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1.
Front Comput Neurosci ; 15: 698386, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34776913

RESUMO

The oscillatory patterns of electroencephalography (EEG), during resting states, are informative and helpful in understanding the functional states of brain network and their contribution to behavioral performances. The aim of this study is to characterize the functional brain network alterations in patients with amnestic mild cognitive impairment (aMCI). To this end, rsEEG signals were recorded before and after a cognitive task. Functional connectivity metrics were calculated using debiased weighted phase lag index (DWPLI). Topological features of the functional connectivity network were analyzed using both the classical graph approach and minimum spanning tree (MST) algorithm. Subsequently, the network and connectivity values together with Mini-Mental State Examination cognitive test were used as features to classify the participants. Results showed that: (1) across the pre-task condition, in the theta band, the aMCI group had a significantly lower global mean DWPLI than the control group; the functional connectivity patterns were different in the left hemisphere between two groups; the aMCI group showed significantly higher average clustering coefficient and the remarkably lower global efficiency than the control. (2) Analysis of graph measures under post-task resting state, unveiled that for the percentage change of post-task vs. pre-task in beta EEG, a significant increase in tree hierarchy was observed in aMCI group (2.41%) than in normal control (-3.89%); (3) Furthermore, the classification analysis of combined measures of functional connectivity, brain topology, and MMSE test showed improved accuracy compared to the single method, for which the connectivity patterns and graph metrics were used as separate inputs. The classification accuracy obtained for the case of post-task resting state was 87.2%, while the one achieved under pre-task resting state was found to be 77.7%. Therefore, the functional network alterations in aMCI patients were more prominent during the post-task resting state. This study suggests that the disintegration observed in MCI functional network during the resting states, preceding and following a task, might be possible biomarkers of cognitive dysfunction in aMCI patients.

2.
Front Pharmacol ; 12: 742954, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803688

RESUMO

Thrombosis is a general pathological phenomenon during severe disturbances to homeostasis, which plays an essential role in cardiovascular and cerebrovascular diseases. Leonurine (LEO), isolated from Leonurus japonicus Houtt, showes a crucial role in anticoagulation and vasodilatation. However, the properties and therapeutic mechanisms of this effect have not yet been systematically elucidated. Therefore, the antithrombotic effect of LEO was investigated in this study. Hematoxylin-Eosin staining was used to detect the thrombosis of zebrafish tail. Fluorescence probe was used to detect the reactive oxygen species. The biochemical indexes related to oxidative stress (lactate dehydrogenase, malondialdehyde, superoxide dismutase and glutathione) and vasodilator factor (endothelin-1 and nitric oxide) were analyzed by specific commercial assay kits. Besides, we detected the expression of related genes (fga, fgb, fgg, pkcα, pkcß, vwf, f2) and proteins (PI3K, phospho-PI3K, Akt, phospho-Akt, ERK, phospho-ERK FIB) related to the anticoagulation and fibrinolytic system by quantitative reverse transcription and western blot. Beyond that, metabolomic analyses were carried out to identify the expressions of metabolites associated with the anti-thrombosis mechanism of LEO. Our in vivo experimental results showed that LEO could improve the oxidative stress injury, abnormal platelet aggregation and coagulation dysfunction induced by adrenalin hydrochloride. Moreover, LEO restored the modulation of amino acids and inositol metabolites which are reported to alleviate the thrombus formation. Collectively, LEO attenuates adrenalin hydrochloride-induced thrombosis partly via modulating oxidative stress, coagulation cascade and platelet activation and amino acid and inositol metabolites.

