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1.
J Craniofac Surg ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830019

RESUMO

The aim of this study was to analyze the characteristics and error speech features of cleft-related lateral misarticulation and provide a basis for clinical evaluation and rational intervention. Participants who were diagnosed with lateral misarticulation after cleft palate repairment were 126 children aged 4, 6 to 16, and 11, and they had complete palatopharyngeal closure, no abnormalities in their speech organs and occlusion, and no hearing or intellectual impairments. The Chinese standard pronunciation clarity word list, the American KAY CSL4500, the Beijing Yangchen YF-16 computer speech analysis workstation, soundproof rooms, Wechsler scales of intelligence-fourth edition, and audiometers were used to evaluate the cleft-related lateral misarticulation. Statistical analysis was performed on the age, gender, error rate, corner of the mouth deviation direction, comorbidity, duration of intervention, period of treatment, and therapeutic effect of concentrated or normal intervention group in different patients. Our results showed that 2 to 3 straight stripes were visible at the onset of consonants /ti:/ /t'i:/, and 3 clear straight lines were visible in /tʂ/, indicating that the lateralized sound had 2 or 3 bursts and lasted for 1 to 2 ms. The onset age of lateralized sound was mostly below 12 years old. Chinese lateralized sound mainly occurred in vowel /i:/, and the occurrence rate of consonants with tongue surface /tɕ]/ /tɕ'/ /ɕ/ was the highest. In addition, the corner of the mouth deviation was also an indicator of lateralization sound, and other types of speech disorders mostly accompanied it. There was a significant difference in the improvement of speech clarity between the concentrated intervention group and the normal group before and after treatment. The 2 groups' average duration and course of treatment were not significantly different. Still, the period of concentrated intervention was shortened considerably, and the speech clarity of both groups of children after treatment exceeded 96%, reaching a normal level.

2.
Respiration ; : 1-9, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38599179

RESUMO

INTRODUCTION: There is no consensus regarding the most appropriate management of suspected malignant pulmonary ground-glass nodules (GGNs). OBJECTIVE: We aimed to explore the feasibility and safety of synchronous computed tomography-guided percutaneous transthoracic needle biopsy (PTNB) and microwave ablation (MWA) for patients highly suspicious of having malignant GGNs. METHODS: We retrospectively reviewed medical records between July 2020 and April 2023 from our medical center. Eligible patients synchronously underwent PTNB and MWA (either MWA immediately after PTNB [PTNB-first group] or PTNB immediately after MWA [MWA-first group]) at the the physician's discretion. We analyzed the rate of definitive diagnosis and technical success, the length of hospital stay, the postoperative efficacy, and periprocedural complications. RESULTS: Of 65 patients who were enrolled, the rate of definitive diagnosis was 86.2%, which did not differ when stratified by the tumor size, the consolidation-to-tumor ratio, or the sequence of the two procedures (all p > 0.05). The diagnostic rate of malignancy was 83.1%. After the median follow-up duration of 18.5 months, the local control rate was 98.2% and the rate of completed ablation was 48.2%. The rate of perioperative minor and major complications was 44.6% and 6.2%, respectively. The most common adverse events included pain, cough, and mild hemorrhage. Mild hemorrhage took place significantly less frequently in the MWA-first group than in the PTNB-first group (16.7% vs. 45.5%, p < 0.05). CONCLUSION: Synchronous PTNB and MWA are feasible and well tolerated for patients highly suspicious of having malignant GGNs, providing an alternative option for patients who are ineligible for surgical resection.

3.
Food Chem ; 442: 138453, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38266407

RESUMO

This study explores the coordination dynamics between dietary polyphenols, specifically kaempferol, quercetin, and myricetin, and Cu ions in aqueous environments. A novel synthesis method for flavonol-Cu(II) coordination compounds is introduced, effectively reducing interference from free metal ions. Our results reveal consistent binding patterns of Cu ions with flavonols (2:1 ratio of flavonol to Cu(II)), predominantly at the 4,5 sites. Various analytical techniques are used to validate these coordination ratios and sites. The binding affinity of the flavonols for Cu ions follows a descending sequence: myricetin > quercetin > kaempferol. Notably, coordination with Cu ions enhances the free-radical scavenging activities of these flavonols. These findings hold substantial importance for food chemistry, biology, and medicine, providing crucial insights into the way dietary flavonols form stable structures in environments similar to human body fluids and their interactions with metal ions, opening new possibilities for their application and understanding in diverse scientific domains.


