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1.
J Plast Surg Hand Surg ; : 1-9, 2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34602014

RESUMO

In this study, we investigated the feasibility of using a geometrically designed anterior ramus graft to reconstruct lateral mandibular defects. This was achieved by assessing the anatomical dimensions of the mandibular ramus on computed-tomographies. The design sequence and application of the graft was also demonstrated using one of our cases. The following dimensions were measured; a and b - horizontal length from mid-ramus to the posterior and anterior ramus border respectively, c - longest length of the graft, Mp - width at the centre of the ramus, h - vertical length of the angle at its cross-section, w - horizontal length of the angle at its cross-section, x - cross-sectional area along the mandible angle. A total of 80 mandibular rami were examined. The mean length of a, b, c were 17.3 ± 1.8 mm, 15.9 ± 1.2 mm, 54.6 ± 3.8 mm, respectively. The mean width of Mp was 9.8 ± 1.1 mm. The mean cross section area of Eo-Md (x) was 326.7 ± 67.8 mm2. The average length of h and w were 26.5 ± 3.2 and 15.6 ± 2.1 mm, respectively. The use of virtual surgical planning (VSP) to geometrically design the graft was also described. Together with VSP, the anterior ramus bone graft will allow for reconstruction of the mandible with greater surgical efficiency, reduced complexity and without the need for extra-oral bone harvest. This may be an useful alternative in situations where simpler reconstructive procedures are preferred.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34508611

RESUMO

OBJECTIVES: To characterize a novel MDR efflux pump gene cluster tnfxB3-tmexCD3-toprJ1b carried by Proteus spp. and Pseudomonas aeruginosa strains from chickens. METHODS: Antimicrobial susceptibility testing, conjugation and WGS were performed to characterize tnfxB3-tmexCD3-toprJ1b-positive isolates. Cloning and reverse transcription-quantitative PCR were performed to investigate the function of tnfxB3-tmexCD3-toprJ1b. RESULTS: The WGS data revealed that a novel efflux pump gene cluster, tnfxB3-tmexCD3-toprJ1b, was identified on the chromosome of the Proteus cibarius strain SDQ8C180-2T, where an SXT/R391-family integrative and conjugative element (ICE) was found to co-carry tet(X6) and tnfxB3-tmexCD3-toprJ1b. Further retrospective analysis found two other tnfxB3-tmexCD3-toprJ1b variants in a Proteus mirabilis isolate and a P. aeruginosa isolate, respectively. tmexCD3-toprJ1b and its variants increased the MICs of tigecycline (8-fold) and other antibiotics (2-8-fold) in Escherichia coli host strains. The TNfxB3 protein down-regulated the expression of the tmexCD3-toprJ1b operon. Moreover, genetic-context analyses showed that tnfxB3-tmexCD3-toprJ1b together with adjacent integrase genes appeared to compose a transferable module 'int1-like+int2-like+hp1+hp2+ISCfr1+tnfxB3-tmexCD3-toprJ1b', which was inserted into the umuC-like gene of this ICE. Further analysis of the tnfxB3-tmexCD3-toprJ1b-harbouring sequences deposited in GenBank revealed similar transferable modules inserted into umuC-like genes in plasmids or chromosomes of Klebsiella pneumoniae, Pseudomonas spp. and Aeromonas spp., implying that these modules could be transferred across different bacterial species. CONCLUSIONS: To the best of our knowledge, this is the first identification of a novel tigecycline gene cluster, tmexCD3-toprJ1b, which co-exists with tet(X6) within an ICE. More attention should be paid to the co-transfer of these two tigecycline resistance determinants via an ICE to other Gram-negative bacteria.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34499729

