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1.
Sci Rep ; 14(1): 13796, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877096

RESUMO

To explore the hub comorbidity genes and potential pathogenic mechanisms of hypopharyngeal carcinoma with esophageal carcinoma, and evaluate their diagnostic value for hypopharyngeal carcinoma with co-morbid esophageal carcinoma. We performed gene sequencing on tumor tissues from 6 patients with hypopharyngeal squamous cell carcinoma with esophageal squamous cell carcinoma (hereafter referred to as "group A") and 6 patients with pure hypopharyngeal squamous cell carcinoma (hereafter referred to as "group B"). We analyzed the mechanism of hub genes in the development and progression of hypopharyngeal squamous cell carcinoma with esophageal squamous cell carcinoma through bioinformatics, and constructed an ROC curve and Nomogram prediction model to analyze the value of hub genes in clinical diagnosis and treatment. 44,876 genes were sequenced in 6 patients with group A and 6 patients with group B. Among them, 76 genes showed significant statistical differences between the group A and the group B.47 genes were expressed lower in the group A than in the group B, and 29 genes were expressed higher. The top five hub genes were GABRG2, CACNA1A, CNTNAP2, NOS1, and SCN4B. GABRG2, CNTNAP2, and SCN4B in the hub genes have high diagnostic value in determining whether hypopharyngeal carcinoma patients have combined esophageal carcinoma (AUC: 0.944, 0.944, 0.972). These genes could possibly be used as potential molecular markers for assessing the risk of co-morbidity of hypopharyngeal carcinoma combined with esophageal carcinoma.


Assuntos
Neoplasias Esofágicas , Regulação Neoplásica da Expressão Gênica , Neoplasias Hipofaríngeas , Humanos , Neoplasias Hipofaríngeas/genética , Neoplasias Hipofaríngeas/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Biomarcadores Tumorais/genética , Idoso , Análise de Sequência de RNA/métodos , Perfilação da Expressão Gênica , Biologia Computacional/métodos , Nomogramas
2.
Talanta ; 277: 126298, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38823330

RESUMO

Combination drug therapy represents an effective strategy for treating certain drug-resistant and intractable cancer cases. However, determining the optimal combination of drugs and dosages is challenging due to clonal diversity in patients' tumors and the lack of rapid drug sensitivity evaluation methods. Microfluidic technology offers promising solutions to this issue. In this study, we propose a versatile microfluidic chip platform capable of integrating all processes, including dilution, treatment, and detection, for in vitro drug sensitivity assays. This platform innovatively incorporates several modules, including automated discrete drug logarithmic concentration generation, on-chip cell perfusion culture, and parallel drug treatments of cancer cell models. Moreover, it is compatible with microplate readers or high-content imaging systems for swift detection and automated monitoring, simplifying on-chip drug evaluation. Proof of concept is demonstrated by assessing the in vitro potency of two drugs, cisplatin, and etoposide, against the lung adenocarcinoma A549 cell line, under both single-drug and combination treatment conditions. The findings reveal that, compared to conventional microplate approaches with static cultivation, this on-chip automated perfusion bioassays yield comparable IC50 values with lower variation and a 50 % reduction in drug preparation time. This versatile dilution-treatment-detection microfluidic platform offers a promising tool for rapid and precise drug assessments, facilitating in vitro drug sensitivity evaluation in personalized cancer chemotherapy.

3.
J Agric Food Chem ; 72(20): 11706-11715, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38728528

RESUMO

In this study, we devised a photothermally stable phytochemical dye by leveraging alizarin in conjunction with the metal-organic framework ZIF-8 (AL@ZIF-8). The approach involved grafting alizarin into the microporous structure of ZIF-8 through physical adsorption and hydrogen-bonding interactions. AL@ZIF-8 significantly enhanced the photostability and thermostability of alizarin. The nanoparticles demonstrate substantial color changes in various pH environments, showcasing their potential for meat freshness monitoring. Furthermore, we introduced an intelligent film utilizing poly(vinyl alcohol)-sodium alginate-AL@ZIF-8 (PA-SA-ZA) for detecting beef freshness. The sensor exhibited a superior water contact angle (52.34°) compared to the alizarin indicator. The color stability of the film was significantly enhanced under visible and UV light (ΔE < 5). During beef storage, the film displayed significant color fluctuations correlating with TVB-N (R2=0.9067), providing precise early warning signals for assessing beef freshness.


