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2.
J Agric Food Chem ; 70(18): 5570-5578, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35499918

RESUMO

Antimicrobial compounds from the commensal gut microbiota have gained much attention due to their multifunctionality in maintaining good health in the host and killing multidrug-resistant bacteria. Our previous study showed that Paenibacillus jilinensis YPG26 isolated from chicken intestine can antagonize multiple pathogens. Herein, we characterized a bacteriocin-like inhibitory substance, jileicin, purified from P. jilinensis YPG26. Mass spectrometry analysis revealed that jileicin was a protein consisting of 211 amino acids, which showed 88.98% identity to the SIMPL domain-containing protein. The jileicin showed a relatively broad-spectrum antibacterial ability, especially against enterococci. Additionally, the jileicin exhibited good stability after various treatments, no detectable resistance, no significant cytotoxicity, and very low levels of hemolytic activity. The mode of action against Enterococcus faecium demonstrated that jileicin could destroy cell membrane integrity, increase cell membrane permeability, and eventually lead to cell death. Furthermore, jileicin was efficient in controlling the growth of E. faecium in milk. In conclusion, jileicin, as a newly identified antibacterial agent, is expected to be a promising candidate for application in the food, pharmaceutical, and biomedical industries.

3.
Cancer Med ; 2022 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-35526267

RESUMO

BACKGROUND: Isocitrate dehydrogenase (IDH) is an appealing target for anticancer therapy, and IDH (IDH1/2) inhibitors have been approved for targeted therapy of acute myeloid leukemia (AML) and Cholangiocarcinoma. The therapeutic potential of IDH inhibitors for non-small-cell lung cancer (NSCLC) patients is under active clinical investigation. Thus, it would be necessary and meaningful to study the molecular and clinical characteristics of IDH mutation in NSCLC patients, especially in the Chinese population. METHODS: A total of 17,978 Chinese patients with NSCLC who underwent next -generation sequencing (NGS) testing were retrospectively reviewed. RESULTS: We identified 161 unique IDH mutations in 361 of 17,978 patients (2.01%). Common active-site mutations, including IDH1R100 , IDH1R132 , IDH2R140 , and IDH2R172 , were detected in 154 patients (0.86%) and were associated with male sex (p = 0.004) and older age (p = 0.02). The IDH mutation spectra observed in NSCLC were quite different from those in glioma or AML. Patients with IDH active-site mutations exhibited significantly higher coalterations in KRAS (p. G12/13/61, 22.1% vs. 8.2%, p < 0.001) or BRAF (p. V600E, 6.5% vs. 1.0%, p < 0.001), but significantly lower coalterations in activating EGFR (e18-e20, 22.7 vs. 37.9%, p < 0.001) than IDH wild-type patients. Furthermore, we found that active-site IDH mutations were correlated with a short PFS (2-5.6 months) and short OS (2-9.5 months), which may arise as a resistance mechanism against common targeted drugs. In vitro, we experimentally observed that the combination of an IDH inhibitor and EGFR TKI could better inhibit lung cancer cell proliferation than an EGFR TKI alone. CONCLUSIONS: Taken together, this study reveals the molecular and clinical characteristics of IDH mutations in Chinese NSCLC patients and provides a theoretical basis for IDH-directed treatment. The potential of IDH mutations as response markers for targeted therapy warrants further investigation.

4.
Molecules ; 27(9)2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35566288

RESUMO

A π-conjugated thiophene-containing oligomer with a D-A-D-A-D (D: donor, A: acceptor) architecture, namely, 2,6-bis{[4-(7-n-hexylthiophen-2-yl)thiophen-2-yl]-(dibenzothiophene-5,5-dioxide-3,3΄-diyl)}-bis((2-ethyl-hexyl)oxy)benzo[1,2-b:4,5-b']dithiophen (BDT(DBTOTTH)2), was synthesized by Stille coupling reactions. There are obvious shifts in the Ultraviolet-visible (UV-vis) and photoluminescence (PL) spectra of the thin film relative to its solution, indicating the existence of the π-π stacking in the solid state of the oligomer BDT(DBTOTTH)2. The optical band gap of the oligomer determined from its absorption onset in UV-Vis spectra is 2.25 eV. It agrees with the value of 2.29 eV determined from the cyclic voltammetry (CV) measurement. Its highest occupied and lowest unoccupied molecular orbital (HOMO/LUMO) energy levels, which were calculated from its onset of oxidation and reduction waves in CV curve, are -5.51 and -3.22 eV, respectively. The oligomer is a P-type semiconductor material with a good thermal stability and solubility, which can be used to fabricate organic field effect transistors (OFETs) by the spin coating technique. The OFET with n-octadecanylltrichlorosilane (OTS)-modified SiO2 dielectric layer exhibited a mobility of 1.6 × 10-3 cm2/Vs.

