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2.
World J Gastrointest Oncol ; 16(4): 1626-1646, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38660634

RESUMO

BACKGROUND: Human-derived gastric cancer organoids (GCOs) are widely used in gastric cancer research; however, the culture success rate is generally low. AIM: To explore the potential influencing factors, and the literature on successful culture rates of GCOs was reviewed using meta-analysis. METHODS: PubMed, Web of Science, and EMBASE were searched for studies. Two trained researchers selected the studies and extracted data. STATA 17.0 software was used for meta-analysis of the incidence of each outcome event. The adjusted Methodological Index for Non-Randomized Studies scale was used to assess the quality of the included studies. Funnel plots and Egger's test were used to detect publication bias. Subgroup analyses were conducted for sex, tissue source, histological classification, and the pathological tumor-node-metastasis (pTNM) cancer staging system. RESULTS: Eight studies with a pooled success rate of 66.6% were included. GCOs derived from women and men had success rates of 67% and 46.7%, respectively. GCOs from surgery or biopsy/endoscopic submucosal dissection showed success rates of 70.9% and 53.7%, respectively. GCOs of poorly-differentiated, moderately-differentiated and signet-ring cell cancer showed success rates of 64.6%, 31%, and 32.7%, respectively. GCOs with pTNM stages I-II and III-IV showed success rates of 38.3% and 65.2%, respectively. Y-27632 and non-Y-27632 use showed success rates of 58.2% and 70%, respectively. GCOs generated with collagenase were more successful than those constructed with Liberase TH and TrypLE (72.1% vs 71%, respectively). EDTA digestion showed a 50% lower success rate than other methods (P = 0.04). CONCLUSION: GCO establishment rate is low and varies by sex, tissue source, histological type, and pTNM stage. Omitting Y-27632, and using Liberase TH, TrypLE, or collagenase yields greater success than EDTA.

3.
BMC Urol ; 24(1): 91, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643096

RESUMO

BACKGROUND: Sleep quality may be related to benign prostatic hyperplasia (BPH), however causal associations have not been established. This study aimed to evaluate causal relationships between six sleep traits ([i] day time napping, [ii] daytime sleepiness, [iii] insomnia, [iv] long sleep duration, [v] short sleep duration, and [vi] sleep duration per hour) and BPH through a bidirectional Mendelian randomization (MR) study. METHODS: Genome-wide association summary statistics of sleep traits and BPH were downloaded from public databases. Inverse variance weighting (IVW) was used as the main approach for causal inference. For causal estimates identified by IVW, various sensitivity analyses were performed to assess the reliability of the results: (i) four additional MR methods to complement IVW; (ii) Cochran's Q test to assess heterogeneity; (iii) MR-Egger intercept test and MR-PRESSO global test to assess horizontal pleiotropy; and (iv) leave-one-out method to assess stability. RESULTS: Forward MR analyses indicated that genetically predicted insomnia symptom significantly increased BPH risk (OR = 1.267, 95% CI: 1.003-1.601, P = 0.048), while reverse MR analyses identified that genetically predicted liability to BPH significantly increased the incidence of insomnia (OR = 1.026, 95% CI: 1.000-1.052, P = 0.048). In a replicate MR analysis based on summary statistics including exclusively male participants, the finding of increased risk of BPH due to genetically predicted insomnia symptom was further validated (OR = 1.488, 95% CI: 1.096-2.022, P = 0.011). No further causal links were identified. In addition, sensitivity tests demonstrated the reliability of the MR results. CONCLUSION: This study identified that a higher prevalence of genetically predicted insomnia symptoms may significantly increase the risk of BPH, while genetically predicted liability to BPH may in turn increase the incidence of insomnia symptom. Therefore, improving sleep quality and reducing the risk of insomnia could be a crucial approach for the prevention of BPH.


