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1.
Nano Lett ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34623162

RESUMO

The formation of membrane nanopores is one of the crucial activities of cells and has attracted considerable attention. However, the understanding of their types and mechanisms is still limited. Herein, we report a novel nanopore formation phenomenon achieved through the insertion of polymeric nanotoroids into the cellular membrane. As revealed by theoretical simulations, the nanotoroid can embed in the membrane, leaving a nanopore on the cell. The through-the-cavity wrapping of lipids is critical for the retention of the nanotoroid in the membrane, which is attributed to both a relatively large inner cavity of the nanotoroid and a moderate attraction between the nanotoroid and membrane lipids. Under the guidance of the simulation predictions, experiments using polypeptide toroids as pore-forming agents were performed, confirming the unique biophysical phenomenon. This work demonstrates a distinctive pore-forming pathway, deepens the understanding of the membrane nanopore phenomenon, and assists in the design of advanced pore-forming materials.

2.
J Cardiothorac Surg ; 16(1): 271, 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34565415

RESUMO

BACKGROUND: We investigated single-port video-assisted thoracoscopic surgery (VATS) combined with a postoperative non-indwelling drain in enhanced recovery after surgery (ERAS). METHODS: The clinical data of 127 patients who underwent double- and single-port VATS from January 2018 to December 2019 were analyzed retrospectively. The groups constituted 71 cases undergoing double-port and 56 cases undergoing single-port VATS (30 cases in the indwelling drain group and 26 cases in the non-indwelling drain group). The incidence of postoperative complications, pain scores, and postoperative hospital stay were compared between the two groups. RESULTS: Compared with the double-port group, the single-port group had shorter postoperative hospital stays and lower pain scores on the first and third postoperative days (P < 0.05). Pain scores on the first and third days were lower in the single-port non-indwelling drain group than in the single-port indwelling drain group (P < 0.05), and the postoperative hospitalization time was significantly shorter in the single-port group (P < 0.05). However, there was no significant difference between the two groups for operation time, incidence of complications, and pain scores 1 month after operation (P > 0.05). CONCLUSIONS: The combination of single-port VATS with a non-indwelling drain can relieve postoperative pain, help patients recover quickly, and is in accordance with ERAS.

3.
Nat Commun ; 12(1): 5243, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475406

RESUMO

Peroxisome, a special cytoplasmic organelle, possesses one or more kinds of oxidases for hydrogen peroxide (H2O2) production and catalase for H2O2 degradation, which serves as an intracellular H2O2 regulator to degrade toxic peroxides to water. Inspired by this biochemical pathway, we demonstrate the reactive oxygen species (ROS) induced tumor therapy by integrating lactate oxidase (LOx) and catalase (CAT) into Fe3O4 nanoparticle/indocyanine green (ICG) co-loaded hybrid nanogels (designated as FIGs-LC). Based on the O2 redistribution and H2O2 activation by cascading LOx and CAT catalytic metabolic regulation, hydroxyl radical (·OH) and singlet oxygen (1O2) production can be modulated for glutathione (GSH)-activated chemodynamic therapy (CDT) and NIR-triggered photodynamic therapy (PDT), by manipulating the ratio of LOx and CAT to catalyze endogenous lactate to produce H2O2 and further cascade decomposing H2O2 into O2. The regulation reactions of FIGs-LC significantly elevate the intracellular ROS level and cause fatal damage to cancer cells inducing the effective inhibition of tumor growth. Such enzyme complex loaded hybrid nanogel present potential for biomedical ROS regulation, especially for the tumors with different redox state, size, and subcutaneous depth.


Assuntos
Antineoplásicos/farmacologia , Nanogéis/química , Peroxissomos/enzimologia , Fotoquimioterapia/métodos , Animais , Antineoplásicos/química , Catalase/química , Catalase/metabolismo , Catálise , Linhagem Celular Tumoral , Óxido Ferroso-Férrico/química , Glutationa/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Verde de Indocianina/química , Camundongos , Oxigenases de Função Mista/química , Oxigenases de Função Mista/metabolismo , Nanopartículas/química , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Oxigênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Microambiente Tumoral/efeitos dos fármacos
4.
Nucleic Acids Res ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34570220

