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1.
Bioact Mater ; 20: 81-92, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35633875

RESUMO

Stem cells from human exfoliated deciduous teeth (SHED) uniquely exhibit high proliferative and neurogenic potential. Charged biomaterials have been demonstrated to promote neural differentiation of stem cells, but the dose-response effect of electrical stimuli from these materials on neural differentiation of SHED remains to be elucidated. Here, by utilizing different annealing temperatures prior to corona poling treatment, BaTiO3/P(VDF-TrFE) ferroelectric nanocomposite membranes with varying charge polarization intensity (d 33 ≈ 0, 4, 12 and 19 pC N-1) were fabricated. Enhanced expression of neural markers, increased cell elongation and more prominent neurite outgrowths were observed with increasing surface charge of the nanocomposite membrane indicating a dose-response effect of surface electrical charge on SHED neural differentiation. Further investigations of the underlying molecular mechanisms revealed that intracellular calcium influx, focal adhesion formation, FAK-ERK mechanosensing pathway and neurogenic-related ErbB signaling pathway were implicated in the enhancement of SHED neural differentiation by surface electrical charge. Hence, this study confirms the dose-response effect of biomaterial surface charge on SHED neural differentiation and provides preliminary insights into the molecular mechanisms and signaling pathways involved.

2.
Macromol Rapid Commun ; : e2200293, 2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35696350

RESUMO

We explore the processing-structure-property relationship using poly(lactic acid) (PLA) and poly(ethylene terephthalate) (PET). Specifically, we show both pre-extension and pre-shear of amorphous PLA and PET above their glass transition temperatures Tg , carried out in the affine deformation limit, can induce a specific type of cold crystallization during annealing, i.e., nano-confined crystallization (NCC) where crystal sizes are limited to a nanoscopic scale in all dimensions so as to render the processed PLA and PET optically transparent. The new polymer structure after pre-melt deformation can show considerably enhanced mechanical properties. For example, pre-melt stretching produces geometric condensation of the chain network. This structural alternation can profoundly change the mechanical characteristics, e.g., turning brittle PLA ductile. In contrast, after pre-shear of amorphous PLA above Tg , the NCC containing PLA remains brittle, showing the importance to have geometric condensation from processing. Both AFM imaging and SAXS measurements have been carried to verify that pre-melt deformation of PLA and PET indeed results in NCC from annealing that permits the strain-induced cold crystallization to take place on the length scale of the mesh size of the deformed chain network. This article is protected by copyright. All rights reserved.

3.
J Genet Genomics ; 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35697272

RESUMO

Ferroptosis has emerged as a crucial regulated cell death involved in a variety of physiological processes or pathological diseases, such as tumor suppression. Though initially being found from anti-cancer drug screening and considered not essential as apoptosis for growth and development, numerous studies have demonstrated that ferroptosis is tightly regulated by key genetic pathways and/or genes, including several tumor suppressors and oncogenes. In this review, we will first introduce the basic concepts of ferroptosis, characterized by the features of non-apoptotic, iron-dependent and overwhelmed accumulation of lipid peroxides, and the underlying regulated circuits are considered to be pro-ferroptotic pathways. Then we discuss several established lipid peroxidation defending systems within cells, including SLC7A11/GPX4, FSP1/CoQ, GCH1/BH4, and mitochondria DHODH/CoQ, all of which serve as anti-ferroptoic pathways to prevent ferroptosis. Moreover, we provide a comprehensive summary of the genetic regulation of ferroptosis via targeting the above-mentioned pro-ferroptotic or anti-ferroptotic pathways. The regulation of pro- and anti-ferroptotic pathways gives rise to more specific responses to the tumor cells in a context-dependent manner, highlighting the unceasing study and deeper understanding of mechanistic regulation of ferroptosis for the purpose of applying ferroptosis induction in cancer therapy.