Assuntos
Hiperplasia Prostática , Distúrbios do Início e da Manutenção do Sono , Humanos , Masculino , Distúrbios do Início e da Manutenção do Sono/genética , Hiperplasia Prostática/complicações , Hiperplasia Prostática/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Reprodutibilidade dos Testes
4.
Mol Carcinog ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578157

RESUMO

Hepatocellular carcinoma (HCC) stands as one of the most malignant tumors characterized by poor prognosis and high mortality rates. Emerging evidence underscores the crucial role of the B7 protein family in various cancers, including HCC. However, the involvement of the human endogenous retrovirus H long-terminal repeat-associated protein 2 (HHLA2, or B7-H5) in HCC remains unclear. Immunohistochemistry was employed to assess the differential expression of HHLA2 between HCC and normal liver tissues. A battery of assays, including CCK8, EdU, tablet clone-forming, Transwell, and wound healing assays, were conducted to elucidate the function and potential mechanisms of HHLA2 in the malignant biological behaviors of HCC. Additionally, a xenograft mouse model was established to evaluate the tumorigenicity of hepatoma cell lines exhibiting different HHLA2 expression levels in vivo. Western blot analysis was used to analyze HHLA2, secretory phosphoprotein 1 (SPP1), and PI3K/AKT/mTOR levels. HHLA2 exhibited elevated expression in HCC tissues, correlating with poor tumor differentiation and shortened overall survival in HCC patients. In vitro experiments demonstrated that HHLA2 overexpression (OE) promoted the proliferation, migration, and invasion of hepatoma cells, while in vivo experiments revealed that HHLA2 OE enhanced HCC tumor growth. Conversely, inhibition of HHLA2 expression yielded the opposite effect. Downregulation of SPP1 inhibited the proliferation, migration, and invasion induced by HHLA2 OE, and this effect was linked to the PI3K/AKT/mTOR signaling pathway. Our findings indicate that HHLA2 promotes the proliferation, migration, and invasion of hepatoma cells via the SPP1/PI3K/AKT signaling pathway, establishing it as a potential therapeutic target for HCC.

5.
Neoplasia ; 52: 100996, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38593698

RESUMO

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, and its incidence has increased rapidly in recent years. The BRAF inhibitor vemurafenib is effective against BRAFV600E-positive PTC; however, acquired resistance to single agent therapy frequently leads to tumor recurrence and metastasis, underscoring the need to develop tailored treatment strategies. We previously showed that the oncogenic kinase PIM1 was associated with the malignant phenotype and prognosis of PTC. In this study, we showed that sustained expression of the PIM1 protein in PTC was affected by the BRAFV600E mutation. Based on this regulatory mechanism, we tested the synergistic effects of inhibitors of BRAF (BRAFi) and PIM1 in BRAFV600E-positive PTC cell lines and xenograft tumors. LC-MS metabolomics analyses suggested that BRAFi/PIMi therapy acted by restricting the amounts of critical amino acids and nucleotides required by cancer cells as well as modulating DNA methylation. This study elucidates the role of BRAFV600E in the regulation of PIM1 in PTC and demonstrates the synergistic effect of a novel combination, BRAFi/PIMi, for the treatment of PTC. This discovery, along with the pathways that may be involved in the powerful efficacy of BRAFi/PIMi strategy from the perspective of cell metabolism, provides insight into the molecular basis of PTC progression and offers new perspectives for BRAF-resistant PTC treatment.


