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1.
Sheng Wu Gong Cheng Xue Bao ; 40(4): 1120-1137, 2024 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-38658153

RESUMO

The leaves and roots of Liriope muscari (Decne.) Baily were subjected to high-throughput Illumina transcriptome sequencing. Bioinformatics analysis was used to investigate the enzyme genes and key transcription factors involved in regulating the accumulation of steroidal saponins, which are the main active ingredient in L. muscari. These analyses aimed to reveal the molecular mechanism behind steroidal saponin accumulation. The sequencing results of L. muscari revealed 31 enzymes, including AACT, CAS, DXS and DXR, that are involved in the synthesis of steroidal saponins. Among these enzymes, 16 were in the synthesis of terpenoid skeleton, 3 were involved in the synthesis of sesquiterpene and triterpene, and 12 were involved in the synthesis of steroidal compound. Differential gene expression identified 15 metabolic enzymes coded by 34 differentially expressed genes (DEGs) in the leaves and roots, which were associated with steroidal saponin synthesis. Further analysis using gene co-expression patterns showed that 14 metabolic enzymes coded by 31 DEGs were co-expressed. In addition, analysis using gene co-expression analysis and PlantTFDB's transcription factor analysis tool predicted the involvement of 8 transcription factors, including GAI, PIF4, PIL6, ERF8, SVP, LHCA4, NF-YB3 and DOF2.4, in regulating 6 metabolic enzymes such as DXS, DXR, HMGR, DHCR7, DHCR24, and CAS. These eight transcription factors were predicted to play important roles in regulating steroidal saponin accumulation in L. muscari. Promoter analysis of these transcription factors indicated that their main regulatory mechanisms involve processes such as abscisic acid response, drought-induction stress response and light response, especially abscisic acid responsive elements (ABRE) response and MYB binding site involved in drought-inducibility (MBS) response pathway. Furthermore, qRT-PCR analysis of these eight key transcription factors demonstrated their specific differences in the leaves and roots.


Assuntos
Biologia Computacional , Liriope (Planta) , Folhas de Planta , Saponinas , Fatores de Transcrição , Transcriptoma , Saponinas/metabolismo , Saponinas/biossíntese , Biologia Computacional/métodos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Folhas de Planta/metabolismo , Folhas de Planta/genética , Liriope (Planta)/genética , Liriope (Planta)/metabolismo , Esteroides/metabolismo , Esteroides/biossíntese , Raízes de Plantas/metabolismo , Raízes de Plantas/genética , Regulação da Expressão Gênica de Plantas , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala
3.
Int J Mol Sci ; 24(19)2023 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-37834448

RESUMO

The WRKY transcription factor (TF) family is one the largest plant-specific transcription factor families. It has been proven to play significant roles in multiple plant biological processes, especially stress response. Although many WRKY TFs have been identified in various plant species, WRKYs in white birch (Betula platyphylla Suk.) remain to be studied. Here, we identified a total of 68 BpWRKYs, which could be classified into four main groups. The basic physiochemical properties of these TFs were analyzed using bioinformatics tools, including molecular weight, isoelectric point, chromosome location, and predicted subcellular localization. Most BpWRKYs were predicted to be located in the nucleus. Synteny analysis found 17 syntenic gene pairs among BpWRKYs and 52 syntenic gene pairs between BpWRKYs and AtWRKYs. The cis-acting elements in the promoters of BpWRKYs could be enriched in multiple plant biological processes, including stress response, hormone response, growth and development, and binding sites. Tissue-specific expression analysis using qRT-PCR showed that most BpWRKYs exhibited highest expression levels in the root. After ABA, salt (NaCl), or cold treatment, different BpWRKYs showed different expression patterns at different treatment times. Furthermore, the results of the Y2H assay proved the interaction between BpWRKY17 and a cold-responsive TF, BpCBF7. By transient expression assay, BpWRKY17 and BpWRKY67 were localized in the nucleus, consistent with the previous prediction. Our study hopes to shed light for research on WRKY TFs and plant stress response.


