Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 293
Filtrar
1.
Front Cell Infect Microbiol ; 11: 740981, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778105

RESUMO

Caries is one of the most prevalent infectious diseases worldwide and is driven by the dysbiosis of dental biofilms adhering to tooth surfaces. The pits and fissured surfaces are the most susceptible sites of caries. However, information on the taxonomic composition and functional characteristics of the plaque microbiota in the pit and fissure sites is very limited. This study aimed to use metagenomic sequencing analyses to investigate the relationship between the plaque microbiome in the pit and fissure site and caries in adolescents. A total of 20 adolescents with active pit and fissure surface caries were involved as well as 20 age-matched, caries-free teenagers for control tests. Plaque samples were collected from the pit and fissure site and were subjected to metagenomic analyses, in which the microbial communities were investigated. Our results showed that the microbiota diversity was similar between those two groups. At the species level, the relative abundances of A. gerencseriae, P. acidifaciens, P. multisaccharivorax, S. oralis, S. mutans, and P. denticolens were higher in the caries-active group. N. elongata, C. hominis, and A. johnsonii were relatively more abundant in the caries-free groups. Functional analysis suggested that the metabolic pathway was the most abundant pathway, and the functional traits of the level 2 pathways included amino acid metabolism, metabolism of cofactors, and vitamins and carbohydrate metabolism. Our results also revealed that the caries group displayed several alterations in metabolic pathways, including enriched functions in carbohydrate digestion and absorption. This study suggested that in addition to the specific anatomical structures of the pit and fissured surfaces, the fundamental differences in the plaque microbiome may also be related to the susceptibility of pit and fissure caries.

2.
Am J Mens Health ; 15(5): 15579883211049044, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34581214

RESUMO

The objective of the current study was to explore the relationship between longitudinal change in body mass index (BMI) and reproductive hormones in middle-aged and elderly Chinese men. A cohort study was conducted in a rural area of China. Local male residents aged 40-80 years were recruited at baseline in 2012 and were followed up in 2016. Information about weight, height, waist circumference, sex hormones, smoking status, and medical history were obtained. The change in BMI reported no significant relationship with the change in total testosterone (TT), calculated free testosterone (cFT), and bioavailable testosterone (BioT) in Pearson correlation analyses. When the change in BMI was divided into three groups-"great loss," "normal fluctuation," and "great gain"-TT, cFT and BioT had the highest increase (or the lowest decrease) in men with "normal fluctuation" in BMI compared with the other two groups. The advantage of maintaining a stable BMI was more evident for those who were overweight, non-smoking, and disease-free. There was a tendency of a continuous increase in cFT and BioT with BMI increase in smoking and diseased populations. Maintaining a stable BMI is associated with maintaining normal levels of reproductive hormones, especially in overweight, non-smoking, and healthy men aged over 40 years.


Assuntos
Globulina de Ligação a Hormônio Sexual , Testosterona , Idoso , Índice de Massa Corporal , Estudos de Coortes , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade
3.
Curr Microbiol ; 78(11): 3996-4003, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34522978

RESUMO

Marine phycosphere hosts cross-kingdom algae-bacteria interactions playing a variety of crucial roles in aquatic ecosystems especially for the prevention and control of harmful algal blooms (HABs). During the investigation of structural composition of phycosphere microbiota (PM) of diverse marine HAB dinoflagellates, a Gram-negative, strictly aerobic, non-motile and rod-shaped bacterium designated LZ-17T was isolated from the phycosphere of highly toxic Alexandrium catenella LZT09. The 16S rRNA gene sequence analysis and the multilocus sequence analysis (MLSA) based on five protein-coding housekeeping genes (atpD, gyrB, mutL, topA and rpoD) indicated that strain LZ-17T was affiliated to the genus Maritimibacter within the family Rhodobacteraceae, and closely related to Maritimibacter alkaliphilus HTCC2654T (99.1%), 'Maritimibacter harenae' DP07T (97.9%) and M. lacisalsi X12M-4T (95.7%). The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain LZ-17T and the type strain of M. alkaliphilus were 96.9% and 74.7%. However, strain LZ-17T could be clearly distinguished from its closest by the phenotypical and phenotypical characteristics. Strain LZ-17T contained Q-10 as its major isoprenoid quinone, and summed feature 8 (C18:1 ω7c and/or C18:1 ω6c), C16:0 and C16:0 2-OH as the predominant fatty acids (>10%). The major polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol and phosphatidylcholine. The DNA G + C content was 64.3 mol%. Based on the polyphasic taxonomic characterization, strain LZ-17T represents a novel species of the genus Maritimibacter, for which the name Maritimibacter alexandrii sp. nov. is proposed, with the type strain LZ-17T (=CCTCC 2019005T = KCTC 72193T).