5.
Sleep Med ; 95: 47-54, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35561474

RESUMO

OBJECTIVE: Different aspects of sleep problems tend to occur simultaneously, which could lead to adolescent health problems. We aimed to identify the distinct patterns of sleep problems and to explore their association with internalizing and externalizing problems. METHODS: Secondary data from 11,831 adolescents from the Shandong Adolescent Behavior and Health Cohort were obtained and after data cleaning, 9,871 (50.1% females, mean age was 15.02 ± 1.45 years) were used in this study. Sleep problems (short weeknight sleep duration, insomnia, daytime sleepiness, no post-lunch napping, and snoring), and covariates were measured at the baseline, and the internalizing and externalizing problems were measured at both the baseline and one-year follow-up. The latent class analysis was used to identify the patterns of sleep problems at the baseline. Linear mixed effect models were used to examine the relationship between classes of sleep problems and internalizing and externalizing problems. RESULTS: Three classes of sleep problems were identified, named as "short and disturbed sleep" (34.1%), "no post-lunch napping" (16.7%), and "no/mild sleep disturbance" (49.2%), respectively. The "short and disturbed sleep" class exhibited higher levels of internalizing and externalizing problems than the other two classes. Also, it showed a steeper decreasing trend in internalizing and externalizing problems over time. CONCLUSIONS: The findings shed light on the importance and significance of identifying the patterns of multiple sleep problems to effectively identify adolescents at higher risk of developing internalizing and externalizing problems, and to designate tailored intervention to eliminate co-occurring sleep problems to promote adolescent emotional and behavioral health.

6.
Front Microbiol ; 13: 828687, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35432256

RESUMO

Previously, we have reported that an endo-type ß-agarase AgaW was responsible for the hydrolysis of agarose into the major product neoagarotetraose in a terrestrial agar-degrading bacterium Cohnella sp. LGH. Here, we identify and characterize the following depolymerization pathway in strain LGH through the genomic and enzymatic analysis. In the pathway, neoagarotetraose was depolymerized by a novel α-neoagarooligosaccharide (NAOS) hydrolase CL5012 into 3,6-anhydro-α-L-galactose (L-AHG) and agarotriose; Agarotriose was further depolymerized by a novel agarolytic ß-galactosidase CL4994 into D-galactose and neoagarobiose; Neoagarobiose was finally depolymerized by CL5012 into L-AHG and D-galactose. Although α-agarase has not been identified in strain LGH, the combined action of CL5012 and CL4994 unexpectedly plays a critical role in the depolymerization of agarotetraose, one theoretical product of α-agarase hydrolysis of agarose. In this pathway, agarotetraose was depolymerized by CL4994 into D-galactose and neoagarotriose; Neoagarotriose was then depolymerized by CL5012 into L-AHG and agarobiose. Furthermore, another novel endo-type ß-agarase CL5055 was identified as an isozyme of AgaW with different pH preference in the hydrolysis of agarose into α-NAOSs. Strain LGH seemed to lack a common exo-type ß-agarase responsible for the direct depolymerization of agarose or neoagarooligosaccharide into neoagarobiose. These results highlight the diversity of agarolytic manner in bacteria and provide a novel insight on the diversity of agarolytic pathways.

