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1.
Sci Prog ; 104(2): 368504211014696, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33950712

RESUMO

COVID-19 is a sudden, infectious disease that can be life-threatening and may cause people to feel panic and anxiety. This study aimed to investigate the clinical characteristics and psychological status of a specific population using an internet consultation platform during the outbreak of COVID-19. The questionnaire survey included questions regarding basic information (e.g. area, sex, age, occupation, and education level), clinical characteristics, and cognitive and psychological status concerning COVID-19 from January 31, 2020 to March 31, 2020. There were 277 patients (43.49%) with three or more symptoms, 121 (12.11%) with a clinical questionnaire score ≥8, and 6.81% who lived in Hubei in the previous 14 days. Of the respondents, 4.9% had contact fever or were confirmed to have COVID-19 in the previous 14 days. The respondents were mostly aware that COVID-19 can be transmitted from person to person and via the respiratory tract, but awareness of general susceptibility and specific symptoms of COVID-19 was low. Multivariate analysis showed that urban residents, clerk/students and higher education groups were well aware of COVID-19. Regarding mental health, the anxiety score of the respondents was 7.12 ± 2.32, and the proportion of anxiety was 54.15%. Younger women were more likely to have anxiety when they experienced positive symptoms. Individuals with a Hubei residence history and those who had contact with an individual with a fever or were confirmed patients in the previous 14 days were more likely to have moderate or severe anxiety. The COVID-19-related knowledge of the respondents was generally good but still could have been improved. Their psychological status was also affected by the pandemic. The internet consultation platform played a positive role in spreading pandemic-related information, providing medical help and psychological counseling, and strengthening early warning to the potential high-risk population.


Assuntos
/psicologia , Saúde Mental , Telemedicina , Adolescente , Adulto , China/epidemiologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Questionário de Saúde do Paciente , Inquéritos e Questionários , Adulto Jovem
3.
Global Spine J ; : 21925682211010760, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33949240

RESUMO

STUDY DESIGN: Descriptive retrospective study. OBJECTIVE: DDH is a common lower limb deformity. It has been reported that this deformity can change the sagittal alignment of spine and pelvis. Sacral obliquity (SO) and iliac obliquity (IO) have been proven simple and reliable pelvic-lower limb coronal parameters to evaluate the coronal balance of the pelvis. To study the spine-pelvic coronal compensation mechanism of pelvic obliquity in patients with developmental dysplasia of the hip (DDH). METHODS: We collected the data of 110 patients with DDH in our hospital from January 2009 to December 2019, who underwent total hip arthroplasty. We used ICC (Intraclass correlation coefficient) to test the reliability of the measurement result of SO and IO in patients with DDH. A paired t-test was used for the statistical analysis. RESULTS: The intra observer reliability of IO and SO was 0.965 and 0.875 respectively, and the inter observer reliability of IO and SO was 0.887 and 0.889 respectively. The sacroiliac joint and spine can compensate for pelvic obliquity in patients with DDH. We classified the compensatory mechanism into 3 types according to the different imaging performances. CONCLUSIONS: The sacroiliac joint has a considerable compensatory ability to ensure coronal balance. We clarified and classified the compensatory mechanism of pelvic obliquity into 3 types. We differentiated the pelvic obliquity in patients with DDH and in those with scoliosis, which is clinical significant to understand the process of development of the disease.

4.
Brief Bioinform ; 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33855351

RESUMO

Consensus molecular subtypes (CMSs) are emerging as critical factor for prognosis and treatment of colorectal cancer. Gene regulators, including chromatin regulator, RNA-binding protein and transcriptional factor, are critical modulators of cancer hallmark, yet little is known regarding the underlying functional mechanism in CMSs. Herein, we identified a core set of 235 functional gene regulators (FGRs) by integrating genome, epigenome, transcriptome and interactome of CMSs. FGRs exhibited significant multi-omics alterations and impacts on cell lines growth, as well as significantly enriched cancer driver genes and pathways. Moreover, common FGRs played different roles in the context of CMSs. In accordance with the immune characteristics of CMSs, we found that the anti-tumor immune pathways were mainly activated by FGRs (e.g. STAT1 and CREBBP) in CMS1, while inhibited by FGRs in CMS2-4. FGRs mediated aberrant expression of ligands, which bind to receptor on immune cells, and modulated tumor immune microenvironment of subtypes. Intriguingly, systematic exploration of datasets using genomic and transcriptome co-similarity reveals the coordinated manner in FGRs act in CMSs to orchestrate their pathways and patients' prognosis. Expression signatures of the FGRs revealed an optimized CMS classifier, which demonstrated 88% concordance with the gold-standard classifier, but avoiding the influence of sample composition. Overall, our integrative analysis identified FGRs to regulate core tumorigenic processes/pathways across CMSs.

