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1.
Am J Rhinol Allergy ; : 19458924241262098, 2024 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-39033418

RESUMO

BACKGROUND: Nasal and paranasal sinus abnormalities may be related to nasolacrimal duct obstructive disease but are strongly debated. Data of acute disease stage are lacking. OBJECTIVE: The purpose of this study was to determine if there are correlations between radiologic signs of sinus inflammation and acute dacryocystitis (AD). METHODS: This cross-sectional controlled study was conducted at Wenzhou, Zhejiang Province, China from February 2021 to November 2023. Forty-four consecutive patients with AD and 50 consecutive patients with orbital tumors (the control group), who completed preoperative computed tomography scans, were enrolled to evaluate the extent of their inflammatory sinonasal disease by the modified Lund-Mackay score system. RESULTS: The inflammation signs of the paranasal sinuses (total mean sinus scores, 95% CI [0.00, 2.00]; P < 0.001), namely the anterior ethmoid sinus(95% CI [0.00, 1.00]; P < 0.001), the posterior ethmoid sinus(95% CI [0.00, 0.00]; P = 0.003), the frontal sinus (95% CI [0.00, 0.00]; P = 0.02), and the ostiomeatal complex (P < 0.001) were more extensive in patients with AD when compared with the controls. The disease course was negatively correlated with the anterior ethmoid (P = 0.03) and frontal scores (P = 0.01). The symptom of eyelid swelling was positively correlated with the anterior ethmoid (P = 0.03), ostiomeatal complex (P = 0.004), and total sinus scores (P = 0.005). CONCLUSION: Inflammatory sinus disease was found to be more frequent in patients with AD, which was gradually alleviated with the prolongation of the disease course. The mutual spread of inflammation particularly in the acute course may play an important role in lacrimal duct obstructive disease.

2.
Mol Ther Nucleic Acids ; 35(3): 102260, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39049874

RESUMO

Space particle radiation is a major environmental factor in spaceflight, and it is known to cause body damage and even trigger cancer, but with unknown molecular etiologies. To examine these causes, we developed a systems biology approach by focusing on the co-expression network analysis of transcriptomics profiles obtained from single high-dose (SE) and multiple low-dose (ME) α-particle radiation exposures of BEAS-2B human bronchial epithelial cells. First, the differential network and pathway analysis based on the global network and the core modules showed that genes in the ME group had higher enrichment for the extracellular matrix (ECM)-receptor interaction pathway. Then, collagen gene COL1A1 was screened as an important gene in the ME group assessed by network parameters and an expression study of lung adenocarcinoma samples. COL1A1 was found to promote the emergence of the neoplastic characteristics of BEAS-2B cells by both in vitro experimental analyses and in vivo immunohistochemical staining. These findings suggested that the degree of malignant transformation of cells in the ME group was greater than that of the SE, which may be caused by the dysregulation of the ECM-receptor pathway.

3.
Cancer Res ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862269

RESUMO

YAP is a central player in cancer development with functions extending beyond its recognized role in cell growth regulation. Recent work has identified a link between YAP/TAZ and the DNA damage response. Here, we investigated the mechanistic underpinnings of the crosstalk between DNA damage repair and YAP activity. Ku70, a key component of the non-homologous end joining pathway to repair DNA damage, engaged in a dynamic competition with TEAD4 for binding to YAP, limiting the transcriptional activity of YAP. Depletion of Ku70 enhanced interaction between YAP and TEAD4 and boosted YAP transcriptional capacity. Consequently, Ku70 loss enhanced tumorigenesis in colon cancer and hepatocellular carcinoma (HCC) in vivo. YAP impeded DNA damage repair and elevated genome instability by inducing PARP1 degradation through the SMURF2-mediated ubiquitin-proteasome pathway. Analysis of HCC patient samples substantiated the link between Ku70 expression, YAP activity, PARP1 levels, and genome instability. In conclusion, this research provides insight into the mechanistic interactions between YAP and key regulators of DNA damage repair, highlighting the role of a Ku70-YAP-PARP1 axis in preserving genome stability.