Assuntos
Alginatos , Colorimetria , Álcool de Polivinil , Alginatos/química , Animais , Álcool de Polivinil/química , Bovinos , Colorimetria/métodos , Antraquinonas/química , Embalagem de Alimentos/instrumentação , Compostos Fitoquímicos/química , Carne Vermelha/análise , Estruturas Metalorgânicas/química
4.
Sci Rep ; 14(1): 11693, 2024 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778168

RESUMO

Cybersickness remains a pivotal factor that impacts user experience in Augmented Reality (AR). Research probing into the relationship between AR reading tasks and cybersickness, particularly focusing on text display patterns and user characteristics, has been scant. Moreover, the influence of cybersickness on searching ability and the broader spectrum of user experience has not been rigorously tested. Recent investigations have aimed to pinpoint the variables that contribute to cybersickness during AR reading sessions. In one such study, 40 participants underwent a series of controlled experiments with randomized text display patterns, including variations in text speed and text movement modes. Post-experiment, participants completed a questionnaire that helped quantify their experiences and the degree of cybersickness encountered. The data highlighted that satiety, text speed, and text movement mode are significant contributors to cybersickness. When participants experienced higher levels of cybersickness, font color stood out as a particularly influential factor, whereas gender differences seemed to affect the onset of cybersickness more noticeably at lower levels. This study also drew attention to the impact of cybersickness on search ability within AR environments. It was noted that as cybersickness intensity increased, search ability was markedly compromised. In sum, the research underscores the importance of text display patterns and user characteristics, such as past AR experience, in understanding cybersickness and its detrimental effects on user experience and search ability, particularly under conditions of intense cybersickness.


Assuntos
Realidade Aumentada , Humanos , Feminino , Masculino , Adulto , Adulto Jovem , Inquéritos e Questionários , Leitura , Interface Usuário-Computador
5.
Front Bioeng Biotechnol ; 12: 1372158, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38576448

RESUMO

Background: Trans-spinal electrical stimulation (tsES) to the intact spinal cord poststroke may modulate the cortico-muscular control in stroke survivors with diverse lesions in the brain. This work aimed to investigate the immediate effects of tsES on the cortico-muscular descending patterns during voluntary upper extremity (UE) muscle contractions by analyzing cortico-muscular coherence (CMCoh) and electromyography (EMG) in people with chronic stroke. Methods: Twelve chronic stroke participants were recruited to perform wrist-hand extension and flexion tasks at submaximal levels of voluntary contraction for the corresponding agonist flexors and extensors. During the tasks, the tsES was delivered to the cervical spinal cord with rectangular biphasic pulses. Electroencephalography (EEG) data were collected from the sensorimotor cortex, and the EMG data were recorded from both distal and proximal UE muscles. The CMCoh, laterality index (LI) of the peak CMCoh, and EMG activation level parameters under both non-tsES and tsES conditions were compared to evaluate the immediate effects of tsES on the cortico-muscular descending pathway. Results: The CMCoh and LI of peak CMCoh in the agonist distal muscles showed significant increases (p < 0.05) during the wrist-hand extension and flexion tasks with the application of tsES. The EMG activation levels of the antagonist distal muscle during wrist-hand extension were significantly decreased (p < 0.05) with tsES. Additionally, the proximal UE muscles exhibited significant decreases (p < 0.05) in peak CMCoh and EMG activation levels by applying tsES. There was a significant increase (p < 0.05) in LI of peak CMCoh of proximal UE muscles during tsES. Conclusion: The cervical spinal cord neuromodulation via tsES enhanced the residual descending excitatory control, activated the local inhibitory circuits within the spinal cord, and reduced the cortical and proximal muscular compensatory effects. These results suggested the potential of tsES as a supplementary input for improving UE motor functions in stroke rehabilitation.