RESUMO

BACKGROUND: The increasing use of colistin causes a serious breach in our last line of defence against MDR Gram-negative pathogens. Our previous study showed that CpxR overexpression increases the susceptibility of acrB and cpxR double-deleted Salmonella enterica serovar Typhimurium to colistin. OBJECTIVES: To identify the mechanism of CpxAR and efflux pumps that synergistically enhance the susceptibility of S. Typhimurium to colistin. METHODS: A series of cpxR- and tolC-deleted mutants and a cpxR-complemented strain from a multidrug-susceptible standard strain of S. Typhimurium (JS) were generated in our previous study. Herein, we investigated the susceptibility of these strains to colistin through the broth microdilution method, time-kill curves and survival assays. Growth curves were measured by OD600 in LB broth, tryptone-soy broth (TSB) and M9-glucose (0.2%) minimal media. Finally, molecular mechanisms underlying the mode of action were elucidated by transcriptomic analysis. RESULTS: We found that in contrast to JS (0.8 mg/L), the MIC of colistin for JSΔtolC::kan showed a 16-fold decrease (0.05 mg/L). Notably, JSΔcpxRΔtolC and JSΔcpxRΔtolC/pcpxR were associated with a 256-fold decrease (0.0031 mg/L) compared with JS. Growth curves identified that JSΔcpxRΔtolC and JSΔcpxRΔtolC/pcpxR displayed a markedly lower growth rate and poorer adaptability. In addition, time-kill curves and survival assays showed that JSΔcpxRΔtolC and JSΔcpxRΔtolC/pcpxR were more susceptible to colistin. Lastly, double deletion of cpxR and tolC enhanced oxidative damage through promoting oxidative phosphorylation, the tricarboxylic acid (TCA) cycle and trimethylamine N-oxide (TMAO) respiration. CONCLUSIONS: Our findings revealed that double deletion of cpxR and tolC significantly increases the susceptibility of S. Typhimurium to colistin.

4.
Neurol Ther ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34478123

RESUMO

BACKGROUND: Pulmonary arterial venous malformation (PAVM) is an abnormal vascular malformation between pulmonary arteries and veins characterized by varying degrees of right-to-left shunts (RLS). Cryptogenic stroke (CS) due to paradoxical embolism (PE) caused by PAVM is relatively rare in the clinic. CASE PRESENTATION: We report the case of a 54-year-old right-handed woman who presented with sudden-onset left-sided limb weakness for 2 h. A physical examination revealed normal vital signs but weakness in her left upper and lower limbs, graded as 1/5 using the Medical Research Council scale. Her National Institutes of Health Stroke Scale (NIHSS) score was 8, and her modified Rankin scale (mRS) was 4. Brain diffusion-weighted imaging showed acute infarction in the right basal ganglia and the radiation crown but brain magnetic resonance angiography found no obvious abnormality. A transcranial Doppler ultrasound with bubble study (TCD-b) found the rain curtain sign of microbubbles in the left middle cerebral artery, reflecting significant RLS. Transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE) were conducted to distinguish between intra- and extracardiac shunts. A pulmonary computerized tomography angiogram (CTA) demonstrated a PAVM. We considered the patient had CS due to PE caused by PAVM. Thrombolytic therapy within the time window was performed. Then, transcatheter device occlusion of the arteriovenous fistula was successfully undertaken, and the patient carried on with rehabilitation training. At a 15-month follow-up, there were no catheter-related complications or recurrent stroke, and her NIHSS and mRS scores were both 0. CONCLUSIONS: PAVM is an important risk factor for PE and CS and should not be ignored as a possible etiology in stroke patients without any other risk factors. CTA of the pulmonary artery is the recommended gold standard for diagnosing and locating a PAVM. Thrombolytic therapy within the time window combined with transcatheter device occlusion of arteriovenous malformation and rehabilitation training may benefit the recovery of patients with CS caused by PE resulting from PAVM.

5.
Autoimmunity ; : 1-11, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34533429

RESUMO

Exosomes isolated from mesenchymal stem cells (MSC) had shown beneficial effect on acute lung injury (ALI). However, the effective components in MSC-derived exosomes need further investigation. ALI mice model was established by lipopolysaccharide (LPS) injection. In vitro inflammatory model was established by LPS stimulation of MLE-12 cells. The cell proliferation was evaluated by EdU assay. TUNEL and Annexin V/PI were applied to evaluate the apoptosis of tissue and cell respectively. HE staining was performed to evaluate the lung injury. Transmission electronic microscope was used to observe isolated exosomes. Level of cytokines, MDA, KGF were determined by ELISA kit. Direct interaction of miR-132-3p and TRAF6 were verified by dual luciferase assay. The level of mRNA or proteins were determined by qRT-PCR or western blots respectively. TRAF6 was upregulated while miR-132-3p was downregulated in LPS-stimulated ALI model. MiR-132-3p negatively regulated TRAF6 by direct binding. MiR-132-3p potentiated proliferation and suppressed apoptosis of LPS-induced MLE-12 cells at least partly dependent on targeting TRAF6. Treatment of exosome alleviated the LPS-induced ALI in mice and LPS-induced inflammatory response in MLE-12 cells. Moreover, overexpression of miR-132-3p promoted the protective effect of exosomes in LPS-induced MLE-12 cells injury and LPS-induced ALI. Mechanically, it was suggested that miR-132-3p inactivated PI3K/Akt signalling via targeting TRAF6. In the present study, our results indicated that miR-132-3p mediated protective effect of MSC-derived exosomes on LPS-induced ALI. Exosomal miR-132-3p ameliorated LPS-induced ALI via targeting TRAF6 and inactivating PI3K/Akt signalling.