4.
Int J Radiat Biol ; 100(6): 834-848, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38506660

RESUMO

PURPOSE: Transforming growth factor (TGF-ß) plays a dual role in tumor progression as well as a pivotal role in radiation response. TGF-ß-related epigenetic regulations, including DNA methylation, histone modifications (including methylation, acetylation, phosphorylation, ubiquitination), chromatin remodeling and non-coding RNA regulation, have been found to affect the occurrence and development of tumors as well as their radiation response in multiple dimensions. Due to the significance of radiotherapy in tumor treatment and the essential roles of TGF-ß signaling in radiation response, it is important to better understand the role of epigenetic regulation mechanisms mediated by TGF-ß signaling pathways in radiation-induced targeted and non-targeted effects. CONCLUSIONS: By revealing the epigenetic mechanism related to TGF-ß-mediated radiation response, summarizing the existing relevant adjuvant strategies for radiotherapy based on TGF-ß signaling, and discovering potential therapeutic targets, we hope to provide a new perspective for improving clinical treatment.


Assuntos
Epigênese Genética , Transdução de Sinais , Fator de Crescimento Transformador beta , Fator de Crescimento Transformador beta/metabolismo , Humanos , Epigênese Genética/efeitos da radiação , Transdução de Sinais/efeitos da radiação , Animais , Neoplasias/radioterapia , Neoplasias/genética , Neoplasias/metabolismo , Metilação de DNA/efeitos da radiação , Tolerância a Radiação
5.
Food Chem Toxicol ; 187: 114603, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38499235

RESUMO

Since humans are especially sensitive to arsenic exposure, predominantly through diet, a strict control of the most widely consumed seaweeds is mandatory. Total arsenic contents and arsenic species in twenty-five different seaweeds from five different origins were studied. Seaweeds selected, included Phaeophyta (brown seaweed), Chlorophyta (green seaweed) and Rhodophyta (red seaweed) genera. The highest arsenic content appears in the Phaeophyta seaweed in the range from 11 to 162 mg kg-1 dried weight. Arsenosugars were found to be the predominant species of arsenic in most seaweeds, being up to 99.7% of total arsenic in some samples. The arsenic dietary intakes for seaweeds studied were assessed and the Target Hazard Quotients (THQ) and the Target Cancer Risk (TCR) were calculated, taking into account inorganic arsenic contents (iAs). iAs species in seaweeds showed low risk of arsenic intake except for Hizikia fusiforme samples.


Assuntos
Arsênio , Arsenicais , Phaeophyceae , Sargassum , Alga Marinha , Humanos , Arsênio/toxicidade , Algas Comestíveis , Medição de Risco , Verduras
7.
Radiat Res ; 201(3): 215-223, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38253057

RESUMO

Stress granules (SGs) are formed through liquid-liquid phase separation (LLPS), in response to external stimuli. YBX1, an integral component of SGs, plays a crucial role in tumor progression and cellular stress response. This study aims to elucidate the mechanisms and specific biological implications of YBX1 in SG formation, along with the identification of key regions and interacting proteins. Our observations indicate that YBX1 rapidly undergoes liquid-liquid phase separation, leading to SG formation in response to 8 Gy X-ray irradiation within 1 h, with SGs reverting to their original state after 5 h. There was a potential interaction between ATXN2L and YBX1, persisting YBX1 within the SGs. Our data suggested a potential interaction between ATXN2L and YBX1, and it remained associated with YBX1 within the SGs. Furthermore, our subsequent studies demonstrate that targeting ATXN2L can diminish the recruitment of YBX1 to stress granules (SGs), consequently enhancing the radiosensitivity of HeLa cells.