Assuntos
Quempferóis , Quercetina , Humanos , Flavonóis/química , Metais , Sítios de Ligação , Íons
4.
J Sci Food Agric ; 104(1): 518-529, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37661343

RESUMO

BACKGROUND: Phenolic acids are widespread in foods and are beneficial to human health. However, the role of metal ions in influencing the binding of proteins with phenolic acids that contain the same parent nucleus structure remains unclear. This study investigated the inhibitory effect of caffeic acid (CA) and chlorogenic acid (CHA) on α-glucosidase and the biological effect of copper on this process. RESULTS: It was found that the esterification of CA with quinic acid could increase the fluorescence quenching, conformational change, and inhibitory effect of CHA on α-glucosidase. Copper ions reduced their fluorescence quenching and conformation-changing ability by binding to the neighboring phenolic hydroxyl group but also increased their ability to alter secondary structure and to inhibit α-glucosidase and in vitro anti-glycation. CONCLUSION: Overall, this study shows that the binding of copper ions to the phenolic hydroxyl group adjacent to CA and CHA synergistically inhibited α-glucosidase. The findings will offer a theoretical basis for investigating the properties of metal ions and phenolic acid in food chemistry and their potential applications in the prevention and treatment of diabetes mellitus. © 2023 Society of Chemical Industry.


Assuntos
Ácido Clorogênico , Cobre , Hidroxibenzoatos , Humanos , Ácido Clorogênico/química , Cobre/metabolismo , alfa-Glucosidases/metabolismo , Ácidos Cafeicos/química , Íons , Inibidores de Glicosídeo Hidrolases/farmacologia
5.
J Glob Health ; 13: 04151, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37974435

RESUMO

Background: Suboptimal health status (SHS) is a non-clinical or pre-disease state between optimal/ideal health and disease. While its etiology remains unclear, lifestyle is considered one of the most important risk factors. We aimed to examine the effects of lifestyles on SHS through a nationwide survey in China. Methods: We conducted a cross-sectional survey in 148 cities across China between 20 June and 31 August 2022, on 30 505 participants from rural and urban communities gathered through stratified quota sampling. We measured SHS with the Short-Form Suboptimal Health Status Questionnaire (SHSQ-SF). We gathered information on participants' lifestyles (ie, smoking, alcohol consumption, breakfast habits, weekly food delivery frequency, intermittent fasting, sleep duration and physical activities) through face-to-face interview. We determined the relationship between lifestyle and SHS logistic regression analysis by based on odds ratios (ORs) and 95% confidence intervals (CIs). Results: We included 22 897 participants (female: 13 056, male: 9841), 12 108 (52.88%) of whom reported exposure to SHS. After adjusting for demographic characteristics, individuals who currently smoked (OR = 1.165; 95% CI = 1.058-1.283) and those who drank alcohol (OR = 1.483; 95% CI = 1.377.1.596) were at a higher risk of SHS than those who have never done either. In a dose-response way, takeaway food consumption was associated with a higher risk of SHS, while increased frequency of breakfast and mild-intensity exercise conversely reduced said risk. Individuals with shorter sleep duration had a higher risk of SHS when compared to those who slept for more than seven hours per day. Conclusions: We observed a relatively high prevalence of SHS across China, highlighting the importance of lifestyle in health promotion. Specifically, adopting healthy dietary habits, engaging in regular physical activity, and ensuring high-quality sleep are key in preventing SHS. Registration: Chinese Clinical Trial Registry (ChiCTR2200061046).


