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1.
Int J Mol Med ; 47(3)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33448312

RESUMO

Atrial fibrillation (AF) is one of the most common tachyarrhythmias observed in the clinic and is characterized by structural and electrical remodelling. Atrial fibrosis, an emblem of atrial structural remodelling, is a complex multifactorial and patient­specific process involved in the occurrence and maintenance of AF. Whilst there is already considerable knowledge regarding the association between AF and fibrosis, this process is extremely complex, involving intricate neurohumoral and cellular and molecular interactions, and it is not limited to the atrium. Current technological advances have made the non­invasive evaluation of fibrosis in the atria and ventricles possible, facilitating the selection of patient­specific ablation strategies and upstream treatment regimens. An improved understanding of the mechanisms and roles of fibrosis in the context of AF is of great clinical significance for the development of treatment strategies targeting the fibrous region. In the present review, a focus was placed on the atrial fibrosis underlying AF, outlining its role in the occurrence and perpetuation of AF, by reviewing recent evaluations and potential treatment strategies targeting areas of fibrosis, with the aim of providing a novel perspective on the management and prevention of AF.

2.
J Youth Adolesc ; 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33449287

RESUMO

Anxiety in youth has been found to be a risk factor for the development of psychological problems and psychiatric symptoms in adulthood. Interparental conflict is considered an important factor in the emergence of symptoms of youth anxiety because conflicts between parents negatively affect parent-child and sibling relationships. Whereas some meta-analyses have investigated the association between interparental conflict and youth anxiety, the exact roles of certain moderators in this association are still not fully clear. Based on the PRISMA method, the present study used a three-level meta-analysis to obtain reliable estimates of effect sizes and examined a range of moderators (sample, publication, study design and outcome, and assessment characteristics). After a systematic search for articles published before September 2020, the present study identified 38 studies, with 12,380 young people and 222 effect sizes. The analysis revealed a significant positive association between interparental conflict and youth anxiety. Moreover, the present study found a significant moderating effect of interparental conflict variable. More specifically, youth anxiety was more strongly associated with parents' use of overt conflict style than with their use of cooperative conflict style. Study design was also found to be a significant moderator of the association between interparental conflict and youth anxiety. This association was smaller in longitudinal than in cross-sectional studies. Finally, the present results demonstrated that informant of interparental conflict was a significant moderator. A stronger correlation between these two variables was found when interparental conflict was reported by children than by parents. The results support the growing consensus that interparental conflict should be addressed when treating youth anxiety.

3.
Curr Microbiol ; 2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33392671

RESUMO

Clear aligners are removable orthodontic appliances that cover the tooth surface. The microbial composition and pH of the inner surface of aligners directly affect the enamel health. In this study, eight subjects who used the same type of clear aligners were instructed to brush their teeth normally and to not clean their aligners until sampling. Saliva and the contents of the inner surface of the aligners (liquid and plaque) were collected at 0 h (T0), 4 h (T4), 8 h (T8), 12 h (T12), and 24 h (T24) after usage, and pH values and microbial compositions were measured. The microbial composition was analyzed with 16S rRNA gene sequencing, and changes were assessed based on operational taxonomic unit abundance. The pH, alpha diversity values, and abundance of specific microbes on the inner surface of the aligners gradually decreased from T0 to T24 (P < 0.05). An insignificant increase in microbial community beta diversity was observed from T0 to T24. Principal component analysis revealed that the microbial composition at T0 was different from at T12 and T24. The relative abundances of phylum Firmicutes (P < 0.01), orders Lactobacillales and Bacteroidales (P < 0.05), and genus Streptococcus and species Streptococcus infantis increased significantly, while those of genera Actinomyces and Rothia and species Rothia aeria decreased significantly at T24 (P < 0.05). These findings reveal that uncleaned aligners might lead to enamel damage, especially after continuous usage for 12 h. Thus, clear aligners should be cleaned after 12 h of usage or at least within 24 h of usage.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33409963

