrome de Guillain-Barré , Insuficiencia Respiratoria , Niño , Humanos , Masculino , Preescolar , Femenino , Síndrome de Guillain-Barré/complicaciones , Síndrome de Guillain-Barré/epidemiología , Síndrome de Guillain-Barré/diagnóstico , Estudios Retrospectivos , Hospitalización , Insuficiencia Respiratoria/epidemiología , Insuficiencia Respiratoria/etiología , Amantadina
9.
Adv Sci (Weinh) ; 11(11): e2305260, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38183387

RESUMEN

It is long been suggested that one-carbon metabolism (OCM) is associated with Alzheimer's disease (AD), whereas the potential mechanisms remain poorly understood. Taking advantage of chemical biology, that mitochondrial serine hydroxymethyltransferase (SHMT2) directly regulated the translation of ADAM metallopeptidase domain 10 (ADAM10), a therapeutic target for AD is reported. That the small-molecule kenpaullone (KEN) promoted ADAM10 translation via the 5' untranslated region (5'UTR) and improved cognitive functions in APP/PS1 mice is found. SHMT2, which is identified as a target gene of KEN and the 5'UTR-interacting RNA binding protein (RBP), mediated KEN-induced ADAM10 translation in vitro and in vivo. SHMT2 controls AD signaling pathways through binding to a large number of RNAs and enhances the 5'UTR activity of ADAM10 by direct interaction with GAGGG motif, whereas this motif affected ribosomal scanning of eukaryotic initiation factor 2 (eIF2) in the 5'UTR. Together, KEN exhibits therapeutic potential for AD by linking OCM with RNA processing, in which the metabolic enzyme SHMT2 "moonlighted" as RBP by binding to GAGGG motif and promoting the 5'UTR-dependent ADAM10 translation initiation.


Asunto(s)
Enfermedad de Alzheimer , Glicina Hidroximetiltransferasa , Animales , Ratones , Regiones no Traducidas 5' , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Glicina Hidroximetiltransferasa/genética , ARN Mensajero/genética
10.
Insects ; 15(1)2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38249032

RESUMEN

In this paper, the effects of maize and its three intercropping plants, sweet potato, soybean and peanut, on the growth and development of FAW, feeding preference of larvae, olfactory response and oviposition preference of adults were studied in the laboratory. The results showed that maize and peanut were suitable for the survival and development of FAW, while sweet potato and soybean were not suitable for multigenerational reproduction. The larvae significantly preferred to feed on maize compared to the other three plants. The olfactory response test indicated that soybean showed a strong deterrent effect against FAW adults. Furthermore, the intercropping plants reduced the host selection rate of adults compared to maize alone. In two-choice tests of the maize vs. the intercropping plants, the female adult preferred to oviposit and lay more eggs on maize rather than on the intercropping plants. The intercropping plants significantly reduced the oviposition selection of FAW adults when the combination (maize + intercropping plant), especially soybean and sweet potato, was compared to maize alone. These may be the reasons for why the maize-soybean intercropping system reduced FAW damage in the field. We also speculated that the maize-sweet potato system may also reduce the FAW damage. This study provided a theoretical basis for the comprehensive management of FAW by utilizing an intercropping system.

11.
Nano Lett ; 24(1): 104-113, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-37943097

RESUMEN

Optical meron is a type of nonplanar topological texture mainly observed in surface plasmon polaritons and highly symmetric points of photonic crystals in the reciprocal space. Here, we report Poynting-vector merons formed at the real space of a photonic crystal for a Γ-point illumination. Optical merons can be utilized for subwavelength-resolution manipulation of nanoparticles, resembling a topological Hall effect on electrons via magnetic merons. In particular, staggered merons and antimerons impose strong radiation pressure on large gold nanoparticles (AuNPs), while focused hot spots in antimerons generate dominant optical gradient forces on small AuNPs. Synergistically, differently sized AuNPs in a still environment can be trapped or orbit in opposite directions, mimicking a coupled galaxy system. They can also be separated with a 10 nm precision when applying a flow velocity of >1 mm/s. Our study unravels a novel way to exploit topological textures for optical manipulation with deep-subwavelength precision and switchable topology in a lossless environment.

