RESUMO

As common clinical-pathological processes, wound healing and tissue remodelling following injury or stimulation are essential topics in medical research. Promoting the effective healing of prolonged wounds, improving tissue repair and regeneration, and preventing fibrosis are important and challenging issues in clinical practice. Ferroptosis, which is characterized by iron overload and lipid peroxidation, is a nontraditional form of regulated cell death. Emerging evidence indicates that dysregulated metabolic pathways and impaired iron homeostasis play important roles in various healing and regeneration processes via ferroptosis. Thus, we review the intrinsic mechanisms of tissue repair and remodeling via ferroptosis in different organs and systems under various conditions, including the inflammatory response in skin wounds, remodeling of joints and cartilage, and fibrosis in multiple organs. Additionally, we summarize the common underlying mechanisms, key molecules, and targeted drugs for ferroptosis in repair and regeneration. Finally, we discuss the potential of therapeutic agents, small molecules, and novel materials emerging for targeting ferroptosis to promote wound healing and tissue repair and attenuate fibrosis.

RESUMO

Background: Metagenomic next-generation sequencing (mNGS) has been widely reported to identify pathogens in infectious diseases (IDs). In this work, we intended to investigate the diagnostic value and clinical acceptance of paired-samples mNGS as compared to the culture method. Methods: A total of 361 patients with suspected infection were retrospectively included. With reference to the clinical diagnosis, we compared the diagnostic performance and clinical acceptance in pathogen detection between mNGS and culture tests. Moreover, the pathogen concordance of paired blood and respiratory tract (RT) samples in mNGS assay was investigated. Results: Among 511 samples, 62.04% were shown to be pathogen positive by mNGS, and that for clinical diagnosis was 51.86% (265/511). When compared to culture assay (n = 428), mNGS had a significantly higher positivity rate (51.87% vs. 33.18%). With reference to the clinical diagnosis, the sensitivity of mNGS outperformed that of culture (89.08% vs. 56.72%). Importantly, mNGS exhibited a clinically accepted rate significantly superior to that of culture. In addition, the mNGS result from 53 paired blood and RT samples showed that most pairs were pathogen positive by both blood and RT, with pathogens largely being partially matched. Conclusion: Through this large-scale study, we further illustrated that mNGS had a clinically accepted rate and sensitivity superior to those of the traditional culture method in diagnosing infections. Moreover, blood and paired RT samples mostly shared partial-matched positive pathogens, especially for pathogens with abundant read numbers in RT, indicating that both blood and RT mNGS can aid the identification of pathogens for respiratory system infection.

Assuntos

Sequenciamento de Nucleotídeos em Larga Escala , Metagenômica , Sensibilidade e Especificidade , Humanos , Estudos Retrospectivos , Metagenômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/microbiologia , Idoso , Adulto Jovem , Adolescente , Criança , Técnicas de Diagnóstico Molecular/métodos , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/microbiologia , Pré-Escolar

RESUMO

The cardiotoxicity induced by immune checkpoint inhibitors (ICIs) is associated with high mortality rates. T cells play an important role in ICI-induced cardiac injury. The inhibition of local T-cell activity is considered an effective strategy for alleviating ICI-related cardiotoxicity. Tumor-derived extracellular vesicles (EVs) contribute to immunosuppression via PD-L1 overexpression. In this study, a bioorthogonal metabolic engineering-driven EV redirecting (Biomeder) strategy for in situ engineered EVs with myocardial-targeting peptides is developed. Accumulated tumor-derived EV (TuEVs) reverses the immune environment in the heart by increasing PD-L1 levels in cardiomyocytes and/or by directly inhibiting T-cell activity. More importantly, it is found that the redirection of TuEVs further disrupts immunosuppression in tumors, which facilitates anti-tumor activity. Thus, redirecting TuEVs to the heart simultaneously enhances the antitumor efficacy and safety of ICI-based therapy. Furthermore, the Biomeder strategy is successfully expanded to prevent ICI-induced type 1 diabetes. This Biomeder technique is a universal method for the treatment of various ICI-related adverse events.

