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1.
Integr Cancer Ther ; 23: 15347354241242120, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590244

RESUMO

OBJECTIVES: To evaluate the effects of Reishimmune-S, a fungal immunomodulatory peptide, on the quality of life (QoL) and natural killer (NK) cell subpopulations in patients receiving adjuvant endocrine therapy (ET) for breast cancer (BC). METHODS: Patients who received adjuvant ET for stage I-III hormone receptor-positive BC without active infection were enrolled in this prospective pilot study. Reishimmune-S was administered sublingually daily for 6 months. QoL scores, circulating immune cell levels, including lymphocyte/NK cell subpopulations, and plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured at baseline and every 4 weeks. Data were analyzed using linear mixed-effect regression models. RESULTS: Nineteen participants were included in the analyses. One patient with underlying asthma did not complete the study owing to the occurrence of skin rashes 15 days after the initiation of Reishimmune-S. No other adverse events were reported. Reishimmune-S supplementation significantly improved the cognitive function at 3 months and significantly decreased the fatigue and insomnia levels at 3 and 6 months, respectively. There was no significant change in the global health/QoL score between baseline and week 4 of treatment. The proportion of CD19+ lymphocytes was significantly higher at 3 and 6 months, and that of NKG2A+ and NKp30+ NK cells was significantly lower at 6 months than at baseline. In addition, fatigue positively correlated with the proportion of NKp30+ NK cells (ß ± standard error: 24.48 ± 8.75, P = .007 in the mixed-effect model). CONCLUSIONS: Short-term supplementation with Reishimmune-S affected the circulating immune cell composition and exerted positive effects on cognitive function, fatigue, and insomnia in patients with BC undergoing adjuvant ET, providing a potential approach for the management of treatment-related adverse reactions in this patient population.


Assuntos
Neoplasias da Mama , Distúrbios do Início e da Manutenção do Sono , Humanos , Feminino , Neoplasias da Mama/psicologia , Qualidade de Vida , Estudos Prospectivos , Projetos Piloto , Fator de Necrose Tumoral alfa , Células Matadoras Naturais , Suplementos Nutricionais , Fadiga/induzido quimicamente
2.
Head Neck ; 46(5): 1009-1019, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38441255

RESUMO

OBJECTIVE: To enhance the accuracy in predicting lymph node metastasis (LNM) preoperatively in patients with papillary thyroid microcarcinoma (PTMC), refining the "low-risk" classification for tailored treatment strategies. METHODS: This study involves the development and validation of a predictive model using a cohort of 1004 patients with PTMC undergoing thyroidectomy along with central neck dissection. The data was divided into a training cohort (n = 702) and a validation cohort (n = 302). Multivariate logistic regression identified independent LNM predictors in PTMC, leading to the construction of a predictive nomogram model. The model's performance was assessed through ROC analysis, calibration curve analysis, and decision curve analysis. RESULTS: Identified LNM predictors in PTMC included age, tumor maximum diameter, nodule-capsule distance, capsular contact length, bilateral suspicious lesions, absence of the lymphatic hilum, microcalcification, and sex. Especially, tumors larger than 7 mm, nodules closer to the capsule (less than 3 mm), and longer capsular contact lengths (more than 1 mm) showed higher LNM rates. The model exhibited AUCs of 0.733 and 0.771 in the training and validation cohorts respectively, alongside superior calibration and clinical utility. CONCLUSION: This study proposes and substantiates a preoperative predictive model for LNM in patients with PTMC, honing the precision of "low-risk" categorization. This model furnishes clinicians with an invaluable tool for individualized treatment approach, ensuring better management of patients who might be proposed observation or ablative options in the absence of such predictive information.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Carcinoma Papilar/cirurgia , Carcinoma Papilar/patologia , Esvaziamento Cervical , Tireoidectomia , Metástase Linfática/patologia , Estudos Retrospectivos , Linfonodos/patologia , Fatores de Risco
3.
Head Neck ; 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38348564

