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1.
World J Gastrointest Oncol ; 16(9): 3955-3979, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39350983

RESUMO

BACKGROUND: Although gastrointestinal (GI) cancers have been becoming a great public health concern in China, there is currently a lack of comprehensive literature on the overall burden and changing trends of GI cancers in the working-age population. AIM: To assess the burden of GI cancers and to examine the overall, age- and gender-specific trends among the working-age population in China from 1990 to 2019. METHODS: Data were extracted from the Global Burden of Disease Study 2019. The burden of GI cancers was indicated by incidence, mortality, disability-adjusted life-years (DALYs), age-standardized incidence rate (ASIR), age-standardized mortality rate, and age-standardized DALYs rate. Trends in the burden of GI cancers from 1990 to 2019 were examined using annual percent change and average annual percent change with Joinpoint regression models. RESULTS: For overall GI cancers, a declining trend was observed in the ASIR, age-standardized mortality rate, and age-standardized DALYs rate, with reductions of 0.74%, 2.23%, and 2.22%, respectively, from 1999 to 2019 in the Chinese working-age population. However, an increasing trend was observed in the ASIR for overall GI cancers from 2016-2019. The number of either incident cases, mortality cases, and DALYs was higher for colon/rectum cancer and liver cancer in younger participants but lower for esophageal, gallbladder, biliary tract, pancreatic, and stomach cancer among older subjects. Moreover, sex disparity in the GI cancers burden was also examined over 30 years. CONCLUSION: The total burden of GI cancers remained heavy among the working-age population in China, although declining trends were observed from 1999 to 2019. Disparities in the GI cancers burden existed between sexes, age groups, and cancer types. Population-based precision prevention strategies are needed to tackle GI cancers among working-age individuals, considering the age, sex, and cancer type disparities in China.

2.
Int J Biol Macromol ; 281(Pt 2): 136238, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39370074

RESUMO

The utilization of environmental friendly and renewable materials has received increasing attention recently. Lignin nanospheres (LNPs) prepared from recovered lignin and residual lignin after DESs and DESs-THF pretreatment were obtained by self-assembly in the present research. Then, films were prepared by incorporating them into polyvinyl alcohol (PVA) solution. The properties of various films were characterized and compared. Results showed that as the LNPs content increased, the UV blocking capacity of the films was gradually enhanced than PVA film. The DES-THF films showed better antioxidant properties up to 69 % due to higher phenolic hydroxyl content. The hydrophobicity of films incorporated with DESs-THF pretreated lignin was consistently better than that of DES pretreated. DES-THF-M films showed a higher Tmax than that of DES-M films, resulting in better thermal stability. Moreover, DES-THF-L films are lighter in color due to a lower degree of condensation, which is favorable to subsequent applications. The incorporation of LNPs improved mechanical and antioxidant properties, thermal stability, and UV shielding ability of PVA films, especially lignin after DES-THF pretreatment. In conclusion, the prepared PVA/LNPs composite films possessed good functional properties that make them potential for packaging materials.

3.
Environ Res ; 263(Pt 2): 120117, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39374751

RESUMO

Glaciers play key roles in capturing, storing, and transforming global carbon and nitrogen, thereby contributing markedly to their cycles. However, an integrated mechanistic approach is still lacking regarding glacier's primary producers (PP), in terms of stable dissolved inorganic carbon isotope (δ13C-DIC) and its relationship with dissolved carbon and nitrogen transformation d ynamic changes/cycling. Here, we sampled waters from glaciers, streams, tributaries, and the Indus River (IR) mainstream in the Upper IR Basin, Western Himalaya. Dissolved organic matter (DOM) appears to increase, on average, by ∼2.5-23.4% with fluctuations when passing from glaciers to streams-tributaries-IR mainstream (the upper and lower parts, respectively) continuum, implying that DOM originates from glaciers PP and is subsequently degraded. The corresponding fluctuations are observed for fluorescent DOM (FDOM), dissolved organic nitrogen (8.0-106.8%), NO3--N (-13.5/+16.6%), NH4+-N (-8.8/+13.0%), and NO2--N (70.7-217.5%). These variations are associated with overall DOM/FDOM transformations, with the production of ending byproducts (e.g. CO2/DIC). The δ13C-DIC values fluctuated from glaciers (-5.3 ± 2.5‰) to streams (-4.4 ± 2.1‰), tributaries (-4.3 ± 1.6‰), and IR mainstream (-4.2 ± 1.3‰). The δ13C-DIC data are consistent with C transformations that involve lighter CO2 emission into the atmosphere, whereas highly depleted DIC/CO2 is the signature of DOM degradation after its fresh production from glaciers PP which originated by photosynthetic activities (e.g. uptake/sink of atmospheric CO2: -8.4‰). Finally, glacier-fed meltwaters would simultaneously contribute to the biogeochemical characteristics of downward margins and specific ecosystems (lake/pond/groundwater/hot springs) via transformation dynamics/cycling of dissolved C and N with high photo/microbial lability. Our results highlight the substantial contribution of western Himalayan glaciers-derived DOM to the global C and N cycles.

