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1.
J Ethnopharmacol ; 288: 114938, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34999144

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Silybum marianum is a traditional Chinese medicine that has been used for treating liver disease. Silybin consisting of silybin A and silybin B, is a member of Silybum marianum, and exerts a therapeutic effect on many diseases. However, the protective effect of silybin on cisplatin-induced neurotoxicity and the stereoisomer contributing to the effect remain unknown. AIM OF THE STUDY: The present study aimed to study the effect of silybin on cisplatin-induced neuronal injury, compare the difference of protective effect between silybin A and silybin B, and the potential mechanism. MATERIALS AND METHODS: High performance liquid chromatography (HPLC) was used to separate silybin A and silybin B. X-ray crystallographic analysis in combination with experimental and calculated ECD were performed to identify the structure of silybin A and silybin B. The toxicity of the silybin or cisplatin against murine hippocampal neuronal HT22 cells was determined through MTT assay. The cell cycle and cell apoptosis were measured by PI staining and Annexin V-FITC/PI staining, respectively, and then subjected to flow cytometry. Western blot analysis was conducted to quantify the expression of proteins related to apoptosis and DNA damage. Immunofluorescence was used to evaluate the expression of DNA damage marker. In vivo experiment, the behavioral analysis was determined through pole test, swimming test and Morris water maze test. The index of superoxide dismutase (SOD), reduced glutathione (GSH), total antioxidant capacity (T-AOC) and lipid peroxidation (LPO) were examined to evaluate the antioxidant capacity in mice brain. Nissl staining and Tunel assay were used to detect the neuronal viability and apoptosis in hippocampus. RESULTS: We successfully separated and identified silybin A and silybin B. We found both silybin A and silybin B alleviated cisplatin-induced apoptosis and cell cycle arrest in HT22 cells, and silybin B was more effective. We chose silybin B for further mechanism investigation, and found silybin B alleviated DNA damage by enhancing phosphorylation of ATR and decreasing expression of γ-H2AX. In the in vivo experiment, we observed that silybin B markedly improved the behavioral abnormalities in cisplatin-treated mice, reduced LPO level while increased SOD, GSH and T-AOC in mice brain tissue. Nissl staining and Tunel assay showed that silybin B alleviated cisplatin-induced hippocampal damage. CONCLUSIONS: These results suggest that silybin B might serve as a promising drug candidate in mitigating cisplatin-induced neural injury in the brain and thereby improving the chemotherapeutic outcomes.

2.
Sci Total Environ ; 817: 153011, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35026272

RESUMO

After China implemented the Air Pollution Prevention and Control Action Plan (APPCAP), PM2.5 concentrations decreased but were still higher than national standards in major areas and ozone (O3) concentration increased unintentionally. To further decrease PM2.5 concentrations and reduce days with severe air pollution, the government promulgated the "Three-year (2018-2020) Action Plan for Cleaner Air" (the Three-year Action Plan) in 2018. During the three-year Action Plan, a few studies reported a continuous decline in PM2.5, but it is unclear whether O3 and its effects also increase with the decrease of PM2.5 like during APPCAP. In this study, for the first time, we systematically assessed changes in ground-level O3 concentrations and related ecological and health risks during the period of the Three-year Action Plan using nationwide O3 measurements. The national MDA8, Exceedance, and SOMO35 indicators were reduced by 3.8%, 28.5%, and 12.6%, respectively, ecological risk indicators of M12, M7, SUM06, AOT40, and W126 were reduced by 5.4%, 5.6%, 19.5%, 15.4%, and 18.6%, respectively, from 2018 to 2020. Spatially, the greatest reduction in all the indicators except MDA8 occurred in Pearl River Delta, followed by Fen Wei Plains, while Beijing-Tianjin-Hebei, Chengdu-Chongqing, and Yangtze River Delta presented relatively small reductions. Between 2018 and 2020, the production losses caused by O3 for wheat and rice decreased by 21.4% and 17.6%, respectively. Long-term exposure to O3 across China over 2020 was estimated to cause about 160,795 (95% CI: 81,515-312,983) for all-cause mortality, 107,128 (95% CI: 36,703-173,823) for cardiovascular mortality, and 34,444 (95% CI: 0-72,609) for respiratory mortality, indicating decreases of 9.93%, 9.86%, and 9.78%, respectively, compared to the year 2018. Taken together, our results provided the first direct evidence for China's efforts to control O3 pollution in recent years.

