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1.
J Sci Food Agric ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563388

RESUMO

BACKGROUND: Biogenic amines (BA) are hazardous components in Huangjiu (HJ). To ensure the quality of Dangshen Huangjiu, an orthogonal experiment L9 (33) was proposed to optimize the process by the main brewing factors (pre-fermentation temperature, pre-(post-) fermentation time) that may affect BA and functional factors in Dangshen Huangjiu. Dangshen Huangjiu (DSHJ) was produced with low BA and high functional factors. Gas chromatography-ion mobility spectrometry combined with a multivariate statistical method (GC-IMS-MSM) was used to analyze the volatile components in the DSHJ brewing process of DSHJ. RESULTS: The optimum brewing process parameters of DSHJ were as follows: pre-fermentation temperature 28°C, pre-fermentation time 9 days, and post-fermentation time 18 days. The average content of BA in DSHJ was 33.12 mg/L, and the sensory score, total phenol content, and DPPH free radical scavenging rate of DSHJ were significantly higher than HJ. A total of 14 esters, 7 acids, 7 alcohols, 1 ketones, 5 aldehydes, and 1 pyrazine in DSHJ and HJ were identified by GC-IMS. There were no significant differences (P>0.05) in DSHJ and HJ in the soaking rice and saccharification stage. 11 components, such as ethyl acetate, and 12 components, such as acetic acid, were the different components of HJ and DSHJ in pre-fermentation and post-fermentation stages, respectively. In the post-fermentation stage, the content of 8 components of DSHJ such as ethyl acetate were higher than in HJ. CONCLUSION: The preparation process parameters of DSHJ optimized by orthogonal experiments can ensure that DSHJ has the advantages of low BA, high total phenol content, and good antioxidant activity. Sensory score and GC-IMS-MSM analysis found that DSHJ prepared by the optimal process had the characteristics of good taste and rich aroma. This article is protected by copyright. All rights reserved.

2.
Cell Death Discov ; 10(1): 167, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589400

RESUMO

The neurotoxic α-synuclein (α-syn) oligomers play an important role in the occurrence and development of Parkinson's disease (PD), but the factors affecting α-syn generation and neurotoxicity remain unclear. We here first found that thrombomodulin (TM) significantly decreased in the plasma of PD patients and brains of A53T α-syn mice, and the increased TM in primary neurons reduced α-syn generation by inhibiting transcription factor p-c-jun production through Erk1/2 signaling pathway. Moreover, TM decreased α-syn neurotoxicity by reducing the levels of oxidative stress and inhibiting PAR1-p53-Bax signaling pathway. In contrast, TM downregulation increased the expression and neurotoxicity of α-syn in primary neurons. When TM plasmids were specifically delivered to neurons in the brains of A53T α-syn mice by adeno-associated virus (AAV), TM significantly reduced α-syn expression and deposition, and ameliorated the neuronal apoptosis, oxidative stress, gliosis and motor deficits in the mouse models, whereas TM knockdown exacerbated these neuropathology and motor dysfunction. Our present findings demonstrate that TM plays a neuroprotective role in PD pathology and symptoms, and it could be a novel therapeutic target in efforts to combat PD. Schematic representation of signaling pathways of TM involved in the expression and neurotoxicity of α-syn. A TM decreased RAGE, and resulting in the lowered production of p-Erk1/2 and p-c-Jun, and finally reduce α-syn generation. α-syn oligomers which formed from monomers increase the expression of p-p38, p53, C-caspase9, C-caspase3 and Bax, decrease the level of Bcl-2, cause mitochondrial damage and lead to oxidative stress, thus inducing neuronal apoptosis. TM can reduce intracellular oxidative stress and inhibit p53-Bax signaling by activating APC and PAR-1. B The binding of α-syn oligomers to TLR4 may induce the expression of IL-1ß, which is subsequently secreted into the extracellular space. This secreted IL-1ß then binds to its receptor, prompting p65 to translocate from the cytoplasm into the nucleus. This translocation downregulates the expression of KLF2, ultimately leading to the suppression of TM expression. By Figdraw.

