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Urate nephropathy, a common complication of hyperuricemia, has garnered increasing attention worldwide. However, the exact pathogenesis of this condition remains unclear. Currently, inflammation is widely accepted as the key factor in urate nephropathy. Therefore, the aim of this study was to elucidate the interaction of lincRNA-p21/AIF-1/CMPK2/NLRP3 via exosomes in urate nephropathy. This study evaluated the effect of lincRNA-p21/AIF-1/CMPK2/NLRP3 using clinical data collected from patients with urate nephropathy and human renal tubular epithelial cells (HK2) cultured with different concentrations of urate. In clinical research section, the level of lincRNA-p21/AIF-1 in exosomes of urine in patients with hyperuricemia or urate nephropathy was found to be increased, particularly in patients with urate nephropathy. In vitro study section, the level of exosomes, inflammation, autophagy, and apoptosis was increased in HK2 cells induced by urate. Additionally, the expression of lincRNA-p21, AIF-1, CMPK2, and NLRP3 was upregulated in exosomes and HK2 cells. Furthermore, manipulating the activity of lincRNA-p21, AIF-1, CMPK2, and NLRP3 through overexpression or interference vectors regulated the level of inflammation, autophagy, and apoptosis in HK2 cells. In conclusion, the pathway of lincRNA-p21/AIF-1/CMPK2/NLRP3 contributed to inflammation, autophagy, and apoptosis of human renal tubular epithelial cell induced by urate via exosomes. Additionally, the specific exosomes in urine might serve as novel biomarkers for urate nephropathy.
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Apoptose , Autofagia , Células Epiteliais , Exossomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , RNA Longo não Codificante , Ácido Úrico , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ácido Úrico/metabolismo , Exossomos/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , RNA Longo não Codificante/metabolismo , RNA Longo não Codificante/genética , Transdução de Sinais , Inflamação/metabolismo , Inflamação/patologia , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Linhagem Celular , Masculino , Fator de Indução de Apoptose/metabolismo , Feminino , Pessoa de Meia-Idade , Hiperuricemia/metabolismo , Hiperuricemia/urina , Proteínas de Ligação ao Cálcio , Proteínas dos MicrofilamentosRESUMO
BACKGROUND: The genetic susceptibility association between viral infection and the risk of colorectal cancer (CRC) has not been established. METHODS: We conducted two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data. In addition to traditional MR methods, we employed several other approaches, including cML, ConMix, MR-RAPS, and dIVW, to comprehensively assess causal effects. Sensitivity analyses were also performed to ensure the robustness of the results. RESULTS: After sensitivity analysis, presence of SNPs linked to increased susceptibility to cold sores infection was found to decrease the risk of CRC (OR: 0.73, 95% CI: 0.57-0.93, P = 0.01). In subgroup analysis, presence of SNPs linked to increased susceptibility to viral hepatitis (OR: 0.89, 95% CI: 0.81-0.98, P = 0.02) and infectious mononucleosis (OR: 0.91, 95% CI: 0.84-0.98, P = 0.02) were associated with a decreased risk of colon cancer, while measles virus (OR: 1.41, 95% CI: 1.07-1.85, P = 0.01) was associated with an increased risk of colon cancer. Presence of SNPs linked to increased susceptibility to herpes zoster (OR: 1.26, 95% CI: 1.05-1.52, P = 0.01) was associated with an increased risk of rectal cancer, while infectious mononucleosis (OR: 0.809, 95% CI: 0.80-0.98, P = 0.02) was associated with a decreased risk. CONCLUSION: The study provides the first evidence of the genetic susceptibility associations between different viral infections and CRC, enhancing our understanding of the etiology of CRC.
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Incorporating a sulfonyl group into parent molecules has been shown to effectively improve their synthetic applications and bioactivities. In this study, we present a straightforward and practical approach for the ring-opening reaction of alkenyl-aryl sulfonium salts with sodium sulfinates to produce a range of sulfur-containing alkyl sulfones. This method offers the benefits of mild reaction conditions, easily accessible raw materials, wide substrate applicability, good functional group compatibility, and operational simplicity. Importantly, the resulting products can be readily converted into sulfoxides, sulfones, sulfoximines, and some heterocyclic compounds.