RESUMO

Transforming growth factor-ß1 signaling pathways are known to involve in the development of post-infarction fibrosis, a process characterized by the aberrant activation, proliferation, and differentiation of fibroblasts, as well as the unbalanced turnover of extracellular matrix proteins. Recent studies have shown that Lefty1, a novel member of TGF-ß superfamily, acts as a brake on the TGF-ß signaling pathway in non-cardiac tissues. However, its role in myocardial infarction (MI)-induced fibrosis and left ventricular remodeling has not been fully elucidated. Here, for the first time, we reported that Lefty1 alleviated post-MI fibroblast proliferation, differentiation, and secretion through suppressing p-Smad2 and p-ERK1/2 signaling pathways in vivo and in vitro. In MI mice or TGF-ß1-treated neonatal rat cardiac fibroblasts (CFBs), the expression of Lefty1 was upregulated. Adenovirus-mediated overexpression of Lefty1 significantly attenuated TGF-ß1-induced CFBs' proliferation, differentiation, and collagen production. Using the adeno-associated virus approach, we confirmed that Lefty1 attenuates MI-induced cardiac injury, as evidenced by the decreased infarct size and preserved cardiac function. These results highlight the importance of Lefty1 in the prevention of post-MI fibrosis and may help identify potential targets for therapeutic intervention of cardiac fibrosis. Graphical abstract.

5.
Nat Neurosci ; 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33432193

RESUMO

Alzheimer's disease (AD) is characterized by the selective vulnerability of specific neuronal populations, the molecular signatures of which are largely unknown. To identify and characterize selectively vulnerable neuronal populations, we used single-nucleus RNA sequencing to profile the caudal entorhinal cortex and the superior frontal gyrus-brain regions where neurofibrillary inclusions and neuronal loss occur early and late in AD, respectively-from postmortem brains spanning the progression of AD-type tau neurofibrillary pathology. We identified RORB as a marker of selectively vulnerable excitatory neurons in the entorhinal cortex and subsequently validated their depletion and selective susceptibility to neurofibrillary inclusions during disease progression using quantitative neuropathological methods. We also discovered an astrocyte subpopulation, likely representing reactive astrocytes, characterized by decreased expression of genes involved in homeostatic functions. Our characterization of selectively vulnerable neurons in AD paves the way for future mechanistic studies of selective vulnerability and potential therapeutic strategies for enhancing neuronal resilience.

6.
J Viral Hepat ; 2021 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-33452699

RESUMO

Hepatitis C virus infection (HCV) may be associated with a greater risk of cardiovascular disease (CVD), and the evidence for whether antiviral therapy for HCV could reduce the risk of CVD events is inconsistent. The aim of this meta-analysis was to investigate the association between anti-HCV treatment and the risk of CVD. We searched Pubmed, Embase, and Cochrane library databases from inception to August 20, 2020. The pooled hazard ratio (HR) with 95% confidence interval (CI) of the risk of CVD events [any CVD, coronary artery disease (CAD), and stroke] was calculated using the random-effects model. A total of eleven studies, including 309,470 subjects, were enrolled in this meta-analysis. Among those, four studies reported on any CVD between anti-HCV treated and untreated patients, five studies reported on CAD, and five studies reported on stroke. Also, five studies reported on any CVD between patients with sustained virological response (SVR) and without. Overall, antiviral therapy for HCV was associated with a reduced risk of any CVD (HR=0.64, 95% CI: 0.50-0.83), CAD (HR=0.73, 95% CI: 0.55-0.96), and stroke (HR=0.74, 95% CI: 0.64-0.86). Besides, we found that SVR was associated with a significant decrease in any CVD compared with non-SVR (HR=0.74, 95% CI: 0.60-0.92). In conclusion, this meta-analysis demonstrated that antiviral therapy for HCV was associated with a reduced risk of CVD events. In addition, the risk of CVD events was lower in individuals with SVR compared with those without SVR.