Assuntos
Dinoflagelados , Microbiota , Rhodobacteraceae , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , Ácidos Graxos , Fosfolipídeos , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
4.
Mol Med Rep ; 24(5)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34490483

RESUMO

Progressive macrophage dysfunction and apoptosis are some of the major events that occur during atherogenesis. To further investigate the intrinsic association between atherosclerosis (AS) and macrophage apoptosis and autophagy, cholesterol crystals (CHCs) were used to stimulate RAW264.7 macrophages to establish a macrophage model of advanced AS. Cells in the CHC group were treated with salvianolic acid B (Sal B) to evaluate its protective effects and reveal its underlying molecular mechanism. The results demonstrated that treatments with Sal B significantly improved autophagy dysfunction and reduced the apoptotic rate of CHC­induced macrophages. Furthermore, Sal B significantly attenuated CHC­induced release of proinflammatory factors (TNF­α and IL­6) by macrophages. Treatment of macrophages with a specific inhibitor of autophagy (3­methyladenine) significantly reversed Sal B­mediated effects on autophagy, suggesting that Sal B­induced autophagy may display a protective effect in CHC­induced macrophages. Furthermore, pretreatment of CHC­induced macrophages with insulin significantly decreased Sal B­induced autophagy, indicating that the Akt/mTOR signaling pathway may serve as a critical mediator in regulating Sal B­mediated cell death. Taken together, the present study demonstrated that Sal B improved autophagic dysfunction and reduced the apoptosis of CHC­induced macrophages via inhibiting the Akt/mTOR signaling pathway.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34545525

RESUMO

Few studies have evaluated the short-term association between hospital admissions and individual exposure to ambient particulate matter (PM2.5). Particularly, no studies focused on hospital admissions for chronic obstructive pulmonary disease (COPD) at the individual level. We assessed the short-term effects of PM2.5 on hospitalization admissions for COPD in Guangzhou, China, during 2014-2015, based on satellite-derived estimates of ambient PM2.5 concentrations at a 1-km resolution near the residential address as individual-level exposure for each patient. Around 40,002 patients with COPD admitted to 110 hospitals were included in this study. A time-stratified case-crossover design with conditional logistic regression models was applied to assess the effects of PM2.5 based on a 1-km grid data of aerosol optical depth provided by the National Aeronautics and Space Administration on hospital admissions for COPD. Further, we performed stratified analyses by individual demographic characteristics and season of hospital admission. Around 10 µg/m3 increase in individual-level PM2.5 was associated with an increase of 1.6% (95% confidence interval [CI]: 0.6%, 2.7%) in hospitalization for COPD at a lag of 0-5 days. The impact of PM2.5 on hospitalization for COPD was greater significantly in males and patients admitted in summer. Our study strengthened the evidence for the adverse effect of PM2.5 based on satellite-based individual-level exposure data.

6.
Zool Res ; 42(5): 666-670, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34490759

RESUMO

In a precautionary response to the current coronavirus (COVID-19) pandemic, China's Ministries permanently banned eating and trading in terrestrial wild (non-livestock) animals on 24 February 2020, and extensively updated the list of Fauna under Special State Protection (LFSSP) in 2020 and 2021, in which pangolins (Manidae spp.) were upgraded to the highest protection level. Examining 509 pangolin prosecution records from China Judgements online prior to these changes (01/01/14-31/12/19), we identified that Guangdong, Guangxi and Yunnan Provinces were hotspots for trade in whole pangolins and their scales. Interrupting trade in these three principal southern provinces would substantially fragment the pangolin trade network and reduce supply of imports from other south-east Asian countries. In the context of the revised legislation and strategies intended to prevent wildlife trade, we conclude that targeting interventions at key trade nodes could significantly reduce illegal trade in pangolins, and that this approach could also be effective with other taxa.


