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1.
J Orthop ; 58: 58-65, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39055286

RESUMO

Background: Managing adult degenerative lumbar scoliosis (ADLS) presents a complex challenge, requiring advanced, minimally invasive surgical techniques. Objective: This study aims to evaluate and compare the efficacy and outcomes of oblique lateral interbody fusion (OLIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in treating ADLS, with an emphasis on surgical methods, recovery times, and spinal correction results. Methods: We reviewed 42 patients with ADLS who did not respond to conservative treatments. These patients underwent either OLIF or MIS-TLIF procedures. Key factors analyzed included surgical duration, blood loss, complications, and changes in preoperative and postoperative lumbar lordosis (LL), anterior and posterior disc height (ADH, PDH), and Cobb angles. Statistical analysis was conducted using SPSS software, with significance determined at p < 0.05. Results: The OLIF technique showed notable benefits in multi-segment spinal corrections, particularly in enhancing intervertebral disc height and correcting Cobb angles. While both surgical methods effectively addressed spinal deformities, OLIF was less invasive, resulting in reduced blood loss, shorter surgery times, and fewer complications. No significant differences were found between the two techniques for single-segment corrections. Conclusion: For multi-segment spinal corrections in ADLS, OLIF is a superior choice due to its minimal invasiveness and favorable recovery profile. However, for patients with primarily radicular symptoms and no significant postural alterations, MIS-TLIF may be more appropriate.

2.
Oncologist ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990195

RESUMO

BACKGROUND: Encouraging antitumor activity of nab-paclitaxel plus S-1 (AS) has been shown in several small-scale studies. This study compared the efficacy and safety of AS versus standard-of-care nab-paclitaxel plus gemcitabine (AG) as a first-line treatment for advanced pancreatic cancer (PC). METHODS: In this multicenter, randomized, phase II trial, eligible patients with unresectable, locally advanced, or metastatic PC were recruited and randomly assigned (1:1) to receive AS (nab-paclitaxel 125 mg/m2 on days 1 and 8; S-1 twice daily on days 1 through 14) or AG (nab-paclitaxel 125 mg/m2 on days 1 and 8; gemcitabine 1000 mg/m2 on days 1 and 8) for 6 cycles. The primary endpoint was progression-free survival (PFS). RESULTS: Between July 16, 2019, and September 9, 2022, 62 patients (AS, n = 32; AG, n = 30) were treated and evaluated. With a median follow-up of 8.36 months at preplanned interim analysis (data cutoff, March 24, 2023), the median PFS (8.48 vs 4.47 months; hazard ratio [HR], 0.402; P = .002) and overall survival (OS; 13.73 vs 9.59 months; HR, 0.226; P < .001) in the AS group were significantly longer compared to the AG group. More patients had objective response in the AS group than AG group (37.50% vs 6.67%; P = .005). The most common grade 3-4 adverse events were neutropenia and leucopenia in both groups, and gamma glutamyl transferase increase was observed only in the AG group. CONCLUSION: The first-line AS regimen significantly extended both PFS and OS of Chinese patients with advanced PC when compared with the AG regimen, with a comparable safety profile. (ClinicalTrials.gov Identifier: NCT03636308).