3.
Medicine (Baltimore) ; 103(11): e37563, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489688

RESUMO

INTRODUCTION: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is one kind of monogenic hereditary small-vessel disease in the brain caused by mutations in the NOTCH3 gene. However, it is rare for CADASIL to recur with different clinical manifestations in 1 patient, and some atypical clinical manifestations can easily lead to misdiagnosis by clinical physicians. CASE CONCERN: A 34-year-old male presented with transient speech disorder accompanied by weakness in the left side of the body for 1 day in June 2020. Magnetic resonance imaging showed acute ischemic infarction in right centrum semiovale, along with multiple abnormal white matter hyperintensities in the brain. Genetic sequencing identified a heterozygous mutation in the NOTCH3 gene. The patient experienced recurrent episodes in 2021 and 2023, with varying clinical symptoms including visual blurring, abnormal limb sensation, and sudden cognitive dysfunction. DIAGNOSIS: The diagnoses of CADASIL is based on clinical manifestations, imaging results, and genetic reports. INTERVISION AND OUTCOMES: The patient was received symptomatic treatment including antiplatelet aggregation therapy, lipid regulation, and plaque stabilization, resulting in improved symptoms. OUTCOMES: During the course of the disease, after medication treatment and rehabilitation exercise, the patient clinical symptoms have significantly improved. Currently, the patient is closely following up and regularly undergoing relevant examinations. LESSONS: In this rare case, we found that CADASIL can recur multiple times in a patient with different clinical symptoms, which can easily lead to clinical misdiagnosis. Clinicians should consider the possibility of CADASIL in young patients with sudden typical neurological dysfunction.


Assuntos
CADASIL , Leucoencefalopatias , Masculino , Humanos , Adulto , CADASIL/complicações , CADASIL/diagnóstico , CADASIL/genética , Receptor Notch3/genética , Encéfalo/patologia , Mutação , Imageamento por Ressonância Magnética , Leucoencefalopatias/complicações , Leucoencefalopatias/diagnóstico , Leucoencefalopatias/patologia
4.
Small ; : e2311057, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38385809

RESUMO

Low-cost and eco-friendly Ni/NiO heterojunctions have been theoretically proven to be the ideal candidate for stepwise electrocatalysis of alkaline hydrogen evolution reaction, attributed to the preferred OHad adsorption by incompletely filled d orbitals of NiO phase and favorable Had adsorption energy of Ni phase. Nevertheless, most Ni/NiO compounds reported so far fail to exhibit excellent catalytic activity, possibly due to the lack of efficient electron transport, limited interfacial active sites, and unregulated Nin+ ratios. To address the above bottlenecks, herein, the ultrasmall Ni/NiOx @C nanocapsules (<5 nm) are directly constructed by graphitization of four-layer Ni-based coordination polymers at record low temperatures of 400 °C. Ascribed to the accelerated electron and mass transfer by the carbon nano-onions coated around Ni/NiOx heterojunctions, the extreme rise in interfaces and Ni3+ defects with t6 2ge1 g electronic configuration owed to the ultrasmall size, the Ni/NiOx @C nanocapsules exhibit the highest catalytic activity and the lowest overpotential of η10 = 80 mV among various Ni/NiO materials (measured on the glassy carbon electrode). This work not only constructs an industrialized high-efficiency electrocatalyst toward alkaline HER, but also provides a novel strategy for the constant-scale preparation of multicomponent transition metals-based nanocrystals below 4 nm.

5.
Hum Brain Mapp ; 45(2): e26609, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38339893

RESUMO

The phenomenon known as the "identifiable victim effect" describes how individuals tend to offer more assistance to victims they can identify with than to those who are vague or abstract. The neural underpinnings of this effect, however, remain elusive. Our study utilized functional magnetic resonance imaging to delve into how the "identifiable victim effect" influences prosocial decision-making, considering different types of helping costs, across two distinct tasks. Participants were instructed to decide whether to help a victim with personal information shown (i.e., the identifiable victim) and an unidentifiable one by costing their money (task 1) or physical effort (task 2). Behaviorally, we observed a pronounced preference in both tasks for aiding identifiable victims over anonymous ones, highlighting a robust "identifiable victim effect." On a neural level, this effect was associated with heightened activity in brain areas like the bilateral temporoparietal junction (TPJ) when participants confronted anonymous victims, potentially indicating a more intensive mentalizing process for less concrete victims. Additionally, we noted that the TPJ's influence on value judgment processes is mediated through its functional connectivity with the medial prefrontal cortex. These insights contribute significantly to our understanding of the psychological and neural dynamics underlying the identifiable victim effect.