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BACKGROUND: Although previous research has indicated a correlation between smoking and the mortality rate in patients with lung cancer, the impact of early life factors on this relationship remains unclear and requires further investigation. This study aimed to investigate the hypothesis that breastfeeding reduces the risk of lung cancer-related death. METHODS: The authors conducted a prospective cohort study involving 501 859 participants recruited from the United Kingdom Biobank to explore the potential association between breastfeeding and the risk of lung cancer mortality using a Cox proportional hazards model. Subsequently, the polygenic risk score for lung cancer was calculated to detect interactions between genes and the environment. RESULTS: Over a median follow-up duration of 11.8 years, encompassing a total of 501 859 participants, breastfeeding was found to reduce the risk of lung cancer-related death and the impact of maternal smoking on lung cancer mortality in adult offspring. This association remained consistent after stratification. Furthermore, the influence of maternal smoking and breastfeeding on the risk of lung cancer mortality was significant at a high genetic risk level. CONCLUSION: Breastfeeding can reduce the risk of lung cancer-related death and the impact of maternal smoking on lung cancer mortality in adult offspring. This correlation has the potential to reduce the probability of lung-cancer-related deaths in subsequent generations.
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Aleitamento Materno , Neoplasias Pulmonares , Fumar , Humanos , Estudos Prospectivos , Feminino , Neoplasias Pulmonares/mortalidade , Aleitamento Materno/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Adulto , Fumar/efeitos adversos , Reino Unido/epidemiologia , Modelos de Riscos Proporcionais , Filhos Adultos , Fatores de Risco , Idoso , GravidezRESUMO
Background: Individuals with subjective cognitive decline (SCD) are at risk of developing Alzheimer's Disease (AD). Traditional seed-based analysis has shown biased functional connectivity (FC) in SCD individuals. To investigate unbiased altered FC by the brain-wide association study (BWAS) and to determine its association with cognition in SCD individuals. Methods: Measure of association (MA) analysis was applied to detect significant voxels with FC changes. Based on these changes, we identified regions of interest (ROIs) and conducted ROI-wise FC analyses. Correlation analyses were then performed between these FC circuits and cognition. Results: MA analysis identified 10 ROIs with significantly altered voxels. ROI-wise FC analyses revealed 14 strengthened FC, predominantly parietal-occipital link alterations. The FC between the right superior occipital gyrus and the right postcentral gyrus correlated positively with executive function, while the FC between the right middle occipital gyrus and the left angular gyrus correlated positively with episodic memory in SCD individuals. Conclusion: SCD involves multifocal impairments, of which regions of default mode network (DMN) and occipital lobe should be specially focused. Cross-hemispheric alterations indicate an internal interactive impairment pattern in SCD. The reduced FC between the right superior occipital gyrus and the right postcentral gyrus, and between the right middle occipital gyrus and the left angular gyrus, which correlate with specific cognitive functions, could serve as potential biomarkers for SCD diagnosis.
