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Cancer-associated fibroblasts (CAFs) are a diverse stromal cell population within the tumour microenvironment, where they play fundamental roles in cancer progression and patient prognosis. Multiple lines of evidence have identified that CAFs are critically involved in shaping the structure and function of the tumour microenvironment with numerous functions in regulating tumour behaviours, such as metastasis, invasion, and epithelial-mesenchymal transition (EMT). CAFs can interact extensively with cancer cells by producing extracellular vesicles (EVs), multiple secreted factors, and metabolites. Notably, CAF-derived EVs have been identified as critical mediators of cancer therapy resistance, and constitute novel therapy targets and biomarkers in cancer management. This review aimed to summarize the biological roles and detailed molecular mechanisms of CAF-derived EVs in mediating cancer resistance to chemotherapy, targeted therapy agents, radiotherapy, and immunotherapy. We also discussed the therapeutic potential of CAF-derived EVs as novel targets and clinical biomarkers in cancer clinical management, thereby providing a novel therapeutic strategy for enhancing cancer therapy efficacy and improving patient prognosis.
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Fibroblastos Associados a Câncer , Resistencia a Medicamentos Antineoplásicos , Vesículas Extracelulares , Neoplasias , Microambiente Tumoral , Humanos , Vesículas Extracelulares/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/terapia , Biomarcadores Tumorais/metabolismo , Animais , Transição Epitelial-Mesenquimal , Relevância ClínicaRESUMO
BACKGROUND: Previous observational studies have indicated associations of physical activity (PA) and air pollution with mortality. A few studies have evaluated air pollution and PA interactions for health. Still, the trade-off between the harmful effects of air pollution exposure and the protective effects of PA remains controversial and unclear. OBJECTIVE: This study aimed to investigate the joint association of air pollution and PA with mortality risks. METHODS: This prospective cohort study included 322,092 participants from 2006 to 2010 and followed up to 2021 in the UK Biobank study. The concentrations of air pollutants (2006-2010), including particulate matter (PM) with diameters <=2.5â¯mm (PM2.5), <=10â¯mm (PM10), and between 2.5 and 10â¯mm (PM2.5-10), and nitrogen oxides (NO2 and NOx) were obtained. Information on PA measured by the International Physical Activity Questionnaire short form (2006-2010) and wrist-worn accelerometer (2013-2015) were collected. All-cause and cause-specific mortalities were recorded. Cox proportional hazard models were used to investigate the associations of air pollution exposure and PA with mortality risks. The additive and multiplicative interactions were also examined. RESULTS: During a mean follow-up of 11.83 years, 16629 deaths were recorded. Compared with participants reporting low PA, higher PA was negatively associated with all-cause [hazard ratio (HR), 0.74; 95% CI, 0.71-0.78], cancer (HR, 0.85; 95% CI, 0.80-0.90), CVD (HR, 0.79; 95% CI, 0.71-0.87), and respiratory disease-specific mortality (HR, 0.51; 95% CI, 0.44-0.60). Exposure to PM2.5 (HR, 1.05; 95% CI, 1.00-1.09) and NOx (HR, 1.06; 95% CI, 1.02-1.10) was connected with increased all-cause mortality risk, and significant PM2.5-associated elevated risks for CVD mortality and NOx-associated elevated risks for respiratory disease mortality were observed. No obvious interaction between PA and PM2.5 or NOx exposure was detected. CONCLUSIONS: Our study provides additional evidence that higher PA and lower air pollutant levels are independently connected with reduced mortality risk. The benefits of PA are not significantly affected by long-term air pollution exposure, indicating PA can be recommended to prevent mortality regardless of air pollution levels. Our findings highlight the importance of public health policies and interventions facilitating PA and reducing air pollution in reducing mortality risks and maximizing health benefits. Future investigation is urgently needed to identify these findings in areas with severe air pollution conditions.
