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1.
Artigo em Inglês | MEDLINE | ID: mdl-35507777

RESUMO

Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have been evaluated in many studies as promising therapeutic agents for pulmonary hypertension (PH). However, low yields and heterogeneity are a major barrier in the translational utility of EVs for clinical studies. To address these limitations, we fabricated MSCs derived nanovesicles (MSC-NVs) by serial extrusion through filters resulting in MSC-NVs with characteristics similar to conventional EVs but with much higher production yields. Herein, we examined the therapeutic efficacy of MSC-NVs in preclinical models of PH in vitro and in vivo. Intervention with MSC-NVs improved the core pathologies of monocrotaline (MCT) induced PH in rat. Intravenous administration of MSC-NVs resulted in significant uptake within hypertensive lungs, pulmonary artery lesions and especially in pulmonary artery smooth muscle cells (PASMCs). In vitro, MSC-NVs inhibited PDGF-induced proliferation, migration, and phenotype switch of PASMCs. miRNA sequencing analysis of the genetic cargo of MSC-NVs revealed that miR-125b-5p and miR-100-5p are highly abundant, suggesting they might account for the therapeutic effects of MSC-NVs in PH. Depletion of miR-125b-5p and miR-100-5p in MSCs almost completely abolished the beneficial effects of MSC-NVs in protecting PASMCs from PDGF stimulated changes in vitro, and also diminished the protective effects of MSC-NVs in MCT induced PH in vivo. These data highlight the efficacy and advantages of MSC-NVs over MSC-EVs as a promising therapeutic strategy against PH.

2.
Sci Total Environ ; 836: 155618, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35513150

RESUMO

Little evidence is available regarding the impact of different sizes of inhaled particulate matter (PM) on inflammatory responses in healthy young adults in connection with toxicological responses. We conducted a five-time repeated measurement panel study on 88 healthy young college students in Guangzhou, China from December 2017 to January 2018. Blood samples were collected from each participant and tested for tumor necrosis factor alpha (TNF-α) levels every week for 5 consecutive weeks. Mass concentrations of ambient PM2.5, PM1, PM0.5 and number concentrations of ambient PM0.1 were measured. RAW 264.7 macrophages were exposed to PM (PM10-2.5, PM2.5-1, PM1-0.2, PM0.2) collected at the same time as the panel study. Cytotoxicity, oxidation and inflammatory parameters, cell cycle and genotoxicity were tested. Particles were characterized for their chemical composition. The trends of associations between PM2.5, PM1, PM0.5 and TNF-α level were consistent in lag 0 and 3 days, and the relative risk decreased as the particle size decreased. All the ambient air pollutants had the similar change trends in lag 1, 4 and 5 days. Similar results in RAW 264.7 macrophages were found; PM10-2.5 induced the greatest TNF-α and macrophage inflammatory protein 2 (MIP-2) productions and oxidative damage. PM1-0.2 and PM0.2 induced more significant dose-dependent increases of cell cycle and genotoxic response. In the component concentrations of PM samples, metal elements were PM10-2.5 > PM2.5-1 > PM0.2 ≥ PM1-0.2; ions and polycyclic aromatic hydrocarbons (PAHs) were PM0.2 > PM1-0.2 > PM2.5-1 > PM10-2.5. Our results suggested that exposure to all particle sizes was significantly associated with inflammation among healthy young adults and toxicological responses in RAW 264.7 macrophages. Different human and toxicological reactions caused by PM samples indicated the importance of investigating various particle sizes.

