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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 285: 121816, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36115305

RESUMO

Fluorine is a necessary element for human, which is closely related to life activities, such as metabolism of teeth and bone tissue. A small amount of fluoride ions can promote the strengthen of our body. However, a large amount of fluoride ions will damage the human immune system to produce organ diseases. Sensitive and rapid detection of fluoride ions has attracted great interests for researchers. In this work, a reactive fluorescent probe SCP for detection of fluoride ions with high quantum yield was designed and synthesized based on the carbazole ring. Subsequently, the photophysical properties of the probe SCP were carefully studied. At last, SCP performed 62.8% quantum yield in physiological condition, excellent ability of quantitative analysis, well selectivity, and distinguishing features for HepG2 cell imaging.

2.
J Ethnopharmacol ; : 115728, 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36126783

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Tongguanteng injection (TGT), the water extract from the stem of the Traditional Chinese hebal medicine of Marsdenia tenacissima (Roxb.) Wight et Arn. has been used as anticancer remedy for decades. TGT was not only used in the treatment of many malignant cancers extensively, but also an adjuvant anticancer drug with chemotherapeutics clinically. AIM OF THE STUDY: To evaluate the effects of TGT on reversing paclitaxel (PTX) resistance and investigated the potential mechanism related to TAB1 in ovarian cancer (OC) in vitro and in vivo. MATERIALS AND METHODS: The synergistic effect and reversal ratio were determined by CCK8 assay and median-effect principle after the combination of TGT and PTX in OC A2780 and its PTX-resistant (A2780/T) cells. The biological functions in cell apoptosis, migration and invasion of A2780/T cells treated by PTX 4 µM with TGT 20, 40, 80 mg mL-1 for 24 h were evaluated by colony formation, flow cytometry, wound healing and transwell assays. Proteomics technique and bioinformatic analysis were used to indentify the change of TAB1 expression in A2780/T cells induced by TGT. The association between TAB1 expression and human OC was analyzed by gene expression databases. In A2780/T cells, western blotting and colony formation assays were used to investigate the relationship between TAB1 expression and PTX resistance after TAB1 overexpression by TAB1 plasmids. The mechanism of TGT and PTX regulating TAB1 and its related proteins were explored by western blotting and flow cytometry assays after TAB1 knock-down using siTAB1. Moreover, TUNEL staining, immunohistochemistry (IHC) and histopathology were used to observe the antitumor effects, TAB1 and p-p38 expression and the tissues impairments in nude mice xenograft model established by A2780/T cells after the co-treatment with TGT and PTX by in vivo. RESULTS: TGT combined with PTX showed the synergistic effect (CI<1), which could reverse the IC50 values of PTX in OC A2780 and A2780/T cells about 23.50 and 6.44 times, respectively. Besides, TGT combined with PTX could significantly inhibit the migration, invasion and promote apoptosis of A2780/T cells. We identified that TGT could induce TAB1 expression in A2780/T cells by proteomics analysis. TAB1 downregulation was significantly associated with tumorigenesis and poor prognosis in OC patients and PTX resistance in A2780/T cells. Furthermore, TGT could activate TAB1/TAK1/p38 MAPK signaling pathway targeting TAB1 and regulate the expression of Bax, Bcl-2 proteins to improve the sensitivity of A2780/T cells to PTX. TGT combined with PTX also showed a greater inhibition in tumor growth than PTX monotherapy in vivo. These promising results show the efficacy of TGT in reversing PTX resistance and provide a potential strategy that targeting TAB1/TAK1/p38 MAPK signaling pathway may improve the chemotherapy sensitivity in OC. CONCLUSIONS: Our results revealed that Tongguanteng injection could reverse paclitaxel resistance and the potential mechanism might be associated with the activation of TAB1/TAK1/p38 MAPK signaling pathway in OC in vitro and in vivo. TAB1 might be a pivotal target for reversing PTX resistance. This study will provide a theoretical basis for the combination of Tongguanteng injection and paclitaxel in clinic.

