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1.
Biochem Pharmacol ; : 116256, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38729448

RESUMO

Endocrine treatment, particularly tamoxifen, has shown significant improvement in the prognosis of patients with estrogen receptor-positive (ER-positive) breast cancer. However, the clinical utility of this treatment is often hindered by the development of endocrine resistance. Therefore, a comprehensive understanding of the underlying mechanisms driving ER-positive breast cancer carcinogenesis and endocrine resistance is crucial to overcome this clinical challenge. In this study, we investigated the expression of MICAL-L2 in ER-positive breast cancer and its impact on patient prognosis. We observed a significant upregulation of MICAL-L2 expression in ER-positive breast cancer, which correlated with a poorer prognosis in these patients. Furthermore, we found that estrogen-ERß signaling promoted the expression of MICAL-L2. Functionally, our study demonstrated that MICAL-L2 not only played an oncogenic role in ER-positive breast cancer tumorigenesis but also influenced the sensitivity of ER-positive breast cancer cells to tamoxifen. Mechanistically, as an estrogen-responsive gene, MICAL-L2 facilitated the activation of the Akt/mTOR signaling pathway in ER-positive breast cancer cells. Collectively, our findings suggest that MICAL-L2 could serve as a potential prognostic marker for ER-positive breast cancer and represent a promising molecular target for improving endocrine treatment and developing therapeutic approaches for this subtype of breast cancer.

2.
BMC Infect Dis ; 24(1): 419, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38644489

RESUMO

OBJECTIVE: To compare the similarities and differences between patients with Coronavirus Disease 2019 (COVID-19) and those with other community-acquired pneumonia (CAP) admitted to the intensive care unit (ICU), utilizing propensity score matching (PSM), regarding hospitalization expenses, treatment options, and prognostic outcomes, aiming to inform the diagnosis and treatment of COVID-19. METHODS: Patients admitted to the ICU of the Third People's Hospital of Datong City, diagnosed with COVID-19 from December 2022 to February 2023, constituted the observation group, while those with other CAP admitted from January to November 2022 formed the control group. Basic information, clinical data at admission, and time from symptom onset to admission were matched using PSM. RESULTS: A total of 70 patients were included in the COVID-19 group and 119 in the CAP group. The patients were matched by the propensity matching method, and 37 patients were included in each of the last two groups. After matching, COVID-19 had a higher failure rate than CAP, but the difference was not statistically significant (73% vs. 51%, p = 0.055). The utilization rate of antiviral drugs (40% vs. 11%, p = 0.003), γ-globulin (19% vs. 0%, p = 0.011) and prone position ventilation (PPV) (27% vs. 0%, p < 0.001) in patients with COVID-19 were higher than those in the CAP, and the differences were statistically significant. The total hospitalization cost of COVID-19 patients was lower than that of CAP patients, and the difference was statistically significant (27889.5 vs. 50175.9, p = 0.007). The hospital stay for COVID-19 patients was shorter than for CAP patients, but the difference was not statistically significant (10.9 vs. 16.6, p = 0.071). CONCLUSION: Our findings suggest that limited medical resources influenced patient outcomes during the COVID-19 pandemic. Addressing substantial demands for ICU capacity and medications during this period could have potentially reduced the mortality rate among COVID-19 patients.


Assuntos
COVID-19 , Infecções Comunitárias Adquiridas , Unidades de Terapia Intensiva , Pontuação de Propensão , SARS-CoV-2 , Humanos , COVID-19/mortalidade , COVID-19/terapia , COVID-19/epidemiologia , Masculino , Feminino , Infecções Comunitárias Adquiridas/mortalidade , Infecções Comunitárias Adquiridas/terapia , Infecções Comunitárias Adquiridas/epidemiologia , Pessoa de Meia-Idade , Unidades de Terapia Intensiva/estatística & dados numéricos , Idoso , Hospitalização/estatística & dados numéricos , China/epidemiologia , Estudos Retrospectivos , Antivirais/uso terapêutico , Tempo de Internação/estatística & dados numéricos , Adulto , Resultado do Tratamento , Prognóstico , Pneumonia/mortalidade , Pneumonia/terapia
3.
Org Lett ; 26(18): 3790-3795, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38666755