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Poluentes Atmosféricos , Poluição do Ar , Exercício Físico , Material Particulado , Humanos , Estudos Prospectivos , Poluição do Ar/efeitos adversos , Poluição do Ar/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Reino Unido , Feminino , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/efeitos adversos , Material Particulado/análise , Material Particulado/efeitos adversos , Idoso , Bancos de Espécimes Biológicos , Mortalidade/tendências , Medição de Risco , Exposição Ambiental/estatística & dados numéricos , Exposição Ambiental/efeitos adversos , Adulto , Doenças Cardiovasculares/mortalidade , Modelos de Riscos Proporcionais , Biobanco do Reino UnidoRESUMO
Bone is one of the most frequent sites for metastasis in breast cancer patients. Bone metastasis significantly reduces the survival time and the life quality of breast cancer patients. Germacrone (GM) can serve humans as an anti-cancer and anti-inflammation agent, but its effect on breast cancer-induced osteolysis remains unclear. This study aims to investigate the functions and mechanisms of GM in alleviating breast cancer-induced osteolysis. The effects of GM on osteoclast differentiation, bone resorption, F-actin ring formation, and gene expression were examined in vitro. RNA-sequencing and Western Blot were conducted to explore the regulatory mechanisms of GM on osteoclastogenesis. The effects of GM on breast cancer-induced osteoclastogenesis, and breast cancer cell malignant behaviors were also evaluated. The in vivo efficacy of GM in the ovariectomy model and breast cancer bone metastasis model with micro-CT and histomorphometry. GM inhibited osteoclastogenesis, bone resorption and F-actin ring formation in vitro. Meanwhile, GM inhibited the expression of osteoclast-related genes. RNA-seq analysis and Western Blot confirmed that GM inhibited osteoclastogenesis via inhibition of MAPK/NF-κB signaling pathways. The in vivo mouse osteoporosis model further confirmed that GM inhibited osteolysis. In addition, GM suppressed the capability of proliferation, migration, and invasion and promoted the apoptosis of MDA-MB-231 cells. Furthermore, GM could inhibit MDA-MB-231 cell-induced osteoclastogenesis in vitro and alleviate breast cancer-associated osteolysis in vivo human MDA-MB-231 breast cancer bone metastasis-bearing mouse models. Our findings identify that GM can be a promising therapeutic agent for patients with breast cancer osteolytic bone metastasis.
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Neoplasias da Mama , NF-kappa B , Osteoclastos , Osteogênese , Osteólise , Transdução de Sinais , Animais , Osteólise/tratamento farmacológico , Camundongos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Humanos , Osteogênese/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Sesquiterpenos de Germacrano/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Diferenciação Celular/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células RAW 264.7RESUMO
BACKGROUND: Breast cancer (BC) is regarded as one of the most common cancers diagnosed among the female population and has an extremely high mortality rate. It is known that Fibronectin 1 (FN1) drives the occurrence and development of a variety of cancers through metabolic reprogramming. Aspartic acid is considered to be an important substrate for nucleotide synthesis. However, the regulatory mechanism between FN1 and aspartate metabolism is currently unclear. METHODS: We used RNA sequencing (RNA seq) and liquid chromatography-mass spectrometry to analyze the tumor tissues and paracancerous tissues of patients. MCF7 and MDA-MB-231 cells were used to explore the effects of FN1-regulated aspartic acid metabolism on cell survival, invasion, migration and tumor growth. We used PCR, Western blot, immunocytochemistry and immunofluorescence techniques to study it. RESULTS: We found that FN1 was highly expressed in tumor tissues, especially in Lumina A and TNBC subtypes, and was associated with poor prognosis. In vivo and in vitro experiments showed that silencing FN1 inhibits the activation of the YAP1/Hippo pathway by enhancing YAP1 phosphorylation, down-regulates SLC1A3-mediated aspartate uptake and utilization by tumor cells, inhibits BC cell proliferation, invasion and migration, and promotes apoptosis. In addition, inhibition of FN1 combined with the YAP1 inhibitor or SLC1A3 inhibitor can effectively inhibit tumor growth, of which inhibition of FN1 combined with the YAP1 inhibitor is more effective. CONCLUSION: Targeting the "FN1/YAP1/SLC1A3/Aspartate metabolism" regulatory axis provides a new target for BC diagnosis and treatment. This study also revealed that intratumoral metabolic heterogeneity plays an important role in the progression of different subtypes of breast cancer.