7.
Theranostics ; 11(6): 2550-2563, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33456559

RESUMO

Antibody-drug conjugates (ADCs) are being developed worldwide with the potential to revolutionize current cancer treatment strategies. Developing novel theranostic ADCs with therapeutic utility and imaging capability is an attractive and challenging subject that promises advances in the field of personalized medicine. In this work, we propose a bifunctional molecule-based strategy for the development of theranostic ADCs. Methods: We developed a theranostic ADC consisting of the anti-Her2 antibody Mil40, monomethyl auristatin E (MMAE) as the active payload, and a 7-amino-3-hydroxyethyl-coumarin (7-AHC)-based dipeptide linker, which functions as a novel bifunctional fluorescence probe that allows self-elimination cleavage in the presence of cathepsin B for payload release and fluorophore activation. The on-off fluorescence properties and the antitumor effect in vitro and in vivo were investigated. Results: A 48-fold fluorescence enhancement was observed within 1 h when the 7-AHC-based linker was exposed to cathepsin B. Cleavage upon exposure to cathepsin B allows MMAE and fluorophore intracellular release and the monitoring of MMAE distribution using confocal microscopy. Additionally, the newly developed ADC retains the advantages of traditional p-aminobenzyloxycarbonyl-containing ADCs, such as good stability (t1/2 > 7 days) and high activity in vitro (IC50 = 0.09-3.74 nM). Importantly, the theranostic ADC exhibited the equivalent antitumor efficacy to the marketed ADC T-DM1 in the classic breast cancer model. Conclusion: We suggest that the present strategy can be universally applied in all p-aminobenzyloxycarbonyl-containing ADCs. Overall, theranostic ADCs may play a role in developing new theranostic systems and promoting personalized medicine research.

8.
Biofabrication ; 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33440361

RESUMO

Bioprinting is a promising technology focusing on tissue manufacturing, whose vital problem is the precise assembly of multiple materials. As the primary solution, the extrusion-based multi-printhead bioprinting (MPB) method could cause material interface defects and inefficient motion time during multimaterial switching. We present a valve-based consecutive bioprinting (VCB) method to resolve these problems, containing an integrated precise switching printhead and a well-matched voxelated digital model. The rotary valve isolates the bio-inks' elastic potential energy in the cartridge from precision interface assembling based on the Maxwell viscoelastic model. We study the coordinated control approach of the valve rotation and pressure adjustment to actualize the seamless switching, leading to a controllable multimaterial interface, including boundary and suture. Furthermore, we compare the VCB method and MPB method, quantitatively and comprehensively, indicating that the VCB method obtained greater mechanical strength (increased by 44.37%) and higher printing efficiency (increased by 29.48%). As an exemplar, we fabricate a muscle-like tissue with vascular tree and suture interface encapsulating C2C12 and human dermal fibroblasts (HDFB) cells, then placed in complete medium with continuous perfusion for five days. Our study suggests that the VCB method is sufficient to fabricate heterogeneous tissues with complex multimaterial interfaces.

9.
Curr Microbiol ; 2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33388938

RESUMO

Strain YIM 132242T, isolated from lichen collected from Pu'er, Yunnan Province, China, was short-rod-shaped, Gram-reaction-negative, aerobic, catalase- and oxidase-positive. Growth of the strain was occurred at 10-39 °C (optimum, 28-35 °C), at pH 4.0-10.0 (optimum, pH 7.0-8.0) and at salinities of 0-8% (w/v) NaCl (optimum, 0-2%). Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain YIM 132242T belonged to the genus Paracoccus and had the highest levels of sequence similarity to Paracoccus aerius KCTC 42845T (97.0% similarity), Paracoccus sediminis CMB17T (96.8% similarity), and Paracoccus fontiphilus MVW-1T (96.4% similarity). The major fatty acid was identified as C18:1 ω7c (77.6%). The predominant respiratory quinone was ubiquinone-10 (Q-10). Polar lipid analysis indicated the presence of phosphatidylglycerol (PG), phosphatidylethanolamine (PE), phosphatidylcholine (PC), diphosphatidylglycerol (DPG), an unidentified lipid (L), and three unidentified phospholipids (PL1-PL3). Based on the draft genome sequence, the DNA G + C content of the strain was 67.1 mol%, and the values of average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) of strain YIM 132242T with Paracoccus aerius KCTC 42845T were 85.4% and 29.1%, respectively. On the basis of the data from this polyphasic characterization, strain YIM 132242T represents a novel species of the genus Paracoccus, for which the name Paracoccus lichenicola sp. nov. is proposed. The type strain is YIM 132242T (= KCTC 72463T = CGMCC1.17191T).