Assuntos
COVID-19/epidemiologia , Crime , Espécies em Perigo de Extinção/legislação & jurisprudência , Pangolins , SARS-CoV-2 , Animais , China , Humanos , Estudos Retrospectivos
7.
J Nanobiotechnology ; 19(1): 244, 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34391417

RESUMO

BACKGROUND: Macromoleculization of nitroxides has been an effective strategy to improve low relaxivities and poor in vivo stability, however, nitroxides-based metal-free magnetic resonance imaging (MRI) macromolecular contrast agents (mCAs) are still under-performed. These mCAs do not possess a high nitroxides content sufficient for a cumulative effect. Amphiphilic nanostructures in these mCAs are not stable enough for highly efficient protection of nitroxides and do not have adequate molecular flexibility for full contact of the paramagnetic center with the peripheral water molecules. In addition, these mCAs still raise the concerns over biocompatibility and biodegradability due to the presence of macromolecules in these mCAs. RESULTS: Herein, a water-soluble biodegradable nitroxides-based mCA (Linear pDHPMA-mPEG-Ppa-PROXYL) was prepared via covalent conjugation of a nitroxides (2,2,5,5-tetramethyl-1-pyrrolidinyl-N-oxyl, PROXYL) onto an enzyme-sensitive linear di-block poly[N-(1, 3-dihydroxypropyl) methacrylamide] (pDHPMA). A high content of PROXYL up to 0.111 mmol/g in Linear pDHPMA-mPEG-Ppa-PROXYL was achieved and a stable nano-sized self-assembled aggregate in an aqueous environment (ca. 23 nm) was formed. Its longitudinal relaxivity (r1 = 0.93 mM- 1 s- 1) was the highest compared to reported nitroxides-based mCAs. The blood retention time of PROXYL from the prepared mCA in vivo was up to ca. 8 h and great accumulation of the mCA was realized in the tumor site due to its passive targeting ability to tumors. Thus, Linear pDHPMA-mPEG-Ppa-PROXYL could provide a clearly detectable MRI enhancement at the tumor site of mice via the T1WI SE sequence conventionally used in clinical Gd3+-based contrast agents, although it cannot be compared with DTPA-Gd in the longitudinal relaxivity and the continuous enhancement time at the tumor site of mice. Additionally, it was demonstrated to have great biosafety, hemocompatibility and biocompatibility. CONCLUSIONS: Therefore, Linear pDHPMA-mPEG-Ppa-PROXYL could be a potential candidate as a substitute of metal-based MRI CAs for clinical application.

8.
J Nanobiotechnology ; 19(1): 205, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34243760

RESUMO

BACKGROUND: In order to address the potential toxicity of metal-based magnetic resonance imaging (MRI) contrast agents (CAs), a concept of non-metallic MRI CAs has emerged. Currently, paramagnetic nitroxides (such as (2,2,5,5-tetramethylpyrrolidine-1-oxyl, PROXYL), (2,2,6,6-tetramethylpiperidine-1-oxide, TEMPO), etc.) are being extensively studied because their good stability and imaging mechanism are similar to metal-based contrast agents (such as Gd3+ chelate-based clinical CAs). However, a lower relaxivity and rapid in vivo metabolism of nitroxides remain to be addressed. Previous studies have demonstrated that the construction of macromolecular nitroxides contrast agents (mORCAs) is a promising solution through macromolecularization of nitroxides (i.e., use of large molecules to carry nitroxides). Macromolecular effects not only increase the stability of nitroxides by limiting their exposure to reductive substances in the body, but also improve the overall 1H water relaxation by increasing the concentration of nitroxides and slowing the molecular rotation speed. RESULTS: Branched pDHPMA-mPEG-Ppa-PROXYL with a high molecular weight (MW = 160 kDa) and a nitroxides content (0.059 mmol/g) can form a nanoscale (~ 28 nm) self-assembled aggregate in a water environment and hydrophobic PROXYL can be protected by a hydrophilic outer layer to obtain strong reduction resistance in vivo. Compared with a small molecular CA (3-Carboxy-PROXYL (3-CP)), Branched pDHPMA-mPEG-Ppa-PROXYL displays three prominent features: (1) its longitudinal relaxivity (0.50 mM- 1 s- 1) is about three times that of 3-CP (0.17 mM- 1 s- 1); (2) the blood retention time of nitroxides is significantly increased from a few minutes of 3-CP to 6 h; (3) it provides long-term and significant enhancement in MR imaging of the tumor, liver, kidney and cardiovascular system (heart and aortaventralis), and this is the first report on nitroxides-based MRI CAs for imaging the cardiovascular system. CONCLUSIONS: As a safe and efficient candidate metal-free magnetic resonance contrast agent, Branched pDHPMA-mPEG-Ppa-PROXYL is expected to be used not only in imaging the tumor, liver and kidney, but also the cardiovascular system, which expands the application scope of these CAs.

