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1.
Heliyon ; 10(9): e30445, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38737261

RESUMO

Objective: To investigate the involvement of the homeobox gene B5 (HOXB5) in the progression and metastasis of osteosarcoma. Methods: The expression of HOXB5 in human osteosarcoma tissues and its correlation with clinical indicators were investigated using bioinformatics analysis and immunohistochemical labelling. Human osteosarcoma cells (HOS, MG63, U2OS, and Saos-2) and normal human osteoblasts (hFOB1.19) were cultivated. The expression of HOXB5 in these cells was detected using western blotting (WB) and RT‒PCR. Two cell lines exhibiting elevated HOXB5 expression were chosen and divided into three groups: the blank group (mock), control group (control) and transfection group (shHOXB5). The transfection group was infected with lentivirus expressing shRNAs targeting HOXB5. The transfection efficiency was detected by WB. Cell proliferation suppression was measured by CCK-8 and 5-ethynyl-2'-deoxyuridine (EdU) assays; the percentage of apoptotic cells was determined by flow cytometry; and cell migration and invasion were detected via the Transwell chamber test. WB was utilized to determine the protein expression of genes linked to metastasis (MMP2, MMP9), apoptosis (Bax, Bcl-2), and the JAK2/STAT3 pathway (JAK2, p-JAK2, STAT3, p-STAT3). Results: In osteosarcoma tissues, HOXB5 expression was elevated and strongly correlated with distant metastasis. Silencing HOXB5 reduced the proliferation, migration and invasion of osteosarcoma cells; prevented the progression and metastasis of tumours in tumour-bearing nude mice; and reduced the activation of key proteins in the JAK2/STAT3 signalling pathway. Conclusion: Through the JAK2/STAT3 signalling pathway, HOXB5 plays a crucial role in the malignant progression of osteosarcoma and is a promising target for osteosarcoma treatment.

2.
Front Immunol ; 15: 1374486, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38745651

RESUMO

A universal recombinant adenovirus type-5 (Ad5) vaccine against COVID19 (Ad-US) was constructed, and immunogenicity and broad-spectrum of Ad5-US were evaluated with both intranasal and intramuscular immunization routes. The humoral immune response of Ad5-US in serum and bronchoalveolar lavage fluid were evaluated by the enzyme-linked immunosorbent assay (ELISA), recombinant vesicular stomatitis virus based pseudovirus neutralization assay, and angiotensin-converting enzyme-2 (ACE2) -binding inhibition assay. The cellular immune response and Th1/Th2 biased immune response of Ad5-US were evaluated by the IFN-γ ELISpot assay, intracellular cytokine staining, and Meso Scale Discovery (MSD) profiling of Th1/Th2 cytokines. Intramuscular priming followed by an intranasal booster with Ad5-US elicited the broad-spectrum and high levels of IgG, IgA, pseudovirus neutralizing antibody (PNAb), and Th1-skewing of the T-cell response. Overall, the adenovirus type-5 vectored universal SARS-CoV-2 vaccine Ad5-US was successfully constructed, and Ad5-US was highly immunogenic and broad spectrum. Intramuscular priming followed by an intranasal booster with Ad5-US induced the high and broad spectrum systemic immune responses and local mucosal immune responses.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Vetores Genéticos , SARS-CoV-2 , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , COVID-19/imunologia , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Camundongos , Humanos , Feminino , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/administração & dosagem , Adenoviridae/genética , Adenoviridae/imunologia , Camundongos Endogâmicos BALB C , Administração Intranasal , Injeções Intramusculares , Imunidade Humoral , Citocinas/metabolismo , Imunidade Celular
3.
Int J Biol Macromol ; : 132335, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38768923