3.
Front Pharmacol ; 12: 771459, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803712

RESUMO

Liver diseases have been a common challenge for people all over the world, which threatens the quality of life and safety of hundreds of millions of patients. China is a major country with liver diseases. Metabolic associated fatty liver disease, hepatitis B virus and alcoholic liver disease are the three most common liver diseases in our country, and the number of patients with liver cancer is increasing. Therefore, finding effective drugs to treat liver disease has become an urgent task. Chinese medicine (CM) has the advantages of low cost, high safety, and various biological activities, which is an important factor for the prevention and treatment of liver diseases. This review systematically summarizes the potential of CM in the treatment of liver diseases, showing that CM can alleviate liver diseases by regulating lipid metabolism, bile acid metabolism, immune function, and gut microbiota, as well as exerting anti-liver injury, anti-oxidation, and anti-hepatitis virus effects. Among them, Keap1/Nrf2, TGF-ß/SMADS, p38 MAPK, NF-κB/IκBα, NF-κB-NLRP3, PI3K/Akt, TLR4-MyD88-NF-κB and IL-6/STAT3 signaling pathways are mainly involved. In conclusion, CM is very likely to be a potential candidate for liver disease treatment based on modern phytochemistry, pharmacology, and genomeproteomics, which needs more clinical trials to further clarify its importance in the treatment of liver diseases.

5.
Eur J Pharmacol ; 912: 174604, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34743980

RESUMO

Betaine is a kind of water-soluble quaternary amine-type alkaloid widely existing in food, such as wheat germ, beet, spinach, shrimp and wolfberry. As an important methyl donor and osmotic pressure regulator in human body, betaine plays an important role in a variety of physiological activities. In recent years, a large number of literatures have shown that betaine has good preventive and therapeutic effects on many liver diseases, including chemical or drug-induced liver injury, nonalcoholic fatty liver disease, alcoholic fatty liver disease, liver fibrosis, hepatitis B and hepatitis C. Therefore, by searching the databases of Web of Science, PubMed, SciFinder and CNKI, this paper has summarized the molecular mechanisms of betaine in improving liver diseases. The results show that the improvement of liver diseases by betaine is closely related to a variety of molecular mechanisms, including inhibition of inflammatory response, improvement of insulin resistance, reduction of endoplasmic reticulum stress, alleviation of liver oxidative stress, increase of autophagy, remodeling of intestinal flora and regulation of epigenetic modification. More importantly, nuclear transcription factor kappa (NF-κB), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor α/γ (PPAR-α/γ), liver X receptor α (LXRα), protein kinase B (Akt), toll-like receptor 4 (TLR4) and cysteinyl aspartate specific proteinase-3 (Caspase-3) signaling pathways are considered as important molecular targets for betaine to improve liver diseases. These important findings will provide a direction and basis for further exploring the pathogenesis of various liver diseases and tapping the potential of betaine in the clinical treatment.

6.
Anal Chem ; 93(45): 14940-14945, 2021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-34735112

RESUMO

A disulfide bond is an important protein post-translational modification and plays a key role in regulating protein oxidation status, protein structure, and stability. Analysis of a disulfide bond using mass spectrometry is challenging because there lacks an efficient method to separate the disulfide-linked peptides from a complex protein digest, and the MS data requires sophisticated interpretation. Here, we developed a novel disulfide bond identification strategy, termed as "carboxypeptidase Y assisted disulfide-bond identification (CADI)". CADI is able to significantly reduce sample complexity by depleting ∼90% of the linear peptides while keeping the disulfide-bonded peptides. Furthermore, all CADI data can be directly analyzed by widely used protein database search engines, such as Mascot and MaxQuant. Our data show that CADI is able to sensitively identify disulfide bonds in peptides and proteins. However, CADI has not yet achieved a satisfied in-depth coverage on complex mammalian cell lysates due to the limited enzymatic activity of carboxypeptidase Y and low occurrences of disulfide bonds in a proteome. Altogether, CADI is a useful method that can get disulfide-linked peptides enriched and analyzed with regular search engines. CADI holds great potentials to deepen the analysis of disulfide bond and other types of cross-linked peptides on the proteome scale.


Assuntos
Dissulfetos , Proteoma , Sequência de Aminoácidos , Animais , Catepsina A , Bases de Dados de Proteínas
7.
Mol Psychiatry ; 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34697451

RESUMO

TDP-43 proteinopathy is linked to neurodegenerative diseases that feature synaptic loss in the cortex and hippocampus, although it remains unclear how TDP-43 regulates mature synapses. We report that, in adult mouse hippocampus, TDP-43 knockdown, but not overexpression, induces robust structural and functional damage to excitatory synapses, supporting a role for TDP-43 in maintaining mature synapses. Dendritic spine loss induced by TDP-43 knockdown is rescued by wild-type TDP-43, but not ALS/FTLD-associated mutants, suggesting a common TDP-43 functional deficiency in neurodegenerative diseases. Interestingly, M337V and A90V mutants also display dominant negative activities against WT TDP-43, partially explaining why M337V transgenic mice develop hippocampal degeneration similar to that in excitatory neuronal TDP-43 knockout mice, and why A90V mutation is associated with Alzheimer's disease. Further analyses reveal that a TDP-43 knockdown-induced reduction in GluN2A contributes to synaptic loss. Our results show that loss of TDP-43 function underlies hippocampal and cortical synaptic degeneration in TDP-43 proteinopathies.

