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1.
World J Clin Cases ; 12(17): 3259-3264, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38898853

RESUMO

BACKGROUND: Prostate cancer is the second most common cancer among men worldwide, and prostate-specific antigen (PSA) is often used in clinical practice to screen for prostate cancer. Normal total PSA (tPSA) level initially excludes prostate cancer. Here, we report a case of prostate cancer with elevated free PSA density (fPSAD). CASE SUMMARY: A patient diagnosed with benign prostatic hyperplasia underwent prostatectomy, and the postoperative pathological results showed acinar adenocarcinoma of the prostate. The patient is currently undergoing endocrine chemotherapy. CONCLUSION: We provide a clinical reference for diagnosis and treatment of patients with normal tPSA but elevated fPSAD.

2.
Polymers (Basel) ; 16(7)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38611271

RESUMO

Stretchable ionogels, as soft ion-conducting materials, have generated significant interest. However, the integration of multiple functions into a single ionogel, including temperature tolerance, self-adhesiveness, and stability in diverse environments, remains a challenge. In this study, a new class of fluorine-containing ionogels was synthesized through photo-initiated copolymerization of fluorinated hexafluorobutyl methacrylate and butyl acrylate in a fluorinated ionic liquid 1-butyl-3-methyl imidazolium bis (trifluoromethylsulfonyl) imide. The resulting ionogels demonstrate good stretchability with a fracture strain of ~1300%. Owing to the advantages of the fluorinated network and the ionic liquid, the ionogels show excellent stability in air and vacuum, as well as in various solvent media such as water, sodium chloride solution, and hexane. Additionally, the ionogels display impressive wide temperature tolerance, functioning effectively within a wide temperature range from -60 to 350 °C. Moreover, due to their adhesive properties, the ionogels can be easily attached to various substrates, including plastic, rubber, steel, and glass. Sensors made of these ionogels reliably respond to repetitive tensile-release motion and finger bending in both air and underwater. These findings suggest that the developed ionogels hold great promise for application in wearable devices.

3.
Br J Oral Maxillofac Surg ; 62(4): 361-366, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38521740

RESUMO

Bone marrow mesenchymal stem cells (BMSC) are promising candidates for the treatment of trans-territory perforator flap necrosis. However, the low retention and survival rate of engrafted BMSCs limit their therapeutic efficacy. Strategies either modifying BMSCs or alleviating the inflammatory environment may solve this problem. Thus, we aimed to explore the therapeutic efficacy of sequential transplantation of exosomes and hypoxia pretreated BMSCs on flap necrosis. After the perforator flap model was created, the exosomes derived from BMSCs were injected immediately into choke zone II followed by transplantation of hypoxia pretreated BMSCs on Day 2. Gross view was performed to assess the flap survival, enzyme-linked immunosorbent assay was performed to evaluate the inflammatory factor level, microvessel number was assessed and quantitative polymerase chain reaction (qPCR) was performed to assess angiogenesis. We found that exosome delivery significantly reduced inflammatory cytokines levels on Day 1 and Day 3 and promoted the engrafted BMSCs' survival on Day 7. After combining with transplantation of hypoxia pretreated BMSCs, the flap survival rate and the angiogenesis-related gene expression were significantly higher than in the other three groups; the von Willebrand factor (vWF) vascular diameter and vWF vascular count were significantly higher than in the phosphate buffered saline (PBS) group. Thus, we concluded that sequential transplantation of exosomes and BMSCs combinatorially pretreated with hypoxia further facilitated flap survival. This sequential transplantation approach provides novel insights into the clinical treatment of flap necrosis.


Assuntos
Exossomos , Sobrevivência de Enxerto , Transplante de Células-Tronco Mesenquimais , Neovascularização Fisiológica , Retalho Perfurante , Ratos Sprague-Dawley , Animais , Ratos , Masculino , Retalho Perfurante/irrigação sanguínea , Transplante de Células-Tronco Mesenquimais/métodos , Necrose , Células-Tronco Mesenquimais , Citocinas/metabolismo , Hipóxia , Hipóxia Celular/fisiologia
4.
Mol Cancer Ther ; 23(3): 394-399, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38015561