Assuntos
Separação de Fases , Grânulos de Estresse , Humanos , Células HeLa , Radiação Ionizante , Estresse Fisiológico , Proteína 1 de Ligação a Y-Box
8.
J Chromatogr A ; 1714: 464586, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38118242

RESUMO

Zwitterions are a promising choice to prepare separation materials because of their hydrophilicity and biocompatibility. We described the preparation of two zwitterionic polymer functionalized stationary phases and evaluation under mixed-mode chromatography. A zwitterionic monomer, S-(4-vinylbenzyl) cysteine (SVC), was synthesized and bonded to silica via reversible addition fragmentation chain transfer (RAFT) polymerization to afford a zwitterionic stationary phase, Sil-SVC. A hydrophobic monomer, N-(4-phenylbutan-2-yl) acrylamide (NPA), was copolymerized with SVC onto the stationary phase (Sil-SVCNPA) for comparison. The stationary phases were characterized with FT-IR, TGA, EA, and zeta-potential measurements. Mobile phase composition (ACN content, pH and salt concentration) was varied to study the retention property. Linear solvation energy relationship and Van't Hoff plot were used to investigate the retention mechanism and how chromatographic conditions influenced it. Both stationary phases showed a mixed-mode of RPLC/HILIC/IEC and satisfactory performance in separating hydrophobic analytes (alkylbenzenes and polycyclic aromatic hydrocarbons), hydrophilic nucleotide and bases, and anions, high column efficiency of 60,000 plates·m-1 was achieved. In summary, zwitterionic polymers are attractive options to prepare stationary phases and the retention property can be easily regulated by copolymer.


Assuntos
Cromatografia de Fase Reversa , Polímeros , Espectroscopia de Infravermelho com Transformada de Fourier , Cromatografia por Troca Iônica/métodos , Interações Hidrofóbicas e Hidrofílicas , Dióxido de Silício/química
9.
Comput Struct Biotechnol J ; 21: 5201-5211, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37928948

RESUMO

In the human genome, 98% of genes can be transcribed into non-coding RNAs (ncRNAs), among which lncRNAs and their encoded peptides play important roles in regulating various aspects of cellular processes and may serve as crucial factors in modulating the biological effects induced by ionizing radiation and microgravity. Unfortunately, there are few reports in space radiation biology on lncRNA-encoded peptides below 10kD due to limitations in detection techniques. To fill this gap, we integrated a variety of methods based on genomics and peptidomics, and discovered 22 lncRNA-encoded small peptides that are sensitive to space radiation and microgravity, which have never been reported before. We concurrently validated the transmembrane helix, subcellular localization, and biological function of these small peptides using bioinformatics and molecular biology techniques. More importantly, we found that these small peptides function independently of the lncRNAs that encode them. Our findings have uncovered a previously unknown human proteome encoded by 'non-coding' genes in response to space conditions and elucidated their involvement in biological processes, providing valuable strategies for individual protection mechanisms for astronauts who carry out deep space exploration missions in space radiation environments.

10.
Adv Sci (Weinh) ; 10(13): e2300314, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36871154

RESUMO

Long noncoding RNAs (lncRNAs) in eukaryotic transcripts have long been believed to regulate various aspects of cellular processes, including carcinogenesis. Herein, it is found that lncRNA AFAP1-AS1 encodes a conserved 90-amino acid peptide located on mitochondria, named lncRNA AFAP1-AS1 translated mitochondrial-localized peptide (ATMLP), and it is not the lncRNA but the peptide that promotes the malignancy of nonsmall cell lung cancer (NSCLC). As the tumor progresses, the serum level of ATMLP increases. NSCLC patients with high levels of ATMLP display poorer prognosis. Translation of ATMLP is controlled by m6 A methylation at the 1313 adenine locus of AFAP1-AS1. Mechanistically, ATMLP binds to the 4-nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1 (NIPSNAP1) and inhibits its transport from the inner to the outer mitochondrial membrane, which antagonizes the NIPSNAP1-mediated regulation of cell autolysosome formation. The findings uncover a complex regulatory mechanism of NSCLC malignancy orchestrated by a peptide encoded by a lncRNA. A comprehensive judgment of the application prospects of ATMLP as an early diagnostic biomarker for NSCLC is also made.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , RNA Longo não Codificante , Humanos , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neoplasias Pulmonares/metabolismo , Metilação , Mitocôndrias/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
11.
Exp Eye Res ; 226: 109343, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36509163