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Objective: To observe the diagnostic value of four serum inflammatory biomarkers, including interleukin 6 (IL-6), interleukin 12P70 (IL-12P70), serum amyloid A (SAA), and procalcitonin (PCT), in rheumatoid arthritis (RA) and to analyze their relationship with the disease activity. Methods: The study included 60 RA patients admitted to the Department of Rheumatology at Anhui Provincial Hospital of Traditional Chinese Medicine between December 2022 and December 2023. Thirty healthy individuals from the hospital's physical examination center served as the control group. Serum levels of IL-6 and IL-12P70 were detected using flow cytometry. SAA levels were determined by immunoturbidimetry, and PCT levels were assessed by chemiluminescence. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), and anticyclic citrullinated peptide (ACCP) were detected using an automated biochemical analyzer. The 28-joint disease activity scores (DAS28-ESR) based on ESR were observed. Statistical analysis included t-tests, rank-sum tests, and Kruskal-Wallis H tests to compare the expression differences of the biomarkers among different groups. The diagnostic value of these biomarkers for RA was analyzed by ROC curve analysis. Spearman correlation analysis was performed to assess the relationships between the four inflammatory biomarkers and CRP, ESR, RF, ACCP, and DAS28-ESR. Results: 1) The expression levels of SAA, IL-6, and IL-12P70 in the RA group were significantly higher than those in the control group (P<0.01). 2) ROC curve analysis showed that the area under the curve (AUC) for PCT was 0.611 (95% confidence interval [CI]: 0.488-0.735, P>0.05), for SAA, it was 0.819 (95% CI: 0.733-0.906, P<0.01), for IL-6, it was 0.875 (95% CI: 0.803-0.946, P<0.01), and for IL-12P70, it was 0.832 (95% CI: 0.746-0.917, P<0.01). The combined index of IL-6, IL-12P70, SAA, and PCT had an AUC of 0.973 (95% CI: 0.942-1.000, P<0.01). This indicates that the four inflammatory biomarkers can assist in the diagnosis of rheumatoid arthritis. 3) The expression levels of PCT and SAA varied significantly among the high, moderate, and low activity RA groups (P<0.01). 4) In RA patients, CRP was positively correlated with SAA (rs =0.75, P<0.01), and IL-6 (rs =0.52, P<0.01). ESR was positively correlated with SAA (rs =0.36, P<0.01). DAS28-ESR was positively correlated with PCT (rs =0.34, P=0.01), SAA (rs =0.51, P<0.01) and IL-6 (rs =0.33, P=0.01). Conclusion: The four inflammatory biomarkers (PCT, SAA, IL-6, and IL-12P70) are closely related to rheumatoid arthritis disease activity and can serve as serum indicators to assist in the diagnosis and assessment of RA.
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Artrite Reumatoide , Biomarcadores , Interleucina-12 , Interleucina-6 , Pró-Calcitonina , Proteína Amiloide A Sérica , Humanos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/sangue , Proteína Amiloide A Sérica/metabolismo , Pró-Calcitonina/sangue , Interleucina-6/sangue , Biomarcadores/sangue , Interleucina-12/sangue , Sedimentação Sanguínea , Masculino , Feminino , Proteína C-Reativa/metabolismo , Proteína C-Reativa/análise , Pessoa de Meia-Idade , Curva ROCRESUMO
In this study, active and intelligent films were fabricated using M. esculenta starch (MES), gum ghatti (GG) and R. nigrum extract (RNE) and their functionality, physicochemical properties and practical application were assessed. Incorporation of GG decreased water vapor permeability (WVP) (9.73 to 8.91 × 10-11 g m-1 s-1 Pa-1), increased tensile strength (TS) (16.63 to 44.45 MPa) and elongation at break (EAB) (4.47 to 6.82%) of MES film. Incorporation of RNE decreased WVP (8.91 to 7.87 × 10-11 g m-1 s-1 Pa-1) and TS (44.45 to 26.33 MPa) of MES-GG film. MES-GG-RNE films showed enhanced thermal stability, light barrier performance, excellent pH and ammonia sensitivities, strong antioxidant activity, and significant visible color change when monitoring beef freshness. Findings supported the application of this strategy in fabrication of MES-GG-RNE films for active and intelligent packaging. Further study on stability, sustainability and consumer acceptability of films is in progress.
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As a host for exchange bias (EB), van der Waals (vdW) magnetic materials have exhibited intriguing and distinct functionalities from conventional magnetic materials. The EB in most vdW systems is far below room temperature, which poses a challenge for practical applications. Here, by using Kerr microscopy, we demonstrate a record-high blocking temperature that approaches room temperature and a huge positive EB field that nears 2 kOe at 100 K in naturally oxidized two-dimensional (2D) vdW ferromagnetic Fe3GaTe2 nanoflakes. Moreover, we realized a reversible manipulation of both the presence/absence and positive/negative signs of EB via a training magnetic field without multiple field cooling processes. Thus, our study clearly reveals the robust, sizable, and sign-tunable EB in vdW magnetic materials up to near room temperature, thereby establishing Fe3GaTe2 as an emerging room-temperature-operating vdW material and paving the way for designing practical 2D spintronic devices.