RESUMO

LncRNAs are not only well-known as non-coding elements, but also serve as templates for peptide translation, playing important roles in fundamental cellular processes and diseases. Here, we describe a database, TransLnc (http://bio-bigdata.hrbmu.edu.cn/TransLnc/), which aims to provide comprehensive experimentally supported and predicted lncRNA peptides in multiple species. TransLnc currently documents approximate 583 840 peptides encoded by 33 094 lncRNAs. Six types of direct and indirect evidences supporting the coding potential of lncRNAs were integrated, and 65.28% peptides entries were with at least one type of evidence. Considering the strong tissue-specific expression of lncRNAs, TransLnc allows users to access lncRNA peptides in any of the 34 tissues involved in. In addition, both the unique characteristic and homology relationship were also predicted and provided. Importantly, TransLnc provides computationally predicted tumour neoantigens from peptides encoded by lncRNAs, which would provide novel insights into cancer immunotherapy. There were 220 791 and 237 915 candidate neoantigens binding by major histocompatibility complex (MHC) class I or II molecules, respectively. Several flexible tools were developed to aid retrieve and analyse, particularly lncRNAs tissue expression patterns, clinical relevance across cancer types. TransLnc will serve as a valuable resource for investigating the translation capacity of lncRNAs and greatly extends the cancer immunopeptidome.

5.
Cancer Res ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380633

RESUMO

While patients with advanced ovarian cancer may respond initially to treatment, disease relapse is common and nearly 50% of patients do not survive beyond five years, indicating an urgent need for improved therapies. To identify new therapeutic targets, we performed single cell and nuclear RNA-seq dataset analyses on 17 human ovarian cancer specimens, revealing the oncostatin M receptor (OSMR) as highly expressed in ovarian cancer cells. Conversely, oncostatin M (OSM), the ligand of OSMR, was highly expressed by tumor-associated macrophages and promoted proliferation and metastasis in cancer cells. Ovarian cancer cell lines and additional patient samples also exhibited elevated levels of OSMR when compared to other cell types in the tumor microenvironment or to normal ovarian tissue samples. OSMR was found to be important for ovarian cancer cell proliferation and migration. Binding of OSM to OSMR caused OSMR-IL6ST dimerization, which is required to produce oncogenic signaling cues for prolonged STAT3 activation. Human monoclonal antibody clones B14 and B21 directed to the extracellular domain of OSMR abrogated OSM-induced OSMR-IL6ST heterodimerization, promoted the internalization and degradation of OSMR, and effectively blocked OSMR-mediated signaling in vitro. Importantly, these antibody clones inhibited the growth of ovarian cancer cells in vitro and in vivo by suppressing oncogenic signaling through OSMR and STAT3 activation. Collectively, this study provides a proof of principle that anti-OSMR antibody can mediate disruption of OSM-induced OSMR-IL6ST dimerization and oncogenic signaling, thus documenting the pre-clinical therapeutic efficacy of human OSMR antagonist antibodies for immunotherapy in ovarian cancer.

6.
Dis Markers ; 2021: 2217663, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34336002

RESUMO

Background: Long noncoding RNA (lncRNA) critically impacts the modulation of tumor developments and progressions. Our study is aimed at investigating the expressing patterns, clinical significance, and biological roles of lncRNA TSPEAR-AS2 (TSPEAR-AS2) in oral squamous cell carcinoma (OSCC). Material and Approach. The expressing states achieved by TSPEAR-AS2 were examined in OSCC specimens and cell lines by RT-PCR. The clinical significance of TSPEAR-AS2 was statistically analyzed. OSCC proliferating, invading, and migrating processes were examined with the use of wound healing assays, transwell, colony formation, and cell counting kit-8. Additionally, the downstream molecular mechanism of TSPEAR-AS2 in OSCC was explored. Results: TSPEAR-AS2 was overexpressed in OSCC tumors and cells. High TSPEAR-AS2 was associated with advanced TNM stage. Patients with high TSPEAR-AS2 expression displayed a shorter disease-free survival and total survival of OSCC patients than those with low TSPEAR-AS2 expressing level. It was found that knockdown of TSPEAR-AS2 could inhibit the proliferating, invading, and migrating processes pertaining to OSCC cells. Luciferase reporter tests and RNA pull-down results revealed that TSPEAR-AS2 enhanced the expressions of PPM1A by regulating miR-487a-3p, and TSPEAR-AS2 could be adopted as a miR-487a-3p sponge to inhibit PPM1A expression. Conclusion: Our study highlighted the significance of the TSPEAR-AS2/miR-487a-3p/PPM1A axis within OSCC progression and offered a novel biomarker and novel strategies for OSCC treatments.