9.
Aging (Albany NY) ; 13(14): 18310-18330, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34270461

RESUMO

Chemoresistance is the most significant reason for the failure of cancer treatment following radical cystectomy. The response rate to the first-line chemotherapy of cisplatin and gemcitabine does not exceed 50%. In our previous research, elevated BMI1 (B-cell specific Moloney murine leukemia virus integration region 1) expression in bladder cancer conferred poor survival and was associated with chemoresistance. Herein, via analysis of The Cancer Genome Atlas database and validation of clinical samples, BMI1 was elevated in patients with bladder cancer resistant to cisplatin and gemcitabine, which conferred tumor relapse and progression. Consistently, BMI1 was markedly increased in the established cisplatin- and gemcitabine-resistant T24 cells (T24/DDP&GEM). Functionally, BMI1 overexpression dramatically promoted drug efflux, enhanced viability and decreased apoptosis of bladder cancer cells upon treatment with cisplatin or gemcitabine, whereas BMI1 downregulation reversed this effect. Mechanically, upon interaction with p53, BMI1 was recruited on the promoter of miR-3682-3p gene concomitant with an increase in the mono-ubiquitination of histone H2A lysine 119, leading to transcription repression of miR-3682-3p gene followed by derepression of ABCB1 (ATP binding cassette subfamily B member 1) gene. Moreover, suppression of P-glycoprotein by miR-3682-3p mimics or its inhibitor XR-9576, could significantly reverse chemoresistance of T24/DDP&GEM cells. These results provided a novel insight into a portion of the mechanism underlying BMI1-mediated chemoresistance in bladder cancer.

10.
J Agric Food Chem ; 69(24): 6850-6859, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34114451

RESUMO

Physical-assisted chemical modification is effective to reduce the allergenicity of α-lactalbumin (ALA). However, there are few in-depth studies on the allergenicity changes of physical-assisted chemical-modified ALA during digestion. The effect of gastroduodenal digestion on the allergenicity changes of ALA treated by sonication-assisted glycation was assessed. Digestion of both ALA and its glycated forms generated peptide fractions, and intact undigested glycated ALA in the hydrolysates still covalently bound to d-galactose. High-resolution mass spectrometry revealed that a higher glycation degree was discovered in sonication-preprocessed ALA compared to native ALA. Enzyme-linked immunosorbent assay and basophil degranulation showed that sonication-assisted glycation could significantly reduce ALA allergenicity. The allergenicity of both gastric and gastroduodenal hydrolysates was further increased, and the hydrolysates of sonication-assisted glycated ALA showed the lowest allergenicity. The reason could be the shielding effect of the linear epitope found to be caused by a higher glycation degree; although linear epitopes were exposed, d-galactose covalently bound to intact undigested glycated ALA in the hydrolysates retained its masking role. These results indicated that sonication-assisted glycation could be a promising method to prepare immunotherapeutic agents for allergen immunotherapy to achieve the purpose of allergy desensitization.


Assuntos
Alérgenos , Lactalbumina , Digestão , Imunoglobulina E , Sonicação
11.
Drug Deliv ; 28(1): 1109-1119, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34121563

RESUMO

During inflammation, inflammatory cells are rapidly recruited to sites of infection or injury, where they cross physiological barriers around the infected site and further infiltrate into the tissues. Other cells, such as erythrocytes, endothelial cells and stem cells, also play prominent roles in host defense and tissue repair. In recent years, nanotechnology has been exploited to deliver drugs to sites of inflammation. For example, nanoparticles camouflaged with a cell membrane are a novel drug-delivery platform that can interact with the immune system and that show great potential for treating inflammation. Encapsulating drugs inside plasma membranes derived from various cells involved in inflammatory processes can be effective against inflammation. This review describes the preparation, characterization, and properties of various types of cell membrane-camouflaged biomimetic nanoparticles. It also summarizes preclinical research into their efficacy against inflammation.


