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1.
J Ethnopharmacol ; 330: 118264, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-38692417

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Optimized New Shengmai Powder (ONSMP) is a sophisticated traditional Chinese medicinal formula renowned for bolstering vital energy, optimizing blood circulation, and mitigating fluid retention. After years of clinical application, ONSMP has shown a significant impact in improving myocardial injury and cardiac function and has a positive effect on treating heart failure. However, many unknowns exist about the molecular biological mechanisms of how ONSMP exerts its therapeutic effects, which require further research and exploration. AIM OF THE STUDY: Exploring the potential molecular biological mechanisms by which ONSMP ameliorates cardiomyocyte apoptosis and ferroptosis in ischemic heart failure (IHF). MATERIALS AND METHODS: First, we constructed a rat model of IHF by inducing acute myocardial infarction through surgery and using echocardiography, organ coefficients, markers of heart failure, antioxidant markers, and histopathological examination to assess the effects of ONSMP on cardiomyocyte apoptosis and ferroptosis in IHF rats. Next, we used bioinformatics analysis techniques to analyze the active components, signaling pathways, and core targets of ONSMP and calculated the interactions between core targets and corresponding elements. Finally, we detected the positive expression of apoptosis and ferroptosis markers and core indicators of signaling pathways by immunohistochemistry; detected the mean fluorescence intensity of core indicators of signaling pathways by immunofluorescence; detected the protein expression of signaling pathways and downstream effector molecules by western blotting; and detected the mRNA levels of p53 and downstream effector molecules by quantitative polymerase chain reaction. RESULTS: ONSMP can activate the Ser83 site of ASK by promoting the phosphorylation of the PI3K/AKT axis, thereby inhibiting the MKK3/6-p38 axis and the MKK4/7-JNK axis signaling to reduce p53 expression, and can also directly target and inhibit the activity of p53, ultimately inhibiting p53-mediated mRNA and protein increases in PUMA, SAT1, PIG3, and TFR1, as well as mRNA and protein decreases in SLC7A11, thereby inhibiting cardiomyocyte apoptosis and ferroptosis, effectively improving cardiac function and ventricular remodeling in IHF rat models. CONCLUSION: ONSMP can inhibit cardiomyocyte apoptosis and ferroptosis through the PI3K/AKT/p53 signaling pathway, delaying the development of IHF.


Assuntos
Apoptose , Combinação de Medicamentos , Medicamentos de Ervas Chinesas , Ferroptose , Insuficiência Cardíaca , Miócitos Cardíacos , Proteínas Proto-Oncogênicas c-akt , Ratos Sprague-Dawley , Transdução de Sinais , Proteína Supressora de Tumor p53 , Animais , Ferroptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Apoptose/efeitos dos fármacos , Masculino , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Ratos , Fosfatidilinositol 3-Quinase/metabolismo , Isquemia Miocárdica/tratamento farmacológico , Modelos Animais de Doenças , Pós
2.
J Sports Sci ; 42(6): 498-510, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38695325

RESUMO

Stair climbing exercise (SE) provides a feasible approach to elevate physical activity, but the effects on metabolic health are unclear. We systematically reviewed the currently available evidence on the effects of SE on fasting and postprandial glycaemia and lipidaemia. Studies were included if they investigated the effects of acute or chronic (at least 2 weeks) SE on fasting and/or postprandial glycaemic (insulin and glucose) and lipidaemic (triacylglycerols and non-esterified fatty acids) responses in healthy, prediabetic or type 2 diabetic adult populations. PubMed, Web of Science and Scopus were searched for eligible studies until July 2022. A total of 25 studies (14 acute and 11 chronic) were eligible for review. Acute bout(s) of SE can reduce postprandial glycaemia in individuals with prediabetes and type 2 diabetes (8 of 9 studies), but not in normoglycemic individuals. The effects of acute SE on postprandial lipidaemic responses and SE training on both fasting and postprandial glycaemia/lipidaemia were unclear. Acute SE may reduce postprandial glucose concentrations in people with impaired glycaemic control, but high-quality studies are needed. More studies are needed to determine the effect of chronic SE training on postprandial glucose and lipid responses, and the acute effects of SE on lipid responses.