RESUMO

A cooperative gold(I)/DMAP system catalyzes the (2 + 3) cycloadditions of yne-enones with oxindole-derived Morita-Baylis-Hillman (MBH) carbonates, yielding diverse bispiro-cyclopentene oxindole products. The mild, scalable protocol demonstrates broad substrate scope and excellent chemo- and diastereoselectivity. Mechanistic study reveals pivotal roles of both catalysts in the unique (2 + 3) cycloaddition. This strategy showcases superiority in achieving transformation with unique chemoselectivity and excellent diastereoselectivity, unattainable through traditional monocatalytic methodologies.

4.
Talanta ; 272: 125764, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38346359

RESUMO

When an acute myocardial infarction (AMI) occurs, myoglobin (Mb) is the biomarker whose concentration firstly increases, and the high sensitive detection of Mb is critical for early diagnosis of AMI. Herein, a sandwich-type electrochemical aptasensor for the sensitive detection of Mb was constructed by using Pt@Cu1.33OCo0.83O as the signal marker. On one hand, nano-flower-like Cu1.33OCo0.83O was synthesized by hydrothermal method and Pt nanoparticles (Pt NPs) were loaded on its surface. Pt@Cu1.33OCo0.83O could immobilize aptamer 2 (Apt2) successfully by the Pt-S bond. And because of the synergistic effect between Pt and bimetallic oxide, Pt@Cu1.33OCo0.83O had an excellent catalytic effect on the signal source of hydrogen peroxide (H2O2) to amplify the current signal, which enhance the sensitivity of the aptasensor. On the other hand, the screen-printed gold electrode (SPGE) was used as the sensing base, which had good conductivity and ensured the immobilization of aptamer 1 (Apt1). The quantitative detection of Mb was achieved by specific recognition between Mb and Apt1, Apt2. As a result, the constructed electrochemical aptasensor had a good linear range (1-1500 ng/mL) with a low detection limit (LOD) of 0.128 ng/mL (S/N = 3), and a high sensitivity of 29.47 µA dec-1. The aptasensor also realized the detection of Mb in human serum samples with good accuracy, and the results were consistent with the hospital's biochemical indicators, which demonstrated the potential application of the prepared sensor in the clinical detection of Mb.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Nanopartículas Metálicas , Humanos , Nanopartículas Metálicas/química , Mioglobina , Óxidos , Peróxido de Hidrogênio/química , Aptâmeros de Nucleotídeos/química , Técnicas Eletroquímicas/métodos , Técnicas Biossensoriais/métodos , Limite de Detecção , Ouro/química
5.
Anal Chim Acta ; 1287: 342058, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38182336

RESUMO

N-glycopeptide is considered as one of significant biomarkers which provide guidance for the diagnosis and drug design of diseases. However, the direct analysis of N-glycopeptides is nearly impracticable mainly owing to their extremely low abundance and grave signal suppression from other interfering substances in the bio-samples. In this research, a multiply-mesoporous hydrophilic TiO2 nanohybrid (mM-TiO2@Cys) was synthesized by immobilizing Cys on a TiO2 substrate with hierarchical mesopores to achieve the highly-performed enrichment of N-glycopeptides. With the advantages of superior hydrophilicity and multiply-mesoporous structure, the obtained material exhibited an excellent selectivity (IgG digests and BSA digests at the molar ratio of 1/500), a high sensitivity (1 fmol µL-1 for IgG digests) and a good size-exclusion ability (IgG digests, IgG and BSA at the molar ratio of 1/500/500) in the enrichment of N-glycopeptides from IgG digests. As a result, 281 N-glycopeptides corresponded with 109 glycoproteins were identified from 2 µL serum digests of the patients with nasopharyngeal carcinoma, and 181 N-glycopeptides corresponded with 78 glycoproteins were identified from 2 µL serum digests of the healthy volunteers, revealing the potential application value of mM-TiO2@Cys in glycoproteomics.


