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BACKGROUND: Exosome therapy shows potential for cardiac repair after injury. However, intrinsic challenges such as short half-life and lack of clear targets hinder the clinical feasibility. Here, we report a noninvasive and repeatable method for exosome delivery through inhalation after myocardial infarction (MI), which we called stem cell-derived exosome nebulization therapy (SCENT). METHODS: Stem cell-derived exosomes were characterized for size distribution and surface markers. C57BL/6 mice with MI model received exosome inhalation treatment through a nebulizer for 7 consecutive days. Echocardiographies were performed to monitor cardiac function after SCENT, and histological analysis helped with the investigation of myocardial repair. Single-cell RNA sequencing of the whole heart was performed to explore the mechanism of action by SCENT. Last, the feasibility, efficacy, and general safety of SCENT were demonstrated in a swine model of MI, facilitated by 3-dimensional cardiac magnetic resonance imaging. RESULTS: Recruitment of exosomes to the ischemic heart after SCENT was detected by ex vivo IVIS imaging and fluorescence microscopy. In a mouse model of MI, SCENT ameliorated cardiac repair by improving left ventricular function, reducing fibrotic tissue, and promoting cardiomyocyte proliferation. Mechanistic studies using single-cell RNA sequencing of mouse heart after SCENT revealed a downregulation of Cd36 in endothelial cells (ECs). In an EC-Cd36fl/- conditional knockout mouse model, the inhibition of CD36, a fatty acid transporter in ECs, led to a compensatory increase in glucose utilization in the heart and higher ATP generation, which enhanced cardiac contractility. In pigs, cardiac magnetic resonance imaging showed an enhanced ejection fraction (Δ=11.66±5.12%) and fractional shortening (Δ=5.72±2.29%) at day 28 after MI by SCENT treatment compared with controls, along with reduced infarct size and thickened ventricular wall. CONCLUSIONS: In both rodent and swine models, our data proved the feasibility, efficacy, and general safety of SCENT treatment against acute MI injury, laying the groundwork for clinical investigation. Moreover, the EC-Cd36fl/- mouse model provides the first in vivo evidence showing that conditional EC-CD36 knockout can ameliorate cardiac injury. Our study introduces a noninvasive treatment option for heart disease and identifies new potential therapeutic targets.
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Exosomas , Ratones Endogámicos C57BL , Infarto del Miocardio , Animales , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/terapia , Infarto del Miocardio/fisiopatología , Exosomas/metabolismo , Ratones , Administración por Inhalación , Modelos Animales de Enfermedad , Porcinos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Masculino , Función Ventricular Izquierda , Humanos , Miocardio/metabolismo , Miocardio/patología , Células Madre/metabolismo , Antígenos CD36/metabolismo , Antígenos CD36/genéticaRESUMEN
The surge of fast-spreading SARS-CoV-2 mutated variants highlights the need for fast, broad-spectrum strategies to counteract viral infections. In this work, we report a physical barrier against SARS-CoV-2 infection based on an inhalable bioadhesive hydrogel, named spherical hydrogel inhalation for enhanced lung defence (SHIELD). Conveniently delivered via a dry powder inhaler, SHIELD particles form a dense hydrogel network that coats the airway, enhancing the diffusional barrier properties and restricting virus penetration. SHIELD's protective effect is first demonstrated in mice against two SARS-CoV-2 pseudo-viruses with different mutated spike proteins. Strikingly, in African green monkeys, a single SHIELD inhalation provides protection for up to 8 hours, efficiently reducing infection by the SARS-CoV-2 WA1 and B.1.617.2 (Delta) variants. Notably, SHIELD is made with food-grade materials and does not affect normal respiratory functions. This approach could offer additional protection to the population against SARS-CoV-2 and other respiratory pathogens.
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COVID-19 , Animales , Chlorocebus aethiops , Ratones , SARS-CoV-2 , Hidrogeles , PrimatesRESUMEN
The intestinal microbiota community is a fundamental component of the human body and plays a significant regulatory role in maintaining overall health and in the management disease states.The intestinal microbiota-gut-brain axis represents a vital connection in the cognitive regulation of the central nervous system by the intestinal microbiota.The impact of intestinal microbiota on cognitive function is hypothesized to manifest through both the nervous system and circulatory system. Imbalances in intestinal microbiota during the perioperative period could potentially contribute to perioperative neurocognitive dysfunction. This article concentrates on a review of existing literature to explore the potential influence of intestinal microbiota on brain and cognitive functions via the nervous and circulatory systems.Additionally, it summarizes recent findings on the impact of perioperative intestinal dysbacteriosis on perioperative neurocognitive dysfunction and suggests novel approaches for prevention and treatment of this condition.