3.
ACS Omega ; 7(36): 32708-32716, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36120006

RESUMO

Thiolate-protected gold nanoclusters (denoted as Au m (SR) n or Au n L m ) have received extensive attention both experimentally and theoretically. Understanding the growth mode of the Au4 unit in Au m (SR) n is of great significance for experimental synthesis and the search for new gold clusters. In this work, we first build six clusters of Au7(AuCl2)3, Au12(AuCl2)4, Au16(AuCl2)6, Au22(AuCl2)6, and Au30(AuCl2)6 with the Au4 unit as the basic building blocks. Density functional theory (DFT) calculations show that these newly designed clusters have high structural and electronic stabilities. Based on chemical bonding analysis, the electronic structures of these clusters follow the superatom network (SAN) model. Inspired by the cluster structures, we further predicted an Au4 two-dimensional (2D) monolayer and a three-dimensional (3D) crystal using graphene and diamond as templates, respectively. The computational results demonstrate that the two structures have high dynamic, thermal, and mechanical stabilities, and both structures exhibit metallic properties according to the band structures calculated at the HSE06 level. The chemical bonding analysis by the solid-state natural density partitioning (SSAdNDP) method indicates that they are superatomic crystals assembled by two electron Au4 - superatoms. With this construction strategy, the new bonding pattern and properties of Au n L m are studied and the structure types of gold are enriched.

4.
Front Pharmacol ; 13: 963118, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120291

RESUMO

Background: DL -3-n-butylphthalide (NBP) is widely used as a neuroprotective drug in stroke patients in China. A systematic review in 2010 suggested NBP to be safe and effective at promoting neurological recovery, but could not conclude whether it decreased risk of long-term death or disability. Since numerous randomized controlled trials (RCTs) have been conducted on NBP since 2010, we performed an updated systematic review and meta-analysis of safety and efficacy data. Method: We searched electronic databases and reference lists to identify RCTs that compared patients who received NBP or not (including placebo). Methodological quality of RCTs was assessed using the Revised Cochrane Risk of Bias Tool 2.0, and data were meta-analyzed using Review Manager 5.4 software. Results: Fifty-seven RCTs involving 8,747 participants were included. Twenty trials examined NBP as a capsule, 29 as an injection, and 8 as sequential injection-capsule therapy. Meta-analyses showed that NBP treatment was associated with a reduction in composite outcome of death and dependency (risk ratio 0.59, 95% CI 0.42 to 0.83; 260 participants; 2 studies), death (risk ratio 0.32, 95% CI 0.13 to 0.75; 2,287 participants; 10 studies), modified Rankin Scale score (mean difference -0.80, 95% CI -0.88 to -0.72; 568 participants; 4 studies), and an increase in Barthel Index, which assesses the ability to engage in basic activities of daily living (mean difference 11.08, 95% CI 9.10 to 13.05; 2,968 participants; 22 studies). Meta-analyses found that NBP significantly reduced neurological deficit based on National Institute of Health Stroke Scale (mean difference -3.39, 95% CI -3.76 to -3.03; 7.283 participants; 46 studies) and Chinese Stroke Scale (mean difference -4.16, 95% CI -7.60 to -0.73; 543 participants; 4 studies). Of the adverse events reported in 31 trials, elevated transaminase (incidence, 1.39-17.53%), rash (0-1.96%) and gastrointestinal discomfort (1.09-6.15%) were most frequent and no serious adverse events were reported. Conclusion: This update review confirms that NBP can help acute ischemic stroke patients regain the ability to perform activities of daily living, reduce their neurological deficit and short-term death rates. However, the available evidence on whether NBP reduces risk of long-term death or dependence after ischemic stroke remains insufficient.

