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PURPOSE: This study aimed to evaluate the effect of static management on individuals' oral health-related quality of life (OHRQoL) according to the dynamic zero-COVID policy in China. METHODS: The digital questionnaire conducted with three sub-questionnaires was sent to 700 patients who accepted treatment at the Department of Stomatology, 363 Hospital. Data on demographic characteristics, the Oral Health Impact Profile-14 and willingness to invest in oral health were collected from the 658 completed questionnaires. According to the state of individuals' lives, participants were divided into two groups: a static management group (Group 1) and a nonstatic management group (Group 2). The scores of the Oral Health Impact Profile-14 and willingness to invest in oral health were compared between these two groups using IBM SPSS Statistics. RESULTS: The results showed that individuals undergoing static management reported better OHRQoL. Meanwhile, they also presented lower willingness to invest money and dental visits in oral health. Furthermore, according to the results of the logistic regression analysis, aging acts as a negative correlation factor for the OHRQoL of people undergoing static management, while the willingness to invest money and dental visits in oral health is defined as a positive predictor for OHRQoL. CONCLUSION: Static management effects the OHRQoL of individuals. Aging and WTIOH in money and dental visits are related the individuals' OHRQoL during static management.
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COVID-19 , Humanos , Saúde Bucal , Qualidade de Vida , Envelhecimento , ChinaRESUMO
OBJECTIVE: Solid tumours respond poorly to immune checkpoint inhibitor (ICI) therapies. One major therapeutic obstacle is the immunosuppressive tumour microenvironment (TME). Cancer-associated fibroblasts (CAFs) are a key component of the TME and negatively regulate antitumour T-cell response. Here, we aimed to uncover the mechanism underlying CAFs-mediated tumour immune evasion and to develop novel therapeutic strategies targeting CAFs for enhancing ICI efficacy in oesophageal squamous cell carcinoma (OSCC) and colorectal cancer (CRC). DESIGN: Anti-WNT2 monoclonal antibody (mAb) was used to treat immunocompetent C57BL/6 mice bearing subcutaneously grafted mEC25 or CMT93 alone or combined with anti-programmed cell death protein 1 (PD-1), and the antitumour efficiency and immune response were assessed. CAFs-induced suppression of dendritic cell (DC)-differentiation and DC-mediated antitumour immunity were analysed by interfering with CAFs-derived WNT2, either by anti-WNT2 mAb or with short hairpin RNA-mediated knockdown. The molecular mechanism underlying CAFs-induced DC suppression was further explored by RNA-sequencing and western blot analyses. RESULTS: A negative correlation between WNT2+ CAFs and active CD8+ T cells was detected in primary OSCC tumours. Anti-WNT2 mAb significantly restored antitumour T-cell responses within tumours and enhanced the efficacy of anti-PD-1 by increasing active DC in both mouse OSCC and CRC syngeneic tumour models. Directly interfering with CAFs-derived WNT2 restored DC differentiation and DC-mediated antitumour T-cell responses. Mechanistic analyses further demonstrated that CAFs-secreted WNT2 suppresses the DC-mediated antitumour T-cell response via the SOCS3/p-JAK2/p-STAT3 signalling cascades. CONCLUSIONS: CAFs could suppress antitumour immunity through WNT2 secretion. Targeting WNT2 might enhance the ICI efficacy and represent a new anticancer immunotherapy.
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Fibroblastos Associados a Câncer/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Esofágicas/metabolismo , Inibidores de Checkpoint Imunológico/uso terapêutico , Proteína Wnt2/metabolismo , Animais , Linfócitos T CD8-Positivos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Células Dendríticas/fisiologia , Modelos Animais de Doenças , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Microambiente TumoralRESUMO
Like many complex human diseases, esophageal squamous cell carcinoma (ESCC) is known to cluster in families. Familial ESCC cases often show early onset and worse prognosis than the sporadic cases. However, the molecular genetic basis underlying the development of familial ESCC is mostly unknown. We reported that SLC22A3 is significantly down-regulated in nontumor esophageal tissues from patients with familial ESCC compared with tissues from patients with sporadic ESCCs. A-to-I RNA editing of the SLC22A3 gene results in its reduced expression in the nontumor esophageal tissues of familial ESCCs and is significantly correlated with lymph node metastasis. The RNA-editing enzyme ADAR2, a familial ESCC susceptibility gene identified by our post hoc genome-wide association study, is positively correlated with the editing level of SLC22A3 Moreover, functional studies showed that SLC22A3 is a metastasis suppressor in ESCC, and deregulation of SLC22A3 facilitates cell invasion and filopodia formation by reducing its direct association with α-actinin-4 (ACTN4), leading to the increased actin-binding activity of ACTN4 in normal esophageal cells. Collectively, we now show that A-to-I RNA editing of SLC22A3 contributes to the early development and progression of familial esophageal cancer in high-risk individuals.
