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1.
Med Int (Lond) ; 4(5): 45, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38983794

RESUMO

Numerous antibody biomarkers have been reported for cancer and atherosclerosis-related diseases. The major complications of atherosclerosis and diabetes mellitus (DM) are acute ischemic stroke (AIS), cardiovascular disease (CVD) and chronic kidney disease (CKD). Cancer development is accompanied by arterial disorders, such as angiogenesis and atherosclerosis, and DM is a risk factor for the development of certain types of cancer. Atherosclerosis-related diseases and cancers are therefore interrelated and could be detected using a common biomarker. In the present study, the initial screening using the protein array method identified KIAA0513 as an antigen recognized by serum IgG antibodies in patients with atherosclerosis. The amplified luminescent proximity homogeneous assay-linked immunosorbent assay revealed significantly higher serum antibody levels against recombinant KIAA0513 protein in patients with AIS, transient ischemic attack (TIA), DM, CVD, obstructive sleep apnea syndrome (OSAS), CKD and solid cancers, such as esophageal, gastric, colon, lung and breast cancers, compared with healthy donors. A receiver operating characteristic (ROC) analysis revealed that the highest areas under the ROC curves of anti-KIAA0513 antibodies were obtained for esophageal cancer, nephrosclerosis-type CKD and DM. Spearman's correlation analysis revealed that serum anti-KIAA0513 antibody levels were associated with maximum intima-media thickness and plaque score, which are indices of atherosclerosis and stenosis. Serum anti-KIAA0513 antibody markers appear to be useful for diagnosing AIS, TIA, DM, CVD, OSAS, CKD and solid cancers, and may reflect common arterial alterations leading to atherosclerotic and cancerous diseases.

2.
Adv Mater ; : e2406632, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38943432

RESUMO

As the core component of all-solid-state batteries, current solid-state electrolytes fail to simultaneously meet multiple demands, such as their own high performance, the chemical, electrochemical and mechanical compatibility of electrode interface. A fresh perspective is rather desired to guide the development of novel solid electrolytes with comprehensive performance. Herein, this work proposes a novel strategy to synthesize solid electrolytes extracted from cathode-electrolyte interphase (CEI), which is inspired by peach trees secreting peach gum to prevent further damage. A proof-of-concept, using LiBH4-Se and LiBH4-S as prototypes, confirms that as-synthesized electrolytes inherited and improved up the advantages of LiBH4 with unexpected compatibility toward multiple cathodes. It is believed that the family of new electrolytes will be continuously expanded under the guidance of this CEI-derived concept.

3.
Int J Mol Sci ; 25(10)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38791507

RESUMO

The relationship between energy production and cancer is attracting attention. This study aimed to investigate the clinicopathological significance of fumarate hydratase (FH), a tricarboxylic acid cycle enzyme, in gastric cancer using autoantibodies as biomarkers. The study analyzed 116 patients who underwent gastric cancer surgery and 96 healthy controls. Preoperative serum FH autoantibody (s-FH-Ab) titers were analyzed using an immunosorbent assay with an amplified luminescent proximity homogeneous assay. Receiver operating characteristic analysis was used to determine the cutoff s-FH-Ab titer. Clinicopathological factors and prognosis were compared between the high and low s-FH-Ab groups. The s-FH-Ab levels were significantly higher in the gastric cancer group than in the control group (p = 0.01). Levels were elevated even in patients with stage I gastric cancer compared with healthy controls (p = 0.02). A low s-FH-Ab level was significantly associated with distant metastasis (p = 0.01), peritoneal dissemination (p < 0.05), and poor overall survival (p < 0.01). Multivariate analysis revealed that low s-FH-Ab levels were an independent risk factor for poor prognosis (p < 0.01). Therefore, s-FH-Ab levels may be a useful biomarker for early diagnosis and the prediction of prognosis in patients with gastric cancer.