RESUMO

Isocitrate dehydrogenase (IDH) enzymes catalyze the decarboxylation of isocitrate to alpha-ketoglutarate (αKG). IDH1/2 mutations preferentially convert αKG to R-2-hydroxyglutarate (R2HG), resulting in R2HG accumulation in tumor tissues. We investigated circulating 2-hydroxyglutate (2HG) as potential biomarkers for patients with IDH-mutant (IDHmt) cholangiocarcinoma (CCA). R2HG and S-2-hydroxyglutarate (S2HG) levels in blood and tumor tissues were analyzed in a discovery cohort of patients with IDHmt glioma and CCA. Results were validated in cohorts of patients with CCA and clear-cell renal cell carcinoma. The R2HG/S2HG ratio (rRS) was significantly elevated in tumor tissues, but not in blood for patients with IDHmt glioma, while circulating rRS was elevated in patients with IDHmt CCA. There were overlap distributions of circulating R2HG and total 2HG in patients with both IDHmt and wild-type (IDHwt) CCA, while there was minimal overlap in rRS values between patients with IDHmt and IDHwt CCA. Using the rRS cut-off value of 1.5, the sensitivity of rRS was 90% and specificity was 96.8%. Circulating rRS is significantly increased in patients with IDHmt CCA compare with patients with IDHwt CCA. Circulating rRS is a sensitive and specific surrogate biomarker for IDH1/2 mutations in CCA. It can potentially be used as a tool for monitoring IDH-targeted therapy.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Glioma , Glutaratos , Humanos , Isocitrato Desidrogenase/genética , Biomarcadores , Glioma/patologia , Mutação , Ácidos Cetoglutáricos , Colangiocarcinoma/genética , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/genética
5.
J Bone Miner Metab ; 42(1): 90-98, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38157037

RESUMO

INTRODUCTION: Previous research has confirmed that patients with type 2 diabetes mellitus tend to have higher bone mineral density (BMD), but it is unknown whether this pattern holds true for individuals without diabetes. This Mendelian randomization (MR) study aims to investigate the potential causal relationship between various glycemic trait (including fasting glucose, fasting insulin, 2-h postprandial glucose, and glycated hemoglobin) and BMD in non-diabetic individuals. The investigation focuses on different age groups (15-30, 30-45, 45-60, and 60 + years) and various skeletal sites (forearm, lumbar spine, and hip). MATERIALS AND METHODS: We utilized genome-wide association study data from large population-based cohorts to identify robust instrumental variables for each glycemic traits parameter. Our primary analysis employed the inverse-variance weighted method, with sensitivity analyses conducted using MR-Egger, weighted median, MR-PRESSO, and multivariable MR methods to assess the robustness and potential horizontal pleiotropy of the study results. RESULTS: Fasting insulin showed a negative modulating relationship on both lumbar spine and forearm. However, these associations were only nominally significant. No significant causal association was observed between blood glucose traits and BMD across the different age groups. The direction of fasting insulin's causal effects on BMD showed inconsistency between genders, with potentially decreased BMD in women with high fasting insulin levels and an increasing trend in BMD in men. CONCLUSIONS: In the non-diabetic population, currently available evidence does not support a causal relationship between glycemic traits and BMD. However, further investigation is warranted considering the observed gender differences.


Assuntos
Diabetes Mellitus Tipo 2 , Análise da Randomização Mendeliana , Humanos , Feminino , Masculino , Adolescente , Densidade Óssea/genética , Diabetes Mellitus Tipo 2/genética , Estudo de Associação Genômica Ampla , Insulina , Glucose , Polimorfismo de Nucleotídeo Único
6.
Front Cardiovasc Med ; 10: 1276035, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38099226

RESUMO

Background: The suggested threshold level of cardiac troponin T elevation after cardiac surgery is not very clear, and the values recommended by various guidelines and literature reports are quite different. Methods: In this retrospective cohort study, we collected clinical data of patients who underwent heart surgery at Tsinghua University First Hospital between January 2015 and December 2022. Using the high-sensitivity cardiac troponin T levels (reference upper limit: 14 ng/L) measured at 1-3 days postoperation, the relationship between the cardiac troponin T level and the 30-day mortality risk was evaluated using Cox regression analysis. Results: Among the 3,128 patients included in this study, the types of operations mainly consisted of coronary artery bypass graft (CABG, 1,164, 37.2%), aortic valve replacement (AVR, 735, 23.5%), and other cardiac operations (1,229, 39.3%). Within 30 days postoperation, 57 patients (1.8%) died and 72 patients (2.3%) developed major vascular complications. In patients undergoing CABG or AVR, the cardiac troponin T threshold level measured within one day postoperation related to an increased 30-day mortality was determined to be 3,012 ng/L (95% CI: 1,435-3,578 ng/L), which is 218 times higher than the reference upper limit. In patients undergoing other cardiac operations, this threshold was 5,876 ng/L (95% CI: 2,458-8,119 ng/L), which is 420 times higher than the reference upper limit. Conclusion: The high-sensitivity cardiac troponin T level associated with an increased 30-day mortality risk after cardiac surgery is significantly higher than the current recommendations for defining clinically important perioperative myocardial injury.