RESUMO

Development of renewable and biodegradable plastics with good properties, such as the gas barrier, UV-shielding, solvent resistance, and antibacterial activity, remains a challenge. Herein, cellulose/ZnO based bioplastics were fabricated by dissolving cellulose carbamate in an aqueous solution of NaOH/Zn(OH)42-, followed by coagulation in aqueous Na2SO4 solution, and subsequent hot-pressing. The carbamate groups detached from cellulose, and ZnO which transformed from cosolvent to nanofiller was uniformly immobilized in the cellulose matrix during the dissolution/regeneration process. The appropriate addition of ZnO (below 10.67 wt%) not only improved the mechanical properties but also enhanced the water and oxygen barrier properties of the material. Additionally, our cellulose/ZnO based bioplastic demonstrated excellent UV-blocking capabilities, increased water contact angle, and enhanced antibacterial activity against S. aureus and E. coli, deriving from the incorporation of ZnO nanoparticles. Furthermore, the material exhibited resistance to organic solvents such as acetone, THF, and toluene. Indeed, the herein developed cellulose/ZnO based bioplastic presents a promising candidate to replace petrochemical plastics in various applications, such as plastic toys, anti-UV guardrails, window shades, and oil storage containers, offering a combination of favorable mechanical, gas barrier, UV-blocking, antibacterial, and solvent-resistant properties.

4.
Heliyon ; 10(6): e27740, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38515674

RESUMO

This review critically examines the progress and challenges in the field of nanostructured tungsten oxide (WO3) gas sensors. It delves into the significant advancements achieved through nanostructuring and composite formation of WO3, which have markedly improved sensor sensitivity for gases like NO2, NH3, and VOCs, achieving detection limits in the ppb range. The review systematically explores various innovative approaches, such as doping WO3 with transition metals, creating heterojunctions with materials like CuO and graphene, and employing machine learning models to optimize sensor configurations. The challenges facing WO3 sensors are also thoroughly examined. Key issues include cross-sensitivity to different gases, particularly at higher temperatures, and long-term stability affected by factors like grain growth and volatility of dopants. The review assesses potential solutions to these challenges, including statistical analysis of sensor arrays, surface functionalization, and the use of novel nanostructures for enhanced performance and selectivity. In addition, the review discusses the impact of ambient humidity on sensor performance and the current strategies to mitigate it, such as composite materials with humidity shielding effects and surface functionalization with hydrophobic groups. The need for high operating temperatures, leading to higher power consumption, is also addressed, along with possible solutions like the use of advanced materials and new transduction principles to lower temperature requirements. The review concludes by highlighting the necessity for a multidisciplinary approach in future research. This approach should combine materials synthesis, device engineering, and data science to develop the next generation of WO3 sensors with enhanced sensitivity, ultrafast response rates, and improved portability. The integration of machine learning and IoT connectivity is posited as a key driver for new applications in areas like personal exposure monitoring, wearable diagnostics, and smart city networks, underlining WO3's potential as a robust gas sensing material in future technological advancements.

5.
J Med Virol ; 96(3): e29454, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38445768

RESUMO

Various vaccines have been challenged by SARS-CoV-2 variants. Here, we reported a yeast-derived recombinant bivalent vaccine (Bivalent wild-type [Wt]+De) based on the wt and Delta receptor-binding domain (RBD). Yeast derived RBD proteins based on the wt and Delta mutant were used as the prime vaccine. It was found that, in the presence of aluminium hydroxide (Alum) and unmethylated CpG-oligodeoxynucleotides (CpG) adjuvants, more cross-protective immunity against SARS-CoV-2 prototype and variants were elicited by bivalent vaccine than monovalent wtRBD or Delta RBD. Furthermore, a heterologous boosting strategy consisting of two doses of bivalent vaccines followed by one dose adenovirus vectored vaccine exhibited cross-neutralization capacity and specific T cell responses against Delta and Omicron (BA.1 and BA.4/5) variants in mice, superior to a homologous vaccination strategy. This study suggested that heterologous prime-boost vaccination with yeast-derived bivalent protein vaccine could be a potential approach to address the challenge of emerging variants.


Assuntos
COVID-19 , Vacinas , Animais , Camundongos , Vacinas Combinadas , Proteínas Fúngicas , Saccharomyces cerevisiae/genética , COVID-19/prevenção & controle , SARS-CoV-2 , Vacinação
6.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 38(2): 145-150, 2024 Feb 15.
Artigo em Chinês | MEDLINE | ID: mdl-38385225