4.
ACS Sens ; 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39356828

RESUMO

The early diagnosis of cancer in a point-of-need manner is of great significance, yet it remains challenging to achieve the necessary sensitivity and speed. Traditional lateral flow immunoassay (LFIA) methods are limited in accuracy and quantification, restricting their suitability for home-based applications. Thus, we explored a new and user-friendly electrochemical LFIA (e-LFIA) test strip to detect α-fetoprotein (AFP), a diagnostic marker for liver cancer. The specific electrochemical immunoprobe utilized in this e-LFIA test strip is characterized by significant signal boosting, resulted from the loading Ag shell into a gold nanoparticle (AuNP)-coated dendritic mesoporous silica nanoscaffold (DMSN). Leveraging the distinct electrochemical characteristics of Ag anodic stripping and the high volume-to-surface area ratio of DMSNs, the developed DMSNs/AuNPs@Ag-based e-LFIA test strip is capable of detecting AFP at a low concentration of 0.85 ng/mL within a rapid 20 min timespan, both of these values are smaller than those in current clinical testing. Furthermore, we utilized homemade screen-printed electrodes in this sensing prototype and demonstrated the high versatility and reliability of this e-LFIA device. We envision that this DMSNs/AuNPs@Ag-based e-LFIA holds substantial potential for the early diagnosis of liver cancer and household health monitoring.

5.
Expert Opin Drug Saf ; : 1-8, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39356232

RESUMO

BACKGROUND: The sodium-dependent glucose transporters 2 inhibitors (SGLT-2i) is associated with body weight loss but the composition of the losing weight remains unclear. RESEARCH DESIGN AND METHODS: Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi- item gamma Poisson shrinker (MGPS) algorithms, were employed to quantify the signals of SGLT-2i-associated musculoskeletal and connective tissue disorders AEs. RESULTS: The search retrieved a total of 3,206 cases of musculoskeletal and connective tissue disorder-related AEs during the reporting period. This included 1,061 cases for Canagliflozin, 1,052 cases for Dapagliflozin, 1,074 cases for Empagliflozin, and 19 cases for Ertugliflozin. Fifteen preferred terms (PTs) with significant disproportionality were retained. No musculoskeletal and connective tissue system-related AE signals were reported for Ertugliflozin. We identified a risk of muscle necrosis with Canagliflozin use, a risk of sarcopenia with Dapagliflozin use, and a chance of muscle atrophy with Dapagliflozin and Empagliflozin prescriptions. Most cases occurred within the first month after SGLT-2i initiation, and AEs can persist beyond 360 days of use. CONCLUSIONS: Our study identified potential new musculoskeletal and connective tissue disorder-related AE signals associated with SGLT-2 inhibitors.