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Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias da Mama/patologia , Fibronectinas/genética , Fibronectinas/metabolismo , Fibronectinas/farmacologia , Ácido Aspártico/genética , Ácido Aspártico/metabolismo , Ácido Aspártico/farmacologia , Apoptose/genética , Western Blotting , Proliferação de Células/genética , Linhagem Celular Tumoral , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Movimento Celular/genética , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: The association of milk consumption with mortality and cardiovascular disease (CVD) outcomes was unclear. OBJECTIVE: The present study was performed to reveal the association of full cream, semi-skimmed, skimmed, soy, and other milk with all-cause mortality and CVD outcomes. METHODS: A prospective cohort study was performed using data from the UK Biobank. This study recruited 450,507 participants without CVD at baseline between 2006 and 2010 from UK Biobank and followed them up through 2021. Cox proportional hazard models were adopted to calculate the hazard ratios (HRs) and 95% confidence interval (CI) to understand the correlation between milk consumption and clinical outcomes. Subgroup and sensitivity analyses were further conducted. RESULTS: Among the participants, 435,486 (96.7%) were milk consumers. Multivariable model indicated that the adjusted HR of association between milk consumption and all-cause mortality was 0.84 (95% CI 0.79 to 0.91; P = 0.000) for semi-skimmed milk; 0.82 (0.76 to 0.88; P = 0.000) for skimmed milk and 0.83 (0.75 to 0.93; P = 0.001) for soy milk. Semi-skimmed, skimmed, and soy milk use were significantly related to lower risks of CVD mortality, CVD event, and stroke. CONCLUSION: Compared with non-milk users, semi-skimmed milk, skimmed milk, and soy milk consumption were related to a lower risk of all-cause mortality and CVD outcomes. Among them, skim milk consumption was more beneficial for all-cause mortality, while soy milk consumption was more beneficial for CVD outcomes.
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Bancos de Espécimes Biológicos , Doenças Cardiovasculares , Humanos , Estudos de Coortes , Estudos Prospectivos , Fatores de Risco , Reino Unido/epidemiologiaRESUMO
BACKGROUND: There are inconsistent results of cohort studies analyzing the association between fish intake and mortality. OBJECTIVE: This study was performed to explore the association of oily fish consumption and nonoily fish consumption with all-cause mortality and cause-specific mortality. METHODS: A total of 431,062 participants from the UK Biobank who were without cancer or cardiovascular disease (CVD) at baseline between 2006 and 2010 were included in this study, and they were followed up through 2021. We constructed Cox proportional hazard models to calculate the hazard ratio (HR) and 95% confidence interval (CI) to assess the correlation of oily fish and nonoily fish intakes with mortality. Then, we performed subgroup analyses, and sensitivity analyses were developed and performed to examine the robustness of this study. RESULTS: Among the participants, 383,248 (88.9%) and 410,499 (95.2%) consumed oily fish and nonoily fish, respectively. Compared with the participants who did not consume oily fish, the adjusted HRs for the association of oily fish consumption (1 serving/week) with all-cause mortality and CVD mortality were 0.93 (0.87 to 0.98; p < 0.05) and 0.85 (0.74 to 0.98; p < 0.05), respectively. The multivariable-adjusted HRs of all-cause mortality for those who reported consuming < 1 serving/week of oily fish were 0.92 (0.86 to 0.98; p < 0.05). CONCLUSION: Compared with participants who reported never consuming oily fish, the consumption of oily fish with 1 serving/week was more beneficial for all-cause and CVD mortality.
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Doenças Cardiovasculares , Dieta , Animais , Fatores de Risco , Dieta/métodos , Causas de Morte , Estudos ProspectivosRESUMO
A non-noble Cu-catalyzed transfer aza-benzyl Michael addition via the C-C bond cleavage of aza-benzyl alcohols has been disclosed. The unstrained C(sp3)-C(sp3) bond of an alcohol was selectively cleaved. This aza-benzyl transfer strategy provides a selective and environmentally benign approach for the C-alkylation of α,ß-unsaturated carbonyl compounds that employs readily available alcohols as carbon nucleophiles and is characterized by a wide range of substrates and good to excellent yields.
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BACKGROUND: Iatrogenic injury to the radial nerve is a risk in surgical treatment for extraarticular fractures of the middle and distal third of the humerus. We aimed to investigate the safety, feasibility and advantages of minimally invasive percutaneous plate osteosynthesis (MIPPO) via an anteromedial approach in the treatment of middle and middle-distal humeral fractures and to evaluate proximity to neurovascular structures. MATERIALS AND METHODS: In 2016, 13 adult cadaver arms were used to simulate a minimally invasive surgical approach to the anteromedial humerus followed by fixation with a locking compression plate (LCP), and several sets of anatomical data were measured to clarify the possible risk of iatrogenic vascular and nerve injury in this surgical approach. Then, a case series study of 12 patients with humeral fractures who were treated with this surgical approach was conducted between 2017 and 2020. RESULTS: The average humeral length was 29.22 ± 1.62 cm, the average width of the medial epicondyle of the humerus was 1.31 ± 0.17 cm, and the average distance from the vertex of the medial epicondyle to the median nerve was 2.96 ± 1.62 cm. Furthermore, the safe area for distal humeral screw placement was 6.28 ± 0.39 cm, and the average distance from the tip of the distal end of the screw in the medial epicondyle to the ulnar nerve was 1.7 ± 1.25 mm. None of the 12 patients had nerve damage or an incisional infection after the operation. CONCLUSIONS: The new approach was performed as described, and no cases of iatrogenic nerve palsy occurred. This approach can be used as an alternative for the treatment of extraarticular fractures of the middle and distal thirds of the humerus. LEVEL OF EVIDENCE: Level IV, therapeutic study.