7.
Anal Chem ; 95(47): 17400-17406, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-37967038

RESUMO

Amine determination is crucial to our daily life, including the prevention of pollution, the treatment of certain disorders, and the evaluation of food quality. Herein, a mixed-linkage donor-acceptor covalent organic framework (named DSE-COF) was first constructed by the polymerization between 2,4-dihydroxybenzene-1,3,5-tricarbaldehyde (DTA) and 4,4'-(benzo[c][1,2,5]selenadiazole-4,7-diyl)dianiline (SEZ). DSE-COF displayed superior turn-on fluorescent responses to primary, secondary, and tertiary aliphatic amines, such as cadaverine, isopropylamine, sec-butylamine, cyclohexylamine, hexamethylenediamine, di-n-butylamine, and triethylamine in absolute acetonitrile than other organic species. Further experiments and theoretical calculations demonstrated that the combination of intramolecular charge transfer (ICT) and photoinduced electron transfer (PET) effects between the DSE-COF and aliphatic amines resulted in enhanced fluorescence. Credibly, DSE-COF can quantitatively detect cadaverine content in actual pork samples with satisfactory results. In addition, DSE-COF-based test papers could rapidly monitor cadaverine from real pork samples, manifesting the potential application of COFs in food quality inspection.


Assuntos
Síndrome de Cockayne , Estruturas Metalorgânicas , Humanos , Cadaverina , Aminas , Cicloexilaminas , Corantes
8.
Front Microbiol ; 14: 1256874, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37920262

RESUMO

Background and aim: Previous studies have reported an association between gut microbiota and cirrhosis. However, the causality between intestinal flora and liver cirrhosis still remains unclear. In this study, bi-directional Mendelian randomization (MR) analysis was used to ascertain the potential causal effect between gut microbes and cirrhosis. Methods: Large-scale Genome Wide Association Study (GWAS) data of cirrhosis and gut microbes were obtained from FinnGen, Mibiogen consortium, and a GWAS meta-analysis of Alcoholic cirrhosis (ALC). Two-sample MR was performed to determine the causal relationship between gut microbiota and cirrhosis. Furthermore, a bi-directional MR analysis was employed to examine the direction of the causal relations. Result: In MR analysis, we found that 21 gut microbiotas were potentially associated with cirrhosis. In reverse MR analysis, 11 gut microbiotas displayed potentially associations between genetic liability in the gut microbiome and cirrhosis. We found that the family Lachnospiraceae (OR: 1.59, 95% CI:1.10-2.29) might be harmful in cirrhotic conditions (ICD-10: K74). Furthermore, the genus Erysipelatoclostridium might be a protective factor for cirrhosis (OR:0.55, 95% CI:0.34-0.88) and PBC (OR:0.68, 95% CI:0.52-0.89). Combining the results from the MR analysis and reverse MR analysis, we firstly identified the Genus Butyricicoccus had a bi-directional causal effect on PBC (Forward: OR: 0.37, 95% CI:0.15-0.93; Reverse: OR: 1.03, 95% CI:1.00-1.05). Conclusion: We found a new potential causal effect between cirrhosis and intestinal flora and provided new insights into the role of gut microbiota in the pathological progression of liver cirrhosis.