10.
Theranostics ; 11(3): 1162-1175, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391527

RESUMO

Introduction: Murine models provide microvascular insights into the 3-D network disarray seen in retinopathy and cardiovascular diseases. Light-sheet fluorescence microscopy (LSFM) has emerged to capture retinal vasculature in 3-D, allowing for assessment of the progression of retinopathy and the potential to screen new therapeutic targets in mice. We hereby coupled LSFM, also known as selective plane illumination microscopy, with topological quantification, to characterize the retinal vascular plexuses undergoing preferential obliteration. Method and Result: In postnatal mice, we revealed the 3-D retinal microvascular network in which the vertical sprouts bridge the primary (inner) and secondary (outer) plexuses, whereas, in an oxygen-induced retinopathy (OIR) mouse model, we demonstrated preferential obliteration of the secondary plexus and bridging vessels with a relatively unscathed primary plexus. Using clustering coefficients and Euler numbers, we computed the local versus global vascular connectivity. While local connectivity was preserved (p > 0.05, n = 5 vs. normoxia), the global vascular connectivity in hyperoxia-exposed retinas was significantly reduced (p < 0.05, n = 5 vs. normoxia). Applying principal component analysis (PCA) for auto-segmentation of the vertical sprouts, we corroborated the obliteration of the vertical sprouts bridging the secondary plexuses, as evidenced by impaired vascular branching and connectivity, and reduction in vessel volumes and lengths (p < 0.05, n = 5 vs. normoxia). Conclusion: Coupling 3-D LSFM with topological quantification uncovered the retinal vasculature undergoing hyperoxia-induced obliteration from the secondary (outer) plexus to the vertical sprouts. The use of clustering coefficients, Euler's number, and PCA provided new network insights into OIR-associated vascular obliteration, with translational significance for investigating therapeutic interventions to prevent visual impairment.

11.
ESC Heart Fail ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33403776

RESUMO

AIMS: This study sought to compare healthcare quality and 30 day, 90 day, and 1 year mortality rates among patients admitted to secondary and tertiary hospitals for heart failure (HF) in Beijing. METHODS AND RESULTS: This study retrospectively enrolled patients hospitalized with a primary discharge diagnosis of HF during January 2014 to December 2015, from five tertiary and four secondary hospitals, in Beijing, China. Mortality data were extracted from Beijing Death Surveillance Database. HF healthcare quality indices were used to evaluate in-hospital care. Associations between hospital level and mortality rates were assessed using generalized linear mixed models, adjusting for patients' baseline characteristics and intra-hospital correlation. Data from 1413 patients (median [interquartile range] age = 74 [65-80] years, 52.7% female) from secondary hospitals and 1250 patients (median [interquartile range] age = 72 [61-79] years, 43.3% female) from tertiary hospitals were collected. Rates of left ventricular ejection fraction assessment (73.2% vs. 90.1%) and combined use of ß-blockers and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (30.1% vs. 49.3%) were lower in secondary hospitals than those in tertiary hospitals, respectively. Patients admitted to secondary hospitals had a higher 90 day mortality [10.8% vs. 5.0%; adjusted odds ratio (OR): 2.06; 95% confidence interval (CI): 1.10-3.84, P = 0.024 and a higher 1 year mortality rate [21.0% vs. 12.1%; adjusted OR: 1.64; 95% CI: 1.02-2.62, P = 0.039], but 30 day mortality rates were not significantly different (5.5% vs. 3.0%; adjusted OR: 1.49; 95% CI: 0.63-3.52, P = 0.368). CONCLUSIONS: Worse quality of care for patients with HF in secondary hospitals was associated with higher 90 day and 1 year mortality rates. Improving care quality in secondary hospitals is crucial to improve prognosis of patients they served.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33035604

RESUMO

Alzheimer's disease (AD) is the most common neurodegenerative disease in elderly population and the leading cause of dementia worldwide. While senile plaques and neurofibrillary tangles have been proposed as the principal histopathologic hallmarks of AD, the exact etiology of this disease is still far from being clearly understood. AD has been recognized as pathological consequences of complex interactions among genetic, aging, medical, life style and psychosocial factors. Recently, the roles of neuroticism personality traits in AD incidence and progression have come into focus. More specifically, increasing evidence has further shown that the trait anxiety, one major component of neuroticism predicting the individual vulnerability in response to stress, is a risk factor for AD and may correlated with various AD pathologies. In this review, we summarized recent literature on the association of trait anxiety with AD. We also discussed the possible neuroendocrinological and neurochemical mechanisms of this association, which may provide clinical implications for AD diagnosis and therapy.