Assuntos
Promoção da Saúde , Estilo de Vida , Humanos , Masculino , Feminino , Estudos Transversais , Nível de Saúde , China/epidemiologia
6.
Arch Virol ; 168(10): 250, 2023 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-37691052

RESUMO

Some members of genus Colletotrichum are important plant pathogens. Here, we report a novel positive single-stranded RNA virus, Colletotrichum camelliae hypovirus 1 (CcHV1), from strain GXNN11-2 of Colletotrichum camelliae. The complete genome of CcHV1 is 9907 nucleotides (nt) in length and contains a single large open reading frame (ORF) from nt 352 to 9006. This ORF encodes a polyprotein with four conserved domains, namely UDP-glycosyltransferase, RNA-dependent RNA polymerase (RdRp), peptidase, and DEAD-like helicase. The CcHV1 polyprotein shares the highest similarity with Fusarium concentricum hypovirus 1. Phylogenetic analysis indicated that CcHV1 clustered with members of the genus Betahypovirus within the family Hypoviridae. This is the first report of a hypovirus in a member of the genus Colletotrichum.


Assuntos
Colletotrichum , Vírus de RNA , Colletotrichum/genética , Filogenia , Vírus de RNA/genética , Vírus de RNA de Cadeia Positiva , Nucleotídeos , Poliproteínas
7.
J Sci Food Agric ; 103(15): 7381-7392, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37390299

RESUMO

BACKGROUND: Diabetes mellitus poses a substantial threat to public health due to rising morbidity and mortality. α-Glucosidase is one of the key enzymes affecting diabetes. Herein, (-)-epigallocatechin-3-gallate (EGCG) and (-)-epigallocatechin (EGC) were applied to clarify the role of the galloyl moiety of tea polyphenols in the inhibition of glycation and α-glucosidase activity. The structure-activity relationship of the galloyl moiety in EGCG on α-glucosidase was investigated in terms of inhibition kinetics, spectroscopy, atomic force microscopy and molecular docking. A bovine serum protein-fructose model was employed to determine the effect of the galloyl moiety on glycation. RESULTS: The results indicated that the introduction of a galloyl moiety enhanced the capacity of EGCG to inhibit glycation and α-glucosidase activity. The IC50 value of EGC is approximately 2400 times higher than that of EGCG. Furthermore, the galloyl moiety in EGCG altered the microenvironment and secondary structure of α-glucosidase, resulting in a high binding affinity of EGCG to α-glucosidase. The binding constant of EGCG to α-glucosidase at 298 K is approximately 28 times higher than that of EGC. CONCLUSION: Overall, the galloyl moiety of EGCG plays a crucial role in inhibiting glycation and α-glucosidase activity, which helps to enhance the molecular understanding of the structure and function of the polyphenol galloyl moiety in the science of food and agriculture. © 2023 Society of Chemical Industry.


Assuntos
Catequina , alfa-Glucosidases , alfa-Glucosidases/metabolismo , Simulação de Acoplamento Molecular , Catequina/farmacologia , Catequina/química , Polifenóis/química , Análise Espectral , Chá/química
8.
Medicine (Baltimore) ; 102(18): e33613, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37144997

RESUMO

RATIONALE: Lymphocytic interstitial pneumonia (LIP) is a rare benign lymphoproliferative disorder, often associated with autoimmune diseases. Most LIPs present with multiple bronchial cysts and diffuse interstitial infiltration. It is histologically characterized by widespread diffuse lymphocytic infiltration of the pulmonary interstitium, and the enlargement and widening of the alveolar septum. PATIENT CONCERNS: A 49-year-old woman was admitted to hospital for finding pulmonary nodules for more than 2 months. 3D imaging chest computed tomography (CT) examination of both lungs showed that there was a middle lobe of the right lung with a size of about 1.5 cm × 1.1 cm ground-glass nodules. DIAGNOSES: A single operating port thoracoscopic wedge resection biopsy of a right middle lung nodule was performed. The pathology showed diffuse lymphocytic infiltration with varying numbers of small lymphocytes, plasma cells, macrophages and histiocytes infiltrating the alveolar septa, widened and enlarged alveolar septa, and scattered lymphoid follicles. Immunohistochemically, CD20 positive in follicular area, CD3 positive in interfollicular area. LIP was considered. INTERVENTIONS: The patient was regularly followed without any specific treatment. OUTCOMES: Follow-up chest CT showed no significant abnormalities in the lungs 6 months after surgery. LESSONS: To the best of our knowledge, our case may be the second reported case of a patient with LIP presenting with a ground glass nodule on chest CT, and it is speculated that the ground glass nodule may be an early manifestation of idiopathic LIP.