Assuntos
Autoanticorpos , Biomarcadores Tumorais , Fumarato Hidratase , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Fumarato Hidratase/sangue , Masculino , Feminino , Autoanticorpos/sangue , Autoanticorpos/imunologia , Pessoa de Meia-Idade , Prognóstico , Idoso , Biomarcadores Tumorais/sangue , Estadiamento de Neoplasias , Adulto , Curva ROC , Estudos de Casos e Controles
4.
Cell Signal ; 120: 111231, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38768760

RESUMO

Glioma is a highly invasive and aggressive type of brain cancer with poor treatment response. Stemness-related transcription factors form a regulatory network that sustains the malignant phenotype of gliomas. We conducted an integrated analysis of stemness-related transcription factors using The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) datasets, established the characteristics of stemness-related transcription factors, including Octamer-Binding Protein 4 (OCT4), Meis Homeobox 1 (MEIS1), E2F Transcription Factor 1 (E2F1), Transcription Factor CP2 Like 1 (TFCP2L1), and RUNX Family Transcription Factor 1 (RUNX1). The characteristic of stemness-related transcription factors was identified as an independent prognostic factor for glioma patients. Patients in the high-risk group have a worse prognosis than those in the low-risk group. The glioma microenvironment in the high-risk group exhibited a more active immune status. Single-cell level analysis revealed that stem cell-like cells exhibited stronger intercellular communication than glioma cells. Meanwhile, patients in different risk stratification exhibited varying sensitivities to immunotherapy and small molecule drug therapy. XMD8-85 was more effective in the high-risk group, and its antitumor effects were validated both in vivo and in vitro. Our results indicate that this prognostic feature will assist clinicians in predicting the prognosis of glioma patients, guiding immunotherapy and personalized treatment, as well as the potential clinical application of XMD8-85 in glioma treatment, and helping to develop effective treatment strategies.


Assuntos
Neoplasias Encefálicas , Glioma , Células-Tronco Neoplásicas , Humanos , Glioma/patologia , Glioma/tratamento farmacológico , Glioma/genética , Glioma/metabolismo , Prognóstico , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Animais , Camundongos , Microambiente Tumoral , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Camundongos Nus , Masculino , Feminino , Fatores de Transcrição/metabolismo
5.
Int J Mol Sci ; 25(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38732153

RESUMO

Inflammation is closely associated with cerebrovascular diseases, cardiovascular diseases, diabetes, and cancers, and it is accompanied by the development of autoantibodies in the early stage of inflammation-related diseases. Hence, it is meaningful to discover novel antibody biomarkers targeting inflammation-related diseases. In this study, Jumonji C-domain-containing 6 (JMJD6) was identified by the serological identification of antigens through recombinant cDNA expression cloning. In particular, JMJD6 is an antigen recognized in serum IgG from patients with unstable angina pectoris (a cardiovascular disease). Then, the serum antibody levels were examined using an amplified luminescent proximity homogeneous assay-linked immunosorbent assay and a purified recombinant JMJD6 protein as an antigen. We observed elevated levels of serum anti-JMJD6 antibodies (s-JMJD6-Abs) in patients with inflammation-related diseases such as ischemic stroke, acute myocardial infarction (AMI), diabetes mellitus (DM), and cancers (including esophageal cancer, EC; gastric cancer; lung cancer; and mammary cancer), compared with the levels in healthy donors. The s-JMJD6-Ab levels were closely associated with some inflammation indicators, such as C-reactive protein and intima-media thickness (an atherosclerosis index). A better postoperative survival status of patients with EC was observed in the JMJD6-Ab-positive group than in the negative group. An immunohistochemical analysis showed that JMJD6 was highly expressed in the inflamed mucosa of esophageal tissues, esophageal carcinoma tissues, and atherosclerotic plaques. Hence, JMJD6 autoantibodies may reflect inflammation, thereby serving as a potential biomarker for diagnosing specific inflammation-related diseases, including stroke, AMI, DM, and cancers, and for prediction of the prognosis in patients with EC.


