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1.
Molecules ; 29(5)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38474531

RESUMO

A enantioselective tandem transformation, concerning asymmetric allylic decarboxylative addition and cyclization of N-nosylimines with vinylethylene carbonates (VECs), in the presence of [Rh(C2H4)2Cl]2, chiral sulfoxide-N-olefin tridentate ligand has been developed. The reaction of VECs with various substituted N-nosylimines proceeded smoothly under mild conditions, providing highly functionalized oxazolidine frameworks in good to high yields with good to excellent enantioselectivity.

2.
Am J Cancer Res ; 14(2): 832-853, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38455420

RESUMO

The inflammation-related tumor microenvironment (TME) is one of the major driving forces of hepatocarcinogenesis. We aimed to investigate cell-to-cell communication among Hepatocellular Carcinoma (HCC) through re-analyzing HCC single-cell RNA-seq data, and to confirm such cellular interaction through in vitro and in vivo study. We found a subset of Regulatory B cells with PD-L1 expression (PD-L1+ Bregs), mainly located in adjacent HCC tissues. In co-localization with PD-L1+ Bregs, a subset of Tumor Associated Macrophages with high expression of CXCL12 (CXCL12+ TAMs) was also mainly located in adjacent HCC tissues. Moreover, CXCL12+ TAMs can be stimulated in vitro using an HCC conditional medium. Using CellChat analysis and Multiplex Immunohistochemistry staining (mIHC), CXCL12+ TAMs were found to be first recruited by Cancer-Associated Fibroblasts (CAFs) through a CD74/macrophage migration inhibitory factor (MIF) pattern, and further differentiated into TGF-ß-enriched tissues. Furthermore, CXCL12+ TAMs recruited PD-L1+ Bregs via the CXCL12/CXCR4 axis, and CXCR4 expression was significantly positively correlated to PD-L1 expression in PD-L1+ Bregs. At last, we confirmed the communications among CAFs, Macrophages and B cells and their tumor-promoting effects by using an orthotopic mouse model of HCC. Immunosuppressive HCC TME involving cell-to-cell communications comprised MIF-secreting CAFs, CXCL12-secreting TAMs, and PD-L1-producing Bregs, and their regulation could be promising therapeutic targets in future immunotherapy for human HCC.

3.
Neuropsychiatr Dis Treat ; 20: 69-81, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38249525

RESUMO

Purpose: The Coronavirus disease 2019 (COVID-19) remains a global public health concern. Many people have been forced to change their lifestyles, which has led to psychological and sleep problem. This study aims to investigate the psychological health problems and factors among patients in the Fangcang Shelter Hospital (FSH) during the COVID-19 pandemic. Patients and Methods: A Cross-Sectional survey was conducted to investigate the sleep, anxiety, depression and stress disorders of 2628 asymptomatic and mild patients treated in FSH of Zhengzhou, Henan Province, from 30 October to 6 December 2022, by scanning a WeChat two-dimensional code. Sociodemographic data and influencing factors in FSH were collected, Insomnia Severity Index (ISI), 9-item Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Impact of Event Scale-Revised (IES-R) were administered. Descriptive statistics, t-tests or analysis of variance, Spearman or Pearson correlation analysis, and multivariate regression analysis were used to explore the relationships between different variables and their impact on psychological health indicators. Results: The proportions of patients with insomnia, depressive disorder, anxiety, and stress disorders were 33.49%, 35.80%, 31.74%, and 43.57%, respectively. Spearman correlation analysis demonstrated that factors such as gender, higher education level, positive nucleic acid test results, longer illness duration, underlying diseases, and extended electronic device use were associated with elevated psychological distress scores. Notably, within FSH, extended exposure to light, a noisy environment, and sleep schedule management significantly impacted the prevalence of insomnia, depression, anxiety, and stress disorders (p<0.01). Multivariable binary logistic regression analysis identified higher education level, light exposure, noisy environment, sleep management, and electronic device usage as the primary risk factors for psychological distress. Conclusion: Patients in FSH face psychological distress influenced by sociodemographic factors, environment, and lifestyle, highlighting the need for integrated psychological support in healthcare, particularly in temporary medical facilities during crises.