12.
Int Urol Nephrol ; 56(1): 45-53, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37676386

RESUMEN

PURPOSE: Previously, we designed a ureteral access sheath with the capability of renal pelvic pressure (RPP) measurement and a medical perfusion and aspiration platform, allowing for the intelligent control of RPP. However, the effect of different RPP levels on perfusion fluid absorption remains unclear. This randomized controlled trial aimed to investigate the effects of exhaled ethanol concentration monitoring and intelligent pressure control on perfusion fluid absorption during flexible ureteroscopic lithotripsy. METHODS: Eighty patients scheduled for flexible ureteroscopic lithotripsy were randomly divided into four groups. In groups A, B, and C, the RPPs were set at 0, - 5, and - 10 mmHg, respectively. Group D was regarded as the controls with unfixed RPP. Isotonic saline containing 1% ethanol was used as the irrigation fluid, with an average irrigation flow rate of 100 mL/min. The primary outcome of this study was the absorption of perfusion fluid that was calculated based on the exhaled ethanol concentration. The secondary outcomes included duration of operation and amounts of perfusion fluid used. Postoperative complications, pre- and postoperative renal function, infection markers, and blood gas analysis were also recorded for safety assessment. RESULTS: In all, 76 patients were involved in this study, whose demographic characteristics and preoperative conditions were comparable among groups. Under the same perfusion flow rate, the groups with fixed RPP exhibited reduced absorption of perfusion fluid, duration of operation, and perfusion volume. In particular, the lowest values were observed in group C (RPP = - 10 mmHg). In contrast to the unfixed RPP group, no considerable difference were observed in levels of BUN, Scr, WBC, CRP, and blood gas values among the fixed RPP groups. Moreover, postoperative complications showed no significant difference among groups. CONCLUSION: In flexible ureteroscopic lithotripsy, the groups with fixed RPP had less absorption of perfusion fluid and perfusion volume, shorter duration of surgery, and higher safety than the unfixed group.


Asunto(s)
Litotricia , Ureteroscopía , Humanos , Pelvis Renal , Perfusión , Litotricia/efectos adversos , Complicaciones Posoperatorias
14.
Anal Methods ; 16(3): 333-343, 2024 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-38126405

RESUMEN

The emerging sample pretreatment technique of magnetic solid-phase extraction (MSPE) has drawn the attention of researchers owing to its advantages of less reagent consumption, fast separation/enrichment process, high adsorption capacity, and simple operation. This paper presents a review of synthesis techniques, classification, and analysis procedures for MSPE in the detection of heavy metals in food. Magnetic adsorbents derived from silica, metal oxides, carbon, polymers, etc., are applied for the detection of heavy metals in food. Then, the recent development of the technology of MSPE for the analysis of heavy metal extraction in food is summarized in detail. Finally, the future outlook for the improvement of MSPE is also discussed.

15.
World J Clin Cases ; 11(31): 7610-7618, 2023 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-38078144

RESUMEN

BACKGROUND: Cough variant asthma (CVA) is one of the most common respiratory diseases in children, which has a serious impact on the quality of life and daily activities of children. For severe CVA, immunomodulatory drugs are needed. AIM: To evaluate the efficacy of salmeterol combined with budesonide in the treatment of pediatric CVA. METHODS: 130 children with CVA from January 2020 to December 2022 were prospectively selected and randomly divided into an observation group (salmeterol combined with budesonide) and a control group (budesonide combined with a placebo). Compare the clinical efficacy of two groups before and after intervention. The evaluation parameters include cough frequency score, nocturnal cough arousal, and lung function indicators. Serum inflammatory markers, immune function markers and airway anatomical indicators were also measured. RESULTS: After the intervention, the total effective rate of the observation group was significantly higher than that of the control group, and the cough frequency score and the night cough wake rate of the observation group were lower than that of the control group, with a statistically significant difference. In addition, the changes of lung function indicators, serum markers and immune function markers in the observation group were better than those in the control group. CONCLUSION: The clinical efficacy of salmeterol combined with Budesonide in the treatment of CVA is better than that of Budesonide alone.