3.
Biomed Res Int ; 2022: 4513998, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35036433

RESUMO

Abnormal production and degradation of amyloid beta (Aß) in the brain lead to oxidative stress and cognitive impairment in Alzheimer's disease (AD). Cirsium japonicum var. maackii (CJM) is widely used as an herbal medicine and has antibacterial and anti-inflammatory properties. This study focused on the protective effect of the ethyl acetate fraction from CJM (ECJM) on Aß 25-35-induced control mice. In the T-maze and novel object recognition test, ECJM provided higher spatial memory and object recognition compared to Aß 25-35 treatment alone. In the Morris water maze test, ECJM-administered mice showed greater learning and memory abilities than Aß 25-35-induced control mice. Additionally, ECJM-administered mice experienced inhibited lipid peroxidation and nitric oxide production in a dose-dependent manner. The present study indicates that ECJM improves cognitive impairment by inhibiting oxidative stress in Aß 25-35-induced mice. Therefore, CJM may be useful for the treatment of AD and may be a potential material for functional foods.

4.
Carbohydr Polym ; 278: 118935, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34973753

RESUMO

It is an urgent task to exploit effective antimicrobial agents due to the rise of drug-resistant pathogens. Herein, antimicrobial quaternized chitosan/Ag composite nanogels (QCS/Ag CNGs) with tunable properties were fabricated through inverse miniemulsion technique with a high encapsulation efficiency of NH2-Ag nanoparticles (NPs). The QCS/Ag CNGs possess superior broad-spectrum antimicrobial activity and low biotoxicity, via synergistic sterilization of Ag NPs and QCS. Furthermore, the NH2-Ag NPs were chemically linked to the QCS matrix through Schiff base reactions, and the QCS/Ag CNGs have reactive groups, making it possible to obtain durable antibacterial cotton fabrics. Thus, QCS/Ag CNGs modified cotton fabrics exhibited laundering durability of antimicrobial effect after 100 washing cycles without sacrificing other inherent properties of cotton fabrics. Our study provides a facile and controllable method to construct polymer/inorganic CNGs to address the urgent need for antibacterial agents/fabrics.

5.
Cancer Lett ; 524: 131-143, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34678434

RESUMO

Aberrant angiogenesis is a hallmark of cancer and is critically associated with tumor progression. Perivascular cells are essential components of blood vessels, and the role of tumor perivascular cell-derived extracellular vesicles (TPC-EVs) in angiogenesis remains elusive. In the present study, using genetic mouse models and pharmacological inhibitors, we found that ablation of perivascular cells inhibited angiogenesis in allografted colorectal cancer tumors. Further studies demonstrated that TPC-EVs promoted the proliferation, migration, invasion, viability, and tube formation of HUVECs. They also facilitated vessel spouting in rat aortic rings and induced neovascularization in chick chorioallantoic membranes (CAMs). Silencing of Gas6 or blockade of the Axl pathway suppressed TPC-EV-induced angiogenesis in vitro and ex vivo. Moreover, inhibition of the Gas6/Axl signaling pathway impaired TPC-EV-mediated angiogenesis in vivo. Our findings present a deeper insight into the biological functions of TPCs and TPC-EVs in tumor angiogenesis and demonstrate that TPC-EV-derived Gas6 could be an attractive and innovative regulator of tumor angiogenesis.