4.
Int J Biol Macromol ; 253(Pt 4): 126961, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37722637

RESUMO

In this study, bacterial cellulose/gum Arabic composite (BC/GA) was synthesized by in-situ modification from lavender residue hydrolysate for the first time. The in-situ modification with GA adding showed great beneficial effect for BC/GA synthesis. Both the product (BC or BC/GA) yield and the product (BC or BC/GA) production per sugars consumption increased greatly by the in-situ modification when compared with the fermentation without GA adding (2.90 g/L vs. 0.91 g/L, and 0.461 g/g vs. 0.138 g/g). It is hypothesized that the combination of BC and GA is the main mechanism for the beneficial effect of the in-situ modification, and the scanning electron microscope (SEM) images confirmed this hypothesis. GA adding showed little effect on the rheological properties of lavender residue hydrolysate, and this environment was suitable for the combination of BC and GA. The in-situ modification had an obvious influence on the crystallinity index and the thermal stability of BC/GA, but affected little on its functional groups and cellulose structural framework. Besides BC/GA synthesis and structure, the in-situ modification could also alter the texture properties of BC/GA. Overall, this study can offer some useful information for the biochemical conversion from green and cost-effective lavender residue hydrolysate to attractive biomaterial BC/GA.


Assuntos
Celulose , Lavandula , Celulose/química , Goma Arábica , Fermentação , Metabolismo dos Carboidratos , Bactérias/metabolismo
5.
World J Gastrointest Surg ; 15(6): 1104-1115, 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37405105

RESUMO

BACKGROUND: Intersphincteric resection (ISR), the ultimate anus-preserving technique for ultralow rectal cancers, is an alternative to abdominoperineal resection (APR). The failure patterns and risk factors for local recurrence and distant metastasis remain controversial and require further investigation. AIM: To investigate the long-term outcomes and failure patterns after laparoscopic ISR in ultralow rectal cancers. METHODS: Patients who underwent laparoscopic ISR (LsISR) at Peking University First Hospital between January 2012 and December 2020 were retrospectively reviewed. Correlation analysis was performed using the Chi-square or Pearson's correlation test. Prognostic factors for overall survival (OS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were analyzed using Cox regression. RESULTS: We enrolled 368 patients with a median follow-up of 42 mo. Local recurrence and distant metastasis occurred in 13 (3.5%) and 42 (11.4%) cases, respectively. The 3-year OS, LRFS, and DMFS rates were 91.3%, 97.1%, and 90.1%, respectively. Multivariate analyses revealed that LRFS was associated with positive lymph node status [hazard ratio (HR) = 5.411, 95% confidence interval (CI) = 1.413-20.722, P = 0.014] and poor differentiation (HR = 3.739, 95%CI: 1.171-11.937, P = 0.026), whereas the independent prognostic factors for DMFS were positive lymph node status (HR = 2.445, 95%CI: 1.272-4.698, P = 0.007) and (y)pT3 stage (HR = 2.741, 95%CI: 1.225-6.137, P = 0.014). CONCLUSION: This study confirmed the oncological safety of LsISR for ultralow rectal cancer. Poor differentiation, (y)pT3 stage, and lymph node metastasis are independent risk factors for treatment failure after LsISR, and thus patients with these factors should be carefully managed with optimal neoadjuvant therapy, and for patients with a high risk of local recurrence (N + or poor differentiation), extended radical resection (such as APR instead of ISR) may be more effective.