4.
Sci Transl Med ; 14(647): eabj2177, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35648811

RESUMO

Antiangiogenesis therapies targeting vascular endothelial growth factor (VEGF) have revolutionized the treatment of neovascular ocular diseases, including neovascular age-related macular degeneration (nAMD). Compelling evidence has implicated the vital role of complement system dysregulation in AMD pathogenesis, implying it as a potential therapeutic strategy for geographic atrophy in dry AMD and to enhance the efficacy of anti-VEGF monotherapies in nAMD. This study reports the preclinical assessment and phase 1 clinical outcomes of a bispecific fusion protein, efdamrofusp alfa (code: IBI302), which is capable of neutralizing both VEGF isoforms and C3b/C4b. Efdamrofusp alfa showed superior efficacy over anti-VEGF monotherapy in a mouse laser-induced choroidal neovascularization (CNV) model after intravitreal delivery. Dual inhibition of VEGF and the complement activation was found to further inhibit macrophage infiltration and M2 macrophage polarization. Intravitreal efdamrofusp alfa demonstrated favorable safety profiles and exhibited antiangiogenetic efficacy in a nonhuman primate laser-induced CNV model. A phase 1 dose-escalating clinical trial (NCT03814291) was thus conducted on the basis of the preclinical data. Preliminary results showed that efdamrofusp alfa was well tolerated in patients with nAMD. These data suggest that efdamrofusp alfa might be effective for treating nAMD and possibly other complement-related ocular conditions.


Assuntos
Neovascularização de Coroide , Degeneração Macular , Inibidores da Angiogênese/uso terapêutico , Animais , Neovascularização de Coroide/tratamento farmacológico , Proteínas do Sistema Complemento , Olho , Humanos , Degeneração Macular/complicações , Degeneração Macular/tratamento farmacológico , Camundongos , Fator A de Crescimento do Endotélio Vascular/uso terapêutico
5.
Hepatol Int ; 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35727500

RESUMO

BACKGROUND: The Baveno VI criteria (B6C) have been recommended to screen high-risk varices (HRV) in patients with liver cirrhosis to avoid the use of esophagogastroduodenoscopy (EGD). Due to conservative nature of B6C and the general unavailability of transient elastography in the medical institutions, clinical application of B6C is restricted. We aimed to optimize B6C and attempted to replace the liver stiffness (LS) score with other parameters that could help patients avoid EGD. METHODS: A total of 1,188 patients with compensated cirrhosis were analyzed and divided into the training cohort (TC) and validating cohort (VC) by the split-sample method. Variables were selected to develop new criteria in the TC before verification in the VC. RESULTS: The parameters of age ≥ 50 years, LS, platelet count (PLT), and spleen area (SA) were independently associated with HRV. The risk of HRV was 2.39 times greater in patients over 50 years, hence alternative B6C (AB6C) and modified B6C (MB6C) criteria were built based on age. MB6C was built by adjusting the cut-off value of LS and PLT (patients aged < 50 years with PLT > 100 × 109/L and LS < 30 kPa; patients aged ≥ 50 years with a combined PLT > 125 × 109/L and LS < 20 kPa). MB6C helped avoid EGD in 310 (51.2%) patients, whereas 7 (2.3%) cases of HRV were missed. The predicting performance HRV showed no statistical difference between PLT, SA, or LS. SA was selected to replace LS and in the built AB6C (patients aged < 50 years with PLT > 100 × 109/L and SA < 55 cm2; patients aged ≥ 50 years with a combined PLT > 125 × 109/L and SA < 44 cm2). Using AB6C avoided 297 (49.1%) EGDs with a total of 8 (2.7%) cases of HRV that were missed. CONCLUSIONS: Our novel MB6C and AB6C were stratified by age and provided excellent performance for ruling out HRV, which performed better than B6C and EB6C (expanded B6C) in helping to avoid EGD screening. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-DDD-17013845.

6.
Transgenic Res ; 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35704130

RESUMO

Base editors (BEs) are efficient and precise tools for generating single base conversions in living organisms. While most BE systems are limited in mediating C-to-T or A-to-G conversions, recently developed C-to-G base editors (CGBEs) could produce C-to-G transversions. CGBEs convert cytosine within the editing window to abasic intermediates, which would be replaced with any base after base excision repair (BER). By far, though the efficiency and editing scope of CGBEs have been investigated in cultured cells via gRNA library and machine-learning, the viability of CGBEs in generating mouse models has not been adequately tested. In this study, we tested the C-to-G transversion efficiency of the CGBE1 and CGBE-XRCC1 systems in mouse embryos. Our results showed that both of the CGBE systems were able to mediate C-to-G transversion on 2 out of 3 targets tested, with up to 20% frequency within the editing window. Notably, most of the groups showed over 40% of other base conversions, predominantly C-to-T. Lastly, we successfully acquired the F1 mouse carrying a disease-causing mutation. In all, our study suggested that CGBEs systems held great potential in generating mouse models and indicated that XRCC1 based system is applicable in mouse embryos.