Assuntos
Mapeamento Encefálico , Encéfalo , Humanos , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(1): 57-65, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38387900

RESUMO

OBJECTIVE: To observe the effect of resveratrol (Res) on T-acute lymphoblastic leukemia (T-ALL) mice, and further explore its mechanism on Notch1 signaling pathway. METHODS: Twenty-five 6-8 weeks old female C57BL/6 mice were randomly divided into control group, T-ALL group and Res group. Res group was further divided into low-Res, middle-Res and high-Res group. The percentage of leukemia cells in peripheral blood and spleen cell suspension were detected by flow cytometry and Wright-Giemsa staining, pathological morphology of spleen and bone marrow tissues were observed by HE staining, the expression levels of Notch1, Hes-1, c-Myc, miR-19b and PTEN mRNA in spleen tissue were detected by RT-qPCR, and the protein levels of Notch1, Hes-1, c-Myc, p-PTEN and PTEN were detected by Western blot. RESULTS: Compared with control group, the leukemia cells in peripheral blood of mice in T-ALL group were markedly increased, accompanied by diffuse infiltration of leukemia cells in spleen and bone marrow tissues, the mRNA levels of Notch1, Hes-1, c-Myc, miR-19b and the protein levels of Notch1, Hes-1, c-Myc were increased (P <0.01), while the expression of PTEN mRNA and protein were significantly decreased in the spleen tissue of T-ALL mice (P <0.01). The above indicators in the H-Res group were reversed compared with T-ALL group after administration of resveratrol. CONCLUSION: Resveratrol may play a role in anti T-ALL by inhibiting Notch1 signaling pathway in mice.


Assuntos
MicroRNAs , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Camundongos , Feminino , Animais , Resveratrol/farmacologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Receptor Notch1/genética , Camundongos Endogâmicos C57BL , Transdução de Sinais , MicroRNAs/farmacologia , RNA Mensageiro
7.
Food Res Int ; 176: 113842, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38163733

RESUMO

Oil autoxidation is an early process of food deterioration, monitoring oil oxidation is therefore of great significance to ensure food quality and safety. In this study, a detection method of the primary and secondary oxidative products was developed by gas chromatography ion mobility spectrometry (GC-IMS).The secondary oxidative products was analyzed by GC-IMS. Then, the relationships between peroxide values and the contents of secondary oxidative products were investigated by constructing a prediction model of peroxide value of rapeseed oil with the help of secondary oxidative products and chemometrics. The coefficient of determination Q2 of the model validation set is 0.96, and the RMSECV is 0.1570 g/100 g. These validation results indicated that secondary oxidative products could also reflect the content of the primary oxidative products. Moreover, 10 characteristic markers related to oxidative rancidity were identified for monitoring edible oil rancidity and oxidative stability.


Assuntos
Qualidade dos Alimentos , Espectrometria de Mobilidade Iônica , Cromatografia Gasosa-Espectrometria de Massas/métodos , Espectrometria de Mobilidade Iônica/métodos , Óleo de Brassica napus , Peróxidos
8.
J Chemother ; : 1-13, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38288951

RESUMO

Rosuvastatin (RSV) is widely used to treat hyperlipidemia and hypercholesterolemia and is recommended for the primary and secondary prevention of cardiovascular diseases (CVD). In this study, we aimed to explore its action and mechanism in lung adenocarcinoma (LUAD) therapy. Lewis and CMT64 cell-based murine subcutaneous LUAD models were employed to explore the effects of RSV monotherapy combined with cisplatin and gemcitabine. Human lung fibroblasts and human LUAD cell lines were used to assess the effects of RSV on normal and LUAD cells. Bioinformatics and RNA interference were used to observe the contribution of cyclin A2 (CCNA2) knockdown to RSV inhibition and to improve chemosensitivity in LUAD. RSV significantly suppressed grafted tumor growth in a murine subcutaneous LUAD model and exhibited synergistic anti-tumor activity with cisplatin and gemcitabine. In vitro and in vivo experiments demonstrated that RSV impaired the proliferation and migration of cancer cells while showing little inhibition of normal lung cells. RNA interference and CCK8 detection preliminarily indicated that RSV inhibited tumor growth and enhanced the chemosensitivity to cisplatin and gemcitabine by downregulating CCNA2. RSV suppressed LUAD progression and enhanced chemosensitivity to cisplatin and gemcitabine by downregulating CCNA2, which should be prior consideration for the treatment of LUAD, especially for patients co-diagnosed with hyperlipidemia and hypercholesterolemia.