Assuntos
Proteínas de Plantas , Fatores de Transcrição , Fatores de Transcrição/metabolismo , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética , Betula/genética , Betula/metabolismo , Regulação da Expressão Gênica de Plantas , Filogenia
4.
Int Arch Allergy Immunol ; 184(11): 1099-1105, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37598674

RESUMO

INTRODUCTION: Small airway dysfunction (SAD) is associated with type 2 inflammation in patients who have non-asthmatic chronic rhinosinusitis with nasal polyps (CRSwNPs); however, the risk factors for abnormal small airway function indicators in CRSwNP patients with and without asthma remain unclear. METHODS: We retrospectively analyzed 41 asthmatic and 109 non-asthmatic CRSwNP patients. Clinical characteristics were compared between groups, correlations between small airway function and clinical parameters were calculated, and independent risk factors for every small airway indicator were identified in each group. RESULTS: Asthmatic CRSwNP patients had significantly reduced small airway function, and the proportion of patients with SAD was higher in asthmatic CRSwNP patients (65.85%) than in patients without asthma (9.17%). With regard to specific airway function indicators, age and a patient's blood eosinophil (%) were identified as independent risk factors for lower FEF50% %pred and FEF25-75% pred, with age being an independent risk factor for FEF75% %pred in asthmatic CRSwNP patients. In non-asthmatic CRSwNP patients, allergic rhinitis comorbidity was found to be an independent risk factor for FEF50% %pred, FEF75% %pred, and FEF25-75% %pred. CONCLUSION: Physicians should pay greater attention to risk factors for abnormal small airway function indicators in patients with CRSwNPs to prevent the occurrence of SAD.


Assuntos
Asma , Pólipos Nasais , Rinite , Sinusite , Humanos , Pólipos Nasais/complicações , Pólipos Nasais/epidemiologia , Estudos Retrospectivos , Rinite/complicações , Rinite/epidemiologia , Asma/complicações , Asma/epidemiologia , Sinusite/complicações , Sinusite/epidemiologia , Fatores de Risco , Doença Crônica
5.
Allergy Asthma Proc ; 44(4): 252-257, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37480201

RESUMO

Background: Allergic asthma accounts for the majority of childhood asthma and is characterized by elevated total serum immunoglobulin E (tIgE). However, whether tIgE can predict allergic asthma in childhood asthma remains unclear. Objective: The purpose of this study was to identify the potential of tIgE for predicting allergic asthma in childhood asthma and provide a reliable reference value. Methods: Clinical characteristics and the level of tIgE from children with asthma in 2008 (n = 280) and 2018 (n = 479) were retrospectively analyzed. Receiver operating characteristic (ROC) curves were generated to determine the optimal cutoff points and predictive values of tIgE for diagnosing allergic asthma in childhood asthma in 2008 and 2018, and the diagnosis efficiency of tIgE was validated in 491 children with asthma of 2019. Results: The level of tIgE was significantly lower in 2018 than that in 2008. Receiver operating characteristic curves showed cutoff values of tIgE were 142.50 IU/mL (area under the curve [AUC] = 0.864) and 96.25 IU/mL (AUC = 0.835) for diagnosing allergic asthma in 2008 and 2018, respectively. The level of tIgE from children with asthma in 2019 was similar to that in 2018 but was significantly lower than that in 2008. We further used the cutoff value of tIgE = 96.25 IU/mL to validate the diagnosis efficiency in children with asthma of 2019 and found that the diagnostic accuracy, sensitivity, specificity of allergic asthma, and the Youden index reached 76.78%, 76.10%, 78.03%, and 0.540, respectively. Conclusion: The tIgE value is an effective predictor for diagnosing allergic asthma in childhood asthma, with tIgE = 96.25 IU/mL being the recommended limit.


Assuntos
Asma , Criança , Humanos , Estudos Retrospectivos , Asma/diagnóstico , Imunoglobulina E , Curva ROC , Valores de Referência
6.
Ear Nose Throat J ; : 1455613231179692, 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37291873

RESUMO

Background: We describe a patient with sinonasal mucosal melanoma (SNMM) and an inverted papilloma, which existed independently in both nasal cavities. Case presentation: We describe an unusual case of a 74-year-old male patient with SNMM and an inverted papilloma. He presented with symptoms of coughing up blood and pain in the left forehead. The patient underwent surgical resection of the lesion, and the SNMM and inverted papilloma were confirmed by histopathology. The patient refused further treatment after surgery, but was re-admitted 7 months later with local recurrence of the left tumor and systemic metastases. Conclusions: Nasal malignant melanoma with an inverted papilloma in the contralateral nasal cavity is rare and can easily be misdiagnosed as the same tumor by imaging. Simultaneous histopathology of bilateral nasal masses is very necessary. The recommended treatment is surgery for the inverted papilloma. An SNMM is a devastating tumor with poor outcomes.