6.
J Control Release ; 338: 773-783, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34530052

RESUMO

Pro-angiogenic growth factors have been studied as potential therapeutics for cardiovascular diseases like critical limb ischemia (CLI). However, the translation of these factors has remained a challenge, in part, due to problems associated with safe and effective delivery. Here, we describe a hydrogel-based delivery system for growth factors where release is modulated by focused ultrasound (FUS), specifically a mechanism termed acoustic droplet vaporization. With these fibrin-based, acoustically-responsive scaffolds (ARSs), release of a growth factor is non-invasively and spatiotemporally-controlled in an on-demand manner using non-thermal FUS. In vitro studies demonstrated sustained release of basic fibroblast growth factor (bFGF) from the ARSs using repeated applications of FUS. In in vivo studies, ARSs containing bFGF were implanted in mice following induction of hind limb ischemia, a preclinical model of CLI. During the 4-week study, mice in the ARS + FUS group longitudinally exhibited significantly more perfusion and less visible necrosis compared to other experimental groups. Additionally, significantly greater angiogenesis and less fibrosis were observed for the ARS + FUS group. Overall, these results highlight a promising, FUS-based method of delivering a pro-angiogenic growth factor for stimulating angiogenesis and reperfusion in a cardiovascular disease model. More broadly, these results could be used to personalize the delivery of therapeutics in different regenerative applications by actively controlling the release of a growth factor.

7.
Nanoscale ; 13(38): 16251-16257, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34549746

RESUMO

Integrating multi-modal imaging and therapy functions into a nanoplatform has been recognized as a promising strategy for cancer theranostics with high accuracy and efficiency. However, there are still some challenges, such as the complicated synthesis process and instability. Herein, we successfully prepared clearable MnCo2O4 nanodots modified with polyacrylic acid (MnCo2O4@PAA) as nanoagents for T1/T2 bimodal MRI imaging-guided PTT. Owing to their intrinsic magnetic properties, single MnCo2O4@PAA nanomaterials can serve as contrasts for T1/T2 bimodal MRI, providing precise diagnotic information. Moreover, excellent absorption in the NIR biowindow endows MnCo2O4@PAA with good photothermal performance, and the ultrasmall size of MnCo2O4@PAA allows them to penetrate deeply into tumors, resulting in a good anticancer effect in vitro and in vivo. What is more, MnCo2O4@PAA can almost be completely cleared from mice at 7 d postinjection, implying their negligible long-term toxicity. These findings demonstrate that MnCo2O4@PAA are promising nanoagents for cancer diagnosis and treatment, which have great potential for clinical applications.


Assuntos
Nanopartículas , Nanoestruturas , Neoplasias , Animais , Imageamento por Ressonância Magnética , Camundongos , Fototerapia , Terapia Fototérmica , Nanomedicina Teranóstica
8.
Ecotoxicol Environ Saf ; 223: 112593, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34358929

RESUMO

The study was done to elucidate the molecular mechanisms underlying the steady maintenance of the green microalga Dunaliella salina GY-H13 in successive subcultures in F/2 medium supplemented with the high cadmium (Cd) concentration (5 mg L-1) for 3 months or 84 days using physiological, metabolomic, and transcriptomic methodologies. Physiological analysis indicated that Cd suppressed growth rate, photosynthetic efficiency, and pigment contents and promoted Cd accumulation, reactive oxygen species (ROS) generation and lipid peroxidation. UPLC-MS/MS-based metabolic analysis identified the top most upregulated and downregulated metabolites, the 5'-dehydroxyadenosine and thiamine acetic acid that were associated with the formation and removal of H2O2. RNA-seq-based transcriptomic analysis showed the overrepresentation of low-CO2-inducible genes in the most downregulated gene set. Metabolomic and transcriptomic analyses further showed that the decreased GSSG/GSH-based redox potential, increased oxidative-phosphorylation gene expression, and reduced activity of TCA cycle in cells after extended exposure to Cd. Taken together, our results imply that cellular defense to Cd in D. salina is achieved by upregulation of ROS-scavenging activities including depletion of thiamine acetic acid. Dynamic redox homeostasis is maintained in cells with extended exposure to Cd by production of both oxidants and antioxidants through multiple pathways.