Assuntos
Glicemia , Diabetes Mellitus Tipo 2 , Período Pós-Prandial , Subida de Escada , Humanos , Período Pós-Prandial/fisiologia , Glicemia/metabolismo , Subida de Escada/fisiologia , Jejum , Estado Pré-Diabético/terapia , Insulina/sangue , Triglicerídeos/sangue , Ácidos Graxos não Esterificados/sangue , Lipídeos/sangue
3.
J Org Chem ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720168

RESUMO

Tracking carboxylesterases (CESs) through noninvasive and dynamic imaging is of great significance for diagnosing and treating CES-related metabolic diseases. Herein, three BODIPY-based fluorescent probes with a pyridine unit quaternarized via an acetoxybenzyl group were designed and synthesized to detect CESs based on the photoinduced electron transfer process. Notably, among these probes, BDPN2-CES exhibited a remarkable 182-fold fluorescence enhancement for CESs within 10 min. Moreover, BDPN2-CES successfully enabled real-time imaging of endogenous CES variations in living cells. Using BDPN2-CES, a visual high-throughput screening method for CES inhibitors was established, culminating in the discovery of an efficient inhibitor, WZU-13, sourced from a chemical library. These findings suggest that BDPN2-CES could provide a new avenue for diagnosing CES-related diseases, and WZU-13 emerges as a promising therapeutic candidate for CES-overexpression pathological processes.

4.
Sci Justice ; 64(3): 269-278, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38735662

RESUMO

A novel technique is introduced to predict the printer model used to produce a given document. Samples containing only a few letters printed under varying conditions (i.e., different printing modes, letter types, fonts) were collected to establish a dataset of 41 inkjet printer models from common manufacturers, such as HP, Canon, and Epson. Morphological features were analyzed by extraction of image features using several algorithms in a series of microscopic images and a Wilcoxon test was used to measure the significance of variations between printed samples. Significant differences between various printing conditions might post potential challenge to questioned document examination. Discriminant analysis and the k-nearest neighbor (KNN) algorithm were also employed for source printer prediction under varying printing condition on 30% images with the rest images as training dataset. The results of a validation experiment demonstrated that while quadratic discriminant analysis (QDA) achieved an accuracy of 96.3%, a combination of KNN and QDA reached 98.6%. As such, this technique could aid in the forensic examination of printed documents.

5.
Metabolites ; 14(4)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38668304

RESUMO

The quality of crops is closely associated with their geographical location and yield, which is reflected in the composition of their metabolites. Hence, we employed GC-MS pseudotargeted metabolomics to investigate the metabolic characteristics of high-, medium-, and low-yield Nicotiana tabacum (tobacco) leaves from the Bozhou (sweet honey flavour) and Shuicheng (light flavour) regions of Guizhou Province. A total of 124 metabolites were identified and classified into 22 chemical categories. Principal component analysis revealed that the geographical location exerted a greater influence on the metabolic profiling than the yield. Light-flavoured tobacco exhibited increased levels of sugar metabolism- and glycolysis-related intermediate products (trehalose, glucose-6-phosphate, and fructose-6-phosphate) and a few amino acids (proline and leucine), while sweet honey-flavoured tobacco exhibited increases in the tricarboxylic acid cycle (TCA cycle) and the phenylpropane metabolic pathway (p-hydroxybenzoic acid, caffeic acid, and maleic acid). Additionally, metabolite pathway enrichment analysis conducted at different yields and showed that both Shuicheng and Bozhou exhibited changes in six pathways and four of them were the same, mainly C/N metabolism. Metabolic pathway analysis revealed higher levels of intermediates related to glycolysis and sugar, amino acid, and alkaloid metabolism in the high-yield samples, while higher levels of phenylpropane in the low-yield samples. This study demonstrated that GC-MS pseudotargeted metabolomics-based metabolic profiling can be used to effectively discriminate tobacco leaves from different geographical locations and yields, thus facilitating a better understanding of the relationship between metabolites, yield, and geographical location. Consequently, metabolic profiles can serve as valuable indicators for characterizing tobacco yield and geographical location.