6.
Angew Chem Int Ed Engl ; 63(22): e202403492, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38482742

RESUMO

The development of self-replicating systems is of great importance in research on the origin of life. As the most iconic molecules, nucleic acids have provided prominent examples of the fabrication of self-replicating artificial nanostructures. However, it is still challenging to construct sophisticated synthetic systems that can create large-scale or three-dimensionally ordered nanomaterials using self-replicating nanostructures. By integrating a template system containing DNA-functionalized colloidal seeds with a simplified DNA strand-displacement circuit programmed subsystem to produce DNA-functionalized colloidal copies, we developed a facile enthalpy-mediated strategy to control the replication and catalytic assembly of DNA-functionalized colloids in a time-dependent manner. The replication efficiency and crystal quality of the resulting superlattice structures can be effectively increased by regulating the molar ratio of the template to the copy colloids. By constructing binary systems from two types of gold nanoparticles (or proteins), superlattice structures with different crystal symmetries can be obtained through the replication and catalytic assembly processes. This programmable enthalpy-mediated approach was easily leveraged to achieve the phase transformation and catalytic amplification of colloidal crystals starting from different initial template crystals. This work offers a potential way to construct self-replicating artificial systems that exhibit complicated phase behaviors and can produce large-scale superlattice nanomaterials.


Assuntos
Coloides , DNA , Coloides/química , DNA/química , Ouro/química , Cristalização , Nanopartículas Metálicas/química , Termodinâmica , Nanoestruturas/química
7.
Adv Sci (Weinh) ; 11(22): e2309852, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38504470

RESUMO

Biosynthesis is the application of enzymes in microbial cell factories and has emerged as a promising alternative to chemical synthesis. However, natural enzymes with limited catalytic performance often need to be engineered to meet specific needs through a time-consuming trial-and-error process. This study presents a quantum mechanics (QM)-incorporated design-build-test-learn (DBTL) framework to rationally design phosphatase BT4131, an enzyme with an ambiguous substrate spectrum involved in N-acetylglucosamine (GlcNAc) biosynthesis. First, mutant M1 (L129Q) is designed using force field-based methods, resulting in a 1.4-fold increase in substrate preference (kcat/Km) toward GlcNAc-6-phosphate (GlcNAc6P). QM calculations indicate that the shift in substrate preference is caused by a 13.59 kcal mol-1 reduction in activation energy. Furthermore, an iterative computer-aided design is conducted to stabilize the transition state. As a result, mutant M4 (I49Q/L129Q/G172L) with a 9.5-fold increase in kcat-GlcNAc6P/Km-GlcNAc6P and a 59% decrease in kcat-Glc6P/Km-Glc6P is highly desirable compared to the wild type in the GlcNAc-producing chassis. The GlcNAc titer increases to 217.3 g L-1 with a yield of 0.597 g (g glucose)-1 in a 50-L bioreactor, representing the highest reported level. Collectively, this DBTL framework provides an easy yet fascinating approach to the rational design of enzymes for industrially viable biocatalysts.


Assuntos
Monoéster Fosfórico Hidrolases , Especificidade por Substrato , Monoéster Fosfórico Hidrolases/metabolismo , Monoéster Fosfórico Hidrolases/genética , Acetilglucosamina/metabolismo , Engenharia de Proteínas/métodos , Teoria Quântica
8.
Food Chem X ; 22: 101289, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38544933

RESUMO

Oligosaccharides are low-molecular-weight carbohydrates between monosaccharides and polysaccharides. They can be extracted directly from natural products by physicochemical methods or obtained by chemical synthesis or enzymatic reaction. Oligosaccharides have important physicochemical and physiological properties. Their research and production involve many disciplines such as medicine, chemical industry, and biology. Functional oligosaccharides, as an excellent functional food base, can be used as dietary fibrer and prebiotics to enrich the diet; improve the microecology of the gut; exert antitumour, anti-inflammatory, antioxidant, and lipid-lowering properties. Therefore, the industrial applications of oligosaccharides have increased rapidly in the past few years. It has great prospects in the field of food and medicinal chemistry. This review summarized the preparation, structural features and biological activities of oligosaccharides, with particular emphasis on the application of functional oligosaccharides in the food industry and human nutritional health. It aims to inform further research and development of oligosaccharides and food chemistry.