9.
Ann Nucl Med ; 38(4): 247-263, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38145430

RESUMO

INTRODUCTION: Functions of existing automatic module systems for synthesis of radiopharmaceuticals mainly focus on the radiolabeling of small molecules. There are few modules which have achieved full-automatic radiolabeling of non-metallic and metallic nuclides on small molecules, peptides, and antibody drugs. This study aimed to develop and test a full-automatic multifunctional module system for the safe, stable, and efficient production of radiopharmaceuticals. METHODS: According to characteristics of labeling process of radioactive drugs, using UG and Solidworks softwares, full-automatic cassette-based synthesis module system Mortenon M1 for synthesis of radiopharmaceuticals with various radionuclides, was designed and tested. Mortenon M1 has at least three significant highlights: the cassettes are disposable, and there is no need of manual cleaning; the synthesis method program is flexible and can be edited freely by users according to special needs; this module system is suitable for radiolabeling of both small-molecule and macromolecular drugs, with potentially various radionuclides including 18F, 64Cu, 68Ga, 89Zr, 177Lu, etc. By program control methods for certain drugs, Mortenon M1 was used for radiolabeling of both small-molecule drugs such as [68Ga]-FAPI-46 and macromolecular drugs such as [89Zr]-TROP2 antibody. Quality control assays for product purity were performed with radio-iTLC and radio-HPLC, and the radiotracers were confirmed for application in microPET imaging in xenograft tumor-bearing mouse models. RESULTS: Functional tests for Mortenon M1 module system were conducted, with [68Ga]-FAPI-46 and [89Zr]-TROP2 antibody as goal synthetic products, and it displayed that with the cassette modules, the preset goals could be achieved successfully. The radiolabeling synthesis yield was good ([68Ga]-FAPI-46, 70.63% ± 2.85%, n = 10; [89Zr]-TROP2, 82.31% ± 3.92%, n = 10), and the radiochemical purity via radio-iTLC assay of the radiolabeled products was above 99% after purification. MicroPET imaging results showed that the radiolabeled tracers had reasonable radioactive distribution in MDA-MB-231 and SNU-620 xenograft tumor-bearing mice, and the tumor targeted radiouptake was satisfactory for diagnosis. CONCLUSION: This study demonstrated that the full-automatic module system Mortenon M1 is efficient for radiolabeling synthesis of both small-molecule and macromolecular substrates. It may be helpful to reduce radiation exposure for safety, provide qualified radiolabeled products and reliable PET diagnosis, and ensure stable production and supply of radiopharmaceuticals.


Assuntos
Neoplasias , Compostos Radiofarmacêuticos , Humanos , Animais , Camundongos , Compostos Radiofarmacêuticos/química , Radioisótopos de Gálio/química , Radioisótopos/química , Peptídeos , Anticorpos
10.
Nanoscale ; 15(48): 19784-19791, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38050429

RESUMO

Research on Ni/NiO electrocatalysts has advanced significantly, but the main obstacles to their use and commercialization remain their relatively ordinary activity and stability. In this paper, a chelating structure based on the coordination of multidentate ligands and Ni(II) is proposed to limit the growth of Ni and Ni oxide grains. These features reduce the particle size of Ni/NiO, increase particle dispersion, and maintain the high activity and stability of the catalyst. Aspartic acid, as a polydentate ligand, could coordinate with Ni2+ to form structurally stable chelate rings. The latter can limit grain growth, but also coat the active core with thin carbon layers after calcination to further achieve the confinement and protection of nanoparticles. The hydrogen evolution overpotential of prepared nitrogen-doped graphitized carbon shells (Ni/NiO@NC) nanoparticles was 100 mV (vs. RHE) when the current density was 10 mA cm-2 in 1 M KOH. The hydrogen evolution overpotential increased by only 4 mV after 6000 continuous cyclic-voltammetry scans. Moreover, when coated on different conductive substrates, the overpotential of this catalyst dropped to 34.6 mV (vs. RHE) at a current density of 10 mV cm-2. The lowest overpotential of the composite was only 194.9 mV at a current density of 100 mA cm-2, which is comparable with that of noble metal-based electrocatalysts. This work provides a plausible method for designing high-performance electrocatalysts of small size.