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Fraturas Distais do Úmero , Fraturas do Úmero , Adulto , Humanos , Fraturas do Úmero/diagnóstico por imagem , Fraturas do Úmero/cirurgia , Úmero , Procedimentos Cirúrgicos Minimamente Invasivos , Fixação Interna de Fraturas/efeitos adversos , Placas Ósseas , Cadáver , Doença Iatrogênica , Resultado do TratamentoRESUMO
Mesenchymal stem cells (MSCs) are multipotent stromal cells that can be obtained from various human tissues and organs. They can differentiate into a wide range of cell types, including osteoblasts, adipocytes and chondrocytes, thus exhibiting great potential in regenerative medicine. Numerous studies have indicated that MSCs play critical roles in cancer biology. The crosstalk between tumour cells and MSCs has been found to regulate many tumour behaviours, such as proliferation, metastasis and epithelial-mesenchymal transition (EMT). Multiple lines of evidence have demonstrated that MSCs can secrete exosomes that can modulate the tumour microenvironment and play important roles in tumour development. Notably, very recent works have shown that mesenchymal stem cell-derived exosomes (MSC-derived exosomes) are critically involved in cancer resistance to chemotherapy agents, targeted-therapy drugs, radiotherapy and immunotherapy. In this review, we systematically summarized the emerging roles and detailed molecular mechanisms of MSC-derived exosomes in mediating cancer therapy resistance, thus providing novel insights into the clinical applications of MSC-derived exosomes in cancer management.
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Exossomos , Células-Tronco Mesenquimais , Neoplasias , Adipócitos , Exossomos/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , Neoplasias/metabolismo , Neoplasias/terapia , Microambiente TumoralRESUMO
BACKGROUND: RNA adenosine modifications, which are primarily mediated by "writer" enzymes (RMWs), play a key role in epigenetic regulation in various biological processes, including tumorigenesis. However, the expression and prognostic role of these genes in osteosarcoma (OS) remain unclear. METHODS: Univariate and multivariate Cox analyses were used to construct the RMW signature for OS using Target datasets. RMW expression in OS tissue was detected by qPCR analysis. Xcell and GSVA were used to determine the relationship between RMWs and immune infiltration. The DGIdb and CMap databases were used for drug prediction. In vivo and in vitro experiments showed that strophanthidin elicited antitumor activity against OS. RESULTS: A 3-RMW (CSTF2, ADAR and WTAP) prognostic signature in OS was constructed using the Target dataset and verified using GEO datasets and 63 independent OS tissues via qPCR analysis. High-risk OS patients had poor overall survival, and the prognostic signature was an independent prognostic factor for OS. Functional studies showed that tumour-, metabolism-, cell cycle- and immune-related pathways were related to high risk. Next, we found that RMW-derived high-risk patients exhibited increased infiltration of M2 macrophages and cDCs. Furthermore, we predicted the potential drugs for OS using the DGIdb and CMap databases. In vivo and in vitro experiments showed that strophanthidin elicited antitumor activity against OS by repressing cell growth and inducing cell cycle arrest at the G1 phase. CONCLUSION: The 3-RWM-based prognostic signature established in this study is a novel gene signature associated with immune infiltration, and strophanthidin was identified as a candidate therapy for OS by repressing OS cell growth and the cell cycle.