Assuntos
Mimetismo Biológico/fisiologia , Membrana Celular/metabolismo , Portadores de Fármacos/farmacologia , Inflamação/tratamento farmacológico , Nanopartículas/metabolismo , Células Sanguíneas/metabolismo , Química Farmacêutica , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Células Eucarióticas/metabolismo , Macrófagos/metabolismo , Tamanho da Partícula , Inibidores de Proteases/metabolismo , Células-Tronco/metabolismo , Propriedades de Superfície , Tecnologia Farmacêutica
12.
Opt Express ; 29(12): 18654-18668, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34154118

RESUMO

Quantum-dot color conversion (QDCC) is a promising technique for next-generation full-color displays, such as QD converted organic light-emitting diodes and micro light-emitting diodes. Although present QDCC research has made some progress on the experimental aspect, the optical model and corresponding mathematical expression that can lay an indispensable foundation for QDCC have not been reported yet. In this paper, we present a theoretical model for precisely describing the complete optical behavior of QDCC, including optical transmission, scattering, absorption, and conversion process. A key parameter of QDCC, called dosage factor (DoF), is defined to quantitatively express the total consumption of QDs that can be calculated as the product of film thickness and QD concentration. Theoretical relations are established between DoF and three key performance indicators of QDCC, namely the light conversion efficiency (LCE), blue light transmittance (BLT), and optical density (OD). The maximum LCE value can be predicted based on this theoretical model, as well as the relationship between the slope of the OD curve and the molar absorption coefficient of blue light. This theoretical model is verified by both simulation and experiment. Results show that the simulation and experimental data highly match the theoretical model, and the goodness of fit reaches higher than 96% for LCE, BLT, and OD. Based on this, the optimal interval of DoF is recommended that provides key guiding significance to the QDCC related experiment.

13.
Opt Express ; 29(12): 18705-18719, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34154121

RESUMO

Dimensions of the edge-lit light guide plate (LGP) have a non-negligible impact on its output performance based on a pre-determined micro-dot array. However, how the LGP's dimension affects the performance has not been systematically researched. In this paper, the dimension of the LGP is numerically established as a function to the light output performance, which can be divided into four successive procedures. Firstly, the micro-structural dot array is designed based on the calculated illuminance distribution of the LGP's bottom surface. Based on this, the light energy output can be derived by defining three key parameters, which are dot density, scatting coefficient, and collision loss coefficient. After that, the ray-tracing simulation is used to determine the above parameters. Finally, the optimal dimensions of the LGP can be obtained with a specific correlation function with the light energy output. The mathematical relation above is demonstrated via both simulation and experiment. Our approach provides a systematic design for balancing the efficiency and uniformity of backlight by combining the dot design and the dimensional optimization, which has important theoretical guiding significance for actual display application.

14.
Opt Express ; 29(8): 12179-12194, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33984983

RESUMO

Current mini-LED backlights improve high-dynamic-range liquid crystal displays (LCDs) by using tens of thousands of direct-lit sources for local dimming. However, relative thick profile and high power consumption are the inherent limitations while compared with edge-lit backlights. By synthesizing edge- and direct-lit advantages, we propose a novel hybrid mini-LED backlight equipped with a specially designed integrated light guiding plate (LGP) for large-area displays. This LGP is seamlessly spliced by multiple physically segmented sub-LGPs with a scattering dot array on the bottom and U-shaped grooves at the corners. Each sub-LGP is a single local dimming zone that can be independently controlled. Scattering dot distribution can be numerically calculated even from multiple edge-lit sources. High optical performance and satisfactory local dimming effect are verified and analyzed via both simulation and experiment. The experimental spatial illuminance uniformity and the light extraction efficiency reach 81% and 83% while the crosstalk can be well suppressed below 0.2% between adjacent local dimming zones. The significant advantages of our design towards state-of-the-art mini-LED backlights include the zero optical distance for an ultra-thin profile, low mini-LED amount for local dimming, high optical efficiency, and infinite extension of zone number, which is expected to have a broad application prospect in the near future.