7.
Angew Chem Int Ed Engl ; 62(27): e202305485, 2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-37138171

RESUMO

Biofilm formation is a major threat to industry, the environment and human health. While killing of embedded microbes in biofilms may inevitably lead to the evolution of antimicrobial resistance (AMR), catalytic quenching of bacterial communications by lactonase is a promising antifouling approach. Given the shortcomings of protein enzymes, it is attractive to engineer synthetic materials to mimic the activity of lactonase. Herein, an efficient lactonase-like Zn-Nx -C nanomaterial was synthesized by tuning the coordination environment around zinc atoms to mimic the active domain of lactonase for catalytical interception of bacterial communications in biofilm formation. The Zn-Nx -C material could selectively catalyze 77.5 % hydrolysis of N-acylated-L-homoserine lactone (AHL), a critical bacterial quorum sensing (QS) signal in biofilm construction. Consequently, AHL degradation downregulated the expression of QS-related genes in antibiotic resistant bacteria and significantly prevented biofilm formation. As a proof of concept, Zn-Nx -C-coated iron plates prevented 80.3 % biofouling after a month exposure in river. Overall, our study provides a nano-enabled contactless antifouling insight to avoid AMR evolution by engineering nanomaterials for mimicking the key bacterial enzymes (e.g., lactonase) functioning in biofilm construction.


Assuntos
Biofilmes , Percepção de Quorum , Humanos , Bactérias/metabolismo , Acil-Butirolactonas/metabolismo , Proteínas de Bactérias/metabolismo
8.
iScience ; 26(5): 106758, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37216118

RESUMO

Inflammation driven by DNA sensors is now understood to be important to disease pathogenesis. Here, we describe new inhibitors of DNA sensing, primarily of the inflammasome forming sensor AIM2. Biochemistry and molecular modeling has revealed 4-sulfonic calixarenes as potent inhibitors of AIM2 that likely work by binding competitively to the DNA-binding HIN domain. Although less potent, these AIM2 inhibitors also inhibit DNA sensors cGAS and TLR9 demonstrating a broad utility against DNA-driven inflammatory responses. The 4-sulfonic calixarenes inhibited AIM2-dependent post-stroke T cell death, highlighting a proof of concept that the 4-sulfonic calixarenes could be effective at combating post-stroke immunosuppression. By extension, we propose a broad utility against DNA-driven inflammation in disease. Finally, we reveal that the drug suramin, by virtue of its structural similarities, is an inhibitor of DNA-dependent inflammation and propose that suramin could be rapidly repurposed to meet an increasing clinical need.

9.
Anal Chem ; 95(14): 6009-6019, 2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-37005435

RESUMO

Fine particulates (FPs) are a major class of airborne pollutants. In mammals, FPs may reach the alveoli through the respiratory system, cross the air-blood barrier, spread into other organs, and induce hazardous effects. Although birds have much higher respiratory risks to FPs than mammals, the biological fate of inhaled FPs in birds has rarely been explored. Herein, we attempted to disclose the key properties that dictate the lung penetration of nanoparticles (NPs) by visualizing a library of 27 fluorescent nanoparticles (FNPs) in chicken embryos. The FNP library was prepared by combinational chemistry to tune their compositions, morphologies, sizes, and surface charges. These NPs were injected into the lungs of chicken embryos for dynamic imaging of their distributions by IVIS Spectrum. FNPs with diameters <16 nm could cross the air-blood barrier in 20 min, spread into the blood, and accumulate in the yolk sac. In contrast, large FNPs (>30 nm) were mainly retained in the lungs and rarely detected in other tissues/organs. In addition to size, surface charge was the secondary determinant for NPs to cross the air-blood barrier. Compared to cationic and anionic particles, neutrally charged FNPs showed the fastest lung penetration. A predictive model was therefore developed to rank the lung penetration capability of FNPs by in silico analysis. The in silico predictions could be well validated in chicks by oropharyngeal exposure to six FNPs. Overall, our study discovered the key properties of NPs that are responsible for their lung penetration and established a predictive model that will greatly facilitate respiratory risk assessments of nanoproducts.