9.
Cell Mol Biol (Noisy-le-grand) ; 70(2): 44-50, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38430041

RESUMO

Molecular pathology and clinical characteristics play a crucial role in guiding treatment selection and predicting the prognosis of diffuse large B-cell lymphoma (DLBCL). The programmed cell death protein 1 (PD-1) and its ligand (PD-L1), have emerged as pivotal regulators of immune checkpoints in cancer. The objectives of this study are to investigate the correlation between the expression levels of PD-1 and soluble PD-L1 (sPD-L1) in the peripheral blood of DLBCL patients, analyze their clinicopathological characteristics, and identify the optimal beneficiary group for PD-1/PD-L1 blockade. Peripheral blood samples were collected from 36 DLBCL patients before their initial treatment at Shandong Cancer Hospital between December 2018 and July 2019. The expression levels of PD-1 and sPD-L1 were measured using flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. The clinicopathological characteristics, including age, sex, Ann Arbor stage, International Prognostic Index (IPI) score, response to treatment, etc., were recorded for each patient. The surface expression of PD-1 on peripheral blood T cells was significantly higher in DLBCL patients compared to healthy controls. There was a significant association between elevated PD-1 expression levels and the advanced Ann Arbor stage (P=0.0153) as well as the B group (P=0.0184). Higher sPD-L1 levels were associated with the GCB subtype according to Hans's classification (P=0.0435). The expression levels of PD-1 and sPD-L1 in the peripheral blood of DLBCL patients are significantly correlated with advanced disease stage, B group, and GCB subtype according to Hans's classification. This suggests that the PD-1/PD-L1 axis play a critical role in specific subgroups of DLBCL. Targeting this axis could serve as a potential therapeutic strategy to enhance the clinical outcomes of DLBCL patients. Further studies are necessary to explore the prognostic implications of PD-1 and sPD-L1 expression levels in DLBCL patients.


Assuntos
Antígeno B7-H1 , Linfoma Difuso de Grandes Células B , Humanos , Antígeno B7-H1/genética , Receptor de Morte Celular Programada 1/genética , Linfoma Difuso de Grandes Células B/genética , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo
10.
J Int Med Res ; 52(3): 3000605241236278, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38483140

RESUMO

OBJECTIVE: To assess the efficacy of dynamic changes in lymphocyte-C-reactive protein ratio (LCR) on differentiating disease severity and predicting disease progression in adult patients with Coronavirus disease 2019 (COVID-19). METHODS: This single-centre retrospective study enrolled adult COVID-19 patients categorized into moderate, severe and critical groups according to the Diagnosis and Treatment of New Coronavirus Pneumonia (ninth edition). Demographic and clinical data were collected. LCR and sequential organ failure assessment (SOFA) score were calculated. Lymphocyte count and C-reactive protein (CRP) levels were monitored on up to four occasions. Disease severity was determined concurrently with each LCR measurement. RESULTS: This study included 145 patients assigned to moderate (n = 105), severe (n = 33) and critical groups (n = 7). On admission, significant differences were observed among different disease severity groups including age, comorbidities, neutrophil proportion, lymphocyte count and proportion, D-Dimer, albumin, total bilirubin, direct bilirubin, indirect bilirubin, CRP and SOFA score. Dynamic changes in LCR showed significant differences across different disease severity groups at different times, which were significantly inversely correlated with disease severity of COVID-19, with correlation coefficients of -0.564, -0.548, -0.550 and -0.429 at four different times. CONCLUSION: Dynamic changes in LCR can effectively differentiate disease severity and predict disease progression in adult COVID-19 patients.


Assuntos
COVID-19 , Adulto , Humanos , COVID-19/diagnóstico , Estudos Retrospectivos , Proteína C-Reativa/análise , SARS-CoV-2 , Biomarcadores , Gravidade do Paciente , Índice de Gravidade de Doença , Linfócitos/metabolismo , Progressão da Doença , Bilirrubina
11.
Cell Mol Life Sci ; 81(1): 122, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38456997