7.
Comput Math Methods Med ; 2022: 9923214, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35432587

RESUMO

Hearing loss is a common disease affecting public health all around the world. In clinic, auditory brainstem response (ABR) has been widely used for the detection of hearing loss based on its convenience and accuracy. The different reference methods directly influence the quality of the ABR waveform which in turn affects the ABR-based diagnosis. Therefore, in this study, a reference electrode standardization technique (REST) was adopted to systematically investigate and evaluate the effect of different reference methods on the quality of ABR waveform in comparison with the conventional average reference (AR) and mean mastoid (MM) methods. In this study, ABR signals induced by click stimulus were acquired via an EEG electrode cap arrays, and those located on the six channels along the midline were compared systemically. The results showed that, when considering the different channels, the ABR in the Cz channel showed the best morphology. Then, the ABR waveforms acquired via the REST method possessed better morphologies with large amplitude (0.06 ± 0.02 µV for wave I, 0.07 ± 0.02 µV for wave III, and 0.21 ± 0.04 µV for wave V) when compared with the traditional method. Summarily, we found that the REST and MM methods improved the quality of ABR on both amplitude and morphology under different stimulation rates and levels without changing the latencies of ABR when compared with the conventional AR method, suggesting that the REST and MM methods have the potential to help physicians with high accurate ABR-based clinical diagnosis. Moreover, this study might also provide a theoretic basis of reference methods on the acquisition of electroencephalogram over public health issues.


Assuntos
Potenciais Evocados Auditivos do Tronco Encefálico , Perda Auditiva , Estimulação Acústica/métodos , Limiar Auditivo/fisiologia , Eletroencefalografia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Humanos
8.
Vet Microbiol ; 268: 109410, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35421831

RESUMO

Zoonotic hepatitis E virus (HEV) infection is an emerging global public health concern. It is usually transmitted to humans from domestic pigs (main host). Since virus-like particles (VLPs) exhibit unique structural and immunological characteristics that make them of momentous applications in vaccine development, the purpose of the present study was the production of immunogenic chimeric VLPs as vaccine candidates for the control of zoonotic HEV in its main host and the prevention of porcine circovirus associated disease, a multi-factorial disease with major economic repercussions on global pig industry. An immuno-informatics approach was applied for the design and screening of new chimeric antigens presenting the dominant immunogenic domains of both HEV and porcine circovirus 2 (PCV2). Then, using molecular cloning techniques, the chimeric proteins were expressed in Escherichia coli. After purification, full characterization of the physicochemical, morphological, and immunological properties of the target proteins has been conducted. The chimeric immunogens were successfully overexpressed and after the optimization of the expression conditions, 5 chimeric proteins were efficiently purified under native conditions. The purified HEV-PCV2 chimeric proteins were found thermo-stable and able to self-assemble into spherical virus-like particles. Four HEV-PCV2 chimeric proteins have displayed optimal antigenicity and immunogenicity properties, with the nPCV2cp-p166 chimeric immunogen slightly outranking the other designed proteins. In conclusion, this study reports the production of stable HEV-PCV2 chimeric VLPs that exhibited optimal antigenicity and immunogenicity and thus with potential applications in diagnostics and vaccine development. Besides, this study provides a reproducible approach for the design, assessment, and production of chimeric antigens.


Assuntos
Infecções por Circoviridae , Circovirus , Vírus da Hepatite E , Hepatite E , Doenças dos Suínos , Vacinas Virais , Animais , Proteínas do Capsídeo , Infecções por Circoviridae/veterinária , Circovirus/genética , Hepatite E/prevenção & controle , Hepatite E/veterinária , Vírus da Hepatite E/genética , Proteínas Recombinantes de Fusão/genética , Suínos , Doenças dos Suínos/prevenção & controle
9.
Biomater Sci ; 10(9): 2315-2327, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35373788

RESUMO

The immunologic response is considered to play a pivotal role in the application of biomaterial implants, and intrinsic properties of biomaterials can significantly modulate the anti-inflammatory effects. However, how physical confinement influences M2 polarization of macrophages and the relevant mechanisms have not been clearly elucidated. In this study, pore size and porosity in cryogels can be mediated by utilizing alginates with different viscosities. Cryogels of small pore size and low porosity can restrict M2 polarization of macrophages in vitro, judging from cell morphology, secretion of cytokines and expression of key M2-related genes. In comparison, cryogels of large pore size or high porosity can induce M2 polarization in vivo, resulting in the anti-inflammation effects. High-throughput RNA-seq analysis demonstrates that the mRNA surveillance pathway is key in the polarization process, and four primary transcription factors (PPAR-γ, STAT6, NF-κB, and STAT1) participate probably by competition in DNA binding to regulate M2-related gene expression. This study confirms that enough physical space inside is necessary to promote M2 polarization for the anti-inflammatory performance, which can be applied widely in the fields of tissue engineering and regenerative medicine.