Assuntos
Neoplasias Colorretais/genética , Vesículas Extracelulares/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Neovascularização Patológica/genética , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/genética , Animais , Aorta/crescimento & desenvolvimento , Aorta/patologia , Movimento Celular/genética , Proliferação de Células/genética , Sobrevivência Celular/genética , Galinhas , Membrana Corioalantoide/enzimologia , Membrana Corioalantoide/patologia , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica/genética , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Neovascularização Patológica/patologia , Neoplasias de Células Epitelioides Perivasculares/genética , Neoplasias de Células Epitelioides Perivasculares/patologia , Ratos
6.
Food Res Int ; 150(Pt A): 110747, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34865765

RESUMO

In this study, the contributions of three strains and different coculture patterns to microbial community diversity and metabolites in the high-salt liquid-state fermentation (HLF) soy sauce moromi were investigated. A comparison of two strains of Zygosaccharomyces rouxii showed that strain QH-25 had a stronger ability to contribute metabolites, including both nonvolatile and volatile types, to the moromi than strain QH-1, except for volatile acids and ketones. Of the various fortification patterns tested, the content of metabolites was significantly increased by inoculating Z. rouxii QH-25 prior to C. versatilis, especially the content of volatiles, including ketones, esters, phenols, and alcohols, which increased 1.61-fold compared with those in the control sample; the contents of these components were increased 3.07-, 1.91-, 1.36-, and 1.22-fold, respectively. In particular, characteristic components such as ethyl octanoate, 4-hydroxy-2(or 5)-ethyl-5(or 2)-methyl-3(2H)-furanone (HEMF), 4-ethyl-2-methoxy-phenol (4-EG), and 3-methyl-1-butanol were increased 3.99-, 3.29-, 1.63-, and 0.70-fold, respectively. Redundancy analysis (RDA) showed that Staphylococcus, Zygosaccharomyces, and Candida were positively correlated with the unique components described above. In addition, the nodes of the interaction network between Zygosaccharomyces and Candida were increased, and the positive correlation of Zygosaccharomyces with Staphylococcus was enhanced by inoculating Z. rouxii prior to C. versatilis. These results suggested that the unique flavor of soy sauce was closely related to the metabolic characteristics of strains affiliated with Z. rouxii, whether cultured singly or cocultured with C. versatilis. This study also provided a reference method for determining the differences in community structure and metabolites between traditional techniques and modern processes for soy sauce fermentation.

7.
BMC Pulm Med ; 21(1): 399, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34872558

RESUMO

BACKGROUND: Drug-resistant tuberculosis (DR-TB), obesity, and malnutrition are growing public health problems in the world. However, little has discussed the impact of different BMI status on the emergence of TB drug resistance. We aimed to explore the drug-resistant profiles of DR-TB and its clinical predictors among underweight, overweight or obesity population. METHODS: 8957 newly diagnosed TB cases with drug susceptibility results and BMI data in Shandong China, from 2004 to 2019 were enrolled. Multivariable and univariable logistic regression models were applied to investigate the impact of BMI on different drug-resistance. Clinical predicators and drug-resistant profiles of DR-TB among obesity, underweight, normal TB group were also described. RESULTS: Among 8957 TB cases, 6417 (71.64%) were normal weight, 2121 (23.68%) were underweight, 373 (4.16%) were overweight, and 46 (0.51%) were obese. The proportion of drug resistance and co-morbidity among normal weight, underweight, overweight, obese TB groups were 18.86%/18.25%/20.38%/23.91% (DR-TB), 11.19%/11.74%/9.65%/17.39% (mono-resistant tuberculosis, MR-TB), 3.41%/3.06%/5.36%/0.00% (multidrug resistant tuberculosis, MDR-TB), 4.21%/3.39%/5.36%/6.52% (polydrug resistant tuberculosis, PDR-TB), 10.57%/8.44%/19.57%/23.91% (co-morbidity), respectively. Compared with normal weight group, underweight were associated with lower risk of streptomycin-related resistance (OR 0.844, 95% CI 0.726-0.982), but contributed to a higher risk of MR-TB (isoniazid) (odds ratio (OR) 1.347, 95% CI 1.049-1.730; adjusted OR (aOR) 1.31, 95% CI 1.017-1.686), P < 0.05. In addition, overweight were positively associated with MDR-TB (OR 1.603, 95% CI 1.002-2.566; aOR 1.639, 95% CI 1.02-2.633), isoniazid + rifampicin + streptomycin resistance (OR 1.948, 95% confidence interval (CI): 1.061-3.577; aOR 2.113, 95% CI 1.141-3.912), Any isoniazid + streptomycin resistance (OR 1.472, 95% CI 1.013-2.14; aOR 1.483, 95% CI 1.017-2.164), P < 0.05. CONCLUSIONS: The higher risk of MDR-TB, isoniazid + rifampicin + streptomycin resistance, Any isoniazid + streptomycin resistance, and co-morbidity among overweight population implies that routine screening for drug sensitivity and more attention on co-morbidity among overweight TB cases may be necessary. In addition, underweight TB cases have a higher risk of isoniazid resistance. Our study suggests that an in-depth study of the interaction between host metabolic activity and infection of DR-TB may contribute more to novel treatment options or preventive measures, and accelerate the implementation of the STOP TB strategy.

