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1.
Int J Radiat Biol ; : 1-15, 2024 Mar 20.
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.

2.
Behav Sci (Basel) ; 14(3)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38540460

RESUMO

Social media fitness influencers are driving the maturation of online fitness, which is especially significant in the current era of globally decreasing levels of physical activity. However, there is a paucity of research on online fitness videos, and the mechanism of influence of fitness videos on exercise intention is not well understood. Therefore, based on the stimulus-organism-response (S-O-R) theoretical framework, this study extends the source credibility theory to the field of fitness and adds an examination of the content quality and electronic word-of-mouth of fitness videos to explore how fitness videos motivate users to participate in physical exercise. Through an online survey, 367 valid samples were collected and validated using a structural equation model. The results showed that the three elements contained in source credibility theory have inconsistent importance in the fitness field, with trustworthiness being the most important, followed by attractiveness, and the influence of expertise is not significant. In summary, the attributes of social media fitness influencers, including trustworthiness and physical attractiveness, as well as the content quality and electronic word-of-mouth of their fitness videos, may lead to viewers' trust and perception of the usefulness of the videos and, furthermore, lead to exercise intention.

4.
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 , Feófitas , Sargassum , Alga Marinha , Humanos , Arsênio/toxicidade , 60578 , Medição de Risco , Verduras
6.
Radiat Res ; 201(3): 215-223, 2024 Mar 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
60422 , Grânulos de Estresse , Humanos , Células HeLa , Radiação Ionizante , Estresse Fisiológico , Proteína 1 de Ligação a Y-Box
7.
Am J Otolaryngol ; 45(2): 104200, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38113779

RESUMO

AIMS: To compare the outcomes of endoscopic dacryocystorhinostomy (En-DCR) in chronic dacryocystitis (CD) with or without previous bicanalicular silicone tube intubation (BSTI), and investigate whether previous BSTI influenced postoperative outcomes. METHODS: We conducted a retrospective review of medical records of CD patients (group A) who had previously undergone BSTI for nasolacrimal duct stenosis and an age- and sex-matched control group of CD patients (group B) without previous intubation receiving En-DCR from November 2017 to January 2022. Sixty-one patients (61 eyes) were included in group A and age- and sex-matched 122 patients (122 eyes) in group B. Dacryocystic parameters were measured by computed tomography-dacryocystography and surgical findings were recorded during surgeries. The surgical success rates of the two groups were compared at 12 months post-operation. RESULTS: The mean horizontal, sagittal, and vertical lengths were 6.06 ± 1.24, 6.03 ± 1.44, and 8.05 ± 2.00 mm, respectively, in group A and 6.33 ± 1.25, 6.26 ± 1.19, and 10.40 ± 2.45 mm, respectively, in group B. There were no differences in the horizontal or sagittal parameters between the two groups. The vertical parameter in group A was significantly lower than that in group B. Scar formation in the sac was observed in 54 patients in group A but was absent in group B. At 12 months postoperatively, the anatomical and functional success rates were 88.52 % and 85.25 %, respectively, in group A and 92.62 % and 89.34 %, respectively, in group B, with no difference between the two groups. CONCLUSION: Previous BSTI reduced dacryocyst vertical parameter and caused dacryocyst scar formation but did not affect postoperative En-DCR efficacy.


Assuntos
Dacriocistite , Dacriocistorinostomia , Obstrução dos Ductos Lacrimais , Humanos , Silicones , Cicatriz , Endoscopia/efeitos adversos , Dacriocistite/cirurgia , Dacriocistite/complicações , Intubação , Obstrução dos Ductos Lacrimais/terapia , Resultado do Tratamento
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.
Talanta ; 270: 125547, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38101029

RESUMO

To realize the potential of ionic liquid functionalized silica to prepare mixed-mode and chiral stationary phases, two ionic liquid silane reagents with different anions were synthesized via a high-efficiency click reaction. Then they were decorated onto the surface of silica by a one-step bonding reaction. The functionalized silica was characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), and elemental analysis (EA). Two stationary phases provided satisfactory performance when compared with a commercial mixed-mode column. Notably, Sil-C10Im-D-BCS with D-3-bromocamphor-8-sulfonate (D-BCS) as anion presented chiral separation capacity towards 1,2,3,4-Tetrahydro-1-naphthol. The separation mechanism was investigated through multiple pathways, and the results revealed that the prepared stationary phases can retain and separate solutes through multiple interactions, like hydrophobic effect, ion exchange, hydrogen-bond interaction, etc. Quantum chemical calculation (QC) was employed to obtain the optimized structures and the binding energy of anions to cations. The results provided some insights into the retention mechanism from a molecular perspective. This work demonstrated the superiority of ionic liquid functionalized silica as mixed-mode stationary phases and the potential of chiral ionic liquid as chiral selectors.

10.
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.