7.
Carbohydr Polym ; 291: 119554, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35698382

RESUMO

Efficient delivery systems for co-delivery of P-glycoprotein (P-gp) inhibitors and chemotherapeutic drugs are essential for inhibiting multi-drug resistance (MDR) breast cancers. Herein, we present a multi-functional carboxymethyl chitosan (CMC) based core-shell nanoplatform to co-deliver MDR1 gene-silenced small interfering RNA (siMDR1) and doxorubicin (DOX) for optimal combinatorial therapy. DOX is linked to CMC through a disulfide bond to model redox-responsive prodrug (CMC-DOX) as the inner core. siMDR1 is encapsulated in oligoethylenimine (OEI), which is electrostatically adsorbed on CMC-DOX as the pH-responsive sheddable shielding shell. AS1411 aptamer and GALA peptide functionalised hyaluronic acid (AHA/GHA) are provided on the surface for tumour-targeting and endo/lysosomal escape. The nanoplatform could stepwise release payloads with acid/redox triggered fashion. AHA effectively improves nanoplatform intracellular uptake and tumour accumulation. GHA facilitates cargos escape from endo/lysosomes to cytoplasm. The multi-functional nanoplatform provides 86.3 ± 2.2% siMDR1 gene silencing and significantly downregulates P-gp expression. Moreover, it ensures 55.7 ± 1.6% MCF-7/ADR cell apoptosis at a low concentration of DOX (30 µg/mL) in vitro and performs synergistic therapeutic effects suppressing tumour growth in vivo. Overall, the multi-functional CMC-based biopolymers can be efficient siRNA/drug co-delivery carriers for cancer chemotherapy.


Assuntos
Neoplasias da Mama , Quitosana , Nanopartículas , Neoplasias da Mama/patologia , Quitosana/farmacologia , Doxorrubicina , Portadores de Fármacos/química , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Células MCF-7 , Nanopartículas/química , RNA Interferente Pequeno/química
8.
Neuroscience ; 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35697320

RESUMO

The neurotrophin receptor p75 (p75NTR) is a circadian rhythm regulator and mediates cognitive deficits induced by sleep deprivation (SD). The soluble extracellular domain of p75NTR (p75ECD) has been shown to exert a neuroprotective function in Alzheimer's disease (AD) and depression animal models. Nevertheless, the role of p75ECD in SD-induced cognitive dysfunction is unclear. In the present study we administrated p75ECD-Fc (10, 3 mg/kg), a recombinant fusion protein of human p75ECD and fragment C of immunoglobulin IgG1, to treat mice via intraperitoneal injection. The results revealed that peripheral supplementation of high-dose p75ECD-Fc (10 mg/kg) recovered the balance between Aß and p75ECD in the hippocampus and rescued the cognitive deficits in SD mice. We also found that p75ECD-Fc ameliorated other pathologies induced by SD, including neuronal apoptosis, synaptic plasticity impairment and neuroinflammation. The current study suggests that p75ECD-Fc is a potential candidate for SD and peripheral supplementation of p75ECD-Fc may be a prospective preventive measure for cognitive decline in SD.

9.
Nano Lett ; 22(10): 4232-4239, 2022 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-35533211

RESUMO

Picturing the atomic migration pathways of catalysts in a reactive atmosphere is of central significance for uncovering the underlying catalytic mechanisms and directing the design of high-performance catalysts. Here, we describe a reduction-controlled atomic migration pathway that converts nanoparticles to single atom alloys (SAAs), which has remained synthetically challenging in prior attempts due to the elusive mechanism. We achieved this by thermally treating the noble-metal nanoparticles M (M = Ru, Rh, Pd, Ag, Ir, Pt, and Au) on metal oxide (CuO) supports with H2/Ar. Atomic-level characterization revealed such conversion as the synergistic consequence of noble metal-promoted H2 dissociation and concomitant CuO reduction. The observed atomic migration pathway offers an understanding of the dynamic mechanisms study of nanomaterials formation and catalyst design.