6.
Heliyon ; 10(19): e37929, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39386873

RESUMO

Background: Few studies have compared the performances of those reported miRNAs as biomarkers for heart failure with reduced EF (HFrEF) in a population at high risk. The purpose of this study is to investigate comprehensively the performance of those miRNAs as biomarkers for HFrEF. Methods: By using bioinformatics methods, we also examined these miRNAs' target genes and possible signal transduction pathways. We collected serum samples from patients with HFrEF at Zhongshan Hospital. Receiver operating characteristic (ROC) curves were used to evaluate the accuracy of those miRNAs as biomarkers for HFrEF. miRWALK2.0, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to predict the target genes and pathways of selected miRNAs. Results: The study included 48 participants, of whom 30 had HFrEF and 18 had hypertension with normal left ventricular ejection fraction (LVEF). MiR-378, miR-195-5p were significantly decreased meanwhile ten miRNAs were remarkably elevated (miR-21-3p, miR-21-5p, miR-106-5p, miR-23a-3p, miR-208a-3p, miR-1-3p, miR-126-5p, miR-133a-3p, miR-133b, miR-223-3p) in the serum of the HFrEF group. Conclusion: The combination of miR 133a-3p, miR 378, miR 1-3p, miR 106b-5p, and miR 133b has excellent diagnostic performance for HFrEF, and there is a throng of mechanisms and pathways by which regulation of these miRNAs may affect the risk of HFrEF.

7.
J Transl Med ; 22(1): 890, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39358724

RESUMO

BACKGROUND: Numerous observational studies have indicated that patients with Guillain-Barré syndrome (GBS) frequently had infections with various pathogens before the onset of the disease, particularly several viral infections. Some of these infections are linked to specific clinical and immunological subgroups of GBS, suggesting a potential correlation between viral infections and the development of GBS. However, observational studies have several limitations, including the presence of confounding factors. METHOD: We explored the potential correlation between HIV, SARS-CoV-2, varicella-zoster virus, herpes simplex virus, Epstein-Barr virus, hepatitis B virus, and influenza virus with GBS using a two-sample Mendelian randomization approach. The data was derived from published summary statistics from genome-wide association studies (GWAS). After removing linkage disequilibrium, selecting strong instrumental variables and addressing confounding factors, we would conduct a two-sample Mendelian randomization analysis along with sensitivity testing and the MR-Steiger directional test. RESULT: HIV may have a causal association with GBS (IVW: p = 0.010, OR [95% CI] 1.240 [1.052-1.463]), while no such relationship exists with COVID-19 (IVW: p = 0.275, OR [95% CI] 0.831[0.596-1.159]), varicella (IVW: p = 0.543, OR [95% CI] 0.919 [0.701-1.206]), herpes zoster (IVW: p = 0.563, OR [95% CI] 0.941 [0.766-1.156]), HSV (IVW: p = 0.280, OR [95% CI] 1.244 [0.837-1.851]), EBV (IVW: p = 0.218, OR [95% CI] 0.883 [0.724-1.076]), HBV (IVW: p = 0.179, OR [95% CI] 1.072 [0.969-1.187]), or influenza virus (IVW: p = 0.917, OR [95% CI] 0.971 [0.553-1.703]). We did not find any abnormal SNPs, pleiotropy, or heterogeneity, nor is there any reverse causation. CONCLUSION: Our study results indicate a causal relationship between HIV and GBS, providing new research directions for the etiology of GBS.


Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Síndrome de Guillain-Barré , Análise da Randomização Mendeliana , Viroses , Humanos , Síndrome de Guillain-Barré/genética , Síndrome de Guillain-Barré/virologia , Viroses/genética , Viroses/complicações , Fatores de Risco , Polimorfismo de Nucleotídeo Único/genética , SARS-CoV-2/genética
8.
Angew Chem Int Ed Engl ; : e202416327, 2024 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-39343746

RESUMO

Host-guest dynamic systems in coordination-driven metallo-organic cages have gained significant attentions since their promising applications in chiral separation, drug delivery, and catalytical fields. To maximize guest-binding affinity, hosts adopting multiple conformations are widely investigated on their structural flexibility for guest accommodation. In this study, a novel metallo-organic cage S with breathing inner cavity and freely twisted side chains was proposed. Single-crystal X-ray diffraction analyses depicted a characteristic "breathing-helical" dynamic system on the semiflexible framework, which led to an unprecedent co-crystallisation of racemic and symmetric conformations via the encapsulation locking of C70 guests. By taking advantages of the high binding affinity, selective extraction of C70 was realized. This research provides new ideas for the modification on the helicities of metallo-organic cages, which could pave a new way for advanced conformational manipulation of supramolecular host systems.