Assuntos
Cádmio , Transcriptoma , Antioxidantes , Cádmio/toxicidade , Cromatografia Líquida , Homeostase , Peróxido de Hidrogênio , Oxirredução , Estresse Oxidativo , Espécies Reativas de Oxigênio , Espectrometria de Massas em Tandem
9.
J Invest Dermatol ; 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34364883

RESUMO

Psoriasis is a common, inflammatory autoimmune skin disease. Early detection of an IFN-1 signature occurs in many psoriasis lesions, but the source of IFN production remains debated. IFN-κ is an important source of IFN-1 production in the epidermis. We identified a correlation between IFN-regulated and psoriasis-associated genes in human lesional skin. We thus wanted to explore the effects of IFN-κ in psoriasis using the well-characterized imiquimod psoriasis model. Three mouse strains aged 10 weeks were used: wild-type C57Bl/6, C57Bl/6 that overexpress Ifnk in the epidermis (i.e., transgenic), and total body Ifnk-/- (i.e., knockout) strain. Psoriasis was induced by topical application of imiquimod on both ears for 8 consecutive days. Notably, the severity of skin lesions and inflammatory cell infiltration was more significantly increased in transgenic than in wild-type than in knockout mice. Gene expression analysis identified greater upregulation of Mxa, Il1b, Tnfa, Il6, Il12, Il23, Il17, and Ifng in transgenic compared to wild-type compared to knockout mice after imiquimod treatment. Furthermore, imiquimod increased CD8+ and CD4+ T-cell infiltration more in transgenic than in wild-type than in knockout mice. In summary, we identified IFN-κ as a rheostat for initiation of psoriasiform inflammation. This suggests that targeting IFN-1s early in the disease may be an effective way of controlling psoriatic inflammation.

10.
Emerg Infect Dis ; 27(9): 2288-2293, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34423766

RESUMO

We estimated the symptomatic, PCR-confirmed secondary attack rate (SAR) for 2,382 close contacts of 476 symptomatic persons with coronavirus disease in Yichang, Hubei Province, China, identified during January 23-February 25, 2020. The SAR among all close contacts was 6.5%; among close contacts who lived with an index case-patient, the SAR was 10.8%; among close-contact spouses of index case-patients, the SAR was 15.9%. The SAR varied by close contact age, from 3.0% for those <18 years of age to 12.5% for those >60 years of age. Multilevel logistic regression showed that factors significantly associated with increased SAR were living together, being a spouse, and being >60 years of age. Multilevel regression did not support SAR differing significantly by whether the most recent contact occurred before or after the index case-patient's onset of illness (p = 0.66). The relatively high SAR for coronavirus disease suggests relatively high virus transmissibility.


Assuntos
COVID-19 , SARS-CoV-2 , Adolescente , Criança , China/epidemiologia , Humanos , Incidência , Modelos Logísticos
11.
Mol Cell Biochem ; 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34346000

RESUMO

Acute lung injury (ALI) is a fatal inflammatory response syndrome. LncRNA XIST (XIST) is a lung cancer-related gene and participates in pneumonia. However, whether XIST participates in lipopolysaccharides (LPS)-induced ALI remains unclear. LPS-induced inflammation model was constructed in vitro, then cell viability, cytokines, cell apoptosis, protein, and mRNA expressions were individually detected by cell counting kit-8, enzyme-linked immunosorbent assay and flow cytometry, Western blot, and qRT-PCR. A dual-luciferase reporter assay confirmed the relationships among XIST, miR-132-3p, and MAPK14. Furthermore, inflammation and conditions after knockdown of XIST were assessed by hematoxylin and eosin staining, lung wet-to-dry weight ratio, PaO2/FiO2 ratio, and malondialdehyde (MDA) contents using LPS-induced in vivo model. Our findings indicated that the LPS challenge decreased cell viability, increased cell apoptosis, and caused secretions of pro-inflammatory cytokines. Noticeably, LPS significantly upregulated XIST, MAPK14, and downregulated miR-132-3p. Mechanistically, XIST acted as a molecular sponge to suppress miR-132-3p, and MAPK14 was identified as a target of miR-132-3p. Functional analyses demonstrated that XIST silencing remarkably increased cell survival and alleviated cell death and lung injury through decreasing TNF-α, IL-1ß, IL-6, accumulation of inflammatory cells, alveolar hemorrhage, MDA release, and increased PaO2/FiO2 ratio, as well as upregulating Bcl-2, and downregulating Bax, MAPK14, and p-extracellular signal-regulated kinases ½. In contrast, inhibition of the miR-132-3p antagonized the effects of XIST silencing. In conclusion, inhibition of XIST exhibited a protective role in LPS-induced ALI through modulating the miR-132-3p/MAPK14 axis.