8.
Front Pharmacol ; 12: 756924, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621179

RESUMO

Liver fibrosis is a chronic pathological process that various pathogenic factors lead to abnormal hyperplasia of hepatic connective tissue, and its main feature is the excessive deposition of extracellular matrix. However, there are currently no drugs approved for the treatment of liver fibrosis. Phillygenin (PHI), a lignan isolated from Forsythiae Fructus, showed potential anti-inflammatory and anti-fibrosis effects but the mechanisms remain unknown. In view of the vital role of gut microbiota in the development of liver fibrosis, this study aimed to explore whether PHI could protect intestinal epithelial barrier and attenuate liver fibrosis by maintaining the homeostasis of intestinal microbiota. Therefore, the liver fibrosis model was induced by intraperitoneal injection of olive oil containing 10% carbon tetrachloride (CCl4) for 4 weeks in C57BL/6J mice. Histological analysis including Hematoxylin-Eosin, Masson, Sirius red, and immunohistochemistry staining were carried out to detect the histopathology and collagen deposition of mice liver tissues. The biochemical indexes related to liver function (ALT, AST, AKP, γ-GT), fibrosis (HYP, HAase, LN, PC III, IV-C) and inflammation (TNF-α, MIP-1, LPS) were determined by specific commercial assay kits. In vivo experimental results showed that PHI could improve liver histopathological injury, abnormal liver function, collagen deposition, inflammation and fibrosis caused by CCl4. Moreover, PHI restored the intestinal epithelial barrier by promoting the expression of intestinal barrier markers, including ZO-1, Occludin and Claudin-1. More importantly, the corrective effect of PHI on the imbalance of gut microbiota was confirmed by sequencing of the 16 S rRNA gene. In particular, PHI treatment enriches the relative abundance of Lactobacillus, which is reported to alleviate inflammation and fibrosis of damaged liver. Collectively, PHI attenuates CCl4-induced liver fibrosis partly via modulating inflammation and gut microbiota.

9.
Cell Chem Biol ; 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34706270

RESUMO

Rapamycin is widely recognized as an inhibitor of mTOR, and has been approved for clinical use as an immunosuppressant. Its potencies in anti-cancer, anti-aging, and neurodegenerative diseases are emergingly established. The exploration of other targets of rapamycin will further elucidate its underlying mechanisms of action. In this study, we use a chemical proteomics strategy that has identified STAT3, a transcription factor considered to be undruggable, as a direct functional protein target of rapamycin. Together with other multi-dimensional proteomics data, we show that rapamycin treatment in cell culture significantly inhibits c-Myc-regulated gene expression. Furthermore, we show that rapamycin suppresses tumor growth along with a decreased expression of STAT3 and c-Myc in an in vivo xenograft mouse model for hepatocellular carcinoma. Our data suggest that rapamycin acts directly on STAT3 to decrease its transcription activity, providing important information for the pharmacological and pharmaceutical development of STAT3 inhibitors for cancer therapy.