6.
Zhongguo Zhong Yao Za Zhi ; 48(13): 3565-3575, 2023 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-37474990

RESUMO

This study aimed to investigate the underlying mechanism of Zhenwu Decoction in the treatment of heart failure by regulating electrical remodeling through the transient outward potassium current(I_(to))/voltage-gated potassium(Kv) channels. Five normal SD rats were intragastrically administered with Zhenwu Decoction granules to prepare drug-containing serum, and another seven normal SD rats received an equal amount of distilled water to prepare blank serum. H9c2 cardiomyocytes underwent conventional passage and were treated with angiotensin Ⅱ(AngⅡ) for 24 h. Subsequently, 2%, 4%, and 8% drug-containing serum, simvastatin(SIM), and BaCl_2 were used to interfere in H9c2 cardiomyocytes for 24 h. The cells were divided into a control group [N, 10% blank serum + 90% high-glucose DMEM(DMEM-H)], a model group(M, AngⅡ + 10% blank serum + 90% DMEM-H), a low-dose Zhenwu Decoction-containing serum group(Z1, AngⅡ + 2% drug-containing serum of Zhenwu Decoction + 8% blank serum + 90% DMEM-H), a medium-dose Zhenwu Decoction-containing serum group(Z2, AngⅡ + 4% drug-containing serum of Zhenwu Decoc-tion + 6% blank serum + 90% DMEM-H), a high-dose Zhenwu Decoction-containing serum group(Z3, AngⅡ + 8% drug-containing serum of Zhenwu Decoction + 2% blank serum + 90% DMEM-H), an inducer group(YD, AngⅡ + SIM + 10% blank serum + 90% DMEM-H), and an inhibitor group(YZ, AngⅡ + BaCl_2 + 10% blank serum + 90% DMEM-H). The content of ANP in cell extracts of each group was detected by ELISA. The relative mRNA expression levels of ANP, Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 were detected by real-time quantitative PCR. The protein expression of Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 was detected by Western blot. I_(to) was detected by the whole cell patch-clamp technique. The results showed that Zhenwu Decoction at low, medium, and high doses could effectively reduce the surface area of cardiomyocytes. Compared with the M group, the Z1, Z2, Z3, and YD groups showed decreased ANP content and mRNA level, increased protein and mRNA expression of Kv4.2, Kv4.3, DPP6, and KChIP2, and decreased protein and mRNA expression of Kv1.4, and the aforementioned changes were the most notable in the Z3 group. Compared with the N group, the Z1, Z2, and Z3 groups showed significantly increased peak current and current density of I_(to). The results indicate that Zhenwu Decoction can regulate myocardial remodeling and electrical remodeling by improving the expression trend of Kv1.4, Kv4.2, Kv4.3, KChIP2, and DPP6 proteins and inducing I_(to) to regulate Kv channels, which may be one of the mechanisms of Zhenwu Decoction in treating heart failure and related arrhythmias.


Assuntos
Remodelamento Atrial , Insuficiência Cardíaca , Ratos , Animais , Miócitos Cardíacos , Ratos Sprague-Dawley , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , RNA Mensageiro/metabolismo , Potássio
7.
J Org Chem ; 88(13): 7998-8009, 2023 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-37279456

RESUMO

An unexpected Ugi cascade reaction was developed for the facile construction of γ-lactam-fused pyridone derivatives with high tolerance of substrates. A C(sp3)-N bond and a C(sp2)-C(sp2) bond were formed together, accompanied by a chromone ring-opening in Ugi adducts, under the basic conditions without any metal catalyst for the whole process. Screening data of several difficult-to-inhibit cancer cell lines demonstrated that 7l displayed a high cytotoxicity against HCT116 cells (IC50 = 5.59 ± 0.78 µM). Taken together, our findings revealed new insights into the molecular mechanisms underlying compound 7l and provided potential usage of this scaffold for cancer therapeutics.


Assuntos
Compostos Heterocíclicos , Lactamas , Lactamas/farmacologia , Piridonas/farmacologia , Piridonas/química , Metais
8.
J Oral Maxillofac Surg ; 81(9): 1155-1160, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37364857

RESUMO

PURPOSE: Iodoform gauze is commonly used to treat patients with localized alveolitis; however, saliva can easily dilute the iodoform concentration. This study aimed to compare the efficacies of platelet-rich fibrin (PRF) and iodoform gauze in treating localized alveolitis. METHODS: This prospective randomized controlled trial enrolled patients with localized alveolitis who received treatment at our hospital from January 2018 to July 2021. They were randomly assigned to the control (treated with iodoform gauze) or experimental (treated with PRF) groups. Treatment method was the predictor variable. The primary outcome variable was clinical efficacy, defined as symptom resolution 1 week after treatment. Secondary outcome variables included granulation tissue (GT) quantitative score, analgesic drug dosage, and pain score determined using a visual analog scale (VAS). Patient demographics were used as covariates. Data analysis was performed by carrying out the χ2 and Mann-Whitney rank sum tests; P values <.05 indicated statistical significance. RESULTS: This study included 60 patients, equally and randomly divided into the control and PRF groups (n = 30 each). There were no significant differences in demographic characteristics of patients between the 2 groups. One week after treatment, the PRF group showed a higher healing rate (93.3% vs 60.0%) and better GT quantitative score (3.13 ± 0.63 vs 1.70 ± 0.75) than the control group (P < .05). Moreover, the number of analgesic tablets consumed within 1 week postoperatively was lesser in the PRF group than in the control group (3.93 ± 1.53 vs 9.67 ± 3.16, P < .05). The PRF group exhibited significantly lower VAS pain scores than those of the control group on the 3rd day (1.10 ± 1.03 vs 4.17 ± 1.49) and 7th day (0.30 ± 0.60 vs 1.73 ± 1.44, P < .05) postoperatively. CONCLUSIONS: Compared with iodoform gauze, PRF is associated with higher healing rate, faster promotion of GT growth in the extraction socket, better relief of alveolar pain, and lower intake of analgesic drugs when treating localized alveolitis.