9.
BMC Musculoskelet Disord ; 24(1): 652, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37587417

RESUMO

OBJECTIVE: The aim of this study was to determine the relationship between multifidus degeneration and sex, age and side of protrusion in patients with lumbar disc herniation(LDH). METHODS: Data were collected from September 2015 to September 2022 from patients with L4/5 and L5/S1 LDH. A total of 104 patients (62 males and 42 females) were included in this study, and there were 35 and 69 cases of L4/5 and L5/S1 LDH, respectively. Patients were divided into 4 groups according to age: group 1 (20-29), group 2 (30-39), group 3 (40-49) and group 4 (50-59). Magnetic resonance spectroscopy analysis was used to observe the fat fraction (FF) and functional cross-sectional area (f-CSA) of the defatted multifidus muscle of the protruding side (affected side) and the nonprotruding side (healthy side) of the L4/5 and L5/S1 gaps to evaluate the relationship between multifidus degeneration and sex, age and protruding side in patients with LDH. RESULTS: Between sexes, the FF of the multifidus muscle was significantly greater in women than in men, regardless of whether it was on the affected or healthy side of the L4/5 segment or on the affected or healthy side of the L5/S1 segment (P < 0.05). Between age groups, there was a significantly positive relationship between the change in FF (%) of the multifidus muscle in patients with LDH and age, with increasing fatty infiltration of the multifidus increasing with age (P < 0.05); notably, there was a significant difference between group 4 and the remaining three groups but no significant difference between groups 1, 2 and 3. The f-CSA of the multifidus (cm2) was negatively correlated with age, with the f-CSA of the multifidus becoming more atrophic with increasing age; specifically, there was a significant difference between group 1 and the other three groups (P < 0.05) but not between groups 2, 3 and 4. Regarding the side of the herniated disc, (1) the differences in FF and f-CSA at the L4/5 and L5/S1 levels were not statistically significant between the affected side and the healthy side in patients with lumbar disc herniation at the L4/5 segment (P > 0.05); (2) the differences in FF and f-CSA at the L5/S1 level were not statistically significant between the affected side and the healthy side in patients with LDH at the L5/S1 segment (P > 0.05); (3) the difference between FF at the L4/5 level and f-CSA and FF at the L5/S1 level was not statistically significant (P > 0.05); and (4) the f-CSA at the L5/S1 level was significantly greater on the healthy side than on the affected side (P < 0.05). CONCLUSION: The proportion of lipoatrophy in female patients with L4/5 and L5/S1 disc herniations was greater than that in male patients. Lipoatrophy of the multifidus muscle increased with age and was significantly worse in patients over 50 years of age. The f-CSA of the multifidus muscle was negatively related to age, and the f-CSA of the multifidus muscle became more atrophic with increasing age. A comparison of degeneration showed no significant difference between the L4/5 patients and the L5/S1 patients in terms of f-CSA atrophy on the affected side of the herniated disc compared to the healthy side.


Assuntos
Deslocamento do Disco Intervertebral , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Músculos Paraespinais/diagnóstico por imagem , Nível de Saúde , Vértebras Lombares/diagnóstico por imagem , Medula Espinal
10.
Braz. j. otorhinolaryngol. (Impr.) ; 89(3): 469-476, May-June 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1447713

RESUMO

Abstract Objective To explore whether Cyclic Adenosine Monophosphate (cAMP)-Epac1 signaling is activated in 1-Desamino-8-D-arginine-Vasopressin-induced Endolymphatic Hydrops (DDAVP-induced EH) and to provide new insight for further in-depth study of DDAVP-induced EH. Methods Eighteen healthy, red-eyed guinea pigs (36 ears) weighing 200-350 g were randomly divided into three groups: the control group, which received intraperitoneal injection of sterile saline (same volume as that in the other two groups) for 7 consecutive days; the DDAVP-7d group, which received intraperitoneal injection of 10 mg/mL/kg DDAVP for 7 consecutive days; and the DDAVP-14d group, which received intraperitoneal injection of 10 μg/mL/kg DDAVP for 14 consecutive days. After successful modeling, all animals were sacrificed, and cochlea tissues were collected to detect the mRNA and protein expression of the exchange protein directly activated by cAMP-1 and 2 (Epac1, Epac2), and Repressor Activator Protein-1 (Rap1) by Reverse Transcription (RT)-PCR and western blotting, respectively. Results Compared to the control group, the relative mRNA expression of Epac1, Epac2, Rap1A, and Rap1B in the cochlea tissue of the DDAVP-7d group was significantly higher (p< 0.05), while no significant difference in Rap1 GTPase activating protein (Rap1gap) mRNA expression was found between the two groups. The relative mRNA expression of Epac1, Rap1A, Rap1B, and Rap1gap in the cochlea tissue of the DDAVP-14d group was significantly higher than that of the control group (p< 0.05), while no significant difference in Epac2 mRNA expression was found between the DDAVP-14d and control groups. Comparison between the DDAVP-14d and DDAVP-7d groups showed that the DDAVP-14d group had significantly lower Epac2 and Rap1A (p< 0.05) and higher Rap1gap (p < 0.05) mRNA expression in the cochlea tissue than that of the DDAVP-7d group, while no significant differences in Epac1 and Rap1B mRNA expression were found between the two groups. Western blotting showed that Epac1 protein expression in the cochlea tissue was the highest in the DDAVP-14d group, followed by that in the DDAVP-7d group, and was the lowest in the control group, showing significant differences between groups (p< 0.05); Rap1 protein expression in the cochlea tissue was the highest in the DDAVP-7d group, followed by the DDAVP-14d group, and was the lowest in the control group, showing significant differences between groups (p< 0.05); no significant differences in Epac2 protein expression in the cochlea tissue were found among the three groups. Conclusion DDAVP upregulated Epac1 protein expression in the guinea pig cochlea, leading to activation of the inner ear cAMP-Epac1 signaling pathway. This may be an important mechanism by which DDAVP regulates endolymphatic metabolism to induce EH and affect inner ear function. Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence Level 5.