5.
Biochem Pharmacol ; 204: 115244, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36087639

RESUMO

Women seeking improved fertility often undergo diagnostic hysteroscopy that could cause uterine thermal injury with unclear impact on uterine contraction, embryo implantation and fertility. We tested whether uterine thermal insult adversely affects myometrium function and contraction related receptors, channels, junctional proteins and remodeling enzymes. Female Sprague-Dawley rats were anesthetized, the left uterine horn was infused with 85 ℃ hot saline (thermal Insult) and the right horn was infused with 25℃ warm saline (control) for 3 min. After 7-days recovery, uterine strips were prepared for tissue histology and measurement of contraction, and mRNA and protein levels of oxytocin receptor, progesterone (P4) receptor A (PR-A), membrane K+ channel TREK-1, junctional protein connexin-43 (CX-43) and matrix metalloproteinases MMP-2 and MMP-9. Uterine tissue histology showed cellular swelling and inflammatory cell infiltration immediately following thermal insult, and recovery with no difference from control 7-days later. KCl (96 mM) and oxytocin (10-13-10-7 M) caused significant contraction that was not different in thermal insult vs control uterine strips. Pretreatment with P4 (10-5 M) for 1 h caused marked inhibition of KCl and oxytocin contraction that was insignificantly greater in thermal vs control uterus. RT-PCR showed decreases in oxytocin receptor, PR-A, TREK-1, CX-43, MMP-2 and MMP-9 mRNA in thermal vs control uterus. Western blots showed decreases in oxytocin receptor, no change in TREK-1 and increased PRA, CX-43, MMP-2, and MMP-9 protein levels in thermal vs control uterus. To assess the impact on fertility, female rats were housed with male rats, and on gestational day 19, the litter size, pup weight and crown-rump length, and placenta weight were not different in thermal vs control uterus. Thus, after thermal insult-induced immediate inflammation and reduced heat-sensitive mRNA expression, the uterus undergoes a recovery and adaptation process involving preserved oxytocin-induced contraction, P4 inhibition and TREK-1 channels. The uterus self-healing process appears to require improved PR-A signaling, intercellular communication via CX-43 and tissue remodeling by MMP-2 and MMP-9. The uterine thermal recovery processes could be essential for maintaining fertility and future pregnancy outcome.

6.
Front Med (Lausanne) ; 9: 919069, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36117969

RESUMO

Background: The purpose of the study was to assess the efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) who are undergoing hepatic arterial infusion chemotherapy (HAIC) combined with programmed cell death protein-1 (PD-1) antibody and lenvatinib. Methods: We retrospectively evaluated 61 patients treated with HAIC combined with PD-1 antibody and lenvatinib at the Second Affiliated Hospital of Nanchang University between September 2020 and January 2022 for advanced HCC. We analyzed tumor response, progression free survival (PFS), and treatment-related adverse events (TRAEs). Results: The objective response rate (ORR) was 36.1% (RECIST 1.1)/57.4% (mRECIST) and the disease control rate (DCR) was 82.0%. The overall median PFS was 6.0 months, 6.7 months for first-line treatment, and 4.3 months for second-line treatment. The most common TRAEs were neutropenia (50.8%), abdominal pain (45.9%), and aspartate aminotransferase increase (39.3%). Conclusion: Hepatic arterial infusion chemotherapy combined with PD-1 antibody and lenvatinib is effective in the treatment of advanced HCC, and the TRAEs are generally controllable.

7.
Chin Herb Med ; 14(3): 464-469, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36118005

RESUMO

Objective: Astragali Radix (AR) is one of the most widely used traditional Chinese medicines (TCMs) for tonic, which can be divided into wild-simulated and cultivated AR according to its cultivation method. However, whether cultivated AR can replace wild-simulated AR has always been a concern. Methods: In this study, a rapid, highly sensitive and specific analytical method using ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS) was developed to quantitatively measure 12 chemical constituents of AR in the different cultivation methods. Results: AR samples were analyzed with a good linear regression relationship (R 2, 0.9983-0.9995), precisions (relative standard deviation (RSD), 1.31%-2.36%), repeatability (RSD, 2.65%-4.92%), stability (RSD, 1.50%-4.05%), and recovery (95.13%-106.52%). Through the determination of AR samples, we found the components of flavonoids in wild-simulated AR were higher than cultivated AR, the saponins in cultivated AR were higher, the ratio of saponins/flavonoids in cultivated AR was higher than wild-simulated AR. Conclusion: Based on this research, it could provide guidance for the quality control of AR.