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Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Proteínas de Transporte de Cátions Orgânicos/genética , Edição de RNA , Actinina/metabolismo , Adenosina Desaminase/genética , Adenosina Desaminase/metabolismo , Adulto , Idoso , Animais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/secundário , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular , Progressão da Doença , Regulação para Baixo , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/secundário , Carcinoma de Células Escamosas do Esôfago , Esôfago/citologia , Esôfago/metabolismo , Técnicas de Silenciamento de Genes , Estudo de Associação Genômica Ampla , Humanos , Metástase Linfática/genética , Masculino , Camundongos , Camundongos SCID , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Proteínas de Transporte de Cátions Orgânicos/deficiência , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Fatores de RiscoRESUMO
Bone tissue is remodeled through the catabolic function of the osteoclasts and the anabolic function of the osteoblasts. The process of bone homeostasis and metabolism has been identified to be co-ordinated with several local and systemic factors, of which mechanical stimulation acts as an important regulator. Very recent studies have shown a mutual effect between bone and other organs, which means bone influences the activity of other organs and is also influenced by other organs and systems of the body, especially the nervous system. With the discovery of neuropeptide (calcitonin gene-related peptide, vasoactive intestinal peptide, substance P, and neuropeptide Y) and neurotransmitter in bone and the adrenergic receptor observed in osteoclasts and osteoblasts, the function of peripheral nervous system including sympathetic and sensor nerves in bone resorption and its reaction to on osteoclasts and osteoblasts under mechanical stimulus cannot be ignored. Taken together, bone tissue is not only the mechanical transmitter, but as well the receptor of neural system under mechanical loading. This review aims to summarize the relationship among bone, nervous system, and mechanotransduction.
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Remodelação Óssea/genética , Osso e Ossos/metabolismo , Mecanotransdução Celular/genética , Fenômenos Fisiológicos do Sistema Nervoso/genética , Remodelação Óssea/fisiologia , Osso e Ossos/fisiologia , Peptídeo Relacionado com Gene de Calcitonina/genética , Humanos , Neuropeptídeo Y/genética , Osteoblastos/metabolismo , Osteoblastos/fisiologia , Osteoclastos/metabolismo , Osteoclastos/fisiologia , Substância P/genética , Peptídeo Intestinal Vasoativo/genéticaRESUMO
Stem cells are promising candidates for cell-based therapies in diverse conditions including regenerating damaged tissues, treating inflammation in virtue of sepsis, acute renal failure, and cardiovascular disease. Advancement of these therapies relies on the ability to guide stem cells to migrate directly and differentiate towards specific cell phenotypes. During the past decade, many researchers have demonstrated that exogenous applied forces could significantly affect the migration and lineage differentiation of stem cells. Besides, recent advances have highlighted the critical role of internal forces due to cell-matrix interaction in the function of stem cells. Stem cells can generate contractile forces to sense the mechanical properties of cell-generated force microenvironment, and thereby perceive mechanical information that directs broad aspects of stem cell functions, including migration and lineage commitment. In the review, we recount the cell-generated force microenvironment of stem cells and discuss the interactions between cell-generated forces with migration and differentiation of stem cells. We also summarize key experimental evidence of a tight linkage between migration and lineage differentiation of stem cells and pose important unanswered questions in this field.