RESUMO

Anthracnose, a fungal disease, commonly infects tea plants and severely impacts the yield and quality of tea. One method for controlling anthracnose is the application of citronellol, a plant extract that exhibits broad-spectrum antimicrobial activity. Herein, the physiological and biochemical mechanism by which citronellol controls anthracnose caused by Colletotrichum camelliae was investigated. Citronellol exhibited excellent antifungal activity based on direct and indirect mycelial growth inhibition assays, with EC50 values of 76.88 mg/L and 29.79 µL/L air, respectively. Citronellol also exhibited good control effects on C. camelliae in semi-isolated leaf experiments. Optical and scanning electron microscopy revealed that citronellol caused C. camelliae mycelia to thin, fracture, fold and deform. Transmission electron microscopy revealed that the mycelial cell walls collapsed inward and separated, and the organelles became blurred after treatment with citronellol. The sensitivity of C. camelliae to calcofluor white staining was significantly enhanced by citronellol, while PI staining showed minimal fluorescence, and the relative conductivity of mycelia were not significantly different. Under citronellol treatment, the expression levels of ß-1,3-glucanase, chitin synthase, and chitin deacetylase-related genes were significantly decreased, while the expression levels of chitinase genes were increased, leading to lower chitinase activity and increased ß-1,3-glucanase activity. Therefore, citronellol disrupted the cell wall integrity of C. camelliae and inhibited normal mycelial growth.

Assuntos

Monoterpenos Acíclicos , Parede Celular , Colletotrichum , Colletotrichum/efeitos dos fármacos , Parede Celular/efeitos dos fármacos , Parede Celular/ultraestrutura , Monoterpenos Acíclicos/farmacologia , Antifúngicos/farmacologia , Monoterpenos/farmacologia , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Micélio/efeitos dos fármacos , Micélio/crescimento & desenvolvimento , Micélio/ultraestrutura , Fungicidas Industriais/farmacologia

RESUMO

The polylactic acid (PLA) coatings of different crystallinity were prepared on biodegradable Mg-2.2Zn-0.3Ca alloy wires to improve the long-term anti-corrosion properties. The composition characteristics and microstructure of the samples were investigated by differential scanning calorimetry (DSC), Fourier transform infrared spectroscope (FTIR), wide angle X-ray diffraction (WAXD) and scanning electron microscope (SEM). The corrosion resistance of all samples was investigated by immersion tests and electrochemical techniques in vitro simulated body fluid (SBF). The results indicated heat treatment improved the crystallinity of PLA coating and heated-coating performed protective behaviors in the short and long-term immersion. The corrosion rate of heated samples was lower than that of unheated samples and exhibited superior long term protective effect for Mg alloy wires. The lifetime of heated sample (H2) increased significantly from 33 to 55 days. The initial electrochemical performance of unheated coating was better than heated coating, but it declined more rapidly during the long-term immersion. These results indicated that PLA coating could not ignore the effect of its crystallinity to anti-corrosion ability, and only the suit heat treatment makes PLA coating more ordering and achieves higher corrosion resistance in vitro immersion. Therefore, it has promising potential by controlling effectively the PLA ordering for surgical implant applications.

RESUMO

BACKGROUND: Studies involving chronic rhinosinusitis with nasal polyps (CRSwNP) have mostly focused on bilateral cases, making unilateral CRSwNP inadequately recognized. This study examined the differences in clinical characteristics, outcomes, and risk factors for poor outcomes between unilateral and bilateral CRSwNP to facilitate a better assessment in the two groups. METHODS: Demographic information, tissue and blood cells, endoscopic scores, Lund-Mackay scores, recurrence rates, and disease control conditions were compared between 310 unilateral and 596 bilateral CRSwNP patients. Furthermore, the stepwise regression multivariate Cox proportional hazard models were performed to generate risk factors for poor outcomes in the two groups. RESULTS: Bilateral cases exhibited higher rates of smoking, AR, and asthma comorbidities, along with higher numbers of tissue eosinophils and blood inflammatory cells when compared to unilateral patients. Endoscopic nasal polyp score, total computed tomography (CT) score (with scores for each sinus cavity), and adjusted CT scores were significantly higher in the bilateral group, except for a markedly higher adjusted maxillary score in the unilateral group. Furthermore, significantly higher proportions of bilateral patients experienced nasal polyp recurrence, uncontrolled status, and most disease control-related symptoms at follow-up. The primary risk factors for poor outcomes were asthma, tissue eosinophils, and total CT score in the bilateral group and blood basophils in the unilateral group. CONCLUSIONS: Bilateral CRSwNP patients experience worse disease severity and outcomes than their unilateral counterparts. Primarily, asthma, tissue eosinophils, and total CT score were risk factors for poor outcomes in bilateral CRSwNP patients, with blood basophils in unilateral cases.