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Neoplasias Ósseas , Osteossarcoma , Adenosina , Biomarcadores Tumorais/genética , Neoplasias Ósseas/genética , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Humanos , Osteossarcoma/genética , Osteossarcoma/patologia , Prognóstico , RNA , EstrofantidinaRESUMO
BACKGROUND: There is still uncertainty on whether ionizing radiation from CT scans can increase the risks of cancer. This study aimed to identify the association of cumulative ionizing radiation from CT scans with pertaining cancer risks in adults. METHODS: Five databases were searched from their inception to November 15, 2020. Observational studies reporting cancer risks from CT scans in adults were included. The main outcome included quantified cancer risks as cancer case numbers in exposed/unexposed adult participants with unified converted measures to odds ratio (OR) for relative risk, hazard ratio. Global background radiation (2.4 mSv per year) was used as control for lifetime attribution risk (LAR), with the same period from incubation after exposure until survival to 100 years. RESULTS: 25 studies were included with a sum of 111,649,943 participants (mean age: 45.37 years, 83.4% women), comprising 2,049,943 actual participants from 6 studies with an average follow-up period as 30.1 years (range, 5 to 80 years); 109,600,000 participants from 19 studies using LAR. The cancer risks for adults following CT scans were inordinately increased (LAR adults, OR, 10.00 [95% CI, 5.87 to 17.05]; actual adults, OR, 1.17 [95%CI, 0.89 to 1.55]; combined, OR, 5.89 [95%CI, 3.46 to 10.35]). Moreover, cancer risks elevated with increase of radiation dose (OR, 33.31 [95% CI, 21.33 to 52.02]), and multiple CT scan sites (OR, 14.08 [95% CI, 6.60 to 30.05]). The risk of solid malignancy was higher than leukemia. Notably, there were no significant differences for age, gender, country, continent, study quality and studying time phrases. CONCLUSIONS: Based on 111.6 million adult participants from 3 continents (Asia, Europe and America), this meta-analysis identifies an inordinately increase in cancer risks from CT scans for adults. Moreover, the cancer risks were positively correlated with radiation dose and CT sites. The meta-analysis highlights the awareness of potential cancer risks of CT scans as well as more reasonable methodology to quantify cancer risks in terms of life expectancy as 100 years for LAR. PROSPERO TRIAL REGISTRATION NUMBER: CRD42019133487.
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Leucemia , Neoplasias , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Masculino , Tomografia Computadorizada por Raios X/efeitos adversos , Neoplasias/diagnóstico por imagem , Neoplasias/epidemiologia , Neoplasias/etiologia , Radiação Ionizante , Razão de ChancesRESUMO
BACKGROUND: To observe the clinicopathological and prognostic value of long non-coding RNA five prime to X inactive specific transcript (lncFTX) in multiple tumors. METHODS: Eligible studies for lncFTX were identified by searching PubMed, Embase, Web of Science and Cochrane Library databases from inception to December 01, 2020. Stata 12.0 software was used to calculate the odds ratio (OR)/hazard ratio (HR) and 95% confidence interval (95% CI). We used The Cancer Genome Atlas (TCGA) dataset to further investigate the differential expression and prognostic value of lncFTX. RESULTS: We included 11 studies involving a total of 1633 patients. The results showed that the expression of lncFTX was positively associated with advanced TNM stage (III-IV versus I-II) (OR = 2.30, 95% CI: 1.74-3.03, P < 0.05), lymph nodes metastasis (OR = 3.01, 95% CI: 2.00-4.52, P < 0.05), distant metastasis (OR = 3.68, 95% CI: 2.13-6.34, P < 0.05), and cancer mortality (HR = 1.83, 95% CI: 1.20-2.81, P < 0.05). However, the expression of lncFTX was not associated with tumor differentiation (poor differentiation versus well or moderate differentiation) and vessel invasion of cancer. Subgroup analysis showed that the higher lncFTX expression was associated with shorter overall survival in cancer patients, regardless of the sample size and cancer type. No publication bias was found, and the sensitivity analysis results suggested that the main findings were robust. Elevated expression and prognostic significance of FTX were confirmed using TCGA dataset. CONCLUSIONS: This study found that the expression of lncFTX was positively associated with advanced tumor node metastasis (TNM) stage, lymph nodes, distant metastasis and, cancer mortality, suggesting that lncFTX might be a potential prognostic biomarker for tumors.