Assuntos
Desenho de Fármacos , Glicopeptídeos , Humanos , Glicoproteínas , Imunoglobulina G
6.
Aesthetic Plast Surg ; 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263498

RESUMO

OBJECTIVE(S): It was the first study to apply and compare two CT methods to assess the validity and clinical significance of structural alterations of the nasal valve in patients with cleft lip nose for assessing nasal ventilation disturbance. METHODS: The study collected data from the NOSE score, as well as internal nasal valve area, internal nasal valve angle, external nasal valve area, and septal deviation angle, to evaluate the differences and correlations between those factors in patients with cleft lip and nose. RESULTS: There were significant differences among INV transverse and coronal area and INV angle on different axial standardized planes between clefted side and non-clefted side. There were statistically significant negative correlations between NOSE scores and those indicators of standard plane and acoustic-axis standardized coronal plane. NOSE score and NSD angle were the indicators of significant differences in the measured data of different complications groups (p = 0.002, p = 0.017). The correlation comparison showed that two standardized CT imaging transverse planes have similar correlations in NOSE score, NSD angle, and complications. CONCLUSION: The results of the two CT evaluation methods showed that there was a significant difference in nasal valve area on the cleft and non-cleft sides, which was significantly associated with nasal ventilation disturbance. The CT evaluation method based on standard axial 3D reconstruction is more convenient to use in the clinic, can be used for pre-surgical evaluation of nasal repair in patients with secondary nasal deformities of unilateral cleft lip, and is valuable for treatment. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

7.
Aesthetic Plast Surg ; 48(3): 388-397, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37798507

RESUMO

BACKGROUND: Supratip deformity, also known as pollybeak deformity, is a common complication of primary and secondary rhinoplasty, characterized by fullness in the supratip region. The correction of pollybeak deformity is a challenging procedure, and its management requires a thorough understanding of the pathogenic mechanism of pollybeak deformity. OBJECTIVES: This study aimed to evaluate the effectiveness of surgical methods for correcting pollybeak deformity in Asian rhinoplasty. METHODS: A retrospective chart review was conducted for 53 patients who underwent pollybeak correction between 2021 and 2022. A modified classification system for pollybeak deformity, the Supratip Fullness Rating Scale (SFRS), was developed to evaluate supratip fullness. The aesthetic outcomes of the patients were assessed by surgeons using the visual analog scale (VAS), and patient was self-assessed using the Rhinoplasty Outcome Evaluation (ROE) scale. RESULTS: The study demonstrated that our surgical method resulted in satisfactory outcomes, with a mean SFRS score change from 2.34[0.65] to 0.23[0.42], a decrease in VAS score from 7.47[1.73] to 1.79[1.67] and a high satisfaction rate of 77.36%, calculated by ROE score. No complications were reported. CONCLUSION: Our surgical method for correcting pollybeak deformity in Asian rhinoplasty can result in satisfactory outcomes, particularly in terms of aesthetic appearance, without any side effects. The use of the modified classification system (SFRS) can provide an objective evaluation of supratip fullness, thereby aiding in the management of this challenging complication. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Assuntos
Deformidades Adquiridas Nasais , Rinoplastia , Humanos , Rinoplastia/métodos , Estudos Retrospectivos , Deformidades Adquiridas Nasais/etiologia , Deformidades Adquiridas Nasais/cirurgia , Resultado do Tratamento , Estética
8.
J Pain Res ; 16: 4165-4180, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38078016

RESUMO

Purpose: This bibliometric research aims to delineate global publication trends and emerging research interests in the use of acupuncture for breast cancer (BC)-related symptoms treatment over the past three decades. Furthermore, it identifies influential institutions, potential collaborative partners, and future research trends, thereby providing guidance for relevant, novel research directions. Methods: Scientific publications related to acupuncture for BC-related symptoms were gathered from the Web of Science Core Collection (WoSCC) from 1993 to 2023. Four software applications were principally used to analyze the resulting data: the "bibliometrix" package in the R environment (version 4.2.3), VOSviewer, CiteSpace6.1.R6, and the bibliometrics website. These applications were employed to evaluate different parameters. Results: A total of 621 papers on acupuncture in BC-related symptoms treatment were analyzed. The United States, China, and South Korea contributed the most, with Memorial Sloan Kettering Cancer Center, and Columbia University leading institutions. It is interesting to mention that Mao, Jun J. and Molassiotis, A. feature among the top 10 authors and co-cited authors. JAMA is the leading journal, with an ongoing focus on acupuncture's effectiveness. Keywords show that the initial research focus was mainly on "vasomotor symptoms", but in recent years there has been a gradual shift towards "pain", "chemotherapy-induced peripheral neuropathy (CIPN)", "electroacupuncture", and "non-specific effects". Conclusion: Acupuncture has demonstrated a unique value in the process of adjuvant treatment of BC-related symptoms, and has been shown to be effective in reducing pain, eliminating fatigue, and improving quality of life. The study of the mechanisms of acupuncture and the application of electroacupuncture are possible future research priorities in this field. This study offers a deep perspective on acupuncture for BC research, highlighting key points and future trends.