RESUMO

The optic nerve (ON) can get compressed in different diseases. However, the pathological and functional changes occurring in the compressed ON over time under constant compression are still unclear. In the present study, we implanted an artificial tube around the optic nerve of a rabbit to primarily create a clinically relevant persistent compressive optic nerve axonopathy (PCOA). Due to the protuberance on the inner ring of the tube, steady and persistent compressions were maintained. In this model, we investigated the thickness of ganglion cell complex (GCC), retinal ganglion cell (RGC) density, axon density of optic nerve, flash visual evoked potential (FVEP), and anterograde axonal transport at various times in four different groups viz. the no comp, 1/2 comp, 3/4 comp, and crush groups. The GCC thickness, RGC density, and axon density of ON were hierarchically and significantly decreased in 1/2 comp, 3/4 comp, and crush groups. Compared to no comp eyes, the P2 amplitude ratio of FVEP was significantly decreased in 3/4 comp but not in 1/2 comp eyes. Only a portion of the optic nerve lost the ability of anterograde axonal transport in the 1/2 comp group. However, it was evident at 2-wpo and more prominent at 4-wpo in 3/4 comp eyes. This study reveals that the compression only induces the homolateral ON axons impairment and the proportion of the affected axons maintains the same for mild compression for at least three months. Furthermore, an underlying threshold effect highlights that mild compression does not require urgent surgery, while the severe compression warrants immediate surgical intervention.


Assuntos
Doenças do Nervo Óptico , Traumatismos do Nervo Óptico , Animais , Coelhos , Potenciais Evocados Visuais , Nervo Óptico/patologia , Células Ganglionares da Retina/patologia , Doenças do Nervo Óptico/patologia , Traumatismos do Nervo Óptico/patologia , Axônios/patologia , Compressão Nervosa , Modelos Animais de Doenças
12.
BMJ Open ; 12(12): e063381, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36456023

RESUMO

INTRODUCTION: Varicocele (VC) is a common clinical disease in andrology. Among a number of ways for VC treatment, surgery is the most common one, but the measurable benefit of surgical repair was slight. A growing exploration of complementary therapies has been conducted in clinical research on acupuncture for VC, but there is no relevant systematic review and meta-analysis to assess the efficacy and safety of acupuncture for VC. METHODS AND ANALYSIS: All relevant publications published from database inception through August 2022 will be searched in three English-language databases (Embase, CENTRAL, MEDLINE) and four Chinese-language databases (China National Knowledge Infrastructure, China Science and Technology Journal Database, Chinese Biomedical Literature Database and Wanfang Data). Randomised controlled trials in English and Chinese concerned with acupuncture for patients with VC will be included. The input clinical data will be processed by the Review Manager software (RevMan). The literature will be appraised with the Cochrane Collaboration risk of bias tool. The Grading of Recommendations Assessment, Development and Evaluation system (GRADE system) will be used to evaluate the quality of evidence. ETHICS AND DISSEMINATION: This study is a secondary study based on clinical studies so it does not relate to any individual patient information or infringe the rights of participants. Hence no ethical approval is required. The results will be reported in peer-reviewed journals or disseminated at relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42022316005.


Assuntos
Terapia por Acupuntura , Infertilidade Masculina , Varicocele , Humanos , Masculino , Povo Asiático , Bases de Dados Factuais , Infertilidade Masculina/etiologia , Infertilidade Masculina/terapia , Varicocele/complicações , Varicocele/terapia , Revisões Sistemáticas como Assunto
13.
J Exp Clin Cancer Res ; 41(1): 338, 2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36476255