RESUMO

For many people living at high altitudes for long or short periods of time, hypoxia is a challenge affecting many aspects of the body, including the immune system. Recently, myeloid-derived suppressor cells (MDSCs) have emerged as an immune cell population that plays an important role in several pathological conditions. However, to the best of our knowledge, there are no data regarding the behavior of MDSCs under hypoxic conditions. Therefore, the aim of this study is to investigate the monocytic type (M)- and polymorphonuclear type (PMN)-MDSC ratios in different hypoxic conditions to reveal the relationship between MDSCs and high-altitude hypoxia, as well as to determine whether MDSCs are involved in the regulation of the immune balance under hypoxic conditions as immunosuppressive factors. For the first time, we showed that MDSC abundance varies under different lengths of hypoxic exposure. We found that acute normobaric hypoxia led to an initial increase in the number of M-MDSCs, which decreased within 30 d. Both M- and PMN-MDSC ratios initially decreased under hypobaric hypoxia conditions within 30 d, but after 6 months in the real high altitude environment, M-MDSC ratio increased significantly. In summary, our data suggest that different hypoxic conditions influence MDSCs in mice, thereby contributing to a better understanding of the process of hypoxia adaptation and the occurrence and development of high-altitude disease.

RESUMO

Low-moisture extrusion (LME) can be used to improve the utilization of dietary fiber-rich Lentinula edodes stems (LES). The incorporation of dietary fiber can affect heat-induced interactions of starch molecules, which are critical for modifying starch characteristics via LME. In this work, a blend of LES and maize starch was extruded into a product at low moisture (30 %, w/v). The structure, physicochemical properties, and in vitro digestibility of extruded maize starches were investigated at different LES levels. The results showed that low levels (<7 %) of LES increased the crystallinity of LME-produced starch, while high levels (>7 %) did not. Because of the LES's soluble to insoluble dietary fiber ratios, the increased crystallinity of LES-added starch led to greater molecular ordering and the formation of an elastic gel after LME. At a suitable LES level (~3 %), highly crystallized starches were resistant to enzymolysis and had a high proportion of resistant starch. The obtained findings would contribute to a better understanding of how dietary fiber-rich LES affects starch extrusion and provide an alternative use for boosting the value of LES by-products.

RESUMO

Myeloid-derived suppressor cells (MDSCs) are a subset of immature myeloid cells that inhibit anti-tumor immunity and contribute to poor cancer outcomes. In this study, the authors used multi-color flow cytometry to detect changes in MDSCs in patients with cancer and tumor-bearing mice. Then the authors studied changes in MDSCs ratio and mouse tumors after administration of hypoxia-inducible factor 1α (HIF-1α) inhibitor. The results showed that the ratio of MDSCs, specifically polymorphonuclear MDSCs (PMN-MDSCs), was higher in patients with cancer, and both PMN-MDSCs and monocytic MDSCs (M-MDSCs) ratio were higher in tumor-bearing mice. When provided with the HIF-1α inhibitor LW-6, the ratio of MDSCs decreased in tumor-bearing mice, particularly PMN-MDSCs, and the volume of liver metastases also decreased. The authors' findings suggest that reducing MDSCs by inhibiting hypoxia-inducible factor 1α may slow tumor progression.

RESUMO

Pulsed electromagnetic field (PEMF) therapy has been extensively investigated in clinical studies for the treatment of angiogenesis-related diseases. However, there is a lack of research on the impact of PEMFs on energy metabolism and mitochondrial dynamics during angiogenesis. The present study included tube formation and CCK-8 assays. A Seahorse assay was conducted to analyze energy metabolism, and mitochondrial membrane potential assays, mitochondrial imaging, and reactive oxygen species assays were used to measure changes in mitochondrial structure and function in human umbilical vein endothelial cells (HUVECs) exposed to PEMFs. Real-time polymerase chain reaction was used to analyze the mRNA expression levels of antioxidants, glycolytic pathway-related genes, and genes associated with mitochondrial fission and fusion. The tube formation assay demonstrated a significantly greater tube network in the PEMF group compared to the control group. The glycolysis and mitochondrial stress tests revealed that PEMFs promoted a shift in the energy metabolism pattern of HUVECs from oxidative phosphorylation to aerobic glycolysis. Mitochondrial imaging revealed a wire-like mitochondrial morphology in the control group, and treatment with PEMFs led to shorter and more granular mitochondria. Our major findings indicate that exposure to PEMFs accelerates angiogenesis in HUVECs, likely by inducing energy metabolism reprogramming and mitochondrial fission.