Assuntos
Autoanticorpos , Biomarcadores , Inflamação , Histona Desmetilases com o Domínio Jumonji , Humanos , Autoanticorpos/imunologia , Autoanticorpos/sangue , Biomarcadores/sangue , Inflamação/imunologia , Inflamação/sangue , Feminino , Histona Desmetilases com o Domínio Jumonji/imunologia , Histona Desmetilases com o Domínio Jumonji/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Neoplasias/diagnóstico , Neoplasias/sangue , Idoso , Adulto , Diabetes Mellitus/imunologia , Diabetes Mellitus/sangue
6.
Pharmaceuticals (Basel) ; 17(4)2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38675458

RESUMO

Acute alcoholic liver disease (ALD) resulting from short-term heavy alcohol consumption has become a global health concern. Moreover, anthocyanins have attracted much attention for their ability to prevent oxidation and inflammation. The present work evaluates the protective effects of Lycium ruthenicum Murray (LRM) against ALD and explores the possible underlying mechanism involved. The total anthocyanin content in LRM was 43.64 ± 9.28 Pt g/100 g dry weight. Mice were orally administered 50, 125, or 375 mg LRM/kg body weight (BW) for 21 days. On days 18-21, mice were orally administered 15 mL of ethanol/kg BW. Markers of liver damage, oxidative stress, and inflammation were examined. Furthermore, the modulatory effect of LRM on Nrf2/HO-1/NF-κB pathway molecules was evaluated through quantitative reverse transcription polymerase chain reaction (RT‒qPCR) and immunohistochemistry analyses. The difference between the groups indicated that LRM improved liver histopathology and the liver index, decreased aspartate transaminase, alanine transaminase, malondialdehyde, reactive oxygen species, IL-6, TNF-α, and IL-1ß expression, but elevated superoxide dismutase, catalase, and glutathione-s-transferase levels. Moreover, LRM upregulated Nrf2 and Ho-1 but downregulated Nf-κb and Tnf-α genes at the transcript level. In summary, LRM alleviated ethanol-induced ALD in mice by reducing oxidative damage and associated inflammatory responses. LRM protects against ALD by reducing damage factors and enhancing defense factors, especially via the Nrf2/HO-1/NF-κB pathway. Thus, LRM has application potential in ALD prophylaxis and treatment.

7.
JMIR Form Res ; 8: e51859, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639996

RESUMO

BACKGROUND: In England, digital technologies are exploited to transform the way health and social care is provided and encompass a wide range of hardware devices and software that are used in all aspects of health care. However, little is known about the extent to which health care providers differ in digital health technology capabilities and how this relates to geographical and regional differences in health care capacities and resources. OBJECTIVE: This paper aims to identify the set of digital technologies that have been deployed by the National Health Services clinical commissioning groups (NHS CCGs) in England. In doing this, we respond to calls to shed light on the internal dynamics and variation in the form of digital capability in England in terms of health service regional differences and health diversity, equity, and inclusion. METHODS: We collected 135 annual reports that belong to 106 NHS CCGs in England, comprising more than 18,000 pages in total, released from 2020 to 2021. Using this data set, we identified 2163 pages related to digital technologies and labeled them using content analysis. We follow the construct taxonomy used by digital options theory, a theory from the management information systems field analyzing organizational resource investment choices, in classifying observed technologies according to digital themes-inherent design patterns that we identified and explained. We then used a hierarchical clustering method to extract groups of NHS CCGs that implement similar technology themes. RESULTS: We found 31 technologies from the reports and grouped them into 9 digital themes. The 9 themes were further assigned to 1 of the 3 constructs of digital options theory, the identification of patients' requirements (we identified information portals [76/106], digital health engagement [67/106], and digital inclusion support [45/106]), the development of new work patterns (we identified telehealth [87/106], telemedicine [35/106], and care home technologies [40/106]), the realization of improvements in efficiency and public accessibility (we identified online booking [26/106], online triage [104/106], and digital mental health services [74/106]). The 3 clusters of CCGs are identified based on the 8 themes (Hopkins=0.9914, silhouette=0.186), namely (1) digitally disengaged, (2) digitally engaged, and (3) digital torchbearer. CONCLUSIONS: Our findings show prominent digital themes within each construct group, namely information portals, telehealth, and online triage, covering people's fundamental health information needs. Almost half of CCGs fell into the digitally disengaged group, and all London CCGs (5/106) belonged to this group. We propose that practitioners should offer specialized assistance to regions with limited digital engagement, emphasizing digital health literacy, inclusion support, and ongoing evaluation, rather than concentrating solely on technical advancements.