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Neoplasias , RNA Longo não Codificante , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Metástase Linfática , Masculino , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/mortalidade , Neoplasias/patologia , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
Osteosarcoma is a prevalent malignant bone cancer. This study aimed to explore the biologic role and potential mechanism of circ_0003732 in osteosarcoma carcinogenesis. Quantitative real-time PCR was implemented to detect the RNA expression of circ_0003732, microRNA-377-3p (miR-377-3p) and cytoplasmic polyadenylation element-binding protein 1 (CPEB1). Cell proliferation was evaluated by cell counting kit-8 assay and colony formation assay. Transwell, wound healing and flow cytometry assays were employed to assess cell migration, invasion and apoptosis. In addition, the interaction between miR-377-3p and circ_0003732 or CPEB1 was validated by dual-luciferase reporter assay. The protein expression was detected by western blot assay or immunohistochemistry assay. Xenograft tumor assay was performed to explore the regulation of circ_0003732 on osteosarcoma tumor growth in vivo. Circ_0003732 was upregulated in osteosarcoma tissues and cells. Knockdown of circ_0003732 suppressed osteosarcoma cell proliferation, migration, invasion and triggered cell apoptosis in vitro, as well as reduced osteosarcoma tumor growth in vivo. Meanwhile, miR-377-3p could bind to circ_0003732 and CPEB1 and miR-377-3p inhibitor could reverse the effects of circ_0003732 silence on osteosarcoma cell progression. Furthermore, CPEB1 overexpression could overturn the suppressive impacts of miR-377-3p on osteosarcoma progression. In addition, circ_0003732 silence restrained Wnt/ß-catenin signaling pathway via regulating miR-377-3p in osteosarcoma cells. Circ_0003732 might play a positive role in the malignant progression of osteosarcoma by regulating the miR-377-3p/CPEB1 axis and activating the Wnt/ß-catenin signaling pathway, which might provide new insights for osteosarcoma therapy.
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Neoplasias Ósseas/genética , Osteossarcoma/genética , RNA Circular/genética , Animais , Apoptose/fisiologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/metabolismo , Fatores de Transcrição/metabolismo , Regulação para Cima , Via de Sinalização Wnt/fisiologia , Fatores de Poliadenilação e Clivagem de mRNA/metabolismoRESUMO
The silver-catalyzed alkynyl borrowing amination of secondary propargyl alcohols via C(sp3)-C(sp) bond cleavage has been developed. This new strategy was based on the ß-alkynyl elimination of propargyl alcohols and alkynyl as the borrowing subject. This alkynyl borrowing amination featured high atom economy, wide functional group tolerance, and high efficiency.
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Álcoois , Prata , Álcoois/química , Aminação , Catálise , Prata/químicaRESUMO
A regio- and chemoselective sulfonylation of propargyl alcohols with sulfinamides in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) was developed. It provided straightforward and mild access to multi-substituted allenyl sulfones by using sulfinamides as the sulfonyl sources. This transformation was promoted by HFIP and did not require any catalysts or oxidants, which allowed for the successful conversion of various tertiary and secondary propargyl alcohols into allenyl sulfones in high yields.
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The immunosuppressive effects of antibiotics and the potential associations with the intestinal microbiota of the host have been increasingly recognized in recent years. However, the detailed underlying mechanisms of immune interference of antibiotics in environmental organisms remain unclear, particularly at the early life stage of high sensitivity. To better understand the gut microbiome and immune function interactions, the vertebrate model, zebrafish, was treated with environmentally relevant concentrations of a frequently detected antibiotic, enrofloxacin (ENR), ranging from 0.01 to 100 µg/L. 16S ribosomal RNA sequencing indicated diminished diversity, richness, and evenness of intestinal flora following ENR treatment. Twenty-two taxa of gut bacteria including Rickettsiales, Pseudomonadales, and Flavobacteriales were significantly correlated with immunosuppressive biomarkers, including a significant decrease in the abundance of macrophages and neutrophils. To validate the immunomodulatory effects due to altered intestinal microbial populations, zebrafish reared under sterile and non-sterile husbandry conditions were compared after ENR treatment. A significant inhibitory effect was induced by ENR treatment under non-sterile conditions, while the number of macrophages and neutrophils, as well as biomarkers of immunosuppressive effects, were significantly salved in zebrafish under sterile conditions, confirming for the first time that immunosuppression by ENR was closely mediated through alterations of the intestinal microbiome in fish.