RESUMO

Objective: To analyze the effect of stump-preserving repair on rotator cuff healing and shoulder function for degenerative total rotator cuff tears. Methods: A clinical data of 152 patients with degenerative total rotator cuff tears, who underwent arthroscopic repair between April 2019 and May 2022, was retrospectively analyzed. There were 76 males and 76 females with an average age of 55.4 years (range, 24-78 years). MRI was performed at 6 months postoperatively to evaluate the rotator cuff healing according to the Sugaya classification. Pre- and intra-operative related factors were included for univariate analysis, including age (≥60 years/<60 years), gender (male/female), passive activity disorder (yes/no), disease duration (≤3 months/>3 months), stump-preserving repair (yes/no), use of suture bridge technique (yes/no), shoulder joint abduction angle at knotting (<45°/≥45°), acromioplasty (yes/no), glucocorticoid injection (yes/no), time for patients to start postoperative passive exercise (≤2 weeks/>2 weeks), and time for patients to start postoperative active exercise (≤3 months/>3 months). The influencing factors of tendon healing were screened; further logistic regression was used to conduct multivariate analysis to screen for risk factors. Two sets of data were balanced by propensity score matching. The American Shoulder and Elbow Surgeons (ASES) score and Constant-Murley score of shoulder joint function at 6 and 12 months postoperatively, as well as rotator cuff healing rate at 6 months postoperatively, were compared between groups based on whether or not stump-preserving repair was used. Results: All patients were followed up 12-33 months (mean, 23.8 months). MRI at 25-31 weeks postoperatively showed the 121 cases of rotator cuff healing and 31 cases of non healing. Univariate analysis showed that the disease duration, stump-preserving repair, shoulder joint abduction angle at knotting, and the time for patients to start postoperative active exercise were the influencing factors of rotator cuff healing ( P<0.05). Multivariate analysis showed that non-stump-preserving repair, shoulder abduction angle more than 45° at knotting, and the time to start active exercise within 3 months postoperatively were risk factors affecting rotator cuff healing ( P<0.05). A total of 51 pairs of cases were matched based on the grouping criteria of whether the disease duration exceeded 3 months, whether the shoulder abduction angle at knotting exceeded 45°, and whether the time to start postoperative active exercise exceeded 3 months. The rotator cuff healing rate, ASES score, and Constant-Murley score of the preserving repair group at 6 months postoperatively were superior to those of the non-preserving repair group, and the differences were significant ( P<0.05). There was no significant difference in ASES score and Constant-Murley score between the two groups at 12 months postoperatively ( P>0.05). Conclusion: For degenerative total rotator cuff tears, the stump-preserving repair can shorten the healing time and promote the shoulder function recovery, but has no significant effect on shoulder function at 1 year postoperatively.


Assuntos
Lesões do Manguito Rotador , Articulação do Ombro , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/cirurgia , Ombro , Estudos Retrospectivos , Resultado do Tratamento , Artroscopia/métodos , Articulação do Ombro/cirurgia , Imageamento por Ressonância Magnética , Amplitude de Movimento Articular
7.
Adv Mater ; 36(15): e2308217, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38198412

RESUMO

Topical therapy is a favored route for treating skin cancers, but remain many challenges, such as low delivery efficiency, limited tumor tissue penetration, and unsatisfactory blood circulation. Here, a self-heating microneedle (MN) patch with multilevel structures, including a dissolvable base for rapid drug release, a degradable tip for sustained drug release, and a self-heating substrate is described. The thermally enhanced drug release performance is validated through both in vitro and in vivo experiments. High tumor therapeutic efficacy can be achieved due to the rapid release of 5-fluorouracil, while the sustained release of thymoquinone endows the MN patch with long-term tumor inhibition ability. It is further demonstrated the feasibility of such an MN patch for in vivo topical therapy of cutaneous squamous cell carcinoma with high efficacy, low side effects, and long-term inhibition of recurrence. This self-heating MN patch holds great promise for potential clinical applications, especially for the treatment of skin cancers.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Calefação , Sistemas de Liberação de Medicamentos , Preparações Farmacêuticas , Pele/patologia
8.
Clin Pharmacol Ther ; 115(2): 256-268, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37994531