16.
Stem Cell Res Ther ; 14(1): 369, 2023 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-38093354

RESUMEN

BACKGROUNDS: Allergic airway inflammation is prevalent worldwide and imposes a considerable burden on both society and affected individuals. This study aimed to investigate the therapeutic advantages of mesenchymal stem cells (MSCs) overexpressed interleukin-10 (IL-10) for the treatment of allergic airway inflammation, as both IL-10 and MSCs possess immunosuppressive properties. METHODS: Induced pluripotent stem cell (iPSC)-derived MSCs were engineered to overexpress IL-10 via lentiviral transfection (designated as IL-10-MSCs). MSCs and IL-10-MSCs were administered intravenously to mice with allergic inflammation induced by ovalbumin (OVA), and the features of allergic inflammation including inflammatory cell infiltration, Th cells in the lungs, and T helper 2 cell (Th2) cytokine levels in bronchoalveolar lavage fluid (BALF) were examined. MSCs and IL-10-MSCs were co-cultured with CD4+ T cells from patients with allergic rhinitis (AR), and the levels of Th2 cells and corresponding type 2 cytokines were studied. RNA-sequence was performed to further investigate the potential effects of MSCs and IL-10-MSCs on CD4+ T cells. RESULTS: Stable IL-10-MSCs were established and characterised by high IL-10 expression. IL-10-MSCs significantly reduced inflammatory cell infiltration and epithelial goblet cell numbers in the lung tissues of mice with allergic airway inflammation. Inflammatory cell and cytokine levels in BALF also decreased after the administration of IL-10-MSCs. Moreover, IL-10-MSCs showed a stronger capacity to inhibit the levels of Th2 after co-cultured with CD4+ T cells from patients with AR. Furthermore, we elucidated lower levels of IL-5 and IL-13 in IL-10-MSCs treated CD4+ T cells, and blockade of IL-10 significantly reversed the inhibitory effects of IL-10-MSCs. We also reported the mRNA profiles of CD4+ T cells treated with IL-10-MSCs and MSCs, in which IL-10 played an important role. CONCLUSION: IL-10-MSCs showed positive effects in the treatment of allergic airway inflammation, providing solid support for the use of genetically engineered MSCs as a potential novel therapy for allergic airway inflammation.


Asunto(s)
Células Madre Mesenquimatosas , Rinitis Alérgica , Animales , Humanos , Ratones , Líquido del Lavado Bronquioalveolar , Citocinas/metabolismo , Modelos Animales de Enfermedad , Inflamación/terapia , Inflamación/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Pulmón , Células Madre Mesenquimatosas/metabolismo , Ratones Endogámicos BALB C , Ovalbúmina
17.
China CDC Wkly ; 5(47): 1052-1057, 2023 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-38047244

RESUMEN

What is already known about this topic?: Poisoning constitutes a significant cause of mortality among individuals aged 1 to 44 in China. Nonetheless, the epidemiological understanding of poisoning incidents within emergency departments remains fragmented across the region. What is added by this report?: In 2019, the NISS recorded 31,382 cases of poisoning, predominantly among males (62.85%) and individuals aged 25-44 (44.13%). In all poisoning cases, 82.60% were unintentional. The predominant substances exposure in poisoning cases presenting to outpatient and emergency departments were alcohol (56.38%), medications (14.21%), and pesticides (9.78%). What are the implications for public health practice?: This study has shed light on the evidence for nonfatal poisoning prevention to a variety of different groups, and informed special attention needed for high-risk population and substance exposed.

18.
China CDC Wkly ; 5(47): 1058-1062, 2023 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-38047245

RESUMEN

Introduction: This study seeks to elucidate the evolving trend and identify disparities among subgroups in the mortality rate due to unintentional drowning in individuals under the age of 20 from the timeframe of 2013 to 2021 in China. Methods: Data retrieved from the National Mortality Surveillance System served as a foundation for estimating the unintentional drowning mortality rate. The inadvertent drowning mortality rate for individuals below the age of 20 was computed, differentiated by categorization groups such as age, gender, areas, and regions within each given year. The linear regression model was employed to calculate the annual percent of change (APC) with its 95% confidence interval (CI), providing a depiction of the mortality rate's shifting trend. Results: In 2021, the inadvertent drowning fatality rate for individuals under 20 years of age in China was recorded at 3.28 per 100,000. A steady reduction was observed in the national drowning mortality rate from 6.60 per 100,000 in 2013 down to 3.28 per 100,000 in 2021, signifying a cumulative decrease of 50.30% [APC=-9.06% (95% CI: -11.31%, -6.76%)]. Across all sexes, regions, age groups, and residential areas, a consistent decline in mortality rates was evident between 2013 and 2021. Conclusion: An analysis of the data from 2013 to 2021 reveals a declining trend in the mortality rate due to unintentional drowning among individuals under 20 years of age in China. However, the rate of decline varied when stratified by sex, urban versus rural locations, age-specific groups, and geographical regions.