RESUMO

Doxorubicin-induced cardiotoxicity (DIC), which is a cardiovascular complication, has become the foremost determinant of decreased quality of life and mortality among survivors of malignant tumors, in addition to recurrence and metastasis. The limited ability to accurately predict the occurrence and severity of doxorubicin-induced injury has greatly hindered the prevention of DIC, but reducing the dose to mitigate side effects may compromise the effective treatment of primary malignancies. This has posed a longstanding clinical challenge for oncologists and cardiologists. Ferroptosis in cardiomyocytes has been shown to be a pivotal mechanism underlying cardiac dysfunction in DIC. Ferroptosis is influenced by multiple factors. The innate immune response, as exemplified by neutrophil extracellular traps (NETs), may play a significant role in the regulation of ferroptosis. Therefore, the objective of this study was to investigate the involvement of NETs in doxorubicin-induced cardiomyocyte ferroptosis and elucidate their regulatory role. This study confirmed the presence of NETs in DIC in vivo. Furthermore, we demonstrated that depleting neutrophils effectively reduced the occurrence of doxorubicin-induced ferroptosis and myocardial injury in DIC. Additionally, our findings showed the pivotal role of high mobility group box 1 (HMGB1) as a critical molecule implicated in DIC and emphasized its involvement in the modulation of ferroptosis subsequent to NETs inhibition. Mechanistically, we obtained preliminary evidence suggesting that doxorubicin-induced NETs could modulate yes-associated protein (YAP) activity by releasing HMGB1, which subsequently bound to toll like receptor 4 (TLR4) on the cardiomyocyte membrane, thereby influencing cardiomyocyte ferroptosis in vitro. Our findings suggest that doxorubicin-induced NETs modulate cardiomyocyte ferroptosis via the HMGB1/TLR4/YAP axis, thereby contributing to myocardial injury. This study offers a novel approach for preventing and alleviating DIC by targeting alterations in the immune microenvironment.


Assuntos
Armadilhas Extracelulares , Ferroptose , Proteína HMGB1 , Cardiopatias , Humanos , Miócitos Cardíacos/metabolismo , Armadilhas Extracelulares/metabolismo , Proteína HMGB1/metabolismo , Receptor 4 Toll-Like/metabolismo , Cardiotoxicidade/metabolismo , Qualidade de Vida , Cardiopatias/metabolismo , Doxorrubicina/efeitos adversos
12.
J Inflamm Res ; 17: 1659-1669, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38504695

RESUMO

Purpose: In this study, our objective was to investigate the potential utility of lymphocyte-C-reactive protein ratio (LCR) as a predictor of disease progression and a screening tool for intensive care unit (ICU) admission in adult patients with acute pancreatitis (AP). Methods: We included a total of 217 adult patients with AP who were admitted to the First Affiliated Hospital of Harbin Medical University between July 2019 and June 2022. These patients were categorized into three groups: mild AP (MAP), moderately severe AP (MSAP), and severe AP (SAP), based on the presence and duration of organ dysfunction. Various demographic and clinical data were collected and compared among different disease severity groups. Results: Height, diabetes, lymphocyte count (LYMPH), lymphocyte percentage (LYM%), platelet count (PLT), D-Dimer, albumin (ALB), blood urea nitrogen (BUN), serum creatinine (SCr), glucose (GLU), calcium ion (Ca2+), C-reactive protein (CRP), procalcitonin (PCT), hospitalization duration, ICU admission, need for BP, LCR, sequential organ failure assessment (SOFA) score, bedside index for severity in AP (BISAP) score, and modified Marshall score showed significant differences across different disease severity groups upon hospitalization. Notably, there were significant differences in LCR between the MAP group and the MSAP and SAP combined group, and the MAP and MSAP combined group and the SAP group, and adult AP patients with ICU admission and those without ICU admission upon hospitalization. Conclusion: In summary, LCR upon hospitalization can be utilized as a simple and reliable predictor of disease progression and a screening tool for ICU admission in adult patients with AP.