3.
J Neurosci ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39019613

RESUMO

Although anesthesia provides favorable conditions for surgical procedures, recent studies have revealed that the brain remains active in processing noxious signals even during anesthesia. However, whether and how these responses affect the anesthesia effect remains unclear. The ventrolateral periaqueductal gray (vlPAG), a crucial hub for pain regulation, also plays an essential role in controlling general anesthesia. Hence, it was hypothesized that the vlPAG may be involved in the regulation of general anesthesia by noxious stimuli. Here, we found that acute noxious stimuli, including capsaicin-induced inflammatory pain, acetic acid-induced visceral pain, and incision-induced surgical pain, significantly delayed recovery from sevoflurane anesthesia in male mice, whereas this effect was absent in the spared nerve injury-induced chronic pain. Pre-treatment with peripheral analgesics could prevent the delayed recovery induced by acute nociception. Furthermore, we found that acute noxious stimuli, induced by the injection of capsaicin under sevoflurane anesthesia, increased c-Fos expression and activity in the GABAergic neurons of the ventrolateral periaqueductal gray (vlPAGGABA). Specific re-activation of capsaicin-activated vlPAGGABA neurons mimicked the effect of capsaicin and its chemogenetic inhibition prevented the delayed recovery from anesthesia induced by capsaicin. Finally, we revealed that the vlPAGGABA neurons regulated the recovery from anesthesia through the inhibition of ventral tegmental area dopaminergic neuronal activity, thus decreasing dopamine release and activation of dopamine D1-like receptors in the brain. These findings reveal a novel, cell- and circuit-based mechanism for regulating anesthesia recovery by nociception and it is important to provide new insights for guiding the management of the anesthesia recovery period.Significance Statement There is evidence that the brain still processes pain signals during anesthesia. However, the significance and mechanisms of this phenomenon are poorly understood. Here, utilizing various pain models under anesthesia and integrating multiple techniques, the current study found that acute, but not chronic, ongoing noxious stimuli delayed the recovery from sevoflurane anesthesia. Furthermore, we identified the vlPAGGABA-VTA circuit as a critical target for mediating this effect by inhibiting the VTA dopaminergic neurons, reducing dopamine release, and decreasing the activation of dopamine D1-like receptors in the brain. This study presents the initial finding that the absence of pain perception under anesthesia does not equate to the absence of harm, offering a new perspective on guiding the administration of anesthesia medications.

4.
Nat Prod Res ; : 1-9, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39021087

RESUMO

A new series of usnic acid (UA) monoesterified derivatives 2-15 were designed and synthesised using UA (1) as starting material. The structural characterisation of all compounds was elucidated using 1H-NMR and 13C-NMR spectral data. In vitro studies demonstrated thatmost UA derivatives exhibited higher inhibitory activity against Candida albicans and Staphylococcus aureus. Among them, compound 7 displayed the highest inhibitory activity against C. albicans with a minimum inhibitory concentration (MIC) of 32 µg/mL. Compounds 5, 8, 9, 11and 13 demonstrated superior inhibition of S. aureus (MIC, 16 µg/mL) and biofilm formation in a concentration-dependent manner. With the exception of 11, compounds 5, 8, 9 and 13 were all more effective than UA in inhibiting S. aureus biofilms. This research highlights the potential of UA monoesterified derivatives for the development of dual antimicrobial and antibiofilm agents.

6.
J Clin Invest ; 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39058792

RESUMO

Patients with autism spectrum disorder (ASD) frequently experience sleep disturbance. Genetic mutations in Neuroligin-3 (NLG3) genes are highly correlative with ASD and sleep disturbance. However, the cellular and neural circuit bases of this correlation remain elusive. Here, we find the conditional knockout of NLG3 (NLG3-CKO) in the medial septum (MS) impairs social memory and reduces sleep. NLG3 knockout in MS causes hyperactivity of MS-GABA neurons during social avoidance and wakefulness. Activation of MSGABA neurons induces social memory deficits and sleep loss in C57BL/6 mice. In contrast, inactivation of these neurons ameliorates social memory deficits and sleep loss in NLG3-CKO mice. Sleep deprivation leads to social memory deficits, while social isolation causes sleep loss, both resulting in a reduction of NLG3 expression and an increase in activity of GABAergic neurons in MS from C57BL/6 mice. Furthermore, MS-GABA-innervated CA2 neurons specifically regulate social memory without impacting sleep, whereas MSGABA-innervating neurons in the preoptic area selectively control sleep without affecting social behavior. Together, these findings demonstrate that the hyperactive MS-GABA neurons impair social memory and disrupt sleep resulting from NLG3 knockout in MS, and achieve the modality specificity through their divergent downstream targets.

