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1.
Life Sci Space Res (Amst) ; 35: 105-112, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36336356

RESUMO

Future lunar missions and beyond will require new and innovative approaches to radiation countermeasures. The Translational Research Institute for Space Health (TRISH) is focused on identifying and supporting unique approaches to reduce risks to human health and performance on future missions beyond low Earth orbit. This paper will describe three funded and complementary avenues for reducing the risk to humans from radiation exposure experienced in deep space. The first focus is on identifying new therapeutic targets to reduce the damaging effects of radiation by focusing on high throughput genetic screens in accessible, sometimes called lower, organism models. The second focus is to design innovative approaches for countermeasure development with special attention to nucleotide-based methodologies that may constitute a more agile way to design therapeutics. The final focus is to develop new and innovative ways to test radiation countermeasures in a human model system. While animal studies continue to be beneficial in the study of space radiation, they can have imperfect translation to humans. The use of three-dimensional (3D) complex in vitro models is a promising approach to aid the development of new countermeasures and personalized assessments of radiation risks. These three distinct and unique approaches complement traditional space radiation efforts and should provide future space explorers with more options to safeguard their short and long-term health.


Assuntos
Radiação Cósmica , Exposição à Radiação , Proteção Radiológica , Voo Espacial , Animais , Humanos , Radiação Cósmica/efeitos adversos , Proteção Radiológica/métodos , Lua
2.
Artigo em Inglês | MEDLINE | ID: mdl-36345132

RESUMO

High charge carrier mobility polymer semiconductors are always semi-crystalline. Amorphous conjugated polymers represent another kind of polymer semiconductors with different charge transporting mechanism. Here we report the first near-amorphous n-type conjugated polymer with decent electron mobility, which features remarkably rigid, straight and planar polymer backbone. The molecular design strategy is to copolymerize two fused-ring building blocks which are both electron-accepting, centrosymmetrical and planar. The polymer is the alternating copolymer of double B←N bridged bipyridine (BNBP) unit and benzobisthiazole (BBTz) unit. It shows a decent electron mobility of 0.34 cm 2 V -1 s -1 in organic field-effect transistors. The excellent electron transporting property of the polymer is possibly due to the ultrahigh backbone stiffness, small π-π stacking distance and high molecular weight.

3.
Ann Med ; 54(1): 3219-3233, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36382627

RESUMO

BACKGROUND: Ulcerative colitis (UC), a chronic inflammatory disease, often cause carcinogenesis, disability, and intestinal perforation. The JingFangFuZiLiZhong formula (JFFZLZ) shows a good effect against UC in the clinic. Hence, we aim to investigate the mechanisms between JFFZLZ and UC via network pharmacology data mining and in vivo experiments. METHODS: We obtained active constituents and related targets from public databases. The overlapped genes between JFFZLZ and UC targets were further analysed by enrichment analysis. The active constituents and hub targets were used to construct molecule docking analysis. We finally screened out nine hub targets and their expressions were verified in the Gene Expression Omnibus database and UC rats' colon tissues after JFFZLZ treatment. RESULTS: The results implied that JFFZLZ mainly regulated signal transduction, metabolites production, and inflammation pathways. The expression of STAT3, CXCL8, IL6, CXCL12, TNF, TP53, and PTPN11 were both upregulated in colon tissues of UC patients and UC rats. While RELA, EGFR, and TP53 were downregulated in UC patients, but upregulated in UC rats. Furthermore, JFFZLZ could repair UC rats' colon mucosal damage and promote the healing of ulcers via regulating the hub targets. CONCLUSION: These results elucidated that the anti-UC effect of JFFZLZ was closely related to the inhibition of inflammatory response, inhibition of oxidative stress, and repairing colon mucosal damage through different signal pathways. The findings could contribute to a better understanding of the regulation mechanisms in JFFZLZ against UC.Key messagesJFFZLZ could reduce the inflammatory infiltration and repair UC rats' colon mucosal damage.Through the network pharmacology-based strategy and public database mining, we obtained the hub targets and key pathways between JFFZLF and UC.The mechanism of JFFZLZ against UC was inhibition of inflammatory response and oxidative stress by regulating the expression of the hub targets.