13.
Neurosurgery ; 88(2): 322-331, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33017018

RESUMO

BACKGROUND: Lumbosacral spondylolisthesis-induced scoliosis is a rare clinical entity. Sagittal reconstruction and the coronal curve evolution after surgery for spondylolisthesis have not been investigated in depth. OBJECTIVE: To compare the curve characteristics between sciatic scoliosis and olisthetic scoliosis and to further investigate the effects of lumbosacral transforaminal lumbar interbody fusion (TLIF) on scoliosis evolution. METHODS: Adolescents with sciatic scoliosis group (SS group) or olisthetic scoliosis group (OS group) who underwent L5/S1 TLIF from 2010 to 2017 and were followed up for at least 2 yr were retrospectively reviewed. Radiographic parameters and patient-reported outcomes were evaluated. RESULTS: There were 20 patients in the SS group (M/F: 8/12; age: 15.6 ± 2.2 yr) and 16 in the OS group (M/F: 6/10; age: 16.8 ± 2.5 yr). Both groups had similar preoperative Cobb angles, but more patients with coronal imbalance were observed in the SS group. Moreover, the OS group showed significantly larger L5 tilt and rotation. After surgery, the slip reduction rate of the SS group and OS group were 76.1% ± 12.4% and 79.4% ± 9.6%, respectively. Scoliosis resolution was observed in all patients in the SS group but only in 9 patients (56.2%) in the OS group. Patients with failed scoliosis resolution in the OS group were older and had a larger Cobb angle and L5 rotation compared with those with successful scoliosis resolution. CONCLUSION: Lumbosacral TLIF can achieve satisfactory slip reduction and scoliosis resolution. Sciatic scoliosis often presents with coronal imbalance but also a preferable curve prognosis. A large Cobb angle and L5 rotation may hinder the resolution of olisthetic scoliosis.

14.
Food Chem ; 335: 127564, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32738541

RESUMO

To fully understand the properties of piscine stefins (family I cystatins), the 294-bp stefinA gene from grass carp (Ctenopharyngodon idella, Ci) was cloned and expressed in E. coli BL21 (DE3). After purification by Ni2+-NTA agarose affinity chromatography, the CiStefin A protein was tested to have a molecular weight of 11.48 kDa and an isoelectric point of 8.7. The typical motif of the cystatins superfamily was characterized from CiStefin A (QVVQG). CiStefin A specifically inhibited the activity of papain and cathepsin B/L. The Ki value of CiStefin A against papain was 6.5 × 10-11 M. CiStefin A showed excellent heat and acid-base tolerance. StefinA gene transcription occurred in all tested tissues of grass carp, with the highest level in the hepatopancreas. Immunolocalization staining with an anti-CiStefinA antibody revealed the CiStefinA protein distribution in all tested tissues at various levels. Overall, these results clarified the physical and biochemical properties of grass carp stefin A.


Assuntos
Carpas/genética , Cistatina A/genética , Cistatina A/metabolismo , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Animais , Clonagem Molecular , Escherichia coli/genética , Expressão Gênica , Filogenia , Transporte Proteico
15.
J Ethnopharmacol ; 265: 113251, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32810615