Assuntos
Sinergismo Farmacológico , Mutação , Proteínas Proto-Oncogênicas B-raf , Proteínas Proto-Oncogênicas c-pim-1 , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Proteínas Proto-Oncogênicas c-pim-1/genética , Proteínas Proto-Oncogênicas c-pim-1/metabolismo , Proteínas Proto-Oncogênicas c-pim-1/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/tratamento farmacológico , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/metabolismo , Animais , Camundongos , Linhagem Celular Tumoral , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Modelos Animais de Doenças , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
6.
World J Gastroenterol ; 30(8): 969-983, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38516239

RESUMO

BACKGROUND: Three-dimensional organoid culture systems have been established as a robust tool for elucidating mechanisms and performing drug efficacy testing. The use of gastric organoid models holds significant promise for advancing personalized medicine research. However, a comprehensive bibliometric review of this bur-geoning field has not yet been published. AIM: To analyze and understand the development, impact, and direction of gastric organoid research using bibliometric methods using data from the Web of Science Core Collection (WoSCC) database. METHODS: This analysis encompassed literature pertaining to gastric organoids published between 2010 and 2023, as indexed in the WoSCC. CiteSpace and VOSviewer were used to depict network maps illustrating collaborations among authors, institutions and keywords related to gastric organoid. Citation, co-citation, and burst analysis methodologies were applied to assess the impact and progress of research. RESULTS: A total of 656 relevant studies were evaluated. The majority of research was published in gastroenterology-focused journals. Globally, Yana Zavros, Hans Clevers, James M Wells, Sina Bartfeld, and Chen Zheng were the 5 most productive authors, while Hans Clevers, Huch Meritxell, Johan H van Es, Marc Van de Wetering, and Sato Toshiro were the foremost influential scientists in this area. Institutions from the University Medical Center Utrecht, Netherlands Institute for Developmental Biology (Utrecht), and University of Cincinnati (Cincinnati, OH, United States) made the most significant contributions. Currently, gastric organoids are used mainly in studies investigating gastric cancer (GC), Helicobacter pylori-infective gastritis, with a focus on the mechanisms of GC, and drug screening tests. CONCLUSION: Key focus areas of research using gastric organoids include unraveling disease mechanisms and enhancing drug screening techniques. Major contributions from renowned academic institutions highlight this field's dynamic growth.


Assuntos
Gastrite , Infecções Intra-Abdominais , Neoplasias Gástricas , Humanos , Centros Médicos Acadêmicos , Bibliometria
7.
Protein Sci ; 33(4): e4944, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38501479

RESUMO

Antibody (Ab)-based drugs have been widely used in targeted therapies and immunotherapies, leading to significant improvements in tumor therapy. However, the failure of Ab therapy due to the loss of target antigens or Ab modifications that affect its function limits its application. In this study, we expanded the application of antibodies (Abs) by constructing a fusion protein as a versatile tool for Ab-based target cell detection, delivery, and therapy. We first constructed a SpaC Catcher (SpaCC for short) fusion protein that included the C domains of Staphylococcal protein A (SpaC) and the SpyCatcher. SpaCC conjugated with SpyTag-X (S-X) to form the SpaCC-S-X complex, which binds non-covalently to an Ab to form the Ab-SpaCC-S-X protein complex. The "X" can be a variety of small molecules such as fluoresceins, cell-penetrating peptide TAT, Monomethyl auristatin E (MMAE), and DNA. We found that Ab-SpaCC-S-FITC(-TAT) could be used for target cell detection and delivery. Besides, we synthesized the Ab-SpaCC-SN3-MMAE complex by linking Ab with MMAE by SpaCC, which improved the cytotoxicity of small molecule toxins. Moreover, we constructed an Ab-DNA complex by conjugating SpaCC with the aptamer (Ap) and found that Ab-SpaCC-SN3-Ap boosted the tumor-killing function of T-cells by retargeting tumor cells. Thus, we developed a multifunctional tool that could be used for targeted therapies and immunotherapies, providing a cheap and convenient novel drug development strategy.