13.
Light Sci Appl ; 13(1): 56, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38403652

RESUMO

Scalable, high-capacity, and low-power computing architecture is the primary assurance for increasingly manifold and large-scale machine learning tasks. Traditional electronic artificial agents by conventional power-hungry processors have faced the issues of energy and scaling walls, hindering them from the sustainable performance improvement and iterative multi-task learning. Referring to another modality of light, photonic computing has been progressively applied in high-efficient neuromorphic systems. Here, we innovate a reconfigurable lifelong-learning optical neural network (L2ONN), for highly-integrated tens-of-task machine intelligence with elaborated algorithm-hardware co-design. Benefiting from the inherent sparsity and parallelism in massive photonic connections, L2ONN learns each single task by adaptively activating sparse photonic neuron connections in the coherent light field, while incrementally acquiring expertise on various tasks by gradually enlarging the activation. The multi-task optical features are parallelly processed by multi-spectrum representations allocated with different wavelengths. Extensive evaluations on free-space and on-chip architectures confirm that for the first time, L2ONN avoided the catastrophic forgetting issue of photonic computing, owning versatile skills on challenging tens-of-tasks (vision classification, voice recognition, medical diagnosis, etc.) with a single model. Particularly, L2ONN achieves more than an order of magnitude higher efficiency than the representative electronic artificial neural networks, and 14× larger capacity than existing optical neural networks while maintaining competitive performance on each individual task. The proposed photonic neuromorphic architecture points out a new form of lifelong learning scheme, permitting terminal/edge AI systems with light-speed efficiency and unprecedented scalability.

14.
Clin Nucl Med ; 49(5): 478-480, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38409759

RESUMO

ABSTRACT: The involvement of the ureter as a site of metastasis of colorectal cancer is quite rare. Here we present FDG PET/CT findings of the right ureter metastasis from colon cancer in a patient after colectomy 6 years ago. 18 F-FDG PET/CT showed increased 18 F-FDG uptake in the right ureter with SUV max of 4.3. The pathology and immunohistochemistry confirmed the diagnosis of ureter metastasis from colon cancer.


Assuntos
Neoplasias do Colo , Ureter , Humanos , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons
15.
Arch Virol ; 169(2): 38, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38300296

RESUMO

Here, a novel mycovirus, Botryosphaeria dothidea narnavirus 5 (BdNV5), was discovered in the plant-pathogenic fungus Botryosphaeria dothidea strain ZM210167-1. The BdNV5 genome sequence is 2,397 nucleotides (nt) in length and contains a putative open reading frame (ORF) encoding an RNA-dependent RNA polymerase (RdRp) with a molecular mass of 72.77 kDa. A BLASTp search using the RdRp amino acid (aa) sequence showed that it was most similar to the RdRp of Botryosphaeria dothidea narnavirus 4 (42.35%). In a phylogenetic tree based on RdRp aa sequences, BdNV5 clustered with members of the family Narnaviridae. BdNV5 is thus a novel member of the family Narnaviridae infecting the phytopathogenic fungus B. dothidea.


Assuntos
Ascomicetos , Vírus de RNA , Filogenia , Ascomicetos/genética , Sequência de Aminoácidos , Vírus de RNA/genética , RNA Polimerase Dependente de RNA/genética
17.
Cancer Med ; 13(3): e6875, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38205938

RESUMO

BACKGROUND: Cervical cancer (CC) has become the fourth most common cancer worldwide and it is mainly caused by the infection of human papillomavirus (HPV), especially high-risk HPV16. Aberrant miRNA expression in CC is closely related to HPV16 infection, and the regulation of HPV16 E6 expression can affect a variety of miRNA expression. This study aims to exploring the miRNAs involved in E6 regulation in CC. METHODS: Our study screened differentially expressed miRNAs in cervical cells of HPV16 infected and uninfected cervical cancer patients by analyzing the GSE81137 dataset of the gene expression omnibus database (GEO), and identified miR-320a that plays an anti-tumor role and is associated with good prognosis of cervical cancer. Explore the effect of HPV16 E6 on the expression of miR-320a in cervical cancer, and verify whether HPV16 E6 regulates the downstream target gene TOP2A expression through miR-320a, thereby affecting cervical cancer cell proliferation, apoptosis, migration, invasion, and EMT in vitro and in vivo. RESULTS: The bioinformatic methods selected the miR-320a, which was differentially expressed in cervical cells from HPV16-infected patients compared to uninfected patients. We further demonstrated that miR-320a level was regulated by HPV16 E6, which promoted the CC cell proliferation, migration, invasion, and inhibited apoptosis. In addition, we predicted the downstream target genes of miR-320a and confirmed that TOP2A was one of its targeting proteins. Moreover, HPV16 E6 promoted the TOP2A expression in CC cells through down-regulating miR-320a, leading to promoting CC development. CONCLUSIONS: We confirmed that HPV16 E6 promoted the TOP2A expression through down-regulation of miR-320a, thus promoting CC development, and the HPV16 E6/miR-320a/TOP2A axis may perform as a potential target for CC treatment.