Assuntos
Ligas , Nanopartículas Metálicas , Catálise
10.
Front Med (Lausanne) ; 9: 872881, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35572990

RESUMO

Background and Aims: Emergency endoscopy is recommended for patients with acute esophageal variceal bleeding (EVB) and their prognosis has improved markedly over past decades due to the increased specialization of endoscopic practice. The study aimed to compare outcomes following emergency endoscopic injection sclerotherapy (EIS) and endoscopic variceal ligation (EVL) in cirrhotic patients with acute EVB. Methods: Cirrhotic patients with acute EVB who underwent emergency endoscopy were retrospectively enrolled from 2013 to 2020 across 34 university hospitals from 30 cities. The primary outcome was the incidence of 5-day rebleeding after emergency endoscopy. Subgroup analysis was stratified by Child-Pugh class and bleeding history. A 1:1 propensity score matching (PSM) analysis was performed. Results: A total of 1,017 and 382 patients were included in EIS group and EVL group, respectively. The 5-day rebleeding incidence was similar between EIS group and EVL group (4% vs. 5%, P = 0.45). The result remained the same after PSM (P = 1.00). Among Child-Pugh class A, B and C patients, there were no differences in the 5-day rebleeding incidence between the two groups after PSM (P = 0.25, 0.82, and 0.21, respectively). As for the patients with or without bleeding history, the differences between EIS group and EVL group were not significant after PSM (P = 1.00 and 0.26, respectively). Conclusion: The nationwide cohort study indicates that EIS and EVL are both efficient emergency endoscopic treatment strategies for acute EVB. EIS should not be dismissed as an economical and effective emergency endoscopic treatment strategy of acute EVB. ClincialTrials.gov number NCT04307264.

12.
Front Microbiol ; 13: 791248, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35531284

RESUMO

To screen, prepare, identify, and evaluate the activities of natural antioxidants for treating chronic diseases caused by oxidative stress. Two algal proteins, namely ZD10 and ZD60, precipitated with 10 and 60% (NH4)2SO4 were extracted from red algae Eucheuma cottonii (E. cottonii) and hydrolyzed using five proteolytic enzymes. The results showed that ZD60 played the most significant role in the enhancement of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH⋅) scavenging activity (25.91 ± 0.24%) among all protein hydrolysates. Subsequently, six antioxidant peptides (EP1-EP6) were isolated from the papain hydrolysate of ZD60 by ultrafiltration and chromatography methods. Their amino acid sequences were identified as Thr-Ala (EP1), Met-Asn (EP2), Tyr-Ser-Lys-Thr (EP3), Tyr-Ala-Val-Thr (EP4), Tyr-Leu-Leu (EP5), and Phe-Tyr-Lys-Ala (EP6) with molecular weights of 190.21, 263.33, 497.55, 452.51, 407.51, and 527.62 Da, respectively. Of which, EP3, EP4, EP5, and EP6 showed strong scavenging activities on DPPH⋅, hydroxyl radical (HO⋅), and superoxide anion radical (O- 2⋅). Moreover, EP4 and EP5 could significantly protect human umbilical vein endothelial cells (HUVECs) from H2O2-induced oxidative damage by increasing the levels of antioxidant enzyme systems including superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) to reduce the levels of reactive oxygen species (ROS) (60.51 and 51.74% of model group) and malondialdehyde (MDA) (75.36 and 64.45% of model group). In addition, EP4 and EP5 could effectively inhibit H2O2-induced apoptosis by preventing HUVECs from early apoptosis to late apoptosis. These results indicated that the antioxidant peptides derived from E. cottonii, especially EP4 and EP5, could serve as the natural antioxidants applied in pharmaceutical products to treat chronic cardiovascular diseases caused by oxidative damage, such as coronary heart disease, atherosclerosis, etc.