7.
Artigo em Inglês | MEDLINE | ID: mdl-39031110

RESUMO

OBJECTIVE: To evaluate the prognostic factors and survival outcomes of patients with surgically treated high-grade neuroendocrine carcinoma of the cervix (NECC). METHODS: This multicenter, retrospective study involved 98 cervical cancer patients with stage IA2-IIA2 and IIIC1/2p high-grade NECC. We divided the patients into two groups based on histology: the pure and mixed groups. All clinicopathologic variables were retrospectively evaluated. Cox regression and Kaplan-Meier methods were used for analysis. RESULTS: In our study, 60 patients were in the pure group and 38 patients were in the mixed group. Cox multivariate analysis showed that mixed histology was a protective factor impacting overall survival (OS) (P = 0.026) and progression free survival (PFS) (P = 0.018) in surgically treated high-grade NECC. Conversely, survival outcomes were negatively impacted by ovarian preservation (OS: HR, 20.84; 95% CI: 5.02-86.57, P < 0.001), age >45 years (OS: HR, 4.50; 95% CI: 1.0-18.83, P = 0.039), tumor size >4 cm (OS: HR, 6.23; 95% CI: 2.34-16.61, P < 0.001), parity >3 (OS: HR, 4.50; 95% CI: 1.02-19.91, P = 0.048), and perineural invasion (OS: HR, 5.21; 95% CI: 1.20-22.53, P = 0.027). Kaplan-Meier survival curves revealed notable differences in histologic type (OS: P = 0.045; PFS: P = 0.024), chemotherapy (OS: P = 0.0056; PFS: P = 0.0041), ovarian preservation (OS: P = 0.00031; PFS: P = 0.0023), uterine invasion (OS: P < 0.0001; PFS: P < 0.0001), and depth of stromal invasion (OS: P = 0.043; PFS: P = 0.022). CONCLUSION: Patients with mixed histologic types who undergo surgery for high-grade NECC have a better prognosis. Meanwhile, ovarian preservation, tumor size >4 cm, parity >3, age >45 years and perineural invasion were poor prognostic predictors. Therefore, patients with high-risk factors should be considered in clinical practice.

8.
J Exp Clin Cancer Res ; 43(1): 213, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39085849

RESUMO

Non-small cell lung cancer (NSCLC) is characterized by a high incidence rate and poor prognosis worldwide. A deeper insight into the pathogenesis of NSCLC and identification of novel therapeutic targets are essential to improve the prognosis of NSCLC. In this study, we revealed that fibrinogen-like protein 1 (FGL1) promotes proliferation, migration, and invasion of NSCLC cells. Mechanistically, we found that Stat3 acts as a transcription factor and can be recruited to the FGL1 promoter, enhancing FGL1 promoter activity. Lysine-specific demethylase 4A (KDM4A) interacts with Stat3 and facilitates the removal of methyl groups from H3K9me3, thereby enhancing Stat3-mediated transcription of FGL1. Furthermore, we observed that Stat3 and KDM4A promote NSCLC cell proliferation, migration, and invasion partly by upregulating FGL1 expression. Additionally, the expression of FGL1 was significantly higher in cancer tissues (n = 90) than in adjacent non-cancerous tissues (n = 90). Furthermore, patients with high FGL1 expression had a shorter overall survival (OS) compared to those with low FGL1 expression. We measured the expression levels of FGL1 on circulating tumor cells (CTCs) in 65 patients and found that patients with a dynamic decrease in FGL1 expression on CTCs exhibited a better therapeutic response. These findings suggest that the dynamic changes in FGL1 expression can serve as a potential biomarker for predicting treatment efficacy in NSCLC. Overall, this study revealed the significant role and regulatory mechanisms of FGL1 in the development of NSCLC, suggesting its potential as a therapeutic target for patients with NSCLC. Future studies should provide more personalized and effective treatment options for patients with NSCLC to improve clinical outcomes.


Assuntos
Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas , Progressão da Doença , Histona Desmetilases com o Domínio Jumonji , Neoplasias Pulmonares , Fator de Transcrição STAT3 , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Camundongos , Animais , Histona Desmetilases com o Domínio Jumonji/metabolismo , Histona Desmetilases com o Domínio Jumonji/genética , Feminino , Metástase Neoplásica , Fibrinogênio/metabolismo , Fibrinogênio/genética , Masculino , Linhagem Celular Tumoral , Proliferação de Células , Movimento Celular , Prognóstico , Regulação Neoplásica da Expressão Gênica
9.
Front Microbiol ; 15: 1363158, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846573