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Eje Cerebro-Intestino , Cognición , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/fisiología , Eje Cerebro-Intestino/fisiología , Cognición/fisiología , Animales , Encéfalo , DisbiosisRESUMEN
AIMS: Epicardium and epicardium-derived cells are critical players in myocardial fibrosis. Mesenchymal stem cell-derived extracellular vesicles (EVs) have been studied for cardiac repair to improve cardiac remodelling, but the actual mechanisms remain elusive. The aim of this study is to investigate the mechanisms of EV therapy for improving cardiac remodelling and develop a promising treatment addressing myocardial fibrosis. METHODS AND RESULTS: Extracellular vesicles were intrapericardially injected for mice myocardial infarction treatment. RNA-seq, in vitro gain- and loss-of-function experiments, and in vivo studies were performed to identify targets that can be used for myocardial fibrosis treatment. Afterward, a lipid nanoparticle-based long non-coding RNA (lncRNA) therapy was prepared for mouse and porcine models of myocardial infarction treatment. Intrapericardial injection of EVs improved adverse myocardial remodelling in mouse models of myocardial infarction. Mechanistically, Tcf21 was identified as a potential target to improve cardiac remodelling. Loss of Tcf21 function in epicardium-derived cells caused increased myofibroblast differentiation, whereas forced Tcf21 overexpression suppressed transforming growth factor-ß signalling and myofibroblast differentiation. LncRNA-Tcf21 antisense RNA inducing demethylation (TARID) that enriched in EVs was identified to up-regulate Tcf21 expression. Formulated lncRNA-TARID-laden lipid nanoparticles up-regulated Tcf21 expression in epicardium-derived cells and improved cardiac function and histology in mouse and porcine models of myocardial infarction. CONCLUSION: This study identified Tcf21 as a critical target for improving cardiac fibrosis. Up-regulating Tcf21 by using lncRNA-TARID-laden lipid nanoparticles could be a promising way to treat myocardial fibrosis. This study established novel mechanisms underlying EV therapy for improving adverse remodelling and proposed a lncRNA therapy for cardiac fibrosis.
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Infarto del Miocardio , ARN Largo no Codificante , Ratones , Animales , Porcinos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN sin Sentido/genética , ARN sin Sentido/metabolismo , Remodelación Ventricular , Infarto del Miocardio/genética , Infarto del Miocardio/terapia , Infarto del Miocardio/metabolismo , Fibrosis , DesmetilaciónRESUMEN
OBJECTIVE: To delve into the primary active ingredients and mechanism of Pueraria lobata for alleviating iron overload in alcoholic liver disease. METHODS: Pueraria lobata's potential targets and signaling pathways in treating alcohol-induced iron overloads were predicted using network pharmacology analysis. Then, animal experiments were used to validate the predictions of network pharmacology. The impact of puerarin or genistein on alcohol-induced iron accumulation, liver injury, oxidative stress, and apoptosis was assessed using morphological examination, biochemical index test, and immunofluorescence. Key proteins implicated in linked pathways were identified using RT-qPCR, western blot analysis, and immunohistochemistry. RESULTS: Network pharmacological predictions combined with animal experiments suggest that the model group compared to the control group, exhibited activation of the MAPK/ERK signaling pathway, suppression of hepcidin expression, and aggravated iron overload, liver damage, oxidative stress, and hepatocyte death. Puerarin and genistein, the active compounds in Pueraria lobata, effectively mitigated the aforementioned alcohol-induced effects. No statistically significant disparities were seen in the effects above between the two groups receiving drug therapy. CONCLUSION: This study preliminarily demonstrated that puerarin and genistein in Pueraria lobata may increase hepcidin production to alleviate alcohol-induced iron overload by inhibiting the MAPK/ERK signaling pathway.