Assuntos
Cisto Broncogênico , Doenças Pulmonares Intersticiais , Feminino , Humanos , Pessoa de Meia-Idade , Doenças Pulmonares Intersticiais/etiologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Plasmócitos/patologia , Cisto Broncogênico/complicações
9.
Molecules ; 28(9)2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37175098

RESUMO

With the increased incidence of wine fraud, a fast and reliable method for wine certification has become a necessary prerequisite for the vigorous development of the global wine industry. In this study, a classification strategy based on three-dimensional fluorescence spectroscopy combined with chemometrics was proposed for oak-barrel and stainless steel tanks with oak chips aged wines. Principal component analysis (PCA), partial least squares analysis (PLS-DA), and Fisher discriminant analysis (FDA) were used to distinguish and evaluate the data matrix of the three-dimensional fluorescence spectra of wines. The results showed that FDA was superior to PCA and PLS-DA in classifying oak-barrel and stainless steel tanks with oak chips aged wines. As a general conclusion, three-dimensional fluorescence spectroscopy can provide valuable fingerprint information for the identification of oak-barrel and stainless steel tanks with oak chips aged wines, while the study will provide some theoretical references and standards for the quality control and quality assessment of oak-barrel aged wines.


Assuntos
Quercus , Vinho , Vinho/análise , Aço Inoxidável , Quercus/química , Espectrometria de Fluorescência , Quimiometria , Madeira/química
10.
Int J Biol Macromol ; 238: 124132, 2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-36958439

RESUMO

As dye adsorbents with great potential, polysaccharide-based hydrogels are significantly hampered in practical application owing to intricate preparation methods, low absorption, and bad degradability. Salecan is a water-soluble extracellular polysaccharide with excellent physicochemical and biological properties. Here, salecan and xanthan gum were first used as a dual-precursors system, their mixed solution was crosslinked by Fe3+ to assemble a photo-degradable ionic gel for malachite green (MG) adsorption. Photo-degradation was done using visible light under very mild conditions, which gave rise to gel network dissolution and homogeneous solution formation. Extensive dynamic coordinate interactions between Fe3+ and polysaccharides maintained gel matrix stability and were systematically investigated. The control of water uptake, micro-structure, and rheology can be facilely implemented by tuning salecan/xanthan gum ratios. Furthermore, various parameters such as polysaccharide ratios, pHs, MG concentrations, and contact time affecting adsorption were optimized using batch experiments. Adsorption process accurately adhered to pseudo-second-order kinetic and Langmuir isotherm model, with the maximum adsorption capacity of 463.0 mg/g. Such mechanism implied monolayer chemisorptive characteristics. The gel exhibited satisfactory reusability and was recycled five times without apparent decrease in adsorption capacity. From these results, the photo-degradable Fe3+-induced salecan/xanthan gum ionic gel is an alternative and sustainable absorbent for MG removal.


Assuntos
Descontaminação , Ferro , Polissacarídeos Bacterianos/química , Corantes/química , Água , Adsorção , Concentração de Íons de Hidrogênio , Cinética
11.
Virol J ; 20(1): 25, 2023 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-36759854

RESUMO

BACKGROUND: Newcastle disease virus (NDV) is a highly infectious viral disease, which can affect chickens and many other kinds of birds. The main virulence factor of NDV, the fusion (F) protein, is located on the viral envelope and plays a major role in the virus' ability to penetrate cells and cause host cell fusion during infection. Multiple highly conserved tyrosine and di-leucine (LL) motifs in the cytoplasmic tail (CT) of the virus may contribute to F protein functionality in the viral life cycle. METHODS: To examine the contribution of the LL motif in the biosynthesis, transport, and function of the F protein, we constructed and rescued a NDV mutant strain, rSG10*-F/L537A, with an L537A mutation using a reverse genetic system. Subsequently, we compared the differences in the syncytium formation ability, pathogenicity, and replication levels of wild-type rSG10* and the mutated strain. RESULTS: Compared with rSG10*, rSG10*-F/L537A had attenuated syncytial formation and pathogenicity, caused by a viral budding defect. Further studies showed that the LL-motif mutation did not affect the replication, transcription, or translation of the virus genome but affected the expression of the F protein at the cell surface. CONCLUSIONS: We concluded that the LL motif in the NDV F CT affected the regulation of F protein expression at the cell surface, thus modulating the viral fusion ability and pathogenic phenotype.