RESUMO

BACKGROUND: The preservation of parathyroid glands is crucial in endoscopic thyroid surgery to prevent hypocalcemia and related complications. However, current methods for identifying and protecting these glands have limitations. We propose a novel technique that has the potential to improve the safety and efficacy of endoscopic thyroid surgery. PURPOSE: Our study aims to develop a deep learning model called PTAIR 2.0 (Parathyroid gland Artificial Intelligence Recognition) to enhance parathyroid gland recognition during endoscopic thyroidectomy. We compare its performance against traditional surgeon-based identification methods. MATERIALS AND METHODS: Parathyroid tissues were annotated in 32 428 images extracted from 838 endoscopic thyroidectomy videos, forming the internal training cohort. An external validation cohort comprised 54 full-length videos. Six candidate algorithms were evaluated to select the optimal one. We assessed the model's performance in terms of initial recognition time, identification duration, and recognition rate and compared it with the performance of surgeons. RESULTS: Utilizing the YOLOX algorithm, we developed PTAIR 2.0, which demonstrated superior performance with an AP50 score of 92.1%. The YOLOX algorithm achieved a frame rate of 25.14 Hz, meeting real-time requirements. In the internal training cohort, PTAIR 2.0 achieved AP50 values of 94.1%, 98.9%, and 92.1% for parathyroid gland early prediction, identification, and ischemia alert, respectively. Additionally, in the external validation cohort, PTAIR outperformed both junior and senior surgeons in identifying and tracking parathyroid glands (p < 0.001). CONCLUSION: The AI-driven PTAIR 2.0 model significantly outperforms both senior and junior surgeons in parathyroid gland identification and ischemia alert during endoscopic thyroid surgery, offering potential for enhanced surgical precision and patient outcomes.

4.
Front Endocrinol (Lausanne) ; 15: 1337322, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38362277

RESUMO

Background: Robotic assistance in thyroidectomy is a developing field that promises enhanced surgical precision and improved patient outcomes. This study investigates the impact of the da Vinci Surgical System on operative efficiency, learning curve, and postoperative outcomes in thyroid surgery. Methods: We conducted a retrospective cohort study of 104 patients who underwent robotic thyroidectomy between March 2018 and January 2022. We evaluated the learning curve using the Cumulative Sum (CUSUM) analysis and analyzed operative times, complication rates, and postoperative recovery metrics. Results: The cohort had a mean age of 36 years, predominantly female (68.3%). The average body mass index (BMI) was within the normal range. A significant reduction in operative times was observed as the series progressed, with no permanent hypoparathyroidism or recurrent laryngeal nerve injuries reported. The learning curve plateaued after the 37th case. Postoperative recovery was consistent, with no significant difference in hospital stay duration. Complications were minimal, with a noted decrease in transient vocal cord palsy as experience with the robotic system increased. Conclusion: Robotic thyroidectomy using the da Vinci system has demonstrated a significant improvement in operative efficiency without compromising safety. The learning curve is steep but manageable, and once overcome, it leads to improved surgical outcomes and high patient satisfaction. Further research with larger datasets and longer follow-up is necessary to establish the long-term benefits of robotic thyroidectomy.


Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias da Glândula Tireoide , Humanos , Feminino , Adulto , Masculino , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/cirurgia
5.
J Transl Med ; 22(1): 125, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38303030

RESUMO

BACKGROUND: Previous studies have shown that changes in the microbial community of the female urogenital tract are associated with Human papillomavirus (HPV) infection. However, research on this association was mostly focused on a single site, and there are currently few joint studies on HPV infection and multiple sites in the female urogenital tract. METHODS: We selected 102 healthy women from Yunnan Province as the research object, collected cervical exfoliation fluid, vaginal, urethral, and rectal swabs for microbial community analysis, and measured bacterial load, and related cytokine content. The link between HPV, microbiota, and inflammation was comprehensively evaluated using bioinformatics methods. FINDINGS: The impact of HPV infection on the microbial composition of different parts varies. We have identified several signature bacterial genera that respond to HPV infection in several detection sites, such as Corynebacterium, Lactobacillus, Campylobacter, and Cutibacterium have been detected in multiple sites, reflecting their potential significance in cross body sites HPV infection responses. There was a solid microbial interaction network between the cervix, vagina, and urethra. The interrelationships between inflammatory factors and different bacterial genera might also affect the immune system's response to HPV infection. INTERPRETATION: It might be an effective strategy to prevent and treat HPV infection by simultaneously understanding the correlation between the microbial changes in multiple parts of the female urogenital tract and rectum and HPV infection, and controlling the microbial network related to HPV infection in different parts.