9.
Discov Oncol ; 15(1): 498, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39331203

RESUMO

OBJECTIVE: The diagnostic value of serum human epididymal secretory protein 4 (HE4) for endometrial cancer (EC) was assessed via evidence-based medicine (EBM) and systematic review (SR) methodologies. METHODS: The Cochrane Library, PubMed, Web of Science, Embase, CBM, CNKI, and Wan Fang databases were searched up to April 1st, 2024, to identify relevant literature. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool was utilized to evaluate the quality of the selected studies. The meta-analysis was conducted via RevMan 5.3, STATA 16.1, and Meta-disc software. RESULTS: A total of 22 studies comprising 9036 cases (3776 cases in the case group and 5260 cases in the control group) were included. The results revealed that HE4 exhibited a pooled sensitivity of 0.59 [95% CI (0.53, 0.64)], specificity of 0.93 [95% CI (0.88, 0.96)], positive likelihood ratio (PLR) of 6.87 [95% CI (4.57, 10.33)], negative likelihood ratio (NLR) of 0.46 [95% CI (0.39, 0.54)], diagnostic odds ratio (DOR) of 14.36 [95% CI (9.37, 21.17)], and area under the receiver operating characteristic curve (AUC) of 0.78 [95% CI (0.75, 0.82)]. CONCLUSIONS: Serum HE4 demonstrates high specificity and moderate sensitivity for diagnosing EC, thus serving as a valuable biomarker for clinicians either alone or in conjunction with other tumour markers.

10.
EMBO Rep ; 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39223385

RESUMO

Dinoflagellates, a class of unicellular eukaryotic phytoplankton, exhibit minimal transcriptional regulation, representing a unique model for exploring gene expression. The biosynthesis, distribution, regulation, and function of mRNA N1-methyladenosine (m1A) remain controversial due to its limited presence in typical eukaryotic mRNA. This study provides a comprehensive map of m1A in dinoflagellate mRNA and shows that m1A, rather than N6-methyladenosine (m6A), is the most prevalent internal mRNA modification in various dinoflagellate species, with an asymmetric distribution along mature transcripts. In Amphidinium carterae, we identify 6549 m1A sites characterized by a non-tRNA T-loop-like sequence motif within the transcripts of 3196 genes, many of which are involved in regulating carbon and nitrogen metabolism. Enriched within 3'UTRs, dinoflagellate mRNA m1A levels negatively correlate with translation efficiency. Nitrogen depletion further decreases mRNA m1A levels. Our data suggest that distinctive patterns of m1A modification might influence the expression of metabolism-related genes through translational control.

11.
Genes Dis ; 11(6): 101100, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39281832

RESUMO

High-intensity interval training (HIIT) has been found to be more effective in relieving heart failure (HF) symptoms, than moderate-intensity continuous aerobic training (MICT). Additionally, higher meteorin-like protein (Metrnl) levels are seen after HIIT versus MICT. We investigated whether Metrnl contributed to post-HF cardiac functional improvements, and the signaling pathways involved. 50 HF patients underwent MICT, and another 50, HIIT, which was followed by cardiac function and serum Metrnl measurements. Metrnl was also measured in both blood and skeletal muscle samples of mice with transverse aortic constriction-induced HF after undergoing HIIT. Afterward, shRNA-containing adenovectors were injected into mice, yielding five groups: control, HF, HF + HIIT + scrambled shRNA, HF + HIIT + shMetrnl, and HF + Metrnl (HF + exogenous Metrnl). Mass spectrometry identified specific signaling pathways associated with increased Metrnl, which was confirmed with biochemical analyses. Glucose metabolism and mitochondrial functioning were evaluated in cardiomyocytes from the five groups. Both HF patients and mice had higher circulating Metrnl levels post-HIIT. Metrnl activated AMPK in cardiomyocytes, subsequently increasing histone deacetylase 4 (HDAC4) phosphorylation, leading to its cytosolic sequestration and inactivation via binding with chaperone protein 14-3-3. HDAC4 inactivation removed its repression on glucose transporter type 4, which, along with increased mitochondrial complex I-V expression, yielded improved aerobic glucose respiration and alleviation of mitochondrial dysfunction. All these changes ultimately result in improved post-HF cardiac functioning. HIIT increased skeletal muscle Metrnl production, which then operated on HF hearts to alleviate their functional defects, via increasing aerobic glucose metabolism through AMPK-HDAC4 signaling.