11.
Mar Drugs ; 21(12)2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38132967

RESUMO

The secondary metabolites of marine fungi with rich chemical diversity and biological activity are an important and exciting target for natural product research. This study aimed to investigate the fungal community in Quanzhou Bay, Fujian, and identified 28 strains of marine fungi. A total of 28 strains of marine fungi were screened for small-scale fermentation by the OSMAC (One Strain-Many Compounds) strategy, and 77 EtOAc crude extracts were obtained and assayed for cancer cell inhibition rate. A total of six strains of marine fungi (P-WZ-2, P-WZ-3-2, P-WZ-4, P-WZ-5, P56, and P341) with significant changes in cancer cell inhibition induced by the OSMAC strategy were analysed by UPLC-QTOF-MS. The ACD/MS Structure ID Suite software was used to predict the possible structures with inhibitory effects on cancer cells. A total of 23 compounds were identified, of which 10 compounds have been reported to have potential anticancer activity or cytotoxicity. In this study, the OSMAC strategy was combined with an untargeted metabolomics approach based on UPLC-QTOF-MS to efficiently analyse the effect of changes in culture conditions on anticancer potentials and to rapidly find active substances that inhibit cancer cell growth.


Assuntos
Fungos , Metabolômica , Cromatografia Líquida de Alta Pressão , Fungos/metabolismo , Fermentação
12.
Eur Radiol ; 2023 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-38001250

RESUMO

OBJECTIVES: Carotid atherosclerosis plays an essential role in the occurrence of ischemic stroke. This study aimed to investigate whether a larger burden of napkin-ring sign (NRS) plaques on cervicocerebral computed tomography angiography (CTA) increased the risk of acute ischemic stroke (AIS). METHODS: This retrospective, single-center, cross-sectional study enrolled patients with NRS plaques identified in the subclavian arteries, brachiocephalic trunk, carotid arterial system, and vertebrobasilar circulation on contrast-enhanced cervicocerebral CTA. Patients were divided into AIS and non-AIS groups based on imaging within 12 h of symptom onset. Univariate and multivariate logistic regression analyses were performed to determine the risk factor of AIS occurrence. RESULTS: A total of 202 patients (66.72 years ± 8.97, 157 men) were evaluated. Plaques with NRS in each subject of the AIS group (N = 98) were significantly more prevalent than that in the control group (N = 104) (1.96 ± 1.17 vs 1.41 ± 0.62). In the AIS group, there were substantially more NRS plaques on the ipsilateral side than contralateral side (1.55 ± 0.90 vs. 0.41 ± 0.66). NRS located on the ipsilateral side of the AIS showed an area under the receiver curve (AUC) of 0.86 to identify ischemic stroke. NRS plaque amounts were an independent risk factor for AIS occurrence (odds ratio, 1.86) after adjusting for other factors. CONCLUSIONS: Increased incidence of napkin-ring sign plaques on cervicocerebral CTA was positively associated with AIS occurrence, which could aid in detecting asymptomatic atherosclerotic patients at high risk of AIS in routine screening or emergency settings. CLINICAL RELEVANCE STATEMENT: Napkin-ring sign plaque provides an important imaging target for estimating acute ischemic stroke risk and identifying high-risk patients in routine screening or emergency settings, so that timely anti-atherosclerotic therapy can be used for prevention. KEY POINTS: • This cross-sectional study investigated the association between high-risk carotid artery plaques and acute ischemic stroke. • Increased incidence of napkin-ring sign plaques on cervicocerebral computed tomography angiography is positively associated with acute ischemic stroke occurrence. • Napkin-ring signs help identify risky patients prone to acute ischemic stroke to facilitate prevention.