Assuntos
Colite Ulcerativa , Humanos , Ratos , Animais , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/genética , Farmacologia em Rede , Mucosa Intestinal/metabolismo , Transdução de Sinais
4.
Front Public Health ; 10: 1037527, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36407996

RESUMO

Background: Discontinuation of Nucleos(t)ide analogs (NAs) remains one of the most controversial topics in the management of hepatitis B-related liver cirrhosis. However, clinical outcomes after NAs discontinuation have not been studied. Aim: The aim of this systematic review is to evaluate existing data on clinical outcomes of NAs withdrawal in chronic hepatitis B (CHB) patients with cirrhosis. Methods: A literature search (until May 2022) was performed in order to identify all published studies including hepatitis B-related cirrhotic patients who discontinued NAs in virological remission with off-therapy follow-up >12 months. Results: Nineteen studies with 1,287 hepatitis B-related cirrhotic patients were included. Most cirrhotic patients were compensated and achieved complete virological suppression when they stopped the antiviral therapy. The pooled proportions of virological relapse and clinical relapse after NAs discontinuation in cirrhotic patients were 55.23 (95% CI: 40.33-69.67) and 43.56% (95% CI: 26.13-61.85), respectively. HBsAg loss was observed in 56 of 500 (pooled proportion = 13.68%, 95% CI: 5.82-24.18) cirrhotic patients. And the pooled proportions of HCC development, hepatic decompensation and overall mortality were 8.76 (95% CI: 2.25-18.95), 3.63 (95% CI: 1.31-7.03), and 0.85% (95% CI: 0.35-1.57), respectively, after NAs discontinuation in cirrhotic patients. Conclusion: In hepatitis B-related compensated cirrhosis, who have achieved complete virological suppression, discontinuation of oral antivirals still carries a high relapse rate, but the incidence of adverse events is generally low and controlled during follow-up of at least 12 months. Of attention is that discontinuation of NAs can achieve a high rate of HBsAg seroclearance. This study may be helpful in the management of NAs in cirrhotic patients. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO, identifier: CRD42020170103.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Humanos , Antivirais/uso terapêutico , Antígenos de Superfície da Hepatite B/uso terapêutico , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/tratamento farmacológico , Recidiva Local de Neoplasia/induzido quimicamente , Recidiva Local de Neoplasia/complicações , Recidiva Local de Neoplasia/tratamento farmacológico , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Cirrose Hepática/etiologia , Cirrose Hepática/induzido quimicamente
5.
Sci Total Environ ; 858(Pt 2): 159954, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36347297

RESUMO

The purpose of this study was to access the effects of thermotolerant nitrifying microorganisms and sulfur-oxidizing bacteria on microbial community and enzyme activity involved in nitrogen­sulfur metabolism during laboratory-scale sewage sludge (SS) composting,and to do a microbial-environmental factor association analysis to promote composting key species for nitrogen­sulfur transformation in the body. The microbial community structure and the activities variation of six key enzyme involved were detected. The microbial inocula added had little impact on the diversity of the microbial community but changed its succession direction, and the abundance of Actinobacteria was decreased obviously of inoculation treatment (TR). The three dominant genera and indicator species in TR were significantly correlated with the conversion of nitrogen and sulfur. The addition of microbial inocula promoted the conversion of nitrogen and sulfur in SS compost, and increased the activities of the key enzymes and the microbial genera involved in nitrogen­sulfur conversion. In other words, the nitrification and sulfur oxidation were enhanced simultaneously in the later stage of composting in TR.