Assuntos
Peptídeos Penetradores de Células , Neoplasias , Humanos , Neoplasias/genética , Neoplasias/terapia , Imunoterapia , Anticorpos , DNA , Linhagem Celular Tumoral
8.
bioRxiv ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38464206

RESUMO

Aberrant formation and deposition of human transthyretin (TTR) aggregates causes transthyretin amyloidosis. To initialize aggregation, transthyretin tetramers must first dissociate into monomers that partially unfold to promote entry into the aggregation pathway. The native TTR tetramer (T) is stabilized by docking of the F87 sidechain into an interfacial cavity enclosed by several hydrophobic residues including A120. We have previously shown that an alternative tetramer (T*) with mispacked F87 sidechains is more prone to dissociation and aggregation than the native T state. However, the molecular basis for the reduced stability in T* remains unclear. Here we report characterization of the A120L mutant, where steric hindrance is introduced into the F87 binding site. The X-ray structure of A120L shows that the F87 sidechain is displaced from its docking site across the subunit interface. In A120S, a naturally occurring pathogenic mutant that is less aggregation-prone than A120L, the F87 sidechain is correctly docked, as in the native TTR tetramer. Nevertheless, 19F-NMR aggregation assays show an elevated population of a monomeric aggregation intermediate in A120S relative to a control containing the native A120, due to accelerated tetramer dissociation and slowed monomer tetramerization. The mispacking of the F87 sidechain is associated with enhanced exchange dynamics for interfacial residues. At 298 K, the T* populations of various naturally occurring mutants fall between 4-7% (ΔG ~ 1.5-1.9 kcal/mol), consistent with the free energy change expected for undocking and solvent exposure of one of the four F87 sidechains in the tetramer (ΔG ~ 1.6 kcal/mol). Our data provide a molecular-level picture of the likely universal F87 sidechain mispacking in tetrameric TTR that promotes interfacial conformational dynamics and increases aggregation propensity.

9.
Food Chem X ; 22: 101289, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38544933

RESUMO

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

10.
Front Cardiovasc Med ; 11: 1340199, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38333413

RESUMO

Background: Calcific aortic valve disease (CAVD) is one of the most prevalent valvular diseases and is the second most common cause for cardiac surgery. However, the mechanism of CAVD remains unclear. This study aimed to investigate the role of pyroptosis-related genes in CAVD by performing comprehensive bioinformatics analysis. Methods: Three microarray datasets (GSE51472, GSE12644 and GSE83453) and one RNA sequencing dataset (GSE153555) were obtained from the Gene Expression Omnibus (GEO) database. Pyroptosis-related differentially expressed genes (DEGs) were identified between the calcified and the normal valve samples. LASSO regression and random forest (RF) machine learning analyses were performed to identify pyroptosis-related DEGs with diagnostic value. A diagnostic model was constructed with the diagnostic candidate pyroptosis-related DEGs. Receiver operating characteristic (ROC) curve analysis was performed to estimate the diagnostic performances of the diagnostic model and the individual diagnostic candidate genes in the training and validation cohorts. CIBERSORT analysis was performed to estimate the differences in the infiltration of the immune cell types. Pearson correlation analysis was used to investigate associations between the diagnostic biomarkers and the immune cell types. Immunohistochemistry was used to validate protein concentration. Results: We identified 805 DEGs, including 319 down-regulated genes and 486 up-regulated genes. These DEGs were mainly enriched in pathways related to the inflammatory responses. Subsequently, we identified 17 pyroptosis-related DEGs by comparing the 805 DEGs with the 223 pyroptosis-related genes. LASSO regression and RF algorithm analyses identified three CAVD diagnostic candidate genes (TREM1, TNFRSF11B, and PGF), which were significantly upregulated in the CAVD tissue samples. A diagnostic model was constructed with these 3 diagnostic candidate genes. The diagnostic model and the 3 diagnostic candidate genes showed good diagnostic performances with AUC values >0.75 in both the training and the validation cohorts based on the ROC curve analyses. CIBERSORT analyses demonstrated positive correlation between the proportion of M0 macrophages in the valve tissues and the expression levels of TREM1, TNFRSF11B, and PGF. Conclusion: Three pyroptosis-related genes (TREM1, TNFRSF11B and PGF) were identified as diagnostic biomarkers for CAVD. These pyroptosis genes and the pro-inflammatory microenvironment in the calcified valve tissues are potential therapeutic targets for alleviating CAVD.