13.
NeuroRehabilitation ; 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35527573

RESUMO

BACKGROUND: The optimization and standardization of emergency nursing and monitoring procedures are of great significance for thrombolytic treatment of acute cerebral infarction. OBJECTIVE: Studies on the emergency nursing and monitoring procedure on cognitive impairment and neurological function in patients with acute cerebral infarction are still limited. METHODS: The study was a randomized controlled trial and 134 patients with acute cerebral infarction were recruited. They were randomly arranged into the control group (n = 67) receiving normal nursing procedure and the intervention group (n = 67) receiving emergency nursing and monitoring procedure after pre-intervention assessment. The cognitive impairment, neurological function and levels of inflammatory biomarkers and neuron-specific enolase of the participants were evaluated and analyzed. RESULTS: Emergency nursing and monitoring procedure improved Mini-mental State Examination and Montreal Cognitive Assessment scores of patients with cerebral infraction compared with the control group. It also improved the scores of National Institutes of Health Stroke Scale, activities of daily living scale, Fugl-Meyer scale in the participants. Emergency nursing and monitoring procedure led to significantly decreased neuron-specific enolase and inflammatory cytokines in the serum of the participants. CONCLUSION: Emergency nursing and monitoring procedure are beneficial for cognitive impairment and neurological function recovery in patients with acute cerebral infarction.

14.
BMC Genomics ; 23(Suppl 4): 361, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35546658

RESUMO

BACKGROUND: Accurate bacteria genome de novo assembly is fundamental to understand the evolution and pathogenesis of new bacteria species. The advent and popularity of Third-Generation Sequencing (TGS) enables assembly of bacteria genomes at an unprecedented speed. However, most current TGS assemblers were specifically designed for human or other species that do not have a circular genome. Besides, the repetitive DNA fragments in many bacterial genomes plus the high error rate of long sequencing data make it still very challenging to accurately assemble their genomes even with a relatively small genome size. Therefore, there is an urgent need for the development of an optimized method to address these issues. RESULTS: We developed B-assembler, which is capable of assembling bacterial genomes when there are only long reads or a combination of short and long reads. B-assembler takes advantage of the structural resolving power of long reads and the accuracy of short reads if applicable. It first selects and corrects the ultra-long reads to get an initial contig. Then, it collects the reads overlapping with the ends of the initial contig. This two-round assembling procedure along with optimized error correction enables a high-confidence and circularized genome assembly. Benchmarked on both synthetic and real sequencing data of several species of bacterium, the results show that both long-read-only and hybrid-read modes can accurately assemble circular bacterial genomes free of structural errors and have fewer small errors compared to other assemblers. CONCLUSIONS: B-assembler provides a better solution to bacterial genome assembly, which will facilitate downstream bacterial genome analysis.


Assuntos
Genoma Bacteriano , Sequenciamento de Nucleotídeos em Larga Escala , Bactérias/genética , DNA , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Análise de Sequência de DNA/métodos
15.
Artigo em Inglês | MEDLINE | ID: mdl-35565041

RESUMO

Compost is an important source of airborne fungi that can adversely affect occupational health. However, the aerosol behavior of fungi and their underlying factors in composting facilities are poorly understood. We collected samples from compost piles and the surrounding air during the composting of animal manure and analyzed the aerosolization behavior of fungi and its potential health effects based on the fungal composition and abundance in two media using high-throughput sequencing and ddPCR. There were differences in fungal diversity and richness between the air and composting piles. Ascomycota and Basidiomycota were the two primary fungal phyla in both media. The dominant fungal genera in composting piles were Aspergillus, Thermomyces, and Alternaria, while the dominant airborne fungal genes were Alternaria, Cladosporium, and Sporobolomyces. Although the communities of total fungal genera and pathogenic/allergenic genera were different in the two media, fungal abundance in composting piles was significantly correlated with abundance in air. According to the analysis on fungal composition, a total of 69.10% of the fungal genera and 91.30% of pathogenic/allergenic genera might escape from composting pile into the air. A total of 77 (26.64%) of the fungal genera and six (20%) of pathogenic/allergenic genera were likely to aerosolize. The influence of physicochemical parameters and heavy metals on the aerosol behavior of fungal genera, including pathogenic/allergenic genera, varied among the fungal genera. These results increase our understanding of fungal escape during composting and highlight the importance of aerosolization behavior for predicting the airborne fungal composition and corresponding human health risks in compost facilities.