6.
Cancer Biomark ; 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36373305

RESUMO

BACKGROUND: Long non-coding RNA (LncRNA) TUG1 plays a critical role in the development of human cancers. This study explored whether TUG1 is involved in the cytotoxicity of dendritic cells and cytokine-induced killer cells (DCs-CIK), an immunotherapy approach, in neuroblastoma. METHODS: A TUG1 expression plasmid was transfected into DCs. Neuroblastoma SK-N-SH cells were incubated with CIK cells, DCs-CIK cells, and TUG1-overexpressing DCs-CIK cells, with or without irradiation. SK-N-SH cell viability, colony formation, migration, and apoptosis were analyzed using CCK-8, colony formation assay, transwell assay, and flow cytometry, respectively. Production of IL-12, IL-2 and IFN-γ in the supernatants was determined using ELISA. A dual luciferase activity assay was performed to confirm the molecular interactions between TUG1 and miR-204. Tumor-bearing mice were established by injection of SK-N-SH cells followed by stimulation with CIK cells, DC-CIK cells, and TUG1-overexpressing DCs-CIK cells. RESULTS: Compared to CIK alone or DC-CIK therapy, overexpression of TUG1 significantly suppressed tumor cell proliferation, colony formation, and migration of neuroblastoma cells. Moreover, upregulation of TUG1 robustly induced apoptosis and altered key molecules associated with apoptosis and epithelial-mesenchymal transition. Contents of IL-12, IL-2 and IFN-γ were dramatically elevated in the supernatants in the coculturing system upon transfection with TUG1. In addition, TUG1 was found to be act as miR-204 sponge. Furthermore, in vivo experiments demonstrated that upregulation of TUG1 potentiated the antitumor activity of DC-CIK immunotherapy. CONCLUSION: Overexpression of TUG1 promotes DC maturation and enhances CIK cytotoxicity, suggesting that TUG1 may be a novel target for enhancing DC-CIK based immunotherapy for neuroblastoma.

7.
Life Sci Space Res (Amst) ; 35: 140-149, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36336359

RESUMO

NASA aims to return humans to the moon within the next five years and to land humans on Mars in a few decades. Space radiation exposure represents a major challenge to astronauts' health during long-duration missions, as it is linked to increased risks of cancer, cardiovascular dysfunctions, central nervous system (CNS) impairment, and other negative outcomes. Characterization of radiation health effects and developing corresponding countermeasures are high priorities for the preparation of long duration space travel. Due to limitations of animal and cell models, the development of novel physiologically relevant radiation models is needed to better predict these individual risks and bridge gaps between preclinical testing and clinical trials in drug development. "Clinical Trial in a Dish" (CTiD) is now possible with the use of human induced pluripotent stem cells (hiPSCs), offering a powerful tool for drug safety or efficacy testing using patient-specific cell models. Here we review the development and applications of CTiD for space radiation biology and countermeasure studies, focusing on progress made in the past decade.


Assuntos
Radiação Cósmica , Células-Tronco Pluripotentes Induzidas , Lesões por Radiação , Voo Espacial , Animais , Humanos , Astronautas , Radiação Cósmica/efeitos adversos , Lua , Lesões por Radiação/prevenção & controle , Ensaios Clínicos como Assunto
8.
Front Oncol ; 12: 1024915, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439512

RESUMO

Background: The role of ferroptosis in tumor progression and immune microenvironment is extensively investigated. However, the potential value of ferroptosis regulators in predicting prognosis and therapeutic strategies for osteosarcoma (OS) patients remains to be elucidated. Methods: Here, we extracted transcriptomic and survival data from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) to investigate the expression and prognostic value of ferroptosis regulators in OS patients. After comprehensive analyses, including Gene set variation analysis (GSVA), single-sample gene-set enrichment analysis (ssGSEA), Estimated Stromal and Immune cells in Malignant Tumor tissues using Expression (ESTIMATE), single-cell RNA sequencing, and biological experiments, our constructed 8-ferroptosis-regulators prognostic signature effectively predicted the immune landscape, prognosis, and chemoradiotherapy strategies for OS patients. Results: We constructed an 8-ferroptosis-regulators signature that could predict the survival outcome of OS. The signature algorithm scored samples, and high-scoring patients were more prone to worse prognoses. The tumor immune landscape suggested the positive relevance between risk score and immunosuppression. Interfering HILPDA and MUC1 expression would inhibit tumor cell proliferation and migration, and MUC1 might improve the ferroptosis resistance of OS cells. Moreover, we predicted chemoradiotherapy strategies of cancer patients following ferroptosis-risk-score groups. Conclusion: Dysregulated ferroptosis gene expression can affect OS progression by affecting the tumor immune landscape and ferroptosis resistance. Our risk model can predict OS survival outcomes, and we propose that HILPDA and MUC1 are potential targets for cancer therapy.