Assuntos
Doença de Newcastle , Vírus da Doença de Newcastle , Animais , Vírus da Doença de Newcastle/genética , Galinhas , Leucina , Mutação , Mutagênese , Proteínas Virais de Fusão/genética , Proteínas Virais de Fusão/metabolismo
12.
BMC Bioinformatics ; 24(1): 12, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624399

RESUMO

Gallbladder carcinoma (GBC), an aggressive malignant tumor of the biliary system, is characterized by high cellular heterogeneity and poor prognosis. Fewer data have been reported in GBC than other common cancer types. Multi-omics data will contribute to the understanding of the molecular mechanisms of cancer, cancer diagnosis and prognosis. Herein, to provide better understanding of the molecular events in GBC pathogenesis, we developed GBCdb ( http://tmliang.cn/gbc/ ), a user-friendly interface for the query and browsing of GBC-associated genes and RNA interaction networks using published multi-omics data, which also included experimentally supported data from different molecular levels. GBCdb will help to elucidate the potential biological roles of different RNAs and allow for the exploration of RNA interactions in GBC. These resources will provide an opportunity for unraveling the potential molecular features of Gallbladder carcinoma.


Assuntos
Neoplasias da Vesícula Biliar , RNA Longo não Codificante , Humanos , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/patologia , RNA Mensageiro/genética , RNA não Traduzido/genética , Linhagem Celular Tumoral , RNA Longo não Codificante/genética , Regulação Neoplásica da Expressão Gênica
13.
AAPS PharmSciTech ; 23(8): 294, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329305

RESUMO

Long-term daily injection of progesterone for the treatment of threatened abortion can be a source of considerable pain to patients. To reduce the frequency of injections and improve patient compliance, a novel injectable phospholipid-based phase separation gel (PPSG) was prepared using small molecular materials such as phospholipids, medium-chain triglycerides (MCTs), and ethanol. Progesterone was loaded into PPSGs to promote rapid gel formation in situ via a sol-gel transformation mechanism, thereby achieving a sustained controlled release. Furthermore, progesterone was distributed in the oil-water interface layer and within the oil phase. Solvent exchange drives phase transitions, and phospholipid vesicle formation and rupture are likely to promote drug release and gel degradation. At a drug loading of 140 mg/mL, a progesterone release of up to 60% could be reached within 9 days according to the release curve in vitro. Pharmacokinetic studies demonstrated that the progesterone-loaded PPSGs released the drug continuously for over 7 days, the half-life was eight times higher than that of progesterone oil solution, and relative bioavailability of up to 184.90% was obtained. Collectively, the sustained release properties for hydrophobic cargos would effectively enhance patient compliance. Moreover, PPSGs are promising drug delivery systems that have high market value and biosafety given the readily accessible and safe excipients.


Assuntos
Fosfolipídeos , Progesterona , Humanos , Fosfolipídeos/química , Preparações de Ação Retardada/química , Géis/química , Liberação Controlada de Fármacos , Sistemas de Liberação de Medicamentos
14.
Genes (Basel) ; 13(6)2022 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-35741849

RESUMO

Prostate adenocarcinoma (PRAD), also named prostate cancer, the most common visceral malignancy, is diagnosed in male individuals. Herein, in order to obtain immune-based subtypes, we performed an integrative analysis to characterize molecular subtypes based on immune-related genes, and further discuss the potential features and differences between identified subtypes. Simultaneously, we also construct an immune-based risk model to assess cancer prognosis. Our findings showed that the two subtypes, C1 and C2, could be characterized, and the two subtypes showed different characteristics that could clearly describe the heterogeneity of immune microenvironments. The C2 subtype presented a better survival rate than that in the C1 subtype. Further, we constructed an immune-based prognostic model based on four screened abnormally expressed genes, and they were selected as predictors of the robust prognostic model (AUC = 0.968). Our studies provide reference for characterization of molecular subtypes and immunotherapeutic agents against prostate cancer, and the developed robust and useful immune-based prognostic model can contribute to cancer prognosis and provide reference for the individualized treatment plan and health resource utilization. These findings further promote the development and application of precision medicine in prostate cancer.