12.
IUBMB Life ; 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39275910

RESUMO

Several chemotherapeutics against breast cancer are constrained by their adverse effects and chemoresistance. The development of novel chemotherapeutics to target metastatic breast cancer can bring effective clinical outcomes. Many breast cancer patients present with tumors that are positive for estrogen receptors (ERs), highlighting the importance of targeting the ER pathway in this particular subtype. Although selective estrogen receptor modulators (SERMs) are commonly used, their side effects and resistance issues necessitate the development of new ER-targeting agents. In this study, we report that a newly synthesized compound, TTP-5, a hybrid of pyrimidine, triazole, and tert-butyl-piperazine-carboxylate, effectively binds to estrogen receptor alpha (ERα) and suppresses breast cancer cell growth. We assessed the impact of TTP-5 on cell proliferation using MTT and colony formation assays and evaluated its effect on cell motility through wound healing and invasion assays. We further explored the mechanism of action of this novel compound by detecting protein expression changes using Western blotting. Molecular docking was used to confirm the interaction of TTP-5 with ERα. The results indicated that TTP-5 significantly reduced the proliferation of MCF-7 cells by blocking the ERα signaling pathway. Conversely, although it did not influence the growth of MDA-MB-231 cells, TTP-5 hindered their motility by modulating the expression of proteins associated with epithelial-mesenchymal transition (EMT), possibly via the Wnt/ß-catenin pathway.

13.
Ultrasonics ; 144: 107450, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39222597

RESUMO

Medical Speed-of-sound (SoS) imaging, which can characterize medical tissue properties better by quantifying their different SoS, is an effective imaging method compared with conventional B-mode ultrasound imaging. As a commonly used diagnostic instrument, a hand-held array probe features convenient and quick inspection. However, artifacts will occur in the single-angle SoS imaging, resulting in indistinguishable tissue boundaries. In order to build a high-quality SoS image, a number of raw data are needed, which will bring difficulties to data storage and processing. Compressed sensing (CS) theory offers theoretical support to the feasibility that a sparse signal can be rebuilt with random but less sampling data. In this study, we proposed an SoS reconstruction method based on CS theory to process signals obtained from a hand-held linear array probe with a passive reflector positioned on the opposite side. The SoS reconstruction method consists of three parts. Firstly, a sparse transform basis is selected appropriately for a sparse representation of the original signal. Then, considering the mathematical principles of SoS imaging, the ray-length matrix is used as a sparse measurement matrix to observe the original signal, which represents the length of the acoustic propagation path. Finally, the orthogonal matching pursuit algorithm is introduced for image reconstruction. The experimental result of the phantom proves that SoS imaging can clearly distinguish tissues that show similar echogenicity in B-mode ultrasound imaging. The simulation and experimental results show that our proposed method holds promising potential for reconstructing precision SoS images with fewer signal samplings, transmission, and storage.


Assuntos
Algoritmos , Imagens de Fantasmas , Ultrassonografia , Ultrassonografia/métodos , Processamento de Imagem Assistida por Computador/métodos , Processamento de Sinais Assistido por Computador , Humanos
14.
Int Orthop ; 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39242395

