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1.
Genome Biol ; 25(1): 179, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38972974

RESUMO

Pathogenic allele silencing is a promising treatment for genetic hereditary diseases. Here, we develop an RNA-cleaving tool, TaqTth-hpRNA, consisting of a small, chimeric TaqTth, and a hairpin RNA guiding probe. With a minimal flanking sequence-motif requirement, in vitro and in vivo studies show TaqTth-hpRNA cleaves RNA efficiently and specifically. In an Alzheimer's disease model, we demonstrate silencing of mutant APPswe mRNA without altering the wild-type APP mRNA. Notably, due to the compact size of TaqTth, we are able to combine with APOE2 overexpression in a single AAV vector, which results in stronger inhibition of pathologies.


Assuntos
Doença de Alzheimer , Inativação Gênica , RNA Mensageiro , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Humanos , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Animais , Camundongos , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Clivagem do RNA , Vetores Genéticos , Dependovirus/genética
2.
World J Clin Cases ; 12(19): 3866-3872, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38994274

RESUMO

BACKGROUND: The incidence of Barrett's esophagus (BE) in China is lower compared to the Western populations. Hence, studies conducted in the Chinese population has been limited. The current treatment options available for BE treatment includes argon plasma coagulation (APC), radiofrequency ablation and cryoablation, all with varying degrees of success. AIM: To determine the efficacy and safety of HybridAPC in the treatment of BE. METHODS: The study cohort consisted of patients with BE who underwent HybridAPC ablation treatment. These procedures were performed by seven endoscopists from different tertiary hospitals. The duration of the procedure, curative rate, complications and recurrent rate by 1-year follow-up were recorded. RESULTS: Eighty individuals were enrolled for treatment from July 2017 to June 2020, comprising of 39 males and 41 females with a median age of 54 years (range, 30 to 83 years). The technical success rate of HybridAPC was 100% and the overall curative rate was 98.15%. No severe complications occurred during the operation. BE cases were classified as short-segment BE and long-segment BE. Patients with short-segment BE were all considered cured without complications. Thirty-six patients completed the one-year follow-up without recurrence. Twenty-four percent had mild dysplasia which were all resolved with one post-procedural treatment. The mean duration of the procedure was 10.94 ± 6.52 min. CONCLUSION: Treatment of BE with HybridAPC was found to be a simple and quick procedure that is safe and effective during the short-term follow-up, especially in cases of short-segment BE. This technique could be considered as a feasible alternative ablation therapy for BE.

3.
Nat Prod Res ; : 1-6, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38980006

RESUMO

A new polyketide, mauritone A (1) with six known polyketides curvulone B (2), curvularin (3), 12-oxocurvularin (4), (10E,15S)-10,11-dehydrocurvularin (5), (11R,15S)-11-hydroxycurvularin (6), and (11S,15S)-11-hydroxycurvularin (7) were isolated from the fungal-bacterial symbiont Aspergillus spelaeus GXIMD 04541/Sphingomonas echinoides GXIMD 04532 derived from Mauritia arabica. Their structures were elucidated by extensive spectral analysis. All compounds (1-7) were evaluated for their anti-inflammatory effects. The inhibitory effects of 4, 5, and 7 on nitric oxide (NO) production were found to be significant, with IC50 values of 5.5 ± 0.26, 2.0 ± 0.31, and 8.3 ± 0.62 µM, respectively, surpassing that of the positive control quercetin (10.6 ± 0.64 µM). Compounds 3 and 6 exhibited moderate inhibition of NO, with IC50 values of 18.6 ± 0.53 and 12.7 ± 0.45 µM, respectively.