9.
Org Lett ; 25(47): 8445-8450, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37975710

RESUMO

Despite the widespread presence of the chiral cyclopentane motif, the asymmetric synthesis of cyclopentanes containing five stereocenters remains a formidable challenge. Here, we present an N-heterocyclic carbene (NHC)-catalyzed cascade reaction of enal and oxindole-dienone, which allows access to spiroxindole cyclopentanes featuring a complete set of chiral centers on the five-membered carbocycle. This strategy, characterized by the formation of multiple bonds and chiral centers, demonstrates a broad substrate scope, exclusive diastereoselectivity, and up to 99:1 er.

10.
Eur J Med Res ; 28(1): 463, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37884978

RESUMO

BACKGROUND: A novel CT-linac (kilovolt fan-beam CT-linac) has been introduced into total marrow and lymphoid irradiation (TMLI) treatment. Its integrated kilovolt fan-beam CT (kV FBCT) can be used not only for image guidance (IGRT) but also to re-calculate the dose. PURPOSE: This study reported our clinical routine on performing TMIL treatment on the CT-linac, as well as dose distribution comparison between planned and re-calculated based on IGRT FBCT image sets. METHODS: 11 sets of data from 5 male and 6 female patients who had underwent the TMLI treatment with uRT-linac 506c were selected for this study. The planning target volumes consist of all skeletal bones exclusion of the mandible and lymphatic sanctuary sites. A planned dose of 10 Gy was prescribed to all skeletal bones exclusion of the mandible in two fractions and 12 Gy in two fractions was prescribed to lymphatic sanctuary sites. Each TMLI plan contained two sub-plans, one dynamic IMRT for the upper body and the other VMAT for the lower extremity. Two attempts were made to obtain homogeneous dose in the overlapping region, i.e., applying two plans with different isocenters for the treatment of two fractions, and using a dose gradient matching scheme. The CT scans, including planning CT and IGRT FBCT, were stitched to a whole body CT scan for dose distribution evaluation. RESULTS: The average beam-on time of Planupper is 30.6 min, ranging from 24.9 to 37.5 min, and the average beam-on time of Planlower is 6.3 min, ranging from 5.7 to 8.2 min. For the planned dose distribution, the 94.79% of the PTVbone is covered by the prescription dose of 10 Gy (V10), and the 94.68% of the PTVlymph is covered by the prescription dose of 12 Gy (V12). For the re-calculated dose distribution, the 92.17% of the PTVbone is covered by the prescription dose of 10 Gy (V10), and the 90.07% of the PTVlymph is covered by the prescription dose of 12 Gy (V12). The results showed that there is a significant difference (p < 0.05) between planning V10, V12 and delivery V10, V12. There is no significant difference (p > 0.05) between planned dose and re-calculated dose on selected organs, except for right lens (p < 0.05, Dmax). The actual delivered maximum dose of right lens is apparently larger than the planned dose of it. CONCLUSION: TMLI treatment can be performed on the CT-linac with clinical acceptable quality and high efficiency. Evaluation of the recalculated dose on IGRT FBCT suggests the treatment was delivered with adequate target coverage.