12.
Neurosci Lett ; 762: 136139, 2021 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-34324959

RESUMO

What is the most useful online consumer review? Consumers face the challenge of identifying useful online consumer reviews, some of which might have been manipulated by retailers. Reviewer's review volumes is the past behavior of a reviewer which is one of the most important cues of the reviewer expertise. While reviewer cues are receiving increasing attention, the effect of reviewer's review volumes on the perceived usefulness of online consumer review remains under-explored. This research explored the underlying neural mechanism of reviewer's review volumes on the perceived usefulness of online consumer reviews by applying the event-related potentials (ERPs) approach. Behaviorally, a higher perceived usefulness rate and reduced reaction time were observed for the high-review-volume condition compared to the low-review-volume condition, indicating that the high-review-volume condition was more desirable to the participants. At the neural level, the high-review-volume condition elicited an attenuated N2 and an increased LPP compared with the low-review volume condition, suggesting a more positive evaluation of the high-review volume condition. These results showed the positive impact of the reviewer's review volumes on the perceived usefulness of online consumer reviews and its potential neural substrates.

13.
Colloids Surf B Biointerfaces ; 206: 111936, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34214839

RESUMO

In this study, the effect of high-pressure steam sterilization (121 °C for 15 min) on whey protein hydrolysate-pectin solutions and emulsions was studied. The interaction and emulsification characteristics of pectin and whey protein concentrate (WPC) were evaluated from the solution system to the emulsion system. Enzymatic hydrolysis of WPC (WPH, 2 % and 8 % degree of hydrolysis) increased the covalent binding with pectin, which reduced the heat-induced aggregation of protein and improved emulsification. The thermodynamic incompatibility between WPC and pectin was not conducive to the covalent bonding under high temperature sterilization and produced serious aggregates, which also made a rapid increase in particle size (up to ∼3 µm), compared to WPH-pectin emulsion (∼ 400 nm). In addition, if emulsion was stirred during the sterilization, the creaming and protein aggregation could be avoided. By comparing low methoxy pectin (LMP) and high methoxy pectin (HMP), it was found that the whey protein-HMP complex had better emulsification stability, and the steric stabilization played a more important role in emulsion stability than the electrostatic repulsion. The changes of whey protein and pectin at the oil-water interface of the emulsion during the sterilization process may provide a reference for the sterilized bioactive ingredient delivery system.


Assuntos
Pectinas , Hidrolisados de Proteína , Emulsões , Temperatura Alta , Esterilização , Temperatura , Soro do Leite , Proteínas do Soro do Leite
14.
Cancer Lett ; 518: 207-213, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34271105

RESUMO

AJCC TNM stage and WHO grade (G) are two widely used staging systems to guide clinical management for pancreatic neuroendocrine neoplasms (panNENs), based on clinical staging and pathological grading information, respectively. We proposed to integrate TNM stage and G grade into one staging system (TNMG) and to evaluate its clinical application as a prognostic indicator for panNENs. Accordingly, 5254 patients diagnosed with panNENs were used to evaluate and to validate the applicability of TNMG to panNENs. The predictive accuracy of TNMG system was compared with that of each separate staging/grading system. We found that TNM stage and G grade were independent risk factors for survival in both the Surveillance, Epidemiology, and End Result (SEER) and multicenter series. The interaction effect between TNM stage and G grade was significant. Twelve subgroups combining the TNM stage and G grade were proposed in the TNMG stage, which were classified into five stages TNMG. According to the TNMG staging classification in the SEER series, the estimated median survival for stages I, II, III, IV, and V were 203, 174, 112, 61, and 8 months, respectively. The predictive accuracy of TNMG stage was higher than that of TNM stage and G grade used independently. The TNMG stage classification was more accurate in predicting panNEN patient's prognosis than either the TNM stage or G grade.