10.
Clin Neurophysiol ; 132(11): 2861-2869, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34600244

RESUMO

OBJECTIVE: Resting-state EEG microstate is a promising neurophysiological tool to explore the temporal dynamics of cognitive activity. Till now, the microstate syntax is far from being fully understood in mild cognitive impairment (MCI) and Alzheimer's disease (AD). We aim to investigate the possible explanation for the alterations of transition probabilities in microstate syntax between different stages of cognitive impairment. METHODS: The artefact-corrected resting-state EEG in patients with MCI (n = 46), AD (n = 43) and healthy controls (HC, n = 43) were used for microstate analysis. Four microstates were labeled A-D according to the study (Koenig et al., 2002). RESULTS: Microstate duration, occurrence and coverage showed overall differences between HC, MCI and AD. Duration and coverage B increased significantly in AD compared with HC and MCI. Coverage C decreased significantly in AD compared with MCI. Microstate syntax had specialized single transitions in MCI and AD. Transitions between symmetrical (C and D) and asymmetrical (A and B) classes showed a decreased pattern. It was only in MCI that an increased transition from A to C was found and only in AD an increased transition from A to B was found. Besides, a negative spearman's correlation was found between the transition probability from A to B and Mini-Mental State Examination (MMSE) scores. CONCLUSION: Altered resting-state EEG microstates in particular specialized single transitions in microstate syntax were showed in MCI and AD. SIGNIFICANCE: For the first time, we discovered which single transitions between pairs of microstates play an important role in microstate syntax in different stages of cognitive impairment.


Assuntos
Doença de Alzheimer/diagnóstico , Doença de Alzheimer/fisiopatologia , Encéfalo/fisiopatologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/fisiopatologia , Eletroencefalografia/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
Br J Cancer ; 125(11): 1570-1581, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34671129

RESUMO

BACKGROUND: Genetic correlations, causalities and pathways between large-scale complex exposures and ovarian and breast cancers need systematic exploration. METHODS: Mendelian randomisation (MR) and genetic correlation (GC) were used to identify causal biomarkers from 95 cancer-related exposures for risk of breast cancer [BC: oestrogen receptor-positive (ER + BC) and oestrogen receptor-negative (ER - BC) subtypes] and ovarian cancer [OC: high-grade serous (HGSOC), low-grade serous, invasive mucinous (IMOC), endometrioid (EOC) and clear cell (CCOC) subtypes]. RESULTS: Of 31 identified robust risk factors, 16 were new causal biomarkers for BC and OC. Body mass index (BMI), body fat mass (BFM), comparative body size at age 10 (CBS-10), waist circumference (WC) and education attainment were shared risk factors for overall BC and OC. Childhood obesity, BMI, CBS-10, WC, schizophrenia and age at menopause were significantly associated with ER + BC and ER - BC. Omega-6:omega-3 fatty acids, body fat-free mass and basal metabolic rate were positively associated with CCOC and EOC; BFM, linoleic acid, omega-6 fatty acids, CBS-10 and birth weight were significantly associated with IMOC; and body fat percentage, BFM and adiponectin were significantly associated with HGSOC. Both GC and MR identified 13 shared factors. Factors were stratified into five priority levels, and visual causal networks were constructed for future interventions. CONCLUSIONS: With analysis of large-scale exposures for breast and ovarian cancers, causalities, genetic correlations, shared or specific factors, risk factor priority and causal pathways and networks were identified.

12.
Front Cell Dev Biol ; 9: 734046, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568342

RESUMO

Repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, has been considered as a potentially effective treatment for the cognitive impairment in patients with mild cognitive impairment (MCI) and Alzheimer's Disease (AD). However, the effectiveness of this therapy is still under debate due to the variety of rTMS parameters and individual differences including distinctive stages of AD in the previous studies. The current meta-analysis is aiming to assess the cognitive enhancement of rTMS treatment on patients of MCI and early AD. Three datasets (PubMed, Web of Science and CKNI) were searched with relative terms and finally twelve studies with 438 participants (231 in the rTMS group and 207 in the control group) in thirteen randomized, double-blind and controlled trials were included. Random effects analysis revealed that rTMS stimulation significantly introduced cognitive benefits in patients of MCI and early AD compared with the control group (mean effect size, 1.17; 95% CI, 0.76 - 1.57). Most settings of rTMS parameters (frequency, session number, stimulation site number) significantly enhanced global cognitive function, and the results revealed that protocols with 10 Hz repetition frequency and DLPFC as the stimulation site for 20 sessions can already be able to produce cognitive improvement. The cognitive enhancement of rTMS could last for one month after the end of treatment and patients with MCI were likely to benefit more from the rTMS stimulation. Our meta-analysis added important evidence to the cognitive enhancement of rTMS in patients with MCI and early AD and discussed potential underlying mechanisms about the effect induced by rTMS.