Assuntos
Alginatos , Criogéis , Anti-Inflamatórios , Criogéis/metabolismo , Macrófagos/metabolismo , Fenótipo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
10.
J Hazard Mater ; 435: 128953, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35462190

RESUMO

The transformation of silver ions (Ag+) mediated by engineered nanomaterials (ENMs) influences the biosafety of Ag-containing products in natural environments. Actually, modification of biomolecules to ENMs in aquatic ecosystems alters their interactions with Ag+. This study discovered that surface functionalization of glutathione (GSH, a sulfhydryl compound ubiquitous in natural waters) on molybdenum disulfide (MoS2) nanoflakes suppressed the redox reaction between 1 T components and Ag+, inhibiting the MoS2-mediated reduction of Ag+ to Ag nanoparticles (AgNPs) in aqueous phase in the dark. However, AgNPs formation (from 2.32 ± 0.35-3.25 ± 0.29 mg/L per day, pH 7.0) and oxidation of MoS2 were remarkably accelerated after GSH binding under light conditions. The dominant electron donator of MoS2 to Ag+ was transformed from the electron-hole pairs to surface ligands driven by the introduction of chromophoric groups was authenticated as the cause for the elevated Ag+ reduction. These processes also occurred between Ag+ and MoS2 at low levels (50 µg/L). Additionally, the joint algal toxicity of GSH-modified MoS2 with Ag+ was weaker than that of pristine MoS2 due to increased retention of free Ag+ and AgNPs formation. Our findings improve the understanding of the interaction between ENMs and Ag+ in aquatic ecosystems.

11.
BMC Womens Health ; 22(1): 102, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35379231

RESUMO

BACKGROUND: Recurrence of pelvic organ prolapse (POP) after transvaginal mesh (TVM) implantation pelvic floor reconstruction surgery remains an unresolved problem in clinical practice. In this retrospective observational study, clinical and pelvic floor ultrasound (PFUS) parameters were analyzed in order to identify high-risk factors of POP recurrence. METHODS: The clinical and PFUS data from September 2013 to November 2019 of patients who underwent TVM were retrospectively analyzed. The patients with prolapse recurrence on postoperative follow-up diagnosed by PFUS were selected as case group, the clinical and PFUS parameters of them were compared with the control group in which the patients had no sign of prolapse recurrence. Univariate and multivariate regression analyses were performed based on age, BMI, gravidity, parity, surgical history (non-POP hysterectomy and incontinence-or-POP surgery), preoperative POP stage, follow-up in years, levator avulsion and hiatal area (HA) on Valsalva. RESULTS: Altogether 102 patients entered the study and the median interval between PFUS and TVM surgery was 2.5 years. Univariate analysis showed that levator avulsion and HA were significantly different between case group and control; multivariate regression analysis showed that only HA was related to prolapse recurrence after TVM (OR = 1.202, 95% CI 1.100-1.313, P < 0.001). The area under the ROC curve was 0.775 (95% CI 0.684-0.867, P < 0.001). CONCLUSIONS: Hiatal area on Valsalva was related to prolapse recurrence after TVM surgery and it is an important parameter for postoperative follow-up of TVM surgery.


Assuntos
Diafragma da Pelve , Prolapso de Órgão Pélvico , Feminino , Humanos , Diafragma da Pelve/diagnóstico por imagem , Prolapso de Órgão Pélvico/diagnóstico por imagem , Prolapso de Órgão Pélvico/etiologia , Prolapso de Órgão Pélvico/cirurgia , Estudos Retrospectivos , Telas Cirúrgicas/efeitos adversos , Ultrassonografia
12.
PeerJ ; 10: e13264, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35441059