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Microbioma Gastrointestinal , Animais , Antibacterianos/farmacologia , Enrofloxacina/farmacologia , Terapia de Imunossupressão , RNA Ribossômico 16S/genética , Peixe-Zebra/genéticaRESUMO
BACKGROUND: For periacetabular osteotomy, traditional approaches usually have a long learning curve. We aimed to evaluate the postoperative results and complications of periacetabular osteotomy under a new double-incision approach. METHODS: The records of 58 consecutive patients (65 hips) who underwent periacetabular osteotomy using the new approach were retrospectively reviewed and evaluated. There were 52 women and 6 men with a mean age of 28.1 years at the time of surgery. RESULTS: The average follow-up period was 35.2 months, during which no patients were converted to total hip arthroplasty. Complications included 6 hips (9.2%) with nerve dysesthesias and 1 hip (1.5%) with delayed wound healing. The mean operative time and intraoperative blood loss were 88.6 min and 402.8 ml, respectively. The mean modified Harris hip score had improved from 72.2 points preoperatively to 91.3 points at the last follow-up. Fifty-five patients (62 hips, 95.4%) were satisfied to their outcomes, and good preoperative functional score was associated with a satisfactory outcome. Furthermore, the average lateral center-edge angle, anterior center-edge angle and acetabular index angle were corrected well after surgery. CONCLUSION: Periacetabular osteotomy using modified Smith-Petersen or Bikini approach with posterolateral assisted small incision can be performed safely and with satisfactory results. In addition, this technique shortens the learning curve, and reduces the operating complexity, especially for beginner.
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Luxação Congênita de Quadril , Luxação do Quadril , Ferida Cirúrgica , Adulto , Feminino , Luxação do Quadril/etiologia , Luxação do Quadril/cirurgia , Luxação Congênita de Quadril/diagnóstico por imagem , Humanos , Masculino , Osteotomia/métodos , Radiografia , Estudos Retrospectivos , Ferida Cirúrgica/etiologia , Resultado do TratamentoRESUMO
BACKGROUND: This study aimed to evaluate a personalized 3D-printed percutaneous vertebroplasty positioning module and navigation template based on preoperative CT scan data that was designed to treat patients with vertebral compression fractures caused by osteoporosis. METHODS: A total of 22 patients with vertebral compression fractures admitted to our hospital were included in the study. Positioning was performed with the new 3D-printed positioning module, and the navigation template was used for patients in the experimental group, and the traditional perspective method was used for patients in the control group. The experimental group consisted of 11 patients, 2 males and 9 females, with a mean age of 67.27 ± 11.86 years (range: 48 to 80 years), and the control group consisted of 11 patients, 3 males and 8 females, with a mean age of 74.27 ± 7.24 years (range: 63 to 89 years). The puncture positioning duration, number of intraoperative fluoroscopy sessions, and preoperative and postoperative visual analog scale (VAS) scores were statistically analyzed in both groups. RESULTS: The experimental group had shorter puncture positioning durations and fewer intraoperative fluoroscopy sessions than the control group, and the differences were statistically significant (P < .05). There were no significant differences in age or preoperative or postoperative VAS scores between the two groups (P > .05). CONCLUSIONS: The new 3D-printed vertebroplasty positioning module and navigation template shortened the operation time and reduced the number of intraoperative fluoroscopy sessions. It also reduced the difficulty in performing percutaneous vertebroplasty and influenced the learning curve of senior doctors learning this operation to a certain degree.
Assuntos
Fraturas por Compressão , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Vertebroplastia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/cirurgia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Fraturas por Osteoporose/cirurgia , Vertebroplastia/métodos , Impressão Tridimensional , Resultado do Tratamento , Estudos RetrospectivosRESUMO
OBJECTIVES: Hip arthroplasty is the most important surgical method for the treatment of hip fractures and necrosis in the femoral head. Limb function recovery is an important criterion to reflect the efficacy of surgery and the quality for life of patients. Postoperative rehabilitation exercises are crucial for limb function recovery. Otago exercise programme (OEP) is a safe, effective, practical, and economical rehabilitation exercise, which has been proven to prevent falls, improve limb function and walking ability, and lower limb strength. This study aims to explore the effect of OEP on limb function rehabilitation in elderly patients with hip arthroplasty for femoral neck fractures. METHODS: A total of 77 elderly patients with hip arthroplasty for femoral neck fractures who met the criteria for inclusion and exclusion were enrolled for this study. They were randomly divided into a control group ( n =39) and an intervention group ( n =38). The control group was given routine rehabilitation training, and the intervention group performed OEP on the basis of the control group. Time get up and go test (TGUT), five times sit to stand test (FTSST), 10-meter walking test (10MWT), Harris Hip Score (HHS), Daily Activity Scale (Barthel index), and the Mos 36-Item Short Form Health Survey (SF-36) were used before the intervention, at discharge, and the 12th week after discharge. RESULTS: Before the intervention, there were no differences in TGUT, FTSST, 10MWT, HHS score, Barthel index, and SF-36 score between the 2 groups (all P >0.05). At the discharge after the intervention, there was no difference in TGUT between the 2 groups ( P >0.05), but the FTSST and 10MWT in the control group were longer than those in the intervention group (both P <0.05), and the HHS score, Barthel index, and SF-36 score in the control group were lower than those in the intervention group ( P <0.05). At the 12th week after discharge, TGUT, FTSST, 10MWT, HHS score, Barthel index, and SF-36 score in the intervention group were better than those in the control group ( P <0.05). CONCLUSIONS: OEP can effectively promote limb stability and hip function recovery in elderly patients with hip arthroplasty for femoral neck fractures, improve daily mobility and quality of life, and it is suitable for clinical application.