5.
Inorg Chem ; 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33844546

RESUMO

Ammonia borane (AB) has received growing research interest as one of the most promising hydrogen-storage carrier materials. However, fast dehydrogenation of AB is still limited by sluggish catalytic kinetics over current catalysts. Herein, highly uniform and ultrafine bimetallic RhNi alloy nanoclusters encapsulated within nitrogen-functionalized hollow mesoporous carbons (defined as RhNi@NHMCs) are developed as highly active, durable, and selective nanocatalysts for fast hydrolysis of AB under mild conditions. Remarkable activity with a high turnover frequency (TOF) of 1294 molH2 molRh-1 min-1 and low activation energy (Ea) of 18.6 kJ mol-1 is observed at room temperature, surpassing the previous Rh-based catalysts. The detailed mechanism studies reveal that when catalyzed by RhNi@NHMCs, a covalently stable O-H bond by H2O first cleaves in electropositive H* and further attacks B-H bond of AB to stoichiometrically produce 3 equiv of H2, whose catalytic kinetics is restricted by the oxidation cleavage of the O-H bond. Compositional and structural features of RhNi@NHMCs result in synergic electronic, functional, and support add-in advantages, kinetically accelerating the cleavage of the attacked H2O (O-H bond) and remarkably promoting the catalytic hydrolysis of AB accordingly. This present work represents a new and effective strategy for exploring high-performance supported metal-based alloy nanoclusters for (electro)catalysis.

6.
Stem Cell Res Ther ; 12(1): 245, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33863385

RESUMO

Breast cancer is the second common cancer and the leading cause of malignancy among females overall. Breast cancer stem cells (BCSCs) are a small population of breast cancer cells that play a critical role in the metastasis of breast cancer to other organs in the body. BCSCs have both self-renewal and differentiation capacities, which are thought to contribute to the aggressiveness of metastatic lesions. Therefore, targeting BCSCs can be a suitable approach for the treatment and metastasis of breast cancer. Growing evidence has indicated that the Wnt, NFκB, Notch, BMP2, STAT3, and hedgehog (Hh) signaling pathways govern epithelial-to-mesenchymal transition (EMT) activation, growth, and tumorigenesis of BCSCs in the primary regions. miRNAs as the central regulatory molecules also play critical roles in BCSC self-renewal, metastasis, and drug resistance. Hence, targeting these pathways might be a novel therapeutic approach for breast cancer diagnosis and therapy. This review discusses known signaling mechanisms involved in the stimulation or prevention of BCSC self-renewal, metastasis, and tumorigenesis.

7.
BMC Surg ; 21(1): 181, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33823821

RESUMO

BACKGROUND: The imaging characteristics of sacral sacralalar-iliac (S2AI) screw trajectory in adult degenerative scoliosis (ADS) patients will be determined. METHODS: S2AI screw trajectories were mapped on three-dimensional computed tomography (3DCT) reconstructions of 40 ADS patients. The starting point, placement plane, screw template, and a circle centered at the lowest point of the ilium inner cortex were set on these images. A tangent line from the starting point to the outer diameter of the circle was selected as the axis of the screw trajectory. The related parameters in different populations were analyzed and compared. RESULTS: The trajectory length of S2AI screws in ADS patients was 12.00 ± 0.99 cm, the lateral angle was 41.24 ± 3.92°, the caudal angle was 27.73 ± 6.45°, the distance from the axis of the screw trajectory to the iliosciatic notch was 1.05 ± 0.81 cm, the distance from the axis of the screw trajectory to the upper edge of the acetabulum was 1.85 ± 0.33 cm, and the iliac width was 2.12 ± 1.65 cm. Compared with females, the lateral angle of male ADS patients was decreased, but the trajectory length was increased (P < 0.05). Compared to patients without ADS in previous studies, the lateral angle of male patients was larger, the lateral angle of female patients was increased, and the caudal angle was decreased (P < 0.05). CONCLUSIONS: There is an ideal trajectory of S2AI screws in ADS patients. A different direction should be noticed in the placement of S2AI screws, especially in female patients.