RESUMO

PURPOSE: Upper cervical fracture combined with non-contiguous lower cervical fracture are not uncommon but complicated. In order to outline a management principle for the upper cervical fracture combined with non-contiguous lower cervical fracture and assess its clinical characteristics, we retrospectively analyzed 59 cases of patients who underwent surgical treatment for upper cervical fracture combined with non-contiguous lower cervical fracture. METHODS: 59 patients of upper cervical fracture combined with non-contiguous lower cervical fracture were treated by surgery in our hospital. According to the AO Spine classification for cervical fractures, there were 21 cases of type B atlas fractures, nine cases of type C atlas fractures; 15 cases of type B axis fractures, 14 cases of type C axis fractures; 19 cases of type B lower cervical fractures, 40 cases of type C lower cervical fractures. The operation time, intraoperative blood loss, complications, VAS scores, JOA scores, ASIA grades, and radiological evaluation of cervical lordosis and stability were collected and recorded. RESULTS: Our results showed the segments of upper cervical fracture combined with non-contiguous lower cervical fracture are mainly concentrated in the atlas-axis and C6, C7 levels. There were 43 cases (72.88%) of associated injuries, mainly involving head trauma and thoracic injuries. Four patients underwent anterior approach surgery only, 43 patients underwent posterior approach surgery only, and 12 patients underwent combined anterior and posterior approach surgery in one stage. All patients had regular follow up with an average duration of 67.83 ± 11.25 months (range, 39 to 103 months). The VAS scores and JOA scores at 12 months postoperatively and at final follow-up showed significant improvement compared to preoperative scores (P < 0.05). At the final follow-up, ASIA grades had improved by 0 to 2 levels. The cervical lordosis at the final follow-up (24.71°±7.39°) showed no statistically significant difference compared to preoperative measurements (26.89°±13.32°). Surgical complications occurred in 17 patients. No cases of vertebral artery injury, screw loosening, or other internal fixation failures were found at final follow-up. CONCLUSIONS: Upper cervical fracture combined with non-contiguous lower cervical fracture can result in varying extents of cervical spinal cord injury and combined trauma in other parts. Surgical treatment of these injuries can achieve favourable clinical and radiological outcomes in the medium to long term follow-up. More research is still needed to optimize clinical decision-making regarding surgical approach.

15.
Mol Neurobiol ; 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39285025

RESUMO

Chronic pain, as a social public health problem, has a serious impact on the quality of patients' life. Currently, the main drugs used to treat chronic pain are opioids, antipyretic, and nonsteroidal anti-inflammatory drugs (NSAIDs). But the obvious side effects limit their use, so it is urgent to find new therapeutic targets. Postsynaptic density (PSD)-95 protein plays an important role in the occurrence and development of chronic pain. The over-expression of the PSD-95 protein and its interaction with other proteins are closely related to the chronic pain. Besides, the PSD-95-related drugs that inhibit the expression of PSD-95 as well as the interaction with other protein have been proved to treat chronic pain significantly. In conclusion, although more deep studies are needed in the future, these studies indicate that PSD-95 and the related proteins, such as NMDA receptor (NMDAR) subunit 2B (GluN2B), AMPA receptor (AMPAR), calmodulin-dependent protein kinase II (CaMKII), 5-hydroxytryptamine 2A receptor (5-HT2AR), and neuronal nitric oxide synthase (nNOS), are the promising therapeutic targets for chronic pain.

16.
ACS Appl Bio Mater ; 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39302413

RESUMO

Reactive nitrogen species (RNS) are more lethal than reactive oxygen species (ROS), which gives them a very promising future in the field of cancer treatment. However, there are still a few drugs available for RNS generation. In this work, two 5th-order nonlinear optical materials, FB-Fe(III)/SNP@PEG and FB-Fe(II)-FB/SNP@PEG, are synthesized. The outstanding nonlinear optical properties of FB-Fe(III)/SNP@PEG help to achieve generation of bounteous superoxide anions (O2•-) in deep tissues, while sodium nitroprusside (SNP) provides NO in the body, both of which are prerequisites for RNS generation. Meanwhile, type I and type II ROS were also generated under irradiation of a 1600 nm laser. Based on the synergistic effect of ROS and RNS, FB-Fe(III)/SNP@PEG induced mitochondrial damage and DNA fragmentation and inhibited tumor cells through apoptosis, possessing better therapeutic effects than FB-Fe(II)-FB/SNP@PEG. This work put forward an innovative strategy to achieve the cooperative release of RNS and ROS in deep tissues, which provides insights and ideas for applying nonlinear optical materials to RNS therapy.