9.
Diabetol Metab Syndr ; 14(1): 181, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36443867

RESUMO

BACKGROUND: As the nonalcoholic fatty liver disease (NAFLD) epidemic matures, understanding how metabolic changes in NAFLD development vary over the age distribution is important to guide precise prevention. We aimed to clarify metabolic trends in age-specific NAFLD incidence. METHODS: We conducted a 4-year longitudinal retrospective cohort study enrolling 10,240 consecutive healthy individuals who received annual physical examination during 2012-2019. Baseline and dynamic changes in metabolism and hepatic steatosis determined with ultrasound were collected and analyzed stratified by age into the following groups: 20-34, 35-49, 50-64, and over 65 years. RESULTS: Overall, 1701 incident NAFLD participants (16.6%) were identified. Adjusted Cox regression analysis showed that the baseline and increased body mass index were the main risk factors for NAFLD in people ≤ 65 years old. Baseline high-density lipoprotein (HR = 0.56; 95% CI 0.39-0.78) was a protective factor for newly onset NAFLD in the 50-to-64-year-old group, while baseline SBP (HR = 1.03; 95% CI 1.01-1.05), baseline uric acid (HR = 1.04; 95% CI 1.01-1.07), triglyceride increase (HR = 4.76; 95% CI 3.69-6.14), fasting blood glucose increase (HR = 1.32; 95% CI 1.06-1.65) were independently associated with incident NAFLD in over-65-year-old group. CONCLUSIONS: NAFLD incidence attributable to potentially metabolic risk factors varied substantially across age groups in a cohort of Chinese people. The adoption of age targeted metabolic prevention strategies might reduce the burden of NAFLD.

10.
Environ Pollut ; 316(Pt 1): 120701, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36423888

RESUMO

Studies exploring the association of tetrabromobisphenol A (TBBPA) with breast cancer and related mechanisms are limited. To investigate the relationship between TBBPA levels in breast adipose and breast cancer, we carried out case-control research. As well as further examine the mediating role of adipose metabolites between TBBPA and breast cancer using the metabolomics approach. In this study, the concentration of TBBPA was determined utilizing ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) after a solid phase extraction (SPE) pretreatment. High-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) was employed to analyze adipose metabolomics. Evaluation of metabolites linked to TBBPA exposure and breast cancer was performed utilizing mediation analysis. With an estimated OR (95%CI) of 1.153 (1.023, 1.299), TBBPA was firmly linked with breast cancer. We also used propensity score matching analysis and sensitivity analysis to reduce the effect of confounding factors on the results. Metabolomics of adipose suggested significant perturbation in the linoleic acid metabolism pathway. In addition, for PC (16:0/16:0) as phospholipids, a mediation effect on the associations of TBBPA exposure with breast cancer risks was observed (estimated mediation percentage: 56.58%). Understanding the relationship between TBBPA exposure and the risk of breast cancer may be facilitated by the findings, which point to potential mediation metabolites.

12.
Artigo em Inglês | MEDLINE | ID: mdl-36322712

RESUMO

AIMS: Diabetic cardiomyopathy (DCM) is characterized by cardiac dysfunction and heart failure. However, the effective therapy for DCM is still lacking. Polysulfide contains chains of sulfur atoms, and accumulative evidences have shown that it actively participates in mammalian physiology or pathophysiology. Nevertheless, the potential effects and mechanisms of polysulfide in DCM need further investigation. In the present study, Na2S4, a polysulfide donor, was employed to investigate the therapeutic effects of polysulfide in DCM. RESULTS: Our results showed that Na2S4 protected cardiomyocytes against high glucose (HG)-induced cardiomyocyte injury. The pathological changes in DCM including cell death, oxidative stress, mitochondrial dysfunction and cardiac hypertrophy were improved by Na2S4 treatment. The left ventricular contractile function in streptozotocin (STZ)-induced diabetic mice was significantly improved by Na2S4. Mechanistically, Na2S4 upregulated and sulfhydrated peroxisome proliferator-activated receptor-γ (PPARγ) and sirtuin 3 (SIRT-3) in cardiomyocytes. Suppression of PPARγ or SIRT-3 with their specific inhibitors or blockade of sulfhydration abolished the protective effects of Na2S4. Moreover, mutations of PPARγ or SIRT-3 at specific cysteines diminished the benefits of Na2S4 in HG-challenged cardiomyocytes. INNOVATION AND CONCLUSION: We demonstrated that Na2S4 prevented the development of DCM via sulfhydration of both PPARγ and SIRT3. Our results imply that polysulfide may be a potential and promising agent to treat DCM.