Assuntos
Fibrina Rica em Plaquetas , Humanos , Extração Dentária/métodos , Estudos Prospectivos , Dor
9.
ACS Appl Mater Interfaces ; 15(5): 7129-7136, 2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36710447

RESUMO

Miniaturized spectrometers have attracted much attention due to their capability to detect spectral information within a small size. However, such technology still faces challenges including large-scale preparation and performance repeatability. In this work, we overcome these challenges by demonstrating a microspectrometer constructed with a series of pixelized graded-bandgap perovskite photodetectors fabricated with inkjet printing. High-quality perovskite films with minimal pinholes and large grains are deposited by optimizing printing conditions including substrate temperature and surface modification. The resulting perovskite photodetectors show decent photosensing performance, and the different photodetectors based on perovskite films with different bandgaps exhibit various spectral responsivities with different cutoff wavelength edges. Microspectrometers are then constructed with the array of the pixelized graded-bandgap perovskite photodetectors, and incident spectra are algorithmically reconstructed by combining their output currents. The reconstruction performance of the miniaturized spectrometer is evaluated by comparing the results to the spectral curve measured with a commercial bulky spectrometer, indicating a reliable spectral reconstruction with a resolution of around 10 nm. More significantly, the miniaturized spectrometers are successfully fabricated on polymer substrates, and they demonstrate excellent mechanical flexibility. Therefore, this work provides a flexible miniaturized spectrometer with large-scale fabricability, which is promising for emerging applications including wearable devices, hyperspectral imaging, and internet of things.

11.
Acta Pharmacol Sin ; 44(4): 841-852, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36253561

RESUMO

Small-cell lung cancer (SCLC) is an aggressive high-grade neuroendocrine carcinoma of the lung associated with early metastasis and an exceptionally poor prognosis. Little progress has been made in developing efficacious targeted therapy for this recalcitrant disease. Herein, we showed that H3.3, encoded by two genes (H3F3A and H3F3B), was prominently overexpressed in SCLC. Darinaparsin (ZIO-101), a derivative of arsenic trioxide, dose- and time-dependently inhibited the viability of SCLC cells in an H3.3-dependent manner. More importantly, ZIO-101 treatment resulted in substantial accumulation of H3.3 and PARP1 besides induction of G2/M cell cycle arrest and apoptosis in SCLC cells. Through integrative analysis of the RNA-seq data from Cancer Cell Line Encyclopedia dataset, JNCI and Genomics of Drug Sensitivity in Cancer 2 datasets, we found that H3F3A expression was negatively correlated with the IC50 values of PARP inhibitors (PARPi). Furthermore, co-targeting H3.3 and PARP1 by ZIO-101 and BMN673/olaparib achieved synergistic growth inhibition against SCLC in vitro and in vivo. In conclusion, it is feasible to target H3.3 by ZIO-101 to potentiate the response rate of PARPi in SCLC patients.


Assuntos
Arsenicais , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Arsenicais/farmacologia , Arsenicais/uso terapêutico , Neoplasias Pulmonares/patologia , Linhagem Celular Tumoral , Ftalazinas/farmacologia
12.
Crit Rev Biotechnol ; 43(7): 1092-1110, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35968918

RESUMO

Sugars are the primary products of photosynthesis and play multiple roles in plants. Although sugars are usually considered to be the building blocks of energy storage and carbon transport molecules, they have also gradually come to be acknowledged as signaling molecules that can initiate senescence. Senescence is an active and essential process that occurs at the last developmental stage and corresponds to programmed degradation of: cells, tissues, organs, and entire organisms. It is a complex process involving: numerous biochemical changes, transporters, genes, and transcription factors. The process is controlled by multiple developmental signals, among which sugar signals are considered to play a vital role; however, the regulatory pathways involved are not fully understood. The dynamic mechanistic framework of sugar accumulation has an inconsistent effect on senescence through the sugar signaling pathway. Key metabolizing enzymes produce different sugar signals in response to the onset of senescence. Diverse sugar signal transduction pathways and a variety of sugar sensors are involved in controlling leaf senescence. This review highlights the processes underlying initiation of sugar signaling and crosstalk between sugars and hormones signal transduction pathways affecting leaf senescence. This summary of the state of current knowledge across different plants aids in filling knowledge gaps and raises key questions that remain to be answered with respect to regulation of leaf senescence by sugar signaling pathways.