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Sobrecarga de Hierro , Isoflavonas , Hepatopatías Alcohólicas , Sistema de Señalización de MAP Quinasas , Pueraria , Pueraria/química , Hepatopatías Alcohólicas/metabolismo , Hepatopatías Alcohólicas/tratamiento farmacológico , Hepatopatías Alcohólicas/patología , Animales , Sobrecarga de Hierro/tratamiento farmacológico , Sobrecarga de Hierro/metabolismo , Isoflavonas/farmacología , Isoflavonas/química , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Estrés Oxidativo/efectos de los fármacos , Genisteína/farmacología , Genisteína/química , Ratones , Apoptosis/efectos de los fármacosRESUMEN
BACKGROUND: The clinical efficacy and safety of intravenous immunoglobulin (IVIg) treatment for COVID-19 remain controversial. This study aimed to map the current status and gaps of available evidence, and conduct a meta-analysis to further investigate the benefit of IVIg in COVID-19 patients. METHODS: Electronic databases were searched for systematic reviews/meta-analyses (SR/MAs), primary studies with control groups, reporting on the use of IVIg in patients with COVID-19. A random-effects meta-analysis with subgroup analyses regarding study design and patient disease severity was performed. Our outcomes of interest determined by the evidence mapping, were mortality, length of hospitalization (days), length of intensive care unit (ICU) stay (days), number of patients requiring mechanical ventilation, and adverse events. RESULTS: We included 34 studies (12 SR/MAs, 8 prospective and 14 retrospective studies). A total of 5571 hospitalized patients were involved in 22 primary studies. Random-effects meta-analyses of very low to moderate evidence showed that there was little or no difference between IVIg and standard care or placebo in reducing mortality (relative risk [RR] 0.91; 95% CI 0.78-1.06; risk difference [RD] 3.3% fewer), length of hospital (mean difference [MD] 0.37; 95% CI - 2.56, 3.31) and ICU (MD 0.36; 95% CI - 0.81, 1.53) stays, mechanical ventilation use (RR 0.92; 95% CI 0.68-1.24; RD 2.8% fewer), and adverse events (RR 0.98; 95% CI 0.84-1.14; RD 0.5% fewer) of patients with COVID-19. Sensitivity analysis using a fixed-effects model indicated that IVIg may reduce mortality (RR 0.76; 95% CI 0.60-0.97), and increase length of hospital stay (MD 0.68; 95% CI 0.09-1.28). CONCLUSION: Very low to moderate certainty of evidence indicated IVIg may not improve the clinical outcomes of hospitalized patients with COVID-19. Given the discrepancy between the random- and fixed-effects model results, further large-scale and well-designed RCTs are warranted.
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COVID-19 , Inmunoglobulinas Intravenosas , Humanos , Inmunoglobulinas Intravenosas/efectos adversos , Estudios Prospectivos , Estudios Retrospectivos , Revisiones Sistemáticas como AsuntoRESUMEN
PURPOSE: To synthesize evidence on the impact of bronchopulmonary dysplasia (BPD) on the Quality of Life (QoL) of affected individuals from three perspectives: (i) QoL of caregiver; (ii) caregiver's perception of BPD patient's QoL; and (iii) BPD patient's self-reported QoL. METHODS: Quantitative studies (case-control, cohort, and case series) on the QoL of BPD patients or their caregivers were considered. We conducted a systematic literature search of 6 databases (PubMed, Embase, World of Science, CINAHL, PsycINFO, and Chinese National Knowledge Infrastructure) for relevant studies. All databases were searched from the date of inception of the databases to 31 March 2022. Populations of interest were caregivers with preterm babies with BPD, or children/adults who were born premature and diagnosed with BPD. The main outcome measures were total and subdomain QoL scores, and factors affecting QoL. RESULTS: A total of 1078 articles were found; 10 were eligible for analysis, which included 247 caregivers and 1632 patients with BPD. The QoL of patients differed by domains-some were poorer or similar, but none of the QoL domains was better than QoL of healthy controls. Poor sleep and acute care needs of BPD patients negatively affected caregiver's QoL, while increasing illness acuity negatively affected the QoL of BPD patients. The QoL of BPD patients and their caregivers was most adversely affected during the immediate post-discharge period and tended to improve with time. The physical QoL of BPD patients was similar to that of preterm babies without BPD when assessed during late childhood and early adulthood. CONCLUSION: QoL assessment should be performed as an outcome measure and incorporated in the care plan for BPD patients and their caregivers. Systematic Review Registration PROSPERO CRD42021292253.