3.
Mol Ther ; 2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35570396

RESUMO

Bispecific T-cell engagers (BiTEs) are bispecific antibodies that redirect T cells to target antigen-expressing tumors. We hypothesized that BiTE-secreting T cells could be a valuable therapy in solid tumors, with distinct properties in mono- or multi-valent strategies incorporating chimeric antigen receptor (CAR) T cells. Glioblastomas represent a good model for solid tumor heterogeneity, representing a significant therapeutic challenge. We detected expression of tumor-associated epidermal growth factor receptor (EGFR), EGFR variant III (EGFRvIII), and interleukin-13 receptor alpha 2 (IL13Rα2) on glioma tissues and cancer stem cells. These antigens formed the basis of a multivalent approach, using a conformation-specific tumor-related EGFR targeting antibody (806) and Hu08, an IL13Rα2-targeting antibody, as the scFvs to generate new BiTE molecules. Compared with CAR T cells, BiTE T cells demonstrated prominent activation, cytokine production, and cytotoxicity in response to target-positive gliomas. Superior response activity was also demonstrated in BiTE secreting bivalent T cells compared with bivalent CAR T cells in a glioma mouse model at early phase, but not in the long-term. In summary, BiTEs secreted by mono- or multi- valent T cells have potent anti-tumor activity in vitro and in vivo with significant sensitivity and specificity, demonstrating a promising strategy in solid tumor therapy.

4.
ACS Omega ; 7(17): 15247-15257, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35572754

RESUMO

Traditional electric cooling in summer and coal heating in winter consume a huge amount of energy and lead to a greenhouse effect. Herein, we developed an energy-free dual-mode superhydrophobic film, which consists of a white side with porous coating of styrene-ethylene-butylene-styrene/SiO2 for radiative cooling and a black side with nanocomposite coating of carbon nanotubes/polydimethylsiloxane for solar heating. In the cooling mode with the white side, the film achieved a high sunlight reflection of 94% and a strong long-wave infrared emission of 92% in the range of 8-13 µm to contribute to a temperature drop of ∼11 °C. In the heating mode with the black side, the film achieved a high solar absorption of 98% to induce heating to raise the air temperature beneath by ΔT of ∼35.6 °C. Importantly, both sides of the film are superhydrophobic with a contact angle over 165° and a sliding angle near 0°, showing typical self-cleaning effects, which defend the surfaces from outdoor contamination, thus conducive to long-term cooling and heating. This dual-mode film shows great potential in outdoor applications as coverings for both cooling in hot summer and heating in winter without an energy input.

5.
JAMA Netw Open ; 5(5): e2213247, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35594042

RESUMO

Importance: Healthy sleep has an important role in the physical and mental health of children. However, few studies have investigated the association between outdoor artificial light at night (ALAN) and sleep disorders in children. Objective: To explore the associations between outdoor ALAN exposure and sleep disorders in children. Design, Setting, and Participants: This population-based cross-sectional study, part of the National Chinese Children Health Study, was conducted from April 1, 2012, to June 30, 2013, in the first stage and from May 1, 2016, to May 31, 2018, in the second stage in 55 districts of 14 cities in China. This analysis included 201 994 children and adolescents aged 2 to 18 years. Data were analyzed from February 20 to March 21, 2022. Exposures: Outdoor ALAN exposure (in nanowatts per centimeters squared per steradian) within 500 m of each participant's residential address obtained from the satellite imagery data, with a resolution of approximately 500 m. Main Outcomes and Measures: Sleep disorders were measured by the Chinese version of the Sleep Disturbance Scale for Children. Generalized linear mixed models were used to estimate the associations of outdoor ALAN with sleep scores and sleep disorders. Results: The study included 201 994 children and adolescents (mean [SD] age, 11.3 [3.2] years; 106 378 boys [52.7%]), 7166 (3.5%) of whom had sleep disorder symptoms. Outdoor ALAN exposure of study participants ranged from 0.02 to 113.48 nW/cm2/sr. Compared with the lowest quintile (Q1) of outdoor ALAN exposure, higher quintiles of exposure (Q2-Q5) were associated with an increase in total sleep scores of 0.81 (95% CI, 0.66-0.96) in Q2, 0.83 (95% CI, 0.68-0.97) in Q3, 0.62 (95% CI, 0.46-0.77) in Q4, and 0.53 (95% CI, 0.36-0.70) in Q5. Higher quintiles of exposure were also associated with odds ratios for sleep disorder of 1.34 (95% CI, 1.23-1.45) in Q2, 1.43 (95% CI, 1.32-1.55) in Q3, 1.31 (95% CI, 1.21-1.43) in Q4, and 1.25 (95% CI, 1.14-1.38) in Q5. Similar associations were observed for sleep disorder subtypes. In addition, greater effect estimates were found among children younger than 12 years. Conclusions and Relevance: The findings of this cross-sectional study suggest that sleep disorders are more prevalent among children residing in areas with high levels of outdoor ALAN and the associations are generally stronger in children younger than 12 years. These findings further suggest that effective control of outdoor ALAN may be an important measure for improving the quality of children's sleep.