13.
Sci Rep ; 12(1): 19497, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36376427

RESUMO

This paper examined the effects of no treatment versus plasma treatment, and femtosecond laser irradiation as pre-annealing processes on indium zinc oxide (IZO) films and annealing at high temperatures. The plasma pre-annealed multilayer stacked IZO TFTs showed better electrical properties with mobility enhancement from 2.45 to 7.81 cm2/Vs, but exhibited diminished on-off current ratio (Ion/Ioff). The IZO thin-film transistor (TFT) prepared with femtosecond laser pre-annealing with low pulse energy generation (power of 3 W at 700 nm wavelength) for 100 s has also exhibited significantly improved electrical performance, the saturation mobility increased to 4.91 cm2/Vs, the Ion/Ioff ratio was enhanced from 4.5 × 105 to 2.1 × 106, the threshold voltage improved from - 1.44 to - 0.25 V, and the subthreshold swing was reduced from 1.21 to 0.61 V/dec. In conclusion, IZO TFTs with improved performance can be prepared using a femtosecond laser pre-annealing process, which has great potential for fabricating low-cost, high-performance devices.

14.
BMC Musculoskelet Disord ; 23(1): 964, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36348396

RESUMO

BACKGROUND: Medial epicondyle fractures are one of the more common humerus fractures, but humeral medial condyle fracture (HMCF) is rare. Nonunion of medial humeral condyle fractures due to functional exercise is less common. CASE PRESENTATION: We report a 5-year-old patient with a nonunion HMCF due to excessive functional exercise, who bruised the elbow 1 year ago and had no positive findings on all imaging studies. On this physical examination, there was a snapping and palpable lump in the elbow joint during movement, but the patient did not feel any discomfort and the range of motion of the joint was normal. X rays and computed tomography (CT) showed that the left HMCF was discontinuous, the broken ends were dislocated, and the joint alignment was poor. Open reduction (OR) and screw fixation was used during the operation, and the patient recovered well at 3-month follow-up. CONCLUSIONS: The rarity and low radiographic appearance of displaced HMCF are easily overlooked and can eventually lead to nonunion HMCF, especially when radiographically difficult to visualize before age 5 years. Therefore, regardless of whether there are signs or imaging abnormalities in the growth process of adolescents, they should be vigilant, shorten the time interval for re-examination, and early detection and timely treatment can avoid some complications caused by this.


Assuntos
Articulação do Cotovelo , Fraturas não Consolidadas , Fraturas do Úmero , Adolescente , Humanos , Pré-Escolar , Articulação do Cotovelo/cirurgia , Fixação Interna de Fraturas/métodos , Fraturas do Úmero/diagnóstico por imagem , Fraturas do Úmero/etiologia , Fraturas do Úmero/cirurgia , Úmero/cirurgia , Fraturas não Consolidadas/diagnóstico por imagem , Fraturas não Consolidadas/etiologia , Fraturas não Consolidadas/cirurgia , Amplitude de Movimento Articular , Resultado do Tratamento
15.
Molecules ; 27(20)2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36296572

RESUMO

The utilization of 6,6-dimethyl-3-((trimethylsilyl)oxy)cyclohex-2-en-1-one made from an unsymmetrical 4,4-dimethylcyclohexane-1,3-dione in iridium-catalyzed allylic enolization involving keto-enol isomerization is accomplished under mild conditions. The chemoselectivity, regioselectivity, and enantioselectivity are facilitated by the quaternary carbon and adjusting the reaction conditions. This method provides the substituted 2-(but-3-en-2-yl)-3-hydroxy-6,6-dimethylcyclohex-2-en-1-ones in good to high yields with high level of chemo-, regio-, and enantioselectivities. The chiral carbon-fluorine bond formation is induced by an adjacent chiral carbon center of the allylated 3-hydroxy-6,6-dimethylcyclohex-2-en-1-one, as well.