Assuntos
Infecções por Papillomavirus , Reto , Feminino , Humanos , China , Vagina/microbiologia , Bactérias , RNA Ribossômico 16S , Papillomaviridae
6.
Gerontology ; 69(10): 1175-1188, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37527625

RESUMO

INTRODUCTION: People with dementia often experience behavioral and psychological symptoms of dementia (BPSD), which are a major cause of caregiver burden and institutionalization. Therefore, we conducted a double-blind, parallel-group randomized controlled trial to examine the efficacy of blue-enriched light therapy for BPSD in institutionalized older adults with dementia. METHODS: Participants were enrolled and randomly allocated into blue-enriched light therapy (N = 30) or the conventional light group (N = 30) for 60 min in 10 weeks with five sessions per week. The primary outcome was sleep quality measured by actigraphy and Pittsburgh Sleep Quality Index (PSQI). The secondary outcome was overall BPSD severity (Cohen-Mansfield Agitation Inventory [CMAI] and Neuropsychiatric Inventory [NPI-NH]). The outcome indicators were assessed at baseline, mid-test, immediate posttest, 1-month, 3-month, and 6-month follow-up. The effects of the blue-enriched light therapy were examined by the generalized estimating equation model. RESULTS: Blue-enriched light therapy revealed significant differences in the objective sleep parameters (sleep efficiency: ß = 5.81, Waldχ2 = 32.60, CI: 3.82; 7.80; sleep latency: ß = -19.82, Waldχ2 = 38.38, CI:-26.09; -13.55), subjective sleep quality (PSQI: ß = -2.07, Waldχ2 = 45.94, CI: -2.66; -1.47), and overall BPSD severity (CMAI: ß = -0.90, Waldχ2 = 14.38, CI: -1.37; -0.44) (NPI-NH: ß = -1.67, Waldχ2 = 30.61, CI: -2.26; -1.08) compared to conventional phototherapy immediate posttest, 1-month, 3-month, and 6-month follow-up. Furthermore, the effects for sleep efficiency and sleep latency lasted for up to 6 months. In the subscale analysis, the differences of the behavioral symptoms changed significantly between the groups in physical/nonaggressive (CI: -1.01; -0.26) and verbal/nonaggressive (CI: -0.97; -0.29). CONCLUSIONS: Blue-enriched light therapy is a feasible low-cost intervention that could be integrated as a comprehensive therapy program for BPSD among older adults with dementia.

7.
Org Lett ; 25(20): 3682-3686, 2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37191623

RESUMO

A palladium catalyzed tandem reaction between ortho-functionalized aryl enones and 2,4-dienyl carbonates has been presented, proceeding through sequential 2,4-dienylation/Michael addition/π-σ-π isomerization/allylic alkylation. A broad array of enantioenriched architectures having fused and spirocyclic frameworks are constructed in moderate to excellent yields and stereoselectivity. Notably, the intrinsic intramolecular Diels-Alder reaction pattern of the dienylated intermediates is well reversed via Pd(0)-π-Lewis base catalysis.

8.
Fitoterapia ; 166: 105443, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36736743

RESUMO

A new hybrid sorbicillinoid named paeciureallin (1) and a new monomeric sorbicillinoid named paecillyketide (2), along with six known analogues (3-8), were isolated from the rhizospheric soil-derived fungus Paecilomyces sp. KMU21009 associated with Delphinium yunnanense. Their structures were elucidated by extensive spectroscopic analysis and comparison with literature values. Paeciureallin (1) is the first example of hybrid sorbicillinoids possessing a rare sorbicillinoid urea unit and containing a ß-D-ribofuranose functionality. In pharmacological studies, compounds 1 and 2 were evaluated for in vitro anti-inflammatory and cytotoxic activities. Paeciureallin (1) exhibited moderate cytotoxicity against SW480 and A549 cell lines, and the IC50 values were 32.0 ± 0.1 and 34.4 ± 2.0 µM, respectively.