RESUMO

A total of 1,348 endophytic fungal strains were isolated from Ferula ovina, F. galbaniflua, and F. persica. They included Eurotiales (16 species), Pleosporales (11 species), Botryosphaeriales (1 species), Cladosporiales (2 species), Helotiales (6 species), Hypocreales (31 species), Sordariales (7 species), Glomerellales (2 species), and Polyporales (1 species). F. ovina had the richest species composition of endophytic fungi, and the endophytic fungi were most abundant in their roots compared to shoots. Chao, Margalef, Shannon, Simpson, Berger-Parker, Menhinick, and Camargo indices showed that F. ovina roots had the most endophytic fungal species. The frequency distribution of fungal species isolated from Ferula spp. fell into the log-series model, and F. ovina roots had the highest Fisher alpha. The dominance indices showed that there are no dominant species in the endophytic fungal community isolated from Ferula spp., indicating community stability. Evenness values were 0.69, 0.90, 0.94, and 0.57 for endophytic fungi isolated from F. ovina roots, F. ovina shoots, F. galbaniflua roots, and F. persica roots, respectively, indicating a species distribution that tends toward evenness. The fungal species community isolated from each of F. ovina roots, F. ovina shoots, F. galbaniflua roots, and F. persica roots was a diverse species group originating from a homogeneous habitat. Their distribution followed a log-normal distribution, suggesting that the interactions of numerous independent environmental factors multiplicatively control species abundances. Principal component analysis showed that the highest species diversity and dominance were observed in the endophytic fungal community isolated from F. ovina and F. persica roots, respectively.

11.
Nat Commun ; 15(1): 4947, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858350

RESUMO

The potential brain mechanism underlying resilience to socially transferred allodynia remains unknown. Here, we utilize a well-established socially transferred allodynia paradigm to segregate male mice into pain-susceptible and pain-resilient subgroups. Brain screening results show that ventral tegmental area glutamatergic neurons are selectively activated in pain-resilient mice as compared to control and pain-susceptible mice. Chemogenetic manipulations demonstrate that activation and inhibition of ventral tegmental area glutamatergic neurons bi-directionally regulate resilience to socially transferred allodynia. Moreover, ventral tegmental area glutamatergic neurons that project specifically to the nucleus accumbens shell and lateral habenula regulate the development and maintenance of the pain-resilient phenotype, respectively. Together, we establish an approach to explore individual variations in pain response and identify ventral tegmental area glutamatergic neurons and related downstream circuits as critical targets for resilience to socially transferred allodynia and the development of conceptually innovative analgesics.


Assuntos
Ácido Glutâmico , Hiperalgesia , Neurônios , Núcleo Accumbens , Área Tegmentar Ventral , Animais , Masculino , Hiperalgesia/fisiopatologia , Área Tegmentar Ventral/fisiopatologia , Camundongos , Ácido Glutâmico/metabolismo , Núcleo Accumbens/fisiopatologia , Neurônios/metabolismo , Mesencéfalo , Camundongos Endogâmicos C57BL , Resiliência Psicológica , Habenula , Modelos Animais de Doenças
12.
Infect Drug Resist ; 17: 2189-2198, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835493

RESUMO

Objective: In this paper, we analyzed the clinical data of patients with meningoencephalitis caused by Streptococcus intermedius to understand better the clinical characteristics of the disease and recommend auxiliary diagnostic mode as well as treatment experience. Methods: We reviewed the clinical data of two patients admitted to our department in 2019 with meningoencephalitis caused by S. intermedius. Results: Two female patients were examined, one of whom had a history of radiotherapy for nasopharyngeal carcinoma while the other had no underlying disease. These two patients were admitted with symptoms of meningoencephalitis. Cerebrospinal fluid examinations revealed elevated levels of leukocytes and protein. After treatment with meropenem, the condition improved for a brief time, but then worsened with a decline in mental status and limb movement. Blood and cerebrospinal fluid cultures demonstrated the absence of pathogenic bacteria, while genome sequencing of cerebrospinal fluids revealed the presence of S. intermedius. Cranial magnetic resonance imaging revealed multiple cerebral abscesses (CAs). After coadministration of linezolid as an anti-infective, clinical symptoms gradually improved, and the CAs shrank on follow-up imaging. The condition exhibited a pattern of improvement-deterioration-improvement. Conclusion: Meningoencephalitis caused by S. intermedius is complex and prone to fluctuation and formation of multiple CAs. The definitive clinical diagnosis of this disease can be aided by genome sequencing technology, and early clarification of the etiology combined with the use of potent antibiotics is effective.