Assuntos
Basidiomycota , Compostagem , Aerossóis , Animais , Fungos , Esterco/microbiologia , Solo
16.
J Magn Reson Imaging ; 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35488516

RESUMO

BACKGROUND: The focus of neuro-oncology research has changed from histopathologic grading to molecular characteristics, and medical imaging routinely follows this change. PURPOSE: To compare the diagnostic performance of amide proton transfer (APT) and four diffusion models in gliomas grading and isocitrate dehydrogenase (IDH) genotype. STUDY TYPE: Prospective. POPULATION: A total of 62 participants (37 males, 25 females; mean age, 52 ± 13 years) whose IDH genotypes were mutant in 6 of 14 grade II gliomas, 8 of 20 of grade III gliomas, and 4 of 28 grade IV gliomas. FIELD STRENGTH/SEQUENCE: APT imaging using sampling perfection with application optimized contrasts by using different flip angle evolutions (SPACE) and DWI with q-space Cartesian grid sampling were acquired at 3 T. ASSESSMENT: The ability of diffusion kurtosis imaging, diffusion kurtosis imaging, neurite orientation dispersion and density imaging (NODDI), mean apparent propagator (MAP), and APT imaging for glioma grade and IDH status were assessed, with histopathological grade and genetic testing used as a reference standard. Regions of interest (ROIs) were drawn by two neuroradiologists after consensus. STATISTICAL TESTS: T-test and Mann-Whitney U test; one-way analysis of variance (ANOVA); receiver operating curve (ROC) and area under the curve (AUC); DeLong test. P value < 0.05 was considered statistically significant. RESULTS: Compared with IDH-mutant gliomas, IDH-wildtype gliomas showed a significantly higher mean, 5th-percentile (APT5 ), and 95th-percentile from APTw, the 95th-percentile value of axial, mean, and radial diffusivity from DKI, and 95th-percentile value of isotropic volume fraction from NODDI, and no significantly different parameters from DTI and MAP (P = 0.075-0.998). The combined APT model showed a significantly wider area under the curve (AUC 0.870) for IDH status, when compared with DKI and NODDI. APT5 was significantly different between two of the three groups (glioma II vs. glioma III vs. glioma IV: 1.35 ± 0.75 vs. 2.09 ± 0.93 vs. 2.71 ± 0.81). DATA CONCLUSION: APT has higher diagnostic accuracy than DTI, DKI, MAP, and NODDI in glioma IDH genotype. APT5 can effectively identify both tumor grading and IDH genotyping, making it a promising biomarker for glioma classification. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

17.
Front Pharmacol ; 13: 841990, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401199

RESUMO

Traditional herbal medicine (THM) is used worldwide for its safety and effectiveness against various diseases. Huoxiang Zhengqi (HXZQ) is an extensively used Chinese THM formula targeting gastrointestinal disordered gastroenteritis via regulating the intestinal microbiome/immuno-microenvironment. However, the specific mechanisms remain largely unexplored, besides as a lifestyle drug, its safety on the gut microbiome homeostasis has never been investigated. In this study, the effects of HXZQ on the gut microbiome of healthy adults were investigated for the first time, and the antibiotic-induced gut microbiota dysbiosis mice model was applied for verification. Based on healthy adults, our results revealed that HXZQ exhibited mild and positive impacts on the bacterial diversity and the composition of the gut microbiome in a healthy state. As for an unhealthy state of the gut microbiome (with low bacterial diversity and deficient compositions), HXZQ significantly restored the bacterial diversity and recovered the abundance of Bacteroidetes. In the antibiotic-induced mice model, HXZQ distinctly revived the deficient gut microbial compositions impaired by antibiotics. At the genus level, the abundances that responded most strongly and positively to HXZQ were Bifidobacterium in healthy adults and Muribaculaceae, Lactobacillus, and Akkermansia in mice. In contrast, the abundance of Blautia in healthy adults, Enterococcus, and Klebsiella in mice showed inversely associated with HXZQ administration. At last, HXZQ might exhibit an anti-inflammatory effect by regulating the concentration of interleukin-6 in plasma while causing no significant changes in the colon tissue structure in mice. In conclusion, our results elucidate that the safety of HXZQ in daily use further reveals the modulatory effects of HXZQ on gut microbial community structure. These results will provide new insights into the interaction of THM and gut microbiome homeostasis and clues about the safe use of THM as a lifestyle drug for its further development.