Assuntos

Angiogênese , Campos Eletromagnéticos , Reprogramação Metabólica , Dinâmica Mitocondrial , Humanos , Angiogênese/efeitos da radiação , Glicólise , Células Endoteliais da Veia Umbilical Humana/metabolismo , Potencial da Membrana Mitocondrial , Reprogramação Metabólica/efeitos da radiação , Mitocôndrias/metabolismo , Mitocôndrias/efeitos da radiação , Dinâmica Mitocondrial/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo

RESUMO

Efficient conversion of biomass wastes into valuable chemicals has been regarded as a sustainable approach for green and circular economy. Herein, a highly efficient catalytic conversion of glycerol (Gly) into glycerol carbonate (GlyC) by carbonylation with the commercially available urea is presented using low-cost transition metal single atoms supported on zinc oxide quantum dots (M1-ZnO QDs) as a catalyst without using any solvent. A facile one-step wet chemical synthesis allows various types of metal single atoms to simultaneously dope and introduce Lewis-acid defects in the ZnO QD structure. It is found that doping with a trace amount of isolated metal atoms greatly boosts the catalytic activity with Gly conversion of 90.7%, GlyC selectivity of 100.0%, and GlyC yield of 90.6%. Congruential results from both Density Functional Theory (DFT) and in situ Diffuse Reflectance Infrared Fourier Transform Spectroscopy (in situ DRIFTS) studies reveal that the superior catalytic performance can be attributed to the enriched Lewis acid sites that endow optimal adsorption, formation of the intermediate for coupling between urea and Gly, and desorption of GlyC. Moreover, the tiny size of ZnO QDs efficiently promotes the accessibility of these active sites to the reactants.

RESUMO

Over a period of 30,000 to 40,000 years, high-altitude Tibetans have physiologically and genetically adapted to conditions such as hypoxia, low temperature, and high-intensity ultraviolet radiation. Based on the unique physiological and morphological characteristics of the Tibetan people, they have outstanding hypoxia adaptation skills and can continue to thrive in plateau hypoxia. The placenta of high-altitude Tibetans is protected from oxidative stress during delivery; however, little is known about changes in placental protein expression during vaginal delivery. In this study, we aimed to reveal these adaptive mechanisms by studying changes in placental protein expression during vaginal delivery in high-altitude Tibetans, low-altitude Tibetans, and low-altitude Han populations. Studying the changing mechanisms of maternal responses to hypoxia at high altitudes can reveal the molecular mechanisms of maternal and fetal adaptation to hypoxia at high altitudes and provide theories for preventing and treating maternal hypoxia and intrauterine growth and development restriction caused by other diseases.

RESUMO

Aberrant RNA editing has emerged as a pivotal factor in the pathogenesis of hepatocellular carcinoma (HCC), but the impact of RNA co-editing within HCC remains underexplored. We used a multi-step algorithm to construct an RNA co-editing network in HCC, and found that HCC-related RNA editings are predominantly centralized within the network. Furthermore, five pairs of risk RNA co-editing events were significantly correlated with the overall survival in HCC. Based on presence of risk RNA co-editings resulted in the categorization of HCC patients into high-risk and low-risk groups. Disparities in immune cell infiltrations were observed between the two groups, with the high-risk group exhibiting a greater abundance of exhausted T cells. Additionally, seven genes associated with risk RNA co-editing pairs were identified, whose expression effectively differentiates HCC tumor samples from normal ones. Our research offers an innovative perspective on the etiology and potential therapeutics for HCC.