8.
Mol Ecol ; 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34878672

RESUMO

Microorganisms are major constituents of the total biomass in permafrost regions, whose underlain soils are frozen for at least two consecutive years. To understand potential microbial responses to climate change, here we examined microbial community compositions and functional capacities across four soil depths in an Alaska tundra site. We showed that a 5-year warming treatment increased soil thaw depth by 25.7% (P = 0.011) within the deep organic layer (15 -25 cm). Concurrently, warming reduced 37% of bacterial abundance and 64% of fungal abundances in the deep organic layer, while it did not affect microbial abundance in other soil layers (i.e., 0 - 5 cm, 5 - 15 cm, and 45 - 55 cm). Warming treatment altered fungal community composition and microbial functional structure (P < 0.050), but not bacterial community composition. Using a functional gene array, we found that the relative abundances of a variety of carbon (C)-decomposing, iron-reducing, and sulfate-reducing genes in the deep organic layer were decreased, which was not observed by the shotgun sequencing-based metagenomics analysis of those samples. To explain the reduced metabolic capacities, we found that warming treatment elicited higher deterministic environmental filtering, which could be linked to water-saturated time, soil moisture, and soil thaw duration. In contrast, plant factors showed little influence on microbial communities in sub-surface soils below 15 cm, despite a 25.2% higher (P < 0.05) aboveground plant biomass by warming treatment. Collectively, we demonstrate that microbial metabolic capacities in sub-surface soils are reduced, likely arising from enhanced thaw by warming.

10.
Front Plant Sci ; 12: 690363, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858444

RESUMO

The plant root is an important storage organ that stores indole-3-acetic acid (IAA) from the apical meristem, as well as nitrogen, which is obtained from the external environment. IAA and nitrogen act as signaling molecules that promote root growth to obtain further resources. Fluctuations in the distribution of nitrogen in the soil environment induce plants to develop a set of strategies that effectively improve nitrogen use efficiency. Auxin integrates the information regarding the nitrate status inside and outside the plant body to reasonably distribute resources and sustainably construct the plant root system. In this review, we focus on the main factors involved in the process of nitrate- and auxin-mediated regulation of root structure to better understand how the root system integrates the internal and external information and how this information is utilized to modify the root system architecture.

11.
Comput Biol Med ; 141: 105144, 2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-34971982

RESUMO

Medical imaging datasets usually exhibit domain shift due to the variations of scanner vendors, imaging protocols, etc. This raises the concern about the generalization capacity of machine learning models. Domain generalization (DG), which aims to learn a model from multiple source domains such that it can be directly generalized to unseen test domains, seems particularly promising to medical imaging community. To address DG, recent model-agnostic meta-learning (MAML) has been introduced, which transfers the knowledge from previous training tasks to facilitate the learning of novel testing tasks. However, in clinical practice, there are usually only a few annotated source domains available, which decreases the capacity of training task generation and thus increases the risk of overfitting to training tasks in the paradigm. In this paper, we propose a novel DG scheme of episodic training with task augmentation on medical imaging classification. Based on meta-learning, we develop the paradigm of episodic training to construct the knowledge transfer from episodic training-task simulation to the real testing task of DG. Motivated by the limited number of source domains in real-world medical deployment, we consider the unique task-level overfitting and we propose task augmentation to enhance the variety during training task generation to alleviate it. With the established learning framework, we further exploit a novel meta-objective to regularize the deep embedding of training domains. To validate the effectiveness of the proposed method, we perform experiments on histopathological images and abdominal CT images.