18.
J Nanobiotechnology ; 20(1): 202, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35477463

RESUMO

As a non-invasive innovative diagnosis platform, advanced flexible contact lenses can dynamically monitor vital ocular indicators, spot abnormalities and provide biofeedback guidance for real-time diagnosis and rehabilitation tracking of chronic eye diseases. However, most of the state-of-the-art reported contact lenses either can only monitor a single indicator at a time or realize multifunctional integration based on multiple materials. Herein, we developed a flexible multifunctional contact lens based on inorganic γ-Fe2O3@NiO magnetic oxide nanosheets, which can be attached conformally and seamlessly to the eyeball to simultaneously monitor glucose level in tears, eyeball movement, and intraocular pressure. The optimized contact lens has a reliable glucose detection limit (0.43 µmol), superior eye movement measurement accuracy (95.27%) and high intraocular pressure sensitivity (0.17 MHz mmHg- 1). This work presents a concept in the biochemical and biophysical integrated sensing of ocular signals using contact lens via an innovative material, and provides a personalized and efficient way for health management.


Assuntos
Lentes de Contato , Óxidos , Glucose , Fenômenos Magnéticos , Tonometria Ocular
19.
Genes (Basel) ; 13(4)2022 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-35456492

RESUMO

Several variants of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are emerging all over the world. Variant surveillance from genome sequencing has become crucial to determine if mutations in these variants are rendering the virus more infectious, potent, or resistant to existing vaccines and therapeutics. Meanwhile, analyzing many raw sequencing data repeatedly with currently available code-based bioinformatics tools is tremendously challenging to be implemented in this unprecedented pandemic time due to the fact of limited experts and computational resources. Therefore, in order to hasten variant surveillance efforts, we developed an installation-free cloud workflow for robust mutation profiling of SARS-CoV-2 variants from multiple Illumina sequencing data. Herein, 55 raw sequencing data representing four early SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, and Delta) from an open-access database were used to test our workflow performance. As a result, our workflow could automatically identify mutated sites of the variants along with reliable annotation of the protein-coding genes at cost-effective and timely manner for all by harnessing parallel cloud computing in one execution under resource-limitation settings. In addition, our workflow can also generate a consensus genome sequence which can be shared with others in public data repositories to support global variant surveillance efforts.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Fluxo de Trabalho
20.
Artigo em Inglês | MEDLINE | ID: mdl-35388762

RESUMO

BACKGROUND: The Compound Sophora flavescenes (Kushen) Decoction was found to reduce the inflammatory symptom of Ulcerative colitis (UC). However, there exists a very limited understanding of the molecular pharmacological mechanisms. OBJECTIVE: To explore the mechanism of Compound Sophora flavescens (Kushen) Decoction in treating ulcerative colitis from the perspective of network pharmacology. METHODS: Active components and potential targets of Compound Sophora flavescens (Kushen) Decoction were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. GeneCards and other databases were used to predict and screen ulcerative colitis related genes. Cytoscape software was applied to construct "drug-active component-disease-target" network. GO function and KEGG pathway enrichment analysis revealed the potential pathway of the Compound Sophora flavescenes (Kushen) Decoction for UC. RESULTS: After screening, a total of 124 active ingredients and 163 potential therapeutic targets for UC, were obtained for the Compound Sophora flavescens (Kushen) Decoction. Protein interaction network analysis showed that 15 key targets could be identified for the possible treatment of UC. GO and KEGG analysis showed that the active ingredients in the Compound Sophora flavescens (Kushen) Decoction were mainly enriched in 2556 biological processes and 172 signaling pathways. CONCLUSION: The study showed that the Compound Sophora flavescens (Kushen) Decoction has therapeutic effects on UC through multi-component, multi-target, and multi-pathway.

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