13.
Sci Rep ; 13(1): 20726, 2023 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-38007505

RESUMO

Owing to the increasing market demand of Codonopsis Radix, the cropper blindly cultivates to expand planting area for economic benefits, which seriously affects the quality of Codonopsis Radix. Therefore, this study synthesized 207 batches of Codonopsis Radix and 115 ecological factors, and analyzed the suitable planting areas of Codonopsis pilosula under current and future climate change based on Geographic Information System (GIS) and MaxEnt model. Secondly, we evaluated the quality of Codonopsis Radix based on the all-in-one functional factor including chromatographic fingerprint, the index components, the effective compounds groups, the nutritional components, and the nutritional elements, and the quality regionalization of Codonopsis Radix was analyzed. Finally, the ecological factors affecting the accumulation of effective components of Codonopsis Radix were analyzed. This study found for the first time that the highly suitable area of Codonopsis pilosula was mainly distributed in the Weihe River system and the Bailongjiang River system in Gansu Province. There were differences in the quality of Codonopsis Radix from different ecologically suitable areas based on the all-in-one functional factors, and the comprehensive high-quality area of Codonopsis Radix was mainly distributed in Longnan and Longxi district of Gansu Province. The precipitation, temperature and altitude play a key role in the accumulation of chemical components in the 10 ecological factors affecting the distribution of Codonopsis pilosula. Under future climatic conditions, the highly suitable area of Codonopsis pilosula is decreased.


Assuntos
Codonopsis , Codonopsis/química , Sistemas de Informação Geográfica , Raízes de Plantas/química , Altitude
14.
Mar Drugs ; 21(10)2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37888447

RESUMO

With the emergence of drug resistance and the consequential high morbidity and mortality rates, there is an urgent need to screen and identify new agents for the effective treatment of cancer. Terphenyls-a group of aromatic hydrocarbons consisting of a linear 1,4-diaryl-substituted benzene core-has exhibited a wide range of biological activities. In this study, we discovered a terphenyllin derivative-CHNQD-00824-derived from the marine compound library as a potential anticancer agent. The cytotoxic activities of the CHNQD-00824 compound were evaluated against 13 different cell lines with IC50 values from 0.16 to 7.64 µM. Further study showed that CHNQD-00824 inhibited the proliferation and migration of cancer cells, possibly by inducing DNA damage. Acridine orange staining demonstrated that CHNQD-00824 promoted apoptosis in zebrafish embryos. Notably, the anti-cancer effectiveness was verified in a doxycin hydrochloride (DOX)-induced liver-specific enlargement model in zebrafish. With Solafinib as a positive control, CHNQD-00824 markedly suppressed tumor growth at concentrations of 2.5 and 5 µM, further highlighting its potential as an effective anticancer agent.


Assuntos
Antineoplásicos , Peixe-Zebra , Animais , Linhagem Celular Tumoral , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Antineoplásicos/farmacologia , Apoptose , Dano ao DNA , Relação Estrutura-Atividade , Estrutura Molecular
15.
BMC Pharmacol Toxicol ; 24(1): 54, 2023 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-37833798

RESUMO

BACKGROUND: AT-533 is a novel heat shock protein 90 inhibitor that exerting anti-inflammatory, antiviral, and antitumor efficacy. Furthermore, the gel made of AT-533 as raw material named AT-533 gel has the function of repairing keratitis and dermatitis caused by herpes virus infection. However, the acute safety evaluation of AT-533 and AT-533 gel has not been conducted. METHODS AND RESULTS: Herein, we performed acute toxicological studies of AT-533 and AT-533 gel in Sprague-Dawley rats. Fifteen-day acute toxicity study of AT-533 was conducted in both male and female Sprague-Dawley rats at doses of 5, 50, 250 and 500 mg/kg and AT-533 gel at 5 g/kg in the study. During experiment, food consumption and mortality were observed and body weight, hematology, serum biochemistry and histopathological assessment of rats were carried out. No abnormal changes were observed in rats percutaneously treated with AT-533 at 5 mg/kg and 50 mg/kg and AT-533 gel. However, loss of appetite and body weight, adverse reactions, toxicologically relevant alterations in hematology and biochemistry were found in rats percutaneously treated with AT-533 at 250 mg/kg and 500 mg/kg during 15-day acute dermic toxicity study. CONCLUSIONS: The aforementioned results suggested that the LD50 of AT-533 is 228.382 mg/kg and the LD50 of AT-533 gel is greater than 5 g/kg. These findings indicated that AT-533 is non-toxic in rats when the dose less than 50 mg/kg and AT-533 gel can be considered a gel with no toxicity at doses less than 5 g/kg.