8.
Clin Appl Thromb Hemost ; 28: 10760296221121286, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36045634

RESUMO

BACKGROUND: Red blood cell distribution width (RDW) was a risk factor for poor prognosis in acute myocardial infarction (AMI). Recent reports suggested that combining RDW with other laboratory metrics could provide a better prediction. This retrospective study aimed to investigate whether the RDW-albumin ratio (RAR) may be associated with mortality after an AMI. METHODS: This cohort study was conducted among adults (over 16 years old) with AMI in the Medical Information Mart for Intensive Care Database III V1.4 (MIMIC-III). The primary outcome was 30-day mortality, and the secondary outcome was 1-year and 3-year mortality. Cox hazard regression model and Kaplan-Meier survival curves were constructed to estimate the effect of biomarkers on mortality. We used three models to adjust for potential bias. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were analyzed for the excellent performance of RAR on prognosis. RESULTS: A total of 826 patients were eventually enrolled in our study. In multivariate analysis, RAR was found to be associated with 30-day mortality (Model 3: HR = 1.23, 95% CI = 1.09-1.39, P < .001). In addition, Subgroup analysis showed that the effect of RAR was higher in female patients than in male patients (P for interaction = .026). Kaplan-Meier survival curves showed that patients in the lower RAR quartile tended to have higher survival rates in the short and long term. AMI patients with RAR ≥ 4 had a 122% increase in 3-year mortality. Results of ROC and AUC showed that the prognostic performance of RAR for mortality was the best (30-day mortality: 0.703; 1-year mortality: 0.729; 3-year mortality: 0.737). CONCLUSIONS: RAR is a simple and stable predictor of prognosis in AMI patients. Our results support RAR = 4.0 as a criterion for prognostic risk stratification of AMI patients.


Assuntos
Índices de Eritrócitos , Infarto do Miocárdio , Adolescente , Adulto , Albuminas/química , Estudos de Coortes , Eritrócitos , Feminino , Humanos , Masculino , Infarto do Miocárdio/diagnóstico , Prognóstico , Curva ROC , Estudos Retrospectivos
9.
Front Immunol ; 13: 942465, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36045674

RESUMO

Follicular helper T (TFH) cells provide specialized help for B cells to ensure optimal humoral immunity. The histone methyltransferase EZH2, as a chromatin repressor, secures the TFH differentiation by promoting TFH lineage associated gene expression during acute viral infection, including Tcf7 and Bcl6. By using conditional deletion murine system, we observed that EZH2 ablation in CD4+ T cells was accompanied by aberrant accumulation of DNA methyltransferases (DNMTs) DNMT1 and DNMT3B in TFH cells. And the loss of EZH2 promoted aggravation of DNA methylation status at Tcf7 locus. Therefore, our findings suggested that EZH2 plays an important role in maintenance of hypomethylation at Tcf7 locus thus affecting TFH differentiation during acute viral infection.


Assuntos
Metilação de DNA , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Fator 1-alfa Nuclear de Hepatócito/genética , Linfócitos T Auxiliares-Indutores , Viroses , Animais , Diferenciação Celular , Histona Metiltransferases/metabolismo , Camundongos , Viroses/imunologia
10.
Elife ; 112022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36048712

RESUMO

Amyloid aggregation of phosphorylated Tau (pTau) into neurofibrillary tangles is closely associated with Alzheimer's disease (AD). Several molecular chaperones have been reported to bind Tau and impede its pathological aggregation. Recent findings of elevated levels of Hsp27 in the brains of patients with AD suggested its important role in pTau pathology. However, the molecular mechanism of Hsp27 in pTau aggregation remains poorly understood. Here, we show that Hsp27 partially co-localizes with pTau tangles in the brains of patients with AD. Notably, phosphorylation of Tau by microtubule affinity regulating kinase 2 (MARK2), dramatically enhances the binding affinity of Hsp27 to Tau. Moreover, Hsp27 efficiently prevents pTau fibrillation in vitro and mitigates neuropathology of pTau aggregation in a Drosophila tauopathy model. Further mechanistic study reveals that Hsp27 employs its N-terminal domain to directly interact with multiple phosphorylation sites of pTau for specific binding. Our work provides the structural basis for the specific recognition of Hsp27 to pathogenic pTau, and highlights the important role of Hsp27 in preventing abnormal aggregation and pathology of pTau in AD.