Assuntos

Carcinoma Hepatocelular , Neoplasias Hepáticas , Edição de RNA , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Humanos , Regulação Neoplásica da Expressão Gênica , Prognóstico , Biomarcadores Tumorais/genética

RESUMO

The elevated levels of lactate in tumor tissue play a pivotal role in fostering an immunosuppressive microenvironment. Therefore, efficiently reducing lactate levels to reprogram tumor immune microenvironment (TIM) is considered a crucial step for boosted immunotherapy. Here, a high-lactate-metabolizing photosynthetic bacteria (LAB-1) is selectively screened for TIM reprogramming, which then improves the efficacy of tumor immunotherapy. The culture medium for LAB-1 screening is initially developed through an orthogonal experiment, simulating the tumor microenvironment (TME) and utilizing lactate as the sole organic carbon source. As demonstrated in a murine 4T1 model, LAB-1 colonizes the TME selectively, resulting in a significant reduction in lactate levels and a subsequent increase in pH values within the tumor tissue. Furthermore, single-cell RNA sequencing analysis reveals that LAB-1 effectively reprograms the TIM, thereby enhancing the effectiveness of antitumor immune therapy. This approach of utilizing lactate-consuming bacteria represents a potent tool for augmenting tumor immunotherapy efficiency.

Assuntos

Ácido Láctico , Microambiente Tumoral , Animais , Ácido Láctico/metabolismo , Camundongos , Linhagem Celular Tumoral , Imunoterapia , Bactérias/metabolismo , Fotossíntese , Neoplasias/imunologia , Neoplasias/metabolismo , Camundongos Endogâmicos BALB C

RESUMO

High-altitude pulmonary edema (HAPE) is a deadly form of altitude sickness, and there is no effective treatment for HAPE. Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cell isolated from dental pulp tissues and possess various functions, such as anti-inflammatory and anti-oxidative stress. DPSCs have been used to treat a variety of diseases, but there are no studies on treating HAPE. In this study, Sprague-Dawley rats were exposed to acute low-pressure hypoxia to establish the HAPE model, and SOD1-modified DPSCs (DPSCsHiSOD1) were administered through the tail vein. Pulmonary arterial pressure, lung water content (LWC), total lung protein content of bronchoalveolar lavage fluid (BALF) and lung homogenates, oxidative stress, and inflammatory indicators were detected to evaluate the effects of DPSCsHiSOD1 on HAPE. Rat type II alveolar epithelial cells (RLE-6TN) were used to investigate the effects and mechanism of DPSCsHiSOD1 on hypoxia injury. We found that DPSCs could treat HAPE, and the effect was better than that of dexamethasone treatment. SOD1 modification could enhance the function of DPSCs in improving the structure of lung tissue, decreasing pulmonary arterial pressure and LWC, and reducing the total lung protein content of BALF and lung homogenates, through anti-oxidative stress and anti-inflammatory effects. Furthermore, we found that DPSCsHiSOD1 could protect RLE-6TN from hypoxic injury by reducing the accumulation of reactive oxygen species (ROS) and activating the Nrf2/HO-1 pathway. Our findings confirm that SOD1 modification could enhance the anti-oxidative stress ability of DPSCs through the Nrf2/HO-1 signalling pathway. DPSCs, especially DPSCsHiSOD1, could be a potential treatment for HAPE. Schematic diagram of the antioxidant stress mechanism of DPSCs in the treatment of high-altitude pulmonary edema. DPSCs can alleviate oxidative stress by releasing superoxide dismutase 1, thereby reducing ROS production and activating the Nrf2/HO-1 signalling pathway to ameliorate lung cell injury in HAPE.

Assuntos

Doença da Altitude , Polpa Dentária , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Ratos Sprague-Dawley , Superóxido Dismutase-1 , Animais , Polpa Dentária/citologia , Polpa Dentária/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Ratos , Superóxido Dismutase-1/metabolismo , Superóxido Dismutase-1/genética , Doença da Altitude/terapia , Doença da Altitude/metabolismo , Masculino , Células-Tronco/metabolismo , Modelos Animais de Doenças , Transdução de Sinais , Edema Pulmonar/metabolismo , Edema Pulmonar/terapia , Hipertensão Pulmonar/terapia , Hipertensão Pulmonar/metabolismo , Humanos , Heme Oxigenase (Desciclizante)/metabolismo , Heme Oxigenase-1/metabolismo , Heme Oxigenase-1/genética