Assuntos
Ratos Sprague-Dawley , Ratos , Masculino , Feminino , Animais , Dose Letal Mediana , Peso Corporal , Administração Oral
16.
Hum Brain Mapp ; 44(17): 6090-6104, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37771259

RESUMO

The present study employed a novel paradigm and functional magnetic resonance imaging (fMRI) to uncover the specific regulatory mechanism of time pressure and empathy trait in prosocial decision-making, compared to self-decision making. Participants were instructed to decide whether to spend their own monetary interest to alleviate themselves (or another person) from unpleasant noise threats under high and low time pressures. On the behavioral level, results showed that high time pressure had a significant effect on reducing participants' willingness to spend money on relieving themselves from the noise, while there is a similar but not significant trend in prosocial decision-making. On the neural level, for self-concerned decision-making, low time pressure activated the bilateral insula more strongly than high time pressure. For prosocial decision-making, high time pressure suppressed activations in multiple brain regions related to empathy (temporal pole, middle temporal gyrus, and inferior frontal gyrus), valuation (medial orbitofrontal cortex), and emotion (putamen). The functional connectivity strength among these regions, especially the connectivity between the medial orbitofrontal cortex and putamen, significantly predicted the effect of time pressure on prosocial decision-making at the behavioral level. Additionally, we discovered the activation of the medial orbitofrontal cortex partially mediated the effect of empathy trait scores on prosocial decision-making. These findings suggest that (1) there are different neural underpinnings for the modulation of time pressure for self and prosocial decision-making, and (2) the empathy trait plays a crucial role in the latter.


Assuntos
Mapeamento Encefálico , Comportamento Social , Humanos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Córtex Cerebral/fisiologia , Emoções/fisiologia , Empatia , Imageamento por Ressonância Magnética
17.
Arch Med Sci ; 19(5): 1201-1206, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37732044

RESUMO

Introduction: The aim of the present study was to evaluate the diagnostic efficacy of different tendon reflexes in detecting diabetic peripheral neuropathy (DPN). Material and methods: According to the changes in tendon reflexes, all patients with diabetes were divided into three strata: impaired Achilles reflex only, impaired lower extremity reflexes, and impaired lower and upper extremity reflexes. Taking nerve conduction studies (NCS) as the gold standard, the sensitivity, specificity, and predictive ability of the tendon reflexes of these three strata, as well as the Toronto clinical scoring system (TCSS) and Michigan Neuropathy Screening Instrument (MNSI), were calculated. Then, the electrophysiological characteristics of diabetic patients with different tendon reflexes were analysed. Results: Among the 240 patients studied, 92 (38.3%) presented evidence of neuropathy, which was confirmed by abnormal NCS, while 148 (61.7%) had normal NCS results. Taking NCS as the gold standard, stratum 1 yielded a sensitivity and specificity of 93.5% and 54.7%, respectively, while stratum 3 had higher specificity (96.6%) and lower sensitivity (34.8%) when compared to stratum 1. However, stratum 2 had the highest specificity (75.7%). Conclusions: The assessment of tendon reflexes can be proposed as a test for screening diabetic polyneuropathy.

18.
Pflugers Arch ; 475(11): 1251-1263, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37747537

RESUMO

Studies have confirmed that hepatic iron overload is one of the important factors causing liver damage in the metabolic syndrome (MS). As a special form of autophagy, ferritinophagy is involved in the regulation of iron metabolism. Our previous studies have shown that chronic intermittent hypobaric hypoxia (CIHH) can improve the iron metabolism disorder. The aim of this study was to investigate how CIHH improves liver damage through ferritinophagy in MS rats. Male Sprague-Dawley rats aged 8-10 weeks were randomly divided into four groups: control (CON), CIHH (exposed to hypoxia at a simulated altitude of 5000 m for 28 days, 6 h daily), MS model (induced by a 16-week high-fat diet and 10% fructose water feeding), and MS + CIHH (exposed to CIHH after a 16-week MS inducement) groups. Liver index, liver function, iron content, tissue morphology, oxidative stress, ferritinophagy, ferroptosis, and iron metabolism-related protein expression were measured, and the ferritinophagy flux in the liver was further analyzed. Compared with CON rats, MS rats had an increased liver index, damaged liver tissue and function, increased iron content and iron deposition, disrupted iron metabolism, significantly increased oxidative stress indicators in the liver, significantly upregulated expression of ferroptosis-related proteins, and downregulated expression of nuclear receptor coactivator 4 (NCOA4) and ferritinophagy flux. After CIHH treatment, the degree of liver damage and various abnormal indicators in MS rats were significantly improved. CIHH may improve liver damage by promoting NCOA4-mediated ferritinophagy, reducing iron overload and oxidative stress, and thereby alleviating ferroptosis in MS rats.