Assuntos
Transtornos do Sono-Vigília , Adolescente , Criança , China/epidemiologia , Estudos Transversais , Humanos , Masculino , Sono , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/etiologia
6.
Anal Chim Acta ; 1208: 339778, 2022 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-35525599

RESUMO

With the emergence of microRNAs as key biomarkers for disease diagnosis such as lung cancer, various techniques have been settled for their detection. However, these current methods require different amplification steps since numerous challenges for detecting circulating miRNAs are attributable to their intrinsic properties accounting for tiny sizes, high sequence similarity, and low abundance. Duplex specific nuclease (DSN)-based microRNA amplification has recently gained interest in biosensing applications thanks to its catalytic activity based on target recycling. In this context, we designed a highly selective, sensitive, and multiplexed fluorescence-based biosensor combining DSN enzyme and magnetic beads to detect three distinct microRNAs, including microRNA-21, microRNA-210, and microRNA-486-5p. By exploiting the above approach, we were able to detect as low as 98 aM, 120 aM, and 300 aM of mir-21, miR-210, and miR-486-5p, respectively. Furthermore, this recommended strategy displays a high selectivity toward an entirely matched target than the off-target. These results are ascribed to the potent DSN enzyme activity and to the locked nucleic acid (LNA)-modified DNA probe that boosted the hetero-duplex probe/target stability. Lastly, our proposed method was applied to detect microRNAs in the serum samples and displayed a high efficacy to discriminate between healthy controls and lung cancer patients. Furthermore, the analytical accuracy of the proposed strategy was validated with the computed tomography (CT) technique of the chest. Thus based on these findings, this strategy could open new directions for detecting microRNAs associated with several diseases.


Assuntos
Técnicas Biossensoriais , Neoplasias Pulmonares , MicroRNAs , Técnicas Biossensoriais/métodos , Sondas de DNA/genética , Endonucleases , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , MicroRNAs/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Oligonucleotídeos
7.
Transl Neurodegener ; 11(1): 27, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35527277

RESUMO

BACKGROUND: Intracellular accumulation of the microtubule-associated protein tau and its hyperphosphorylated forms is a key neuropathological feature of Alzheimer's disease (AD). Melatonin has been shown to prevent tau hyperphosphorylation in cellular and animal models. However, the molecular mechanisms by which melatonin attenuates tau hyperphosphorylation and tau-related pathologies are not fully understood. METHODS: Immunofluorescence, immunoblotting analysis and thioflavin-S staining were employed to examine the effects of early and late treatment of melatonin on tau-related pathology in hTau mice, in which nonmutated human tau is overexpressed on a mouse tau knockout background. High-throughput microRNA (miRNA) sequencing, quantitative RT-PCR, luciferase reporter assay and immunoblotting analysis were performed to determine the molecular mechanism. RESULTS: We found that both early and late treatment of melatonin efficiently decreased the phosphorylation of soluble and insoluble tau at sites related to AD. Moreover, melatonin significantly reduced the number of neurofibrillary tangles (NFTs) and attenuated neuronal loss in the cortex and hippocampus. Furthermore, using miRNA microarray analysis, we found that miR-504-3p expression was upregulated by melatonin in the hTau mice. The administration of miR-504-3p mimics dramatically decreased tau phosphorylation by targeting p39, an activator of the well-known tau kinase cyclin-dependent kinase 5 (CDK5). Compared with miR-504-3p mimics alone, co-treatment with miR-504-3p mimics and p39 failed to reduce tau hyperphosphorylation. CONCLUSIONS: Our results suggest for the first time that melatonin alleviates tau-related pathologies through upregulation of miR-504-3p expression by targeting the p39/CDK5 axis and provide novel insights into AD treatment strategies.