14.
Int J Biol Macromol ; 269(Pt 2): 132168, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38729496

RESUMO

Ferula spp. are plants that produce oleo-gum-resins (OGRs), which are plant exudates with various colors. These OGRs have various industrial applications in pharmacology, perfumery, and food. The main constituents of these OGRs are terpenoids, a diverse group of organic compounds with different structures and functions. The biosynthesis of OGRs in Ferula spp., particularly galbanum, holds considerable economic and ecological importance. However, the molecular and genetic underpinnings of this biosynthetic pathway remain largely enigmatic. This review provides an overview of the current state of knowledge on the biosynthesis of OGRs in Ferula spp., highlighting the major enzymes, genes, and pathways involved in the synthesis of different terpenoid classes, such as monoterpenes, sesquiterpenes, and triterpenes. It also examines the potential of using omics techniques, such as transcriptomics and metabolomics, and genome editing tools, such as CRISPR/Cas, to increase the yield and quality of Ferula OGRs, as well as to create novel bioactive compounds with enhanced properties. Moreover, this review addresses the current challenges and opportunities of applying gene editing in Ferula spp., and suggests some directions for future research and development.


Assuntos
Ferula , Ferula/química , Gomas Vegetais/química , Vias Biossintéticas/genética , Resinas Vegetais/química , Terpenos/metabolismo , Terpenos/química , Edição de Genes
15.
Biochem Biophys Res Commun ; 716: 150038, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38704891

RESUMO

Hyperuricemia (HUA) is caused by increased synthesis and/or insufficient excretion of uric acid (UA). Long-lasting HUA may lead to a number of diseases including gout and kidney injury. Harpagoside (Harp) is a bioactive compound with potent anti-inflammatory activity from the roots of Scrophularia ningpoensis. Nevertheless, its potential effect on HUA was not reported. The anti-HUA and nephroprotective effects of Harp on HUA mice were assessed by biochemical and histological analysis. The proteins responsible for UA production and transportation were investigated to figure out its anti-HUA mechanism, while proteins related to NF-κB/NLRP3 pathway were evaluated to reveal its nephroprotective mechanism. The safety was evaluated by testing its effect on body weight and organ coefficients. The results showed that Harp significantly reduced the SUA level and protected the kidney against HUA-induced injury but had no negative effect on safety. Mechanistically, Harp significantly reduced UA production by acting as inhibitors of xanthine oxidase (XOD) and adenosine deaminase (ADA) and decreased UA excretion by acting as activators of ABCG2, OAT1 and inhibitors of GLUT9 and URAT1. Moreover, Harp markedly reduced infiltration of inflammatory cells and down-regulated expressions of TNF-α, NF-κB, NLRP3 and IL-1ß in the kidney. Harp was a promising anti-HUA agent.


Assuntos
Glicosídeos , Hiperuricemia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piranos , Ácido Úrico , Animais , Hiperuricemia/tratamento farmacológico , Hiperuricemia/metabolismo , Ácido Úrico/sangue , Masculino , Glicosídeos/farmacologia , Glicosídeos/uso terapêutico , Piranos/farmacologia , Piranos/uso terapêutico , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , NF-kappa B/metabolismo , Camundongos Endogâmicos C57BL
16.
Curr Med Sci ; 44(2): 333-345, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38622424