6.
Angew Chem Int Ed Engl ; : e202402215, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38581164

RESUMO

The development of a methodology for synthesizing value-added urea (CO(NH2)2) via a renewable electricity-driven C-N coupling reaction under mild conditions is highly anticipated. However, the complex catalytic active sites that act on the carbon and nitrogen species make the reaction mechanism unclear, resulting in a low efficiency of C-N coupling from the co-reduction of carbon dioxide (CO2) and nitrate (NO3 -). Herein, we propose a novel tandem catalyst of Mo-PCN-222(Co), in which the Mo sites serve to facilitate nitrate reduction to the *NH2 intermediate, while the Co sites enhance CO2 reduction to carbonic oxide (CO), thus synergistically promoting C-N coupling. The synthesized Mo-PCN-222(Co) catalyst exhibited a noteworthy urea yield rate of 844.11 mg h-1 g-1, alongside a corresponding Faradaic efficiency of 33.90 % at -0.4 V vs. reversible hydrogen electrode (RHE). By combining in situ spectroscopic techniques with density functional theory calculations, we demonstrate that efficient C-N coupling is attributed to a tandem system in which the *NH2 and *CO intermediates produced by the Mo and Co active sites of Mo-PCN-222(Co) stabilize the formation of the *CONH2 intermediate. This study provides an effective avenue for the design and synthesis of tandem catalysts for electrocatalytic urea synthesis.

7.
Inorg Chem ; 63(17): 7780-7791, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38625744

RESUMO

Pharmacosiderite Mo4P3O16 (Pharma-MoPO) consists of [Mo4O4] cubane unit and [PO4] tetrahedral to form an open framework with a microporous structure similar to that of LTA-type zeolite. Although attractive applications are expected due to its microporous structure and redox-active components, its physicochemical properties have been poorly investigated due to the specificity of its synthesis, which requires a high hydrothermal synthesis temperature of 360 °C. In this study, we succeeded in synthesizing Pharma-MoPO by hydrothermal synthesis at 230 °C, which can be applied using a commercially available autoclave by changing the metal source. Through the study of the solids and liquids obtained after hydrothermal syntheses, the formation process of Pharma-MoPO under our studied synthesis conditions was proposed. Advanced characterizations provided detailed structural information on Pharma-MoPO, including the location site of a countercation NH4+. Pharma-MoPO could adsorb CO2 with the amount close to the number of cages without removing NH4+. Pharma-MoPO exhibited stable catalytic activity for the hydrodesulfurization of thiophene while maintaining its crystal structure, except for the introduction of sulfide by replacing lattice oxygens. Pharmacosiderite Mo4P3O16 was successfully obtained by hydrothermal synthesis at a moderate temperature, and its microporosity for CO2 adsorption and catalytic properties for hydrodesulfurization were discovered.

8.
Zhongguo Zhong Yao Za Zhi ; 49(4): 1102-1112, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621917

RESUMO

This study systematically combed the randomized controlled trial(RCT) of Chinese patent medicines in treatment of type 2 diabetes mellitus(T2DM) in recent five years by using the method of evidence map. It understood the distribution and quality of evidence in this field and found the existing Chinese patent medicines in treatment of T2DM and the problems in its research. The study collected the commonly used Chinese patent medicines for the treatment of T2DM from three drug catalogs, retrieved Chinese and English databases to obtain RCT literature related to Chinese patent medicines in recent five years, and extracted information such as sample size, study drug, combination medication, course of treatment, and outcome indicators from the literature. It also conducted quality evaluation based on the Cochrane collaborative network bias risk assessment tool and used charts to display the analysis results. A total of 19 kinds of Chinese patent medicines are collected, of which 13 kinds of Chinese patent medicines are mentioned in 131 articles related to RCT. The literature concerning Shenqi Jiangtang Capsules/Granules, Jinlida Granules, and Xiaoke Pills accounts for a large proportion. Outcome indicators include blood glucose, blood lipids, pancreatic islet cell function, and clinical symptoms. In terms of literature quality, 75 articles have correct random methods, and 1 article performs allocation hiding and blind methods. Therefore, the clinical orientation of Chinese patent medicines for the treatment of T2DM is broad, failing to reflect their own characteristics and lacking safety information. Insufficient attention has been paid to TCM syndrome scores, quality of life, and blood lipid outcome indicators that reflect the characteristics of traditional Chinese medicine(TCM). The number of studies on the treatment of T2DM by Chinese patent medicines varies greatly among varieties, and the quality of the studies is low. It is suggested that the holders of the marketing license of T2DM Chinese patent medicines should carry out a post-marketing re-evaluation of the varieties of traditional Chinese patent medicines for treating T2DM according to the relevant requirements of the State Food and Drug Administration, standardize the clinical positioning, and revise and improve the safety information in the instructions. It is recommended that researchers construct a core indicator dataset for Chinese patent medicine treatment of T2DM, improve the efficacy evaluation system, and develop an experimental plan based on CONSORT before conducting RCT.