RESUMO

OBJECTIVE: The aim of this study is to evaluate the efficacy and cost-effectiveness of various induction chemotherapy (IC) regimens as first-line treatment for Locoregionally advanced nasopharyngeal carcinoma (LA-NPC), aiming to provide clinicians and patients with informed insights to aid in treatment decision-making. PATIENTS AND METHODS: We conducted a network meta-analysis (NMA) and cost-effectiveness analysis (CEA) based on data from 10 clinical trials investigating IC regimens for the treatment of LA-NPC. A Bayesian NMA was performed, with the primary outcomes being hazard ratios (HRs) for disease-free survival (DFS) and overall survival (OS). To model the disease progression of LA-NPC, we developed a dynamic partitioned survival model consisting of three disease states: progression-free survival (PFS), progression disease (PD), and death. The model was run on a 3-week cycle for a research period of 10 years, with quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) serving as outcome measures. RESULTS: According to the surface under the cumulative ranking curve (SUCRA) estimates derived from the NMA, TPC and TP, as IC regimens, appear to exhibit superior efficacy compared to other treatment modalities. In terms of CEA, concurrent chemoradiotherapy (CCRT), TPF + CCRT, and GP + CCRT were found to be dominated (more costs and less QALYs). Comparatively, TPC + CCRT emerged as a cost-effective option with an ICER of $1260.57/QALY when compared to PF + CCRT. However, TP + CCRT demonstrated even greater cost-effectiveness than TPC + CCRT, with an associated increase in costs of $3300.83 and an increment of 0.1578 QALYs per patient compared to TPC + CCRT, resulting in an ICER of $20917.62/QALY. CONCLUSION: Based on considerations of efficacy and cost-effectiveness, the TP + CCRT treatment regimen may emerge as the most favorable first-line therapeutic approach for patients with LA-NPC.

Assuntos

Análise Custo-Benefício , Quimioterapia de Indução , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Metanálise em Rede , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/economia , Carcinoma Nasofaríngeo/mortalidade , Quimioterapia de Indução/economia , Quimioterapia de Indução/métodos , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/economia , Anos de Vida Ajustados por Qualidade de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Análise de Custo-Efetividade

RESUMO

Endogenous hydrogen sulfide (H2S) plays an important role in bone metabolism. However, the exact role of H2S in intestinal calcium and phosphorus absorption and its potential in preventing and treating primary osteoporosis remains unknown. Therefore, this study aimed to investigate the potential of H2S in promoting intestinal calcium and phosphorus absorption and alleviating primary osteoporosis. We measured the apparent absorptivity of calcium, femoral bone density, expression and sulfhydration of the duodenal endoplasmic reticulum protein of 57 kDa (ERp57), duodenal cystathionine γ-lyase (CSE) expression, and serum H2S content in adult and old CSE-knockout and wild-type mice. We also assessed intracellular reactive oxygen species (ROS) and Ca2+ content in CSE-overexpressing or knockout intestinal epithelial cell (IEC)-6 cells. In senile mice, CSE knockout decreased endogenous H2S, ERp57 sulfhydration, and intestinal calcium absorption and worsened osteoporosis, which were partially reversed by GYY4137, an H2S donor. CSE overexpression in IEC-6 cells increased ERp57 sulfhydration, protein kinase A and C activity, and intracellular Ca2+, whereas CSE knockout exerted the opposite effects. Furthermore, hydrogen peroxide (H2O2) stimulation had similar effects as in CSE knockout, which were reversed by pretreatment with sodium hydrosulfide before H2O2 stimulation and restored by DL-dithiothreitol. These findings suggest that H2S attenuates primary osteoporosis by preventing ROS-induced ERp57 damage in intestinal epithelial cells by enhancing ERp57 activity and promoting intestinal calcium absorption, thereby aiding in developing therapeutic interventions to prevent osteoporosis.