12.
J Biol Chem ; : 101544, 2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-34971706

RESUMO

Uncontrolled gluconeogenesis results in elevated hepatic glucose production in type 2 diabetes. The SUMO-specific protease 2 (SENP2) is known to catalyze deSUMOylation of target proteins, with broad effects on cell growth, signal transduction, and developmental processes. However, the role of SENP2 in hepatic gluconeogenesis and the occurrence of type 2 diabetes remains unknown. Herein, we established SENP2 hepatic knockout mice and found that SENP2 deficiency could protect against high fat diet-induced hyperglycemia. Pyruvate or glucagon-induced elevation in blood glucose was attenuated by disruption of SENP2 expression, whereas overexpression of SENP2 in the liver facilitated high fat diet-induced hyperglycemia. Using an in vitro assay, we showed that SENP2 regulated hepatic glucose production. Mechanistically, the effects of SENP2 on gluconeogenesis were found to be mediated by the cellular fuel sensor kinase AMPKα, which is a negative regulator of gluconeogenesis. SENP2 interacted with and deSUMOylated AMPKα, thereby promoting its ubiquitination and reducing its protein stability. Inhibition of AMPKα kinase activity dramatically reversed impaired hepatic gluconeogenesis and reduced blood glucose levels in SENP2-deficient mice. Our study highlights the novel role of hepatic SENP2 in regulating gluconeogenesis and furthers our understanding of the pathogenesis of type 2 diabetes.

13.
Bioorg Chem ; 119: 105469, 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34915285

RESUMO

Targeting EGFR and HER-2 is an essential direction for cancer treatment. Here, a series of N-(1,3,4-thiadiazol-2-yl)benzamide derivatives containing a 6,7-methoxyquinoline structure was designed and synthesized to serve as EGFR/HER-2 dual-target inhibitors. The kinase assays verified that target compounds could inhibit the kinase activity of EGFR and HER-2 selectively. The results of CCK-8 and 3D cell viability assays confirmed that target compounds had excellent anti-proliferation ability against breast cancer cells (MCF-7 and SK-BR-3) and lung cancer cells (A549 and H1975), particularly against SK-BR-3 cells, while the inhibitory effect on healthy breast cells (MCF-10A) and lung cells (Beas-2B) was weak. Among them, the hit compound YH-9 binded to EGFR and HER-2 stably in molecular dynamics studies. Further studies found thatYH-9could induce the release of cytochrome c and inhibit proliferation by promoting ROS expression in SK-BR-3 cells. Moreover,YH-9could diminish the secretion of VEGF and bFGF factors in SK-BR-3 cells, then inhibited tube formation and angiogenesis. Notably,YH-9could effectively inhibit breast cancer growth and angiogenesis with little toxicity in the SK-BR-3 cell xenograft model. Taken together,in vitroandin vivoresults revealed that YH-9 had high drug potential as a dual-target inhibitor of EGFR/HER-2 to inhibit breast cancer growth and angiogenesis.

14.
Zhonghua Nan Ke Xue ; 27(5): 433-436, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34914319

RESUMO

Objective: To evaluate the effect of the York-Mason procedure (posterior sagittal approach) in the treatment of urethrorectal fistula. METHODS: Ten 15-80 (mean 54) years old male patients with urethrorectal fistula were treated by the York-Mason procedure, 3 by anoplasty for congenital anal atresia, 5 by laparoscopic radical prostatectomy, and the other 2 by radical rectal cancer resection. All the cases were single fistula with a history of 3 months to 18 years. Enterostomy was performed in 6 of the cases before the York-Mason procedure. RESULTS: The York-Mason procedure lasted 90-130 (mean 104) minutes, with no perioperative complications. Nine of the cases were successfully repaired in the first surgery and 1 in the second. The patients were discharged after an average of 7 hospital days postoperatively and followed up for 6-90 months without recurrence. CONCLUSIONS: The York-Mason procedure is a reliable and effective option for the treatment of urethrorectal fistula, with the advantages low morbidity, short operation time and fast recovery.