7.
J Mater Sci Mater Med ; 32(8): 92, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34374884

RESUMO

It suggests that the poly (3-hydroxybutyric acid-co-3-hydroxyvaleric acid) (PHBV) scaffold can be used for cartilage tissue engineering, but PHBV is short of bioactivity that is required for cartilage regeneration. To fabricate a bioactive cartilage tissue engineering scaffold that promotes cartilage regeneration, quercetin (QUE) modified PHBV (PHBV-g-QUE) fibrous scaffolds were prepared by a two-step surface modification method. The PHBV-g-QUE fibrous scaffold facilitates the growth of chondrocytes and maintains chondrocytic phenotype resulting from the upregulation of SOX9, COL II, and ACAN. The PHBV-g-QUE fibrous scaffold inhibited apoptosis of chondrocyte and reduced oxidative stress of chondrocytes by regulating the transcription of related genes. Following PHBV-g-QUE fibrous scaffolds and PHBV fibrous scaffolds with adhered chondrocytes were implanted into nude mice for 4 weeks, it demonstrated that PHBV-g-QUE fibrous scaffolds significantly promoted cartilage regeneration compared with the PHBV fibrous scaffolds. Hence, it suggests that the PHBV-g-QUE fibrous scaffold can be potentially applied in the clinical treatment of cartilage defects in the future.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34392674

RESUMO

A kind of silicone rubber (SR)/paraffin (Pa)@silicon dioxide (SiO2)@polydopamine (PDA) phase-change composite was prepared in this work. The double-shelled Pa@SiO2@PDA phase-change microcapsules were constructed by oxidative self-polymerization of dopamine (DA) in Tris-HCl buffer solution. The effect of the DA content on the properties of Pa@SiO2@PDA microcapsules and SR/Pa@SiO2@PDA composites was researched. Due to the protective effect of SiO2, PDA layer, and SR matrix, the SR/Pa@SiO2@PDA composites have good leak-proofing performance, and the leakage rate of SR/Pa@SiO2@PDA-2 is as low as 0.45%. Phase-change enthalpies of the Pa@SiO2@PDA microcapsules and SR/Pa@SiO2@PDA composites are reduced slightly with increasing DA content. Meanwhile, the composites displayed improved mechanical strength. The tensile strength of SR/Pa@SiO2@PDA-2 can be up to 0.560 MPa, which is 1.85 times higher than the tensile strength of pure SR/Pa@SiO2 because the interface compatibility between Pa@SiO2 microcapsules and SR is improved through hydrogen bonding between the abundant groups on the PDA surface and the matrix. Moreover, the rough surface of the PDA-modified microcapsules also enhances the interface interaction through physical "interlocking". The new kind of SR/Pa@SiO2@PDA composite can be used for thermal management.

9.
Chemosphere ; 286(Pt 2): 131714, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34426125

RESUMO

In this study, a field-scale and pot experiment were performed to evaluate the remedial efficiency of Cd contaminated soil by tobacco and explore rhizosphere micro-characteristics under different cadmium levels, respectively. The results indicated that tobacco could remove 12.9 % of Cd from soil within a short growing period of 80 d. The pot experiment revealed that tobacco could tolerate soil Cd concentrations up to 5.8 mg kg-1 and bioaccumulate 68.1 and 40.8 mg kg-1 Cd in shoots and roots, respectively. The high Cd bioaccumulation in tobacco might be attributed to strong acidification in the rhizosphere soil and the increase in Cd bioavailability. Rhizobacteria did not appear to be involved in Cd mobilization. In contrast, tobacco tended to enrich sulfate-reducing bacteria (such as Desulfarculaceae) under high Cd treatment (5.8 mg kg-1) but enrich plant growth-promoting bacteria (such as Bacillus, Dyadobacter, Virgibacillus and Lysobacter) to improve growth under low Cd treatment (0.2 mg kg-1), suggesting that tobacco employed different microbes for responding to Cd stress. Our results demonstrate the advantages of using tobacco for bioremediating Cd contaminated soil and clarify the rhizosphere mechanisms underlying Cd mobilization and tolerance.