Assuntos
Antineoplásicos , Paecilomyces , Estrutura Molecular , Paecilomyces/química , Antineoplásicos/farmacologia , Anti-Inflamatórios
9.
J Oral Pathol Med ; 52(3): 245-254, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36273268

RESUMO

BACKGROUND: Accumulating evidence shows that high expression of casein kinase 2 (CK2) and phosphorylated acetyl CoA carboxylase (pACC) in patients with squamous cell carcinoma of the head and neck (SCCHN) correlates with decreased survival rates. Computational analysis has shown that ACC is a potential substrate for CK2, and its inhibition can suppress ACC phosphorylation in vitro. CX-4945, also known as silmitasertib, is an orally administered, highly specific, ATP-competitive inhibitor of CK2 and is under clinical investigation as a treatment for malignancies. We hypothesize that inhibition of CK2 by CX-4945 can reduce CK2-downstream phosphorylation of ACC as a therapeutic strategy against SCCHN. METHODS: Three aggressive SCCHN cell lines (OSC-19, FaDu and HN31) were cultured to investigate the anticancer mechanism of the CK2 inhibitor, CX-4945. Cell cycle analysis, Annexin V/PI staining, and cleavage of PARP were performed to detect apoptosis. Western blot, electron microscopy and analysis of acidic vesicular organelle development were used to detect autophagy. Interference with cellular metabolism by CX-4945 treatment was determined by Seahorse XF24 Extracellular Flux Analyzer and mass spectrometry. RESULTS: Cellular metabolism was impeded by CX-4945 in aggressive SCCHN cells by Seahorse XF24 Extracellular Flux Analyzer and mass spectrometry, and consequently time- and dose-dependent lipid droplet accumulation and non-apoptotic cell death were observed. The lipogenic enzyme ACC was demonstrated to be associated with CK2, and its repressive phosphorylation could be removed by the CK2 inhibitor CX-4945. Overexpression of ACC resulted in impaired cell survival following transient transfection. CONCLUSION: The findings demonstrate that CK2 inhibition impairs normal cellular energy metabolism and may be an attractive therapy for treating aggressive SCCHN.


Assuntos
Caseína Quinase II , Neoplasias de Cabeça e Pescoço , Humanos , Gotículas Lipídicas , Morte Celular , Fenazinas , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Linhagem Celular Tumoral
10.
Angew Chem Int Ed Engl ; 62(5): e202214135, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36478374

RESUMO

Carbene insertion reactions initiated with diazo compounds have been widely used to develop unnatural enzymatic reactions. However, alternative functionalization of diazo compounds in enzymatic processes has been unexploited. Herein, we describe a photoenzymatic strategy for radical-mediated stereoselective hydroalkylation with diazo compounds. This method generates carbon-centered radicals through an ene reductase catalyzed photoinduced electron transfer process from diazo compounds, enabling the synthesis of γ-stereogenic carbonyl compounds in good yields and stereoselectivities. This study further expands the possible reaction patterns in photo-biocatalysis and offers a new approach to solving the selectivity challenges of radical-mediated reactions.

11.
J Am Chem Soc ; 144(3): 1087-1093, 2022 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-35007081

RESUMO

Enantioselective [3 + 2] annulation of N-heteroarenes with alkynes has been developed via a cobalt-catalyzed dearomative umpolung strategy in the presence of chiral ligand and reducing reagent. A variety of electron-deficient N-heteroarenes, including quinolines, isoquinolines, quinoxaline, and pyridines, and internal or terminal alkynes are employed in this reaction, showing a broad substrate scope and good functionality tolerance. Annulation of electron-rich indoles with alkynes is also developed. This protocol provides a straightforward access to a variety of N-spiroheterocyclic molecules in excellent enantioselectivities (76 examples, up to 99% ee).