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Células-Tronco/citologia , Animais , Fenômenos Biomecânicos , Diferenciação Celular , Linhagem da Célula , Movimento Celular , Terapia Baseada em Transplante de Células e Tecidos , Microambiente Celular , Matriz Extracelular/metabolismo , Humanos , Células-Tronco/metabolismoRESUMO
Stem cell-based tissue engineering provides a prospective strategy to bone tissue repair. Bone tissue repair begins at the recruitment and directional movement of stem cells, and ultimately achieved on the directional differentiation of stem cells. The migration and differentiation of stem cells are regulated by nucleoskeletal stiffness. Mechanical properties of lamin A/C contribute to the nucleoskeletal stiffness and consequently to the regulation of cell migration and differentiation. Nuclear lamin A/C determines cell migration through the regulation of nucleoskeletal stiffness and rigidity and involve in nuclear-cytoskeletal coupling. Moreover, lamin A/C is the essential core module regulating stem cell differentiation. The cells with higher migration ability tend to have enhanced differentiation potential, while the optimum amount of lamin A/C in migration and differentiation of MSCs is in conflict. This contrary phenomenon may be the result of mechanical microenvironment modulation.
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Movimento Celular/genética , Lamina Tipo A/genética , Nicho de Células-Tronco/genética , Células-Tronco/metabolismo , Diferenciação Celular/genética , Núcleo Celular/genética , Núcleo Celular/metabolismo , Humanos , Engenharia Tecidual/tendênciasRESUMO
Owing to the development of new technologies, the epigenome, a second dimensional method for genome analysis has emerged. Epigenetic mechanisms, including DNA methylation, histone modifications and noncoding RNAs, regulate gene expression without changing the genetic sequence. These epigenetic mechanisms normally modulate gene expression, trans-generational effects and inherited expression states in various biological processes. Abnormal epigenetic patterns typically cause pathological conditions, including cancers, age-related diseases, and specific cartilage and bone diseases. Facing the rapidly developing epigenetic field, we reviewed epigenetic mechanisms and their involvement with the skeletal system and their role in skeletal development, homeostasis and degeneration. Finally, we discuss the prospects for the future of epigenetics.
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Doenças Ósseas/genética , Epigênese Genética , Animais , Metilação de DNA , Histonas/metabolismo , Humanos , RNA não TraduzidoRESUMO
Obesity shapes anti-tumor immunity through lipid metabolism; however, the mechanisms underlying how colorectal cancer (CRC) cells utilize lipids to suppress anti-tumor immunity remain unclear. Here, we show that tumor cell-intrinsic ATP6V0A1 drives exogenous cholesterol-induced immunosuppression in CRC. ATP6V0A1 facilitates cholesterol absorption in CRC cells through RAB guanine nucleotide exchange factor 1 (RABGEF1)-dependent endosome maturation, leading to cholesterol accumulation within the endoplasmic reticulum and elevated production of 24-hydroxycholesterol (24-OHC). ATP6V0A1-induced 24-OHC upregulates TGF-ß1 by activating the liver X receptor (LXR) signaling. Subsequently, the release of TGF-ß1 into the tumor microenvironment by CRC cells activates the SMAD3 pathway in memory CD8+ T cells, ultimately suppressing their anti-tumor activities. Moreover, we identify daclatasvir, a clinically used anti-hepatitis C virus (HCV) drug, as an ATP6V0A1 inhibitor that can effectively enhance the memory CD8+ T cell activity and suppress tumor growth in CRC. These findings shed light on the potential for ATP6V0A1-targeted immunotherapy in CRC.