Assuntos
Doença de Alzheimer , Quinase 5 Dependente de Ciclina , Melatonina , MicroRNAs , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Animais , Quinase 5 Dependente de Ciclina/genética , Melatonina/farmacologia , Camundongos , MicroRNAs/genética , Emaranhados Neurofibrilares/metabolismo
8.
Sci Total Environ ; : 155705, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35523323

RESUMO

Landfill sites have been regarded as a significant source of chemicals of emerging concern (CECs) in groundwater. However, our understanding about the compositions of CECs in landfill leachate and adjacent groundwater is still very limited. Here we investigated the CECs in landfill leachates and groundwater of Guangzhou in South China by target, suspect and non-target analysis using high-resolution mass spectrometry (HRMS). A variety of CECs (n = 242), including pharmaceuticals (n = 64), pharmaceutical intermediates (n = 18), personal care products (n = 9), food additives (n = 18), industrial chemicals (n = 82, e.g., flame retardants, plasticizers, antioxidants and catalysts), pesticides (n = 26), transformation products (n = 8) and other organic compounds (n = 17) were (tentatively) identified by non-target and suspect screening. 142 CECs were quantitated with target analysis, and among them 37, 24 and 27 CECs were detected respectively in the raw leachate (272-1780 µg/L), treated leachate (0.25-0.81 µg/L) and groundwater (0.10-53.7 µg/L). The CECs in the raw leachates were efficiently removed with the removal efficiencies greater than 88.7%. Acesulfame, bisphenol F and ketoprofen were the most abundant compounds in both treated leachate and groundwater. The CECs in groundwater was found most likely to be originated from the landfill sites. Our results highlight the importance of non-target screening in identifying CECs, and reveal the contamination risk of groundwater by landfill leachate.

10.
Plants (Basel) ; 11(9)2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35567270

RESUMO

Chitinase (EC 3.2.1.14) is a kind of chitin-degrading glycosidase, which plays important roles in the abiotic and biotic defense of plants. In this study, we conducted whole-genome annotation, molecular evolution, and gene expression analyses on the chitinase-like (CTL) gene family members of Petunia axillaris. Thirty-three Petunia axillarischitinase-like genes (PaCTLs) were identified from the latest Petunia genome database. According to the phylogenetic analyses, these genes were divided into GH18 and GH19 subgroups and further subdivided into five classes (Class I to Class V). Conserved motif arrangements indicated their functional relevance within each group. The expansion and homeology analyses showed that gene replication events played an important role in the evolution of PaCTLs and the increase of the GH18 subgroup members was the main reason for the expansion of the PaCTL gene family in the evolution progress. By qRT-PCR analysis, we found that most of the PaCTLs showed a very low expression level in the normal growing plants. But lots of PaCTLs showed upregulated expression profiles when the plants suffered different abiotic stress conditions. Among them, five PaCTLs responded to high temperature and exhibited significantly upregulate expression level. Correspondingly, many hormone responses, as well as biotic and abiotic stress elements were found in the promoters of PaCTLs by using cis-acting element analysis. These results provide a foundation for the exploration of PaCTLs' function and enrich the evolutionary process of the CTL gene family.

11.
BMC Surg ; 22(1): 186, 2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35568886

RESUMO

BACKGROUNDS: High level of anion gap (AG) was associated with organic acidosis. This study aimed to explore the relationship between delta AG (ΔAG = AGmax - AGmin) during first 3 days after intensive care unit (ICU) admission and hospital mortality for patients admitted in the cardiothoracic surgery recovery unit (CSRU). METHODS: In this retrospective cohort study, we identified patients from the open access database called Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC III). A logistic regression model was established to predict hospital mortality by adjusting confounding factors using a stepwise backward elimination method. We conducted receiver operating characteristic (ROC) curves to compare the diagnostic performance of acid-base variables. Cox regression model and Kaplan Meier curve were applied to predict patients' 90-day overall survival (OS). RESULTS: A total of 2,860 patients were identified. ΔAG was an independent predictive factor of hospital mortality (OR = 1.24 per 1 mEq/L increase, 95% CI: 1.11-1.39, p < 0.001). The area under curve (AUC) values of ΔAG suggested a good diagnostic accuracy (AUC = 0.769). We established the following formula to estimate patients' hospital mortality: Logit(P) = - 15.69 + 0.21ΔAG + 0.13age-0.21BE + 2.69AKF. After calculating Youden index, patients with ΔAG ≥ 7 was considered at high risk (OR = 4.23, 95% CI: 1.22-14.63, p = 0.023). Kaplan Meier curve demonstrated that patients with ΔAG ≥ 7 had a poorer 90-day OS (Adjusted HR = 3.20, 95% CI: 1.81-5.65, p < 0.001). CONCLUSION: ΔAG is a prognostic factor of hospital mortality and 90-day OS. More prospective studies are needed to verify and update our findings.