Assuntos
Ílio , Sacro , Escoliose , Adulto , Parafusos Ósseos , Feminino , Humanos , Ílio/diagnóstico por imagem , Ílio/cirurgia , Imageamento Tridimensional , Masculino , Sacro/diagnóstico por imagem , Sacro/cirurgia , Escoliose/diagnóstico por imagem , Escoliose/cirurgia , Cirurgia Assistida por Computador , Tomografia Computadorizada por Raios X
8.
Bioorg Chem ; 111: 104886, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33836342

RESUMO

Our present and previous phytochemical investigations on Leptopus lolonum have resulted in the isolation of almost 30 phenylpropanoid-conjugated pentacyclic triterpenoids (PCPTs). During the continuous study on PCPTs, this kind of triterpenoid ester is considered as a natural product with low toxicity because of it's widely distribution in natural plants and edible fruits including kiwi fruit, durian, jujube, pawpaw, apple and pear. In the present work, we report the isolation, structural elucidation and cytotoxic evaluation of four new PCPTs (1-4) which obtained from L. lolonum. In addition, the possible biosynthesis pathway for 28-norlupane triterpenoid and potent effect of phenylpropanoid moiety for increasing the cytotxic effect of triterpenoids were also discussed. Among these compounds, compound 1 exhibited the highest cytotoxic effect on HepG2 cells with IC50 value of 11.87 µM. Further flow cytometry and western blot analysis demonstrated that 1 caused G1 cell cycle arrest by up-regulated the expression of phosphorylated p53 protein in HepG2 cells and induced cell apoptosis via MAPK and Akt pathways. These results emphasized the potential of PCPTs as lead compounds for developing anti-cancer drugs.

9.
Inorg Chem ; 60(7): 4380-4384, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33710863

RESUMO

Ternary noble metal-metalloid-nonmetal PdBS alloy mesoporous nanospheres (MSs) with three-dimensional central-radial pore channels were prepared for an electrocatalytic hydrogen evolution reaction. The synthesis was performed via precise control in the reduction and nucleation growth of ternary PdBS alloy MSs along confined cylinder mesophases assembled by amphiphilic dioctadecyldimethylammonium chloride. The resultant PdBS alloy MSs disclosed a remarkably improved electrocatalytic performance due to their structural and compositional synergies. This finding extended our knowledge on the rational design and targeted synthesis of novel noble metal-metalloid-nonmetal alloys with desired structures and morphologies for catalysis and other applications.

10.
Hum Vaccin Immunother ; : 1-8, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33687314

RESUMO

Objective: This study aimed to assess the knowledge of Chinese dentists on human papilloma virus (HPV), their willingness and factors prevention them from recommending patients for HPV vaccination, and to identify ways through which dentists can acquire HPV-related knowledge.Methods: This was a cross-sectional study based on Chinese dentists. The anonymous self-filled questionnaire method was used to collect demographic information of participants, their knowledge of HPV, willingness and barriers to recommending HPV vaccines to patients, and the strategies they can adopt to obtain HPV-related knowledge.Results: A total of 517 dentists completed the questionnaire, and 89.94% of dentists were willing to recommend HPV vaccination to patients. Participants aged 30-39 years, male dentists and dentist-in-charge had relatively lower knowledge scores than other groups. Besides, participants aged 30-39 years, working in private hospitals, and practicing in Southern China had a lower willingness to recommend HPV vaccination to patients. Recommending HPV vaccination to patients is not within the scope of practicing dentists, and concerns about the safety of the HPV vaccine were found to be the main barriers preventing its recommendation. Notably, 97.87% of dentists were eager to acquire HPV-related knowledge, and agreed for the first time to enroll in relevant educational courses.Conclusion: Chinese dentists had expressed a strong desire to recommend HPV vaccines to patients, even though their knowledge of HPV was scanty. Therefore, measures to improve their understanding of HPV vaccines and eliminate barriers suppressing their willingness to recommend HPV vaccines are urgently needed.