Assuntos
Diabetes Mellitus Tipo 2 , Medicamentos de Ervas Chinesas , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Medicamentos de Ervas Chinesas/efeitos adversos , Medicina Tradicional Chinesa , Medicamentos sem Prescrição/uso terapêutico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Front Med (Lausanne) ; 11: 1376319, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38633307

RESUMO

Objectives: Regarding increased nuchal translucency (NT), the cutoff values used are heterogeneous in clinical practice, this study aims to assess the efficacy of prenatal detection for chromosomal abnormalities and pregnancy outcomes in fetuses with varying NT thicknesses, in order to provide data that supports informed prenatal diagnosis and genetic counseling for such cases. Methods: We included 2,272 pregnant women under 35 with singleton pregnancies who underwent invasive prenatal diagnosis between 2014 and 2022. The cohort comprised 2,010 fetuses with increased NT (≥2.5 mm) and 262 fetuses with normal NT but exhibiting a single soft marker. Prenatal diagnoses were supported by chromosomal microarray (CMA) and copy number variation sequencing (CNV-seq) analyses. Results: The detection rates of numerical chromosomal abnormalities were 15.4% (309/2,010) and 17.3% (297/1,717) in the NT ≥2.5 and ≥ 3.0 groups, respectively. Pathogenic/likely pathogenic CNV incidence increased with NT thickness (χ2 = 8.60, p < 0.05), peaking at 8.7% (22/254) in the NT 4.5-5.4 mm group. Structural defects were found in 18.4% of fetuses with NT values between 2.5 mm and 2.9 mm. Chromosomal abnormality rates in the isolated increased NT groups of 2.5-2.9 mm and 3.0-3.4 mm were 6.7% (16/239) and 10.0% (47/470), respectively, with no statistical significance (χ2 = 2.14, p > 0.05). Fetuses with NT thickness between 2.5 and 2.9 mm combined with the presence of soft markers or non-lethal structural abnormalities exhibited a significantly higher chromosomal abnormality risk (19.0%) compared to fetuses with isolated increased NT ranging from 3.5 to 4.4 mm (13.0%). Pregnancy termination rates increased with NT thickness (χ2 = 435.18, p < 0.0001), ranging from 12.0% (30/249) in the NT 2.5-2.9 mm group to 87.0% (141/162) in the NT ≥ 6.5 mm group. Conclusion: CMA or CNV-seq exhibited good performance in identifying genomic aberrations in pregnancies with increased NT thickness. NT ranging from 2.5 mm to 2.9 mm elevated the risk of fetal chromosomal abnormalities, particularly when combined with other soft markers.

10.
Gut ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38684237
11.
Mitochondrial DNA B Resour ; 9(4): 465-469, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38591052

RESUMO

Strobilanthes dalzielii of Acanthaceae is an herb species with potentially extensive applications for its pharmaceutical and ornamental values. Due to taxonomic complications and limited genetic information, the structural characteristics, and phylogenetic relationships of the S. dalzielii chloroplast genome were assembled and characterized here for the first time. The complete chloroplast genome of S. dalzielii was 144,580 bp in length. The genome is quadripartite in structure and consists of a large single-copy region (92,137 bp) and a small single-copy region (17,669 bp), which are separated by a pair of inverted repeats (each 17,387 bp). A total of 125 genes were annotated, including 80 protein-coding, 37 transfer RNA, and eight ribosomal RNA genes. The overall GC content was 36.4%. Phylogenetic analysis based on the complete chloroplast genome sequence of 21 taxa within the tribe Ruellieae of Acanthaceae using the maximum likelihood and Bayesian inference methods revealed that Strobilanthes diverged after Ruellia; S. dalzielii is closely related to S. tonkinensis. The genomic data obtained from this study will serve as valuable information to the species delimitation and genetic classification of Strobilanthes.