RESUMO

In this study, we identified a key enhancer RNA (eRNA) region in breast cancer (BRCA) by applying an integrated analysis method. Reported eRNA region and genes affected by them were selected as presumed target pairs. Kaplan-Meier (KM) survival and correlation analyses were performed to screen valuable eRNA region. Based on the KM value and its correlation with the paired target genes, we carefully selected ELOVL2-AS1 as a potential key eRNA region in BRCA. Subsequently, we analyzed the expression of ELOVL2-AS1 and ELOVL2 in four BRCA subtypes and in different BRCA cell lines. The expression of ELOVL2-AS1 and ELOVL2 in triple negative breast cancer (TNBC) was significantly lower than those in Luminal A. After that, we analyzed the function of genes that are positively correlated with ELOVL2-AS1. We found that the co-expression gene mainly related to cilia and cilia characteristics of TNBC is significantly weaker than that of Luminal A. Considering the stronger invasion and metastasis of TNBC (compared with Luminal A) and the close relationship between decreased cilia and metastasis, we overexpressed ELOVL2-AS1 in TNBC and observed its effect on cell migration. The results show that it can inhibit the migration of TNBC. Finally, we analyzed the assay for transposase-accessible chromatin sequencing data, chromatin interaction analysis with paired-end tag sequencing data, and chromatin immunoprecipitation sequencing data and identified the chromatin interaction between ELOVL2-AS1 and ELOVL2, suggesting a direct regulatory interaction.

13.
Sci Rep ; 12(1): 6752, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35474239

RESUMO

Myeloid sarcoma is a rare manifestation of acute myeloid leukemia (AML) and is associated with poor overall survival (OS). The optimal treatment remains unclear. The study retrospectively evaluated 118 patients with myeloid sarcoma who were treated at the First Affiliated Hospital of Zhengzhou University from January 2010 to July 2021. All cases were diagnosed by tissue biopsy. 41 patients underwent genetic mutation analysis. The most frequent genetic mutations were KIT (16.6%), followed by TET2 (14.6%), and NRAS (14.6%). The median survival time of 118 patients was 4 months (range, 1-51 months), while the median survival time of 11 patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) was 19 months (range, 8-51 months). 4 (36.4%) of the 11 patients experienced relapse within 1 year after transplantation. 1 patient died from a severe infection. Of the 6 surviving patients, 5 patients have received maintenance treatment with decitabine after transplantation, and all remained in a state of recurrence-free survival. Patients with myeloid sarcoma have a very unfavorable outcome. Allo-HSCT is an effective treatment option. Recurrence remains the main cause of transplant failure. Maintenance treatment with decitabine after transplantation can prolong the recurrence-free survival time, although these results must be verified in a study with expanded sample size.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Sarcoma Mieloide , Decitabina , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Prognóstico , Estudos Retrospectivos , Sarcoma Mieloide/diagnóstico , Sarcoma Mieloide/genética , Sarcoma Mieloide/terapia
14.
Nanoscale ; 14(15): 5869-5875, 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35362506

RESUMO

Two-dimensional transition metal dichalcogenide (TMDC) nanosheets have received significant attention as anode materials for lithium-ion batteries, especially in their metallic 1T/1T' phase. However, controllable synthesis of few-layer 1T/1T' phase is still a challenge. In the present study, we report a facile two-step hydrothermal method to controllably synthesize few-layer 1T'-phase WS2. By tuning the redox-temperature of (NH4)2WS4 from 160 to 200 °C, the thickness of 1T'-phase WS2 can be adjusted from 4-6 to 20 layers. A higher reversible capacity is achieved in 1T'-phase WS2 with a smaller thickness, but the cycling stability decreases due to the lower crystallinity. The 1T'-phase WS2 synthesized by reduction of (NH4)2WS4 at 180 °C shows a moderate thickness of 10 layers and crystallinity, exhibiting the optimal Li-ion storage properties, i.e. a reversible capacity of 855.9 mA h g-1 at 100 mA g-1 and a good rate performance of 354.4 mA h g-1 at 5000 mA g-1. These results provide new insights into understanding the impacts of layer number on the Li-ion storage properties of 1T'-phase WS2.