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Displasia Broncopulmonar , Recién Nacido , Lactante , Adulto , Humanos , Niño , Calidad de Vida/psicología , Cuidadores , Cuidados Posteriores , Alta del PacienteRESUMEN
BACKGROUND: Osteoporosis is a chronic condition affecting patients' morbidity and mortality and represents a big socioeconomic burden. Because stem cells can proliferate and differentiate into bone-forming cells, stem cell therapy for osteoporosis has been widely studied. However, cells as a live drug face multiple challenges because of their instability during preservation and transportation. In addition, cell therapy has potential adverse effects such as embolism, tumorigenicity, and immunogenicity. RESULTS: Herein, we sought to use cell-mimicking and targeted therapeutic nanoparticles to replace stem cells. We fabricated nanoparticles (NPs) using polylactic-co-glycolic acid (PLGA) loaded with the secretome (Sec) from mesenchymal stem cells (MSCs) to form MSC-Sec NPs. Furthermore, we cloaked the nanoparticles with the membranes from C-X-C chemokine receptor type 4 (CXCR4)-expressing human microvascular endothelial cells (HMECs) to generate MSC-Sec/CXCR4 NP. CXCR4 can target the nanoparticles to the bone microenvironment under osteoporosis based on the CXCR4/SDF-1 axis. CONCLUSIONS: In a rat model of osteoporosis, MSC-Sec/CXCR4 NP were found to accumulate in bone, and such treatment inhibited osteoclast differentiation while promoting osteogenic proliferation. In addition, our results showed that MSC-Sec/CXCR4 NPs reduce OVX-induced bone mass attenuation in OVX rats.
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Células Madre Mesenquimatosas , Nanopartículas , Osteoporosis/metabolismo , Receptores CXCR4/metabolismo , Secretoma/metabolismo , Animales , Membrana Celular/química , Membrana Celular/metabolismo , Modelos Animales de Enfermedad , Células Endoteliales/química , Células Endoteliales/metabolismo , Células Madre Mesenquimatosas/química , Células Madre Mesenquimatosas/metabolismo , Sistema de Administración de Fármacos con Nanopartículas , RatasRESUMEN
OBJECTIVE: To evaluate how public perceptions and trust in government communications affected the adoption of protective behaviour in Singapore during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We launched our community-based cohort to assess public perceptions of infectious disease outbreaks in mid-2019. After the first case of COVID-19 was reported in Singapore on 23 January, we launched a series of seven COVID-19 surveys to both existing and regularly enrolled new participants every 2 weeks. As well as sociodemographic properties of the participants, we recorded changing responses to judge awareness of the situation, trust in various information sources and perceived risk. We used multivariable logistic regression models to evaluate associations with perceptions of risk and self-reported adopted frequencies of protective behaviour. FINDINGS: Our cohort of 633 participants provided 2857 unique responses during the seven COVID-19 surveys. Most agreed or strongly agreed that information from official government sources (99.1%; 528/533) and Singapore-based news agencies (97.9%; 522/533) was trustworthy. Trust in government communication was significantly associated with higher perceived threat (odds ratio, OR: 2.2; 95% confidence interval, CI: 1.6-3.0), but inversely associated with perceived risk of infection (OR: 0.6; 95% CI: 0.4-0.8) or risk of death if infected (OR: 0.6; 95% CI: 0.4-0.9). Trust in government communication was also associated with a greater likelihood of adopting protective behaviour. CONCLUSION: Our findings show that trust is a vital commodity when managing an evolving outbreak. Our repeated surveys provided real-time feedback, allowing an improved understanding of the interplay between perceptions, trust and behaviour.
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COVID-19 , Gobierno , Conocimientos, Actitudes y Práctica en Salud , Opinión Pública , Confianza , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Medición de Riesgo , Singapur , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Given increasing antimicrobial resistance, we aimed to determine antibiotic susceptibility and presence of resistance genes in uropathogens in primary care, factors associated with resistance to commonly prescribed antibiotics, and effect of treatment on early symptom resolution. We conducted a prospective study of primary care patients with urinary tract infection (UTI) symptoms and culture-confirmed UTI in Singapore from 2015 to 2016. Cohort characteristics and antimicrobial susceptibility of cultured isolates were analyzed. Among Enterobacteriaceae isolates, early symptom resolution (within 3 days) according to antibiotic prescribed and isolate susceptibility and factors associated with antibiotic resistance were evaluated. Of 695 symptomatic patients, 299 were urine culture positive; of these 299 patients, 259 (87%) were female. Escherichia coli was the most common uropathogen (76%). Enterobacteriaceae isolates (n = 283) were highly susceptible to amoxicillin-clavulanate (86%), nitrofurantoin (87%), and fosfomycin (98%), but >20% were resistant to ciprofloxacin and co-trimoxazole. Isolates resistant to appropriate indicator antibiotics were further tested to determine proportions positive for blaCTX-M (14/26, 54%), plasmid-mediated ampC (12/24, 50%), qnr (7/69, 10%), and fos (1/6, 17%) resistance genes. A total of 67% of patients given antibiotics with susceptible isolates reported early resolution versus 45% given antibiotics with nonsusceptible isolates (P = 0.001) and 27% not treated (P = 0.018). On multivariable analysis, Indian ethnicity and diabetes mellitus were associated with amoxicillin-clavulanate resistance. Genitourinary abnormalities, UTI in the past 12 months, and hospitalization in the past 6 months were associated with ciprofloxacin and co-trimoxazole resistance. Patients given active empirical antibiotics were most likely to report early symptom resolution, but correlation with in vitro susceptibility was imperfect. Factors associated with resistance may guide the decision to obtain initial urine culture.