17.
Sci Rep ; 14(1): 22588, 2024 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-39343774

RESUMO

To clarify the survival benefit of sequential curative treatment post transcatheter arterial chemoembolization (TACE) for Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC), we retrospectively analyzed HCC patients at a hospital. From July 2017 to July 2020, 787 treatment-naïve HCC patients underwent initial treatment; 77 (9.8%) meeting inclusion criteria were enrolled. Their initial treatments were TACE only (n = 68, 88.3%) or TACE with other treatments (n = 9, 11.7%). Median survival of the TACE-only group was 30 months. Treatment response was evaluated after 2 or 3 consecutive TACEs for patients (54/68, 79.4%) with available pre-/post-TACE computerized tomography (CT) or magnetic resonance imaging (MRI). Treatment responses was divided into 4 groups: complete (n = 14, 26%, group (Gr) 1), incomplete without new tumor growth (n = 28, 52.0%, Gr2), incomplete with new growth (n = 6, 11%, Gr3), and progression (n = 6, 11%, Gr4). Of Gr2, further treatment after TACE were had radiofrequency ablation (n = 13, Gr2a), TACE (n = 9, Gr2b), other modalities (n = 6, Gr2c. Gr2a's median survival was longer than Gr2b's (> 60 vs. 20 months, p = 0.007). Nine patients in Gr2a (69%, 9/13) achieved a complete response, but none in Gr2b (p = 0.001). Conclusively, in TACE-suitable BCLC stage B HCC patients, a partial response without new tumor growth can serve as an indicator of treatment effectiveness following initial TACE treatment. This can facilitate the selection of appropriate candidates to receive RFA, potentially resulting in improved patient survival.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Estadiamento de Neoplasias , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Quimioembolização Terapêutica/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Resultado do Tratamento , Adulto , Idoso de 80 Anos ou mais
18.
Int Immunopharmacol ; 142(Pt B): 113184, 2024 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-39306894

RESUMO

BACKGROUND: Mucinous carcinoma (MC) is a distinct histologic subtype of colorectal cancer (CRC) that is less studied and associated with poor prognosis. This study aimed to identify MC-specific therapeutic targets and biomarkers to improve the prognosis of this aggressive disease. METHODS: CRC samples from The Cancer Genome Atlas (TCGA) were categorized into MC and non-MC (NMC) groups based on histologic type. A multi-scale embedded gene co-expression network analysis (MEGENA) was constructed to identify gene modules associated with the MC group. The potential functions of Basonuclin Zinc Finger Protein 2 (BNC2) were further analyzed using the Biomarker Exploration for Solid Tumors (BEST) database. In vivo and in vitro experiments were conducted to validate the predicted results. RESULTS: We identified the stromal component-related gene, BNC2, in the MC population. This gene is associated with a shorter progression-free interval (PFI) in CRC patients. BNC2 promotes FAP (encoding Fibroblast Activation Protein Alpha) transcription in cancer-associated fibroblasts (CAFs) and is involved in angiogenesis through two pathways. Additionally, BNC2 enhances tumor cell invasiveness in a CAF-dependent manner. Patients with high BNC2 expression benefited less from immunotherapy compared to those with low BNC2 expression. CONCLUSIONS: Our study highlights the clinical importance of BNC2 in MC, and targeting BNC2 on stromal cells (fibroblasts and endothelial cells) may be an effective strategy for treating MC.


Assuntos
Adenocarcinoma Mucinoso , Neoplasias Colorretais , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/metabolismo , Animais , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/imunologia , Adenocarcinoma Mucinoso/metabolismo , Células Estromais/metabolismo , Células Estromais/imunologia , Regulação Neoplásica da Expressão Gênica , Camundongos , Linhagem Celular Tumoral , Fibroblastos Associados a Câncer/metabolismo , Masculino , Feminino , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Tolerância Imunológica , Camundongos Nus
19.
Spectrochim Acta A Mol Biomol Spectrosc ; 325: 125147, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39299065