Assuntos
Adenocarcinoma , Neoplasias da Próstata , Adenocarcinoma/genética , Humanos , Masculino , Medicina de Precisão , Prognóstico , Próstata , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Microambiente Tumoral/genética
15.
Plant Dis ; 106(12): 3154-3165, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35549326

RESUMO

Pearl plum (Prunus salicina Lindl.) is mainly cultivated in Tian'e County in Guangxi Province, southern China. Anthracnose is a devastating disease on pearl plum, causing extensive leaf blight. Diseased leaves were sampled from 21 orchards in Tian'e County. Isolates were first screened for ones resembling Colletotrichum, and 21 representative isolates were selected for sequencing of portions of the ribosomal internal transcribed spacer (ITS), the intergenic region of apn2 and MAT1-2-1 genes (ApMAT), actin (ACT), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), calmodulin (CAL), chitin synthase (CHS-1), and ß-tubulin 2 (TUB2). Based on colony, conidial, and appressorial morphology and sequence analyses, the Colletotrichum isolates associated with pearl plum anthracnose were identified as four species: Colletotrichum fructicola (16 isolates), C. gloeosporioides (3 isolates), C. cigarro (1 isolate), and C. siamense (1 isolate). The results of pathogenicity tests showed that isolates of all four species were pathogenic to wounded leaves of pearl plum seedlings. In this study, we microscopically observed the infection processes of isolates of these four species on attached pearl plum leaves. For C. cigarro and C. siamense, the entire infection processes took 120 h; for C. fructicola and C. gloeosporioides, it only took 72 h. This is the first report of C. fructicola and C. cigarro causing anthracnose on pearl plum worldwide, and also the first report of C. siamense causing anthracnose on pearl plum in China.


Assuntos
Colletotrichum , Prunus domestica , Doenças das Plantas , DNA Fúngico/genética , Filogenia , China
17.
Comput Struct Biotechnol J ; 19: 5722-5734, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745457

RESUMO

Cholangiocarcinomas (CCAs) are tumors that arise from the cholangiocytes. Although some genes have been shown with important roles in pathological process, interactions or cross-talks among different RNAs are important to understand the detailed molecular mechanisms in cancer development, especially discussing cross-talks among isomiRs and other RNAs. Herein, to characterize crucial genes in CCA, the protein expression profile was performed to survey potential crucial mRNAs and related non-coding RNAs (ncRNAs) in mRNA-ncRNA network, mainly including miRNAs/isomiRs and lncRNAs. Deregulated mRNAs were firstly obtained if consistent expression patterns were found at protein and mRNA levels, and related miRNAs/isomiRs were screened according to regulatory relationships. Diverse isomiRs from a given miRNA locus also contributed to interactions between the small RNAs and target mRNAs, and miRNAs were further used to survey related lncRNAs to expand the interactions. Thus, several groups of RNAs were constructed as candidate competitive endogenous RNA (ceRNA) networks. Finally, we found that RAB11FIP1:miR-101-3p:MIR3142HG may be a potential ceRNA network, and the interactions among them may be more complex due to variety of isomiRs. Simultaneously, RAB11FIP1 and miR-194-5p were also detected other related lncRNAs (FBXL19-AS1, SNHG1 and PVT1) that may be crucial in coding-non-coding RNA regulatory network. Our results show that diverse isomiRs with sequence and expression heterogeneities contribute to ceRNA regulatory network that may have crucial roles in CCA, which will expand our understanding of interactions among diverse RNAs and their contributions in cancer development.