11.
Braz J Otorhinolaryngol ; 89(3): 469-476, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37116375

RESUMO

OBJECTIVE: To explore whether Cyclic Adenosine Monophosphate (cAMP)-Epac1 signaling is activated in 1-Desamino-8-D-arginine-Vasopressin-induced Endolymphatic Hydrops (DDAVP-induced EH) and to provide new insight for further in-depth study of DDAVP-induced EH. METHODS: Eighteen healthy, red-eyed guinea pigs (36 ears) weighing 200-350 g were randomly divided into three groups: the control group, which received intraperitoneal injection of sterile saline (same volume as that in the other two groups) for 7 consecutive days; the DDAVP-7d group, which received intraperitoneal injection of 10 mg/mL/kg DDAVP for 7 consecutive days; and the DDAVP-14d group, which received intraperitoneal injection of 10 µg/mL/kg DDAVP for 14 consecutive days. After successful modeling, all animals were sacrificed, and cochlea tissues were collected to detect the mRNA and protein expression of the exchange protein directly activated by cAMP-1 and 2 (Epac1, Epac2), and Repressor Activator Protein-1 (Rap1) by Reverse Transcription (RT)-PCR and western blotting, respectively. RESULTS: Compared to the control group, the relative mRNA expression of Epac1, Epac2, Rap1A, and Rap1B in the cochlea tissue of the DDAVP-7d group was significantly higher (p <  0.05), while no significant difference in Rap1 GTPase activating protein (Rap1gap) mRNA expression was found between the two groups. The relative mRNA expression of Epac1, Rap1A, Rap1B, and Rap1gap in the cochlea tissue of the DDAVP-14d group was significantly higher than that of the control group (p <  0.05), while no significant difference in Epac2 mRNA expression was found between the DDAVP-14d and control groups. Comparison between the DDAVP-14d and DDAVP-7d groups showed that the DDAVP-14d group had significantly lower Epac2 and Rap1A (p <  0.05) and higher Rap1gap (p < 0.05) mRNA expression in the cochlea tissue than that of the DDAVP-7d group, while no significant differences in Epac1 and Rap1B mRNA expression were found between the two groups. Western blotting showed that Epac1 protein expression in the cochlea tissue was the highest in the DDAVP-14d group, followed by that in the DDAVP-7d group, and was the lowest in the control group, showing significant differences between groups (p <  0.05); Rap1 protein expression in the cochlea tissue was the highest in the DDAVP-7d group, followed by the DDAVP-14d group, and was the lowest in the control group, showing significant differences between groups (p <  0.05); no significant differences in Epac2 protein expression in the cochlea tissue were found among the three groups. CONCLUSION: DDAVP upregulated Epac1 protein expression in the guinea pig cochlea, leading to activation of the inner ear cAMP-Epac1 signaling pathway. This may be an important mechanism by which DDAVP regulates endolymphatic metabolism to induce EH and affect inner ear function. OXFORD CENTRE FOR EVIDENCE-BASED MEDICINE 2011 LEVELS OF EVIDENCE: Level 5.


Assuntos
Orelha Interna , Hidropisia Endolinfática , Cobaias , Animais , Desamino Arginina Vasopressina/farmacologia , Transdução de Sinais , Hidropisia Endolinfática/induzido quimicamente , Cóclea
12.
Food Funct ; 14(8): 3686-3700, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-36971300

RESUMO

The possible mechanism by which the active components of Anhua fuzhuan tea act on FAM in NAFLD lesions was investigated. 83 components of Anhua fuzhuan tea were analysed by UPLC-Q-TOF/MS. Luteolin-7-rutinoside and other compounds were first discovered in fuzhuan tea. According to the TCMSP database and the Molinspiration website tool to predict and review the literature reports, 78 compounds were identified in fuzhuan tea with possible biological activities. The PharmMapper, Swiss target prediction, and SuperPred databases were used to predict the action targets of biologically active compounds. The GeneCards, CTD, and OMIM databases were mined for NAFLD and FAM genes. Then, a fuzhuan Tea-NAFLD-FAM Venn diagram was constructed. Using the STRING database and CytoHubba program of Cytoscape software, protein interaction analysis was performed, and 16 key genes, including PPARG, were screened. GO function and KEGG enrichment analyses of the screened key genes showed that Anhua fuzhuan tea may regulate FAM in the process of NAFLD through the AMPK signalling pathway, nonalcoholic fatty liver disease pathway, etc. After constructing an active ingredient-key target-pathway map with Cytoscape software, combined with literature reports and BioGPS database analysis, we believe that among the 16 key genes, SREBF1, FASN, ACADM, HMGCR, and FABP1 have potential in the treatment of NAFLD. Animal experiments confirmed the effect of Anhua fuzhuan tea in improving NAFLD and confirmed that this tea can interfere with the gene expression of the above five targets by the AMPK/PPAR pathway, providing support for Anhua fuzhuan tea interfering with FAM in NAFLD lesions.