4.
J Med Chem ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38996004

RESUMO

The discovery of effective and safe antiobesity agents remains a challenging yet promising field. Our previous studies identified Bouchardatine derivatives as potential antiobesity agents. However, the 8a-aldehyde moiety rendered them unsuitable for drug development. In this study, we designed two series of novel derivatives to modify this structural feature. Through a structure-activity relationship study, we elucidated the role of the 8a-aldehyde group in toxicity induction. We identified compound 14d, featuring an 8a-N-acylhydrazone moiety, which exhibited significant lipid-lowering activity and reduced toxicity. Compound 14d shares a similar lipid-lowering mechanism with our lead compound 3, but demonstrates improved pharmacokinetic properties and safety profile. Both oral and injectable administration of 14d significantly reduced body weight gain and ameliorated metabolic syndrome in diet-induced obese mice. Our findings identify 14d as a promising antiobesity agent and highlight the potential of substituting the aldehyde group with an N-acylhydrazone to enhance drug-like properties.

5.
World J Clin Cases ; 12(20): 4247-4255, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39015909

RESUMO

BACKGROUND: Colorectal cancer is the second leading cause of cancer-related deaths among digestive tract malignancies, following gastric cancer. Sleep is of great significance for maintaining human health. The incidence of sleep disorders in patients with cancer is approximately twice that observed in the general population. Lack of sleep can prolong hospital stays, increase the likelihood of infection, and increase mortality rates. Therefore, studying the factors related to sleep quality is significant for improving the quality of life of patients with malignant tumors of the digestive tract. AIM: To investigate the relationships among sleep quality, disease uncertainty, and psychological resilience in patients undergoing chemotherapy for digestive tract malignancies. METHODS: A total of 131 patients with malignant digestive tract tumors who were treated at Hefei BOE Hospital between April 2021 and September 2022 were selected as research participants. Based on their Pittsburgh Sleep Quality Index (PSQI) scores, participants were divided into either the sleep disorder group (PSQI score > 7) or the normal sleep group (PSQI score ≤ 7). The clinical data-together with the Mishel Uncertainty in Illness Scale for Adults (MUIS-A) and Connor-Davidson Resilience Scale (CD-RISC) scores-were compared. RESULTS: In this study, 78 (59.54%) patients with digestive tract malignancies developed sleep disorders after chemotherapy. Sleep disorder incidence was higher in patients with colorectal cancer than in those with gastric and esophageal cancers (P < 0.05). The total MUIS-A score and those for each item in the sleep disorder group were higher than those in the normal sleep group. The total CD-RISC score and those for each item in the sleep disorder group were lower than those in the normal sleep group (P < 0.05). The PSQI scores of patients with malignant digestive tract tumors were positively correlated with the scores for lack of disease information, disease uncertainty, and unpredictability in the MUIS-A and negatively correlated with the scores for tenacity, self-improvement, and optimism in the CD-RISC (P < 0.05). CONCLUSION: Patients undergoing chemotherapy for digestive tract malignancies are prone to sleep problems related to disease uncertainty and psychological resilience. Therefore, interventions can be implemented to improve their sleep quality.

6.
Int J Oncol ; 65(2)2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38873993

RESUMO

Genes encoding subunits of SWI/SNF (BAF) chromatin­remodeling complexes are recurrently mutated in a broad array of tumor types, and among the subunits, ARID1A is the most frequent target with mutations. In the present study, it was reported that ARID1A inhibits the epithelial­mesenchymal transition (EMT) and stemness of ovarian cancer cells, accompanied by reduced cell viability, migration and colony formation, suggesting that ARID1A acts as a tumor suppressor in ovarian cancer. Mechanistically, ARID1A exerts its inhibitory effects on ovarian cancer cells by activating the Hippo signaling pathway. Conversely, the overexpression of a gain­of­function transcriptional co­activator with PDZ­binding motif (TAZ) mutant (TAZ­Ser89) effectively reverses the effects induced by ARID1A. In addition, activation of Hippo signaling apparently upregulates ARID1A protein expression, whereas ectopic expression of TAZ­Ser89 results in the markedly decreased ARID1A levels, indicating a feedback of ARID1A­TAZ in regulating ovarian cancer cell EMT and stemness. Thus, the present study uncovered the role of ARID1A through the Hippo/TAZ pathway in modulating EMT and stemness of ovarian cancer cells, and providing with evidence that TAZ inhibitors could effectively prevent initiation and metastasis of ovarian cancer cases where ARID1A is lost or mutated.