13.
BMC Genomics ; 22(1): 665, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34521340

RESUMO

BACKGROUND: It is important to resolve the evolutionary history of species genomes as it has affected both genome organization and chromosomal architecture. The rapid innovation in sequencing technologies and the improvement in assembly algorithms have enabled the creation of highly contiguous genomes. DNA Zoo, a global organization dedicated to animal conservation, offers more than 150 chromosome-length genome assemblies. This database has great potential in the comparative genomics field. RESULTS: Using the donkey (Equus asinus asinus, EAS) genome provided by DNA Zoo as an example, the scaffold N50 length and Benchmarking Universal Single-Copy Ortholog score reached 95.5 Mb and 91.6%, respectively. We identified the cytogenetic nomenclature, corrected the direction of the chromosome-length sequence of the donkey genome, analyzed the genome-wide chromosomal rearrangements between the donkey and horse, and illustrated the evolution of the donkey chromosome 1 and horse chromosome 5 in perissodactyls. CONCLUSIONS: The donkey genome provided by DNA Zoo has relatively good continuity and integrity. Sequence-based comparative genomic analyses are useful for chromosome evolution research. Several previously published chromosome painting results can be used to identify the cytogenetic nomenclature and correct the direction of the chromosome-length sequence of new assemblies. Compared with the horse genome, the donkey chromosomes 1, 4, 20, and X have several obvious inversions, consistent with the results of previous studies. A 4.8 Mb inverted structure was first discovered in the donkey chromosome 25 and plains zebra chromosome 11. We speculate that the inverted structure and the tandem fusion of horse chromosome 31 and 4 are common features of non-caballine equids, which supports the correctness of the existing Equus phylogeny to an extent.


Assuntos
Cromossomos Humanos Par 1 , Equidae , Animais , Cromossomos/genética , Cromossomos Humanos Par 5 , Equidae/genética , Genoma , Cavalos/genética , Humanos
14.
JACS Au ; 1(7): 1066-1075, 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34467350

RESUMO

Biocompatible reactions are powerful tools to probe protein functions in their native environment. Due to the difficulty of penetrating the live-cell membrane and the complex intracellular environment, the biocompatible reactions inside live cells are challenging, especially at the subcellular level with spatial resolution. Here we report the first biocompatible photocatalytic azide conjugation reaction inside live cells to achieve the mitochondria-selective proteins labeling. The organic dyes acridine orange, fluorescein, and rhodamine 123 were developed as the biocompatible photocatalysts for the proteins labeling with aryl azides, which yielded benzazirines and ketenimines from triplet nitrenes for the protein nucleophilic residue trapping. The photocatalytic azide conjugation reaction with rhodamine 123 selectively labeled the mitochondrial proteins via the organic dye's mitochondrial localization. In response to the mitochondrial stress induced by rotenone, this photocatalytic azide-promoted labeling method mapped the dynamic mitochondrial proteome changes with high temporal-spatial precision and identified several potential mitochondrial stress-response proteins for the first time. The high temporal-spatial precision of this photocatalytic azide-promoted labeling method holds excellent potential for intracellular protein network investigations.

15.
Am J Transl Res ; 13(8): 9315-9323, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540048

RESUMO

OBJECTIVE: To investigate the administration of early enteral nutrition combined with poisoning severity score (PSS)-based nursing in the treatment of organophosphorus pesticide poisoning (OPP). METHODS: A total of 99 OPP patients treated in our hospital between June 2019 and June 2020 were enrolled in this study and were divided into the conventional group (n=46, early enteral nutrition support + routine care) and the combined group (n=53, PSS-based nursing + early enteral nutrition support + routine care). The nutritional status indicators, the hemoglobin (Hb) and blood glucose levels, the Glasgow coma scale (GCS) scores, and the complications were compared between the two groups. RESULTS: The total protein (TP), albumin (ALB), and prealbumin (PAB) levels were reduced in the conventional group after the intervention (P<0.05) but were significantly lower than they were in the combined group (P<0.05). The Hb and blood glucose levels were decreased in the conventional group after the intervention (P<0.05) and were significantly higher than they were in the combined group (P<0.05). The GCS scores increased significantly as the treatment progressed (P<0.05), and the GCS scores in the combined group were significantly higher than the GCS scores in the conventional group at 3 and 5 days after the treatment (P<0.05). The time to the recovery of 60% cholinesterase (CHE) activity, the durations of the mechanical ventilation, the lengths of the hospital stays, and the hospital costs in the combined group were significantly lower than they were in the conventional group (P<0.05). The complication rate in the combined group (9.43%) was significantly lower than the complication rate in the conventional group (32.61%) (P<0.05). CONCLUSION: Early enteral nutrition combined with PSS-based nursing can effectively control the blood glucose, improve the nutritional disorders, promote recovery, and reduce complications in OPP patients.