RESUMO

Sacituzumab govitecan is widely used for the treatment of breast cancer and urothelial carcinoma, but available information regarding adverse events (AEs) is limited. We aim to explore the AE induced by sacituzumab govitecan by mining the FDA Adverse Event Reporting System (FAERS) database. The association between sacituzumab govitecan and AEs was evaluated using the information component. A multivariate logistic regression analysis was conducted for all identified signals to explore the risk factors associated with AEs leading to hospitalization. In total, 1,884 reports related to sacituzumab govitecan were retrieved, and 114 AE signals involving 20 systems were identified. The median time for onset of AEs was ~ 6-7 days after initiating treatment with sacituzumab govitecan, with over 80% of AEs occurring within 30 days. Subgroup analysis revealed that 14 signals were reported in men and 110 in women. There were 58 signals reported in patients under 65 following the use of sacituzumab govitecan, 59 signals in patients over 65, and 31 signals were present in both groups. Multivariable analysis showed that being male and the occurrence of colitis, pneumonitis, febrile neutropenia, pyrexia, sepsis, dehydration, and diarrhea were risk factors leading to hospitalization with an area under the curve (AUC) of 0.89. Additionally, sensitivity analysis revealed that this study had good robustness. This is the first retrospective analysis based on FAERS to review the safety of sacituzumab govitecan. The results highlight the need to closely monitor adverse reactions such as neutropenia, diarrhea, colitis, and sepsis when using sacituzumab govitecan.


Assuntos
Anticorpos Monoclonais Humanizados , Camptotecina/análogos & derivados , Carcinoma de Células de Transição , Colite , Imunoconjugados , Sepse , Neoplasias da Bexiga Urinária , Humanos , Masculino , Feminino , Farmacovigilância , Estudos Retrospectivos , Diarreia
9.
Front Pharmacol ; 14: 1231320, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38044938

RESUMO

Objective: While several drugs have been linked to acute pancreatitis (AP), the AP-related risk of most drugs remains unclear. This study investigated the risk factors for drug-induced AP by analyzing a large dataset from the FDA Adverse Event Reporting System (FAERS). Methods: The reporting odds ratios (ROR) were used to assess the reports of drug-induced AP from the first quarter of 2004 to the second quarter of 2022. Single-factor, LASSO, and multi-factor regression analysis were performed to explore drug-related AP-related risk factors. Bonferroni correction was applied for the multiple comparisons performed. Results: A total of 264 drugs associated with AP, including antineoplastic drugs (35/264), antidiabetic drugs (28/264), antibacterial drugs (24/264), immunomodulatory drugs (11/264), antipsychotic drugs (6/264), and other drugs (160/264) were retrieved. Multi-factor analysis showed that males, age 41-54 years old, and 36 drugs, including Tigecycline, were risk factors for drug-related AP. The median time to drug-related AP onset was 31 days (interquartile range [IQR] 7-102 days) and about 75% of adverse events occurred within 100 days. Conclusion: These findings may help clinicians to identify drug-related AP at the early stage and can be used to inform future studies of drug-related AP pathogenesis.

10.
Immun Inflamm Dis ; 11(11): e1050, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38018586

RESUMO

OBJECTIVE: The aim of this study was to elucidate the mechanism of beraprost sodium (BPS) in the intervention of myocardial fibrosis after myocardial infarction (MI) through glycogen synthase kinase-3ß (GSK-3ß) and to provide new ideas for intervention in myocardial fibrosis. MATERIALS AND METHODS: MI model rats given BPS and cardiac fibroblasts (CFs) treated with BPS and TGF-ß. HE staining and Masson staining were used to detect the pathological changes of myocardial tissue. Fibrotic markers were detected by immunohistochemical staining. The expressions of GSK-3ß, cAMP response element binding protein (CREB), and p-CREB were analyzed by qPCR and western blot analysis. EDU staining was used to detect the proliferation of CFs. The promoter activity of GSK-3ß was detected by luciferase assay. Chromatin immunoprecipitation assay was used to detect the binding levels of GSK-3ß promoter and Y-box binding protein 1 (YBX1). The levels of intracellular cyclic adenosine monophosphate (cAMP) were analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: After operation, BPS improved myocardial fibrosis and upregulated GSK-3ß protein expression in male SD rats. BPS can down-regulate α-smooth muscle actin (α-SMA) level and up-regulate GSK-3ß protein expression in CFs after TGF-ß stimulation. Furthermore, GSK-3ß knockdown can reverse the effect of BPS on TGF-ß-activated CFs, enhance α-SMA expression, and promote the proliferation of CFs. BPS could regulate GSK-3ß expression by promoting the binding of GSK-3ß promoter to YBX1. BPS induced upregulation of p-CREB and cAMP, resulting in reduced fibrosis, which was reversed by the knockdown of GSK-3ß or prostaglandin receptor (IPR) antagonists. CONCLUSION: BPS treatment increased the binding of YBX1 to the GSK-3ß promoter, and GSK-3ß protein expression was upregulated, which further caused the upregulation of p-CREB and cAMP, and finally inhibited myocardial fibrosis.