8.
Cancer Sci ; 115(7): 2209-2219, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38634426

RESUMO

Given that esophageal cancer is highly malignant, the discovery of novel prognostic markers is eagerly awaited. We performed serological identification of antigens by recombinant cDNA expression cloning (SEREX) and identified SKI proto-oncogene protein and transmembrane p24 trafficking protein 5 (TMED5) as antigens recognized by serum IgG antibodies in patients with esophageal carcinoma. SKI and TMED5 proteins were expressed in Escherichia coli, purified by affinity chromatography, and used as antigens. The serum anti-SKI antibody (s-SKI-Ab) and anti-TMED5 antibody (s-TMED5-Ab) levels were significantly higher in 192 patients with esophageal carcinoma than in 96 healthy donors. The presence of s-SKI-Abs and s-TMED5-Abs in the patients' sera was confirmed by western blotting. Immunohistochemical staining showed that the TMED5 protein was highly expressed in the cytoplasm and nuclear compartments of the esophageal squamous cell carcinoma tissues, whereas the SKI protein was localized predominantly in the nuclei. Regarding the overall survival in 91 patients who underwent radical surgery, the s-SKI-Ab-positive and s-TMED5-Ab-negative statuses were significantly associated with a favorable prognosis. Additionally, the combination of s-SKI-Ab-positive and s-TMED5-Ab-negative cases showed an even clearer difference in overall survival as compared with that of s-SKI-Ab-negative and s-TMED5-Ab-positive cases. The s-SKI-Ab and s-TMED5-Ab biomarkers are useful for diagnosing esophageal carcinoma and distinguishing between favorable and poor prognoses.


Assuntos
Biomarcadores Tumorais , Neoplasias Esofágicas , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas , Humanos , Neoplasias Esofágicas/imunologia , Prognóstico , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores Tumorais/sangue , Idoso , Proteínas Proto-Oncogênicas/imunologia , Proteínas de Ligação a DNA/imunologia , Adulto , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas do Esôfago/imunologia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Idoso de 80 Anos ou mais , Proteínas de Membrana/imunologia
9.
Pharmaceuticals (Basel) ; 17(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38543108

RESUMO

Cadmium (Cd) is a hazardous heavy metal environmental pollutant that has carcinogenic, teratogenic, and mutagenic properties. Excessive exposure to Cd can induce oxidative stress, which greatly harms the male reproductive system. Anthocyanins have remarkable antioxidative, anti-inflammatory, and anti-stress properties. In this study, we investigated the effects of anthocyanins and the underlying mechanisms through which anthocyanins mitigate Cd-induced reproductive damage. We isolated and purified Lycium ruthenicum Murray anthocyanin extract (LAE) and performed UHPLC-MS/MS to identify 30 different anthocyanins. We established an ICR mouse Cd injury model by administering 5 mg/kg/day CdCl2 for 28 consecutive days. LAE at 500 mg/kg/day effectively ameliorated testicular damage and preserved spermatogenesis. The mice in the LAE-treated group had elevated testosterone and inhibin B levels. Additionally, the treatment restored the activity of antioxidant enzymes, including T-SOD, CAT, and GR, and substantially increased the levels of the non-enzymatic antioxidant GSH. Research findings indicate that LAE can activate the SIRT1/Nrf2/Keap1 antioxidant pathway. This activation is achieved through the upregulation of both the SIRT1 gene and protein levels, leading to the deacetylation of Nrf2. Moreover, LAE reduces the expression of Keap1, alleviating its inhibitory effect on Nrf2. This, in turn, facilitates the uncoupling process, promoting the translocation of Nrf2 to the nucleus, where it governs downstream expression, including that of HO-1 and GPX1. LAE effectively mitigated toxicity to the reproductive system associated with exposure to the heavy metal Cd by alleviating oxidative stress in the testes.

10.
J Exp Child Psychol ; 242: 105908, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38502999

RESUMO

Influenced by the epidemic and the rapid popularization of smart devices, media multitasking has become increasingly common in people's lives and has attracted the attention of researchers, particularly among adolescents who are native to the digital era. However, previous studies have focused primarily on the relationship between multitasking and general cognitive functions, paying less attention to the connection between multitasking and metacognition, and there is a lack of research specifically addressing adolescents in this context. To address this gap, the current study conducted two experiments with upper primary and secondary school students to explore the relationship between multitasking and adolescents' metacognition under intrinsic and extrinsic cue conditions using metacognitive monitoring as an indicator. The results revealed that multitasking significantly reduced adolescents' metacognitive monitoring accuracy. However, the scores on the media multitasking questionnaire did not significantly correlate with metacognitive monitoring accuracy in the laboratory task. This finding suggested that multitasking, under both intrinsic and extrinsic cue conditions, impairs the accuracy of metacognitive monitoring for primary and secondary school students. However, daily media multitasking activities among these students were not significantly correlated with metacognitive monitoring accuracy.