11.
Environ Sci Pollut Res Int ; 31(12): 18842-18855, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38351355

RESUMO

Copper-containing stainless steel (SS) has been reported to mitigate biofilms in industrial and clinical environments. However, the impact of copper released from copper-containing SS in natural seawater on biofilms and corrosion is still unclear. In this study, three kinds of 316L SS were immersed in natural seawater for 6 months, and the pitting depth decreased in the order: 316L-Cu SS (annealed) > 316L SS > 316L-Cu SS (aged). The biofilm thickness and number of sessile cells on the surface of 316L-Cu SS (annealed) and 316L SS were similar but notably greater than those of 316L-Cu SS (aged). Furthermore, the results of the community analysis indicated that the addition of copper in 316L-Cu SS (aged) reduced the diversity and richness of the microbial community, resulting in a significant reduction in the number of genera constituting the biofilms. Copper ions exhibit a broad-spectrum bactericidal effect, effectively reducing the abundance of dominant populations and microbial genera in the biofilms, thereby mitigating pitting corrosion induced by microorganisms. In addition, the PCoA scatter plot showed that time also played an important role in the regulation of microbial community structure.


Assuntos
Cobre , Aço Inoxidável , Cobre/química , Aço Inoxidável/química , Corrosão , Biofilmes , Água do Mar
12.
Vet Res ; 55(1): 26, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38414065

RESUMO

Pyroptosis is a form of programmed cell death characterized by cell swelling, pore formation in the plasma membrane, lysis, and releases of cytoplasmic contents. To date, the molecular mechanism of human and murine Gasdermin D-mediated pyroptosis have been fully investigated. However, studies focusing on molecular mechanism of bovine Gasdermin D (bGSDMD)-mediated pyroptosis and its function against pathogenic infection were unclear. In the present study, we demonstrate that bovine caspase-1 (bCaspase-1) cleaves bGSDMD at amino acid residue D277 to produce an N-terminal fragment (bGSDMD-p30) which leads to pyroptosis. The amino acid residues T238 and F239 are critical for bGSDMD-p30-mediated pyroptosis. The loop aa 278-299, L293 and A380 are the key sites for autoinhibitory structure of the full length of bGSDMD. In addition, bCaspase-3 also cleaves bGSDMD at residue Asp86 without inducing cell death. Therefore, our study provides the first detailed elucidation of the mechanism of bovine GSDMD-mediated pyroptosis. The results will establish a significant foundation for future research on the role of pyroptosis in bovine infectious diseases.


Assuntos
Gasderminas , Piroptose , Animais , Bovinos , Humanos , Camundongos , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Neoplasias/química , Proteínas de Neoplasias/metabolismo , Aminoácidos , Inflamassomos/metabolismo
13.
Arch Esp Urol ; 77(1): 92-97, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38374018