Assuntos
Galinhas , Nanopartículas , Embrião de Galinha , Animais , Barreira Alveolocapilar , Nanopartículas/química , Pulmão , Corantes , Tamanho da Partícula , Mamíferos
10.
Laryngoscope Investig Otolaryngol ; 7(5): 1634-1642, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36258845

RESUMO

Background: Pain management, as a key component of enhanced recovery after surgery (ERAS), can effectively relieve perioperative pain and anxiety. However, there are few studies on the application of pain management based on ERAS in pediatric surgery patients. We aimed to examine the effect of ERAS-based perioperative pain management in children with obstructive sleep apnea (OSA) undergoing adenotonsillectomy. Methods: From March 2021 to July 2021, a randomized controlled single-blind study was conducted on children with OSA and scheduled to undergo adenotonsillectomy. The children were randomly assigned to either control group (n = 60) or ERAS group (n = 60). Traditional analgesia measures were provided to children in the control group, whereas ERAS-based optimized analgesia measures were provided to children in the ERAS group. The pain scores, anxiety scores and diet quality scores were compared between the two groups. Results: The pain scores after surgery in the ERAS group were significantly lower than those in the control group at 6 h, 1 day, 3 days, and 5 days after surgery. Furthermore, the diet quality scores in the ERAS group were significantly higher than those in the control group at 6 h, 1 day, 3 days, and 5 days after surgery. The anxiety scores after surgery in the ERAS group were significantly lower than those in the control group. Conclusions: Perioperative pain management based on ERAS can significantly alleviate postoperative pain, improve quality of life, and promote the accelerated rehabilitation of children with OSA undergoing adenotonsillectomy. Level of evidence: 1.

11.
Natl Sci Rev ; 9(7): nwab232, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35967587

RESUMO

Small-cell lung cancer (SCLC) is a recalcitrant cancer characterized by high metastasis. However, the exact cell type contributing to metastasis remains elusive. Using a Rb1 L/L /Trp53 L/L mouse model, we identify the NCAMhiCD44lo/- subpopulation as the SCLC metastasizing cell (SMC), which is progressively transitioned from the non-metastasizing NCAMloCD44hi cell (non-SMC). Integrative chromatin accessibility and gene expression profiling studies reveal the important role of the SWI/SNF complex, and knockout of its central component, Brg1, significantly inhibits such phenotypic transition and metastasis. Mechanistically, TAZ is silenced by the SWI/SNF complex during SCLC malignant progression, and its knockdown promotes SMC transition and metastasis. Importantly, ectopic TAZ expression reversely drives SMC-to-non-SMC transition and alleviates metastasis. Single-cell RNA-sequencing analyses identify SMC as the dominant subpopulation in human SCLC metastasis, and immunostaining data show a positive correlation between TAZ and patient prognosis. These data uncover high SCLC plasticity and identify TAZ as the key molecular switch in orchestrating SCLC phenotypic transition and metastasis.

12.
Part Fibre Toxicol ; 19(1): 55, 2022 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-35933442

RESUMO

As an emerging pollutant in the life cycle of plastic products, micro/nanoplastics (M/NPs) are increasingly being released into the natural environment. Substantial concerns have been raised regarding the environmental and health impacts of M/NPs. Although diverse M/NPs have been detected in natural environment, most of them display two similar features, i.e.,high surface area and strong binding affinity, which enable extensive interactions between M/NPs and surrounding substances. This results in the formation of coronas, including eco-coronas and bio-coronas, on the plastic surface in different media. In real exposure scenarios, corona formation on M/NPs is inevitable and often displays variable and complex structures. The surface coronas have been found to impact the transportation, uptake, distribution, biotransformation and toxicity of particulates. Different from conventional toxins, packages on M/NPs rather than bare particles are more dangerous. We, therefore, recommend seriously consideration of the role of surface coronas in safety assessments. This review summarizes recent progress on the eco-coronas and bio-coronas of M/NPs, and further discusses the analytical methods to interpret corona structures, highlights the impacts of the corona on toxicity and provides future perspectives.