10.
Adv Healthc Mater ; 10(18): e2100619, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34309242

RESUMO

The emergence of nanosilver (silver in nanoscale shapes and their assemblies) benefits the landscape of modern healthcare; however, this brings about concerns over its safety issues associated with an ultrasmall size and high mobility. By reviewing previous reporting details about the synthesis and characterization of nanosilver and its biological responses, a gap between materials synthesis and their biomedical uses is characterized by the insufficient understanding of the interacting and interplaying nanoscale actions of silver. To improve reporting quality and advance clinical translations, it is suggested that researchers have a comprehensive recognition of the "Indications for use" before designing innovative nanosilver-based materials and an "Action-network" concept addressing the acting range and strength of those nanoscale actions is implemented. Although this discussion is specific to nanosilver, the idea of "Indications for use" centered design and synthesis is generally applicable to other biomedical nanomaterials.


Assuntos
Nanopartículas Metálicas , Nanoestruturas , Biologia , Prata
11.
Int J Biol Sci ; 17(9): 2167-2180, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34239347

RESUMO

Rac GTPase activating protein 1 (RACGAP1) has been characterized in the pathogenesis and progression of several malignancies, however, little is known regarding its role in the development of gallbladder cancer (GBC). This investigation seeks to describe the role of RACGAP1 and its associated molecular mechanisms in GBC. It was found that RACGAP1 was highly expressed in human GBC tissues, which was associated to poorer overall survival (OS). Gene knockdown of RACGAP1 hindered tumor cell proliferation and survival both in vitro and in vivo. We further identified that RACGAP1 was involved in DNA repair through its binding with DNA ligase 3 (LIG3), a crucial component of the alternative-non-homologous end joining (Alt-NHEJ) pathway. RACGAP1 regulated LIG3 expression independent of RhoA activity. RACGAP1 knockdown resulted in LIG3-dependent repair dysfunction, accumulated DNA damage and Poly(ADP-ribosyl) modification (PARylation) enhancement, leading to increased apoptosis and suppressed cell growth. We conclude that RACGAP1 exerts a tumor-promoting role via binding LIG3 to reduce apoptosis and facilitate cell growth in GBC, pointing to RACGAP1 as a potential therapeutic target for GBC.

12.
Nat Commun ; 12(1): 4543, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34315889

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19) is a global health emergency. Various omics results have been reported for COVID-19, but the molecular hallmarks of COVID-19, especially in those patients without comorbidities, have not been fully investigated. Here we collect blood samples from 231 COVID-19 patients, prefiltered to exclude those with selected comorbidities, yet with symptoms ranging from asymptomatic to critically ill. Using integrative analysis of genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles, we report a trans-omics landscape for COVID-19. Our analyses find neutrophils heterogeneity between asymptomatic and critically ill patients. Meanwhile, neutrophils over-activation, arginine depletion and tryptophan metabolites accumulation correlate with T cell dysfunction in critical patients. Our multi-omics data and characterization of peripheral blood from COVID-19 patients may thus help provide clues regarding pathophysiology of and potential therapeutic strategies for COVID-19.


Assuntos
COVID-19/genética , COVID-19/metabolismo , Estado Terminal , Genômica/métodos , Humanos , Lipidômica/métodos , Metabolômica/métodos , Neutrófilos/metabolismo , Transcriptoma/genética
13.
Spectrochim Acta A Mol Biomol Spectrosc ; 263: 120182, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34303219

RESUMO

A new fluorescence probe method for the detection of Hg(II) in serum was established, which has the detection limit of 3.57 nM and quantification limit of 5 nM, based on the electrostatic induced agglomeration quenching and complexation between Hg(II) and silicon-nitrogen-doped carbon nanodots (Si/N-CDs). Furthermore, the fluorescence probe also showed the satisfactory results in the determination of Hg(II) in human serum. Subsequently, take advantage of the uric acid (UA) to recover the fluorescence of the Si/N-CDs-Hg(II) complex probe, another enzyme-free ways to determine UA was developed. The complex probe can selectively detect the UA content in the 0.5-30 µM range, and its detection limit can reach 0.14 µM, which has successfully detected the UA in total serum, and the results were no significant difference comparing with the controls.