Assuntos
Doença de Alzheimer , Proteínas de Choque Térmico/metabolismo , Chaperonas Moleculares/metabolismo , Tauopatias , Proteínas tau/metabolismo , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Humanos , Microtúbulos/metabolismo , Fosforilação , Tauopatias/patologia
11.
Front Med (Lausanne) ; 9: 965836, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36106325

RESUMO

Objectives: We investigated the prevalence of pretreatment drug resistance (PDR), the molecular transmission network among HIV-positive individuals, and the impact of virological failure on those who received antiretroviral therapy (ART) in China. Methods: Based on the World Health Organization (WHO) surveillance guidelines for PDR, a baseline survey and follow-up were conducted in 2018 and 2021, respectively. Demographic information and plasma samples were obtained from all participants. HIV pol gene region sequences were used to analyze the PDR and molecular transmission networks using the Stanford HIV database algorithm and HIV-TRACE, respectively. This study assessed the odds ratios (OR) of PDR to virological failure (viral load ≥ 50 copies/mL) after 3 years of ART using multivariable logistic regression. Results: Of the 4,084 individuals, 370 (9.1%) had PDR. The prevalence of PDR to non-nucleoside reverse transcriptase inhibitors (5.2%) was notably higher than that to nucleoside reverse transcriptase inhibitors (0.7%, p < 0.001), protease inhibitors (3.0%, p < 0.001), and multidrug resistance (0.3%, p < 0.001). A total of 1,339 (32.8%) individuals from 361 clusters were enrolled in the molecular transmission network. Of the 361 clusters, 22 included two or more individuals with PDR. The prevalence of virological failure among HIV-positive individuals after 3 years of ART without PDR, those with PDR to Chinese listed drugs, and those with PDR to other drugs was 7.9, 14.3, and 12.6%, respectively. Compared with that in HIV-positive individuals without PDR, virological failure after 3 years of ART was significantly higher (OR: 2.02, 95% confidence interval (CI): 1.25-3.27) and not significantly different (OR: 1.72, 95% CI: 0.87-3.43) in individuals with PDR to Chinese listed drugs and those with PDR to other drugs, respectively. Missed doses in the past month were significantly associated with virological failure (OR, 2.82; 95% CI: 4.08-5.89). Conclusion: The overall prevalence of PDR was close to a high level and had an impact on virological failure after 3 years of ART. Moreover, HIV drug-resistant strains were transmitted in the molecular transmission network. These results illustrate the importance of monitoring PDR and ensuring virological suppression through drug adherence.

12.
Front Pediatr ; 10: 932734, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110116

RESUMO

Background: Social distancing and school closures during the COVID-19 pandemic reduced the physical activities of the preschool children living in China. However, the effects of home-based exercise on the physical fitness of Chinese preschool children during COVID-19 school closures are still unknown. This study aimed to investigate the effects of home-based exercise on the physical fitness of Chinese preschool children during COVID-19 school closure. Methods: In this retrospective analysis, data from 1,608 Chinese preschool children (aged 3-5.5 years) in a second-tier city of Guangdong Province of China (Zhongshan city) were extracted from three successive National Physical Fitness Measurement (NPFM) from 2019 to 2021. NPFM consists of weight, height, and six subtests of physical fitness including 10-m shuttle run test (SRT), standing long jump (SLJ), balance beam walking (BBW), sit-and-reach (SR), tennis throwing (TT), and double-leg timed hop (DTH) tests. The change differences or change ratios of all the items in NPFM between any two successive years from 2019 to 2021 were compared. The exercise profiles about home-based and outdoor exercise before, during, and after COVID-19 school closure were obtained from 185 preschool children via retrospective telephone survey. Results: Between 2019 and 2021, 1,608 preschool children were included in this study. We observed larger changes in SLJ, SR, TT, and DTH tests during school closure than after school closure. But the children showed lower reduction rates in the completion time of SRT and BBW. During school closure, higher change ratios in SLJ and TT were observed in the children primarily participating in home-based exercise than those primarily participating in outdoor exercise. However, no statistical differences were observed in the changes in SRT and BBW between home-based and outdoor training groups. Conclusion: The home-based exercise program might be an alternative approach to improve the physical fitness of preschool children during COVID-19 school closure, but could not be beneficial to speed-agility and balance functions. A specific guideline geared toward a home-based exercise program during the COVID-19 outbreak is highly needed.