15.
Front Cell Dev Biol ; 10: 836880, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35399524

RESUMO

Stimulator of interferon genes (STING) is a cytosolic DNA sensor or directly recognizes bacterial cyclic dinucleotides, which is required for the detection of microbial infection. Extracellular traps (ETs) are known to be part of the antimicrobial defense system. However, the implication of STING in ETs formation during microbial infection remains unknown. Here, we showed that STING contributed to Staphylococcus aureus (S. aureus)-induced ETs formation through the ROS-ERK signaling. STING deficiency exhibited decreased cell-free DNA (cfDNA) level, reduced expression of citrullinated histone H3 (CitH3), and diminished DNA colocalization with CitH3 and myeloperoxidase (MPO). Interestingly, NADPH oxidase-derived reactive oxygen species (ROS) promoted ETs formation, accompanied by increased activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) in S. aureus-stimulated bone marrow-derived macrophages (BMDMs). Corresponding to less ROS production, decreased ERK1/2 activation was shown in STING-/- BMDMs after S. aureus infection. Importantly, inhibiting the ROS-ERK signal reduced the ETs formation and the differences disappeared between WT and STING-/- BMDMs after S. aureus infection. Moreover, STING-/- BMDMs exhibited significantly increased levels of extracellular bacteria compared to WT BMDMs regardless of phagocytosis. In addition, such differences disappeared after DNase I treatment. DNase I treatment also facilitated pathogen colonization without affecting the inflammatory cells infiltration and pro-inflammatory factors secretion following pulmonary S. aureus infection. Furthermore, STING-/- mice presented decreased levels of cfDNA and CitH3, along with increased bacterial colonization compared to WT mice. Altogether, these findings highlighted that STING promoted ETs formation via the ROS-ERK signal for host defense against S. aureus infection.

16.
Br J Ophthalmol ; 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35410876

RESUMO

BACKGROUND/AIMS: Quantity of cataract surgery has long been an important public health indicator to assess health accessibility, however the quality of care has been less investigated. We aimed to summarise the up-to-date evidences to assess the real-world visual outcomes after cataract surgery in different settings. METHODS: A systematic review was undertaken in October 2021. Population-based cross-sectional and longitudinal studies reporting vision-related outcomes after cataract surgery published from 2006 onward were included. A meta-analysis was not planned. RESULTS: Twenty-six cross-sectional studies from low-income and middle-income countries (LMICs) and five cross-sectional studies from high-income countries (HICs) were included. The proportions of participants with postoperative presenting visual acuity (VA) ≥0.32 (20/60) were all over 70% in all HICS studies, but mostly below 70% in LMICS studies, ranging from 29.9% to 80.5%. Significant difference in postoperative VA was also observed within countries. The leading causes for postoperative visual impairment (defined mostly as presenting VA <20/60) mainly included refractive error, ocular comorbidities and surgical complications including posterior capsule opacification, except for one study in Nigeria wherein the leading cause was aphakia. Only four population-based cohort studies were included with 5-20 years of follow-up time, generally demonstrating no significant changes in postoperative visual outcomes during the follow-up. CONCLUSIONS: We observed large inequality in the visual outcomes and principal causes of visual impairment after cataract surgery among different countries and regions. Structured quality control and enhancement programmes are needed to improve the outcomes of cataract surgery and reduce inequality.

17.
Front Med (Lausanne) ; 9: 777645, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35237620

RESUMO

BACKGROUND AND AIM: To assess the reproducibility of the novel ultrasound biomicroscopy, Insight 100 and its agreement with a swept-source optical coherence tomography, CASIA2. METHODS: A total of 96 volunteers (96 eyes) were enrolled. The radius of anterior lens curvature (RAL), the radius of posterior lens curvature (RPL), lens thickness (LT), and lens diameter (LD) were measured with Insight 100 and CASIA2. A semiautomated software was used to adjust the measurement of LT (LTS) and LD (LDS) by Insight 100. Intraobserver and interobserver reproducibility of Insight 100 measurements, and the agreement of results from Insight 100 and CASIA2 were assessed with 95% limit of agreement (LoA), intraclass correlation coefficient (ICC), Pearson correlation, and linear regression. RESULTS: For Insight 100 measurements, the intraobserver ICCs of RAL, RPL, LTS, and LDS measurement were 0.996, 0.973, 0.936, and 0.889, and the interobserver ICCs were 0.987, 0.890, 0.974, and 0.816, respectively. There was an excellent correlation in LT measurements (R = 0.961, P < 0.001) but poor agreements in other parameters between the two devices. The LD measurements tended to be larger (95% CI: 0.768-0.928) in CASIA2 when compared with Insight 100. CONCLUSION: Insight 100 could obtain highly repeatable lens biometry in vivo. With better signal penetration, it shows promising potential in future clinical applications.