Assuntos
Radioterapia de Intensidade Modulada , Humanos , Masculino , Feminino , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Medula Óssea , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Irradiação Linfática , Tomografia Computadorizada por Raios X/métodos
11.
Purinergic Signal ; 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37870716

RESUMO

Diabetic neuropathic pain (DNP) is a common and destructive complication of diabetes mellitus. The discovery of effective therapeutic methods for DNP is vitally imperative because of the lack of effective treatments. Although 2 Hz electroacupuncture (EA) was a successful approach for relieving DNP, the mechanism underlying the effect of EA on DNP is still poorly understood. Here, we established a rat model of DNP that was induced by streptozotocin (STZ) injection. P2X4R was upregulated in the spinal cord after STZ-injection. The upregulation of P2X4R was mainly expressed on activated microglia. Intrathecal injection of a P2X4R antagonist or microglia inhibitor attenuated STZ-induced nociceptive thermal hyperalgesia and reduced the overexpression of brain-derived neurotrophic factor (BDNF), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in the spinal cord. We also assessed the effects of EA treatment on the pain hypersensitivities of DNP rats, and further investigated the possible mechanism underlying the analgesic effect of EA. EA relieved the hyperalgesia of DNP. In terms of mechanism, EA reduced the upregulation of P2X4R on activated microglia and decreased BDNF, IL-1ß and TNF-α in the spinal cord. Mechanistic research of EA's analgesic impact would be beneficial in ensuring its prospective therapeutic effect on DNP as well as in extending EA's applicability.

12.
Aesthetic Plast Surg ; 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37749417

RESUMO

BACKGROUND: Nasal septal mucosal defects following rhinoplasty in Asian patients are uncommon complications. However, the reconstruction of such defects presents a challenging task in plastic surgery. The aim of this study was to present comprehensive surgical strategies for the reconstruction of nasal septal mucosal defect after rhinoplasty. METHODS: Thirteen cases presenting with nasal septal mucosal defects between January 2016 and October 2021 were retrospectively reviewed. The size, location, and severity of the defect as well as the extent of cartilage exposure were taken into consideration during evaluation, and surgical approaches were employed for repair accordingly. Patient satisfaction was evaluated using a questionnaire with visual analog scale (VAS) and nasal obstruction symptom evaluation scale (NOSE). RESULTS: The average postoperative follow-up period in this study group was 10.15 months. Reconstruction of nasal septal mucosal defects resulted in successful treatment for all patients. There was no evidence of flap failure or nasal valve stenosis. All patients were satisfied with the reconstruction outcome. CONCLUSIONS: The successful application of surgical techniques for nasal septal mucosal defects after rhinoplasty requires comprehensive consideration. The utilization of the retrograde-flow superior labial artery mucosal flap appears to be a secure, efficient, and effective technique for nasal septal mucosal defect reconstruction in rhinoplasty, particularly in cases with cartilage exposure. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

13.
J Plast Reconstr Aesthet Surg ; 85: 414-422, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37579651

RESUMO

BACKGROUND: The nasal contracture after rhinoplasty is one of the most severe complications in East Asian patients. The classification and treatment algorithm of nasal contracture have not yet been established. This study aimed to develop a new classification system and treatment algorithm of contracted noses in East Asian patients to improve treatment outcomes. METHODS: A retrospective study was conducted with 62 patients with nasal contracture who underwent a revision rhinoplasty between March 2017 and March 2021. The authors classified the 62 patients into 3 groups based on the classification system. All patients underwent rhinoplasty designed according to the corresponding classification. The patients were followed up after surgery, and the rhinoplasty outcomes evaluation (ROE) was used to evaluate their satisfaction rate. RESULTS: A total of 59 female patients and 3 male patients (mean age, 29.45 ± 7.73 years) were included in this study. Forty-five cases presented mild nasal contracture (72.58%), 11 presented moderate nasal contracture (17.74%), and 6 presented severe nasal contracture (9.68%). There were statistically significant differences in the number of prior rhinoplasty procedures, infection history, and preoperative ROE scores among the three groups, with no differences in sex ratio, age, kinds of initial implant materials, and postoperative ROE scores. Almost all patients achieved satisfactory outcomes after the revision surgery designed by different classifications. CONCLUSION: The authors have established a new classification system and treatment algorithm for contracted noses based on the change in pathological anatomy of nose, which is effective for guiding the treatment of contracted noses with good results.