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Farmacorresistencia Bacteriana , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Enterobacteriaceae/efectos de los fármacos , Enterobacteriaceae/genética , Genes Bacterianos , Infecciones Urinarias/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Enterobacteriaceae/aislamiento & purificación , Infecciones por Enterobacteriaceae/microbiología , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Atención Primaria de Salud , Estudios Prospectivos , Singapur , Resultado del Tratamiento , Infecciones Urinarias/microbiología , Adulto JovenRESUMEN
The gut microbiota possesses diverse metabolic activities, but its contribution toward heterogeneous toxicological responses is poorly understood. In this study, we investigated the role of the liver-gut microbiota axis in underpinning the hepatotoxicity of tacrine. We employed an integrated strategy combining pharmacokinetics, toxicology, metabonomics, genomics, and metagenomics to elucidate and validate the mechanism of tacrine-induced hepatotoxicity in Lister hooded rats. Pharmacokinetic studies in rats demonstrated 3.3-fold higher systemic exposure to tacrine in strong responders that experienced transaminitis, revealing enhanced enterohepatic recycling of deglucuronidated tacrine in this subgroup, not attributable to variation in hepatic disposition gene expression. Metabonomic studies implicated variations in gut microbial activities that mapped onto tacrine-induced transaminitis. Metagenomics delineated greater deglucuronidation capabilities in strong responders, based on differential gut microbial composition (e.g., Lactobacillus, Bacteroides, and Enterobacteriaceae) and approximately 9% higher ß-glucuronidase gene abundance compared with nonresponders. In the validation study, coadministration with oral ß-glucuronidase derived from Escherichia coli and pretreatment with vancomycin and imipenem significantly modulated the susceptibility to tacrine-induced transaminitis in vivo. CONCLUSION: This study establishes pertinent gut microbial influences in modifying the hepatotoxicity of tacrine, providing insights for personalized medicine initiatives. (Hepatology 2018;67:282-295).
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Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Microbioma Gastrointestinal/efectos de los fármacos , Tacrina/toxicidad , Animales , Biopsia con Aguja , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Inmunohistoquímica , Pruebas de Función Hepática , Masculino , Distribución Aleatoria , Ratas , Ratas Endogámicas , Valores de Referencia , Índice de Severidad de la Enfermedad , Tacrina/farmacocinética , Tacrina/farmacologíaRESUMEN
BACKGROUND: Women with urinary tract infections (UTIs) often present with urinary complaints such as frequency of micturition, dysuria, foul-smelling urine and other non-specific symptoms like fever. Physicians may order urine microscopy to guide empirical antibiotic prescription. However, the performance of this approach has not been assessed. OBJECTIVES: This study aimed to determine the accuracy of UTI symptoms and urine microscopy associated with culture-positive UTI in Asian women. METHODS: A cross-sectional study of adult women who presented with UTI-related symptoms was conducted at three public primary care clinics in Singapore. Demographic data and information on their symptoms were collected, followed by urine microscopy and culture to diagnose UTI. The sensitivity, specificity, positive (PPV), negative predictive values (NPV), accuracy (ACC) and area under curve (AUC) of combinations of symptom and urine investigations were analysed in association with culture-positive UTI, which was regarded as a benchmark. RESULTS: Data on 564 women (73.9% Chinese, 11.5% Malay, 8.2% Indian) were analysed, of which 259 (45.9%) had culture-positive UTI. Frequency and foul-smelling urine, pyuria (WBC ≥10/hpf) and semi-quantitative bacterial count (≥2+) were significantly associated with positive urine culture. The ACC and AUC for single or multiple urinary and/or general symptoms were low. Urine pyuria (minimally >10/hpf) alone or in combination with symptoms and/or semi-quantitative bacterial count achieved high sensitivity (>85%) and PPV, NPV, ACC and AUC of >70%. CONCLUSION: Urinary symptoms have limited accuracy in diagnosing culture-positive UTI. Concurrent urine microscopy showing presence of pyuria and/or bacterial count increased the diagnostic accuracy of culture-positive UTI.