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Application of cyclosporine A (CsA) as a rescue treatment in acute severe ulcerative colitis (UC) is limited by its narrow therapeutic window and great interpatient variability. As a substrate of cytochrome P450 3A enzyme (CYP3A) and P-glycoprotein (P-gp), the oral pharmacokinetics of CsA is susceptible to disease status and concomitant medications. Combined treatment with ginseng, a famous medicinal herb frequently prescribed for ameliorating abnormal immune response in many diseases including UC, showed immunologic safety in CsA-based immunosuppression. AIM OF THE STUDY: Since the therapeutic levels of CsA can be achieved within 24 h, this study first assessed the impact of acute colitis and ginseng intervention on the single oral dose pharmacokinetics of CsA and explored the underlying mechanisms in dextran sulfate sodium (DSS)-induced colitis rats and Caco-2 cells. MATERIALS AND METHODS: Rats received drinking water (normal group), 5% DSS (UC group), or 5% DSS plus daily oral ginseng extract (GS+UC group). On day 7, GS+UC group only received an oral dose of CsA (5 mg/kg), while animals of normal or UC group received an oral, intravenous (1.25 mg/kg), or intraperitoneal dose of CsA (1.25 mg/kg), respectively. Blood, liver/intestine tissues and fecal samples were collected for determining CsA and main hydroxylated metabolite HO-CsA or measuring hepatic/intestinal CYP3A activity. Caco-2 cells were incubated with gut microbial culture supernatant (CS) of different groups or ginseng (decoction or polysaccharides), and then CYP3A, P-gp and tight junction (TJ) proteins were determined. RESULTS: Oral CsA exhibited enhanced absorption, systemic exposure and tissue accumulation, and lower fecal excretion, while intravenous or intraperitoneal CsA showed lower systemic exposure and enhanced distribution, in colitis rats. Diminished intestinal and hepatic P-gp expression well explained the changes with DSS-induced colitis. Moreover, blood exposures of HO-CsA in both normal and colitis after oral dosing were significantly higher than intravenous/intraperitoneal dosing, supporting the dominant role of intestinal first-pass metabolism. Interestingly, colitis reduced CYP3A expression in intestine and liver but only potentiated intestinal CYP3A activity, causing higher oral systemic exposure of HO-CsA. Oral ginseng mitigated colitis-induced down-regulation of CYP3A and P-gp expression, facilitated HO-CsA production, biliary excretion and colonic sequestration of CsA, while not affected CsA oral systemic exposure. In Caco-2 cells, gut microbial CS from both colitis and GS+UC group diminished P-gp function, while ginseng polysaccharides directly affected ZO-1 distribution and suppressed TJ proteins expression, explaining unaltered oral CsA systemic exposure. CONCLUSIONS: DSS-induced colitis significantly altered oral CsA disposition through regulating intestinal and hepatic P-gp and CYP3A. One-week ginseng treatment enhanced colonic accumulation while not altered the systemic exposure of CsA after single oral dosing, indicating pharmacokinetic compatibility between the two medications.

16.
J Ethnopharmacol ; 265: 113271, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32853742

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cyclophosphamide (CTX) is a first line chemotherapeutic agent, but often limited for its unstable therapeutic effect and serious side effects. Ginsenosides could facilitate the anti-tumor efficiency of CTX, including benefiting therapeutic effect and decreasing side effects. AIM OF THE STUDY: To investigate the potential mechanism of ginsenosides on benefiting the anti-tumor efficiency of CTX. MATERIALS AND METHODS: Mammary carcinoma mice were applied to investigate the anti-tumor efficiency and potential mechanism of combinational treatment of ginsenosides and CTX. Therapeutic effect was evaluated based on survival rate, tumor burden, tumor growth inhibition rate, and apoptosis and histological changes of tumor tissues. Anti-tumor immunity was studied by measuring serum level of anti-tumor cytokines. Gut mucositis, one of lethal side effects of CTX, was evaluated by diarrhea degree, gut permeability and tight junction proteins expressions. Gut microbial diversity was analyzed by 16S rRNA gene sequencing, and fecal transplant and antibiotics sterilized animals were performed to evaluate the therapeutic effect of gut microbiota on tumor suppression. RESULTS: Ginsenosides facilitated the therapeutic effect of CTX in mice, which manifested as prolonged survival rate, decreased tumor burden, as well as enhanced tumor growth inhibition rate and apoptosis. The favoring effect was related to elevation of anti-tumor immunity which manifested as the increased anti-tumor cytokines (INF-γ, IL-17, IL-2 and IL-6). Further studies indicated the elevation was ascribed to ginsenosides promoted reproduction of gut probiotics including Akkermansia, Bifidobacterium and Lactobacillus. Moreover, co-administration of ginsenosides in mice alleviated CTX-induced gut mucositis, including lower gut permeability, less diarrhea, less epithelium damage and higher tight junction proteins. Further researches suggested the alleviation was related to ginsenosides activated Nrf2 and inhibited NFκB pathways. CONCLUSION: Ginsenosides show dual roles to facilitate the anti-tumor efficiency of CTX, namely promote the anti-tumor immunity through maintaining gut microflora and ameliorate gut mucositis by modulating Nrf2 and NFκB pathways.