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Linfócitos T CD8-Positivos , Colesterol , Neoplasias Colorretais , Transdução de Sinais , Fator de Crescimento Transformador beta1 , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Humanos , Animais , Colesterol/metabolismo , Camundongos , Linhagem Celular Tumoral , Fator de Crescimento Transformador beta1/metabolismo , Memória Imunológica , ATPases Vacuolares Próton-Translocadoras/metabolismo , Microambiente Tumoral/imunologia , Receptores X do Fígado/metabolismo , Hidroxicolesteróis/metabolismo , Hidroxicolesteróis/farmacologia , Pirrolidinas/farmacologia , Proteína Smad3/metabolismo , Camundongos Endogâmicos C57BL , Carbamatos/farmacologiaRESUMO
Objectives: To investigate the efficiency of photobiomodulation on accelerating the tooth movement in the alignment phase of orthodontic treatment. Materials and methods: The data search was performed with PubMed, Embase, Scopus, and the Cochrane Library. Randomized clinical trials and controlled clinical trials evaluating the efficiency of photobiomodulation on accelerating tooth movement in the alignment phase were selected, and the characteristics of the included studies were collected in a customized data form. Data analysis was conducted by the random-effects model after risk of bias and certainty of evidence were assessed. Results: Five randomized clinical trials and three controlled clinical trials were included in the final analysis. All included studies reported positive results except the study of Shehawy et al. The results of the analysis showed that photobiomodulation significantly increased the rate of tooth movement and reduced the treatment duration, compared with the control group. Although the heterogeneity was large among the included studies, it was improved after subgroup analysis. Conclusions: This systematic review offered evidence that photobiomodulation can accelerate tooth movement in alignment procedures and reduce treatment time. Future studies are needed to find the best PBM protocol for orthodontic practice.
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Gastric cancer (GC) is characterized by its vigorous chemoresistance to current therapies, which is attributed to the highly heterogeneous and immature phenotype of cancer stem cells (CSCs) during tumor initiation and progression. The secretory WNT2 ligand regulates multiple cancer pathways and has been demonstrated to be a potential therapeutic target for gastrointestinal tumors; however, its role involved in gastric CSCs (GCSCs) remains unclear. Here, we found that overexpression of WNT2 enhanced stemness properties to promote chemoresistance and tumorigenicity in GCSCs. Mechanistically, WNT2 was positively regulated by its transcription factor SOX4, and in turn, SOX4 was upregulated by the canonical WNT2/FZD8/ß-catenin signaling pathway to form an auto-regulatory positive feedback loop, resulting in the maintenance of GCSCs self-renewal and tumorigenicity. Furthermore, simultaneous overexpression of both WNT2 and SOX4 was correlated with poor survival and reduced responsiveness to chemotherapy in clinical GC specimens. Blocking WNT2 using a specific monoclonal antibody significantly disrupted the WNT2-SOX4 positive feedback loop in GCSCs and enhanced the chemotherapeutic efficacy when synergized with the chemo-drugs 5-fluorouracil and oxaliplatin in a GCSC-derived mouse xenograft model. Overall, this study identified a novel WNT2-SOX4 positive feedback loop as a mechanism for GCSCs-induced chemo-drugs resistance and suggested that the WNT2-SOX4 axis may be a potential therapeutic target for gastric cancer treatment.
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5'-Methylthioadenosine phosphorylase (MTAP) is a key enzyme in the methionine salvage pathway and has been reported to suppress tumorigenesis. The MTAP gene is located at 9p21, a chromosome region often deleted in breast cancer (BC). However, the clinical and biological significance of MTAP in BC is still unclear. Here, we reported that MTAP was frequently downregulated in 41% (35/85) of primary BCs and 89% (8/9) of BC cell lines. Low expression of MTAP was significantly correlated with a poor survival of BC patients (P=0.0334). Functional studies showed that MTAP was able to suppress both in vitro and in vivo tumorigenic ability of BC cells, including migration, invasion, angiogenesis, tumor growth and metastasis in nude mice with orthotopic xenograft tumor of BC. Mechanistically, we found that downregulation of MTAP could increase the polyamine levels by activating ornithine decarboxylase (ODC). By treating the MTAP-repressing BC cells with specific ODC inhibitor Difluoromethylornithine (DFMO) or treating the MTAP-overexpressing BC cells with additional putrescine, metastasis-promoting or -suppressing phenotype of these MTAP-manipulated cells was significantly reversed, respectively. Taken together, our data suggested that MTAP has a critical metastasis-suppressive role by tightly regulating ODC activity in BC cells, which may serve as a prominent novel therapeutic target for advanced breast cancer treatment.