13.
Elife ; 112022 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-36264609

RESUMO

Functionally distinct subtypes/clusters of dorsal root ganglion (DRG) neurons may play different roles in nerve regeneration and pain. However, details about their transcriptomic changes under neuropathic pain conditions remain unclear. Chronic constriction injury (CCI) of the sciatic nerve represents a well-established model of neuropathic pain, and we conducted single-cell RNA-sequencing (scRNA-seq) to characterize subtype-specific perturbations of transcriptomes in lumbar DRG neurons on day 7 post-CCI. By using PirtEGFPf mice that selectively express an enhanced green fluorescent protein in DRG neurons, we established a highly efficient purification process to enrich neurons for scRNA-seq. We observed the emergence of four prominent CCI-induced clusters and a loss of marker genes in injured neurons. Importantly, a portion of injured neurons from several clusters were spared from injury-induced identity loss, suggesting subtype-specific transcriptomic changes in injured neurons. Moreover, uninjured neurons, which are necessary for mediating the evoked pain, also demonstrated cell-type-specific transcriptomic perturbations in these clusters, but not in others. Notably, male and female mice showed differential transcriptomic changes in multiple neuronal clusters after CCI, suggesting transcriptomic sexual dimorphism in DRG neurons after nerve injury. Using Fgf3 as a proof-of-principle, RNAscope study provided further evidence of increased Fgf3 in injured neurons after CCI, supporting scRNA-seq analysis, and calcium imaging study unraveled a functional role of Fgf3 in neuronal excitability. These findings may contribute to the identification of new target genes and the development of DRG neuron cell-type-specific therapies for optimizing neuropathic pain treatment and nerve regeneration.


Assuntos
Neuralgia , RNA Citoplasmático Pequeno , Ratos , Camundongos , Masculino , Feminino , Animais , Gânglios Espinais/metabolismo , Transcriptoma , Análise de Célula Única , Cálcio/metabolismo , Ratos Sprague-Dawley , Neuralgia/metabolismo , Neurônios/metabolismo , Hiperalgesia/metabolismo , Proteínas de Transporte/metabolismo , Proteínas de Membrana/metabolismo
14.
J Inflamm Res ; 15: 5801-5814, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36238765

RESUMO

Background: Hepatocellular carcinoma (HCC) is one of the most malignant tumors worldwide. The ST6 ß-galactoside α-2, 6-sialyltransferase 1 (ST6GAL1) has been found aberrantly expressed in a variety of cancers including HCC, but its function and mechanism in regulating liver inflammation remain to be investigated. This study aimed to explore the role of ST6GAL1 in HCC. The data of ST6GAL1 expression, prognosis, and clinical parameters were collected and further analyzed from the public databases including The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), and Gene Expression Omnibus (GEO). The HCC rat model was constructed by intraperitoneal injection of diethylnitrosamine. The mRNA and protein expression levels of ST6GAL1 in rat liver tissues were detected by real-time quantitative polymerase chain reaction, capillary electrophoresis, and Western blot. Results: The ST6GAL1 mRNA and protein expression levels were both lower in HCC tissues compared with normal liver tissues in the public databases and HCC rat model. The survival analysis showed that upregulation of ST6GAL1 was an independent prognostic factor for good prognosis in HCC patients. The ST6GAL1 mRNA expression showed a negative correlation with ST6GAL1 methylation levels. Enrichment analysis showed that ST6GAL1 expression was most associated with metabolic, cancer, estrogen, axon guidance, cAMP, and PI3K-AKT signaling pathways. The ST6GAL1 mRNA expression negatively correlated with liver inflammation status and proportion of NK CD56bright, NK CD56dim, pDC, and CD8+ T cells in liver. Conclusion: Compared with normal tissues, ST6GAL1 was lower expressed in HCC tumor tissues, and the downregulation of ST6GAL1 was associated with a poor prognosis in HCC patients. ST6GAL1 could further affect the infiltration of immune cells to exert anti-inflammation function in liver. Our study indicated that ST6GAL1 could be a potential biomarker and therapeutic target to assess the prognosis and regulate the immune cells infiltration level of HCC.