Assuntos
Medicamentos de Ervas Chinesas , Hepatopatia Gordurosa não Alcoólica , Animais , Proteínas Quinases Ativadas por AMP/genética , Farmacologia em Rede , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Bases de Dados Factuais , Chá , Medicamentos de Ervas Chinesas/farmacologia , Simulação de Acoplamento Molecular
13.
Antioxidants (Basel) ; 12(2)2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36829795

RESUMO

Redox balance is essential to maintain the body's normal metabolism. Once disrupted, it may lead to various chronic diseases, such as diabetes, neurodegenerative diseases, cardiovascular diseases, inflammatory diseases, cancer, aging, etc. Oxidative stress can cause or aggravate a series of pathological processes. Inhibition of oxidative stress and related pathological processes can help to ameliorate these chronic diseases, which have been found to be associated with Nrf2 activation. Nrf2 activation can not only regulate the expression of a series of antioxidant genes that reduce oxidative stress and its damage, but also directly regulate genes related to the above-mentioned pathological processes to counter the corresponding changes. Therefore, targeting Nrf2 has great potential for the prevention or treatment of chronic diseases, and many natural phytochemicals have been reported as Nrf2 activators although the defined mechanisms remain to be elucidated. This review article focuses on the possible mechanism of Nrf2 activation by natural phytochemicals in the prevention or treatment of chronic diseases and the regulation of oxidative stress. Moreover, the current clinical trials of phytochemical-originated drug discovery by targeting the Nrf2-ARE pathway were also summarized; the outcomes or the relationship between phytochemicals and chronic diseases prevention are finally analyzed to propose the future research strategies and prospective.

14.
J Tradit Chin Med ; 43(1): 42-50, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36639994

RESUMO

OBJECTIVE: To investigate the efficacy of tilianin extracted from Xiangqinglan () on apoptosis of H9c2 cell after oxygen-glucose deprivation/reoxygenation (OGD/R) and the mechanism. METHODS: Tilianin was obtained from Beijing Inluck Science and Technology Development Co. Ltd., with purity ≥ 98%. The OGD/R model was established in H9c2 cells. Flow cytometry detected the mitochondrial membrane potential, apoptosis rates, mitochondrial reactive oxygen species (ROS) and calcium ion concentration. Succinate dehydrogenase (SDH) activity, succinate content and levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1 ß (IL-1ß) were detected with enzyme-linked immunosorbent assay. Western blot measured protein levels. RESULTS: Tilianin significantly reduced the apoptotic rates, ROS levels, calcium ion concentration, succinate content, and, levels of TNF-α, IL-6 and IL-1ß of OGD/R cells, while significantly increased the membrane potential and SDH activity in mitochondria. Western blot analysis showed that tilianin significantly up-regulated p-Calmodulin-dependent protein kinase Ⅱ and voltage-dependent anion selective channel levels in OGD/R cells, while significantly down-regulated p-protein kinase B, Bcl-2-associated X, and dynamin-related protein 1 levels related to apoptosis in the mitochondrial pathway. Moreover, tilianin significantly up-regulated B-cell lymphoma-2 and mitochondrial protein 2 related to the inhibition of apoptosis. Furthermore, tilianin down-regulated phosphorylated-apoptosis signal-regulated kinase 1, phosphorylated-p38 and C/EBP homologous protein related to endoplasmic reticulum stress. CONCLUSIONS: Tilianin may inhibit OGD/R-induced H9c2 cell apoptosis mediated by mitochondrial pathway and endoplasmic reticulum stress, thus protecting cardiomyocytes.