Assuntos
Poluentes Ambientais , Nanopartículas , Microplásticos , Nanopartículas/toxicidade , Medição de Risco
13.
Front Genet ; 13: 811679, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35711945

RESUMO

LncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) networks are thought to be involved in regulating the development of various inflammatory diseases. Up to now, the mechanism of such a network in allergic rhinitis (AR) remains unclear. In the study, we investigated the differential expression of lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) by performing a microarray analysis of peripheral blood obtained from AR patients and healthy control subjects. StarBase 2.0 was used to predict miRNAs that might interact with various DElncRNAs and DEmRNAs. We constructed a ceRNA network based on potential lncRNA-miRNA-mRNA interactions. The Cluster Profiler R package was used to perform a functional enrichment analysis of the hub-ceRNA, and Molecular Complex Detection (MCODE) was used for further identification of the hub-ceRNA network. The expression levels of genes contained in the hub-ceRNA network were validated by RT-PCR. In total, 247 DEmRNAs and 18 DelncRNAs were aberrantly expressed in the PBMCs of AR patients. A ceRNA network consisting of 3 lncRNAs, 45 miRNAs, and 75 mRNAs was constructed. A GO analysis showed that negative regulation of immune response, response to interferon-beta, and response to interferon-alpha were important terms. A KEGG pathway analysis showed that 75 mRNAs were significantly enriched in "NOD-like receptor signaling pathway" and "tryptophan metabolism". Ultimately, a hub-ceRNA network was constructed based on 1 lncRNA (AC011511.5), 5 miRNAs (hsa-miR-576-5p, hsa-miR-520c-5p, hsa-miR-519b-5p, hsa-miR-519c-5p, and hsa-miR-518d-5p), and 2 mRNAs (ZFP36L1 and SNX27). Following further verification, we found that overexpression of lncRNA AC011511.5 or inhibitor of miR-576-5p upregulated SNX27 expression. The expression of SNX27 in the lncRNA AC011511.5 overexpression & miR-576-5p inhibitor group was not different from that in the miR-576-5p inhibitor group or lncRNA AC011511.5 overexpression group, indicating that overexpression of lncRNA AC011511.5 could not further upregulate the expression of SNX27 in miR-576-5p inhibitor Jurkat cells. This network may provide new insights to search for biomarkers that can be used for the diagnosis and clinical treatment of AR.

14.
ACS Appl Mater Interfaces ; 14(27): 31502-31509, 2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35764924

RESUMO

Black phosphorus/two-dimensional (2D) metal-organic framework (BP@MOF) heterojunctions were synthesized via templated growth of 2D MOF-Fe/Co nanoplatelets on the surface of exfoliated BP nanosheets at room temperature. Because Fe3+ and Co2+ ions were absorbed onto the BP surface through coordination with the lone pair electrons of 2D BP, the BP@MOF heterojunction had an intimate interface with strong interactions. Electrochemical oxygen and hydrogen evolution reactions were studied using BP@MOF as the electrocatalyst. High activity of the overall water splitting in 1.0 M KOH was observed under a current density of 10 mA cm-2. The corresponding overpotentials for HER and OER were as low as 180 and 246 mV, respectively. Meanwhile, the BP@MOF exhibited good environmental stability and long-term electrocatalytic activity for OER and HER, owing to the encapsulation of BP nanosheets by the 2D MOF-Fe/Co. Through this study, a unique hybrid 2D nanomaterial is discovered for the efficient electrolytic splitting of water.