11.
Redox Biol ; 41: 101954, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33774474

RESUMO

Increasing lines of evidence identified that dexmedetomidine (DEX) exerted protective effects against sepsis-stimulated acute lung injury via anti-inflammation, anti-oxidation and anti-apoptosis. However, the mechanisms remain unclear. Herein, we investigated whether DEX afforded lung protection by regulating the process of mitochondrial dynamics through the HIF-1a/HO-1 pathway in vivo and in vitro. Using C57BL/6J mice exposed to lipopolysaccharide, it was initially observed that preemptive administration of DEX (50µg/kg) alleviated lung pathologic injury, reduced oxidative stress indices (OSI), improved mitochondrial dysfunction, upregulated the expression of HIF-1α and HO-1, accompanied by shifting the dynamic course of mitochondria into fusion. Moreover, HO-1-knockout mice or HO-1 siRNA transfected NR8383 cells were pretreated with HIF-1α stabilizer DMOG and DEX to validate the effect of HIF-1a/HO-1 pathway on DEX-mediated mitochondrial dynamics in a model of endotoxin-induced lung injury. We found that pretreatment with DEX and DMOG distinctly relieved lung injury, decreased the levels of mitochondrial ROS and mtDNA, reduced OSI, increased nuclear accumulation of HIF-1a and HO-1 protein in wild type mice but not HO-1 KO mice. Similar observations were recapitulated in NC siRNA transfected NR8383 cells after LPS stimulation but not HO-1 siRNA transfected cells. Concertedly, DEX reversed the impaired mitochondrial morphology in LPS stimulated-wild type mice or NC siRNA transfected NR8383 cells, upregulated the expression of mitochondrial fusion protein, while downregulated the expression of fission protein in HIF-1a/HO-1 dependent pathway. Altogether, our data both in vivo and in vitro certified that DEX treatment ameliorated endotoxin-induced acute lung injury by preserving the dynamic equilibrium of mitochondrial fusion/fission through the regulation of HIF-1a/HO-1 signaling pathway.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33723912

RESUMO

Optimizing the hydrogen adsorption Gibbs free energy (ΔGH ) of active sites is essential to improve the overpotential of the electrocatalytic hydrogen evolution reaction (HER). We doped graphene-like Co0.85 Se with sulfur and found that the active sites are reversed (from cationic Co sites to anionic S sites), which contributed to an enhancement in electrocatalytic HER performance. The optimal S-doped Co0.85 Se composite has an overpotential of 108 mV (at 10 mA cm-2 ) and a Tafel slope of 59 mV dec-1 , which exceeds other reported Co0.85 Se-based electrocatalysts. The doped S sites have much higher activity than the Co sites, with a hydrogen adsorption Gibbs free energy (ΔGH ) close to zero (0.067 eV), which reduces the reaction barrier for hydrogen production. This work provides inspiration for optimizing the intrinsic HER activity of other related transition metal chalcogenides.

13.
Bioorg Chem ; 107: 104628, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33461038

RESUMO

Most of Euphorbiaceae plants are considered as folk medicinal plants because of their various pharmacological effects. However, there are eight Leptopus genus plants which belong to Euphorbiaceae have never be investigated. Thus, four Leptopus genus plants were collected to study their chemical constituents and pharmacological activities. In the present work, the cytotoxicities of the extracts of four Leptopus genus plants were evaluated before phytochemical experiments. And nine new phenylpropanoid-conjugated pentacyclic triterpenoids, along with twenty-two known compounds were isolated from the whole plants of Leptopus lolonum. The structures of these new compounds were unequivocally elucidated by HRESIMS and 1D/2D NMR data. All triterpenoids were screened for their cytotoxicities against four cancer cell lines including HepG2, MCF-7, A549 and HeLa. Among these isolates, the triterpenoid with a phenylpropanoid unit showed increasing cytotoxicity on cancer cells, which suggested the importance of the phenylpropanoid moiety.