Assuntos
Sobrecarga de Ferro , Síndrome Metabólica , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Hipóxia/metabolismo , Fígado/metabolismo , Ferro
19.
Aging (Albany NY) ; 15(17): 8976-8992, 2023 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-37695739

RESUMO

OBJECTIVE: Our study aimed to reveal the molecular mechanisms underlying the regulation of cerebral infarction by herpes virus latency infection via the OTUD1/NF-κB signaling pathway using evidence-based medicine Meta-analysis and bioinformatics analysis. METHODS: We conducted a Meta-analysis by searching Pubmed, Embase, and Web of Science databases to evaluate the correlation between herpes virus infection and increased risk of cerebral infarction. We obtained wild-type or mutant herpes virus latent infection-related brain tissue datasets from the GEO database and performed differential analysis to identify differentially expressed genes (DEGs) in the brain tissue after herpes virus latent infection. We further conducted WGCNA co-expression analysis on the cerebral infarction-related datasets from the GEO database to obtain key module genes and intersect them with the DEGs. We used ROC curve analysis to identify the key gene OTUD1 for predicting the occurrence of cerebral infarction and combined correlation and pathway enrichment analyses to identify the downstream pathways regulated by OTUD1. RESULTS: Our meta-analysis revealed that herpes virus infection is associated with an increased risk of cerebral infarction. By integrating the differential analysis and WGCNA co-expression analysis of GEO chip data, we identified three key genes mediating cerebral infarction after herpes virus latent infection. ROC curve analysis identified the key gene OTUD1, and the correlation and pathway enrichment analyses showed that OTUD1 regulates the NF-κB signaling pathway to mediate cerebral infarction. CONCLUSION: Herpes virus latent infection promotes cerebral infarction by activating the OTUD1/NF-κB signaling pathway.


Assuntos
Infecção Latente , Acidente Vascular Cerebral , Viroses , Humanos , NF-kappa B , Transdução de Sinais , Acidente Vascular Cerebral/genética , Infarto Cerebral , Proteases Específicas de Ubiquitina
20.
Front Physiol ; 14: 1170537, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37576337

RESUMO

Objectives: The study aimed to examine the association of three anemia-related biomarkers with the adequacy of peritoneal dialysis (PD) in patients with chronic kidney disease (CKD). Methods: This study included 127 PD patients. The total Kt/V urea (Kt/V) was calculated according to the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. All patients were classified into two groups based on Kt/V, viz., adequate (Kt/V ≥1.7) and inadequate (Kt/V <1.7) groups. Effect sizes are expressed as odds ratios (ORs) and 95% confidence interval (CI). Results: After adjusting for age, gender, hypertension, diabetes, and PD duration, 20 g/L increment in hemoglobin (Hgb) was observed to significantly reduce the risk of inadequate PD by 19% (OR; 95% CI; P: 0.81; 0.70 to 0.95; 0.009), 5 g/L increment in the mean corpuscular hemoglobin concentration (MCHC) by 7% (0.93; 0.88 to 0.98; 0.009), and 5% increment in transferrin saturation (TS) by 23% (0.77; 0.64 to 0.94; 0.012). The gender-specific nomogram model was constructed by incorporating three significant anemia-related biomarkers and convenient influencing factors, and the prediction accuracy was good (concordance index (C-index): 0.686 for men and 0.825 for women). Conclusion: Our findings indicate that the deterioration of three anemia-related biomarkers (Hgb, MCHC, and TS) can precipitate the development of inadequate PD in Chinese patients with CKD.

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