Assuntos
Artroplastia de Quadril , Fraturas do Colo Femoral , Idoso , Humanos , Artroplastia de Quadril/métodos , Terapia por Exercício/métodos , Fraturas do Colo Femoral/cirurgia , Qualidade de Vida , Recuperação de Função Fisiológica , Resultado do TratamentoRESUMO
Stem cells are a class of undifferentiated cells with great self-renewal and differentiation capabilities that can differentiate into mature cells in specific tissue types. Stem cell differentiation plays critical roles in body homoeostasis, injury repair and tissue generation. The important functions of stem cell differentiation have resulted in numerous studies focusing on the complex molecular mechanisms and various signalling pathways controlling stem cell differentiation. Circular RNAs (circRNAs) are a novel class of noncoding RNAs with a covalently closed structure present in eukaryotes. Numerous studies have highlighted important biological functions of circRNAs, and they play multiple regulatory roles in various physiological and pathological processes. Importantly, multiple lines of evidence have shown the abnormal expression of numerous circRNAs during stem cell differentiation, and some play a role in regulating stem cell differentiation, highlighting the role of circRNAs as novel biomarkers of stem cell differentiation and novel targets for stem cell-based therapy. In this review, we systematically summarize and discuss recent advances in our understanding of the roles and underlying mechanisms of circRNAs in modulating stem cell differentiation, thus providing guidance for future studies to investigate stem cell differentiation and stem cell-based therapy.Abbreviations: CircRNAs: circular RNAs; ESCs: embryonic stem cells; ADSCs: adipose-derived mesenchymal stem cells; ecircRNAs: exonic circRNAs; EIciRNAs: exon-intron circRNAs; eiRNAs: circular intronic RNAs; tricRNAs: tRNA intronic circRNAs; pol II: polymerase II; snRNP: small nuclear ribonucleoprotein; m6A: N6-methyladenosine; AGO2: Argonaute 2; RBPs: RNA-binding proteins; MBNL: muscleblind-like protein 1; MSCs: mesenchymal stem cells; hiPSCs: human induced pluripotent stem cells; hiPSC-CMs: hiPSC-derived cardiomyocytes; hBMSCs: human bone marrow mesenchymal stem cells; hADSCs: human adipose-derived mesenchymal stem cells; hDPSCs: human dental pulp stem cells; RNA-seq: high-throughput RNA sequencing; HSCs: haematopoietic stem cells; NSCs: neural stem cells; EpSCs: epidermal stem cells; hESCs: human embryonic stem cells; mESCs: murine embryonic stem cells; MNs: motor neurons; SSUP: small subunit processome; BMSCs: bone marrow-derived mesenchymal stem cells; OGN: osteoglycin; GIOP: glucocorticoidinduced osteoporosis; CDR1as: cerebellar degeneration-related protein 1 transcript; SONFH: steroid-induced osteogenesis of the femoral head; rBMSCs: rat bone marrow-derived mesenchymal stem cells; QUE: quercetin; AcvR1b: activin A receptor type 1B; BSP: bone sialoprotein; mADSCs: mouse ADSCs; PTBP1: polypyrimidine tract-binding protein; ER: endoplasmic reticulum; hUCMSCs: MSCs derived from human umbilical cord; MSMSCs: maxillary sinus membrane stem cells; SCAPs: stem cells from the apical papilla; MyoD: myogenic differentiation protein 1; MSTN: myostatin; MEF2C: myocyte enhancer factor 2C; BCLAF1: BCL2-associated transcription factor 1; EpSCs: epidermal stem cells; ISCs: intestinal stem cells; NSCs: neural stem cells; Lgr5+ ISCs: crypt base columnar cells; ILCs: innate lymphoid cells.