Assuntos
Contratura , Deformidades Adquiridas Nasais , Rinoplastia , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Estudos Retrospectivos , Deformidades Adquiridas Nasais/etiologia , Deformidades Adquiridas Nasais/cirurgia , Nariz/cirurgia , Rinoplastia/métodos , Resultado do Tratamento , Algoritmos , Contratura/cirurgia , Septo Nasal/cirurgia
14.
Front Endocrinol (Lausanne) ; 14: 973930, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37265689

RESUMO

Unexplained recurrent spontaneous abortion (URSA) is a severe challenge to reproductive females worldwide, and its etiology and pathogenesis have not yet been fully clarified. Abnormal intercellular communication between macrophages (Mφ) and decidual stromal cells (DSCs) or trophoblasts has been supposed to be the key to URSA. However, the exact molecular mechanisms in the crosstalk are not yet well understood. This study aimed to explore the potential molecule mechanism that may be involved in the communication between Mφ and DSC or trophoblast cells and determine their diagnostic characteristics by using the integrated research strategy of bioinformatics analysis, machine learning and experiments. First, microarrays of decidual tissue (GSE26787, GSE165004) and placenta tissue (GSE22490) in patients with URSA, as well as microarrays involving induced decidualization (GSE94644) and macrophage polarization in vitro (GSE30595) were derived from the gene expression omnibus (GEO) database. And 721 decidua-differentially expressed genes (DEGs), 613 placenta-DEGs, 510 Mφ polarization DEGs were obtained in URSA by differential expression analysis. Then, the protein-protein interaction (PPI) network was constructed, and the hub genes were identified by CytoHubba in Cytoscape software and validated by real-time PCR assay. Subsequently, immune enrichment analysis on decidua-DEGs and placenta-DEGs by ClueGO verified their regulation effects on Mφ. Besides, functional enrichment analysis was performed on Mφ polarization DEGs and the essential module genes derived from the weighted gene co-expression network analysis (WGCNA) to uncover the biological function that were related to abnormal polarization of Mφ. Furthermore, we screened out 29, 43 and 22 secreted protein-encoding genes from DSC-DEGs, placenta-DEGs and Mφ polarization DEGs, respectively. Besides, the hub secreted-protein-encoding genes were screened by CytoHubba. Moreover, we conducted functional enrichment analysis on these genes. And spearman correlation analysis between hub secreted-protein-encoding genes from donor cells and hub genes in recipient cells was performed to further understand the molecular mechanism of intercellular communication further. Moreover, signature genes with diagnostic value were screened from secreted protein-encoding genes by machine learning and validated by immunofluorescence co-localization analysis with clinical samples. Finally, three biomarkers of DSCs (FGF9, IL1R2, NID2) and three biomarkers of Mφ (CFB, NID2, CXCL11) were obtained. In conclusion, this project provides new ideas for understanding the mechanism regulatory network of intercellular communication involving macrophages at the maternal-fetal interface of URSA. Also, it provides innovative insights for the diagnosis and treatment of URSA.


Assuntos
Aborto Habitual , Transcriptoma , Gravidez , Feminino , Humanos , Perfilação da Expressão Gênica , Comunicação Celular/genética , Macrófagos/metabolismo
15.
Discov Med ; 35(176): 405-417, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37272107