Assuntos
Metacognição , Adolescente , Humanos , Estudantes , Instituições Acadêmicas
11.
Artigo em Inglês | MEDLINE | ID: mdl-38284383

RESUMO

A Gram-stain-negative, strictly aerobic and filamentous bacterial strain, designated as DQS-5T, was isolated from the activated sludge of a municipal sewage treatment plant in Shenzhen, PR China. Optimal growth was observed at 28 °C and pH 7.5. Catalase and oxidase activities were detected. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain DQS-5T was most closely related to the genera Chitinimonas and Chitinivorax (91.0-93.4 % and 92.5 % 16S rRNA gene sequence similarity, respectively) and was close to the member of the family Burkholderiaceae. The complete genome sequence of strain DQS-5T contains 5 653 844 bp and 57.3 mol% G+C. The average nucleotide identity, digital DNA-DNA hybridization and average amino acid identity values between the genome of strain DQS-5T and those of its close relatives were 75.9-77.2, 19.0-20.3 and 57.2-61.8 %, respectively. Chemotaxonomic analysis of strain DQS-5T indicated that the sole respiratory quinone was ubiquinone-8, the predominant cellular fatty acids were C16 : 0 and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), and the major polar lipids consisted of phosphatidylethanolamine, phosphatidylglycerol, aminophospholipid and aminolipid. The phylogenetic, genotypic, phenotypic and chemotaxonomic data demonstrate that strain DQS-5T represents a novel species in a novel genus within the family Burkholderiaceae, for which the name Parachitinimonas caeni gen. nov., sp. nov., is proposed. Strain DQS-5T (=KCTC 92788T=CCTCC AB 2022320T) is the type and only strain of P. caeni.


Assuntos
Burkholderiaceae , Ácidos Graxos , Ácidos Graxos/química , Fosfolipídeos/química , Esgotos , Filogenia , RNA Ribossômico 16S/genética , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Análise de Sequência de DNA , China
12.
Mol Neurobiol ; 61(8): 4962-4975, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38151613

RESUMO

Copper is essential in living organisms and crucial to various physiological processes. Normal physiological conditions are in a state of copper homeostasis to ensure normal biochemical and metabolic processes. Dysregulation of copper homeostasis has been associated with multiple diseases, especially cancer. Cuproptosis is a copper-dependent cell death mediated by excess copper or homeostasis dysregulation. Elesclomol is a common inducer of cuproptosis, carrying copper into the cell and producing excess copper. Cuproptosis modulates tumor proliferation-related signaling pathways and is closely associated with remodeling the tumor microenvironment. In gliomas, the role of cuproptosis and copper homeostasis needs to be better characterized. This study systematically analyzed cuproptosis-related genes (CRGs) and constructed a cuproptosis signature for gliomas. The signature closely links the subtypes and clinical features of glioma patients. The results showed a greater tendency toward dysregulation of copper homeostasis as the malignant grade of glioma patients increased. In addition, CRGs-signature effectively predicted the sensitivity of glioma cells to elesclomol and verified that elesclomol inhibited glioma mainly through inducing cellular cuproptosis. In summary, we found different copper homeostatic features in gliomas and verified the anticancer mechanism of elesclomol, which provides a theoretical basis for developing novel therapeutic strategies for gliomas.