14.
Front Microbiol ; 11: 567769, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33304326

RESUMO

Phages are viruses that infect bacteria. The phages can be classified into two different categories based on their lifestyles: temperate and lytic. Now, the metavirome can generate a large number of fragments from the viral genomic sequences of entire environmental community, which makes it impossible to determine their lifestyles through experiments. Thus, there is a need to development computational methods for annotating phage contigs and making prediction of their lifestyles. Alignment-based methods for classifying phage lifestyle are limited by incomplete assembled genomes and nucleotide databases. Alignment-free methods based on the frequencies of k-mers were widely used for genome and metagenome comparison which did not rely on the completeness of genome or nucleotide databases. To mimic fragmented metagenomic sequences, the temperate and lytic phages genomic sequences were split into non-overlapping fragments with different lengths, then, I comprehensively compared nine alignment-free dissimilarity measures with a wide range of choices of k-mer length and Markov orders for predicting the lifestyles of these phage contigs. The dissimilarity measure, d 2 S , performed better than other dissimilarity measures for classifying the lifestyles of phages. Thus, I propose that the alignment-free method, d 2 S , can be used for predicting the lifestyles of phages which derived from the metagenomic data.

15.
Int J Lab Hematol ; 2020 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-33369192

RESUMO

Acute myeloid leukaemia (AML) is a frequently fatal malignant disease of haematopoietic stem and progenitor cells. The molecular and phenotypic characteristics of AML are highly heterogeneous. Our previous study concluded that CaMKIIγ was the trigger of chronic myeloid leukaemia progression from the chronic phase to blast crisis, but how CaMKIIγ influences AML stem-like cells remains elusive. In this study, we found that CaMKIIγ was overexpressed in AML patients and AML cell lines, as measured by qRT-PCR and Western blot assays. Moreover, CaMKIIγ decreased when the disease was in remission. Using an shRNA lentivirus expression system, we established CaMKIIγ stable-knockdown AML cell lines and found that knockdown of CaMKIIγ inhibited the viability and self-renewal of AML stem-like cell lines. Additionally, the ratio of CD34 + AML cell lines decreased, and CaMKIIγ knockdown induced the downregulation of Alox5 levels. We further detected downstream molecules of the Alox5/NF-κB pathway and found that c-myc and p-IκBα decreased while total IκBα remained normal. In conclusion, our study describes a new role for CaMKIIγ as a stem-like cell marker that is highly regulated by the Alox5/NF-κB pathway in AML stem-like cells. CaMKIIγ can participate in the viability and self-renewal of AML stem-like cells by regulating the Alox5/NF-κB pathway.

16.
Front Genet ; 11: 971, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193579

RESUMO

A part of colorectal cancer which is characterized by simultaneous numerous hypermethylation CpG islands sites is defined as CpG island methylator phenotype (CIMP) status. Stage II and III CIMP-positive (CIMP+) right-sided colon cancer (RCC) patients have a better prognosis than CIMP-negative (CIMP-) RCC treated with surgery alone. However, there is no gold standard available in defining CIMP status. In this work, we selected the gene pairs whose relative expression orderings (REOs) were associated with the CIMP status, to develop a qualitative transcriptional signature to individually predict CIMP status for stage II and III RCC. Based on the REOs of gene pairs, a signature composed of 19 gene pairs was developed to predict the CIMP status of RCC through a feature selection process. A sample is predicted as CIMP+ when the gene expression orderings of at least 12 gene pairs vote for CIMP+; otherwise the CIMP-. The difference of prognosis between the predicted CIMP+ and CIMP- groups was more significantly different than the original CIMP status groups. There were more differential methylation and expression characteristics between the two predicted groups. The hierarchical clustering analysis showed that the signature could perform better for predicting CIMP status of RCC than current methods. In conclusion, the qualitative transcriptional signature for classifying CIMP status at the individualized level can predict outcome and guide therapy for RCC patients.

17.
Front Genet ; 11: 566928, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193655

RESUMO

About 20-30% of early-stage breast cancer patients suffer relapses after surgery. To identify such high-risk patients, many signatures have been reported, but they lack robustness in data measured on different platforms. Here, we developed a signature which is robust across multiple profiling platforms, and identified reproducible omics features characterizing metastasis of estrogen receptor (ER)-positive breast cancer from the Gene Expression Omnibus database with the aid of the signature. Based on the stable within-sample relative expression orderings (REOs), we constructed a signature consisting of five gene pairs, named 5-GPS, whose REOs were significantly correlated with relapse-free survival using the univariate Cox regression model. Using 5-GPS, patients were classified into the low-risk and high-risk groups. Patients in the high-risk group have worse survival compared to those in the low-risk group using Kaplan-Meier curve analysis with the log-rank test. Applying 5-GPS to the RNA-sequencing data of stage I-IV breast cancer samples archived in The Cancer Genome Atlas (TCGA), we found that the proportion of the high-risk patients increases with the stage. The proposed REO-based signature shows potential in identifying early-stage ER+ breast cancer patients with high risk of relapse after surgery.