12.
Nanotechnology ; 33(16)2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-34963107

RESUMO

Bulk heterojunction is one key concept leading to breakthrough in organic photovoltaics. The active layer is expectantly formed of distinct morphologies that carry out their respective roles in photovoltaic performance. The morphology-performance relationship however remains stymied, because unequivocal morphology at the nanoscale is not available. We used scattering-type scanning near-field optical microscopy operating with a visible light source (visibles-SNOM) to disclose the nanomorphology of P3HT:PCBM and pBCN:PCBM blends. Donor and acceptor domain as well as intermixed phase were identified and their intertwined distributions were mapped. We proposed energy landscapes of the BHJ active layer to shed light on the roles played by these morphologies in charge separation, transport and recombination. This study shows that visibles-SNOM is capable of profiling the morphological backdrop pertaining to the operation of high performance organic solar cells.

13.
Chem Commun (Camb) ; 57(44): 5454-5457, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33954323

RESUMO

The mechanism of the deactivation and regeneration of PtSn intermetallic compound nanoparticle (iNP) catalysts was studied by in situ TEM investigation. Our study reveals the reversible dynamic structural transition of the iNPs during deactivation and regeneration, which provides a direct correlation between the atomic structure and the catalytic activity of the iNPs.

14.
Int J Mol Sci ; 21(18)2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32961983

RESUMO

Reprogramming of cellular energy metabolism, such as lipid metabolism, is a hallmark of squamous cell carcinoma of the head and neck (SCCHN). However, whether protein expression related to fatty acid oxidation (FAO) affects survival in SCCHN remains unclear. We aimed to investigate FAO-related enzyme expression and determine its correlation with clinicopathological variables in SCCHN patients. Immunohistochemical analysis (IHC) of FAO-related protein expression, including carnitine palmitoyltransferase 1 (CPT1), the acyl-CoA dehydrogenase family, and fatty acid synthase (FAS), was performed using tissue microarrays from 102 resected SCCHN tumors. Expressions were categorized according to IHC scores, and the statistical association with clinicopathological factors was determined. Moderate-to-high expression of long-chain acyl-CoA dehydrogenase (LCAD) had a protective role against cancer-related death (adjusted hazard ratio (HR), 0.2; 95% confidence interval (CI), 0.05-0.87) after covariate adjustment. Age and clinical stage remained independent predictors of survival (adjusted HR, 1.75; 95% CI, 1.22-2.49 for age; adjusted HR, 14.33; 95% CI, 1.89-108.60 for stage III/IV disease). Overexpression of medium-chain acyl-CoA dehydrogenase and FAS correlated with advanced tumor stage (T3/T4); however, none of these factors were independent predictors of survival. Several FAO-related enzymes were upregulated and LCAD overexpression had a protective effect on overall survival in advanced SCCHN patients. FAO-related-enzyme expression might have a prognostic impact on survival outcomes in SCCHN.


Assuntos
Acil-CoA Desidrogenase de Cadeia Longa/metabolismo , Ácidos Graxos/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carnitina O-Palmitoiltransferase/metabolismo , Ácido Graxo Sintases/metabolismo , Feminino , Neoplasias de Cabeça e Pescoço/enzimologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Carcinoma de Células Escamosas de Cabeça e Pescoço/enzimologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Análise Serial de Tecidos , Regulação para Cima
15.
J Am Chem Soc ; 142(36): 15276-15281, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32815720

RESUMO

A highly branch- and enantioselective 1,4-enynes synthesis from readily available terminal alkynes and racemic allylic carbonates by Sonogashira type synergistic Rh and Cu catalysis under neutral conditions has been developed. Aliphatic and aromatic terminal alkynes with various functional groups could be used directly. An inner-sphere reductive elimination C(sp)-C(sp3) bond formation mechanism is supported by the stoichiometric reaction.

16.
Org Lett ; 22(9): 3519-3523, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32301619

RESUMO

Cobalt-catalyzed highly branched- and enantioselective allylic alkylation of malononitriles has been developed. Chiral γ,δ-unsaturated malononitriles could be synthesized with >20:1 branched/linear regioselectivity and up to 99% enantiomeric excess from easily accessible racemic allylic carbonates under mild reaction conditions. The electron-rich and sterically less hindered bisoxazolinephosphine ligand is essential to realize the high reactivity in the carbon-carbon bond formation process.