Assuntos
Proteínas de Ligação a DNA , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Via de Sinalização Hippo , Células-Tronco Neoplásicas , Neoplasias Ovarianas , Proteínas Serina-Treonina Quinases , Transdução de Sinais , Fatores de Transcrição , Humanos , Feminino , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Linhagem Celular Tumoral , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Movimento Celular , Proliferação de Células , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética
7.
Environ Int ; 190: 108841, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38917626

RESUMO

OBJECTIVES: Evidence on the link between long-term ambient particulate matter (PM) exposures and childhood sleep disorders were scarce. We examined the associations between long-term exposures to PM2.5 and PM1 (PM with an aerodynamic equivalent diameter <2.5 µm and <1 µm, respectively) with sleep disorders in children. METHODS: We performed a population-based cross-sectional survey in 177,263 children aged 6 to 18 years in 14 Chinese cities during 2012-2018. A satellite-based spatiotemporal model was employed to estimate four-year annual average PM2.5 and PM1 exposures at residential and school addresses. Parents or guardians completed a checklist using the Sleep Disturbance Scale for Children. We estimated the associations using generalized linear mixed models with adjustment for characteristics of children, parents, and indoor environments. RESULTS: Long-term PM2.5 and PM1 exposures were positively associated with odds of sleep disorders for almost all domains. For example, increments in PM2.5 and PM1 per 10 µg/m3 were associated with odds ratios of global sleep disorder of 1.24 (95 % confidence interval [CI]: 1.14, 1.35) and 1.31 (95 %CI: 1.18, 1.46), respectively. Similar results were observed for subtypes of sleep disorder. These associations were heterogeneous regionally, with stronger associations among children residing in southeast region than in northeast and northwest regions. Moreover, larger estimates of PM1 were found than that of PM2.5 in southeast region. CONCLUSION: Long-term PM2.5 and PM1 exposures are independently associated with higher risks of childhood sleep disorders, and these associations vary by geographical region.

8.
Future Sci OA ; 10(1): FSO906, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827794

RESUMO

The feasibility of surgery after immunotherapy for mediastinal liposarcoma remains uncertain. Besides, the case of immunotherapy for liposarcoma is still lacking. We report a case of recurrence after resection of a left mediastinal liposarcoma. After recurrence, one course of pembrolizumab plus anlotinib hydrochloride showed no tumor shrinkage, and genetic testing showed CDK4 amplification and PD-L1 TPS <1%; therefore, the plan was changed to one course of pembrolizumab plus palbociclib, but the tumor still did not shrink. Thus, second tumor resection was performed. In addition, the postoperative pathology was still well-differentiated liposarcoma. The significance of immunotherapy in liposarcoma still needs to be further explored. In the absence of surgical contraindications, secondary surgery might be feasible.

9.
Genomics ; 116(4): 110876, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849019

RESUMO

Timely accurate and cost-efficient detection of colorectal cancer (CRC) is of great clinical importance. This study aims to establish prediction models for detecting CRC using plasma cell-free DNA (cfDNA) fragmentomic features. Whole-genome sequencing (WGS) was performed on cfDNA from 620 participants, including healthy individuals, patients with benign colorectal diseases and CRC patients. Using WGS data, three machine learning methods were compared to build prediction models for the stratification of CRC patients. The optimal model to discriminate CRC patients of all stages from healthy individuals achieved a sensitivity of 92.31% and a specificity of 91.14%, while the model to separate early-stage CRC patients (stage 0-II) from healthy individuals achieved a sensitivity of 88.8% and a specificity of 96.2%. Additionally, the cfDNA fragmentation profiles reflected disease-specific genomic alterations in CRC. Overall, this study suggests that cfDNA fragmentation profiles may potentially become a noninvasive approach for the detection and stratification of CRC.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Masculino , Pessoa de Meia-Idade , Feminino , Detecção Precoce de Câncer/métodos , Idoso , Ácidos Nucleicos Livres/genética , Ácidos Nucleicos Livres/sangue , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , Aprendizado de Máquina , Adulto , Sequenciamento Completo do Genoma/métodos , Fragmentação do DNA
10.
Entropy (Basel) ; 26(6)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38920537