15.
Nat Cancer ; 3(5): 614-628, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35449308

RESUMO

Small cell lung cancer (SCLC) lacks effective treatments to overcome chemoresistance. Here we established multiple human chemoresistant xenograft models through long-term intermittent chemotherapy, mimicking clinically relevant therapeutic settings. We show that chemoresistant SCLC undergoes metabolic reprogramming relying on the mevalonate (MVA)-geranylgeranyl diphosphate (GGPP) pathway, which can be targeted using clinically approved statins. Mechanistically, statins induce oxidative stress accumulation and apoptosis through the GGPP synthase 1 (GGPS1)-RAB7A-autophagy axis. Statin treatment overcomes both intrinsic and acquired SCLC chemoresistance in vivo across different SCLC PDX models bearing high GGPS1 levels. Moreover, we show that GGPS1 expression is negatively associated with survival in patients with SCLC. Finally, we demonstrate that combined statin and chemotherapy treatment resulted in durable responses in three patients with SCLC who relapsed from first-line chemotherapy. Collectively, these data uncover the MVA-GGPP pathway as a metabolic vulnerability in SCLC and identify statins as a potentially effective treatment to overcome chemoresistance.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Linhagem Celular Tumoral , Farnesiltranstransferase/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Ácido Mevalônico/farmacologia , Fosfatos de Poli-Isoprenil , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico
16.
Environ Int ; 164: 107258, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35483183

RESUMO

Potential immune responses resulting from exposure to metal oxide nanoparticles (MeONPs) have been the subject of intensive discussion in the last decade. Despite the extensive use of MeONPs in several applications, their toxic effects on immune cells have rarely been predicted in silico because of the complexity of immune responses and the complicated properties of MeONPs. In the present study, machine learning (ML) methods coupled with high-throughput in vitro bioassays were used to develop models for predicting the toxicity of MeONPs in immune cells. An ML model with a high prediction accuracy (97% and 96% in the training and test sets, respectively) was constructed by resolving the class imbalance problem in training and applying an ensembled algorithm. Further, to verify the model, MeONPs outside the scope of the datasets were selected to examine their cytotoxicity experimentally. The model was validated against independent MeONPs, with an accuracy of 91%. ML methods coupled with intracellular imaging revealed that the toxic ions released in the lysosome were an important determinant of toxicity in immune cells. Furthermore, ζ-potential, electronegativity, and size are crucial factors for predicting nanotoxicity. We believe the established modeling framework will provide useful insights for designing and applying safe nanoparticles and facilitating decision-making for environmental and health protection.


Assuntos
Nanopartículas Metálicas , Óxidos , Lisossomos , Aprendizado de Máquina , Nanopartículas Metálicas/toxicidade , Compostos Orgânicos , Óxidos/toxicidade
17.
STAR Protoc ; 2(4): 100983, 2021 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-34927092

RESUMO

A key observation of tissue injury, such as stroke and burn, is a state of systemic immunosuppression characterized by loss of T cells and rise of infections. Here, we present an in vitro model for cell-cell interactions between innate (macrophages) and adaptive (T cells) immune cells. This protocol facilitates bone marrow-derived macrophages (BMDMs) and splenic T cells in a coculture model. The procedure mimics injury-induced T cell death, which is driven by inflammasome activation in macrophages. For complete details on the use and execution of this protocol, please refer to Roth et al. (2021).


Assuntos
Morte Celular/fisiologia , Técnicas de Cocultura/métodos , Macrófagos/citologia , Modelos Imunológicos , Linfócitos T/citologia , Animais , Feminino , Inflamassomos/imunologia , Inflamassomos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Baço/citologia , Ferimentos e Lesões/imunologia , Ferimentos e Lesões/metabolismo
18.
BMC Pulm Med ; 21(1): 254, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34332562