17.
Medicine (Baltimore) ; 99(12): e19577, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32195970

RESUMO

RATIONALE: The diagnosis of anaplastic lymphoma kinase (ALK)-negative inflammatory myofibroblastic tumors (IMT) remains challenging because of their morphological resemblance with spindle cell sarcoma with myofibroblastic characteristics. PATIENT CONCERNS: A 69-year-old female patient presented with loco-regional recurrent IMT several times within 8 years after primary treatment and neck lymph node metastasis 3.5 years after last recurrence. DIAGNOSIS: The primary, recurrence, and lymph node metastasis lesions were diagnosed as ALK-negative IMTs based on the histopathological features. INTERVENTIONS: Biopsy samples were obtained during repeated surgeries and evaluated for genomic alterations during first and recurrent presentations. The evaluation was done using pathway-driven massive parallel sequencing, and genomic alterations between primary and recurrent tumors were compared. OUTCOMES: Copy number gains and overexpression of mouse double minute 2 homolog (MDM2) and cyclin dependent kinase 4 (CDK4) were observed in the primary lesion, and additional gene amplification of Discoidin Domain Receptor Tyrosine Kinase 2 (DDR2), Succinate Dehydrogenase Complex II subunit C (SDHC), and thyroid stimulating hormone receptor (TSHR) Q720H were found in the recurrent tumors. Metastases to the neck lymph node were observed 3.5 years after recurrence. LESSONS: Our results indicated genetic evolution in a microscopically benign condition and highlighted the importance of molecular characterization of fibro-inflammatory lesions of uncertain malignant potential.


Assuntos
Granuloma de Células Plasmáticas/metabolismo , Neoplasias de Cabeça e Pescoço/secundário , Recidiva Local de Neoplasia/patologia , Neoplasias de Tecido Muscular/metabolismo , Quinase do Linfoma Anaplásico/metabolismo , Quinase 4 Dependente de Ciclina/metabolismo , Diagnóstico Diferencial , Feminino , Amplificação de Genes , Granuloma de Células Plasmáticas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Metástase Linfática , Mediastino/patologia , Pessoa de Meia-Idade , Miofibroblastos/patologia , Neoplasias de Tecido Muscular/patologia , Neoplasias de Tecido Muscular/radioterapia , Proteínas Proto-Oncogênicas c-mdm2/metabolismo
18.
Cancers (Basel) ; 11(10)2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31569404

RESUMO

MicroRNAs (miRNAs) have been shown to play a crucial role in the progression of human cancers, including urothelial carcinoma (UC), the sixth-most common cancer in the world. Among them, miR-34a has been implicated in the regulation of cancer stem cells (CSCs); however, its role in UC has yet to be fully elucidated. In this study, bioinformatics and experimental analysis confirmed that miR-34a targets CD44 (a CSC surface marker) and c-Myc (a well-known cell cycle regulator) in UC. We found that, surprisingly, most UC cell lines and patient samples did express miR-34a, although epigenetic silencing by promoter hypermethylation of miR-34a expression was observed only in UMUC3 cells, and a subset of patient samples. Importantly, overexpression of c-Myc, a frequently amplified oncogene in UC, was shown to upregulate CD44 expression through a competing endogenous RNA (ceRNA) mechanism, such that overexpression of the c-Myc 3'UTR upregulated CD44, and vice versa. Importantly, we observed a positive correlation between the expression of c-Myc and CD44 in clinical samples obtained from UC patients. Moreover, overexpression of a dominant-negative p53 mutant downregulated miR-34a, but upregulated c-Myc and CD44, in UC cell lines. Functionally, the ectopic expression of miR-34a was shown to significantly suppress CD44 expression, and subsequently, suppression of cell growth and invasion capability, while also reducing chemoresistance. In conclusion, it appears that aberrant promoter methylation, and c-Myc-mediated ceRNA mechanisms, may attenuate the function of miR-34a, in UC. The tumor suppressive role of miR-34a in controlling CSC phenotypes in UC deserves further investigation.