18.
Cancer Biol Ther ; 21(10): 972-982, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33047994

RESUMO

Cervical cancer (CC) is the second most common malignancy in women worldwide. The mechanism underlying CC development remains unclear. Recently, Circular RNAs (circRNAs)have attracted attention because of its role in tumorigenesis. To investigate circRNAsin CC, RNA sequencing was employed to characterize circRNA expression profile between CC tissues and matched adjacent normal tissues. The expression of hsa_circ_0003204 was examined in CC tissues and cell lines by real-time PCR. Migration assay and invasion assay were used to verify the effect of hsa_circ_0003204 on migration and invasion ability in CC cell lines. Tumor formation assay in nude mice was used to analyze the effect of hsa_circ_0003204 on the tumorigenicity of CC cell lines in vitro. Western blotting analyzes were performed to investigate the role of hsa_circ_0003204 in the regulation of MAPK signaling activation. We found that circRNA hsa_circ_0003204 was significantly upregulated in CC tissues. The function and potential molecular mechanisms of hsa_circ_0003204 were also investigated in vitro and in vivo. Hsa_circ_0003204 knockdown reduced cell growth, migration, and invasion but promoted cells apoptosis. However, the over-expression of hsa_circ_0003204 had the opposite effect. The MAPK pathway was different in hsa_circ_0003204 over-expression or down-expression cells, compared to parental cells. In addition, over-expression of hsa_circ_0003204 significantly increased tumor volume and tumor weight in vivo.Taken together, results indicated hsa_circ_0003204 may serve as a potential therapeutic target for patients with CC.

19.
Sci Rep ; 10(1): 17673, 2020 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-33077778

RESUMO

Nature reserves play an extraordinarily important role in conserving animal populations and their habitats. However, landscape change and unreasonable zoning designations often render these protected areas inadequate. Therefore, regular evaluation of the efficacy of protected lands is critical for maintaining and improving management strategies. Using species distribution models and GAP analysis, we assessed the changes in suitable habitat for the Brown Eared-pheasant (Crossoptilon mantchuricum) in two Chinese nature reserves between 1995 and 2013. Our results showed that the habitat suitability of Brown Eared-pheasant has changed dramatically during this period, and fragmentation analyses showed an increase in concentration area and decrease in patch area. In particular, our findings show that the national nature reserves need to adjust their ranges to ensure the conservation of this flagship species. Our study further provides a new viewpoint for evaluating the efficacy of protected lands, particularly in highly urbanized regions where conservation goals must be balanced with changing landscapes.

20.
Gut ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33122176

RESUMO

OBJECTIVE: Macrophages are among the most abundant cells in the colon tumour microenvironment, and there is a close relationship among monocytes, macrophages and the gut microbiota. Alterations in the gut microbiota are involved in tumour development, but the underlying mechanisms remain unclear. We aim to elucidate the temporal changes in macrophage subsets and functions, and how these dynamics are regulated by microbial cues in the initiation of colitis-associated cancer. DESIGN: A mouse model of colitis-associated tumourigenesis was established to determine macrophage dynamics. The role of monocyte-like macrophage (MLM) was confirmed by targeting its chemotaxis. The effects of the gut microbiota were assessed by antibiotic treatment and faecal microbiota transplantation. RESULTS: A selective increase in MLMs was observed in the initial stages of colitis-associated cancer, with an enhanced secretion of inflammatory cytokines. MLM accumulation was regulated by CCL2 expression of colonic epithelial cells, which was influenced by bacteria-derived lipopolysaccharide (LPS). LPS further stimulated interleukin 1ß production from MLMs, inducing interleukin-17-producing T-helper cell activation to promote inflammation. These observations were also supported by altered microbial composition associated with human colitis and colorectal cancer, evolving transcriptional signature and immune response during human colitis-associated tumourigenesis. CONCLUSIONS: The gut microbiota uses LPS as a trigger to regulate MLM accumulation in a chemokine-dependent manner and generate a precancerous inflammatory milieu to facilitate tumourigenesis.

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