RESUMO

BACKGROUND: Aberrant RNA editing of adenosine-to-inosine (A-to-I) has been linked to multiple human cancers, but its role in intrahepatic cholangiocarcinoma (iCCA) remains unknown. We conducted an exome-wide investigation to search for dysregulated RNA editing that drive iCCA pathogenesis. METHODS: An integrative whole-exome and transcriptome sequencing analysis was performed to elucidate the RNA editing landscape in iCCAs. Putative RNA editing sites were validated by Sanger sequencing. In vitro and in vivo experiments were used to assess the effects of an exemplary target gene Kip1 ubiquitination-promoting complex 1 (KPC1) and its editing on iCCA cells growth and metastasis. Crosstalk between KPC1 RNA editing and NF-κB signaling was analyzed by molecular methods. RESULTS: Through integrative omics analyses, we revealed an adenosine deaminases acting on RNA 1A (ADAR1)-mediated over-editing pattern in iCCAs. ADAR1 is frequently amplified and overexpressed in iCCAs and plays oncogenic roles. Notably, we identified a novel ADAR1-mediated A-to-I editing of KPC1 transcript, which results in substitution of methionine with valine at residue 8 (p.M8V). KPC1 p.M8V editing confers loss-of-function phenotypes through blunting the tumor-suppressive role of wild-type KPC1. Mechanistically, KPC1 p.M8V weakens the affinity of KPC1 to its substrate NF-κB1 p105, thereby reducing the ubiquitinating and proteasomal processing of p105 to p50, which in turn enhances the activity of oncogenic NF-κB signaling. CONCLUSIONS: Our findings established that amplification-driven ADAR1 overexpression results in overediting of KPC1 p.M8V in iCCAs, leading to progression via activation of the NF-κB signaling pathway, and suggested ADAR1-KPC1-NF-κB axis as a potential therapeutic target for iCCA.


Assuntos
NF-kappa B , Humanos
14.
Front Genet ; 13: 956094, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36330438

RESUMO

Background: Cellular senescence plays a complicated and vital role in cancer development because of its divergent effects on tumorigenicity. However, the long non-coding RNAs (lncRNAs) associated with tumor senescence and their prognostic value in hepatocellular carcinoma (HCC) remain unexplored. Methods: The trans-cancer oncogene-induced senescence (OIS) signature was determined by gene set variation analysis (GSVA) in the cancer genome atlas (TCGA) dataset. The OIS-related lncRNAs were identified by correlation analyses. Cox regression analyses were used to screen lncRNAs associated with prognosis, and an optimal predictive model was created by regression analysis of the least absolute shrinkage and selection operator (LASSO). The performance of the model was evaluated by Kaplan-Meier survival analyses, nomograms, stratified survival analyses, and receiver operating characteristic curve (ROC) analyses. Gene set enrichment analysis (GSEA) and cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) were carried out to explore the functional relevance and immune cell infiltration, respectively. Results: Firstly, we examined the pan-cancer OIS signature, and found several types of cancer with OIS strongly associated with the survival of patients, including HCC. Subsequently, based on the OIS signature, we identified 76 OIS-related lncRNAs with prognostic values in HCC. We then established an optimal prognostic model based on 11 (including NRAV, AC015908.3, MIR100HG, AL365203.2, AC009005.1, SNHG3, LINC01138, AC090192.2, AC008622.2, AL139423.1, and AC026356.1) of these lncRNAs by LASSO-Cox regression analysis. It was then confirmed that the risk score was an independent and potential risk indicator for overall survival (OS) (HR [95% CI] = 4.90 [2.74-8.70], p < 0.001), which outperforms those traditional clinicopathological factors. Furthermore, patients with higher risk scores also showed more advanced levels of a proinflammatory senescence-associated secretory phenotype (SASP), higher infiltration of regulatory T (Treg) cells and lower infiltration of naïve B cells, suggesting the regulatory effects of OIS on immune microenvironment. Additionally, we identified NRAV as a representative OIS-related lncRNA, which is over-expressed in HCC tumors mainly driven by DNA hypomethylation. Conclusion: Based on 11 OIS-related lncRNAs, we established a promising prognostic predictor for HCC patients, and highlighted the potential immune microenvironment-modulatory roles of OIS in HCC, providing a broad molecular perspective of tumor senescence.