RESUMO

OBJECTIVE: Peritoneal fibrosis (PF) is the main cause of declining efficiency and ultrafiltration failure of the peritoneum, which restricts the long-term application of peritoneal dialysis (PD). This study aimed to investigate the therapeutic effects and mechanisms of bone marrow mesenchymal stem cells-derived exosomes (BMSC-Exos) on PF in response to PD. METHODS: Small RNA sequencing analysis of BMSC-Exos was performed by second-generation sequencing. C57BL/6J mice were infused with 4.25% glucose-based peritoneal dialysis fluid (PDF) for 6 consecutive weeks to establish a PF model. A total of 36 mice were randomly divided into 6 groups: control group, 1.5% PDF group, 2.5% PDF group, 4.25% PDF group, BMSC-Exos treatment group, and BMSC-Exos+TP53 treatment group. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed to measure the expression level of miR-27a-3p in BMSC-Exos and peritoneum of mice treated with different concentrations of PDF. HE and Masson staining were performed to evaluate the extent of PF. The therapeutic potential of BMSC-Exos for PF was examined through pathological examination, RT-qPCR, Western blotting, and peritoneal function analyses. Epithelial-mesenchymal transition (EMT) of HMrSV5 was induced with 4.25% PDF. Cells were divided into control group, 4.25% PDF group, BMSC-Exos treatment group, and BMSC-Exos+TP53 treatment group. Cell Counting Kit-8 assay was used to measure cell viability, and transwell migration assay was used to verify the capacity of BMSC-Exos to inhibit EMT in HMrSV5 cells. RESULTS: Small RNA sequencing analysis showed that miR-27a-3p was highly expressed in BMSC-derived exosomes compared to BMSCs. The RT-qPCR results showed that the expression of miR-27a-3p was upregulated in BMSC-Exos, but decreased in PD mice. We found that PF was glucose concentration-dependently enhanced in the peritoneum of the PD mice. Compared with the control mice, the PD mice showed high solute transport and decreased ultrafiltration volume as well as an obvious fibroproliferative response, with markedly increased peritoneal thickness and higher expression of α-SMA, collagen-I, fibronectin, and ECM1. The mice with PD showed decreased miR-27a-3p. Peritoneal structural and functional damage was significantly attenuated after BMSC-Exos treatment, while PF and mesothelial damage were significantly ameliorated. Additionally, markers of fibrosis (α-SMA, collagen-I, fibronectin, ECM1) and profibrotic cytokines (TGF-ß1, PDGF) were downregulated at the mRNA and protein levels after BMSC-Exos treatment. In HMrSV5 cells, BMSC-Exos reversed the decrease in cell viability and the increase in cell migratory capacity caused by high-glucose PDF. Western blotting and RT-qPCR analysis revealed that BMSC-Exos treatment resulted in increased expression of E-cadherin (epithelial marker) and decreased expression of α-SMA, Snail, and vimentin (mesenchymal markers) compared to those of the 4.25% PDF-treated cells. Importantly, a dual-luciferase reporter assay showed that TP53 was a target gene of miR-27a-3p. TP53 overexpression significantly reversed the decreases in PF and EMT progression induced by BMSC-Exos. CONCLUSION: The present results demonstrate that BMSC-Exos showed an obvious protective effect on PD-related PF and suggest that BMSC-derived exosomal miR-27a-3p may exert its inhibitory effect on PF and EMT progression by targeting TP53.


Assuntos
Exossomos , MicroRNAs , Diálise Peritoneal , Fibrose Peritoneal , Camundongos , Animais , Fibrose Peritoneal/genética , Fibrose Peritoneal/terapia , Fibronectinas , Exossomos/metabolismo , Camundongos Endogâmicos C57BL , Diálise Peritoneal/efeitos adversos , MicroRNAs/genética , MicroRNAs/metabolismo , Glucose , Colágeno
17.
Sci China Life Sci ; 67(7): 1413-1426, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38565741

RESUMO

Endocrine therapy that blocks estrogen signaling is the most effective treatment for patients with estrogen receptor positive (ER+) breast cancer. However, the efficacy of agents such as tamoxifen (Tam) is often compromised by the development of resistance. Here we report that cytokines-activated nuclear IKKα confers Tam resistance to ER+ breast cancer by inducing the expression of FAT10, and that the expression of FAT10 and nuclear IKKα in primary ER+ human breast cancer was correlated with lymphotoxin ß (LTB) expression and significantly associated with relapse and metastasis in patients treated with adjuvant mono-Tam. IKKα activation or enforced FAT10 expression promotes Tam-resistance while loss of IKKα or FAT10 augments Tam sensitivity. The induction of FAT10 by IKKα is mediated by the transcription factor Pax5, and coordinated via an IKKα-p53-miR-23a circuit in which activation of IKKα attenuates p53-directed repression of FAT10. Thus, our findings establish IKKα-to-FAT10 pathway as a new therapeutic target for the treatment of Tam-resistant ER+ breast cancer.