Assuntos
Mercúrio , Pontos Quânticos , Carbono , Humanos , Nitrogênio , Ácido Úrico
14.
Signal Transduct Target Ther ; 6(1): 263, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34248142

RESUMO

Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses tumor progression, potentially displaying opposing effects on therapeutic outcomes. Chronic inflammation facilitates tumor progression and treatment resistance, whereas induction of acute inflammatory reactions often stimulates the maturation of dendritic cells (DCs) and antigen presentation, leading to anti-tumor immune responses. In addition, multiple signaling pathways, such as nuclear factor kappa B (NF-kB), Janus kinase/signal transducers and activators of transcription (JAK-STAT), toll-like receptor (TLR) pathways, cGAS/STING, and mitogen-activated protein kinase (MAPK); inflammatory factors, including cytokines (e.g., interleukin (IL), interferon (IFN), and tumor necrosis factor (TNF)-α), chemokines (e.g., C-C motif chemokine ligands (CCLs) and C-X-C motif chemokine ligands (CXCLs)), growth factors (e.g., vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-ß), and inflammasome; as well as inflammatory metabolites including prostaglandins, leukotrienes, thromboxane, and specialized proresolving mediators (SPM), have been identified as pivotal regulators of the initiation and resolution of inflammation. Nowadays, local irradiation, recombinant cytokines, neutralizing antibodies, small-molecule inhibitors, DC vaccines, oncolytic viruses, TLR agonists, and SPM have been developed to specifically modulate inflammation in cancer therapy, with some of these factors already undergoing clinical trials. Herein, we discuss the initiation and resolution of inflammation, the crosstalk between tumor development and inflammatory processes. We also highlight potential targets for harnessing inflammation in the treatment of cancer.

15.
Br J Cancer ; 125(5): 734-747, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34188196

RESUMO

BACKGROUND: SLC2A5 is a high-affinity fructose transporter, which is frequently upregulated in multiple human malignant tumours. However, the function and molecular mechanism of SLC2A5 in colorectal cancer (CRC) remain unknown. METHODS: We detected the expression levels of SLC2A5 in CRC tissues and CRC cell lines by western blotting, qRT-PCR and immunohistochemistry. CRC cell lines with stable overexpression or knockdown of SLC2A5 were constructed to evaluate the functional roles of SLC2A5 in vitro through conventional assays. An intrasplenic inoculation model was established in mice to investigate the effect of SLC2A5 in promoting metastasis in vivo. Methylation mass spectrometry sequencing, methylation specific PCR, bisulphite sequencing PCR, ChIP-qPCR and luciferase reporter assay were performed to investigate the molecular mechanism underlying transcriptional activation of SLC2A5. RESULTS: We found that SLC2A5 was upregulated in colorectal tumour tissues. Functionally, a high level of SLC2A5 expression was associated with increased invasion and metastasis capacities of CRC cells both in vitro and in vivo. Mechanistically, we unveiled that S100P could integrate to a specific region of SLC2A5 promoter, thereby reducing its methylation levels and activating SLC2A5 transcription. CONCLUSIONS: Our results reveal a novel mechanism that S100P mediates the promoter demethylation and transcription activation of SLC2A5, thereby promoting the metastasis of CRC.

16.
Anal Methods ; 13(28): 3196-3204, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34184019

RESUMO

Herein, cobalt and nitrogen co-doped carbon dots (Co-N-CDs) were fabricated via a one-pot hydrothermal approach. The obtained Co-N-CDs displayed peroxidase-like activity and fluorescence properties. It could catalyze the oxidization of guaiacol (GA) in the presence of hydrogen peroxide (H2O2), and thus, resulted in color change, accompanied by a new absorption peak in 470 nm. Owing to the inner filter effect, the oxidized product of GA (known as 2-PQ) largely absorbed the Co-N-CD fluorescence which was excited at 380 nm. Such changes in absorbance and fluorescence intensity were H2O2 concentration-dependent. Specifically, H2O2 could be generated by glucose oxidase to catalyze the oxidation of glucose, and thus, a colorimetric and fluorimetric sensor for glucose was established with high selectivity and excellent sensitivity. After the optimization of experimental conditions, this colorimetric sensor has a good linear range from 2 to 100 µM for glucose and the detection limit was 1.16 µM. Besides, the linear relationship between the fluorescence quenching value (ΔF) and the glucose concentration (0.4-40 µM) was obtained with a detection limit of 0.18 µM. Meanwhile, the proposed sensor has also been successfully applied for glucose detection in human serum samples, and the results were consistent with those of the standard method.