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Antibacterianos/uso terapéutico , Pueblo Asiatico/estadística & datos numéricos , Microscopía , Urinálisis , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/tratamiento farmacológico , Adulto , Estudios Transversales , Disuria/diagnóstico , Disuria/tratamiento farmacológico , Femenino , Fiebre/etiología , Humanos , Persona de Mediana Edad , Atención Primaria de Salud , SingapurRESUMEN
OBJECTIVE: To compare the effectiveness and safety of suprapubic tube drainage (SPT) with those of transurethral catheterization (TUC) after robot-assisted radical prostatectomy (RARP). METHODS: We searched PubMed, EMBASE, Cochrane Library, CNKI, VIP, WanFang Data and China Biology Medicine Disc from their inception to December 2017 for randomized controlled trials and cohort studies comparing the effectiveness and safety of SPT and TUC after RARP. Two reviewers independently screened the literature, extracted data and assessed the risk of bias of the included studies, followed by a meta-analysis with the RevMan 5.3 software. RESULTS: Ten studies met the eligibility criteria and were included in this meta-analysis, involving 1 248 cases of RARP, 482 in the SPT group and the other 766 in the TUC group. The severity of postoperative penile pain was significantly lower in the SPT than in the TUC group (RR = 0.63, 95% CI: 0.50 to 0.80, P = 0.0002), but no statistically significant differences were shown between the two groups in the overall pain severity at 1ï¼3 days (ï¼»MD = ï¼0.26, 95% CI: ï¼1.34 to 0.83, P = 0.64ï¼½ and 6ï¼7 days postoperatively (ï¼»MD = ï¼0.50, 95% CI: ï¼1.54 to 0.54, P=0.34ï¼½, urinary incontinence (RR = 0.80, 95% CI: 0.56 to 1.15, P = 0.23), bacteriuria (RR = 0.63, 95% CI: 0.20 to 1.97, P = 0.42), bladder neck contracture (RR = 0.77, 95% CI: 0.39 to 1.53, P = 0.45), urethral stricture (RR = 1.32, 95% CI: 0.08 to 20.7, P = 0.84), anastomotic stricture (RR = 0.20, 95% CI: 0.02 to 1.79, P = 0.15), or urinary retention (RR = 0.93, 95% CI: 0.43 to 2.00, P = 0.85). CONCLUSIONS: SPT after RARP is associated with a lower severity of postoperative penile pain than TUC, but there are no statistically significant differences between the two strategies in other parameters. This conclusion, however, has to be further supported by more higher-quality randomized controlled trials.
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Prostatectomía , Procedimientos Quirúrgicos Robotizados , Cateterismo , China , Drenaje , Humanos , Masculino , Prostatectomía/métodos , UretraRESUMEN
In fiber-optic communications, in order to achieve more data channels in the wavelength division multiplexing (WDM) system without changing the modulation wavelength range, a new type of small-sized narrowband polarizing beam splitter was designed. It can be used for data communication network expansion and improve the Signal to Noise Ratio (SNR) of the optical signal. Two kinds new film system designed were deposited on the polarizing beam splitter. One layer is narrowband filter film, while the other layer is polarizing beam splitter film. TFCalc software was used for simulation analysis, and the results shown that the bandwidth of the narrowband filter film was about 0.4 nm, and the permeability of p light from the polarizing beam splitter film was better than 99.8% in the range of 1 530ï½1 560 nm. Based on the above film system design, two groups film system was made on BK7 optical glass. In the experiment, light through film was spectral analysis with Agilent 8164-A type optical measuring instrument. Experimental results show that the actual bandwidth of the narrowband filter film is better than 0.4 nm, gain flatness is not less than -0.05 dB. It has a narrower bandwidth compared to the existing common 0.8 nm filter film, and it can be realized to increase the amount of data channels in the wavelength division multiplexing system with the same modulation wavelength range. Actual transmittance of p light was 99.6% through polarizing filter film, and it's slightly lower than the simulated values, but it remains better than the design requirements. Compared to conventional polarizing beam splitter, its optical signal was stronger, and it has a higher SNR. In summary, the polarizing beam splitter has better application value and practical significance.