12.
Postgrad Med J ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598956

RESUMO

BACKGROUND: Marital status is associated with cardiovascular disease (CVD) incidence and overall mortality, yet limited research on this topic in elderly individuals is available. Our aim was to comprehensively assess the impact of marital status and other family factors on CVD incidence and long-term mortality among elderly people. METHODS: Data from the Chinese Longitudinal Healthy Longevity Survey (2002/2005/2008-2018) for participants aged ≥60 years were analysed. A cross-sectional study initially examined the correlation between spouses, offspring, living arrangements, and CVD using logistic regression. Subsequently, a retrospective cohort study investigated the long-term associations of these factors with overall mortality via Kaplan-Meier and Cox regression analyses. RESULTS: The study involved 48 510 subjects (average age: 87 years). The cross-sectional analysis revealed a correlation between living with a spouse and an increased incidence of heart disease (adjusted OR 1.27, 95% CI 1.04-1.55) and cerebrovascular disease/stroke (adjusted OR 1.26, 95% CI 1.11-1.42). According to the retrospective cohort analysis, living with a spouse significantly reduced overall mortality (adjusted HR 0.84, 95% CI 0.80-0.87), irrespective of marital relationship quality. Conversely, living with offspring (adjusted HR 1.12, 95% CI 1.08-1.16), having more children (adjusted Pnonlinearity = 0.427) or cohabitants (adjusted Pnonlinearity < 0.0001) were associated with increased overall mortality. CONCLUSION: In the elderly population, being married and living with a spouse were not significantly associated with a decrease in CVD incidence but were associated with a reduction in long-term overall mortality. Living with offspring, having more children, or having a larger family size did not replicate the protective effect but indicated greater overall mortality.

13.
Gut Microbes ; 16(1): 2333790, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38533566

RESUMO

Chemotherapy resistance is one of the main reasons for the poor prognosis of colorectal cancer (CRC). Moreover, dysbiosis of gut bacteria was found to be a specific environmental risk factor. In this study, enrichment of F. nucleatum was elucidated to be significantly associated with CRC recurrence after chemotherapy. Functional experiments showed that F. nucleatum could inhibit pyroptosis induced by chemotherapy drugs, thereby inducing chemoresistance. Furthermore, mechanistic investigation demonstrated that F. nucleatum could regulate the Hippo pathway and promote the expression of BCL2, thereby inhibiting the Caspase-3/GSDME pyroptosis-related pathway induced by chemotherapy drugs and mediating CRC cell chemoresistance. Taken together, these results validated the significant roles of F. nucleatum in CRC chemoresistance, which provided an innovative theoretical basis for the clinical diagnosis and therapy of CRC.


Assuntos
Neoplasias Colorretais , Microbioma Gastrointestinal , Humanos , Fusobacterium nucleatum/fisiologia , Neoplasias Colorretais/microbiologia , Via de Sinalização Hippo , Resistencia a Medicamentos Antineoplásicos , Piroptose , Recidiva Local de Neoplasia
14.
Cell Host Microbe ; 32(4): 489-505.e5, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38513657

RESUMO

Immunotherapy has revolutionized cancer treatment, but inconsistent responses persist. Our study delves into the intriguing phenomenon of enhanced immunotherapy sensitivity in older individuals with cancers. Through a meta-analysis encompassing 25 small-to-mid-sized trials of immune checkpoint blockade (ICB), we demonstrate that older individuals exhibit heightened responsiveness to ICB therapy. To understand the underlying mechanism, we reanalyze single-cell RNA sequencing (scRNA-seq) data from multiple studies and unveil distinct upregulation of exhausted and cytotoxic T cell markers within the tumor microenvironment (TME) of older patients. Recognizing the potential role of gut microbiota in modulating the efficacy of immunotherapy, we identify an aging-enriched enterotype linked to improved immunotherapy outcomes in older patients. Fecal microbiota transplantation experiments in mice confirm the therapeutic potential of the aging-enriched enterotype, enhancing treatment sensitivity and reshaping the TME. Our discoveries confront the prevailing paradox and provide encouraging paths for tailoring cancer immunotherapy strategies according to an individual's gut microbiome profile.


Assuntos
Microbioma Gastrointestinal , Humanos , Animais , Camundongos , Idoso , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia , Envelhecimento , Complexo CD3
15.
PLoS One ; 19(3): e0290648, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38446803

RESUMO

Under the repeated action of aircraft taxiing load, the subgrade plastic deformation becomes the key factor affecting the service performance of the airfields when salinized silt is used to fill the subgrade. In this study, the dynamic triaxial tests were carried out on a region in the northern part of China to study the effects of different salt contents on the dynamic characteristics of silt under cyclic loading. A prediction model for the salinized silt dynamic strength with a plastic strain of 4% as the failure criterion for the subgrade was thus proposed. It is found that with the increase of dynamic stress amplitude, the salinized silt plastic deformation transforms gradually from plastic deformation to incremental failure. The salt contents significantly influence the plastic strain and critical dynamic stress of silt. The strength of the salinized silt specimen is related to the ion concentration in the soil pores and the arrangement pattern of soil particles, as indicated by the progressive strength increase of the salinized silt at the low salt content of 1% and a further gradual decrease at high salt content.