12.
Redox Biol ; 53: 102326, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35525025

RESUMO

The nonunion following a fracture is associated with severe patient morbidity and economic consequences. Currently, accumulating studies are focusing on the importance of macrophages during fracture repair. However, details regarding the process by which macrophages facilitate endochondral ossification (EO) are largely unknown. In this study, we present evidence that apoptotic chondrocytes (ACs) are not inert corpses awaiting removal, but positively modulate the osteoinductive ability of macrophages. In vivo experiments revealed that fatty acid (FA) metabolic processes up-regulated following EO. In vitro studies further uncovered that FAs derived from ACs are taken up by macrophages mainly through macrophage scavenger receptor 1 (MSR1). Then, our functional experiments confirmed that these exogenous FAs subsequently activate peroxisome proliferator-activated receptor α (PPARα), which further facilitates lipid droplets generation and fatty acid oxidation (FAO). Mechanistically, elevated FAO is involved in up-regulating the osteoinductive effect by generating BMP7 and NAD+/SIRT1/EZH2 axis epigenetically controls BMP7 expression in macrophages cultured with ACs culture medium. Our findings advanced the concept that ACs could promote bone regeneration by regulating metabolic and function reprogram in macrophages and identified macrophage MSR1 represents a valuable target for fracture treatments.

13.
EBioMedicine ; 80: 104050, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35561453

RESUMO

BACKGROUND: Cancer elicits a complex adaptive response in an organism. Limited information is available for the body-wide effects induced by cancer. Here, we evaluated multiorgan changes in mouse models of pancreatic ductal adenocarcinoma (PDAC) and its precursor lesions (pancreatic intraepithelial neoplasia, PanIN) to decipher changes that occur during PDAC development. METHODS: RNA-sequencing was employed in the brain, colon, stomach, kidney, heart, liver, and lung tissues of mice with PanIN and PDAC. A combination of differential expression analysis and functional-category enrichment was applied for an in-depth understanding of the multiorgan transcriptome. Differentially expressed genes were verified by quantitative real-time polymerase chain reaction. Neutrophil and macrophage infiltration in multiple organs was analyzed by immunohistochemical staining. Leukotriene B4 (LTB4) levels in mouse and human serum samples were determined by enzyme-linked immunosorbent assay. FINDINGS: Transcriptional changes within diverse organs during PanIN and PDAC stages were identified. Using Gene Ontology enrichment analysis, increased neutrophil infiltration was discovered as a central and prominent affected feature, which occurred in the liver, lung, and stomach at the PanIN stage. The brain appeared to be well protected from the sequels of PanIN or PDAC. Importantly, serum LTB4 was able to discriminate PDAC from normal controls, chronic pancreatitis, and intraductal papillary mucinous neoplasms with high performance. INTERPRETATION: Our study provides a high-resolution cartographic view of the dynamic multiorgan transcriptomic landscape of mice with PDAC and its precursor lesions. Our findings suggest that LTB4 could serve as a biomarker for the early detection of PDAC. FUNDING: The complete list of funders can be found in the Acknowledgement section.