Assuntos
Colorimetria , Peróxido de Hidrogênio , Carbono , Cobalto , Glucose , Humanos , Limite de Detecção , Nitrogênio , Peroxidases
17.
J Hepatol ; 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34171432

RESUMO

BACKGROUND & AIMS: Our previous genomic whole-exome sequencing (WES) data identified the key ErbB pathway mutations that play an essential role in regulating the malignancy of gallbladder cancer (GBC). Herein, we tested the hypothesis that individual cellular components of the tumor microenvironment (TME) in GBC function differentially to participate in ErbB pathway mutation-dependent tumor progression. METHODS: We engaged single-cell RNA-sequencing to reveal transcriptomic heterogeneity and intercellular crosstalk from 13 human GBCs and adjacent normal tissues. In addition, we performed WES analysis to reveal the genomic variations related to tumor malignancy. A variety of bulk RNA-sequencing, immunohistochemical staining, immunofluorescence staining and functional experiments were employed to study the difference between tissues with or without ErbB pathway mutations. RESULTS: We identified 16 cell types from a total of 114,927 cells, in which epithelial cells, M2 macrophages, and regulatory T cells were predominant in tumors with ErbB pathway mutations. Furthermore, epithelial cell subtype 1, 2 and 3 were mainly found in adenocarcinoma and subtype 4 was present in adenosquamous carcinoma. The tumors with ErbB pathway mutations harbored larger populations of epithelial cell subtype 1 and 2, and expressed higher levels of secreted midkine (MDK) than tumors without ErbB pathway mutations. Increased MDK resulted in an interaction with its receptor LRP1, which is expressed by tumor-infiltrating macrophages, and promoted immunosuppressive macrophage differentiation. Moreover, the crosstalk between macrophage-secreted CXCL10 and its receptor CXCR3 on regulatory T cells was induced in GBC with ErbB pathway mutations. Elevated MDK was correlated with poor overall survival in patients with GBC. CONCLUSIONS: This study has provided valuable insights into transcriptomic heterogeneity and the global cellular network in the TME, which coordinately functions to promote the progression of GBC with ErbB pathway mutations; thus, unveiling novel cellular and molecular targets for cancer therapy. LAY SUMMARY: We employed single-cell RNA-sequencing and functional assays to uncover the transcriptomic heterogeneity and intercellular crosstalk present in gallbladder cancer. We found that ErbB pathway mutations reduced anti-cancer immunity and led to cancer development. ErbB pathway mutations resulted in immunosuppressive macrophage differentiation and regulatory T cell activation, explaining the reduced anti-cancer immunity and worse overall survival observed in patients with these mutations.

18.
Virol J ; 18(1): 117, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34088317

RESUMO

BACKGROUND: To date, specific cytokines associated with development of acute respiratory distress syndrome (ARDS) and extrapulmonary multiple organ dysfunction (MOD) in COVID-19 patients have not been systematically described. We determined the levels of inflammatory cytokines in patients with COVID-19 and their relationships with ARDS and extrapulmonary MOD. METHODS: The clinical and laboratory data of 94 COVID-19 patients with and without ARDS were analyzed. The levels of inflammatory cytokines (interleukin 6 [IL-6], IL-8, IL-10, and tumor necrosis factor α [TNF-α]) were measured on days 1, 3, and 5 following admission. Seventeen healthy volunteers were recruited as controls. Correlations in the levels of inflammatory cytokines with clinical and laboratory variables were analyzed, furthermore, we also explored the relationships of different cytokines with ARDS and extrapulmonary MOD. RESULTS: The ARDS group had higher serum levels of all 4 inflammatory cytokines than the controls, and these levels steadily increased after admission. The ARDS group also had higher levels of IL-6, IL-8, and IL-10 than the non-ARDS group, and the levels of these cytokines correlated significantly with coagulation parameters and disseminated intravascular coagulation (DIC). The levels of IL-6 and TNF-α correlated with the levels of creatinine and urea nitrogen, and were also higher in ARDS patients with acute kidney injury (AKI). All 4 inflammatory cytokines had negative correlations with PaO2/FiO2. IL-6, IL-8, and TNF-α had positive correlations with the APACHE-II score. Relative to survivors, non-survivors had higher levels of IL-6 and IL-10 at admission, and increasing levels over time. CONCLUSIONS: The cytokine storm apparently contributed to the development of ARDS and extrapulmonary MOD in COVID-19 patients. The levels of IL-6, IL-8, and IL-10 correlated with DIC, and the levels of IL-6 and TNF-α were associated with AKI. Relative to survivors, patients who died within 28 days had increased levels of IL-6 and IL-10.