RESUMO

OBJECTIVE: In this article, the associated factors for erectile dysfunction (ED) after radical prostatectomy (RP) were explored, and a clinical risk assessment model was constructed. METHODS: A total of 155 patients who underwent RP in People's Hospital of Hunan Province from November 2020, to November 2021, were selected as the study group. In accordance with the results of International Index of Erectile Function (IIEF-5) at 6 months after surgery, 88 patients were included in the ED group (IIEF-5 <22), and 67 patients were included in the non-ED group (IIEF-5 ≥22). Univariate and multivariate logistic regression analyses were conducted to screen the risk factors for ED after RP, and a risk model was constructed on this basis. In addition, 43 patients with ED after RP and 41 patients with non-ED after RP from January 2022, to January 2023, were included in the test group to evaluate the predictive efficacy of the clinical risk assessment model on the basis of the receiver operating characteristic curve. RESULTS: The study group had a lower postoperative IIEF-5 score than before surgery (p < 0.001). The incidence of ED after RP in the study group was 56.77% (88/155). Multivariate analysis showed that advanced age (odds ratio (OR) = 1.155), large prostate volume (OR = 1.077), smoking (OR = 5.676), drinking (OR = 3.495), hypertension (OR = 8.079), diabetes (OR = 6.082), low preoperative serum testosterone (T) level (OR = 0.684) and high preoperative serum endothelin-1 (ET-1) level (OR = 1.192) were risk factors for ED after RP (p < 0.05). A risk model was constructed as follows: Z = 0.144 × (age) + 0.074 × (prostate volume) + 1.736 × (smoking) + 1.251 × (drinking) + 2.089 × (hypertension) + 1.805 × (diabetes) - 0.380 × (preoperative serum T) + 0.175 × (preoperative serum ET-1). The area under curve (AUC), sensitivity, specificity and 95% CI of this model were 0.906, 97.70%, 73.20%, and 0.848-0.964, respectively (p < 0.001). CONCLUSIONS: The clinical risk assessment model constructed on the basis of the above factors provides some references for the scientific prevention and treatment of ED after RP.


Assuntos
Diabetes Mellitus , Disfunção Erétil , Hipertensão , Neoplasias da Próstata , Masculino , Humanos , Recém-Nascido , Disfunção Erétil/epidemiologia , Disfunção Erétil/etiologia , Próstata , Estudos Retrospectivos , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/epidemiologia , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Medição de Risco , Fatores de Risco , Diabetes Mellitus/etiologia , Diabetes Mellitus/cirurgia , Hipertensão/complicações , Hipertensão/cirurgia , Ereção Peniana
14.
Cell Death Discov ; 10(1): 23, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216595

RESUMO

Extracellular vesicles (EVs) have gained increasing recognition as significant regulators of intercellular communication in various physiological and pathological processes. These vesicles play a pivotal role in cancer progression by facilitating the transfer of diverse cargoes, including lipids, proteins, and nucleic acids. Regulated cell death (RCD), the orderly and autonomous death of cells, is controlled by a variety of biomacromolecules and, in turn, influences various biological processes and cancer progression. Recent studies have demonstrated that EV cargoes regulate diverse oncogenes and tumor suppressors to mediate different nonapoptotic forms of RCD, notably ferroptosis, pyroptosis, and necroptosis. Nevertheless, comprehensive exploration of EV-mediated nonapoptotic RCD forms in the context of cancer has not been performed. This review summarizes the progress regarding the biological functions and underlying mechanisms of EVs in mediating nonapoptotic RCD by delivery of cargoes to regulate tumor progression. Additionally, the review delves into the potential clinical applications of EV-mediated cell death and its significance in the areas of cancer diagnosis and therapy.

15.
J Mater Chem B ; 12(7): 1846-1853, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38284427

RESUMO

Combining phototherapy with other treatments has significantly advanced cancer therapy. Here, we designed and fabricated calcium-enriched carbon nanoparticles (Ca-CNPs) that could effectively deplete glutathione (GSH) and release calcium ions in tumors, thereby enhancing the efficacy of photodynamic therapy (PDT) and the calcium overload effect that leads to mitochondrial dysfunction. Due to the electrostatic interaction, π-π stacking interaction, multiple hydrogen bonds, and microporous structures, indocyanine green (ICG) was loaded onto the surface of Ca-CNPs with a high loading efficiency of 44.7 wt%. The obtained Ca-CNPs@ICG can effectively improve the photostability of ICG while retaining its ability to generate singlet oxygen (1O2) and undergo photothermal conversion (Ca-CNPs@ICG vs. ICG, 45.1% vs. 39.5%). In vitro and in vivo experiments demonstrated that Ca-CNPs@ICG could be used for near-infrared fluorescence imaging-guided synergistic calcium overload, photothermal therapy, and GSH depletion-enhanced PDT. This study sheds light on the improvement of 1O2 utilization efficiency and calcium overload-induced mitochondrial membrane potential imbalance in tumor cells.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Verde de Indocianina/farmacologia , Verde de Indocianina/química , Cálcio , Terapia Fototérmica , Nanopartículas/química , Neoplasias/terapia , Imagem Óptica , Carbono/farmacologia
16.
Vet Microbiol ; 288: 109922, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38086162