RESUMO

OBJECTIVES: Over the past two decades, great progress has been made in advancing the early detection and multimodal treatment of non-small cell lung cancer (NSCLC). However, overall cure rates and survival rates of NSCLC are still not satisfactory, and research into new therapies is needed. This study attempted to construct human Fibroblast Activation Protein-Chimeric Antigen Receptor Natural killer (NK)-92 cells (hFAP-CAR-NK-92 cells) and explore their potential therapeutic effects in NSCLC. METHODS: Immunohistochemistry analysis was carried out to examine fibroblast activation protein (FAP) and Gasdermin E (GSDME) expression in clinical specimens of lung adenocarcinoma and squamous cell carcinoma tissue. Then the engineered hFAP-CAR-NK-92 cells efficiency was determined in vitro with lactate dehydrogenase (LDH) cytotoxicity assay and the cell morphology of A549, H226, and cancer-related fibroblast (CAF) was observed by electron microscopy. After the co-culture of target cells and effect cells, flow cytometry was employed for examining the CD107a expression in the effect cells, and western blotting was conducted for the cleavage levels of Caspase 3 and GSDME proteins in the target cells. The safety and efficacy of hFAP-CAR-NK-92 cells adoptive transfer immunotherapy in a tumor-bearing mouse were evaluated. RESULTS: Clinical studies have shown FAP positivity in patients with NSCLC. Compared with A549 or H226 cells alone, FAP expression was notably raised in A549+CAF cells or H226+CAF cells in nude mice, respectively (p < 0.05). The killing efficiency of K562 cells was not significantly different between hFAP-CAR-NK-92 and NK-92 cells (p > 0.05). The hFAP-CAR-NK-92 cells presented a higher killing efficiency against the hFAP-target (A549-hFAP, H226-hFAP and CAF-hFAP) cells than the NK-92 cells (p < 0.05). The degranulation of CD107a and cleavage levels of GSDME and Caspase 3 protein in the hFAP-CAR-NK-92 group were higher than those in the NK-92 group (p < 0.05). The 300 nM Granzyme B also induced pyroptosis in hFAP- or GSDME-positive cells (p < 0.05). In vivo experiments revealed that hFAP-CAR-NK-92 cells inhibited tumor progression of hFAP-positive NSCLC (p < 0.05). CONCLUSIONS: In this study, we successfully constructed hFAP-CAR-NK-92 cells and confirmed that hFAP-CAR-NK-92 cells could target hFAP-positive NSCLC to inhibit the progression of NSCLC by activating the Caspase-3/GSDME pyroptosis pathway.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Receptores de Antígenos Quiméricos , Humanos , Animais , Camundongos , Receptores de Antígenos Quiméricos/metabolismo , Carcinoma Pulmonar de Células não Pequenas/terapia , Caspase 3/metabolismo , Camundongos Nus , Linhagem Celular Tumoral , Neoplasias Pulmonares/terapia , Células Matadoras Naturais/metabolismo , Imunoterapia Adotiva
16.
Chem Commun (Camb) ; 59(47): 7279-7282, 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37227142

RESUMO

In this study, we report an organocatalytic formal coupling strategy for aryl-naphthoquinones with thiosugars that provides straightforward access to the axially chiral naphthoquinone thioglycoside with excellent stereoselectivity. Mechanistic studies revealed the key role of H-bonding in stereochemical recognition. The reaction pathway involves the atroposelective addition, followed by stereoretentive oxidation of the hydroquinone intermediate.


Assuntos
Naftoquinonas , Tioglicosídeos , Tioaçúcares
17.
Talanta ; 259: 124524, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37054624

RESUMO

The development of facilely synthetic materials acts an essential role in glycoproteome analysis, especially for the highly efficient enrichment of N-linked glycopeptides. In this work, a facile and timesaving route was introduced in which COFTP-TAPT served as a carrier and poly (ethylenimine) (PEI) and carrageenan (Carr) were successively coated on the surface via electrostatic interaction. The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol µL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). Due to the brilliant hydrophilicity and electrostatic interactions between COFTP-TAPT@PEI@Carr and positively charged glycopeptides, the prepared materials could be applied in the identification and analysis in the human plasma of healthy subjects and patients with nasopharyngeal carcinoma. As a result, 113 N-glycopeptides with 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins were enriched from 2 µL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma, respectively. 22 glycopeptides were identified only from the normal controls and 53 glycopeptides were detected only from the other set. The results demonstrated that this hydrophilic material was promising on a large scale and further N-glycoproteome research.