RESUMO

Coreference resolution is a key task in Natural Language Processing. It is difficult to evaluate the similarity of long-span texts, which makes text-level encoding somewhat challenging. This paper first compares the impact of commonly used methods to improve the global information collection ability of the model on the BERT encoding performance. Based on this, a multi-scale context information module is designed to improve the applicability of the BERT encoding model under different text spans. In addition, improving linear separability through dimension expansion. Finally, cross-entropy loss is used as the loss function. After adding BERT and span BERT to the module designed in this article, F1 increased by 0.5% and 0.2%, respectively.

11.
Phytochemistry ; 225: 114193, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38908463

RESUMO

Lathyrisone A (1), a diterpene with an undescribed tricyclic 6/6/6 fused carbon skeleton, along with spirolathyrisins B-D (3-5), three diterpenes with a rare [4.5.0] spirocyclic carbon skeleton, and one known compound (2) were isolated from the roots of Euphorbia lathyris. Their chemical structures were characterized by extensive spectroscopic analysis, X-ray crystallography, ECD and quantum chemistry calculation. A plausible biosynthetic pathway for compounds 1-5 was proposed, which suggested it is a competitive pathway for ingenol biosynthesis in the plant. The anti-fungal activities of these compounds were tested, especially, compound 2 showed stronger anti-fungal activities against Fusarium oxysporum and Alternaria alternata than the positive control fungicide thiophanate-methyl. The preliminary structure-activity relationship of compounds 1-5 was also discussed. These results not only expanded the chemical diversities of E. lathyris, but also provided a lead compound for the control of plant pathogens.


Assuntos
Alternaria , Antifúngicos , Diterpenos , Euphorbia , Fusarium , Testes de Sensibilidade Microbiana , Raízes de Plantas , Euphorbia/química , Diterpenos/química , Diterpenos/farmacologia , Diterpenos/isolamento & purificação , Raízes de Plantas/química , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/isolamento & purificação , Relação Estrutura-Atividade , Fusarium/efeitos dos fármacos , Alternaria/efeitos dos fármacos , Estrutura Molecular , Descoberta de Drogas , Cristalografia por Raios X , Relação Dose-Resposta a Droga
12.
Immunotargets Ther ; 13: 273-286, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38881648

RESUMO

Background: Cytokines act a vital role in autoimmune neuroinflammatory diseases (ANDs) with undetermined causal relationships. Mendelian randomization (MR) analysis was performed to estimate the causal effects of circulating levels of cytokines on the risk of ANDs. Methods: The causal relationship between 34 circulating cytokines and 4 kinds of ANDs, including multiple sclerosis (MS), neuromyelitis optica (NOM), chronic inflammatory demyelinating polyneuropathy (CIDP) and myasthenia gravis (MG) were explored using four methods of MR analysis. MR-PRESSO, MR-Egger regression methods and Cochran's Q statistic were utilized to identify the instrumental variables (IVs) with potential pleiotropy and heterogeneity. The Bonferroni correction was used for multiple group comparisons. P-value less than 3.68E-04 (0.05/ (34*4)) was considered statistically significant. Results: Negative causal effects of circulating levels of interleukin (IL)-8 (OR = 0.648, 95% CI: 0.494-0.851, P = 0.002) on risk of MS, chemokine (C-C Motif) ligand (CCL)-5 (OR = 0.295, 95% CI: 0.103-0.841, P = 0.022) and stem cell growth factor-beta (SCGF-ß) (OR = 0.745, 95% CI: 0.565-0.984, P = 0.038) on risk of CIDP, as well as positive causal effects of circulating levels of IL-2 receptor α (IL-2Rα) (OR = 1.216, 95% CI: 1.120-1.320, P = 3.20E-06) and chemokine C-X-C motif ligand (CXCL)-10 (OR = 1.404, 95% CI: 1.094-1.803, P = 0.008) on MS were observed. Nevertheless, only IL-2Rα still had a causal effect on MS after Bonferroni correction. Conclusion: The results identify a genetically predicted causal effect of IL-2Rα, IL-8 and CXCL-10 on MS, CCL-5 and SCGF-ß on CIDP.