15.
J Oncol ; 2021: 6660486, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936204

RESUMO

Id4 is one of the inhibitors of DNA-binding proteins (Id) and involved in the pathogenesis of numerous cancers. The specific mechanism underlying the Id4-mediated regulation of proliferation, invasion, and metastasis of colorectal cancer (CRC) cells is still largely unclear. In the present study, results showed CRC cells had a lower baseline Id4 expression than normal intestinal epithelial NCM460 cells. In order to explore the role of Id4 in the tumorigenicity, CRC HCT116 cells with stable Id4 expression were used, and results showed Id4 overexpression arrested the cell cycle at the G0/G1 phase, inhibited the cell proliferation and the colony formation, as well as suppressed the migration and invasion. In the in vivo model, Id4 overexpression inhibited the tumor growth and metastasis in the nude mice. Furthermore, Id4 overexpression upregulated the expression of proteins associated with cell proliferation, inhibited the PI3K/AKT pathway, and suppressed epithelial-mesenchymal transition (EMT) of HCT116 cells. Moreover, Id4 significantly decreased cytokeratin 18 (CK18) expression, but CK18 overexpression in Id4 expressing HCT116-Id4 cells rescued the activation of AKT, p-AKT, MMP2, MMP7, and E-cadherin. Collectively, our study indicated Id4 may inhibit CRC growth and metastasis through inhibiting the PI3K/AKT pathway in a CK18-dependent manner and suppressing EMT. Id4 may become a target for the treatment of CRC.

16.
Carbohydr Polym ; 264: 118015, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33910717

RESUMO

Owing to its outstanding water-retention ability, viscoelasticity, biocompatibility and non-immunogenicity, Hyaluronic acid (HA), a natural linear polymer alternating linked by d-glucuronic acid and N-acetylglucosamine, has been widely employed in cosmetic, medical and clinical applications. With the development of synthetic biology and bioprocessing optimization, HA production via microbial fermentation is an economical and sustainable alternative over traditional animal extraction methods. Indeed, recently Streptococci and other recombinant systems for HA synthesis has received increasing interests due to its technical advantages. This review summarizes the production of HA by microorganisms and demonstrates its synthesis mechanism, focusing on the current status in various production systems, as well as common synthetic biology strategies include driving more carbon flux into HA biosynthesis and regulating the molecular weight (MW), and finally discusses the major challenges and prospects.


Assuntos
Ácido Hialurônico/biossíntese , Ácido Hialurônico/química , Animais , Fermentação , Humanos , Hialuronoglucosaminidase/metabolismo , Microbiologia Industrial/métodos , Peso Molecular , Polímeros/química , Streptococcus/crescimento & desenvolvimento , Streptococcus/metabolismo , Biologia Sintética/métodos , Viscosidade
17.
J Chromatogr A ; 1645: 462085, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-33848654

RESUMO

Chirality control plays a critical role in developing stereoisomeric drugs. Due to the complexity and lack of predictability in chiral separations, column screening remains the gold standard to initiate chiral method development for active pharmaceutical ingredients (APIs) and synthetic intermediates. Chiral reversed-phase (RP) liquid chromatography (LC) has gained favor over other modes due to its versatility and compatibility in analyzing a wide range of chiral compounds in various matrices. Herein, we established a tier-based chiral RPLC screen strategy by constructing and analyzing a database of 101 chiral screens with a total of 3,401 entries (unique LC runs) for proprietary APIs or intermediates at Bristol Myers Squibb. Up to 17 polysaccharide-based chiral stationary phases (CSPs) and four mobile phases (MPs) have been screened with gradient elution. A selection of ten CSPs with two MPs was found sufficient to achieve successful separation for 82% of the total screens. Two RPLC screen tiers (Tier 1: AZ, OD, ID, and IG) and (Tier 2: AY, OJ, OZ, IA, IC, and IH) were proposed along with two MPs (acidic and neutral) to target ~70% hit rate for Tier 1, and ~80% for the combined set. We also implemented a user-friendly workflow to enable walk-up chiral RPLC screening with automated reports and system suitability tests.


Assuntos
Cromatografia de Fase Reversa/métodos , Preparações Farmacêuticas/análise , Polissacarídeos/química , Preparações Farmacêuticas/química , Preparações Farmacêuticas/isolamento & purificação , Estereoisomerismo
18.
Int J Biol Macromol ; 181: 743-751, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-33798575