Assuntos
Neoplasias Encefálicas , Cobre , Glioma , Homeostase , Cobre/metabolismo , Glioma/genética , Glioma/patologia , Glioma/metabolismo , Glioma/tratamento farmacológico , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Hidrazinas
13.
Reg Anesth Pain Med ; 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38050183

RESUMO

BACKGROUND: Cancer pain has a significant impact on patient's quality of life. Astrocytes play an important role in cancer pain signaling. The direct targeting of astrocytes can effectively suppress cancer pain, however, they can cause many side effects. Therefore, there is an urgent need to identify the specific signaling pathways or proteins involved within astrocytes in cancer pain as targets for treating pain. METHODS: A neuropathic cancer pain (NCP) model was established by inoculating mouse S-180 sarcoma cells around the right sciatic nerve in C57BL/6 mice. Spontaneous persistent pain and paw withdrawal thresholds were measured using von Frey filaments. The NCP spinal cord dorsal horn (L4-L6) and mouse astrocyte cell line MA-C were used to study protein palmitoylation using acyl-biotin exchange, real-time polymerase chain reaction, ELISA, western blotting, and immunofluorescent staining. RESULTS: In a cancer pain model, along with tumor growth, peripheral nerve tissue invasion, and cancer pain onset, astrocytes in the dorsal horn of the spinal cord were activated and palmitoyltransferase ZDHHC23 expression was upregulated, leading to increased palmitoylation levels of GFAP and increased secretion of inflammatory factors, such as (C-X-C motif) ligand (CXCL)10 (CXCL-10), interleukin 6, and granulocyte-macrophage colony-stimulating factor. These factors in turn activate astrocytes by activating the signal transducer and activator of transcription 3 (STAT3) signaling pathway. A competitive peptide targeting GFAP palmitoylations was designed to effectively alleviate morphine tolerance in cancer pain treatment as well as cancer pain signaling and inflammatory factor secretion. CONCLUSIONS: In a rodent model, targeting GFAP palmitoylation appears to be an effective strategy in relieving cancer pain and morphine tolerance. Human translational research is warranted.

14.
Molecules ; 28(24)2023 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-38138618

RESUMO

In this study, we designed and developed a DOX nanodrug delivery system (PEG-GA@ZIF-8@DOX) using ZIF-8 as the carrier and glycyrrhetinic acid (GA) as the targeting ligand. We confirmed that DOX was loaded and PEG-GA was successfully modified on the surface of the nanoparticles. The in vitro release profile of the system was investigated at pH 5.0 and 7.4. The cellular uptake, in vitro cytotoxicity, and lysosomal escape characteristics were examined using HepG2 cells. We established an H22 tumor-bearing mouse model and evaluated the in vivo antitumor activity. The results showed that the system had a uniform nanomorphology. The drug loading capacity was 11.22 ± 0.87%. In acidic conditions (pH 5.0), the final release rate of DOX was 57.73%, while at pH 7.4, it was 25.12%. GA-mediated targeting facilitated the uptake of DOX by the HepG2 cells. PEG-GA@ZIF-8@DOX could escape from the lysosomes and release the drug in the cytoplasm, thus exerting its antitumor effect. When the in vivo efficacy was analyzed, we found that the tumor inhibition rate of PEG-GA@ZIF-8@DOX was 67.64%; it also alleviated the loss of the body weight of the treated mice. This drug delivery system significantly enhanced the antitumor effect of doxorubicin in vitro and in vivo, while mitigating its toxic side effects.


Assuntos
Ácido Glicirretínico , Neoplasias Hepáticas , Camundongos , Animais , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Sistemas de Liberação de Medicamentos/métodos
15.
BMC Cancer ; 23(1): 1115, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37974107