13.
Front Med ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38907157

RESUMO

RNA modification is an essential component of the epitranscriptome, regulating RNA metabolism and cellular functions. Several types of RNA modifications have been identified to date; they include N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N7-methylguanosine (m7G), N6,2'-O-dimethyladenosine (m6Am), N4-acetylcytidine (ac4C), etc. RNA modifications, mediated by regulators including writers, erasers, and readers, are associated with carcinogenesis, tumor microenvironment, metabolic reprogramming, immunosuppression, immunotherapy, chemotherapy, etc. A novel perspective indicates that regulatory subunits and post-translational modifications (PTMs) are involved in the regulation of writer, eraser, and reader functions in mediating RNA modifications, tumorigenesis, and anticancer therapy. In this review, we summarize the advances made in the knowledge of different RNA modifications (especially m6A) and focus on RNA modification regulators with functions modulated by a series of factors in cancer, including regulatory subunits (proteins, noncoding RNA or peptides encoded by long noncoding RNA) and PTMs (acetylation, SUMOylation, lactylation, phosphorylation, etc.). We also delineate the relationship between RNA modification regulator functions and carcinogenesis or cancer progression. Additionally, inhibitors that target RNA modification regulators for anticancer therapy and their synergistic effect combined with immunotherapy or chemotherapy are discussed.

14.
Artigo em Inglês | MEDLINE | ID: mdl-38904613

RESUMO

Objective: To analyze the efficacy and safety of bevacizumab combined with chemotherapy in the treatment of malignant pleural effusion of lung cancer. Methods: Lung cancer patients with malignant pleural effusion (n = 60 cases) treated in our hospital from January 2020 to December 2022 were retrospectively analyzed. They were divided into a control group (patients receiving conventional chemotherapy) and an observation group (patients receiving bevacizumab combined with chemotherapy). The two groups were age and sex-matched. The therapeutic effects, adverse reactions, quality of life (physiological status, social and family status, emotional status, and functional status), levels of serum tumor markers (cytokeratin 19 fragment, tumor-specific growth factor, and carcinoembryonic antigen), pain degree of the two groups before and after treatment, and the psychological states before and after treatment (anxiety and depression scores) of the two groups were compared. Results: The results obtained shows that the observation group has improved treatment outcome than the control group, P < .05. Similarly, the observation group reported higher physiological status, social and family status, emotional status, functional status and other quality of life compared to the control group, P < .05. Interestingly, the observation group showed lower levels of serum tumor markers than the control group, P < .05. Upon comparison of the pain degree of the two groups after treatment, the observation group reported a lesser degree of pain than the control group, P < .05. Although no significant difference was observed in the depression and anxiety scores of the two groups prior to the treatment, the observation group displayed improved psychological state compared to the control group, P < .05. Conclusion: Bevacizumab combined with chemotherapy has outstanding curative effect on malignant pleural effusion of lung cancer.