14.
J Toxicol Pathol ; 35(2): 193-203, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35516842

RESUMO

Liver fibrosis results from liver inflammation and progresses to liver cirrhosis or liver cancer. It is known that nonalcoholic liver disease is mediated by the Toll-like receptor 4 (TLR4)/myeloid differentiation factor-2 (MD-2)-tumor necrosis factor-alpha (TNF-α) signaling pathway. This study aimed to investigate whether alcoholic liver disease is also mediated by this pathway. To this end, we first established rat models of liver fibrosis by administering alcohol. Next, the rats were injected with anti-TLR4 and anti-MD-2 antibodies. Real Time Quantitative PCR (RT-qPCR) and Western blotting were used to detect the activation of the TLR4/MD-2-TNF-α signaling pathway and hepatic stellate cells (HSCs). Moreover, the expression of molecules related to liver fibrosis was estimated. The morphology of rat liver tissue was observed through hematoxylin-eosin staining and Masson staining. For in vitro studies, Kupffer cells (KCs) isolated from the liver were transfected with si-TLR4 and si-MD-2 and co-cultured with HSCs to determine the activity of HSCs. It was found that alcohol treatment activated the TLR4/MD-2-TNF-α signaling pathway and upregulated the molecules associated with liver fibrosis. However, inhibition of TLR4 and MD-2 partially reversed this trend. Notably, in vitro studies indicated that knockdown of TLR4 and MD-2 in KCs partially inhibited LPS-induced activation of KCs and HSCs. Overall, this study showed that alcohol induces liver fibrosis via the LPS-TLR4/MD-2-TNF-α signaling pathway.

15.
Brain Res ; 1787: 147923, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35461832

RESUMO

The combined use of two or more different drugs can better promote nerve recovery and its prognosis for treatment of stroke. Salvianolate lyophilized injection (SLI) made from the aqueous extraction of salvia miltiorrhiza and Xueshuantong injection (lyophilized) (XST) made from the Panax Notoginseng extraction are two herbal standardized preparations that have been widely used in China for the treatment of ischemic stroke. In this study, we investigated the neuroprotective effects of XST combined with SLI in the recovery stage of middle cerebral artery occlusion / reperfusion (MCAO/R) injury rat. Wistar rats were subjects to MCAO/R, then were treated with SLI or XST alone, or with their combination (1X1S) via tail injection daily for 14 days. The pathological status of the brain was detected by neurological deficit scores, TTC, regional cerebral blood flow and Nissl staining. Golgi-Cox staining was used to assess dendritic, axonal and synaptic remodeling. The expression of MAP-2, ß-Tubulin, PSD95, SYN, BDNF and VEGF were analyzed by western blotting and immunofluorescence. The results showed that administration of 1X1S not only significantly decreased neurological scores and infarct volumes, but also increased regional cerebral blood flow, strengthened dendritic and synaptic remodeling compared with XST, SLI used alone. And the mechanism of combined of 1X1S to exert neuroprotection may be associated with PI3K/ AKT/ mTOR and RhoA/ROCK2 pathways. Overall, these findings suggest that combination of XST and SLI promotes dendritic spine density and synaptic plasticity via upregulation of the PI3K/ AKT/ mTOR pathways and inhabitation the RhoA/ROCK2 signaling pathway in rat with MCAO/R, showing its multiple-action-multiple-target efficacy and suggest a potential new strategy for ischemia.

16.
J Neural Eng ; 19(3)2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35472693

RESUMO

Objective.The investigation of neurophysiologic mechanisms of anesthetic drug-induced loss of consciousness (LOC) by using the entropy, complexity, and information integration theories at the mesoscopic level has been a hot topic in recent years. However, systematic research is still lacking.Approach.We analyzed electrocorticography (ECoG) data recorded from nine rats during isoflurane-induced unconsciousness. To characterize the complexity and connectivity changes, we investigated ECoG power, symbolic dynamic-based entropy (i.e. permutation entropy (PE)), complexity (i.e. permutation Lempel-Ziv complexity (PLZC)), information integration (i.e. permutation cross mutual information (PCMI)), and PCMI-based cortical brain networks in the frontal, parietal, and occipital cortical regions.Main results.Firstly, LOC was accompanied by a raised power in the ECoG beta (12-30 Hz) but a decreased power in the high gamma (55-95 Hz) frequency band in all three brain regions. Secondly, PE and PLZC showed similar change trends in the lower frequency band (0.1-45 Hz), declining after LOC (p< 0.05) and increasing after recovery of consciousness (p< 0.001). Thirdly, intra-frontal and inter-frontal-parietal PCMI declined after LOC, in both lower (0.1-45 Hz) and higher frequency bands (55-95 Hz) (p< 0.001). Finally, the local network parameters of the nodal clustering coefficient and nodal efficiency in the frontal region decreased after LOC, in both the lower and higher frequency bands (p< 0.05). Moreover, global network parameters of the normalized average clustering coefficient and small world index increased slightly after LOC in the lower frequency band. However, this increase was not statistically significant.Significance. The PE, PLZC, PCMI and PCMI-based brain networks are effective metrics for qualifying the effects of isoflurane.