19.
BMC Gastroenterol ; 19(1): 119, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286888

RESUMO

BACKGROUND: The effectiveness in surveillance colonoscopy largely depends on the quality of bowel preparation. We aimed to investigate the quality of bowel preparation segmentally and its effect on Adenoma Detection Rate (ADR) and Advanced Adenoma Detection Rate (AADR) at corresponding bowel segments. METHODS: This is a single-centered and cross-sectional study. A consecutive of 5798 patients who underwent colonoscopy examination were included. Bowel preparation was evaluated based on Bowel Bubble Scale (BBS) in general and Boston Bowel Preparation Scale (BBPS) in each segment (right side, transverse and left side of colon) and total BBPS scores. The quality of bowel preparation was correlated with ADR and AADR. RESULTS: Four thousand nine hundred forty colonoscopies (14,820 bowel segments) were included in the final analysis. In which 30.9% scored 3, 57.5% scored 2, 11.2% scored 1 and 0.4% scored 0 on basis of BBPS. For each score, ADR were 10.8, 7.7, 4.9 and 3.2%, respectively; whereas AADR were 4.5, 2.8,1.8 and 1.6% (P < 0.05). 36.9% of the colonoscopies showed presence of minimal bubbles and 34.3% with no bubble. For bowels without bubbles and with a large amount of bubbles, ADR were 28.3 and 20.0% respectively; and AADR were 13.3 and 7.1% respectively. CONCLUSIONS: Segmental bowels' cleanliness and the amount of bubbles in bowels significantly affect ADR and AADR. The better the bowel preparation at each segment is and the less bubbles in the bowel there are, the higher ADR and AADR we got. We suggest repeating colonoscopy if any segment of the bowel preparation is poor, or if there is more bubbles, even if the total score of BBPS indicates good or fair bowel preparation.


Assuntos
Adenoma/diagnóstico , Catárticos/normas , Colonoscopia/estatística & dados numéricos , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/estatística & dados numéricos , Vigilância da População/métodos , Idoso , Catárticos/uso terapêutico , Colo/efeitos dos fármacos , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Front Microbiol ; 10: 789, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31057508

RESUMO

OBJECTIVE: This study aims to identify suitable lactobacilli that have anti-carbapenem-resistant Enterobacteriaceae (CRE) activity with in vitro tolerance to pepsin and bile salts. METHODS: Fifty-seven Lactobacillus spp. strains encompassing nine species were collected for investigation. Their viabilities in the presence of pepsin and bile salts were tested using tolerance tests. Their anti-CRE effects were assessed by agar well diffusion and broth microdilution assay, as well as time-kill test. RESULTS: Of the 57 Lactobacillus isolates collected, 31 had a less than 2-log reduction in their viability in both pepsin and bile salt tolerance tests. Of these 31 isolates, 5 (LUC0180, LUC0219, LYC0289, LYC0413, and LYC1031) displayed the greatest anti-CRE activity with a CRE zone of inhibition greater than 15 mm in agar well diffusion assays. The minimal inhibitory percentages of supernatants from these five strains against CREs ranged from 10 to 30%. With the exception of LUC0180, which had a minimal bactericidal percentage ≥ 40%, the bactericidal percentage of all the strains ranged from 20 to 40%. The inhibitory effect of the cell-free culture supernatants from these Lactobacillus strains did not change after heating but was abolished as the pH changed to 7.0. After a 24-h incubation, five of the Lactobacillus strains at a concentration of 108 CFU/ml totally inhibited the growth of carbapenem-resistant Escherichia coli (CRE316) and Klebsiella pneumoniae (CRE632). After a 48-h incubation, the growth of CRE316 was completely inhibited under each concentration of lactobacilli based on time-kill test. Furthermore, when the concentration of lactobacilli was at 108 CFU/ml, the decline in pH was faster than at other concentrations. CONCLUSION: Some Lactobacillus strains exhibit anti-CRE activity, which suggests potential applications for controlling or preventing CRE colonization or infection.

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