15.
Int J Ophthalmol ; 15(11): 1765-1771, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36404979

RESUMO

AIM: To evaluate the outcome of endoscopic dacryocystorhinostomy (En-DCR) with mucosal anastomosis in chronic dacryocystitis patients, with various categories of ethmoid sinuses. METHODS: Between July 2015 and September 2019, 1439 adult patients, representing 1623 affected eyes, presented with chronic dacryocystitis and were scheduled for En-DCR. The categories of ethmoid sinuses were preoperatively determined, using computed tomography-dacryocystography (CT-DCG), and were classified as category 1 (C1), category 2 (C2), and category 3 (C3). No sinuses anterior to the posterior lacrimal crest defined as C1. Sinuses found between the anterior edge of the lacrimal bone and the posterior lacrimal crest defined as C2. Sinuses found anterior to the lacrimal bone suture defined as C3. At the end of surgery, the dacryocyst and nasal mucosa were anastomosed in C1, and the dacryocyst mucosa and anterior ethmoid sinus were anastomosed in C2 and C3 ethmoid sinus patients. The surgical success rate and related complications, in patients with 3 categories of ethmoid cells, were monitored and documented. RESULTS: Postoperative data was obtained for 179 C1 affected eyes, 878 C2 affected eyes, and 432 C3 affected eyes. The overall success rate of En-DCR was 93.0% (1385/1489). Additionally, the success rates were comparable among the different ethmoid categories at 12mo post operation. We demonstrated that the major reason for surgical failure was intranasal ostial closure, due to granulation or scar tissue. CONCLUSION: En-DCR is a feasible and highly effective primary treatment for chronic dacryocystitis. To ensure surgical success, the surgery protocol must be designed in accordance with the category of ethmoid sinuses present in individual patient.

16.
Comput Struct Biotechnol J ; 20: 5978-5983, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36382188

RESUMO

Single-cell transcriptomics offers opportunities to investigate ligand-receptor (LR) interactions between heterogeneous cell populations within tissues. However, most existing tools for the inference of intercellular communication do not allow prioritization of functional LR associations that provoke certain biological responses in the receiver cells. In addition, current tools do not enable the identification of the impact on the downstream cell types of the receiver cells. We present CommPath, an open-source R package and webserver, to analyze and visualize the LR interactions and pathway-mediated intercellular communication chain with single-cell transcriptomic data. CommPath curates a comprehensive signaling pathway database to interpret the consequences of LR associations and therefore infers functional LR interactions. Furthermore, CommPath determines cell-cell communication chain by considering both the upstream and downstream cells of user-defined cell populations. Applying CommPath to human hepatocellular carcinoma dataset shows its ability to decipher complex LR interaction patterns and the associated intercellular communication chain, as well as their changes in disease versus homeostasis.

17.
Neoplasia ; 32: 100828, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35908380

RESUMO

The carcinogenic risk from space radiation has always been a health risk issue of great concern during space exploration. In recent years, a large number of cellular and animal experiments have demonstrated that space radiation, composed of high-energy protons and heavy ions, has shown obvious carcinogenicity. However, different from radiation on Earth, space radiation has the characteristics of high energy and low dose rate. It is rich in high-atom-number and high-energy particles and, as it is combined with other space environmental factors such as microgravity and a weak magnetic field, the study of its carcinogenic effects and mechanisms of action is difficult, which leads to great uncertainty in its carcinogenic risk assessment. Here, we review the latest progress in understanding the effects and mechanisms of action related to cell transformation and carcinogenesis induced by space radiation in recent years and summarize the prediction models of cancer risk caused by space radiation and the methods to reduce the uncertainty of prediction to provide reference for the research and risk assessment of space radiation.


Assuntos
Radiação Cósmica , Voo Espacial , Animais , Carcinogênese , Transformação Celular Neoplásica , Prótons
18.
Radiat Res ; 198(3): 297-305, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35439322