Assuntos
Flúor , Irídio , Irídio/química , Estereoisomerismo , Catálise , Isomerismo , Carbono
16.
Front Cell Dev Biol ; 10: 992714, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36158200

RESUMO

The ETO-family transcriptional corepressors, including ETO, ETO2, and MTGR1, are all involved in leukemia-causing chromosomal translocations. In every case, an ETO-family corepressor acquires a DNA-binding domain (DBD) to form a typical transcription factor-the DBD binds to DNA, while the ETO moiety manifests transcriptional activity. A directly comparative study of these "homologous" fusion transcription factors may clarify their similarities and differences in regulating transcription and leukemogenesis. Here, we performed a side-by-side comparison between AML1-ETO and ETO2-GLIS2, the most common fusion proteins in M2-and M7-subtypes of acute myeloid leukemia, respectively, by inducible expression of them in U937 leukemia cells. We found that, although AML1-ETO and ETO2-GLIS2 can use their own DBDs to bind DNA, they share a large proportion of genome-wide binding regions dependent on other cooperative transcription factors, including the ETS-, bZIP- and bHLH-family proteins. AML1-ETO acts as either transcriptional repressor or activator, whereas ETO2-GLIS2 mainly acts as activator. The repressor-versus-activator functions of AML1-ETO might be determined by the abundance of cooperative transcription factors/cofactors on the target genes. Importantly, AML1-ETO and ETO2-GLIS2 differentially regulate key transcription factors in myeloid differentiation including PU.1 and C/EBPß. Consequently, AML1-ETO inhibits, but ETO2-GLIS2 facilitates, myeloid differentiation of U937 cells. This function of ETO2-GLIS2 is reminiscent of a similar effect of MLL-AF9 as previously reported. Taken together, this directly comparative study between AML1-ETO and ETO2-GLIS2 in the same cellular context provides insights into context-dependent transcription regulatory mechanisms that may underlie how these seemingly "homologous" fusion transcription factors exert distinct functions to drive different subtypes of leukemia.

17.
Front Endocrinol (Lausanne) ; 13: 858176, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35784569

RESUMO

Background: Endometriosis (EMS), an endocrine-related inflammatory disease, is characterized by estrogen and progesterone imbalance in ectopic lesions. However, its pathogenic mechanism has not been fully elucidated. While SCM-198 is the synthetic form of leonurine and has multiple pharmacological activities such as antioxidation and anti-inflammation, it remains unknown whether it could inhibit the progress of EMS by regulating estrogen signaling and inflammation. Methods: The therapeutic effects of SCM-198 on EMS and its potential mechanism were analyzed by establishing EMS mouse models and performing an RNA sequencing (RNA-seq) assay. ELISA was performed to detect estrogen and tumor necrosis factor (TNF) -α concentrations in normal endometrial stromal cells (nESCs) and ectopic endometrial stromal cells (eESCs) with or without SCM-198 treatment. Western blotting, RNA silencing, and plasmid overexpression were used to analyze the relationship between inflammation, endocrine factors, and autophagy and the regulatory activity of SCM-198 on the inflammation-endocrine-autophagy axis. Results: Increased estrogen-estrogen receptor (ER) α signaling and decreased progesterone receptor isoform B (PRB) expression synergistically led to a hypo-autophagy state in eESCs, which further inhibited the apoptosis of eESCs. The high expression of TNF-α in eESCs enhanced the antiapoptotic effect mediated by low autophagy through the activation of the aromatase-estrogen-ERα signaling pathway. SCM-198 inhibited the growth of ectopic lesions in EMS mice and promoted the apoptosis of eESCs both in vivo and in vitro. The apoptotic effect of SCM-198 on eESCs was attained by upregulating the autophagy level via the inhibition of the TNF-α-activated aromatase-estrogen-ERα signal and the increase in PRB expression. Conclusion: Inflammation facilitated the progress of EMS by disrupting the estrogen regulatory axis. SCM-198 inhibited EMS progression by regulating the inflammation-endocrine-autophagy axis.