15.
United European Gastroenterol J ; 12(6): 772-779, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38753528

RESUMO

OBJECTIVES: Detection of early neoplastic lesions is crucial for improving the survival rates of patients with gastric cancer. Optical enhancement mode 2 is a new image-enhanced endoscopic technique that offers bright images and can improve the visibility of neoplastic lesions. This study aimed to compare the detection of neoplastic lesions with optical enhancement mode 2 and white-light imaging (WLI) in a high-risk population. METHODS: In this prospective multicenter randomized controlled trial, patients were randomly assigned to optical enhancement mode 2 or WLI groups. Detection of suspicious neoplastic lesions during the examinations was recorded, and pathological diagnoses served as the gold standard. RESULTS: A total of 1211 and 1219 individuals were included in the optical enhancement mode 2 and WLI groups, respectively. The detection rate of neoplastic lesions was significantly higher in the optical enhancement mode 2 group (5.1% vs. 1.9%; risk ratio, 2.656 [95% confidence interval, 1.630-4.330]; p < 0.001). The detection rate of neoplastic lesions with an atrophic gastritis background was significantly higher in the optical enhancement mode 2 group (8.6% vs. 2.6%, p < 0.001). The optical enhancement mode 2 group also had a higher detection rate among endoscopists with different experiences. CONCLUSIONS: Optical enhancement mode 2 was more effective than WLI for detecting neoplastic lesions in the stomach, and can serve as a new method for screening early gastric cancer in clinical practice. CLINICAL REGISTRY: United States National Library of Medicine (https://www. CLINICALTRIALS: gov), ID: NCT040720521.


Assuntos
Detecção Precoce de Câncer , Gastroscopia , Aumento da Imagem , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Neoplasias Gástricas/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Gastroscopia/métodos , Detecção Precoce de Câncer/métodos , Idoso , Aumento da Imagem/métodos , Gastrite Atrófica/diagnóstico , Gastrite Atrófica/patologia , Gastrite Atrófica/diagnóstico por imagem , Adulto
17.
Eur J Histochem ; 68(2)2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38742403

RESUMO

Chronic kidney disease (CKD) is a leading public health issue associated with high morbidity worldwide. However, there are only a few effective therapeutic strategies for CKD. Emodin, an anthraquinone compound from rhubarb, can inhibit fibrosis in tissues and cells. Our study aims to investigate the antifibrotic effect of emodin and the underlying molecular mechanism. A unilateral ureteral obstruction (UUO)-induced rat model was established to evaluate the effect of emodin on renal fibrosis development. Hematoxylin and eosin staining, Masson's trichrome staining, and immunohistochemistry staining were performed to analyze histopathological changes and fibrotic features after emodin treatment. Subsequently, a transforming growth factor-beta 1 (TGF-ß1)-induced cell model was used to assess the inhibition of emodin on cell fibrosis in vitro. Furthermore, Western blot analysis and real-time quantitative reverse transcription-polymerase chain reaction were performed to validate the regulatory mechanism of emodin on renal fibrosis progression. As a result, emodin significantly improved histopathological abnormalities in rats with UUO. The expression of fibrosis biomarkers and mitochondrial biogenesis-related proteins also decreased after emodin treatment. Moreover, emodin blocked TGF-ß1-induced fibrotic phenotype, lipid accumulation, and mitochondrial homeostasis in NRK-52E cells. Conversely, peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α) silencing significantly reversed these features in emodin-treated cells. Collectively, emodin plays an important role in regulating PGC-1α-mediated mitochondria function and energy homeostasis. This indicates that emodin exhibits great inhibition against renal fibrosis and acts as a promising inhibitor of CKD.


Assuntos
Emodina , Fibrose , Mitocôndrias , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Insuficiência Renal Crônica , Animais , Emodina/farmacologia , Emodina/uso terapêutico , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Fibrose/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Homeostase/efeitos dos fármacos , Rim/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Obstrução Ureteral/patologia , Obstrução Ureteral/tratamento farmacológico , Fator de Crescimento Transformador beta1/metabolismo , Linhagem Celular
18.
ACS Appl Mater Interfaces ; 16(22): 29132-29140, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38783827