RESUMO

In this study, an active component UP1-1 was isolated from Chinese Huangshan Umbilicaria esculenta via hot water extraction and purified by anion-exchange and gel-filtration chromatography. UP1-1 mainly composed of galactose, mannose and glucose in a molar ratio of 0.8:1.0:4.6 with an average molecular weight of 281 kDa. Methylation analysis of UP1-1 revealed the major glycosidic bonds comprised 1,6-linked Glcp, 1,4-linked Glcp, t-linked Glcp, 1,3,6-linked Manp, 1,3-linked Galp, t-linked Galp at the ratio of 2.28:0.38:0.32:0.63:0.25:0.29. Structural analysis results revealed that the backbone of UP1-1 consisted of →6)-ß-D-Glcp-(1→, →6)-ß-D-Manp-(1→, →4)-ß-D-Glcp-(1 → residues with side chains of →3)-ß-D-Galp-(1→, ß-D-Galp-(1 → and ß-D-Glcp-(1 → branches located at O-3 position of →6)-ß-D-Manp-(1→. Immunostimulatory activity tests showed that UP1-1 could promote the phagocytic activity and NO production of RAW 264.7 cells in a dose-dependent manner. UP1-1 could significantly improve the proliferation effect of RAW 264.7 cells at the concentration of 50 µg/mL. Thus, UP1-1 exerted good immunostimulatory activity, suggesting that UP1-1 has a great potential application in pharmacological industry.


Assuntos
Adjuvantes Imunológicos/farmacologia , Ascomicetos/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/isolamento & purificação , Animais , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Glicosídeos/química , Camundongos , Monossacarídeos/análise , Polissacarídeos/isolamento & purificação , Espectroscopia de Prótons por Ressonância Magnética , Células RAW 264.7 , Espectroscopia de Infravermelho com Transformada de Fourier
19.
Cytotechnology ; 73(2): 233-242, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33927478

RESUMO

Hepatic stellate cells (HSCs) activation is a key step that promotes hepatic fibrosis. Emerging evidence suggests that aerobic glycolysis is one of its important metabolic characteristics. Our previous study has reported that CD147, a glycosylated transmembrane protein, contributes significantly to the activation of HSCs. However, whether and how it is involved in the aerobic glycolysis of HSCs activation is unknown. The objective of the present study was to validate the effect of CD147 in HSCs activation and the underlying molecular mechanism. Our results showed that the silencing of CD147 decreased the expression of α-smooth muscle-actin (α-SMA) and collagen I at both mRNA and protein levels. Furthermore, CD147 silencing decreased the glucose uptake, lactate production in HSCs, and repressed the lactate dehydrogenase (LDH) activity, the expression of hexokinase 2 (HK2), glucose transporter 1 (Glut1). The effect of galloflavin, a well-defined glycolysis inhibitor, was similar to CD147 siRNA. Mechanistically, CD147 silencing suppressed glycolysis-associated HSCs activation through inhibiting the hedgehog signaling. Moreover, the hedgehog signaling agonist SAG could rescue the above effect of CD147 silencing. In conclusion, CD147 silencing blockade of aerobic glycolysis via suppression of hedgehog signaling inhibited HSCs activation, suggesting CD147 as a novel therapeutic target for hepatic fibrosis. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-021-00460-9.

20.
Open Med (Wars) ; 16(1): 553-557, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33869777

RESUMO

Camrelizumab (SHR-1210), a human monoclonal antibody against programmed death receptor 1 (PD-1), blocks the binding of PD-1 to PD-L1, consequently inhibiting immune system evasion by tumor cells. A 65-year-old man underwent radical esophagectomy 5 months ago following the diagnosis of esophageal cancer by gastroscopy. Approximately 40 days later, capecitabine was administered at a dosage of 1.5 g Po bid for 14 days, and anti-PD-1 (camrelizumab 200 mg) was administered twice. Around 20 days later, abnormal liver function was detected. He received a diagnosis of drug-induced liver injury. Chest computed tomography scanning revealed interstitial inflammatory lesions in both lower lungs. Liver biopsy revealed immune injury with ductopenia. Therefore, the diagnosis was revised as immune-related pneumonia and hepatitis associated with camrelizumab. The treatment regimen of methylprednisolone was adjusted to 40 mg/day and gradually increased to 80 mg/day. Mycophenolate mofetil was administered at a dose of 2 g/day. Consequently, chest tightness and shortness of breath resolved, and pulmonary inflammation improved. However, jaundice did not improve and continued to exacerbate. The last measured prothrombin time was 41 s, prothrombin activity was 19%, and the international normalized ratio was 4.03. The cause of death was diagnosed as liver failure, cardiopulmonary failure, and septic shock.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...