RESUMO

To investigate the effects of steric hindrance fluorene and heavy-atom bromine on the general optoelectronic properties of star-shaped organic emitters based on 9-(2-cyanophenyl) carbazole (OCzPhCN) frameworks, heavy element of bromine and steric hindrance fluorene were introduced into OCzPhCN to produce four derivatives of 2-(3-bromo-9H-carbazol-9-yl)benzonitrile (BrCzPhCN), 2-(3-bromo-6-(9-(4-ethoxyphenyl)-9H-fluoren-9-yl)-9H-carbazol-9-yl)benzonitrile (BrFCzPhCN), 2-(3-(9-(4-ethoxyphenyl)-9H-fluoren-9-yl)-9H-carbazol-9-yl)benzonitrile (FCzPhCN) and 2-(3,6-bis(9-(4-ethoxyphenyl)-9H-fluoren-9-yl)-9H-carbazol-9-yl)benzonitrile (2FCzPhCN). The fluorene units obviously improve the thermal stability of the obtained compounds, and 2FCzPhCN has the highest thermal stability with 5 % mass heat loss temperature reaching 447 °C. In different polar solvents, the absorption peaks wavelength of OCzPhCN, FCzPhCN and 2FCzPhCN are basically unchanged, and the redshifted emission peaks are positively correlated with solvent polarity. The photoluminescence quantum yields (PLQYs) of OCzPhCN, BrCzPhCN, FCzPhCN, BrFCzPhCN and 2FCzPhCN powders were 20.17 %, 5.43 %, 30.75 %, 3.27 % and 23.56 %. The fluorescence and phosphorescent quantum efficiencies of OCzPhCN, BrCzPhCN, FCzPhCN, BrFCzPhCN and 2FCzPhCN powders are 9.76 % and 10.41 %, 1.2 % and 3.23 %, 28.45 % and 2.3 %, 3.27 % and 0 %, 23.56 % and 0 %. OCzPhCN, BrCzPhCN and FCzPhCN powders show obvious room temperature phosphorescent emission, and the phosphorescent emission lifetime of OCzPhCN, BrCzPhCN and FCzPhCN powders at 561 nm, 576 nm and 568 nm are 193.17 ms, 18.65 ms and 7.25 ms. Compared with OCzPhCN, the introduction of bromine decreases the PLQY and the phosphorescent lifetime of BrCzPhCN powder, while the fluorescence quantum efficiency of the compound FCzPhCN powder has been improved. The corresponding single-triplet energy splitting (ΔEST) of OCzPhCN, FCzPhCN and 2FCzPhCN in solutions are 0.49 eV, 0.63 eV and 0.63 eV, and the corresponding ΔEST values of OCzPhCN, BrCzPhCN FCzPhCN powders are 1.19 eV, 0.74 eV and 0.55 eV. The steric hindrance fluorene units result in smaller and stabilized ΔEST in the solid powder states, and the same situation is opposite in the unimolecular solutions. The maximum external quantum efficiency of organic light-emitting diode based on 10,10'-(4,4'-sulfonylbis (4,1-phenylene)) bis (9,9-dimethyl-9,10-dihydroacridine) hosted by OCzPhCN reaches 12.7 %, and the external quantum efficiency at 100 cd/m2 rolls down to 11 %. OCzPhCN is the best emitters in terms of room temperature phosphorescent emission and host applications.

20.
Front Oncol ; 14: 1409503, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39246321

RESUMO

Background: Enterostomy is important for radical resection of colorectal cancer (CRC). Nevertheless, the notable occurrence of complications linked to enterostomy results in a reduction in patients' quality of life and impedes adjuvant therapy. This study sought to forecast early stoma-related complications (ESRCs) by leveraging easily accessible nutrition-inflammation markers in CRC patients. Methods: This study involved 470 individuals with colorectal cancer who underwent intestinal ostomy at Changhai Hospital Affiliated with Naval Medical University as the internal cohort. Between January 2016 and December 2018, the patients were enrolled and randomly allocated into a primary training group and a secondary validation group, with a ratio of 2:1 being upheld. The research encompassed collecting data on each patient's clinical and pathological status, along with preoperative laboratory results. Independent risk factors were identified through Lasso regression and multivariate analysis, leading to the development of clinical models represented by a nomogram. The model's utility was assessed using decision curve analysis, calibration curve, and ROC curve. The final model was validated using an external validation set of 179 individuals from January 2015 to December 2021. Results: Among the internal cohort, stoma complications were observed in 93 cases. Multivariate regression analysis confirmed that age, stoma site, and elevated markers (Mon, NAR, and GLR) in conjunction with diminished markers (GLB and LMR) independently contributed to an increased risk of ESRCs. The clinical model was established based on these seven factors. The training, internal, and external validation groups exhibited ROC curve areas of 0.839, 0.812, and 0.793, respectively. The calibration curve showed good concordance among the forecasted model with real incidence of ostomy complications. The model displayed outstanding predictive capability and is deemed applicable in clinical settings, as evidenced by Decision Curve Analysis. Conclusion: This study identified nutrition-inflammation markers (GLB, NAR, and GLR) in combination with demographic data as crucial predictors for forecasting ESRCs in colorectal cancer patients. A novel prognostic model was formulated and validated utilizing these markers.

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