Assuntos
COVID-19/sangue , Síndrome da Liberação de Citocina/sangue , Citocinas/sangue , Síndrome do Desconforto Respiratório/sangue , Injúria Renal Aguda/diagnóstico , Idoso , Nitrogênio da Ureia Sanguínea , COVID-19/patologia , Creatinina/sangue , Síndrome da Liberação de Citocina/diagnóstico , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/patologia , Feminino , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Interleucina-8/sangue , Masculino , Síndrome do Desconforto Respiratório/patologia , Estudos Retrospectivos , SARS-CoV-2 , Fator de Necrose Tumoral alfa/sangue
19.
J Tissue Eng Regen Med ; 15(8): 732-744, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34032003

RESUMO

Since chondrocyte hypertrophy greatly limits the efficiency of cartilage defects repairing via cartilage tissue engineering (CTE), it is critical to develop a functional CTE scaffold able to inhibit chondrocyte hypertrophy during this period of cartilage regeneration. In this study, we tested the applicability of using decellularized sturgeon cartilage ECM (dSCECM) scaffold to cease chondrocyte hypertrophy during cartilage damage repair. The dSCECM scaffolds with interconnected porous structure and pore size of 114.1 ± 20.9 µm were successfully prepared with freeze-dry method. Chondrocytes displayed a round shape and aggregated to form cellular spheroids within dSCECM scaffolds, which is similar to their chondrocytic phenotype within cartilage in vivo. Higher transcriptional level of chondrogenic related genes and integrin related genes was observed in chondrocytes incubated with dSCECM scaffolds instead of type I collagen (COL I) scaffolds, which were used as the control due to their widely usage in CTE and clinic applications. Furthermore, it confirmed that, compared with COL I scaffolds, dSCECM scaffolds significantly reduced the transcription of chondrocyte hypertrophy related genes in chondrocytes following the hypertrophic induction treatment. To test the ability of dSCECM scaffold to inhibit chondrocytes hypertrophy in vivo, chondrocytes with dSCECM scaffolds and COL I scaffolds were cultured with hypertrophic media and were implanted into nude mice respectively. Following 4 weeks implantation, interestingly, only the specimens derived from COL I scaffolds displayed consequences of chondrocyte hypertrophy like calcification deposition, demonstrating that chondrocyte hypertrophy is ceased by the dSCECM scaffold following hypertrophic induction. It suggests that the dSCECM scaffold can be potentially applied in clinical treating cartilage defects via the CTE approach to avoid the risk of chondrocyte hypertrophy.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33950669

RESUMO

Passive daytime radiative cooling (PDRC) involves cooling down an object by simultaneously reflecting sunlight and thermally radiating heat to the cold outer space through the Earth's atmospheric window. However, for practical applications, current PDRC materials are facing unprecedented challenges such as complicated and expensive fabrication approaches and performance degradation arising from surface contamination. Herein, we develop scalable cellulose-fiber-based composites with excellent self-cleaning and self-cooling capabilities, through air-spraying ethanolic poly(tetrafluoroethylene) (PTFE) microparticle suspensions embedded partially within the microsized pores of the cellulose fiber to form a dual-layered structure with PTFE particles atop the paper. The formed superhydrophobic PTFE coating not only protects the cellulose-fiber-based paper from water wetting and dust contamination for real-life applications but also reinforces its solar reflectivity by sunlight backscattering. It results in a subambient cooling performance of 5 °C under a solar irradiance of 834 W/m2 and a radiative cooling power of 104 W/m2 under a solar intensity of 671 W/m2. The self-cleaning surface of composites maintains their good cooling performance for outdoor applications, and the recyclability of the composites extends their life span after one life cycle. Additionally, dyed cellulose-fiber-based paper can absorb appropriate visible wavelengths to display specific colors and effectively reflect near-infrared lights to reduce solar heating, which synchronously achieves effective radiative cooling and esthetic varieties.

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