Assuntos
Fístula Retal , Fístula Urinária , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Prostatectomia , Fístula Retal/cirurgia , Fístula Urinária/cirurgia
15.
Open Forum Infect Dis ; 8(12): ofab535, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34926714

RESUMO

Background: China implemented the globally synchronized switch from trivalent oral poliovirus vaccine (tOPV) to bivalent OPV (bOPV) on May 1, 2016. During April 2018 to May 2019, the first outbreak caused by type 2 circulating vaccine-derived poliovirus (cVDPV2) after the switch occurred in Xinjiang and Sichuan, China. Methods. We performed sequence analysis of VP1 and the whole genome to determine the genomic characteristics of type 2 cVDPVs, and carried out coverage surveys to assess the risk of viral propagation. Surveillance for environment and acute flaccid paralysis was intensified to enhance case ascertainment. Results. Comparison of the complete genomes between early (Xinjiang strain) and late strains (Sichuan strains) revealed that recombination pattern and reverse mutation of attenuation sites had been fixed early, but the mutations of the neutralizing antigenic sites were introduced over the circulation. The Markov Chain Monte Carlo tree showed that the cVDPV2 initial infection was April 2016, earlier than the switch. So, we speculated that the cVDPV2 was originated from tOPV recipients and spread among children with a low level of immunity against the type 2. Conclusions: The detection of this outbreak combined acute flaccid paralysis (AFP) surveillance with environmental surveillance (ES) indicates that ES should be expanded geographically to further complement AFP surveillance.

17.
Biomolecules ; 11(11)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34827600

RESUMO

Long noncoding RNAs (lncRNAs) are transcripts greater than 200 nucleotides that do not code for proteins but regulate gene expression. Recent studies indicate that lncRNAs are involved in the modulation of biological functions in human disease. KCNQ1 Opposite Strand/Antisense Transcript 1 (KCNQ1OT1) encodes a lncRNA from the opposite strand of KCNQ1 in the CDKN1C/KCNQ1OT1 cluster that is reported to play a vital role in the development and progression of cancer. KCNQ1OT1 regulates cancer cell proliferation, cell cycle, migration and invasion, metastasis, glucose metabolism, and immune evasion. The aberrant expression of KCNQ1OT1 in cancer patients is associated with poor prognosis and decreased survival. This review summarizes recent literature related to the biological functions and molecular mechanisms of KCNQ1OT1 in various human cancers, including colorectal, bladder, breast, oral, melanoma, osteosarcoma, lung, glioma, ovarian, liver, acute myeloid leukemia, prostate, and gastric. We also discuss the role of KCNQ1OT1 as a promising diagnostic biomarker and a novel therapeutic target in human cancers.

18.
Mol Psychiatry ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34819637

RESUMO

(R,S)-ketamine elicits rapid-acting and sustained antidepressant actions in treatment-resistant patients with depression. (R)-ketamine produces longer-lasting antidepressant effects than (S)-ketamine in rodents; however, the precise molecular mechanisms underlying antidepressant actions of (R)-ketamine remain unknown. Using isobaric Tag for Relative and Absolute Quantification, we identified nuclear receptor-binding protein 1 (NRBP1) that could contribute to different antidepressant-like effects of the two enantiomers in chronic social defeat stress (CSDS) model. NRBP1 was localized in the microglia and neuron, not astrocyte, of mouse medial prefrontal cortex (mPFC). (R)-ketamine increased the expression of NRBP1, brain-derived neurotrophic factor (BDNF), and phosphorylated cAMP response element binding protein (p-CREB)/CREB ratio in primary microglia cultures thorough the extracellular signal-regulated kinase (ERK) activation. Furthermore, (R)-ketamine could activate BDNF transcription through activation of CREB as well as MeCP2 (methyl-CpG binding protein 2) suppression in microglia. Single intracerebroventricular (i.c.v.) injection of CREB-DNA/RNA heteroduplex oligonucleotides (CREB-HDO) or BDNF exon IV-HDO blocked the antidepressant-like effects of (R)-ketamine in CSDS susceptible mice. Moreover, microglial depletion by colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX3397 blocked the antidepressant-like effects of (R)-ketamine in CSDS susceptible mice. In addition, inhibition of microglia by single i.c.v. injection of mannosylated clodronate liposomes (MCLs) significantly blocked the antidepressant-like effects of (R)-ketamine in CSDS susceptible mice. Finally, single i.c.v. injection of CREB-HDO, BDNF exon IV-HDO or MCLs blocked the beneficial effects of (R)-ketamine on the reduced dendritic spine density in the mPFC of CSDS susceptible mice. These data suggest a novel ERK-NRBP1-CREB-BDNF pathways in microglia underlying antidepressant-like effects of (R)-ketamine.