19.
J Control Release ; 364: 546-561, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37939851

RESUMEN

Noise-induced hearing loss (NIHL) is one of the most prevalent acquired sensorineural hearing loss etiologies and is characterized by the loss of cochlear hair cells, synapses, and nerve terminals. Currently, there are no agents available for the treatment of NIHL because drug delivery to the inner ear is greatly limited by the blood-labyrinth barrier. In this study, we used mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) as nanoscale vehicles to deliver brain-derived neurotrophic factor (BDNF) and evaluated their protective effects in a mouse model of NIHL. Following intravenous administration, BDNF-loaded sEVs (BDNF-sEVs) efficiently increased the expression of BDNF protein in the cochlea. Systemic application of sEVs and BDNF-sEVs significantly attenuated noise-induced cochlear hair cell loss and NIHL in CBA/J mice. BDNF-sEVs also alleviated noise-induced loss of inner hair cell ribbon synapses and cochlear nerve terminals. In cochlear explants, sEVs and BDNF-sEVs effectively protected hair cells against H2O2-induced cell loss. Additionally, BDNF-sEVs remarkably ameliorated H2O2-induced oxidative stress, cell apoptosis, and cochlear nerve terminal degeneration. Transcriptomic analysis revealed that many mRNAs and miRNAs were involved in the protective actions of BDNF-sEVs against oxidative stress. Collectively, our findings reveal a novel therapeutic strategy of MSC-sEVs-mediated BDNF delivery for the treatment of NIHL.


Asunto(s)
Vesículas Extracelulares , Pérdida Auditiva Provocada por Ruido , Animales , Ratones , Factor Neurotrófico Derivado del Encéfalo , Cóclea/metabolismo , Vesículas Extracelulares/metabolismo , Pérdida Auditiva Provocada por Ruido/tratamiento farmacológico , Pérdida Auditiva Provocada por Ruido/prevención & control , Peróxido de Hidrógeno/metabolismo , Ratones Endogámicos CBA
20.
Int Immunopharmacol ; 125(Pt A): 111143, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37913569

RESUMEN

BACKGROUND: Sepsis is a critical systemic inflammatory syndrome which usually leads to multiple organ dysfunction. Caffeic acid (CA), a phenolic compound derived from various plants, has been proved to be essential in neuroprotection, but its role in septic organ damage is unclear. This research aimed to investigate whether CA protects against organ injury in a mouse model of cecal ligation and puncture (CLP). METHODS: CA (30 mg/kg) or vehicle was administered by intraperitoneal injection immediately after CLP. The samples of blood, lungs, and livers were collected 24 h later. Organ injury was assessed by histopathological examination (HE staining), neutrophil infiltration (myeloperoxidase fluorescence), oxidative stress levels (MDA, SOD, HO-1), and inflammatory cytokines (TNF-α, IL-1ß, and IL-6) release in lung and liver tissues. Neutrophil extracellular trap (NET) formation was analyzed by immunofluorescence. In vitro experiments were performed to investigate the potential mechanisms of CA using small interfering RNA (siRNA) techniques in neutrophils, and the effect of CA on neutrophil apoptosis was analyzed by flow cytometry. RESULTS: Results showed that CA treatment improved the 7-day survival rate and attenuated the histopathological injury in the lung and liver of CLP mice. CA significantly reduced neutrophil infiltration in the lungs and livers of CLP mice. TNF-α, IL-1ß, IL-6 and LTB4 were reduced in serum, lung, and liver of CA-treated CLP mice, and phosphorylation of MAPK (p38, ERK, JNK) and p65 NF-κB was inhibited in lungs and livers. CA treatment further increased HO-1 levels and enhanced superoxide dismutase (SOD) activity, but reduced malondialdehyde (MDA) levels and NET formation. Similarly, in vitro experiments showed that CA treatment and 5-LOX siRNA interference inhibited inflammatory activation and NET release in neutrophils, suppressed MAPK and NF-κB phosphorylation in LPS-treated neutrophils, and decreased LTB4 and cfDNA levels. Flow cytometric analysis revealed that CA treatment reversed LPS-mediated delayed apoptosis in human neutrophils, and Western blot also indicated that CA treatment inhibited Bcl-2 expression but increased Bax expression. CA treatment did not induce further changes in neutrophil apoptosis, inflammatory activation, and NET release when 5-LOX was knocked down by siRNA interference. CONCLUSIONS: CA has a protective effect on lung and liver injury in a murine model of sepsis, which may be related to inhibition of the 5-LOX/LTB4 pathway.


Asunto(s)
Neutrófilos , Sepsis , Humanos , Ratones , Animales , Neutrófilos/metabolismo , FN-kappa B/metabolismo , Factor de Necrosis Tumoral alfa , Leucotrieno B4 , Interleucina-6 , Lipopolisacáridos , Sepsis/metabolismo , ARN Interferente Pequeño , Superóxido Dismutasa , Ratones Endogámicos C57BL
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