18.
Eur J Cancer ; 165: 157-168, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35235873

RESUMO

PURPOSE: Panphila evaluated pyrotinib plus trastuzumab, docetaxel and carboplatin as neoadjuvant therapy for early breast cancer (BC), and investigated the predictive role of immune cell subpopulations. PATIENTS AND METHODS: In this multicentre phase 2 study, patients with human epidermal growth factor receptor 2-positive, stage T2-3N0-3M0 BC received pyrotinib 400 mg once daily plus docetaxel (75 mg/m2, day 1), carboplatin (6 mg/mL/min, day 1) and trastuzumab (8 mg/kg loading dose and 6 mg/kg maintenance dose, day 1) for 6 cycles of 21 days each. Simon's 2-stage design was adopted. The primary end-point was pathological complete response (pCR, ypT0/is ypN0) rate. Tumour-infiltrating lymphocytes (TILs) were assessed by haematoxylin and eosin staining and multiplex immunohistochemistry. RESULTS: In the modified intention-to-treat population (n = 69), 38 patients (55.1%) achieved pCR. In the safety population (n = 74), the most common grade ≥3 adverse events were diarrhoea (43.2%), anaemia (37.8%), vomiting (16.2%) and platelet count decrease (10.8%). No treatment-related deaths occurred. Analysis of single immune subpopulations revealed a significant association of pCR with higher baseline infiltration by stromal (s)-CD20+, s-CD8+ and s-CD4+ TILs. Unsupervised hierarchical clustering of stromal immune markers identified a group of patients characterised by high s-CD20+, s-CD8+, s-CD4+ and s-FOXP3+ immune cells infiltration, which was independently associated with pCR. CONCLUSION: Neoadjuvant pyrotinib plus trastuzumab-based chemotherapy exhibits promising efficacy and manageable toxicity in patients with human epidermal growth factor receptor 2-positive early BC, and thus phase 3 trials are warranted. Our findings also contribute to understanding the potential role of the immune microenvironment in response to neoadjuvant pyrotinib-based therapy.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Acrilamidas , Aminoquinolinas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Carboplatina , Docetaxel/uso terapêutico , Feminino , Humanos , Linfócitos do Interstício Tumoral , Terapia Neoadjuvante/efeitos adversos , Receptor ErbB-2/metabolismo , Trastuzumab , Microambiente Tumoral
19.
Cancer Lett ; 534: 215618, 2022 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-35259457

RESUMO

Basal-like breast cancer (BLBC) is the most aggressive subtype of breast cancer with a poor prognosis. Long noncoding RNAs (lncRNAs) play critical roles in human cancers. Krüppel-like Factor 5 (KLF5) is a key oncogenic transcription factor in BLBC. However, the underlying mechanism of mutual regulation between KLF5 and lncRNA remains largely unknown. Here, we demonstrate that lncRNA KPRT4 promotes BLBC cell proliferation in vitro and in vivo. Mechanistically, KLF5 directly binds to the promoter of KPRT4 to promote KPRT4 transcription. Reciprocally, KPRT4 recruits the YB-1 transcription factor to the KLF5 promoter by interacting with YB-1 at its 5' domain and forming an RNA-DNA-DNA triplex structure at its 3' domain, resulting in enhanced transcription of KLF5 and ultimately establishing a feedforward circuit to promote cell proliferation. Moreover, the antisense oligonucleotide (ASO)-based therapy targeting KPRT4 substantially attenuated tumor growth in vivo. Clinically, the expression levels of YB-1, KLF5 and KPRT4 are positively correlated in clinical breast specimens. Together, our data suggest that KPRT4 is a major molecule for BLBC progression and that the feedforward circuit between KLF5 and KPRT4 may represent a potential therapeutic target in BLBC.


Assuntos
Neoplasias da Mama , Fatores de Transcrição Kruppel-Like , RNA Longo não Codificante , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , RNA Longo não Codificante/genética , Fatores de Transcrição/genética
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