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Expansion microscopy (ExM) is a promising technology that enables nanoscale imaging on conventional optical microscopes by physically magnifying the specimens. Here, we report the development of a strategy that enables i) on-demand labeling of subcellular organelles in live cells for ExM through transfection of fluorescent proteins that are well-retained during the expansion procedure; and ii) non-fluorescent chromogenic color-development towards efficient bright-field and photoacoustic imaging in both planar and volumetric formats, which is applicable to both cultured cells and biological tissues. Compared to the conventional ExM methods, our strategy provides an expanded toolkit, which we term as expansion fluorescence and photoacoustic microscopy (ExFLPAM), by allowing on-demand fluorescent protein labeling of cultured cells, as well as non-fluorescent absorption contrast-imaging of biological samples.
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Continued emergence of SARS-CoV-2 variants of concern that are capable of escaping vaccine-induced immunity highlights the urgency of developing new COVID-19 therapeutics. An essential mechanism for SARS-CoV-2 infection begins with the viral spike protein binding to the human ACE2. Consequently, inhibiting this interaction becomes a highly promising therapeutic strategy against COVID-19. Herein, we demonstrate that ACE2-expressing human lung spheroid cells (LSC)-derived exosomes (LSC-Exo) could function as a prophylactic agent to bind and neutralize SARS-CoV-2, protecting the host against SARS-CoV-2 infection. Inhalation of LSC-Exo facilitates its deposition and biodistribution throughout the whole lung in a female mouse model. We show that LSC-Exo blocks the interaction of SARS-CoV-2 with host cells in vitro and in vivo by neutralizing the virus. LSC-Exo treatment protects hamsters from SARS-CoV-2-induced disease and reduced viral loads. Furthermore, LSC-Exo intercepts the entry of multiple SARS-CoV-2 variant pseudoviruses in female mice and shows comparable or equal potency against the wild-type strain, demonstrating that LSC-Exo may act as a broad-spectrum protectant against existing and emerging virus variants.
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COVID-19 , Exosomas , Cricetinae , Femenino , Animales , Humanos , Ratones , SARS-CoV-2 , Enzima Convertidora de Angiotensina 2 , Distribución Tisular , Glicoproteína de la Espiga del Coronavirus , Anticuerpos NeutralizantesRESUMEN
Chemotherapy-induced cardiotoxicity with subsequent heart failure (HF) is a major cause of morbidity and mortality in cancer survivors worldwide. Chemotherapy-induced HF is exceptionally challenging as it generally manifests in patients who are typically not eligible for left ventricular device implantation or heart transplantation. To explore alternative treatment strategies for cancer survivors suffering from chemotherapy-induced HF, we developed a minimally invasive infusible cardiac stromal cell secretomes adhesive (MISA) that could be delivered locally through an endoscope-guided intrapericardial injection. To mimic the typical clinical presentation of chemotherapy-induced HF in elder patients, we established an aged rat model in which restrictive cardiomyopathy with sequential HF was induced via consecutive doxorubicin injections. In vitro, we prove that MISA not only enhanced cardiomyocytes proliferation potency and viability, but also inhibited their apoptosis. In vivo, we prove that MISA improved the ventricular contractility indexes and led to beneficial effects on histological and structural features of restrictive cardiomyopathy via promoting cardiomyocyte proliferation, angiogenesis, and mitochondrial respiration. Additionally, we also evaluated the safety and feasibility of MISA intrapericardial delivery in a healthy porcine model with an intact immune system. In general, our data indicates that MISA has a strong potential for translation into large animal models and ultimately clinical applications for chemotherapy-induced HF prior to the final option of heart transplantation.
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BACKGROUND: Myopia, commonly known as near-sightedness, has emerged as a global epidemic, impacting almost one in three individuals across the world. The increasing prevalence of myopia during early childhood has heightened the risk of developing high myopia and related sight-threatening eye conditions in adulthood. This surge in myopia rates, occurring within a relatively stable genetic framework, underscores the profound influence of environmental and lifestyle factors on this condition. In this comprehensive narrative review, we shed light on both established and potential environmental and lifestyle contributors that affect the development and progression of myopia. MAIN BODY: Epidemiological and interventional research has consistently revealed a compelling connection between increased outdoor time and a decreased risk of myopia in children. This protective effect may primarily be attributed to exposure to the characteristics of natural light (i.e., sunlight) and the release of retinal dopamine. Conversely, irrespective of outdoor time, excessive engagement in near work can further worsen the onset of myopia. While the exact mechanisms behind this exacerbation are not fully comprehended, it appears to involve shifts in relative peripheral refraction, the overstimulation of accommodation, or a complex interplay of these factors, leading to issues like retinal image defocus, blur, and chromatic aberration. Other potential factors like the spatial frequency of the visual environment, circadian rhythm, sleep, nutrition, smoking, socio-economic status, and education have debatable independent influences on myopia development. CONCLUSION: The environment exerts a significant influence on the development and progression of myopia. Improving the modifiable key environmental predictors like time spent outdoors and engagement in near work can prevent or slow the progression of myopia. The intricate connections between lifestyle and environmental factors often obscure research findings, making it challenging to disentangle their individual effects. This complexity underscores the necessity for prospective studies that employ objective assessments, such as quantifying light exposure and near work, among others. These studies are crucial for gaining a more comprehensive understanding of how various environmental factors can be modified to prevent or slow the progression of myopia.