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Neoplasias da Mama , Ornitina Descarboxilase , Purina-Núcleosídeo Fosforilase , Animais , Neoplasias da Mama/enzimologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Regulação para Baixo , Feminino , Xenoenxertos , Humanos , Camundongos , Camundongos Nus , Ornitina Descarboxilase/metabolismo , Purina-Núcleosídeo Fosforilase/genética , Purina-Núcleosídeo Fosforilase/metabolismoRESUMO
BACKGROUND: Next-generation sequencing (NGS) is a massively unbiased sequencing technology. The objective of this study was to evaluate the performance of NGS-based approach in the detection of microorganisms from septic patients and compare with results of blood culture (BC). METHODS: The observational and non-interventional study was conducted from April 2019 to August 2019. RESULTS: A total of 96 sets of BC and 48 NGS results obtained from 48 septic patients were analyzed in this study. Thirty-two microorganisms (27 bacteria, 3 fungi and 2 viral) were detected by NGS in 23 (47.9%) patients; and 18 bacteria in 18 (37.5%) patients by BC. Exclusion of skin commensals, the positivity of NGS and BC was 62.5% and 14.5%, respectively (P < 0.001). Microorganisms identified by NGS demonstrated positive agreement with BC in 12 (25%) patients, including concordant results in 11 (22.9%) cases, and discrepancy results in 1 (2%). Of 11 patients with concordant results, 4 had additional microorganisms detected by NGS. NGS-positive but BC-negative was found in 9 (18.7%) patients. Using NGS, difficult-to-culture micro-organisms such as Pneumocystic jirovecii was identified in 2 patients, and Leptospira interrogans in one. Six (12.5%) patients with BC-positive but NGS-negative, whereas skin commensals were isolated in 4 (66.6%) cases. The number of patients that were positive by BC only increase from 29% to 47.9% when combining NGS and BC analyses (P = 0.033). CONCLUSIONS: Our study support the advantage of NGS for the diagnosis of infecting microorganisms in sepsis, especially for microorganisms that are currently difficult or impossible to culture.
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Hemocultura , Sepse , Humanos , Sepse/diagnóstico , Sepse/microbiologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Bactérias/genética , Fungos/genéticaRESUMO
In this study, bacterial cellulose was synthesized by Taonella mepensis from traditional Chinese medicinal herb residues hydrolysate. To overcome the inhibitory effect of fermentation environment, in-situ fermentation with gellan gum adding was carried out for the first time. After 10 days' static fermentation, both high-acyl gellan gum and low-acyl gellan gum adding showed certain beneficial effects for bacterial cellulose production that the highest bacterial cellulose yield (0.866 and 0.798 g/L, respectively) was 59% and 47% higher than that (0.543 g/L) without gellan gum adding. Besides, gellan gum based bacterial cellulose showed some better texture characteristics. Gellan gum was loaded in the nano network of bacterial cellulose, and gellan gum adding had some influence on the crystal structure and thermal degradation behaviors of bacterial cellulose but affected little on its functional groups. Overall, this in-situ fermentation technology is attractive for bacterial cellulose production from low-cost but inhibitory substrates.
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Celulose/biossíntese , Polissacarídeos Bacterianos/biossíntese , Rhodospirillaceae/metabolismo , Celulose/química , China , Fermentação , Hidrólise , Medicina Tradicional Chinesa , Microscopia Eletrônica de Varredura/métodos , Plantas Medicinais/química , Polissacarídeos Bacterianos/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodosRESUMO
Numerous previous studies have found that C-reactive protein (CRP) is associated with cardiac arrhythmia and cardiac remodeling. However, the underlying mechanisms of this association remain unclear. Sodium-calcium exchanger 1 (NCX1) serves an important role in the regulation of intracellular calcium concentration, which is closely related with cardiac arrhythmia and cardiac remodeling. The present study aimed to evaluate the effects of CRP on NCX1 and intracellular calcium concentration in cardiomyocytes. Primary neonatal mouse ventricular cardiomyocytes were cultured and treated with varying concentrations of CRP (0, 5, 10, 20 and 40 µg/ml). The cardiomyocytes were also treated with NF-κB-specific inhibitor PTDC and a specific inhibitor of the reverse NCX1 KB-R7943 before their intracellular calcium concentrations were measured. mRNA and protein expression levels of NCX1 were detected by reverse transcription-quantitative PCR and western blotting, respectively and intracellular calcium concentration was evaluated by flow cytometry. CRP treatment significantly increased mRNA and protein expression levels of NCX1 in myocytes (P=0.024), as well as intracellular calcium concentration (P=0.01). These results were significantly attenuated by the NF-κB-specific inhibitor PDTC and a specific inhibitor of the reverse NCX1, KB-R7943. CRP significantly upregulated NCX1 expression and increased intracellular calcium concentration in cardiomyocytes via the NF-κB pathway, suggesting that CRP may serve a pro-arrhythmia role via direct influence on the calcium homeostasis of cardiomyocytes.