Assuntos
Cloreto de Sódio na Dieta , Cloreto de Sódio , Aeronaves , Automóveis , Solo
16.
Int J Biol Sci ; 20(5): 1669-1687, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481813

RESUMO

Direct tubular injury caused by several medications, especially chemotherapeutic drugs, is a common cause of AKI. Inhibition or loss of cyclin-dependent kinase 12 (CDK12) triggers a transcriptional elongation defect that results in deficiencies in DNA damage repair, producing genomic instability in a variety of cancers. Notably, 10-25% of individuals developed AKI after treatment with a CDK12 inhibitor, and the potential mechanism is not well understood. Here, we found that CDK12 was downregulated in the renal tubular epithelial cells in both patients with AKI and murine AKI models. Moreover, tubular cell-specific knockdown of CDK12 in mice enhanced cisplatin-induced AKI through promotion of genome instability, apoptosis, and proliferative inhibition, whereas CDK12 overexpression protected against AKI. Using the single molecule real-time (SMRT) platform on the kidneys of CDK12RTEC+/- mice, we found that CDK12 knockdown targeted Fgf1 and Cast through transcriptional elongation defects, thereby enhancing genome instability and apoptosis. Overall, these data demonstrated that CDK12 knockdown could potentiate the development of AKI by altering the transcriptional elongation defect of the Fgf1 and Cast genes, and more attention should be given to patients treated with CDK12 inhibitors to prevent AKI.


Assuntos
Injúria Renal Aguda , Fator 1 de Crescimento de Fibroblastos , Humanos , Camundongos , Animais , Fator 1 de Crescimento de Fibroblastos/genética , Quinases Ciclina-Dependentes/genética , Rim , Injúria Renal Aguda/induzido quimicamente , Instabilidade Genômica
17.
J Control Release ; 368: 413-429, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38431093

RESUMO

Exosomes continue to attract interest as a promising nanocarrier drug delivery technology. They are naturally derived nanoscale extracellular vesicles with innate properties well suited to shuttle proteins, lipids, and nucleic acids between cells. Nonetheless, their clinical utility is currently limited by several major challenges, such as their inability to target tumor cells and a high proportion of clearance by the mononuclear phagocyte system (MPS) of the liver and spleen. To overcome these limitations, we developed "Smart Exosomes" that co-display RGD and CD47p110-130 through CD9 engineering (ExoSmart). The resultant ExoSmart demonstrates enhanced binding capacity to αvß3 on pancreatic ductal adenocarcinoma (PDAC) cells, resulting in amplified cellular uptake in in vitro and in vivo models and increased chemotherapeutic efficacies. Simultaneously, ExoSmart significantly reduced liver and spleen clearance of exosomes by inhibiting macrophage phagocytosis via CD47p110-130 interaction with signal regulatory proteins (SIRPα) on macrophages. These studies demonstrate that an engineered exosome drug delivery system increases PDAC therapeutic efficacy by enhancing active PDAC targeting and prolonging circulation times, and their findings hold tremendous translational potential for cancer therapy while providing a concrete foundation for future work utilizing novel peptide-engineered exosome strategies.


Assuntos
Carcinoma Ductal Pancreático , Exossomos , Neoplasias Pancreáticas , Humanos , Exossomos/metabolismo , Antígeno CD47 , Linhagem Celular Tumoral , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia
18.
J Dig Dis ; 25(1): 27-35, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38342693