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Due to low success rates and long cycles of traditional drug development, the clinical tendency is to apply omics techniques to reveal patient-level disease characteristics and individualized responses to treatment. However, the heterogeneous form of data and uneven distribution of targets make drug discovery and precision medicine a non-trivial task. This study takes pyroptosis therapy for triple-negative breast cancer (TNBC) as a paradigm and uses data mining of a large TNBC cohort and drug databases to establish a biofactor-regulated neural network for rapidly screening and optimizing compound pyroptosis drug pairs. Subsequently, biomimetic nanococrystals are prepared using the preferred combination of mitoxantrone and gambogic acid for rational drug delivery. The unique mechanism of obtained nanococrystals regulating pyroptosis genes through ribosomal stress and triggering pyroptosis cascade immune effects are revealed in TNBC models. In this work, a target omics-based intelligent compound drug discovery framework explores an innovative drug development paradigm, which repurposes existing drugs and enables precise treatment of refractory diseases.
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Descoberta de Drogas , Piroptose , Neoplasias de Mama Triplo Negativas , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Humanos , Piroptose/efeitos dos fármacos , Feminino , Descoberta de Drogas/métodos , Animais , Mitoxantrona/farmacologia , Mitoxantrona/uso terapêutico , Xantonas/farmacologia , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Camundongos , Inteligência Artificial , Mineração de Dados , Redes Neurais de ComputaçãoRESUMO
Objective To measure the serum contents of cytokines in patients with rheumatoid arthritis (RA) and explore the clinical application value of combined detection of inflammatory cytokines in evaluating the severity of RA. Methods This study recruited 28 RA patients and 15 healthy individuals who received health checkups during the same period. The expression of inflammatory cytokines including interleukin 1ß (IL-1ß), IL-2, IL-5, IL-6, IL-8, IL-12P70, IL-17, tumor necrosis factor-α (TNF-α), interferon α (IFN-α), IFN-γ, IL-4 and IL-10 were detected with the multiplexed microsphere-based flow cytometric immunoassay. C-reactive protein (CRP) was detected with an automatic biochemical instrument, and erythrocyte sedimentation rate (ESR) was measured by the Westergren method. The disease activity score in 28 joints (DAS28) in the RA group was calculated, and the area under the curve (AUC) of each cytokine and RA disease activity was compared. The correlation of serum levels of inflammatory cytokines with CRP and ESR was analyzed in RA patients. Results In RA patients, the serum levels of IL-2, IL-6, IL-12P70, IL-4 and IL-10 were significantly correlated with the indicator of RA disease activity DAS28-CRP, and the serum levels of IL-12P70, TNF-α and IL-4 were markedly correlated with the indicator of RA disease activity DAS28-ESR. CRP was positively correlated with IL-6 (r=0.515), IL-12P70 (r=0.530), IL-4 (r=0.539), and IL-10(r=0.434). ESR was positively correlated with IL-6 (r=0.403), IL-12P70 (r=0.475), TNF-α (r=0.497), and IL-4 (r=0.450). Compared with the normal CRP and ESR group, the abnormal CRP group showed an increase in the levels of IL-6, IL-12P70, IL-2, IL-4 and IL-10, and the abnormal ESR group exhibited an elevation in the levels of IL-12P70, IL-4 and TNF-α. The expression of IL-8, IFN-α and IFN-γ was higher in the experimental group than in the control group. Conclusion Serum inflammatory cytokines detection has shed light on the early diagnosis and severity evaluation of RA and can be used as a pivotal indcator for the diagnosis of RA.
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Artrite Reumatoide , Citocinas , Diagnóstico Precoce , Humanos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/sangue , Citocinas/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Proteína C-Reativa/análise , Sedimentação Sanguínea , Idoso , Inflamação/diagnóstico , Inflamação/sangue , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Accumulating evidence indicates that PSAT1 not only reprogrammed metabolic function but also exhibits "moonlighting" functions in promoting tumor malignancy. However, the underlying molecular mechanisms of PSAT1 promoting ER-negative breast cancer cell migration need further investigation. METHODS: Briefly, the PSAT1 and ITGA2 expression in cells and tissues was detected using qRT-PCR, immunofluorescence staining and western blot assay. The effect of PSAT1 and ITGA2 was verified both in vitro and in vivo. RNA-seq analysis explored a series of differently expressed genes. The regulation between SP1 and ITGA2 was investigated by ChIP analysis. RESULTS: We reported PSAT1 was highly expressed in ER-breast cancer tissues and tumor cells and positively correlated with metastasis. Moreover, RNA-seq analysis explored a series of differently expressed genes, including ITGA2, in PSAT1 overexpressed cells. Mechanistically, PSAT1 facilitated breast cancer metastasis via the p-AKT/SP1/ITGA2 axis. We further elucidated that PSAT1 promoted the entry of SP1 into the nucleus through the upregulation of p-AKT and confirmed ITGA2 is a target of SP1. In addition, enhanced cell migration was remarkably reversed by ITGA2 depletion or p-AKT inhibitor treatment. CONCLUSION: This study clarified the mechanism of PSAT1 in promoting ER-negative breast cancer metastasis, which may provide mechanistic clues for attenuating breast cancer metastasis.