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Emodin (1, 3, 8-trihydroxy-6-methylanthraquinone) is a derived anthraquinone compound extracted from roots and barks of pharmaceutical plants, including Rheum palmatum, Aloe vera, Giant knotweed, Polygonum multiflorum and Polygonum cuspidatum. The review aims to provide a scientific summary of emodin in pharmacological activities and toxicity in order to identify the therapeutic potential for its use in human specific organs as a new medicine. Based on the fundamental properties, such as anticancer, anti-inflammatory, antioxidant, antibacterial, antivirs, anti-diabetes, immunosuppressive and osteogenesis promotion, emodin is expected to become an effective preventive and therapeutic drug of cancer, myocardial infarction, atherosclerosis, diabetes, acute pancreatitis, asthma, periodontitis, fatty livers and neurodegenerative diseases. This article intends to provide a novel insight for further development of emodin, hoping to reveal the potential of emodin and necessity of further studies in this field.
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Antraquinonas/farmacologia , Antraquinonas/toxicidade , Emodina/farmacologia , Emodina/toxicidade , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Humanos , Estrutura Molecular , Casca de Planta , Raízes de PlantasRESUMO
Dental caries is the most common oral disease. The bacteriological aetiology of dental caries promotes the use of antibiotics or antimicrobial agents to prevent this type of oral infectious disease. Antibiotics have been developed for more than 80 years since Fleming discovered penicillin in 1928, and systemic antibiotics have been used to treat dental caries for a long time. However, new types of antimicrobial agents have been developed to fight against dental caries. The purpose of this review is to focus on the application of systemic antibiotics and other antimicrobial agents with respect to their clinical use to date, including the history of their development, and their side effects, uses, structure types, and molecular mechanisms to promote a better understanding of the importance of microbial interactions in dental plaque and combinational treatments.
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Antibacterianos/uso terapêutico , Cárie Dentária/tratamento farmacológico , Antibacterianos/classificação , Anti-Infecciosos/uso terapêutico , Placa Dentária/tratamento farmacológico , Placa Dentária/microbiologia , Resistência Microbiana a Medicamentos , Humanos , Interações Microbianas , Probióticos/uso terapêutico , Remineralização DentáriaRESUMO
Esophageal cancer (EC) seriously threatens human health, and a promising new avenue for EC treatment involves cancer immunotherapy. To improve the efficacy of EC immunotherapy and to develop novel strategies for EC prognosis prediction or clinical treatment, understanding the immune landscapes in EC is required. EC cells harbor abundant tumor antigens, including tumor-associated antigens and neoantigens, which have the ability to initiate dendritic cell-mediated tumor-killing cytotoxic T lymphocytes in the early stage of cancer development. As EC cells battle the immune system, they obtain an ability to suppress antitumor immunity through immune checkpoints, secreted factors, and negative regulatory immune cells. Cancer-associated fibroblasts also contribute to the immune evasion of EC cells. Some factors of the immune landscape in EC tumor microenvironment are associated with cancer development, patient survival, or treatment response. Based on the immune landscape, peptide vaccines, adoptive T cell therapy, and immune checkpoint blockade can be used for EC immunotherapy. Combined strategies are required for better clinical outcome in EC. This review provides directions to design novel and effective strategies for prognosis prediction and immunotherapy in EC.