RESUMO

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer (NSCLC) and is the leading cause of cancer death worldwide. Its progression is characterized by genomic instability. In turn, the level of genomic instability affects the prognosis and immune status of patients with LUAD. However, the impact of molecular features associated with genomic instability on the tumor microenvironment (TME) has not been well characterized. In addition, the effect of the genes related to genomic instability in LUAD on individualized treatment of LUAD is unknown. METHODS: The RNA-Sequencing, somatic mutation, and clinical data of LUAD patients were downloaded from publicly available databases. A genetic signature associated with genomic instability (GSAGI) was constructed by univariate Cox regression, Lasso regression, and multivariate Cox regression analysis. Bioinformatics analysis investigated the differences in prognosis, immune characteristics, and the most appropriate treatment strategy among different subtypes of LUAD patients. CCK-8 and colony formation verified the various effects of Etoposide on different subtypes of LUAD cell lines. Cell-to-cell communication analysis was performed using the "CellChat" R package. The expression of the risk factors in the GSAGI was verified using real-time quantitative PCR (qRT-PCR) and Immunohistochemistry (IHC). RESULTS: We constructed and validated the GSAGI, consisting of five genes: ANLN, RHOV, KRT6A, SIGLEC6, and KLRG2. The GSAGI was an independent prognostic factor for LUAD patients. Patients in the high-risk group distinguished by the GSAGI are more suitable for chemotherapy. More immune cells are infiltrating the tumor microenvironment of patients in the low-risk group, especially B cells. Low-risk group patients are more suitable for receiving immunotherapy. The single-cell level analysis confirmed the influence of the GSAGI on TME and revealed the Mode of action between tumor cells and other types of cells. qRT-PCR and IHC showed increased ANLN, RHOV, and KRT6A expression in the LUAD cells and tumor tissues. CONCLUSION: This study confirms that genes related to genomic instability can affect the prognosis and immune status of LUAD patients. The GSAGI we identified has the potential to guide clinicians in predicting clinical outcomes, assessing immunological status, and even developing personalized treatment plans for LUAD patients.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Linfócitos B , Instabilidade Genômica , Prognóstico , Microambiente Tumoral/genética
16.
Biochem Biophys Res Commun ; 687: 149196, 2023 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-37939504

RESUMO

Brain gliomas are difficult in the field of tumor therapy because of their high recurrence rate, high mortality rate, and low selectivity of therapeutic agents. The efficacy of Traditional Chinese Medicine (TCM) in the treatment for tumours has been widely recognized. Here, three Chinese herb related molecules, namely Catechins, Caudatin and Cucurbitacin-I, were screened by bioinformatic means, and were found to inhibit the proliferation of glioblastoma T98G cells using Colony-forming and CCK-8 assays. Notably, the simultaneous use of all three molecules could more significantly inhibit the proliferation of glioma cells. Consistent with this, temozolomide, each in the combination with three molecules, could synergistically inhibit the proliferation of T98G cells. Results of qPCR assay was also showed that this inhibition was through the activation of the KDELR2-mediated endoplasmic reticulum stress (ER) pathway. Molecular docking experiments further revealed that Catechins, Caudatin and Cucurbitacin-I could activate ER stress might by targeting KDELR2. Taken together, these results suggest that these herbal molecules have the potential to inhibit the growth of glioma cells and could provide a reference for clinical therapeutic drug selection.


Assuntos
Antineoplásicos , Catequina , Glioblastoma , Glioma , Humanos , Glioblastoma/patologia , Catequina/farmacologia , Cucurbitacinas/farmacologia , Cucurbitacinas/uso terapêutico , Simulação de Acoplamento Molecular , Glioma/patologia , Antineoplásicos/farmacologia , Proliferação de Células , Estresse do Retículo Endoplasmático , Linhagem Celular Tumoral , Apoptose , Proteínas de Transporte Vesicular/metabolismo
17.
Int J Syst Evol Microbiol ; 73(11)2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37990978

RESUMO

A floc-forming bacterial strain, designated HF-7T, was isolated from the activated sludge of an industrial wastewater treatment plant in Hefei, PR China. Cells of this strain were Gram-stain-positive, catalase- and oxidase-negative, facultatively anaerobic, and rod-shaped. Growth occurred at 20-42 °C (optimum, 28 °C), at pH 5.5-10.5 (optimum, pH 7.5) and with 0-8.0 % (w/v) NaCl (optimum, 1 %). The major fatty acid was anteiso-C15 : 0. The polar lipid profile contained phosphatidylglycerol, diphosphatidylglycerol and phosphatidylinositol. The DNA G+C content was 67 mol% from whole genomic sequence analysis. Based on the results of 16S rRNA gene sequence analysis, this strain should be assigned to the genus Tessaracoccus and is closely related to Tessaracoccus arenae CAU 1319T (95.87 % similarity), Tessaracoccus lapidicaptus IPBSL-7T (95.19 %) and Tessaracoccus bendigoensis Ben 106T (94.63 %) but separated from them by large distances in different phylogenetic trees. Based on whole genome analysis, the orthologous average nucleotide identity and in silico DNA-DNA hybridization values against two of the closest relatives were 75.21-76.50 % and 14.2-24.4 %, respectively. The phylogenetic, genotypic, phenotypic and chemotaxonomic data demonstrated that strain HF-7T could be distinguished from its phylogenetically related species and represents a novel species within the genus Tessaracoccus, for which the name Tessaracoccus caeni sp. nov. is proposed. The type strain is HF-7T (=KCTC 49959T=CCTCC AB 2023019T).