RESUMO

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with high recurrence and metastasis rates, and more than half of the patients diagnosed with NSCLC receive local radiotherapy. However, the intrinsic radio-resistance of cancer cells is a major barrier to effective radiotherapy for NSCLC. CRYBG3 is a long noncoding RNA (lncRNA) that was originally identified to be upregulated in NSCLC and enhanced metastasis of NSCLC cells by interacting with eEF1A1 to promote murine double minute 2 (MDM2) expression. The aims of this study were to reveal the contribution of CRYBG3 to the radioresistance of NSCLC and determine whether that is associated with MDM2-p53 pathway. Therefore, CRYBG3 was stably downregulated in A549 (wild-type p53) and H1299 (deficient p53) cells by infecting short hairpin RNA (shRNA) lentiviral particles. The results showed that downregulation of CRYBG3 increased DNA damage, enhanced apoptosis and pro-apoptotic protein expression in A549 or p53-overexpressed H1299 cells but not in H1299 or p53-silenced A549 cells after X-ray irradiation. However, the contribution of CRYBG3 to radioresistance was abolished by eEF1A1 or MDM2 knockdown in A549 cells. Thus, we concluded that downregulation of CRYBG3 enhanced radiosensitivity by reducing MDM2 expression then leading to decreased MDM2-mediated degradation of p53 in wild-type p53 expressing NSCLC cells. These findings suggested that CRYBG3 can be a potential target for therapeutic intervention of certain lung cancer subtypes.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , RNA Longo não Codificante , Apoptose/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Linhagem Celular Tumoral , Regulação para Baixo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , RNA Longo não Codificante/genética , RNA Interferente Pequeno/genética , Tolerância a Radiação/genética , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
19.
Laryngoscope ; 132(9): 1743-1749, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35385151

RESUMO

OBJECTIVE: To investigate the feasibility, efficacy, and safety of an endoscopic transethmoidal-sphenoidal approach in removing a small cavernous hemangioma (CH) located in the deep lateral orbital apex. METHODS: This study involved 19 patients diagnosed with a CH located in the deep lateral orbital apex. All patients underwent an endoscopic transethmoidal-sphenoidal approach for removal of the CH. The best-corrected visual acuity (BCVA), visual field, and surgery-related complications were analyzed and compared. RESULTS: All tumors in this study were completely removed. The mean BCVA was LogMAR 0.97 ± 0.97 preoperatively and LogMAR 0.38 ± 0.64 postoperatively (p < 0.05). The mean visual field index was 52.26% ± 33.26% preoperatively and 75.47% ± 30.49% postoperatively (p < 0.05). The mean deviation index was -17.48 ± 12.43 dB preoperatively and -10.10 ± 10.85 dB postoperatively (p < 0.05), and the pattern standard deviation was 6.37 ± 3.77 dB preoperatively and 4.90 ± 3.56 dB postoperatively (p > 0.05). Four (21.1%) patients developed oculomotor limitations and two (10.5%) patients developed ptosis after surgery. All of these symptoms resolved spontaneously, and no other complications occurred. The mean follow-up time was 6.71 ± 3.89 months. CONCLUSION: The endoscopic transethmoidal-sphenoidal approach is an effective and minimally invasive treatment for removing small CH in the deep lateral orbital apex. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1743-1749, 2022.


Assuntos
Hemangioma Cavernoso , Neoplasias Orbitárias , Endoscopia , Hemangioma Cavernoso/diagnóstico por imagem , Hemangioma Cavernoso/cirurgia , Humanos , Neoplasias Orbitárias/patologia , Neoplasias Orbitárias/cirurgia
20.
Int J Ophthalmol ; 15(3): 413-419, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35310051

RESUMO

AIM: To demonstrate the outcomes of endoscopic endonasal dacryocystorhinostomy (En-DCR) with an novel lacrimal ostium stent (LOS) which was performed in patients with recurrent epiphora after failed external dacryocystorhinostomy (Ex-DCR) and analyze the causes of failed Ex-DCR. METHODS: From September 2015 and December 2017, the clinic data of 29 cases suffered from recurrent epiphora after failed Ex-DCR was reviewed. The LOS were implanted into the ostium at the end of the revisional surgery. The causes of failed Ex-DCR were analyzed before revisional surgeries. Outcome of revisional surgeries with the new device were evaluated as well. RESULTS: The major causes of failure of the external approach were synechiae formation in the nasal ostium (29/29), followed by inadequate removal of the bony wall (21/29), nasal synechiae formation between lateral wall of nose and middle turbinate (11/29), and the bone opening was not in good location (7/29). The rate of success after revisional surgery was 82.76%. Re-obstruction of the ostiums were found in 5 failed cases. CONCLUSION: Endoscopic approach with a novel LOS may be an effective procedure to manage recurrent epiphora after previous failed Ex-DCR surgery. Synechiae formation in the nasal ostium and inadequate removal of the bony wall were the major causes of failure of Ex-DCR.

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