13.
Patient Educ Couns ; 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36114042

RESUMO

OBJECTIVE: When diagnosed as having pulmonary nodules, patients may be mired in the conflict of medical decision-making and suffered from distress. The purpose of this study was to investigate the mediating role of decision-making conflict in the relationship between participation satisfaction in medical decision-making (PSMD) and distress among Chinese patients with incidental pulmonary nodules. METHODS: A total of 163 outpatients with incidental pulmonary nodules detected in a tertiary hospital were recruited and investigated by Impact of Event Scale (IES), Decision Conflict Scale (DCS), participation satisfaction in medical decision-making Scale (PSMDS), and demographic questionnaire. RESULTS: The mean IES score was 37.35 ± 16.65, representing a moderate level. PSMD was negatively associated with distress, while decision-making conflict was positively associated with distress. The final regression model contained three factors: having a first-degree relative diagnosed with lung cancer, worrying about getting lung cancer someday, and decision-making conflict. These three factors explained 49.4 % of the variance of distress. The total effect of PSMD on distress and indirect effect of SPMD on distress caused-by decision-making conflict were significant (P < 0.05). However, the direct effect of PSMD on distress was not significant. CONCLUSIONS: Participation of patients in medical decision-making can lower their distress by reducing patient's decision-making conflict. PRACTICE IMPLICATIONS: Interventions targeting at the decision-making conflict will help alleviate the distress level of patients with pulmonary nodules. DATA AVAILABILITY: The data that support the findings of this study are available on request from the corresponding author.

14.
Front Endocrinol (Lausanne) ; 13: 943408, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060978

RESUMO

Emerging studies have provided a preliminary understanding of the thyroid-gut axis, indicating that intestinal microbiota and its metabolites may act directly or indirectly on the thyroid by influencing intestinal microelements uptake, iodothyronine conversion and storage, and immune regulation, providing new insights into the pathogenesis of thyroid disorders and clinical management strategies. However, the research on gut microbiota and thyroid has only presented the tip of the iceberg. More robust clinical data and basic experiments are still required to elucidate the specific relationships and mechanisms in the future. Here we will characterize the associations between the microbiota and thyroid diseases to evaluate their potential implications in the pathophysiology and open up scientific avenues for future precision studies of the thyroid-gut axis.


Assuntos
Microbioma Gastrointestinal , Doença de Graves , Doenças da Glândula Tireoide , Doença de Graves/patologia , Humanos , Doenças da Glândula Tireoide/complicações
15.
Front Immunol ; 13: 966591, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059556

RESUMO

Leukocyte chemotactic factor 2-associated (ALECT2) amyloidosis is one of the recently reported types of amyloidosis, which is caused by the extracellular deposition of leukocyte chemotactic factor 2 (LECT2). There have not been any reports involving the concurrence of ALECT2 amyloidosis with Sjögren's syndrome (SS) or systemic lupus erythematosus (SLE)s. Herein, we report a case of a 68-year-old Chinese woman presenting with long duration of sicca symptoms. The clinical evaluation and laboratory findings showed that she had SS overlapped with SLE. Kidney biopsy revealed a membranoproliferative glomerulonephritis (MPGN) with glomerular deposition of dominant IgG3-kappa by immunofluorescene, which was related to SS/SLE. Furthermore, patchy congophilic amyloid deposits in the tubulointerstitium were detected, which were positive for LECT2 protein by immunohistochemical staining and immunoelectron microscopy. This is the first case of ALECT2 amyloidosis that coexisted with SS/SLE, and the causal relationship between ALECT2 amyloidosis and autoimmune diseases remain unclear.