Assuntos
Endometriose , Animais , Aromatase/genética , Aromatase/metabolismo , Autofagia , Endometriose/metabolismo , Endometriose/prevenção & controle , Endométrio/patologia , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Estrogênios/metabolismo , Estrogênios/farmacologia , Feminino , Ácido Gálico/análogos & derivados , Humanos , Camundongos , Receptores de Progesterona/metabolismo , Células Estromais/metabolismo , Células Estromais/patologia , Fator de Necrose Tumoral alfa/metabolismo
18.
World J Clin Cases ; 10(12): 3930-3935, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35647173

RESUMO

BACKGROUND: Both autoimmune pancreatitis (AIP) and gastric varices are related to various diseases. However, AIP complicated by gastric varices is extremely rare, and has only been reported in a few studies. Here, we report a case of AIP complicated by gastric varices in a female Chinese patient. CASE SUMMARY: A 59-year-old Chinese woman was admitted to our hospital with mild abdominal pain. Computed tomography and magnetic resonance cholangiopancreatography revealed a diffusely enlarged pancreas, an obstructed splenic vein and slight splenomegaly. Esophagogastroduodenoscopy showed gastric varices in the partial gastric fundus and the red-color sign was positive. Blood chemistry showed that IgG4 was notablely elevated. The patient was diagnosed with AIP complicated by gastric varices. Steroid therapy was administered to this patient with the risk of gastrointestinal bleeding. After one year of therapy, the pancreas, spleen and splenic vein recovered to the normal states, and the gastric varices had disappeared. CONCLUSION: We present this case together with evidence from the literature to demonstrate the effectiveness of steroid therapy in the treatment of AIP complicated by gastric varices.

19.
J Sci Food Agric ; 102(15): 7087-7097, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35707876

RESUMO

BACKGROUND: The exopolysaccharides (EPS) produced by Lactobacillus and other probiotics are associated with many benefits, such as immune regulation, antioxidant properties, antitumor effect, and regulation of intestinal microbe homeostasis. In the present study, the modulatory effect of EPS produced by Lactobacillus rhamnosus ZFM231 on the intestinal flora of mice with inflammatory bowel disease induced by dextran sulfate solution was investigated. RESULTS: Results indicated that weight loss, colonic length, the disease activity index score and colonic tissue damage in mice were significantly improved by EPS treatment. Compared with the model group, in the EPS-treated group, the diversity of and the composition of gut microbiota at both phylum and genus levels were found to recover to the levels of normal group, indicating the effective modulation on gut microbiota by EPS; short-chain fatty acids, including acetic acid, propionic acid and butyric acid produced by intestinal microbial metabolism, increased significantly; the level of anti-inflammatory factor transforning growth factor-ß significantly increased and the level of pro-inflammatory factor tumor necrosis factor-α significantly decreased in the colonic cells of EPS-treated mice. CONCLUSION: It is clear that EPS produced by L. rhamnosus ZFM231 could find application in functional foods with the property of anti-ulcerative colitis. The experimental results provide new insights into the probiotic effect of EPS. © 2022 Society of Chemical Industry.


Assuntos
Colite , Microbioma Gastrointestinal , Lacticaseibacillus rhamnosus , Probióticos , Camundongos , Animais , Sulfato de Dextrana/efeitos adversos , Colite/induzido quimicamente , Probióticos/metabolismo , Colo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
20.
ACS Appl Mater Interfaces ; 14(12): 14455-14465, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35311251

RESUMO

Spectrum reconstruction with filter-free microspectrometers has attracted much attention owing to their promising potential in in situ analysis systems, on-chip spectroscopy characterizations, hyperspectral imaging, etc. Further efforts in this field can be devoted to improving the performance of microspectrometers by employing high-performance photosensitive materials and optimizing the reconstruction algorithms. In this work, we demonstrate spectrum reconstruction with a set of photodetectors based on graded-band-gap perovskite quantum dot (PQD) heterojunctions using both calculation and machine learning algorithms. The photodetectors exhibit good photosensitivities with nonlinear current-voltage curves, and the devices with different PQD band gaps show various spectral responsivities with different cutoff wavelength edges covering the entire visible range. Reconstruction performances of monochromatic spectra with the set of PQD photodetectors using two different algorithms are compared, and the machine learning method achieves relatively better accuracy. Moreover, the nonlinear current-voltage variation of the photodetectors can provide increased data diversity without redundancy, thus further improving the accuracy of the reconstructed spectra for the machine learning algorithm. A spectral resolution of 10 nm and reconstruction of multipeak spectra are also demonstrated with the filter-free photodetectors. Therefore, this study provides PQD photodetectors with the corresponding optimized algorithms for emerging flexible microspectrometer systems.

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