16.
Curr Pharm Des ; 27(40): 4160-4170, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34477512

RESUMO

BACKGROUND: Vascular endothelial growth factor (VEGF) is a supergene family derived from a platelet growth factor. It plays a pivotal role in regulating angiogenesis and lymphangiogenesis. sFlt-1 is a soluble antagonist of VEGF with an essential effect of maintaining the balance of vascular growth. Recently, sFlt-1 has emerged as a new marker for early diagnosis and disease surveillance of angiogenesis-related diseases. However, few comprehensive reviews focus on the relationship between sFlt-1 and related diseases despite that many results have yielded. METHODS: In this review, we analyzed the relationship between sFlt-1 and angiogenesis-related diseases by searching PubMed, Web of Science, and other databases, and summarized our current understanding of the role of sFlt-1 in angiogenesis-related diseases. RESULTS: sFlt-1 is associated with pre-eclampsia, perinatal cardiomyopathy, diabetic nephropathy, hypertension, tumor, atherosclerosis, and other diseases. The mechanisms of sFlt-1 that regulate those diseases are mainly associated with the bioavailability of VEGF and vascular endothelial cell integrity. CONCLUSION: From the summary article, sFlt-1 is a double regulator in angiogenesis-related diseases; too much or too little may cause different diseases. Therefore, maintaining the stability of sFlt-1 content in the body is essential to control the development of related diseases.

17.
Eur J Pharmacol ; 910: 174447, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34461126

RESUMO

Cholestasis is a common manifestation of obstruction of bile flow in various liver diseases. If the bile acid accumulation is not treated in time, it will further lead to hepatocyte damage, liver fibrosis and ultimately to cirrhosis, which seriously affects human life. The pathogenesis of cholestatic liver injury is very complicated, mainly including oxidative stress and inflammation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important transcription factor responsible for upregulating expression of various genes with cytoprotective functions. Nrf2 activation has been proved to inhibit oxidative stress and inflammatory reaction, modulate bile acid homeostasis, and alleviate fibrosis during cholestasis. Therefore, Nrf2 emerges as a potential therapeutic target for cholestatic liver injury. In recent years, natural products with various biological activities including anti-inflammatory, anti-oxidant, anti-tumor and anti-fibrotic effects have received growing attention for being hepatoprotective agents. Natural products like asiatic acid, diosmin, rutin, and so forth have shown significant potential in activating Nrf2 pathway which can lead to attenuate cholestatic liver injury. Therefore, this paper emphasizes the effect of Nrf2 signaling pathway on alleviating cholestasis, and summarizes recent evidence about natural Nrf2 activators with hepatoprotective effect in various models of cholestatic liver injury, thus providing theoretical reference for the development of anti-cholestatic drug.

18.
J Appl Microbiol ; 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34411380

RESUMO

AIMS: Dietary protein, as an important macronutrient, widely participates in host growth and metabolism. In this study, effects of different protein levels (14, 20 and 26%) on the gut development, microbial compositions and mucin expressions were studied in C57BL/6 mice. METHODS AND RESULTS: The results showed that body weight and the relative weight of stomach and gut were decreased in low-protein diet-fed mice, whereas high-protein diet significantly reduced the villus length and area of jejunum. Goblet cells number in the jejunum was reduced in the low-protein group, which was reversed by dietary a high-protein diet. In addition, high-protein diet notably reduced microbial diversity and changed the microbial compositions at the phylum level, such as Bacteroides, Proteobacteria, Actinomycetes and Deferribacteres. Furthermore, high-protein diet significantly increased mucin2, mucin3 and mucin4 expressions in the jejunum, but downregulated mucin1, mucin2, mucin4 and TFF3 in the ileum, indicating a tissue-dependent manner. CONCLUSIONS: Together, high-protein diet may impair gut development, microbial balance and mucin system, and a low-protein diet is suggested to promote a healthy lifestyle. SIGNIFICANCE AND IMPACT OF STUDY: Mucin influenced gut development (villus index and goblet cell number) through remodelling gut microbes, as low and high protein levels resulted in contrary expression levels of mucin in jejunum and ileum.