RESUMO

Lead halide perovskite nanocrystals (PNCs) have demonstrated great potential in emerging display technologies. However, the practical application of PNCs is hindered by the inherent instability of their ionic surface. Here, we proposed a surface modification approach to enhance the stability of CsPbBr3 PNCs by postsynthetic treatment with aluminum phenylbutyrate (Al(PA)3). Our study reveals that Al(PA)3 displaces ammonium ligands and binds tightly on surface halide, providing excellent air and moisture resistance while preserving a high quantum efficiency of 81.6%. The modified PNCs maintain a constant photoluminescence intensity under continuous UV light illumination for 500 h. Additionally, the Al(PA)3 ligand is compatible with styrene, enabling homogeneous dispersion of PNCs in polystyrene matrices to form bright and uniform PNC-PS thin films. We demonstrated the application of the composite films for display backlighting, which exhibits a wide color gamut of 125% NTSC. The result highlights the potential of AlPA-modified PNCs in light-emitting and other optoelectronic devices.

19.
Cell Biol Toxicol ; 40(1): 28, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38695990

RESUMO

The Rab small GTPases are characterized by the distinct intracellular localization and modulate various endocytic, transcytic and exocytic transport pathways. Rab proteins function as scaffolds that connect signaling pathways and intracellular membrane trafficking processes through the recruitment of effectors, such as tethering factors, phosphatases, motors and kinases. In different cancers, Rabs play as either an onco-protein or a tumor suppressor role, highly dependending on the context. The molecular mechanistic research has revealed that Rab proteins are involved in cancer progression through influences on migration, invasion, metabolism, exosome secretion, autophagy, and drug resistance of cancer cells. Therefore, targeting Rab GTPases to recover the dysregulated vesicle transport systems may provide potential strategy to restrain cancer progression. In this review, we discuss the regulation of Rab protein level and activity in modulating pathways involved in tumor progression, and propose that Rab proteins may serve as a prognostic factor in different cancers.


Assuntos
Neoplasias , Proteínas rab de Ligação ao GTP , Humanos , Proteínas rab de Ligação ao GTP/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/enzimologia , Transdução de Sinais , Animais , Autofagia/fisiologia
20.
Technol Health Care ; 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38820029

RESUMO

BACKGROUND: The substitution of missing teeth with implants is a dependable and anticipated therapeutic approach. Despite numerous studies affirming long-term success rates, there exists a spectrum of potential biological and aesthetic complications. OBJECTIVE: The primary objective of this study was to assess patient responses subsequent to surgical interventions, with a specific emphasis on the utilization of xenogenic collagen matrix (XCM), both with and without the application of a stent secured over healing abutments, in the context of keratinized gingival mucosa augmentation. The principal aim was to evaluate and draw comparisons between the clinical outcomes resulting from these two procedural approaches, with a particular focus on critical parameters encompassing post-operative complications, patient comfort, and the overall efficacy in achieving successful keratinized tissue augmentation. methods: Sixty patients were selected for this study. The patients were divided into three groups: A, B, and a control group, with each group comprising 20 participants. We used XCM in experimental group A, XCM covered with surgical stent in experimental group B, and free gingival graft (FGG) in the control group. After the surgical procedure, patients were required to complete a visual analogue scale (VAS) questionnaire for post-operative complications, and a quality of life (QOL) questionnaire on days 1, 3, and 7. RESULTS: Patients in the experimental groups A and B demonstrated markedly improved outcomes when compared with the control group. Assessments conducted on days 1, 3, and 7 demonstrated diminished levels of pain, bleeding, and swelling in both experimental groups, with experimental group B showing the least discomfort. The incorporation of XCM, either with or without stents, was associated with a reduction in analgesic consumption, underscoring its favorable influence on post-operative comfort, notwithstanding the exception of halitosis in experimental group B. CONCLUSION: Using XCM with or without a stent for keratinized tissue augmentation has better post-operative outcomes associated with reduced swelling, bleeding, and pain based on the QOL survey. This study provides data to support the clinical application of XCM and stents.

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