Assuntos

Cálcio , Sulfeto de Hidrogênio , Osteoporose , Isomerases de Dissulfetos de Proteínas , Animais , Masculino , Camundongos , Cálcio/metabolismo , Linhagem Celular , Cistationina gama-Liase/metabolismo , Sulfeto de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/farmacologia , Absorção Intestinal/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteoporose/metabolismo , Osteoporose/prevenção & controle , Isomerases de Dissulfetos de Proteínas/metabolismo , Espécies Reativas de Oxigênio/metabolismo

RESUMO

Infectious diseases pose a severe threat to human health and are accompanied by significant economic losses. Studies of urban outbreaks of infectious diseases are diverse. However, previous studies have neglected the identification of critical events and the evaluation of scenario-based modeling of urban infectious disease outbreak emergency management mechanisms. In this paper, we aim to conduct an empirical analysis and scenario extrapolation using a questionnaire survey of 18 experts, based on the CIA-ISM method and scenario theory, to identify the key factors influencing urban infectious disease outbreaks. Subsequently, we evaluate the effectiveness of urban infectious disease outbreak emergency management mechanisms. Finally, we compare and verify the actual situation of COVID-19 in China, drawing the following conclusions and recommendations. (1) The scenario-based urban infectious disease emergency management model can effectively replicate the development of urban infectious diseases. (2) The establishment of an emergency command center and the isolation and observation of individuals exposed to infectious diseases are crucial factors in the emergency management of urban outbreaks of infectious disease.

Assuntos

COVID-19 , Surtos de Doenças , Humanos , COVID-19/epidemiologia , China/epidemiologia , Inquéritos e Questionários , População Urbana/estatística & dados numéricos , SARS-CoV-2 , Doenças Transmissíveis/epidemiologia

RESUMO

BACKGROUND: Brain-derived exosomes circulate in the bloodstream and other bodily fluids, serving as potential indicators of neurological disease progression. These exosomes present a promising avenue for the early and precise diagnosis of neurodegenerative conditions. Notably, miRNAs found in plasma extracellular vesicles (EVs) offer distinct diagnostic benefits due to their stability, abundance, and resistance to breakdown. RESULTS: In this study, we introduce a method using transferrin conjugated magnetic nanoparticles (TMNs) to isolate these exosomes from the plasma of patients with neurological disorders. This TMNs technique is both quick (<35 min) and cost-effective, requiring no high-priced ingredients or elaborate equipment for EV extraction. Our method successfully isolated EVs from 33 human plasma samples, including those from patients with Parkinson's disease (PD), Multiple Sclerosis (MS), and Dementia. Using quantitative polymerase chain reaction (PCR) analysis, we evaluated the potential of 8 exosomal miRNA profiles as biomarker candidates. Six exosomal miRNA biomarkers (miR-195-5p, miR-495-3p, miR-23b-3P, miR-30c-2-3p, miR-323a-3p, and miR-27a-3p) were consistently linked with all stages of PD. SIGNIFICANCE: The TMNs method provides a practical, cost-efficient way to isolate EVs from biological samples, paving the way for non-invasive neurological diagnoses. Furthermore, the identified miRNA biomarkers in these exosomes may emerge as innovative tools for precise diagnosis in neurological disorders including PD.

Assuntos

Exossomos , Nanopartículas de Magnetita , MicroRNAs , Doença de Parkinson , Transferrina , Humanos , Doença de Parkinson/diagnóstico , Doença de Parkinson/sangue , Exossomos/química , MicroRNAs/sangue , Nanopartículas de Magnetita/química , Transferrina/química , Encéfalo/metabolismo , Biomarcadores/sangue , Masculino , Feminino

RESUMO

The Retraction Watch Database (RWDB) is widely used to retrieve retraction data. However, its lack of affiliation normalization hinders the retrieval efficiency of retraction data for specific research-performing organizations. A query for a university name in the RWDB may yield retraction data entries for other universities with similar names, giving rise to the issue of affiliation naming proximity. This study assessed the impact of this issue on the retrieval efficiency of retraction records for 2,692 Chinese university names in English. The analysis revealed that the retrieval efficiency of retraction records for 206 Chinese university names can be influenced by 408 university names. As of 2022, the retrieval efficiency of retraction records for 96 Chinese university names was compromised by the involvement of 402 university names, resulting in an overall retraction inflation rate of 37.9% and an average rate of 45.0%. The findings highlight the importance of curating retraction data through affiliation-specific queries in the RWDB, adhering to the official English names of Chinese universities for scholarly publishing, and adopting the Research Organization Registry system for affiliation disambiguation. Given the significance of this issue concerning the English names of universities in non-English-speaking countries, the identified causes of the problem and proposed solutions can offer valuable insights for improving the retrieval of retraction records for non-Chinese universities in the RWDB.