Assuntos
MicroRNAs , Neoplasias do Colo do Útero , Feminino , Humanos , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias do Colo do Útero/patologia
18.
Chem Biol Drug Des ; 103(1): e14414, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38230796

RESUMO

Among all types of cancers, non-small cell lung cancer (NSCLC) exhibits the highest mortality rate with a five-year survival rate below 17% for patients. The Buzhong Yiqi decoction (BZYQD), traditional Chinese medicine (TCM) formula, has been reported to exhibit clinical efficacy in the treatment of NSCLC. Nevertheless, the underlying molecular mechanism remains elusive. This study aimed to assess the mechanistic actions exerted by BZYQD against NSCLC using network pharmacological analysis and experimental validation. The public databases were searched for active compounds in BZYQD, their potential targets, and NSCLC-related targets. The protein-protein interaction (PPI) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the core targets and signaling pathways of BZYQD against NSCLC. After screening, this study validated the results of predictions through in vitro experiments and public databases. We found 192 common targets between BZYQD and NSCLC. KEGG analysis showed that the anti-NSCLC effects of BZYQD were mediated through the PI3K-AKT signaling pathway. The results of in vitro experiment indicated that BZYQD could inhibit cell viability and proliferation of A549 and H1299 cells apart from inducing cell apoptosis. In addition, western blot results substantiated that BZYQD could treat NSCLC by inhibiting the activation of the PI3K-AKT signaling pathway. The current study investigated the pharmacological mechanism of BZYQD against NSCLC via network pharmacology and in vitro analyses. Overall, the results revealed that BZYQD could be a promising therapeutic agent for the treatment of NSCLC in the future. Still, more experimental investigations are needed to confirm the applicability of BZYQD for clinical trials.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Medicamentos de Ervas Chinesas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Neoplasias Pulmonares/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Simulação de Acoplamento Molecular
19.
Opt Express ; 32(1): 104-112, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38175041

RESUMO

In this study, we present an ultralow noise single-frequency fiber laser operating at 1550 nm, utilizing a traveling-wave ring cavity configuration. The frequency noise of the laser approaches the thermal noise limit, achieving a white noise level of 0.025 Hz2/Hz, resulting in an instantaneous linewidth of 0.08 Hz. After amplification, the output power reaches 4.94 W while maintaining the same low white noise level as the laser oscillator. The integration linewidths of the laser oscillator and amplifier are 221 Hz and 665 Hz, respectively, with both exhibiting relative intensity noises that approach the quantum shot noise limit. To the best of our knowledge, this work shows the lowest frequency noise combined with relatively high power for this type of ring cavity fiber laser.

20.
Sci Rep ; 14(1): 516, 2024 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-38177197

RESUMO

To explore the anti-tumor effects of Radix Astragali on hypopharyngeal carcinoma and its mechanism. We have bioinformatically analyzed the potential targets of Radix Astragali and predicted the molecular mechanism of Radix Astragali treating of hypopharyngeal carcinoma. The binding process of the hub targets that could prolong the survival time of hypopharyngeal cancer patients with Radix Astragali was simulated by molecular docking. The results showed that 17 out of 36 hub targets could effectively improve the 5-year survival rate of hypopharyngeal cancer patients. Radix Astragali acts on hypopharyngeal carcinoma by regulating a signaling network formed by hub targets connecting multiple signaling pathways and is expected to become a drug for treating and prolonging hypopharyngeal carcinoma patients' survival time.


Assuntos
Astrágalo , Neoplasias Hipofaríngeas , Humanos , Astrágalo/química , Simulação de Acoplamento Molecular , Neoplasias Hipofaríngeas/tratamento farmacológico , Farmacologia em Rede
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