19.
Front Endocrinol (Lausanne) ; 12: 763897, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777258

RESUMO

Purpose: To explore the characteristics of C-TIRADS by comparing it with ACR-TIRADS, Kwak-TIRADS, KSThR-TIRADS and EU-TIRADS. Methods: A total of 1096 nodules were collected from 884 patients undergoing thyroidectomy in our center between May 2018 and December 2020. Divided the nodules into two groups: ">10mm" and "≤10mm". Ultrasound characteristics of each nodule were observed and recorded by 2 doctors, then classified based on ACR-TIRADS, Kwak-TIRADS, KSThR-TIRADS, EU-TIRADS, and C-TIRADS. Results: A total of 682 benign nodules cases (62.23%) and 414 malignant nodules cases (37.77%) were identified. The ICC value of each guideline was:0.937(ACR-TIRADS), 0.858(EU-IRADS), 0.811(Kwak-TIRADS), 0.835(KTA/KSThR-TIRADS) and 0.854(C-TIRADS). The nodule malignancy rates in the groups(Kwak-TIRADS 4B, C-TIRADS 4B、4C) of two sizes were significantly different (all p<0.05). There was no statistical difference in the other grades of two sizes (all p>0.05). Unnecessary biopsy rates were the lowest in C-TIRADS (49.02% p<0.001). Furthermore, Kwak-TIRADS had the highest sensitivity and NPV (89.9%, 91.0%, all p<0.05), while C-TIRADS had the highest specificity and PPV (82.3%, 69.2%, all p<0.05). C-TIRADS and Kwak-TIRADS had the highest accuracy (76.0%, 72.5%, P=0.071). The AUCs of the 5 guidelines were C-TIRADS(0.816, P<0.05), Kwak-TIRADS(0.789, P<0.05) KTA/KSThR-TIRADS and ACR-TIRADS(0.773, 0.763, P=0.305), EU-TIRADS(0.734, P<0.05). The AUCs of the five guidelines were not statistically different between "nodules>10mm" and "nodules ≤ 10mm" (all P>0.05). Conclusions: All five guides showed excellent interobserver agreement. C-TIRADS was slightly efficient than Kwak-IRADS, KTA/KSThR-TIRADS and ACR-TIRADS, and had greater advantages than EU-TIRADS. The diagnostic abilities of the five guidelines for "nodules ≤ 10mm" were not inferior to that of "nodules> 10mm". C-TIRADS is simple and easy to implement and can provide effective thyroid tumor risk stratification for thyroid nodule diagnosis, especially in China.

20.
Org Lett ; 23(22): 9000-9005, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34748354

RESUMO

An efficient iodine-imine synergistic promoted Povarov-type multicomponent reaction was reported for the synthesis of a practical 2,2'-biquinoline scaffold. The tandem annulation has reconciled iodination, Kornblum oxidation, and Povarov aromatization, where the methyl group of the methyl azaarenes represents uniquely reactive input in the Povarov reaction. This method has broad substrate scope and mild conditions. Furthermore, these 2,2'-biquinoline derivatives had been directly used as bidentate ligands in metal-catalyzed reactions.

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