Assuntos
Infarto do Miocárdio , Ratos , Animais , Masculino , Glicogênio Sintase Quinase 3 beta , Ratos Sprague-Dawley , Infarto do Miocárdio/tratamento farmacológico , Fator de Crescimento Transformador beta , Fibrose
11.
Drug Des Devel Ther ; 17: 3249-3267, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37954484

RESUMO

Background: Combination of Panax quinquefolium L and Salvia miltiorrhiza Bunge. (PS) has been widely used in the clinical treatment of ischemic heart disease. The purpose of this study was to explore the therapeutic effect and mechanism of PS on angiogenesis in rats after acute myocardial infarction (AMI). Methods: A rat model of AMI was established by ligating the left anterior descending (LAD) artery. The grouping and administration scheme were as follows: sham group, model group, PS low-dose (PS-L) group, PS high-dose (PS-H) group, PX-478 group and angiotensin converting enzyme inhibitor (ACEI) group. After 28 days of treatment, echocardiography, myocardial infarct size, some angiogenesis markers and the miR-155-5p/HIF-1α/VEGF axis were measured. Results: PS improved cardiac structure and function, reduced infarct size, and alleviated myocardial fibrosis and inflammatory cell infiltration in AMI rats. Mechanistically, PS enhanced the expression of HGF and bFGF in serum, increased the levels of MVD and CD31 in myocardial tissues, and inhibited the activation of the miR-155-5p/HIF-1α/VEGF pathway, which ultimately promoted angiogenesis. In addition, the regulatory effect of PS on angiogenesis was partly abolished by PX-478. Conclusion: PS increased the expression of MVD and CD31 in the myocardium and stimulated angiogenesis. The above effects of PS may be associated with the inhibition of the miR-155-5p/HIF-1α/VEGF axis.


Assuntos
MicroRNAs , Infarto do Miocárdio , Panax , Salvia miltiorrhiza , Animais , Ratos , Subunidade alfa do Fator 1 Induzível por Hipóxia , MicroRNAs/metabolismo , Infarto do Miocárdio/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
12.
Chin Med ; 18(1): 132, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37833746

RESUMO

Ferroptosis is a non-apoptotic form of regulated cell death characterized by iron-dependent lipid peroxidation. It can be triggered by various mechanisms, including the glutathione peroxidase 4 (GPX4)-glutathione (GSH) axis, iron metabolism, lipid metabolism, the GTP cyclohydrolase 1 (GCH1)-tetrahydrobiopterin (BH4) pathway, and the ferroptosis suppressor protein 1 (FSP1)-coenzyme Q10 axis. The redox balance is disrupted when ferroptosis occurs in cells, which is fatal to cancer cells. Additionally, some tumor-associated genes are involved in ferroptosis. Hence, targeting ferroptosis might be an effective strategy for treating cancer. Several small-molecule compounds exhibit anti-tumor effects through ferroptosis, including sorafenib and altretamine, which induce ferroptosis by inhibiting System-Xc and GPX4 respectively, but many problems, such as poor druggability, still exist. Some studies have shown that many traditional Chinese medicine (TCM) induce ferroptosis by inhibiting GPX4, solute carrier family 7 member 11 (SLC7A11), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), or by increasing the expression of Acyl-CoA synthetase long-chain family member 4 (ACSL4), transferrin (TF), and transferrin receptor 1 (TFR1). These changes can lead to the lysosomal degradation of ferritin, accumulation of iron, lipid peroxidation and the production of reactive oxygen species (ROS), which in turn can promote anti-tumor activities or synergistic effects with chemotherapeutic drugs. In this study, we elucidated the underlying mechanisms of ferroptosis, and the anti-tumor pharmacology of TCM targeting ferroptosis including prescriptions, Chinese herbs, extracts, and natural compounds. Our findings might act as valuable reference for research on anti-tumor drugs targeting ferroptosis, especially those drugs developed from TCM.