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Neoplasias da Mama , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Integrina alfa2 , Metástase Neoplásica , Proteínas Proto-Oncogênicas c-akt , Fator de Transcrição Sp1 , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Feminino , Proteínas Proto-Oncogênicas c-akt/metabolismo , Movimento Celular/genética , Fator de Transcrição Sp1/metabolismo , Fator de Transcrição Sp1/genética , Integrina alfa2/metabolismo , Integrina alfa2/genética , Linhagem Celular Tumoral , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/genética , Animais , Camundongos , Transdução de Sinais , Camundongos Nus , Células MCF-7 , Antígenos de Superfície , Proteínas de NeoplasiasRESUMO
BACKGROUND: Breast cancer is a prevalent public health concern affecting numerous women globally and is associated with palmitoylation, a post-translational protein modification. Despite increasing focus on palmitoylation, its specific implications for breast cancer prognosis remain unclear. The work aimed to identify prognostic factors linked to palmitoylation in breast cancer and assess its effectiveness in predicting responses to chemotherapy and immunotherapy. METHODS: We utilized the "limma" package to analyze the differential expression of palmitoylation-related genes between breast cancer and normal tissues. Hub genes were identified using the "WGCNA" package. Using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis, we identified a prognostic feature associated with palmitoylation and developed a prognostic nomogram with the "regplot" package. The predictive values of the model for chemotherapy and immunotherapy responses were assessed using immunophenoscore (IPS) and the "pRophetic" package. RESULTS: We identified 211 differentially expressed genes related to palmitoylation, among which 44 demonstrated prognostic potential. Subsequently, a predictive model comprising eleven palmitoylation-related genes was developed. Patients were classified into high-risk and low-risk groups based on the median risk score. The findings revealed that individuals in the high-risk group exhibited lower survival rates, while those in the low-risk group showed increased immune cell infiltration and improved responses to chemotherapy and immunotherapy. Moreover, the BC-Palmitoylation Tool website was established. CONCLUSION: This study developed the first machine learning-based predictive model for palmitoylation-related genes and created a corresponding website, providing clinicians with a valuable tool to improve patient outcomes.
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Biomarcadores Tumorais , Neoplasias da Mama , Regulação Neoplásica da Expressão Gênica , Lipoilação , Aprendizado de Máquina , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Prognóstico , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Nomogramas , Biologia Computacional/métodos , Resultado do Tratamento , Transcriptoma , Redes Reguladoras de Genes , Imunoterapia/métodosRESUMO
The magnitude of terrestrial carbon (C)-climate feedback largely depends on the temperature sensitivity of soil organic matter (SOM) decomposition (Q10). However, our understanding of determinants of Q10 for SOM fractions such as particulate and mineral-associated organic matter (POM and MAOM, respectively) is still inadequate. Particularly, it remains unclear whether microbial effects on Q10 are fraction-dependent, which induces large uncertainties in projecting soil C dynamics. Here, we conducted large-scale topsoil sampling on the Tibetan Plateau, in combination with SOM fractionation and 300-day laboratory incubation to assess SOM fraction-dependent linkages between Q10 and microbial properties. We found that compared with MAOM, POM had larger Q10 and greater microbial diversity, and also structured distinct microbial communities as well as their co-occurrence patterns. Furthermore, associations of Q10 with microbial properties differed between the two SOM fractions. Bacterial community composition and relative abundance of bacterial keystone taxa affected Q10 for POM and MAOM respectively, while bacterial alpha diversity showed opposite relationships with Q10 for POM and MAOM. These findings highlight the necessity of incorporating SOM fraction-dependent microbial properties and their linkages with Q10 into Earth system models to accurately predict terrestrial C-climate feedback.