15.
Cell Metab ; 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36257317

RESUMO

Accumulating evidence indicates that interoception maintains proper physiological status and orchestrates metabolic homeostasis by regulating feeding behaviors, glucose balance, and lipid metabolism. Continuous skeletal remodeling consumes a tremendous amount of energy to provide skeletal scaffolding, support muscle movement, store vital minerals, and maintain a niche for hematopoiesis, which are processes that also contribute to overall metabolic balance. Although skeletal innervation has been described for centuries, recent work has shown that skeletal metabolism is tightly regulated by the nervous system and that skeletal interoception regulates bone homeostasis. Here, we provide a general discussion of interoception and its effects on the skeleton and whole-body metabolism. We also discuss skeletal interoception-mediated regulation in the context of pathological conditions and skeletal pain as well as future challenges to our understanding of these process and how they can be leveraged for more effective therapy.

16.
Front Pharmacol ; 13: 985084, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36133813

RESUMO

The Chinese traditional medicine KangXianYiAi formula (KXYA) is used to treat hepatic disease in the clinic. Here we aim to confirm the therapeutic effects and explore the pharmacological mechanisms of KXYA on hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). We first collected and analyzed clinical data of 40 chronic hepatitis B (CHB) patients with precancerous liver lesions under KXYA treatment. Then, the cell viability, migration, cell cycle, and apoptosis of HepAD38 cells with KXYA treatment were examined. Next, we performed network pharmacological analysis based on database mining to obtain the key target pathways and genes of KXYA treatment on HBV-related HCC. We finally analyzed the expression of the key genes between normal and HBV-related HCC tissues in databases and measured the mRNA expression of the key genes in HepAD38 cells after KXYA treatment. The KXYA treatment could reduce the liver nodule size of CHB patients, suppress the proliferation and migration capabilities, and promote apoptosis of HepAD38 cells. The key pathways of KXYA on HBV-related HCC were Cancer, Hepatitis B, Viral carcinogenesis, Focal adhesion, and PI3K-Akt signaling, and KXYA treatment could regulate the expression of the key genes including HNF4A, MAPK8, NR3C1, PTEN, EGFR, and HDAC1. The KXYA exhibited a curative effect via inhibiting proliferation, migration, and promoting apoptosis of HBV-related HCC and the pharmacological mechanism was related to the regulation of the expression of HNF4A, MAPK8, NR3C1, PTEN, EGFR, and HDAC1.

17.
Front Oncol ; 12: 926920, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36172155

RESUMO

Background: Commensal microbiota have been proven to colonize the mammary gland, but whether their composition is altered in patients with breast cancer (BC) remains elusive. This study intends to explore the breast microbiome differences between benign and malignant diseases and to investigate the impact of neoadjuvant chemotherapy (NAC) on the breast microbiota in patients with BC. Methods: Breast normal adipose tissues (NATs) were collected from 79 patients with BC and 15 controls between July 2019 and November 2021. The BC group consisted of 29 patients who had received NAC and 50 who were non-NAC patients. Participants diagnosed with benign breast disease were recruited as controls. 16S rRNA gene sequencing was used to analyze the bacterial diversity of NATs. Results: The community structure of the NAT microbiome was significantly different between the BC and control groups. Proteobacteria decreased (47.40% versus 39.74%), whereas Firmicutes increased (15.71% versus 25.33%) in patients with BC when compared with that in control tissues. Nine genera were enriched in BC NATs, and four genera levels increased in the control group. The associations between differential bacterial genera and breast tumor grade were calculated by Spearman's correlation. The results showed that tumor grade was positively associated with the relative abundance of Streptococcus and negatively related to Vibrio, Pseudoalteromonas, RB41, and Photobacterium. Moreover, menopause was associated with the microbiota composition change of non-NAC BC patients and related to the significant reduction in the abundance level of Pseudoalteromonas, Veillonella, and Alcaligenes. In addition, NAC was related to the beta diversity of patients with BC and associated with the decrease of Clostridium_sensu_stricto_7 and Clostridium_sensu_stricto_2 in postmenopausal patients. Of note, Tax4Fun functional prediction analysis revealed that the metabolic state was more exuberant in the BC group with upregulating of multiple metabolism-related pathways. Conclusion: Our results offer new insight into the relationship between NAC and breast microbiota and help to better characterize the breast microbial dysbiosis that occurs in patients with BC. Further epidemiological studies with larger sample size and well-designed animal experiments are required to elucidate the role of breast microbiota in the therapeutic outcome of BC.