13.
Molecules ; 28(18)2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37764486

RESUMO

The application of semiconductor metal oxides in chemiresistive methane gas sensors has seen significant progress in recent years, driven by their promising sensitivity, miniaturization potential, and cost-effectiveness. This paper presents a comprehensive review of recent developments and future perspectives in this field. The main findings highlight the advancements in material science, sensor fabrication techniques, and integration methods that have led to enhanced methane-sensing capabilities. Notably, the incorporation of noble metal dopants, nanostructuring, and hybrid materials has significantly improved sensitivity and selectivity. Furthermore, innovative sensor fabrication techniques, such as thin-film deposition and screen printing, have enabled cost-effective and scalable production. The challenges and limitations facing metal oxide-based methane sensors were identified, including issues with sensitivity, selectivity, operating temperature, long-term stability, and response times. To address these challenges, advanced material science techniques were explored, leading to novel metal oxide materials with unique properties. Design improvements, such as integrated heating elements for precise temperature control, were investigated to enhance sensor stability. Additionally, data processing algorithms and machine learning methods were employed to improve selectivity and mitigate baseline drift. The recent developments in semiconductor metal oxide-based chemiresistive methane gas sensors show promising potential for practical applications. The improvements in sensitivity, selectivity, and stability achieved through material innovations and design modifications pave the way for real-world deployment. The integration of machine learning and data processing techniques further enhances the reliability and accuracy of methane detection. However, challenges remain, and future research should focus on overcoming the limitations to fully unlock the capabilities of these sensors. Green manufacturing practices should also be explored to align with increasing environmental consciousness. Overall, the advances in this field open up new opportunities for efficient methane monitoring, leak prevention, and environmental protection.

14.
Molecules ; 28(18)2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37764496

RESUMO

Graphene is an emerging nanomaterial increasingly being used in electrochemical biosensing applications owing to its high surface area, excellent conductivity, ease of functionalization, and superior electrocatalytic properties compared to other carbon-based electrodes and nanomaterials, enabling faster electron transfer kinetics and higher sensitivity. Graphene electrochemical biosensors may have the potential to enable the rapid, sensitive, and low-cost detection of cancer biomarkers. This paper reviews early-stage research and proof-of-concept studies on the development of graphene electrochemical biosensors for potential future cancer diagnostic applications. Various graphene synthesis methods are outlined along with common functionalization approaches using polymers, biomolecules, nanomaterials, and synthetic chemistry to facilitate the immobilization of recognition elements and improve performance. Major sensor configurations including graphene field-effect transistors, graphene modified electrodes and nanocomposites, and 3D graphene networks are highlighted along with their principles of operation, advantages, and biosensing capabilities. Strategies for the immobilization of biorecognition elements like antibodies, aptamers, peptides, and DNA/RNA probes onto graphene platforms to impart target specificity are summarized. The use of nanomaterial labels, hybrid nanocomposites with graphene, and chemical modification for signal enhancement are also discussed. Examples are provided to illustrate applications for the sensitive electrochemical detection of a broad range of cancer biomarkers including proteins, circulating tumor cells, DNA mutations, non-coding RNAs like miRNA, metabolites, and glycoproteins. Current challenges and future opportunities are elucidated to guide ongoing efforts towards transitioning graphene biosensors from promising research lab tools into mainstream clinical practice. Continued research addressing issues with reproducibility, stability, selectivity, integration, clinical validation, and regulatory approval could enable wider adoption. Overall, graphene electrochemical biosensors present powerful and versatile platforms for cancer diagnosis at the point of care.


Assuntos
Grafite , Neoplasias , Reprodutibilidade dos Testes , Carbono , Anticorpos , Biomarcadores Tumorais , Neoplasias/diagnóstico
15.
Am J Chin Med ; 51(7): 1627-1651, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37638827