Assuntos
Glucose , Oxigênio , Humanos , Oxigênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Glucose/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Cálcio/metabolismo , Interleucina-6/metabolismo , Mitocôndrias/metabolismo , Apoptose , Estresse do Retículo Endoplasmático
15.
Chinese Pharmacological Bulletin ; (12): 1973-1979, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013962

RESUMO

Aim To investigate the effeets of Dracocephalum Moldavica total flavonoids (TFDM) on the foaming lipoprotein (ox-LDL), and to further elucidate the mechanism of anti-atherosclerosis (AS) of TFDM. Methods RAW264. 7 maerophages were cultured in vitro and induced to become foam cells by ox-LDL stimulation, and inflammation of mouse monocyte macrophage leukemia cells (RAW264. 7) induced by oxi-dized low density TFDM(25, 50, 100 mg • L"

16.
Neuroscience Bulletin ; (6): 1683-1702, 2023.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-1010651

RESUMO

Parvalbumin interneurons belong to the major types of GABAergic interneurons. Although the distribution and pathological alterations of parvalbumin interneuron somata have been widely studied, the distribution and vulnerability of the neurites and fibers extending from parvalbumin interneurons have not been detailly interrogated. Through the Cre recombinase-reporter system, we visualized parvalbumin-positive fibers and thoroughly investigated their spatial distribution in the mouse brain. We found that parvalbumin fibers are widely distributed in the brain with specific morphological characteristics in different regions, among which the cortex and thalamus exhibited the most intense parvalbumin signals. In regions such as the striatum and optic tract, even long-range thick parvalbumin projections were detected. Furthermore, in mouse models of temporal lobe epilepsy and Parkinson's disease, parvalbumin fibers suffered both massive and subtle morphological alterations. Our study provides an overview of parvalbumin fibers in the brain and emphasizes the potential pathological implications of parvalbumin fiber alterations.


Assuntos
Camundongos , Animais , Epilepsia do Lobo Temporal/patologia , Parvalbuminas/metabolismo , Doença de Parkinson/patologia , Neurônios/metabolismo , Interneurônios/fisiologia , Modelos Animais de Doenças , Encéfalo/patologia
17.
International Eye Science ; (12): 1260-1263, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-978615

RESUMO

AIM: To investigate the effect of the expression of miR-375 on the proliferation and invasion of choroidal melanoma(CM)MUM-2B cells.METHODS: MUM-2B cells were cultured and were transfected with miR-375 mimic sequence(mimic group), miR-375 inhibitor sequence(inhibitor group), negative control group and no treatment(blank group). The qRT-PCR, CCK-8, apoptosis and Transwell experiments were used respectively to detect the expression of miR-375, cell proliferation activity, apoptosis, cell migration and invasion.RESULTS: Compared with the negative control group(1.01±0.10)and the blank group(1.03±0.07), the expression level of miR-375 in the cells of the mimic group(2.65±0.15)was increased, while the expression level of miR-375 in the cells of the inhibitor group(0.28±0.06)was decreased(P&#x003C;0.05). Compared with the blank group and negative control group, the OD values of the cells in the mimic group at 24, 48, 72, and 96h were decreased(P&#x003C;0.05), while the OD values of the cells in the inhibitor group at 24, 48, 72, and 96h were increased(P&#x003C;0.05). Compared with the apoptosis rates in the blank group and negative control group, which were(20.54±4.01)% and(22.80±4.28)%, the apoptosis rate in the mimic group(39.11±3.37)% was increased(P&#x003C;0.05), while it was decreased in the inhibitor group(10.13±2.17)%(P&#x003C;0.05). Compared with the blank group and negative control group, the number of migration cell and the number of invasion cell in the mimic group were decreased(P&#x003C;0.05), while the number of migration cell and the number of invasion cell in the inhibitor group were increased(P&#x003C;0.05). CONCLUSIONS: Up-regulating the expression of miR-375 in MUM-2B cells can reduce cell proliferation activity, accelerate cell apoptosis, and inhibit cell migration and invasion, while down-regulating the expression of miR-375 has the opposite effect. It indicates that miR-375 may play the function of tumor suppressor in the course of CM.

18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-973239

RESUMO

ObjectiveArtificial intelligence (AI) full smear automated diatom detection technology can perform forensic pathology drowning diatom detection more quickly and efficiently than human experts.However, this technique was only used in conjunction with the strong acid digestion method, which has a low extraction rate of diatoms. In this study, we propose to use the more efficient proteinase K tissue digestion method (hereinafter referred to as enzyme digestion method) as a diatom extraction method to investigate the generalization ability and feasibility of this technique in other diatom extraction methods. MethodsLung tissues from 6 drowned cadavers were collected for proteinase K ablation and made into smears, and the smears were digitized using the digital image matrix cutting method and a diatom and background database was established accordingly.The data set was divided into training set, validation set and test set in the ratio of 3:1:1, and the convolutional neural network (CNN) models were trained, internally validated, and externally tested on the basis of ImageNet pre-training. ResultsThe results showed that the accuracy rate of the external test of the best model was 97.65 %, and the area where the model features were extracted was the area where the diatoms were located. The best CNN model in practice had a precision of more than 80 % for diatom detection of drowned corpses. ConclusionIt is shown that the AI automated diatom detection technique based on CNN model and enzymatic digestion method in combination can efficiently identify diatoms and can be used as an auxiliary method for diatom detection in drowning identification.