RESUMO

BACKGROUND: Aspiration pneumonitis is an inflammatory disease of the lungs which is difficult to diagnose accurately. Large-volume aspiration of oropharyngeal or gastric contents is essential for the development of aspiration pneumonitis. The role of cerebrospinal fluid (CSF) rhinorrhea is often underestimated as a rare etiological factor for aspiration in the diagnosis process of aspiration pneumonitis. CASE PRESENTATION: We present a case of a patient with 4 weeks of right-sided watery rhinorrhea accompanied by intermittent postnasal drip and dry cough as the main symptoms. Combined with clinical symptoms, imaging examination of the sinuses, and laboratory examination of nasal secretions, she was initially diagnosed as spontaneous sphenoid sinus meningoencephalocele with CSF rhinorrhea, and intraoperative endoscopic findings and postoperative pathology also confirmed this diagnosis. Her chest computed tomography showed multiple flocculent ground glass density shadows in both lungs on admission. The patient underwent endoscopic resection of meningoencephalocele and repair of skull base defect after she was ruled out of viral pneumonitis. Symptoms of rhinorrhea and dry cough disappeared, and pneumonitis was improved 1 week after surgery and cured 2 months after surgery. Persistent CSF rhinorrhea caused by spontaneous sphenoid sinus meningoencephalocele was eventually found to be a major etiology for aspiration pneumonitis although the absence of typical symptoms and well-defined risk factors for aspiration, such as dysphagia, impaired cough reflex and reflux diseases. CONCLUSIONS: We report a rare case of aspiration pneumonitis caused by spontaneous sphenoid sinus meningoencephalocele with CSF rhinorrhea, which can bring more attention and understanding to the uncommon etiology for aspiration, so as to make more accurate diagnosis of the disease and early surgical treatment.


Assuntos
Rinorreia de Líquido Cefalorraquidiano/complicações , Encefalocele/complicações , Meningocele/complicações , Pneumonia Aspirativa/etiologia , Seio Esfenoidal/patologia , Rinorreia de Líquido Cefalorraquidiano/diagnóstico , Rinorreia de Líquido Cefalorraquidiano/patologia , Rinorreia de Líquido Cefalorraquidiano/cirurgia , Encefalocele/diagnóstico , Encefalocele/cirurgia , Endoscopia , Feminino , Humanos , Pulmão/diagnóstico por imagem , Meningocele/diagnóstico , Meningocele/cirurgia , Pessoa de Meia-Idade , Pneumonia Aspirativa/diagnóstico , Pneumonia Aspirativa/cirurgia , Base do Crânio/diagnóstico por imagem , Base do Crânio/patologia , Base do Crânio/cirurgia , Seio Esfenoidal/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
19.
J Genet Genomics ; 48(7): 640-651, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34167917

RESUMO

Small cell lung cancer (SCLC) is a phenotypically heterogeneous disease with an extremely poor prognosis, which is mainly attributed to the rapid development of resistance to chemotherapy. However, the relation between the growth phenotypes and chemo-resistance of SCLC remains largely unclear. Through comprehensive bioinformatic analyses, we found that the heterogeneity of SCLC phenotype was significantly associated with different sensitivity to chemotherapy. Adherent or semiadherent SCLC cells were enriched with activation of the PI3K/Akt/mTOR pathway and were highly chemoresistant. Mechanistically, activation of the PI3K/Akt/mTOR pathway promotes the phenotypic transition from suspension to adhesion growth pattern and confers SCLC cells with chemo-resistance. Such chemo-resistance could be largely overcome by combining chemotherapy with PI3K/Akt/mTOR pathway inhibitors. Our findings support that the PI3K/Akt/mTOR pathway plays an important role in SCLC phenotype transition and chemo-resistance, which holds important clinical implications for improving SCLC treatment.


Assuntos
Carcinoma de Pequenas Células do Pulmão
20.
Angew Chem Int Ed Engl ; 60(21): 12097-12102, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-33709569

RESUMO

A facile synthesis is reported of two-dimensional (2D) bimetallic (Fe/Co=1:2) metal-organic frameworks (MOF, ca. 2.2 nm thick) via simple stirring of the reaction mixture of Fe/Co salts and 1,4-benzene dicarboxylic acid (1,4-BDC) in the presence of triethylamine and water at room temperature. The mechanism of the 2D, rather than bulk, MOF was revealed by studying the role of each component in the reaction mixture. It was found that these 2D MOF-Fe/Co(1:2) exhibited excellent electrocatalytic activity for the oxygen evolution reaction (OER) under basic conditions. The electrocatalytic mechanism was disclosed via both experimental results and density functional theory (DFT) calculation. The 2D morphology and co-doping of Fe/Co contributed to the superior OER performance of the 2D MOF-Fe/Co(1:2). The simple and efficient synthetic method is suitable for the mass production and future commercialization of functional 2D MOF with low cost and high yield.

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