RESUMO

Mycobacterial PE_PGRS family proteins play key roles in pathogen-host interaction. However, the function of most PE_PGRS proteins remains unknown. In this study, we characterized the role of PE12 of Mycobacterium bovis (M. bovis) on bacterial growth, bacterial survival, and host cell apoptosis. Transcriptome sequencing of infected THP-1 cells was also performed. Compared to Ms_Vec, we found that M. bovis PE12 did not alter the colony morphology of M. smegmatis. The survival of Ms_PE12 was obviously higher than that of Ms_Vec. Furthermore, PE12 significantly suppressed the apoptosis of THP-1 induced by M. smegmatis infection. Transcriptome analysis results showed that there were 70 downregulated genes in the Ms_PE12 infection group in comparison with the Ms_Vec infection group, and these differentially expressed genes were enriched in 240 downregulated GO terms and 6 KEGG pathways. The downregulated expression genes are involved in cell adhesion, phagocytosis, apoptosis, inflammatory response, glycolysis and transmembrane transporter activity. Taken together, our study reveals that PE12 can suppress apoptosis and inhibit proinflammatory cytokine response. We propose that PE12 is related to macrophage phagocytosis and apoptosis, providing useful information to the pathogenic mechanisms of M. bovis.


Assuntos
Mycobacterium bovis , Mycobacterium tuberculosis , Animais , Mycobacterium smegmatis/genética , Mycobacterium smegmatis/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Macrófagos/microbiologia , Citocinas/metabolismo , Apoptose , Fagocitose , Mycobacterium tuberculosis/genética
17.
Recent Pat Anticancer Drug Discov ; 19(3): 308-315, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37723963

RESUMO

BACKGROUND: Gefitinib, an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI), frequently causes side effects when used to treat non-small cell lung cancer. OBJECTIVE: The purpose of this experiment was to investigate the side effect of gefitinib on the skin and colon of mice. METHODS: Male Balb/c nu-nu nude mice aged 4-5 weeks were used as xenograft tumor models, and gefitinib at 150 mg/kg and 225 mg/kg was started at 9 days after the xenograft tumor grew out. The mice's weights and tumor volumes were tracked concurrently, and the mouse skin adverse reactions and diarrhea were observed during the treatment. The animal tissues were subjected to biochemical and pathological evaluations after 14 days. RESULTS: Gefitinib effectively decreased the size and weight of transplanted tumors in nude mice, while also lowering body weight and raising indexes of the liver and spleen. Gefitinib could cause skin adverse reactions and diarrhea in mice. Further pathological investigation revealed tight junction- related markers in the mice's skin and colon to be reduced and macrophages and neutrophils to be increased after gefitinib treatment. CONCLUSION: The findings imply that gefitinib has negative effects on the skin and colon. Gefitinib- induced skin and colon adverse reactions in mice have been successfully modeled in this study.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Masculino , Camundongos , Animais , Gefitinibe/uso terapêutico , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Camundongos Nus , Quinazolinas/efeitos adversos , Receptores ErbB/metabolismo , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Colo/metabolismo , Colo/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Antineoplásicos/efeitos adversos , Resistencia a Medicamentos Antineoplásicos
18.
Environ Sci Pollut Res Int ; 31(1): 1644-1653, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38038922