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Microbiota , Microbiologia do Solo , Solo , Temperatura , Solo/química , Tibet , Bactérias/classificação , Bactérias/metabolismo , Bactérias/isolamento & purificação , Carbono/análise , Carbono/metabolismoRESUMO
Background: The newest clinical evidence that the relationship between the peritoneal cancer index (PCI) and the postoperative prognosis of advanced ovarian cancer patients remains controversial, and there are no large-sample and multicenter studies to clarify this matter. Therefore, in this paper, we used meta-analysis to systematically assess the postoperative prognostic value of PCI in subjects with advanced ovarian cancer to provide individualized treatment plans and thus improve the prognosis of patients. Methods: Literature on the correlation between PCI and the postoperative prognosis in subjects with advanced OC undergoing cytoreductive surgery (CRS) was searched in the Cochrane Library, Pubmed, Embase, and Web of Science from the database inception to April 20, 2023. The search was updated on February 28, 2024. We only included late-stage (FIGO stage: III-IV) patients who did not undergo neoadjuvant chemotherapy (NACT) or hyperthermic intraperitoneal chemotherapy (HIPEC). Afterwards, literature screening and data extraction were conducted using Endnote20 software. The literature quality was assessed using the Newcastle-Ottawa Scale (NOS). Lastly, statistical analysis was performed with STATA 15.0 software. Results: Five studies with 774 patients were included. The result indicated that patients with high PCI had a worse prognosis than those with low PCI. The combined hazard ratio was 2.79 [95%CI: (2.04, 3.82), p<0.001] for overall survival (OS) in patients with high PCI. Further subgroup analysis by the FIGO staging revealed that in stage III [HR: 2.61, 95%CI: (2.00, 3.40), p<0.001] and stage III-IV patients [HR: 2.69, 95%CI: (1.66, 4.36), p<0.001], a high PCI score was significantly associated with a worse prognosis. The PCI score had a greater impact on the OS of patients with higher stages. The combined hazard ratio was 1.89 [95%CI: (1.51, 2.36), p<0.001] for progression-free survival (PFS) in patients with high PCI. Conclusion: PCI may be used as a postoperative prognosis indicator in patients with advanced OC on primary debulking surgery. High PCI indicates a worse prognosis. However, further research is warranted to confirm these findings. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023424010.
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Organoids are in vitro 3D models that maintain their own tissue structure and function. They largely overcome the limitations of traditional tumor models and have become a powerful research tool in the field of oncology in recent years. Gynecological malignancies are major diseases that seriously threaten the life and health of women and urgently require the establishment of models with a high degree of similarity to human tumors for clinical studies to formulate individualized treatments. Currently, organoids are widely studied in exploring the mechanisms of gynecological tumor development as a means of drug screening and individualized medicine. Ovarian, endometrial, and cervical cancers as common gynecological malignancies have high morbidity and mortality rates among other gynecological tumors. Therefore, this study reviews the application of modelling, drug efficacy assessment, and drug response prediction for ovarian, endometrial, and cervical cancers, thereby clarifying the mechanisms of tumorigenesis and development, and providing precise treatment options for gynecological oncology patients.
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Hypoxia promotes tumorigenesis and lactate accumulation in esophageal squamous cell carcinoma (ESCC). Lactate can induce histone lysine lactylation (Kla, a recently identified histone marks) to regulate transcription. However, the functional consequence of histone Kla under hypoxia in ESCC remains to be explored. Here, we reveal that hypoxia facilitates histone H3K9la to enhance LAMC2 transcription for proliferation of ESCC. We found that global level of Kla was elevated under hypoxia, and thus identified the landscape of histone Kla in ESCC by quantitative proteomics. Furthermore, we show a significant increase of H3K9la level induced by hypoxia. Next, MNase ChIP-seq and RNA-seq analysis suggest that H3K9la is enriched at the promoter of cell junction genes. Finally, we demonstrate that the histone H3K9la facilitates the expression of LAMC2 for ESCC invasion by in vivo and in vitro experiments. Briefly, our study reveals a vital role of histone Kla triggered by hypoxia in cancer.