Assuntos
Amiloidose , Doenças Autoimunes , Lúpus Eritematoso Sistêmico , Idoso , Amiloidose/diagnóstico , Amiloidose/etiologia , Amiloidose/metabolismo , Doenças Autoimunes/diagnóstico , Fatores Quimiotáticos , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Leucócitos/metabolismo
16.
Contrast Media Mol Imaging ; 2022: 1032557, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072623

RESUMO

TYMP1 is a cancer driver in several human malignancies. However, its significance in ovarian cancer (ovarian carcinoma) remains uncertain. This research aims to understand the TYMP1's role in ovarian carcinoma carcinogenesis and cisplatin (DDP) resistance and its molecular ovarian marchionesses. Circ TYMP1 overexpression in ovarian carcinoma samples led to an accelerated tumor stage. Bioinformatics identified miR-182A-3p as the TYMP1's target transcript. Circ TYMP1 functioned as a sponge for miR-182A-3p, lowering its inhibitory effect on TGF1B. Downregulating circ TYMP1 decreased A2780-Res cell proliferation, invasion, and death resistance. Malignant ovarian carcinoma cells recovered following miR-182A-3p downregulation. TGF1B overexpression boosted A2780-Res cell proliferation, aggression, and cisplatin resistance while reducing Smad2/3 phosphorylation. TYMP1 sequesters miR-182A-3p and promotes TGF1B in ovarian carcinoma, boosting carcinogenesis and cisplatin resistance. This might lead to novel ovarian carcinoma treatments.


Assuntos
MicroRNAs , Neoplasias Ovarianas , RNA Circular , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Cisplatino/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Fosforilação , RNA Circular/genética , Proteína Smad2/metabolismo , Proteína Smad3 , Fator de Crescimento Transformador beta1
17.
Artigo em Inglês | MEDLINE | ID: mdl-36111385

RESUMO

The harsh conditions of the gastrointestinal tract limit the potential health benefits of oral probiotics. It is promising that oral bioavailability is improved by strengthening the self-protection of probiotics. Here, we report the encapsulation of a probiotic strain by endogenous production of hyaluronan to enhance the effects of oral administration of the strain. The traditional probiotic Streptococcus thermophilus was engineered to produce hyaluronan shells by using traceless genetic modifications and clustered regularly interspaced short palindromic repeat interference. After oral delivery to mice in the form of fermented milk, hyaluronan-coated S. thermophilus (204.45 mg/L hyaluronan in the milk) exhibited greater survival and longer colonization time in the gut than the wild-type strain. In particular, the engineered probiotic strain could also produce hyaluronan after intestinal colonization. Importantly, S. thermophilus self-encapsulated with hyaluronan increased the number of goblet cells, mucus production, and abundance of the microorganisms related to the biosynthesis of short-chain fatty acids, resulting in the enhancement of the intestinal barrier. The coating formed by endogenous hyaluronan provides an ideal reference for the effective oral administration of probiotics.

18.
Artigo em Inglês | MEDLINE | ID: mdl-36056105

RESUMO

Cocaine self-administration can disrupt the capacity of humans and rodents to flexibly modify familiar behavioral routines, even when they become maladaptive or unbeneficial. However, mechanistic factors, particularly those driving long-term behavioral changes, are still being determined. Here, we capitalized on individual differences in oral cocaine self-administration patterns in adolescent mice and revealed that the post-synaptic protein PSD-95 was reduced in the orbitofrontal cortex (OFC) of escalating, but not stable, responders, which corresponded with later deficits in flexible decision-making behavior. Meanwhile, NMDA receptor GluN2B subunit content was lower in the OFC of mice that were resilient to escalatory oral cocaine seeking. This discovery led us to next co-administer the GluN2B-selective antagonist ifenprodil with cocaine, blocking the later emergence of cocaine-induced decision-making abnormalities. GluN2B inhibition also prevented cocaine-induced dysregulation of neuronal structure and function in the OFC, preserving mature, mushroom-shaped dendritic spine densities on deep-layer pyramidal neurons, which were otherwise lower with cocaine, and safeguarding functional BLA→OFC connections necessary for action flexibility. We posit that cocaine potentiates GluN2B-dependent signaling, which triggers a series of durable adaptations that result in the dysregulation of post-synaptic neuronal structure in the OFC and disruption of BLA→OFC connections, ultimately weakening the capacity for flexible choice. And thus, inhibiting GluN2B-NMDARs promotes resilience to long-term cocaine-related sequelae.