19.
Journal of Acute Care Surgery ; (2): 105-111, 2023.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-1000649

RESUMO

Purpose@#The consequences of severe traumatic injury extend beyond hospital admission and have the potential for long-term functional, psychological, and economic sequalae. This study investigated patient outcomes 6 months following major trauma. @*Methods@#Using the National Trauma Registry, database of patients who were admitted between 2016-18 in a tertiary trauma hospital for major trauma [Injury Severity Score (ISS) ≥ 16] a review was performed on 6-month outcomes [including functional outcomes, self-reported state of health and outcome scores (EuroQol-5 Dimension score and Glasgow Outcome Scale Extended)].Result: There were 637 patients who were treated for major trauma (ISS ≥ 16); the median age was 64 years (range 16-100) and 435 (68.3%) patients were male. The most common injury mechanisms included falling from height (56.5%) and motor vehicle accident (27.0%). The median ISS was 24 (range 16-75). After 6 months, 87.6% of responders were living at home, 25.0% were back to work, and 55.1% were ambulating independently. The median self-rated state of health was 73 at baseline and 64 at 6 months. Age and length of stay were independent predictors of return to ambulation using multivariate analysis. Age, Abbreviated Injury Scale external, Glasgow Coma Scale on Emergency Department arrival, heart rate, and need for transfusion were independent predictors of failure to return to work at 6 months using multivariate analysis. Charlson Comorbidity Index, Glasgow Coma Scale on arrival, temperature, pain and need for inpatient rehabilitation were independent predictors of mortality at 6 months. @*Conclusion@#Recovery from major trauma is multi-faceted and requires a team-based approach well beyond discharge.

20.
Chinese Journal of School Health ; (12): 1294-1298, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-988818

RESUMO

Objective@#To investigate the prevalence of Internet addiction and depression of students, and to analyze the co-occurrence and trend, so as to provide a theoretical basis for prevention and controlling measures of Internet addiction and depression.@*Methods@#A total of 6 317,7 152,81 808,71 180 and 89 932 students aged 10 to 24 years from 12 leagues (103 banners) in Inner Mongolia Autonomous Region were selected by stratified random cluster sampling in September each year from 2017 to 2021. The Internet Addiction Scale and the Central for Epidemiologic Studies Depression Scale(CES-D) was used to measure Internet addiction and depression. And the annual inspection rate, group difference and annual change trend in students were calculated. Multivariate linear regression and restricted cubic spline analysis were used to estimate the linear and non linear associations between Internet addiction and depression in students.@*Results@#The Internet addiction proportion in students gradually decreased from 4.1% in 2017 to 2.1% in 2020, but increased to 3.9% in 2021. And the depressive symptoms proportion increased from 20.9% in 2017 to 28.0% in 2020 and 27.0% in 2021. The detection rate of Internet addiction and depression comorbidities remained at 1.8% to 2.5 %. The Internet addiction proportion in boys was higher than that in girls( χ 2=42.82, P <0.05). The depressive symptoms prevalence in girls was higher than that in boys( χ 2= 553.90, P <0.05). Taking reversal in prevalence of Internet addiction in urban and rural areas was observed in 2019. The detection rates of depressive symptoms and comorbidity were higher in urban areas than these in suburban counties on the whole, and the difference showed a trend of decreasing or even equalizing year by year. Internet addiction was positively correlated with depressive symptoms score ( B=1.67, 95%CI =1.64-1.71), the proportion of depressive symptoms ( OR=1.39, 95%CI =1.38-1.41) and the proportion of major depressive symptoms ( OR=1.35, 95%CI =1.33-1.36) among students in 2021 ( P <0.05). An N-shaped curve was found in the significant nonlinear associations between internet addiction and depression across sex, region and school stage.@*Conclusion@#Internet addiction and depression in students show significant linear and non-linear associations, which are consistent in different sexes, regions and school stages. Therefore, relevant measures should be made and implemented in each region, especially in suburb areas, so as to prevent the increasingly development of adolescents and children s Internet addiction and depression.

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