17.
Inflammation ; 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35474551

RESUMO

Gastrodin is a major active phenolic glycoside extract from Gastrodia elata, an important herb used in traditional medicine. Previous research has reported that gastrodin possesses anti-inflammatory and anti-oxidant properties. Therefore, we aimed to investigate its hepatoprotective effects and mechanisms on acetaminophen (APAP)-induced liver injury in a mouse model. Mice included in this study were intraperitoneally administered with a hepatotoxic APAP dose (300 mg/kg). At 30 min after APAP administration, gastrodin was intraperitoneally injected at concentrations of 0, 15, 30, and 45 mg/kg. Then, all mice were sacrificed at 16 h after APAP injection for further analysis. The results showed that gastrodin treatment ameliorated acute liver injury caused by APAP, as indicated by serum alanine aminotransferase level, hepatic myeloperoxidase activity, and cytokine (TNF-α, IL-1ß, and IL-6) production. It also significantly decreased hepatic malondialdehyde activity but increased superoxide dismutase activity. In addition, gastrodin decreased ERK/JNK MAPK expression but promoted Nrf2 expression. These results demonstrated that gastrodin may be a potential therapeutic target for the prevention of APAP-induced hepatotoxicity via amelioration of the inflammatory response and oxidative stress, inhibition of ERK/JNK MAPK signaling pathways, and activation of Nrf2 expression levels.

18.
J Dermatol ; 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35437858

RESUMO

The exact efficacy of cyclosporine in the treatment of Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) still needs evidence from more clinical data. This study was designed to compare the effectiveness and side-effects of combined use of cyclosporine in the treatment TEN with glucocorticoids (GC)/i.v. immunoglobulin G (IVIG). A total of 46 patients with SJS/TEN were enrolled and classified into two groups based on the therapeutic drugs used. Clinical characteristics, interventions, outcomes, and disease progressions were collected and compared between the two groups. In our cohort, seven patients eventually died and the overall fatality rate was 15.2%, but there was no difference between the two groups (p = 0.557). On discharge, the median SCORe of Toxic Epidermal Necrosis (SCORTEN) fell from 2.0 at admission to 1.0 and the median body surface area detached fell from 32.0% at admission to 9.5%. Patients in the cyclosporine group had a higher rate of re-epithelialized area than patients in the non-cyclosporine group (p < 0.05). Cyclosporine significantly reduced the length of stay (19.0 vs. 13.0 days, p = 0.019) and the rate of systemic infection (71.4% vs. 36.0%, p = 0.017) compared with the non-cyclosporine group. SCORTEN was the only significant risk factor for death and the risk ratio was 1.96 (1.17-3.31, p = 0.011). Conclusively, the combined use of cyclosporine could reduce the occurrence of systemic infection and accelerate the re-epithelialization.

19.
NPJ Breast Cancer ; 8(1): 52, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35449176

RESUMO

The prevalence and clinical relevance of pathogenic germline variants in MMR genes have not been investigated in large series of breast cancers. In this study, we screened the germline variants in MMR genes in 8085 consecutive Chinese breast cancer patients, and investigated the MMR/PD-L1 protein expression and tumor mutation burden (TMB) of breast tumors from MMR variant carriers. We found that 15 of 8085 patients (0.19%) carried a pathogenic germline variant in MMR genes. Compared with non-carriers, MMR variant carriers might have worse recurrence-free survival (unadjusted hazard ratios [HR] = 2.70, 95% CI: 1.12-6.49, P = 0.027) and distant recurrence-free survival (unadjusted HR = 3.24, 95% CI: 1.45-7.22, P = 0.004). More importantly, some of the breast cancers from MMR carriers displayed MMR protein loss (5/13), TMB-high (2/10), and PD-L1 positive expression (9/13). This study showed that MMR variant carriers were rare in breast cancer. They might have worse survival and part of them might benefit from immunotherapy.

20.
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