Assuntos
Ácidos Graxos , Propionibacteriaceae , Ácidos Graxos/química , Esgotos/microbiologia , Filogenia , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Análise de Sequência de DNA , Composição de Bases , Técnicas de Tipagem Bacteriana , China , Fosfolipídeos/química
18.
BMC Endocr Disord ; 23(1): 239, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37904164

RESUMO

BACKGROUND: Autoantibodies develop in autoimmune diseases, cancer, diabetes mellitus (DM), and atherosclerosis-related diseases. However, autoantibody biomarkers have not been successfully examined for diagnosis and therapy. METHODS: Serological identification of antigens through recombinant cDNA expression cloning (SEREX) was used for primary screening of antigens. The cDNA product was expressed in bacteria and purified. Amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) was used to evaluate antibody levels in serum samples. RESULTS: Phosphoenolpyruvate carboxykinase 1 (PCK1) was recognized as an antigen by serum IgG antibodies in the sera of patients with atherosclerosis. AlphaLISA showed significantly higher serum antibody levels against recombinant PCK1 protein in patients with DM and cardiovascular disease than in healthy donors, but not in those with acute ischemic stroke, transient ischemic attack, or obstructive sleep apnea syndrome. The area under the receiver operating characteristic curve for anti-PCK1 antibodies was 0.7024 for DM. The serum anti-PCK1 antibody levels were associated with age, platelet count, and blood pressure. Anti-PCK1-antibody-positive patients showed significantly lower overall survival than the negative patients. CONCLUSIONS: Serum anti-PCK1 antibody levels were found to be associated with DM. The anti-PCK1 antibody marker is useful for predicting the overall survival of patients with DM.


Assuntos
Aterosclerose , Diabetes Mellitus , AVC Isquêmico , Humanos , DNA Complementar , Prognóstico , Diabetes Mellitus/diagnóstico , Autoanticorpos , Proteínas Recombinantes , Fosfoenolpiruvato Carboxiquinase (GTP) , Peptídeos e Proteínas de Sinalização Intracelular
19.
Org Lett ; 25(41): 7507-7511, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37801002

RESUMO

Two total syntheses are presented for trigoxyphins K and L, tricyclic terpenoids from Trigonostemon xyphophylloides. The first proceeds via electrophlic cyclization in A/C-ring substrates to close the B ring at C4-C5 and then 1O2-mediated hydroxybutenolide formation to trigoxyphin L, with Luche reduction leading to trigoxyphin K. The second route develops from tetralone ring expansion to a B/C-ring intermediate that, by one-step O-demethylation-lactonization-isomerization, affords trigoxyphin K and then trigoxyphin L following enolate oxygenation.

20.
Adv Sci (Weinh) ; 10(32): e2302618, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37747261

RESUMO

All-solid-state sodium-ion batteries have the potential to improve safety and mitigate the cost bottlenecks of the current lithium-ion battery system if a high-performance electrolyte with cost advantages can be easily synthesized. In this study, a one-step dehydrogenation-assisted strategy to synthesize the novel thio-borohydride (Na-B-H-S) electrolyte is proposed, in which both raw material cost and preparation temperature are significantly reduced. By using sodium borohydride (NaBH4 ) instead of B as a starting material, B atoms can be readily released from NaBH4 with much less energy and thus became more available to generate thio-borohydride. The synthesized Na-B-H-S (NaBH4 /Na-B-S) electrolyte exhibits excellent compatibility with current cathode materials, including FeF3 (1.0-4.5 V), Na3 V2 (PO4 )3 (2.0-4.0 V), and S (1.2-2.8 V). This novel Na-B-H-S electrolyte will take a place in mainstream electrolytes because of its advantages in preparation, cost, and compatibility with various cathode materials.

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