RESUMO

OBJECTIVE: To investigate the clinical potential and safety of Moluodan to reverse gastric precancerous lesions. METHODS: Patients aged 18-70 years diagnosed with moderate-to-severe atrophy and/or moderate-to-severe intestinal metaplasia, with or without low-grade dysplasia, and negative for Helicobacter pylori were recruited in this randomized, double-blind, parallel-controlled trial. The primary outcome was the improvement of global histological diagnosis at 1-year follow-up endoscopy using the operative link for gastritis assessment, the operative link for gastric intestinal metaplasia assessment, and the disappearance rate of dysplasia. RESULTS: Between November 3, 2017 and January 27, 2021, 166 subjects were randomly assigned to the Moluodan group, 168 to the folic acid group, 84 to the combination group, and 84 to the high-dose Moluodan group. The improvement in global histological diagnosis was achieved in 60 (39.5%) subjects receiving Moluodan, 59 (37.8%) receiving folic acid, 26 (32.1%) receiving the combined drugs, and 36 (47.4%) receiving high-dose Moluodan. Moluodan was non-inferior to folic acid (95% confidence interval: -9.2 to 12.5; P = 0.02). High-dose Moluodan had a trend for better protective efficacy, though there was no statistical significance. The disappearance rate of dysplasia was 82.8% in the Moluodan group, which was superior to folic acid (53.9%; P = 0.006). No drug-related serious adverse events were observed. CONCLUSIONS: One pack of Moluodan three times daily for 1 year was safe and effective in reversing gastric precancerous lesions, especially dysplasia. Doubling its dose showed a better efficacy trend.


Assuntos
Medicamentos de Ervas Chinesas , Gastrite Atrófica , Infecções por Helicobacter , Helicobacter pylori , Lesões Pré-Cancerosas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Gastrite Atrófica/tratamento farmacológico , Gastrite Atrófica/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Lesões Pré-Cancerosas/tratamento farmacológico , Lesões Pré-Cancerosas/patologia , Metaplasia , Ácido Fólico/uso terapêutico , Mucosa Gástrica/patologia
19.
Surg Laparosc Endosc Percutan Tech ; 34(2): 124-128, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38372527

RESUMO

BACKGROUND: Hemangiomas represent 3% of all benign esophageal tumors. Conventional esophagectomy is the standard treatment with its invasive nature and possible surgical complications. Now, less invasive techniques are used with better results. Endoscopic submucosal dissection (ESD) is one of the novel noninvasive methods used for en bloc removal of tumors. No available data about the use of ESD in removing esophageal hemangioma. Here, we studied the validity and safety of ESD as a minimally invasive procedure to remove esophageal hemangioma. METHODS: Three patients were diagnosed with esophageal hemangioma and underwent ESD with en bloc resection. Endoscopic ultrasound (EUS) was performed before ESD to better evaluate the layer of origin and vascularity and guard against perforation. Patients were followed up postintervention to document possible complications. RESULTS: Among the 3 studied patients, one presented with chronic abdominal pain, the second was complaining of dysphagia, and the third patient was diagnosed accidentally. Pathology reports confirmed the diagnosis of hemangiomas in all cases with no atypia and complete removal of the lesions. No complications were reported during the procedure or over the follow-up period. CONCLUSIONS: ESD is a proper, minimally invasive method with good en bloc resection that can be used in cases of esophageal hemangiomas.


Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Esofágicas , Hemangioma , Humanos , Ressecção Endoscópica de Mucosa/métodos , Resultado do Tratamento , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Endossonografia , Hemangioma/cirurgia , Hemangioma/etiologia , Estudos Retrospectivos
20.
Front Plant Sci ; 15: 1333207, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38344186

RESUMO

With the rapid development of the livestock industry, finding new sources of feed has become a critical issue that needs to be addressed urgently. China is one of the top five sunflower producers in the world and generates a massive amount of sunflower stalks annually, yet this resource has not been effectively utilized. Therefore, in order to tap into the potential of sunflower stalks for animal feed, it is essential to explore and develop efficient methods for their utilization.In this study, various proportions of alfalfa and sunflower straw were co-ensiled with the following mixing ratios: 0:10, 2:8, 4:6, 5:5, 6:4, and 8:2, denoted as A0S10, A2S8, A4S6, A5S5, A6S4, and A8S2, respectively. The nutrient composition, fermentation quality, microbial quantity, microbial diversity, and broad-spectrum metabolomics on the 60th day were assessed. The results showed that the treatment groups with more sunflower straw added (A2S8, A4S6) could start fermentation earlier. On the first day of fermentation, Weissella spp.dominated overwhelmingly in these two groups. At the same time, in the early stage of fermentation, the pH in these two groups dropped rapidly, which could effectively reduce the loss of nutrients in the early stage of fermentation.In the later fermentation period, a declining trend in acetic acid levels was observed in A0S10, A2S8, and A4S6, while no butyric acid production was detected in A0S10 and A2S8 throughout the process. In A4S6, butyric acid production was observed only after 30 days of fermentation. From the perspective of metabolites, compared with sunflower ensiling alone, many bioactive substances such as flavonoids, alkaloids, and terpenes are upregulated in mixed ensiling.

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