17.
Phytomedicine ; 81: 153436, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33360346

RESUMO

BACKGROUND: Depression is a pervasive or persistent mental disorder that causes mood, cognitive and memory deficits. Uncaria rhynchophylla has been widely used to treat central nervous system diseases for a long history, although its efficacy and potential mechanism are still uncertain. PURPOSE: The present study aimed to investigate anti-depression effect and potential mechanism of U. rhynchophylla extract (URE). STUDY DESIGN AND METHODS: A mouse depression model was established using unpredictable chronic mild stress (UCMS). Effects of URE on depression-like behaviours, neurotransmitters, and neuroendocrine hormones were investigated in UCMS-induced mice. The potential target of URE was analyzed by transcriptomics and bioinformatics methods and validated by RT-PCR and Western blot. The agonistic effect on 5-HT1A receptor was assayed by dual-luciferase reporter system. RESULTS: URE ameliorated depression-like behaviours, and modulated levels of neurotransmitters and neuroendocrine hormones, including 5-hydroxytryptamine (5-HT), 5-hydroxyindole acetic acid (5-HIAA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), corticosterone (CORT), corticotropin-releasing hormone (CRH), and adrenocorticotropic hormone (ACTH), in UCMS-induced mice. Transcriptomics and bioinformatics results indicated that URE could regulate glutamatergic, cholinergic, serotonergic, and GABAergic systems, especially neuroactive ligand-receptor and cAMP signaling pathways, revealing that Htr1a encoding 5-HT1A receptor was a potential target of URE. The expression levels of downstream proteins of 5-HT1A signaling pathway 5-HT1A, CREB, BDNF, and PKA were increased in UCMS-induced mice after URE administration, and URE also displayed an agonistic effect against 5-HT1A receptor with an EC50 value of 17.42 µg/ml. CONCLUSION: U. rhynchophylla ameliorated depression-like behaviours in UCMS-induced mice through activating 5-HT1A receptor.

18.
Environ Pollut ; 268(Pt B): 115676, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33038572

RESUMO

Little is known about interactive effects of pH-aluminum (Al) on reactive oxygen species (ROS) and methylglyoxal (MG) metabolisms in plants. Citrus sinensis seedlings were fertilized with nutrient solution at an Al concentration of 1 or 0 mM and a pH of 4.0, 3.5, 3.0 or 2.5 for 18 weeks. Thereafter, gas exchange and chlorophylls in leaves, H2O2 generation, electrolyte leakage, total soluble proteins, MG, malondialdehyde (MDA), antioxidants, sulfur-containing compounds, enzymes [viz., antioxidant enzymes, sulfur metabolism-related enzymes, ascorbate oxidase, phosphomannose isomerase, glyoxalase I and glyoxalase II] involved in ROS and MG detoxification in leaves and roots were measured. Effects of low pH and Al-toxicity on these parameters displayed obvious synergism. Without Al-toxicity, low pH increased H2O2 production, electrolyte leakage, MDA and MG concentrations by 45.7%-90.3% (52.4%-73.6%), 24.3%-74.5% (26.7%-86.2%), 18.6%-44.8% (35.6%-53.7%) and 16.3%-47.1% (13.8%-51.7%) in leaves (roots) relative to pH 4, respectively; low pH-induced upregulation of enzymes involved in ROS and MG detoxification and sulfur-containing compounds in leaves and/or roots could not protect them against oxidative damage. At pH 2.5-3.0, Al-toxicity increased H2O2 production, electrolyte leakage, MDA and MG concentrations by 34.2%-35.5% (23.9%-72.7%), 10.2%-29.5% (23.7%-56.8%), 15.6%-35.7% (27.5%-33.9%) and 21.5%-26.8% (21.0%-49.2%) in leaves (roots), respectively, and decreased total soluble protein concentration by 46.2%-47.4% (18.8%-20.8%) in leaves (roots); at pH 3.5-4.0, Al-toxicity did not affect significantly the five parameters in leaves and roots except for Al-induced increases in root MDA concentration at pH 3.5-4.0 and root electrolyte leakage at pH 3.5, and Al-induced decrease in root total soluble protein concentration at pH 4.0. Raised pH conferred the ability to maintain a balance between production and detoxification of ROS and MG in leaves and roots, thus protecting them against oxidative damage, and hence alleviating Al-induced increase in electrolyte leakage and decrease in total soluble protein level.