RESUMO

Harmful algal blooms, particularly those of Microcystis aeruginosa, present significant ecological and health risks. To address this issue, this study utilized a custom static algal growth assessment apparatus to investigate the anti-algal performance of a copper-alloyed 316L stainless steel (SS), named 316L-Cu SS. This material was compared with traditional 316L SS, which is widely utilized in freshwater systems for its corrosion resistance. Algal growth dynamics were monitored through optical density (OD) and chlorophyll A concentration measurements. Notably, 316L-Cu SS exhibited superior inhibitory effects on Microcystis aeruginosa growth compared to 316L SS and control groups. Inductively coupled plasma mass spectrometry (ICP-MS) confirmed that the copper ion release from 316L-Cu SS played a critical role in this algal suppression, which interfered with photosynthesis, induced oxidative stress, and damaged algal cell membranes. In contrast, other metal ions (Ni, Cr, Fe) had a negligible impact on algal growth. The study highlights 316L-Cu SS as a promising material for mitigating harmful algal blooms, thereby offering potential benefits for both aquatic ecosystem conservation and public health protection.


Assuntos
Cianobactérias , Microcystis , Cobre/química , Aço Inoxidável/química , Clorofila A , Ecossistema
19.
Reprod Sci ; 31(3): 764-772, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37828362

RESUMO

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in reproductive-aged women. The occurrence of PCOS was reported to be associated with the alteration of gut microbiota. Microbiota-derived indoles may possibly play a key role in glycemic control. The purpose of this work is to reveal the alteration of plasma indoles in PCOS patients and to investigate the correlation between indoles levels and glucose metabolism. Sixty-five patients with PCOS and twenty-eight age-matched women were enrolled in this work. The concentrations of plasma indoles, including indoxyl sulfate (IS), indole-3-acetic acid (IAA), indole-3-propionate (IPA), indole (IND), and 3-methylindole (3-MI), were measured by HPLC with the fluorescence detection. The plasma levels of IS, IAA, and IND were significantly elevated in patients with PCOS compared to those in the control group (p < 0.05). Furthermore, the plasma levels of IS, IAA, and IND were positively correlated with fasting glucose, fasting insulin, and the homeostatic model of insulin resistance index (HOMA-IR) (p < 0.05). Besides, the 3-MI level in the plasma was positively correlated with the fasting glucose level, whereas plasma levels of IS, IAA, IND, and 3-MI were negatively correlated with glucagon-like peptide 1 (p < 0.05). Moreover, IS and IND were considered to be risk factors for PCOS after age, BMI, T, LH, and HOMA-IR adjustment. The area under the receiver-operating characteristic curve of the combined index of five indoles was 0.867 for PCOS diagnosis. Additionally, plasma indoles altered in PCOS, which was closely associated with the glucose metabolism.


Assuntos
Resistência à Insulina , Síndrome do Ovário Policístico , Feminino , Humanos , Adulto , Índice de Massa Corporal , Insulina , Indóis , Glucose , Glicemia/metabolismo
20.
Chem Asian J ; 19(3): e202301020, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38149729

RESUMO

Metal complexes represented by platinum complexes play a very important role in cancer treatment due to their diverse chemical structures and anti-tumor activities. Recently, ferroptosis has emerged as a newly occurring cell death form in the anti-tumor process. It has been reported that metal complexes could inhibit the proliferation and metastasis of tumors and combat chemotherapy resistance by targeting ferroptosis. In this review, we briefly describe ferroptosis as a fundamental process for tumor suppression and triggering anti-tumor immune responses. We summarize recent developments on metal complexes that induce ferroptosis. Finally, we outline the prospects for the application of metal complexes to the treatment of tumors based on ferroptosis and the associated problems that need to be solved, and discussed other potential research directions of metal complexes.


Assuntos
Complexos de Coordenação , Ferroptose , Neoplasias , Humanos , Complexos de Coordenação/farmacologia , Neoplasias/tratamento farmacológico , Morte Celular , Platina
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