19.
Phytomedicine ; 91: 153694, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34403879

RESUMO

BACKGROUND: Atherosclerosis is a chronic vascular inflammatory disease with complex pathogenesis. Its serious consequence is insufficient blood supply to heart and brain, which eventually leads to myocardial ischemia, infarction and stroke. Hydroxysafflor yellow A (HSYA), a single chalcone glycoside compound with a variety of pharmacological effects, which has shown a potential biological activity for prevention and treatment of atherosclerosis. PURPOSE: The main purpose of this review is to comprehensively elucidate the mechanism of HSYA on atherosclerosis and its risk factors (hyperlipidemia, hypertension and diabetes mellitus). METHOD: The literatures on HSYA in the treatment of atherosclerosis and its risk factors were searched in PubMed, Google Scholar, China National Knowledge Infrastructure, including in vitro (cell), in vivo (animal) and clinical (human) studies, and summarized reasonably. RESULTS: HSYA is a promising natural product for treating atherosclerosis. It can suppress foam cell formation, vascular endothelial cell dysfunction, vascular smooth muscle cell proliferation and migration, and platelet activation. The mechanisms are achieved by regulating the reverse cholesterol transport process, fatty acid synthesis, oxidative stress, PI3K/Akt/mTOR, NLRP3 inflammasome, TNFR1/NF-κB, NO-cGMP, Bax/Bcl-2, MAPKs, CDK/CyclinD and TLR4/Rac1/Akt signaling pathways. Besides, HSYA is devoted to lowering blood lipids, regulating ion channels, reducing vascular inflammation, and protecting pancreatic beta cells, which is conducive to reducing the harm of independent risk factors of atherosclerosis. CONCLUSIONS: HSYA exhibits the preventive and therapeutic effects on atherosclerosis and its risk factors in vivo and in vitro, which is relevant to multiple mechanisms. The clinical trials of HSYA need to be further investigated to provide a solid foundation for its clinical application.


Assuntos
Aterosclerose , Carthamus tinctorius , Chalcona , Quinonas , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Carthamus tinctorius/química , Chalcona/análogos & derivados , Chalcona/farmacologia , Humanos , Compostos Fitoquímicos/farmacologia , Quinonas/farmacologia
20.
Toxicol Lett ; 351: 37-52, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34454010

RESUMO

Acetaminophen (APAP), one of the most widely used antipyretic and analgesic drugs, principally contributes to drug-induced liver injury when taken at a high dose. APAP-induced liver injury (AILI) results in extensive necrosis of hepatocytes along with the occurrence of multiple intracellular events such as metabolic activation, cell injury, and signaling pathway activation. However, the specific role of the immune response in AILI remains controversial for its complicated regulatory mechanisms. A variety of inflammasomes, immune cells, inflammatory mediators, and signaling transduction pathways are activated in AILI. These immune components play antagonistic roles in aggravating the liver injury or promoting regeneration. Recent experimental studies indicated that natural products showed remarkable therapeutic effects against APAP hepatotoxicity due to their favorable efficacy. Therefore, this study aimed to review the present understanding of the immune response in AILI and attempted to establish ties among a series of inflammatory cascade reactions. Also, the immune molecular mechanisms of natural products in the treatment of AILI were extensively reviewed, thus providing a fundamental basis for exploring the potential pharmacological targets associated with immune interventions.


Assuntos
Acetaminofen/efeitos adversos , Analgésicos não Narcóticos/efeitos adversos , Produtos Biológicos/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Testes de Toxicidade/métodos , Animais , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Humanos
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