Assuntos
Citrus sinensis , Citrus , Alumínio/toxicidade , Antioxidantes , Peróxido de Hidrogênio , Concentração de Íons de Hidrogênio , Folhas de Planta , Raízes de Plantas , Aldeído Pirúvico/toxicidade , Espécies Reativas de Oxigênio , Plântula
19.
J Eukaryot Microbiol ; 68(1): e12822, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32770809

RESUMO

The morphology and phylogeny of two metopid ciliates, collected from anaerobic habitats in China, were investigated using live observation, protargol staining method, and SSU rDNA sequencing. The new species Metopus paravestitus nov. spec. can be distinguished by a combination of the following features: oblong cell with densely arranged ectobiotic prokaryotes perpendicular to cell surface, filiform intracytoplasmic structures packed in the anterior portion of the cell. Our work also demonstrates the wide geographical distribution of Metopus es (Müller, 1776) Lauterborn, 1916. The order Metopida is consistently depicted as a paraphylum in SSU rDNA phylogeny. Metopus paravestitus nov. spec. is closely related to its marine congeners than to freshwater forms. The present study confirms once again the non-monophyly of the genus Metopus and genus Metopidae.

20.
Eur J Drug Metab Pharmacokinet ; 46(1): 93-104, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32894450

RESUMO

BACKGROUND AND OBJECTIVE: Ginseng is usually consumed as a dietary supplement for health care in the normal state or prescribed as a herbal medicine in pathologic conditions. Although metabolic studies of ginseng are commonly performed on healthy organisms, the metabolic characteristics in pathologic organisms remain unexplored. This study aimed to uncover the difference in intestinal metabolism of ginseng between normal and cyclophosphamide-induced immunosuppressed rats and further discuss the potential mechanisms involved. METHODS: Twelve Sprague-Dawley rats (6-8 weeks old) were randomly divided into two groups: the normal group (NG) and immunosuppressed group (ISG). Rats in the NG and ISG groups were intraperitoneally administered normal saline and cyclophosphamide injections (40 mg/kg) on the 1st, 2nd, 3rd and 10th days; on the 12th day, all rats were intragastrically administered ginseng water extract (900 mg/kg). The difference in intestinal metabolism of ginseng was compared using an ultra-high-performance liquid chromatography coupled with quadruple time-of-flight mass spectrometry-based metabolomics approach, and the diversities of gut microbiota were analyzed by 16S rRNA gene sequencing between the two groups. RESULTS: The intestinal metabolomic characteristics of ginseng were significantly different between the normal and immunosuppressed rats, with the ginsenoside F2 (F2), 20S-ginsenoside Rg3 (20(S)-Rg3), pseudo-ginsenoside Rt5 (Pseudo-Rt5), ginsenoside Rd (Rd), ginsenoside Rh1 (Rh1), 20S-ginsenoside Rg1 (20(S)-Rg1), ginsenoside compound K (CK), ginsenoside Rg2 (Rg2) and 20S-panaxatriol (S-PPT) more abundant in immunosuppressed ones (P < 0.05). Additionally, the composition of gut microbiota was remarkably altered in the two groups, with some specific bacterial communities such as Bacteroides spp., Eubacterium spp. and Lachnospiraceae_UCG-010 spp. increased and Bifidobacterium spp. decreased in immunosuppressed rats compared with normal ones. CONCLUSION: The intestinal metabolism of ginseng in immunosuppressed rats was significantly different from that in normal ones, which might be partly attributed to the changes in the intensity of specific gut bacteria. The outcomes of this study could provide scientific data for rationalization of ginseng use as both a dietary supplement and herbal medicine.

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