18.
Environ Health ; 21(1): 83, 2022 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-36085159

RESUMO

BACKGROUND: Perfluoroalkyl substances (PFASs) are a large family of synthetic chemicals, some of which are mammary toxicants and endocrine disruptors. Recent studies have implicated exposure to PFASs as a risk factor for breast cancer in Europe and America. Little is known about the role of PFASs with respect to breast cancer in the Chinese population. METHODS: Participants who were initially diagnosed with breast cancer at Tianjin Medical University Cancer Institute and Hospital between 2012 and 2016 were recruited as cases. The controls were randomly selected from the participants with available blood samples in the Chinese National Breast Cancer Screening Program (CNBCSP) cohort. Ultimately, we enrolled 373 breast cancer patients and 657 controls. Plasma PFASs were measured by an ultra-performance liquid chromatography (UPLC) system coupled to a 5500 Q-Trap triple quadrupole mass spectrometer. A logistic regression model with least absolute shrinkage and selection operator (LASSO) regularization was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to assess the relationships between PFASs and breast cancer. The three most predictive variables in the LASSO model were selected from 17 PFASs, which was based on the optimal penalty coefficient (λ = 0.0218) identified with the minimum criterion. Additionally, Bayesian kernel machine regression (BKMR) and quantile g-computation models were applied to evaluate the associations between separate and mixed exposure to PFASs and breast cancer. RESULTS: Perfluorooctanesulfonic acid (PFOS) exhibited the highest concentration in both the cases and controls. Perfluorooctanoic acid (PFOA) and perfluoro-n-decanoic acid (PFDA) were positively associated with breast cancer, and perfluoro-n-tridecanoic acid (PFTrDA) was negatively associated with breast cancer according to both the continuous-PFASs and the quartile-PFASs logistic regression models. Of note, PFOA was associated with the occurrence of estrogen receptor (ER)-, progesterone receptor (PR)-, and human epidermal growth factor receptor 2 (HER2)-positive breast cancer (ORER+ = 1.47, 95% CI: 1.19, 1.80; ORPR+ = 1.36, 95% CI: 1.09, 1.69; ORHER2 = 1.62, 95% CI: 1.19, 2.21). CONCLUSIONS: Overall, we observed that PFASs were associated with breast cancer in Chinese women. Prospective cohort studies and mechanistic experiments are warranted to elucidate whether these associations are causal.


Assuntos
Neoplasias da Mama , Fluorcarbonetos , Teorema de Bayes , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/epidemiologia , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Estudos Prospectivos , Fatores de Risco
19.
Front Genet ; 13: 919857, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118862

RESUMO

Long non-coding RNAs (lncRNAs) can influence the proliferation, autophagy, and apoptosis of non-small cell lung cancer (NSCLC). LncRNAs also emerge as valuable prognostic factors for NSCLC patients. Consequently, we set out to discover more autophagy-associated lncRNAs. We acquired autophagy-associated genes and information on lncRNAs from The Cancer Genome Atlas database (TCGA), and the Human Autophagy Database (HADb). Then, the prognostic prediction signature was constructed through using co-expression and Cox regression analysis. The signature was constructed including 7 autophagy-associated lncRNAs (ABALON, NKILA, LINC00941, AL161431.1, AL691432.2, AC020765.2, MMP2-AS1). After that, we used univariate and multivariate Cox regression analysis to calculate the risk score. The survival analysis and ROC curve analysis confirmed good performances of the signature. GSEA indicated that the high-risk group was principally enriched in the adherens junction pathway. In addition, biological experiments showed that ABALON promoted the proliferation, metastasis and autophagy levels of NSCLC cells. These findings demonstrate that the risk signature consisting of 7 autophagy-associated lncRNAs accurately predicts the prognosis of NSCLC patients and should be investigated for potential therapeutic targets in clinic.

20.
Artigo em Inglês | MEDLINE | ID: mdl-36061412

RESUMO

ICG-based dynamic contrast-enhanced fluorescence imaging (DCE-FI) and intraoperative DCE- magnetic resonance imaging (MRI) have been carried out nearly simultaneously in three lower extremity bone infection cases to investigate the relationship between these two imaging modalities for assessing bone blood perfusion during open orthopedic surgeries. Time-intensity curves in the corresponding regions of interest of two modalities were derived for comparison. The results demonstrated that ICG-based DCE-FI has higher sensitivity to perfusion changes while DCE-MRI provides superior and supplemental depth-related perfusion information. Research applying the depth-related perfusion information derived from MRI to improve the overall analytic modeling of intraoperative DCE-FI is ongoing.

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