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Glutathione (GSH) is an important antioxidant that is generated and degraded via the GSH cycle. Quantification of the main components in the GSH cycle is necessary to evaluate the process of GSH. In this study, a robust ultra-performance liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of 10 components (GSH; γ-glutamylcysteine; cysteinyl-glycine; n-acetylcysteine; homocysteine; cysteine; cystine; methionine; glutamate; pyroglutamic acid) in GSH cycle was developed. The approach was optimized in terms of derivative, chromatographic, and spectrometric conditions as well as sample preparation. The unstable thiol groups of GSH, γ-glutamylcysteine, cysteinyl-glycine, n-acetylcysteine, cysteine, and homocysteine were derivatized by n-ethylmaleimide. The derivatized and underivatized analytes were separated on an amino column with gradient elution. The method was further validated in terms of selectivity (no interference), linearity (R2 > 0.99), precision (% relative standard deviation [RSD%] range from 0.57 to 10.33), accuracy (% relative error [RE%] range from -3.42 to 10.92), stability (RSD% < 5.68, RE% range from -2.54 to 4.40), recovery (RSD% range from 1.87 to 7.87) and matrix effect (RSD% < 5.42). The validated method was applied to compare the components in the GSH cycle between normal and oxidative stress cells, which would be helpful in clarifying the effect of oxidative stress on the GSH cycle.
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Glutationa , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Glutationa/análise , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Homocisteína/análise , Cisteína/análise , Ácido Pirrolidonocarboxílico/análise , Ácido Pirrolidonocarboxílico/química , Ácido Pirrolidonocarboxílico/metabolismo , Dipeptídeos/análise , Acetilcisteína/análise , Acetilcisteína/química , Cistina/análiseRESUMO
Hepatitis C virus (HCV) can cause a range of kidney diseases. HCV is the primary cause of mixed cryoglobulinaemia, which leads to cryoglobulinaemic vasculitis and cryoglobulinaemic glomerulonephritis (GN). Patients with acute cryoglobulinaemic vasculitis often exhibit acute kidney disease due to HCV infection, which typically progresses to acute kidney injury (AKI). HCV also increases the risk of chronic kidney disease (CKD) and the likelihood of developing end-stage renal disease (ESRD). Currently, direct-acting antiviral agents (DAAs) can be used to treat kidney disease at different stages. This review focuses on key findings regarding HCV and kidney disease, discusses the impact of DAAs, and highlights the need for further research and treatment.
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The highly dispersed small-size metal co-catalysts can effectively improve the photocatalytic efficiency of semiconductor photocatalysts by separating photogenerated electrons and enriching active sites. However, this system tends to aggregate in the absence of carrier, resulting in the decrease of active sites. Here, MOF-derived carbon skeleton (MDCS) encapsulated Ni nanoparticles (Ni@MDCS) and BiOBr was loaded onto carbonized cellulose fibers (CCF) with the help of polydopamine (PDA) to construct high-performance and recyclable photocatalytic paper for photocatalytic degradation of organic dyes in water. The characterization results showed that MDCS promoted good dispersion of Ni nanoparticles and provided sufficient active sites. And Ni@MDCS as a co-catalyst accelerated the separation of photogenerated carriers in BiOBr. The PDA improved the loading state of Ni@MDCS on CCF and converted into N-doped C in the carbonization process for further increasing the transfer efficiency of photogenerated electrons. In the composite paper, the stable loading of Ni@MDCS/BiOBr hybrid on CCF improved the dispersion and reusability of photocatalyst. The degradation rate of rhodamine B on CCF/PDA-C/Ni@MDCS/BiOBr paper was as high as 94.6 % after 60 min visible light irradiation, which was about 2.5 times higher than that of CCF/BiOBr paper. During 10 cycles, CCF/PDA-C/Ni@MDCS/BiOBr paper maintained high photocatalytic efficiency and good structural stability. This study provides a new way for developing high-performance and recyclable photocatalytic paper.