RESUMO

The tumor microenvironment (TME) plays an important role in the development of tumors. Immunoregulatory cells and cytokines facilitate cancer cells to avoid immune surveillance. Overexpression of immune checkpoint molecules such as CTLA-4 and PD-1/PD-L1 inhibits immune function and enables cancer cells to avoid clearance by the immune system. Thus, minimizing tumor immunosuppression could be an important strategy for cancer therapy. Currently, many immune checkpoint-targeted drugs, such as PD-1/PD-L1 inhibitors, have been approved for marketing and have shown unique advantages in the clinical treatment of cancers. The concept of "strengthening resistance to eliminate pathogenic factors" in traditional Chinese medicine (TCM) is consistent with the immunotherapy of cancer. According to previous studies, the role of TCM in tumor immunotherapy is mainly associated with the positive regulation of natural killer cells, CD8/CD4 T cells, dendritic cells, M2 macrophages, interleukin-2, tumor necrosis factor-[Formula: see text], and IFN-[Formula: see text], as well as with the negative regulation of Tregs, myeloid-derived suppressor cells, cancer-associated fibroblasts, PD-1/PD-L1, transforming growth factor-[Formula: see text], and tumor necrosis factor-[Formula: see text]. This paper summarizes the current research on the effect of TCM targeting the TME, and further introduces the research progress on studying the effects of TCM on immune checkpoints. Modern pharmacological studies have demonstrated that TCM can directly or indirectly affect the TME by inhibiting the overexpression of immune checkpoint molecules and enhancing the efficacy of tumor immunotherapy. TCM with immunomodulatory stimulation could be the key factor to achieve benefits from immunotherapy for patients with non-inflammatory, or "cold", tumors.


Assuntos
Antígeno B7-H1 , Neoplasias , Humanos , Antígeno B7-H1/farmacologia , Medicina Tradicional Chinesa , Proteínas de Checkpoint Imunológico/farmacologia , Receptor de Morte Celular Programada 1 , Neoplasias/patologia , Imunoterapia , Fatores de Necrose Tumoral/farmacologia , Microambiente Tumoral
16.
Adv Mater ; 35(42): e2305368, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37459236

RESUMO

The development of safe and high-energy metal anodes represents a crucial research direction. Here, the achievement of highly reversible, dendrite-free transition metal anodes with ultrahigh capacities by regulating aqueous electrolytes is reported. Using nickel (Ni) as a model, theoretical and experimental evidence demonstrating the beneficial role of chloride ions in inhibiting and disrupting the nickel hydroxide passivation layer on the Ni electrode is provided. As a result, Ni anodes with an ultrahigh areal capacity of 1000 mAh cm-2 (volumetric capacity of ≈6000 mAh cm-3 ), and a Coulombic efficiency of 99.4% on a carbon substrate, surpassing the state-of-the-art metal electrodes by approximately two orders of magnitude, are realized. Furthermore, as a proof-of-concept, a series of full cells based on the Ni anode is developed. The designed Ni-MnO2 full battery exhibits a long lifespan of 2000 cycles, while the Ni-PbO2 full battery achieves a high areal capacity of 200 mAh cm-2 . The findings of this study are important for enlightening a new arena toward the advancement of dendrite-free Ni-metal anodes with ultrahigh capacities and long cycle life for various energy-storage devices.

17.
Org Lett ; 25(26): 4874-4879, 2023 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-37358471

RESUMO

Two novel cinnamoyl-containing nonribosomal peptides (CCNPs) grisgenomycin A and B were identified in Streptomyces griseus NBRC 13350 (CGMCC 4.5718) and ATCC 12475, through genome mining using conserved adjacent LuxR family regulators as probes and activators. Notably, grisgenomycins represent a new group of bicyclic decapeptides featuring an unprecedented C-C bond between the tryptophan carbocycle and the cinnamoyl group. A plausible biosynthetic pathway for grisgenomycins was deduced by a bioinformatics analysis. Grisgenomycins exhibited activity against human coronaviruses at the micromolar level.


Assuntos
Streptomyces griseus , Streptomyces , Humanos , Streptomyces/genética , Streptomyces/metabolismo , Peptídeos/química , Genoma Bacteriano , Vias Biossintéticas/genética , Família Multigênica
18.
Med Sci Monit ; 29: e939350, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37221818