11.
J Int Soc Sports Nutr ; 20(1): 2258850, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37735799

RESUMO

BACKGROUND: There is epidemiological evidence which suggests an association between 25-hydroxyvitamin D [25(OH)D] levels and bone and muscle function; however, it is unclear whether vitamin D supplementation has an added benefit beyond bone health. Here, we investigated the effects of vitamin D3 supplementation (1 month) on physical performance in Chinese university students in winter. METHODS: One hundred and seventeen eligible subjects with 25(OH)D (19.2 ± 7.8 ng/mL) were randomly assigned to either vitamin D3 supplement (N = 56; 1000 IU/day) or the control (N = 61) group for 1 month. Pre- and post-measurements included: 1) serum levels of 25(OH)D; 2) musculoskeletal and pulmonary function [vertical jump height (VJH) and right handgrip strength (RHS), forced vital capacity (FVC), and forced expiratory volume at 1s (FEV1)]; 3) bone turnover markers [parathyroid hormone (PTH), n-terminal osteocalcin (N-MID), and calcium]; 4) hemoglobin-related parameters [hemoglobin (Hb), hematocrit (HCT), red blood cells (RBC), and red cell distribution width (RDW)]; 5) lipid parameters [total triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)]; 6) Fatigue-related indicators [serum creatine kinase (CK), lactate dehydrogenase (LDH), and total testosterone (T)]. In addition, aerobic capacity was assessed by measuring maximal oxygen uptake (VO2max) at baseline. RESULTS: During wintertime, supplementation with 1000 IU/d of vitamin D3 significantly increased serum 25(OH)D levels (from 18.85 ± 7.04 to 26.98 ± 5.88 ng/mL, p < 0.05), accompanied by a decrease of PTH (p < 0.05). However, vitamin D3 supplementation did not significantly impact the physical performance, serum lipid parameters, and bone turnover markers of students. Furthermore, 25(OH)D was found to be positively correlated with VJH and negatively correlated with PTH and TC at the beginning and end of the study (p < 0.05). In addition, the multiple linear regression analysis showed that 25(OH)D combined with athletic, gender, height, weight, Hb, and FVC could account for 84.0% of the VO2max value. CONCLUSIONS: The study demonstrated that one-month of 1000 IU/d of vitamin D3 supplementation during the winter had beneficial effects on 25(OH)D status and PTH. However, vitamin D3 intervention was not sufficient to improve physical performance. Furthermore, 25(OH)D levels combined with athletic, Hb and FVC could be a predictor of VO2max.


Assuntos
Colecalciferol , Força da Mão , Humanos , Universidades , Vitamina D , Desempenho Físico Funcional , HDL-Colesterol
12.
Nat Commun ; 14(1): 3758, 2023 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-37353497

RESUMO

Phosphodiesterase type 5 inhibitors (PDE5is) constitute the primary therapeutic option for treating erectile dysfunction (ED). Nevertheless, a substantial proportion of patients, approximately 30%, do not respond to PDE5i treatment. Therefore, new treatment methods are needed. In this study, we identified a pathway that contributes to male erectile function. We show that mechano-regulated YAP/TAZ signaling in smooth muscle cells (SMCs) upregulates adrenomedullin transcription, which relaxed the SMCs to maintain erection. Using single-nucleus RNA sequencing, we investigated how penile erection stretches the SMCs, inducing YAP/TAZ activity. Subsequently, we demonstrate that YAP/TAZ plays a role in erectile function and penile rehabilitation, using genetic lesions and various animal models. This mechanism relies on direct transcriptional regulation of adrenomedullin by YAP/TAZ, which in turn modulates penile smooth muscle contraction. Importantly, conventional PDE5i, which targets NO-cGMP signaling, does not promote erectile function in YAP/TAZ-deficient ED model mice. In contrast, by activating the YAP/TAZ-adrenomedullin cascade, mechanostimulation improves erectile function in PDE5i nonrespondent ED model rats and mice. Furthermore, using clinical retrospective observational data, we found that mechanostimulation significantly promotes erectile function in patients irrespective of PDE5i use. Our studies lay the groundwork for exploring the mechano-YAP/TAZ-adrenomedullin axis as a potential target in the treatment of ED.


Assuntos
Adrenomedulina , Disfunção Erétil , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional , Proteínas de Sinalização YAP , Animais , Humanos , Masculino , Camundongos , Ratos , Adrenomedulina/fisiologia , Disfunção Erétil/genética , Ereção Peniana/fisiologia , Pênis , Estudos Retrospectivos , Proteínas de Sinalização YAP/fisiologia , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional/fisiologia
13.
Int J Mol Sci ; 24(6)2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36982776

RESUMO

A magnetic copper ferrite and biochar composite (CuFe2O4@BC) catalyst was prepared by an improved sol-gel calcination method and initially used for the removal of antibiotics ciprofloxacin (CIP) by activated peroxymonosulfate (PMS). Using CuFe2O4@BC as the activator, 97.8% CIP removal efficiency could be achieved in 30 min. After a continuous degradation cycle, CuFe2O4@BC catalyst still exhibited great stability and repeatability and could also be quickly recovered by an external magnetic field. Meanwhile, the CuFe2O4@BC/PMS system presented good stability for metal ion leaching, which was far less than the leaching of metal ions in the CuFe2O4/PMS system. Moreover, the effects of various influencing factors, such as initial solution pH, activator loading, PMS dosage, reaction temperature, humic acid (HA), and the inorganic anions were explored. The quenching experiments and the electron paramagnetic resonance (EPR) analysis manifested that hydroxyl radical (•OH), sulfate radical (SO4•-), superoxide radical (O2•-), and singlet oxygen (1O2) were generated in the CuFe2O4@BC/PMS system, while 1O2 and O2•- are mainly involved in the degradation process. The synergistic effect between CuFe2O4 and BC enhanced the structural stability and electrical conductivity of the material, which promoted the bonding between the catalyst and PMS, resulting in the enhanced catalytic activity of CuFe2O4@BC. This indicates that CuFe2O4@BC activating PMS is a promising remediation technique for CIP-contaminated water.


Assuntos
Ciprofloxacina , Peróxidos , Peróxidos/química , Água , Fenômenos Magnéticos
14.
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
15.
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
16.
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
17.
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
18.
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.

19.
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.

20.
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.

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