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Miopía , Preescolar , Niño , Humanos , Estudios Prospectivos , Miopía/epidemiología , Miopía/genética , Miopía/prevención & control , Refracción Ocular , Acomodación Ocular , Ritmo CircadianoRESUMEN
Decellularized extracellular matrix (dECM)-based hydrogels are widely applied to additive biomanufacturing strategies for relevant applications. The extracellular matrix components and growth factors of dECM play crucial roles in cell adhesion, growth, and differentiation. However, the generally poor mechanical properties and printability have remained as major limitations for dECM-based materials. In this study, heart-derived dECM (h-dECM) and meniscus-derived dECM (Ms-dECM) bioinks in their pristine, unmodified state supplemented with the photoinitiator system of tris(2,2-bipyridyl) dichlororuthenium(II) hexahydrate and sodium persulfate, demonstrate cytocompatibility with volumetric bioprinting processes. This recently developed bioprinting modality illuminates a dynamically evolving light pattern into a rotating volume of the bioink, and thus decouples the requirement of mechanical strengths of bioprinted hydrogel constructs with printability, allowing for the fabrication of sophisticated shapes and architectures with low-concentration dECM materials that set within tens of seconds. As exemplary applications, cardiac tissues are volumetrically bioprinted using the cardiomyocyte-laden h-dECM bioink showing favorable cell proliferation, expansion, spreading, biomarker expressions, and synchronized contractions; whereas the volumetrically bioprinted Ms-dECM meniscus structures embedded with human mesenchymal stem cells present appropriate chondrogenic differentiation outcomes. This study supplies expanded bioink libraries for volumetric bioprinting and broadens utilities of dECM toward tissue engineering and regenerative medicine.
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Bioimpresión , Matriz Extracelular Descelularizada , Hidrogeles , Tinta , Ingeniería de Tejidos , Bioimpresión/métodos , Hidrogeles/química , Animales , Matriz Extracelular Descelularizada/química , Ingeniería de Tejidos/métodos , Miocitos Cardíacos/citología , Andamios del Tejido/química , Proliferación Celular , Humanos , Materiales Biocompatibles/química , Matriz Extracelular/química , Matriz Extracelular/metabolismoRESUMEN
Environmental behaviors of heavy metal in soil are strongly influenced by seasonal freeze-thaw events at the mid-high altitudes. However, the potential impact mechanisms of freeze-thaw cycles on the vertical migration of heavy metal are still poor understood. This study aimed to explore how exogenous cadmium (Cd) migrated and remained in soil during the in-situ seasonal freeze-thaw action using rare earth elements (REEs) as tracers. As a comparison, soil which was incubated in the controlled laboratory (25 °C) was employed. Although there was no statistically significant difference in the Cd levels of different soil depths under different treatments, the original aggregate sources of Cd in the 5-10 cm and 10-15 cm soil layers differed. From the distributions of REEs in soil profile, it can be known that Cd in the subsurface of field incubated soil was mainly from the breakdown of >0.50 mm aggregates, while it was mainly from the <0.106 mm aggregates for the laboratory incubated soil. Furthermore, the dissolved and colloidal Cd concentrations were 0.47 µg L-1 and 0.62 µg L-1 in the leachates from field incubated soil than those from control soil (0.21 µg L-1 and 0.43 µg L-1). Additionally, the colloid-associated Cd in the leachate under field condition was mainly from the breakdown of >0.25 mm aggregates and the direct migration of <0.106 mm aggregates, while it was the breakdown of >0.50 mm and the direct migration of <0.106 mm aggregates for the soil under laboratory condition. Our results for the first time provided insights into the fate of exogenous contaminants in seasonal frozen regions using the rare earth element tracing method.