19.
Oncologist ; 26(10): e1844-e1853, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34132450

RESUMO

BACKGROUND: GSK2849330, an anti-HER3 monoclonal antibody that blocks HER3/Neuregulin 1 (NRG1) signaling in cancer cells, is engineered for enhanced antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. This phase I, first-in-human, open-label study assessed the safety, pharmacokinetics (PK), pharmacodynamics, and preliminary activity of GSK2849330 in patients with HER3-expressing advanced solid tumors. PATIENTS AND METHODS: Patients with various tumor types were prospectively selected for HER3 expression by immunohistochemistry; a subset was also screened for NRG1 mRNA expression. In the dose-escalation phase, patients received GSK2849330 1.4-30 mg/kg every 2 weeks, or 3 mg/kg or 30 mg/kg weekly, intravenously (IV). In the dose-expansion phase, patients received 30 mg/kg GSK2849330 IV weekly. RESULTS: Twenty-nine patients with HER3-expressing cancers, of whom two expressed NRG1, received GSK2849330 (dose escalation: n = 18, dose expansion: n = 11). GSK2849330 was well tolerated. No dose-limiting toxicities were observed. The highest dose, of 30 mg/kg weekly, expected to provide full target engagement, was selected for dose expansion. Treatment-emergent adverse events (AEs) were mostly grade 1 or 2. The most common AEs were diarrhea (66%), fatigue (62%), and decreased appetite (31%). Dose-proportional plasma exposures were achieved, with evidence of HER3 inhibition in paired tissue biopsies. Of 29 patients, only 1 confirmed partial response, lasting 19 months, was noted in a patient with CD74-NRG1-rearranged non-small cell lung cancer (NSCLC). CONCLUSION: GSK2849330 demonstrated a favorable safety profile, dose-proportional PK, and evidence of target engagement, but limited antitumor activity in HER3-expressing cancers. The exceptional response seen in a patient with CD74-NRG1-rearranged NSCLC suggests further exploration in NRG1-fusion-positive cancers. IMPLICATIONS FOR PRACTICE: This first-in-human study confirms that GSK2849330 is well tolerated. Importantly, across a variety of HER3-expressing advanced tumors, prospective selection by HER3/NRG1 expression alone was insufficient to identify patients who could benefit from treatment with this antibody-dependent cell-mediated cytotoxicity- and complement-dependent cytotoxicity-enhanced anti-HER3 antibody. The only confirmed durable response achieved was in a patient with CD74-NRG1-rearranged lung cancer. This highlights the potential utility of screening for NRG1 fusions prospectively across tumor types to enrich potential responders to anti-HER3 agents in ongoing trials.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Neoplasias , Anticorpos Monoclonais Humanizados , Humanos , Dose Máxima Tolerável , Neoplasias/tratamento farmacológico , Estudos Prospectivos
20.
BMC Geriatr ; 21(1): 225, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33794800

RESUMO

BACKGROUND: Sepsis is a critical challenge for the older adults as the immune function is less responsive by aging. Although cell numbers seem preserved in the older adults, macrophages present age-related function decline, which including reduced chemokines, phagocytosis, and autophagy. ABT-263, an inhibitor of the anti-apoptotic protein Bcl-2, is reported had a senolytic effect which can selectively clear the senescent cells in vivo and rejuvenate the aged tissues. METHODS: We treated the aged (12-16 months) and young (4-6 months) C57BL/6 mouse with ABT-263, then gave the animals cecal slurry injection to induce sepsis to observe the effect of senolytic compound ABT-263 on the survival rate of sepsis. Additionally, we isolated peritoneal macrophages from the aged mouse to investigate the cell function and molecular mechanism. 3-methyladenine (3-MA), a phosphatidylinositol 3-kinases (PI3K) inhibitor, and rapamycin, an autophagy-enhancer, were used to block or mimic the autophagy, respectively. RT-PCR and Western Blot were used to detect autophagy related gene and protein changes in sepsis. EGFP-expressing E. coli was used as a marker to evaluate the phagocytic ability of macrophages. RESULTS: The results showed ABT-263 treatment improved the survival rate of sepsis in the aged mouse which related to autophagy, while blocking the autophagy can eliminate this effect. It is revealed that ABT-263 enhanced the phagocytic ability of the peritoneal macrophages by increasing the Trem-2 receptor. Additionally, ABT-263 blocked the binding of Bcl-2 to Beclin-1, thus induced Beclin-1-dependent autophagy. CONCLUSION: ABT-263 enhanced the macrophage function in aged mouse by increasing the Trem-2 receptors and inducing a beclin-1-dependent autophagy, consequently, protected the aged mouse from sepsis.


Assuntos
Escherichia coli , Fosfatidilinositol 3-Quinases , Idoso , Compostos de Anilina , Animais , Autofagia , Proteína Beclina-1 , Humanos , Macrófagos , Camundongos , Camundongos Endogâmicos C57BL , Fagocitose , Sulfonamidas
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