RESUMO

BACKGROUND The purpose of this study was to determine whether PA is associated with asthma control using data from the National Health and Nutrition Examination Survey (NHANES) for 2011-2020. We did not find a relationship between physical activity (PA) and asthma control. MATERIAL AND METHODS In this study, we measured asthma control by counting asthma attacks and emergency room visits for asthma in the past year. Physical activity was divided into recreational physical activity and work physical activity. A total of 3158 patients (≥20 years old) were included in the study, of which 2375 were in the asthma attack group and 2844 were in the emergency care group, with indicators of asthma control and physical activity as dichotomous variables. Multiple sets of covariates were selected, such as age, gender, and race. Multiple logistic regression analysis and subgroup analysis were used to analyze the data. RESULTS Active workload was significantly correlated with acute asthma attacks, but the relationship with emergency care was not statistically significant. We found that the relationship between physical activity and emergency care was influenced by race, education, and economic level. CONCLUSIONS The amount of work activity was correlated with acute asthma attacks, and the relationship between physical activity and emergency case was influenced by race, education, and economic level.


Assuntos
Asma , Serviços Médicos de Emergência , Humanos , Adulto , Adulto Jovem , Inquéritos Nutricionais , Exercício Físico , Escolaridade
19.
Front Immunol ; 14: 1142394, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37006275

RESUMO

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV) variants has been associated with the transmission and pathogenicity of COVID-19. Therefore, exploring the optimal immunisation strategy to improve the broad-spectrum cross-protection ability of COVID-19 vaccines is of great significance. Herein, we assessed different heterologous prime-boost strategies with chimpanzee adenovirus vector-based COVID-19 vaccines plus Wuhan-Hu-1 (WH-1) strain (AdW) and Beta variant (AdB) and mRNA-based COVID-19 vaccines plus WH-1 strain (ARW) and Omicron (B.1.1.529) variant (ARO) in 6-week-old female BALB/c mice. AdW and AdB were administered intramuscularly or intranasally, while ARW and ARO were administered intramuscularly. Intranasal or intramuscular vaccination with AdB followed by ARO booster exhibited the highest levels of cross-reactive IgG, pseudovirus-neutralising antibody (PNAb) responses, and angiotensin-converting enzyme-2 (ACE2)-binding inhibition rates against different 2019-nCoV variants among all vaccination groups. Moreover, intranasal AdB vaccination followed by ARO induced higher levels of IgA and neutralising antibody responses against live 2019-nCoV than intramuscular AdB vaccination followed by ARO. A single dose of AdB administered intranasally or intramuscularly induced broader cross-NAb responses than AdW. Th1-biased cellular immune response was induced in all vaccination groups. Intramuscular vaccination-only groups exhibited higher levels of Th1 cytokines than intranasal vaccination-only and intranasal vaccination-containing groups. However, no obvious differences were found in the levels of Th2 cytokines between the control and all vaccination groups. Our findings provide a basis for exploring vaccination strategies against different 2019-nCoV variants to achieve high broad-spectrum immune efficacy.


Assuntos
COVID-19 , Vacinas Virais , Feminino , Humanos , Animais , Camundongos , Vacinas contra COVID-19 , SARS-CoV-2 , COVID-19/prevenção & controle , RNA Mensageiro , Imunização , Vacinação , Anticorpos Neutralizantes , Imunidade Celular
20.
Int J Biol Macromol ; 239: 124358, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37028615

RESUMO

The Fructus cannabis protein extract powder (FP), was firstly used as a green and high effective corrosion inhibitor through a simple water-extraction method. The composition and surface property of FP were characterized by FTIR, LC/MS, UV, XPS, water contact angle and AFM force-curve measurements. Results indicate that FP contains multiply functional groups, such as NH, CO, CN, CO, etc. The adsorption of FP on the carbon steel surface makes it higher hydrophobicity and adhesion force. The corrosion inhibition performance of FP was researched by electrochemical impedance, polarization curve and differential capacitance curve. Moreover, the inhibitive stability of FP, and the effects of temperature and chloride ion on its inhibition property were also investigated. The above results indicate that the FP exhibits excellent corrosion inhibition efficiency (~98 %), and possesses certain long-term inhibitive stability with inhibition efficiency higher than 90 % after 240 h immersion in 1 M HCl solution. The high temperature brings about the FP desorption on the carbon steel surface, while high concentration of chloride ion facilitates the FP adsorption. The adsorption mechanism of FP follows the Langmuir isotherm adsorption. This work will provide an insight for protein as a green corrosion inhibitor.


Assuntos
Cannabis , Pós , Aço/química , Corrosão , Cloretos , Carbono , Água/química
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