Assuntos
Neoplasias da Mama , Resistencia a Medicamentos Antineoplásicos , Quinase I-kappa B , Transdução de Sinais , Tamoxifeno , Animais , Feminino , Humanos , Antineoplásicos Hormonais/farmacologia , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Citocinas/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Quinase I-kappa B/metabolismo , Células MCF-7 , Transdução de Sinais/efeitos dos fármacos , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética
18.
Fitoterapia ; 176: 105976, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38685511

RESUMO

Phytochemical research on an extract of Notopterygium incisum yielded fifteen compounds (1-15), including four previously undescribed compounds (10-13). The structures of the unreported compounds were elucidated by spectroscopic and spectrometric data analysis such as 1D and 2D NMR, IR and HR-ESI-MS. Compounds 1-5 and 10-14 were isolated from N. incisum for the first time. 7S⁎,8R⁎-Phenethyl-(7-methoxy-8-isoeugenol)-ferulate (10), 7S⁎,8R⁎-p-hydroxyphenethyl-(7-methoxy-8-isoeugenol)-ferulate (11), 7S⁎,8R⁎-benzyl-(7-methoxy-8-isoeugenol)-ferulate (12) and p-hydroxyphenethyl-(4-benzoy-3-methoxy)-cinnamate (13) are the undescribed ferulic acid derivatives. Additionly, the anti-neuroinflammatory effects of compounds were evaluated in lipopolysaccharide (LPS)-induced BV2 cells. The pharmacological results showed that 6ß,10ß-epoxy-4α-hydroxy-guaiane (6), teuclatriol (7) and 7S⁎,8R⁎-p-hydroxyphenethyl-(7-methoxy-8-isoeugenol)-ferulate (11) inhibited the production and expression of nitric oxide (NO) in the LPS-induced BV2 cells in a concentration-dependent manner. Acorusnol (4), teucladiol (9), 7S⁎,8R⁎-benzyl-(7-methoxy-8-isoeugenol)-ferulate (12) and p-hydroxyphenethyl-(4-benzoy-3-methoxy)-cinnamate (13) only inhibited the release of NO at concentration of 20 µM. Moreover, 7S⁎,8R⁎-p-hydroxyphenethyl-(7-methoxy-8-isoeugenol)-ferulate (11) reduced the level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in LPS-stimulated BV2 cells. The results demonstrated 7S⁎,8R⁎-p-hydroxyphenethyl-(7-methoxy-8-isoeugenol)-ferulate (11) could be a potential anti-neuroinflammatory agent and is worthy of further study.


Assuntos
Anti-Inflamatórios , Apiaceae , Compostos Fitoquímicos , Camundongos , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Apiaceae/química , Linhagem Celular , Óxido Nítrico/metabolismo , China , Microglia/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química
19.
World J Gastrointest Oncol ; 16(3): 659-669, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38577461

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of less than 10%, owing to its late-stage diagnosis. Early detection of pancreatic cancer (PC) can significantly increase survival rates. AIM: To identify the serum biomarker signatures associated with early-stage PDAC by serum N-glycan analysis. METHODS: An extensive patient cohort was used to determine a biomarker signature, including patients with PDAC that was well-defined at an early stage (stages I and II). The biomarker signature was derived from a case-control study using a case-cohort design consisting of 29 patients with stage I, 22 with stage II, 4 with stage III, 16 with stage IV PDAC, and 88 controls. We used multiparametric analysis to identify early-stage PDAC N-glycan signatures and developed an N-glycan signature-based diagnosis model called the "Glyco-model". RESULTS: The biomarker signature was created to discriminate samples derived from patients with PC from those of controls, with a receiver operating characteristic area under the curve of 0.86. In addition, the biomarker signature combined with cancer antigen 19-9 could discriminate patients with PDAC from controls, with a receiver operating characteristic area under the curve of 0.919. Glyco-model demonstrated favorable diagnostic performance in all stages of PC. The diagnostic sensitivity for stage I PDAC was 89.66%. CONCLUSION: In a prospective validation study, this serum biomarker signature may offer a viable method for detecting early-stage PDAC.

20.
Dalton Trans ; 53(18): 7669-7676, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38646797

RESUMO

A dinuclear Fe(II) spin crossover (SCO) complex with the formula [Fe2L5(NCS)4]·2DMF·2H2O (1) was synthesised from 1-naphthylimino-1,2,4-triazole (L). Complex 1 exhibits an incomplete thermally induced spin transition with a transition temperature T1/2 of 95 K and a thermally trapped metastable high-spin state at low temperatures. Furthermore, it undergoes a reversible light-induced spin crossover by alternate irradiation with 532 and 808 nm lasers.

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