Assuntos
Estruturas Metalorgânicas , Neoplasias Nasofaríngeas , Humanos , Glicopeptídeos/análise , Carcinoma Nasofaríngeo , Interações Hidrofóbicas e Hidrofílicas , Imunoglobulina G
18.
Anal Chim Acta ; 1260: 341212, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37121659

RESUMO

Adenosine, as an endogenous nucleoside modulator, plays an important role in heart rate regulation, neurotransmission, and control of the respiratory system and thus it is significantly important to realize its sensitive detection. Herein, a highly sensitive electrochemical aptasensor for adenosine detection was proposed by using multi-walled carbon nanotubes (MWCNTs) as support matrix loading PtCu nanoparticles (PtCu-MWCNTs) to amplify signal. On one hand, disposable screen-printing gold electrodes (SPGEs) were used as superb sensing base to ensure the stable connection of aptamers 1 (ssDNA1). On the other hand, the PtCu-MWCNTs complex was synthesized through a one-pot method, which not only can precisely control the proportion of metal mass in the product but also exhibited superior electrocatalytic activity towards H2O2. The recognition reactions were achieved by stepwise incubation of ssDNA1, ssDNA2-PtCu-MWCNTs (denoted as ssDNA2-label), and adenosine on the SPGEs. As a result, the constructed electrochemical aptasensor exhibited a wide linear range from 10 nM to 1.0 µM with a low detection limit of 1.0 nM (S/N = 3) for adenosine detection. The aptasensor also successfully realized the adenosine detection in human serum samples, which means that the proposed aptasensor holds a potential application in point-of-care detection.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Nanopartículas Metálicas , Nanotubos de Carbono , Humanos , Adenosina , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Eletrodos , Ouro , Peróxido de Hidrogênio , Limite de Detecção , Platina/química , Cobre/química
19.
Aesthetic Plast Surg ; 47(4): 1364-1376, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36856780

RESUMO

BACKGROUND: The upper lip area is an important component of facial aesthetics, and aging produces an increase in the vertical height of the upper lip. Different upper lip lifting techniques are described in the literature. OBJECTIVES: This systematic review aimed to assess both invasive and noninvasive upper lip lifting techniques with patient satisfaction, adverse effects, and quantitative measurements of lifting efficiency. METHODS: This study was conducted per PRISMA guidelines. MEDLINE (via PubMed), EMBASE (OvidSP), and Cochrane Library database were searched from September 14, 2022, to October 12, 2022. Inclusion criteria were reporting on upper lip lift efficiency with quantitative measurements of the lifting degree. RESULTS: Out of 495 studies through the search strategy, nine articles were included in the systematic review, eight for surgical procedures and one for nonsurgical. Surgical procedures seem to have better longevity than nonsurgical techniques. Reported patient satisfaction for both surgical and nonsurgical treatments was good with no severe complaints. The quantitative measures differ between researches and may be classified into two metrics: anatomy ratio computation using photographic analysis or direct height measurement with a caliper and precise parameters utilizing a three-dimensional method. CONCLUSION: In general, surgical therapies seem to have a longer-lasting lifting effect on upper lip lifts with an inevitable scar, while nonsurgical techniques are minimally invasive but temporary. There was a lack of consistency in the measurements used to assess lifting efficiency. A consistent quantitative assessment can be beneficial for both clinical decision-making and high-level evidence research. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Assuntos
Envelhecimento , Lábio , Humanos , Lábio/cirurgia , Lábio/anatomia & histologia , Cicatriz , Satisfação do Paciente , Medicina Baseada em Evidências , Estética
20.
Mol Clin Oncol ; 18(3): 22, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36844467

RESUMO

Breast cancer (BC) is common worldwide. c-Myc and AXL are both overexpressed in BC, promoting its progression. The present study aimed to investigate the role of AXL in c-Myc expression in BC. Overexpression of AXL increased c-Myc expression while knockdown of AXL decreased c-Myc expression as determined by western blot analysis. Pharmaceutical inhibition of AXL also suppressed c-Myc expression. AKT and ERK inhibitor LY294002 and U0126 suppressed c-Myc expression, respectively. AXL overexpression which activates AKT and ERK signaling, upregulates c-Myc expression, while kinase-dead AXL which cannot activate AKT and ERK signaling, does not upregulate c-Myc expression, emphasizing the important role of these two signaling pathways in c-Myc upregulation. Finally, expression data of BC tissues from The Cancer Proteome Atlas displayed an association between AXL and c-Myc. Taken together, the present study revealed that AXL upregulates c-Myc expression through AKT and ERK signaling pathways in BC.

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