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Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/terapia , Humanos , Imunoterapia , PrognósticoRESUMO
Cancer-associated fibroblasts (CAFs) play critical roles in cancer progression and treatment failure. CAFs display extreme phenotypic heterogeneity and functional diversity. Some subpopulations of CAFs have the ability to reconstitute cancer stemness by promoting the expansion of cancer stem cells (CSCs) or by inducing the generation of CSCs from differentiated cancer cells. CAFs regulate cancer stemness in different types of solid tumors by activating a wide array of CSC-related signaling by secreting proteins and exosomes. As feedback, the CSCs can also induce the proliferation and further activation of CAFs to promote their CSC-supporting activities, thus completing the loop of CAF-CSC crosstalk. Current research on targeting CAF-CSC crosstalk could be classified into (i) specific depletion of CAF subpopulations that have CSC-supporting activities and (ii) targeting molecular signaling in CAF-CSC crosstalk, such as the IL6/STAT3, TGF-ß/SDF-1/PI3K, WNT/ß-catenin, HGF/cMET and SHH/Hh pathways. Strategies targeting CAF-CSC crosstalk may open new avenues for overcoming cancer progression and therapeutic resistance.
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Esophageal squamous cell carcinoma (ESCC) occurs with the highest frequency in China, especially in the high-risk Northern Chinese. Recent studies have reported that SLC22A3 is significantly downregulated in non-tumor (NT) esophageal tissues from familial ESCC patients compared with those from sporadic ESCC. However, the mechanism of how SLC22A3 regulates familial ESCC remains unknown. In this study, post hoc genome-wide association studies (GWAS) in 496 cases with a family history of upper gastrointestinal tract cancers and 1056 controls were performed and the results revealed that SLC22A3 is a novel susceptibility gene for familial ESCC. Reduced expression of SLC22A3 in NT esophageal tissues from familial ESCC patients significantly correlates with its promoter hypermethylation. Moreover, case-control study of Chinese descendants from different risk areas of China revealed that the methylation of the SLC22A3 gene in peripheral blood leukocyte (PBL) DNA samples could be a risk factor for developing ESCC in this high-risk population. Functional studies showed that SLC22A3 is a novel antioxidant gene, and deregulation of SLC22A3 facilitates heat stress-induced oxidative DNA damage and formation of γ-H2AX foci in normal esophageal epithelial cells. Collectively, we show that epigenetic alterations of SLC22A3 predispose susceptible individuals to increased risk of esophageal cancer.
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Epigênese Genética/genética , Neoplasias Esofágicas/genética , Estudo de Associação Genômica Ampla/métodos , Proteínas de Transporte de Cátions Orgânicos/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Estudos de Casos e Controles , Dano ao DNA/genética , Metilação de DNA/genética , Feminino , Imunofluorescência , Predisposição Genética para Doença/genética , Resposta ao Choque Térmico , Humanos , Lentivirus/genética , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Regiões Promotoras Genéticas/genética , Espécies Reativas de Oxigênio/metabolismoRESUMO
Telemedicine interventions may be associated with reductions in hospital admission rate and mortality in patients with heart failure (HF). The present study is an updated analysis (as of June 30, 2016) of randomized controlled trials, where patients with HF underwent telemedicine care or the usual standard care. Data were extracted from 39 eligible studies for all-cause and HF-related hospital admission rate, length of stay, and mortality. The overall all-cause mortality (pooled OR=0.80, 95% CI 0.71 to 0.91, p<0.001), HF-related admission rate (pooled OR=0.63, 95% CI 0.53 to 0.76, p<0.001), and HF-related length of stay (pooled standardized difference in means=-0.37, 95% CI -0.72 to -0.02, p=0.041) were significantly lower in the telemedicine group (teletransmission and telephone-supported care), as compared with the control group. In subgroup analysis, all-cause mortality (pooled OR=0.69, 95% CI 0.56 to 0.86, p=0.001), HF-related admission rate (OR=0.61, 95% CI 0.42 to 0.88, p=0.008), HF-related length of stay (pooled standardized difference in means=-0.96, 95% CI -1.88 to -0.05, p=0.039) and HF-related mortality (OR=0.68, 95% CI 0.54 to 0.85, p=0.001) were significantly lower in the teletransmission group, as opposed to the standard care group, whereas only HF-related admission rate (OR=0.64, 95% CI 0.52 to 0.79, p<0.001) was lower in the telephone-supported care group. Overall, telemedicine was shown to be beneficial, with home-based teletransmission effectively reducing all-cause mortality and HF-related hospital admission, length of stay and mortality in patients with HF.