19.
Cell Cycle ; : 1-14, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36045598

RESUMO

Long non-coding ribonucleic acid 01555 (linc01555) is a brand-new long non-coding RNA (lncRNA) that acts a carcinogenic function in various cancers. However, its role in small cell lung cancer (SCLC) is uncertain. This research was to figure out the role of linc01555 in cisplatin (DDP) resistance of SCLC cells and its possible latent mechanism. After establishment of the resistant sub-strain H446/DDP or DMS-53/DDP, detection of linc01555, microRNA (miR)-122-5p and CLICl was done in the H446/DDP or DMS-53/DDP cell line. After intervention, cell biological functions were determined, as well as tube formation ability. The detection of angiomotin (Amot)-p130 and the validation of the regulatory mechanism were performed. Furthermore, tumor xenografts were applied in nude mice to evaluate the effect of linc01555 on DDP resistance in SCLC in vivo. Linc01555 was elevated in SCLC tissues and cells, and in H446/DDP cells or DMS-53/DDP vs. its parental cells; Restraining linc01555 or elevating miR-122-5p repressed the proliferation and metastasis of H446/DDP or DMS-53/DDP cells and vasculogenic mimicry (VM) formation. CLIC1 mediated miR-122-5p to influence the occurrence and development of SCLC. Linc01555 competitively combined with miR-122-5p, which targeted CLIC1. Refrained linc01555 elevated Amot-p130 via the miR-122-5p/CLIC1 axis. Reduced linc01555 refrained tumor growth and DDP resistance in vivo.In short, linc01555 may cause changes in DDP resistance via miR-122-5p/CLIC1 in SCLC. The finding may offer drug targets for SCLC resistance.

20.
Headache ; 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36047917

RESUMO

OBJECTIVE: The purpose of this study was to identify the prevalence of severe headache or migraine and the association between dietary thiamine and riboflavin intake with headache history using a large, nationally representative population sample. BACKGROUND: Severe headache and migraine are common and disabling neurological disorders worldwide. Previous studies revealed that the B vitamin group, as an important nutrient of diet, can reduce migraine disability. METHODS: We performed a cross-sectional study of American adults surveyed in the National Health and Nutrition Examination Survey (NHANES) 1999-2004. Information on headache history was collected in the Miscellaneous Pain section of the Questionnaire Data. Dietary intake data of thiamine and riboflavin were obtained by 24-h dietary recall interview. RESULTS: The present study included 13,439 participants and indicated that 2745/13,439 (21.6%) adults (aged ≥20 years) experienced severe headache or migraine in the past 3 months. Dietary thiamine intake was significantly inversely associated with severe headache or migraine (odds ratio [OR] = 0.93, 95% confidence interval [CI] = 0.88-1.00, p = 0.046). In the stratified analysis, the relationship was maintained in the female group (OR = 0.90, 95% CI = 0.82-0.98, p = 0.022), and the sex interaction term was significant (p = 0.020). However, no significant interaction was found between the age groups (p = 0.352). For dietary riboflavin, no significant negative association was observed between dietary riboflavin intake and headache history (OR = 0.98, 95% CI = 0.94-1.02, p = 0.367). After stratifying by sex or age, there remained no significant relationship between dietary riboflavin and migraine. CONCLUSIONS: We found that high intake of thiamine was significantly associated with lower odds of migraine, especially in females. In the future, more clinical studies are needed to confirm our conclusions, and additional experiments are needed to explore the possible mechanisms of prevention and treatment for migraine.

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