15.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207032

RESUMO

The gastrointestinal tract is a heterogeneous ecosystem with distinct, stratified environments, which leads to different microbial composition in different intestinal segments. The regional heterogeneity of intestinal microbiota complicates the relationship between diet and microbiota. Few studies have focused on the effects of different diets on microbiota in different intestinal segments. This study aimed to investigate the effects of functional fiber on the microbial composition in multiple intestinal segments from a high-fat diet compared with a normal chow diet. We found that the response of microbiota from different intestinal segments to diet was related to the intestinal physiologic function and the physicochemical properties of dietary nutrients. A high-fat diet drove changes in the microbial composition in the hindgut, possibly by affecting the digestive environment of the foregut, and increased the regional heterogeneity of the whole intestinal microbiota. The supplementation of functional fiber promoted the microbial transfer and colonization from the anterior to the posterior intestinal segments, and increased the regional similarity of intestinal microbiota accordingly, particularly within the hindgut. The gut fermentation of the functional fiber, which mainly occurred in the hindgut, resulted in a significant change in the microbial composition and metabolism in the cecum and colon, with richer carbohydrate metabolism-related bacteria, including Mucispirillum, Prevotella, Anaerostipes, Oscillospira, Ruminococcus, Bacteroides, Coprococcus, Ruminococcus (Lachnospiraceae), and Allobaculum, and higher production of acetate and butyrate. We concluded that multiple regulatory mechanisms of diets which affect microbiota composition exist, including microbial metabolism, microbial migration, and the regulation of the intestinal environment.


Assuntos
Fibras na Dieta , Microbioma Gastrointestinal , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Obesidade/etiologia , Obesidade/metabolismo , Animais , Biodiversidade , Ceco/metabolismo , Ceco/microbiologia , Colo/metabolismo , Colo/microbiologia , Modelos Animais de Doenças , Suscetibilidade a Doenças , Ácidos Graxos Voláteis/metabolismo , Fezes/microbiologia , Camundongos , Camundongos Obesos , Especificidade de Órgãos
16.
ACS Appl Mater Interfaces ; 13(30): 35568-35578, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34286585

RESUMO

Mitochondria-targeted synergistic therapy, including photothermal (PTT) and photodynamic therapy (PDT), has aroused wide attention due to the high sensitivity to reactive oxygen species (ROS) and heat shock of mitochondria. However, most of the developed nanosystems for the combinatorial functions require the integration of different components, such as photosensitizers and mitochondria-targeted molecules. Consequently, it indispensably requires sophisticated design and complex synthetic procedures. In this work, a well-designed Bi2S3-based nanoneedle, that localizes to mitochondria and produces extra ROS with inherent photothermal effect, was reported by doping of Fe (denoted as FeBS). The engineered intrinsic characteristics certify the capacity of such "one-for-all" nanosystems without additional molecules. The lipophilicity and surface positive charge are demonstrated as crucial factors for specifical mitochondria targeting. Significantly, Fe doping overcomes the disadvantage of the narrow band gap of Bi2S3 to prevent the fast recombination of electron-hole, hence resulting in the generation of ROS for PDT. The "one-for-all" nanoparticles integrate with mitochondria-targeting and synergistic effect of PDT and PTT, thus exhibit enhanced therapeutic effect and inhibit the growth of tumors observably. This strategy may open a new direction in designing the mitochondria-targeted materials and broadening the properties of inorganic semiconductor materials for satisfactory therapeutic outcomes.

17.
Aging (Albany NY) ; 13(14): 18423-18441, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34315133

RESUMO

We investigated the mechanisms underlying the therapeutic effects of Yiqi Jiemin decoction (YJD), a traditional Chinese medicine (TCM), in the ovalbumin (OVA)-induced allergic rhinitis (AR) model in guinea pigs. YJD significantly decreased infiltration of mast cells and eosinophils into the nasal mucosa of AR model guinea pigs. YJD also increased expression of TGF-ß in the nasal mucosa, restored the balance of Th1/Th2 immune cell responses, and decreased serum levels of various pro-inflammatory mediators, including histamine (HA), neuropeptide Y (NPY), acetylcholine (ACH), norepinephrine and immunoglobulin E (IgE). Metabolic analyses using liquid chromatography coupled with high-resolution mass spectrometry revealed that YJD improved cellular metabolism in AR model guinea pigs and increased serum levels of glycocholic acid while decreasing levels 1-palmitoyl lysophosphatidic acid. RNA-sequencing analysis identified BPIFB2 as a potential diagnostic biomarker and therapeutic target for AR. Functional enrichment analyses showed that YJD significantly inhibited cytokine secretion pathways in AR model guinea pigs. These findings demonstrate that YJD protects against OVA-induced AR in guinea pigs by suppressing inflammation in the nasal mucosa, restoring Th1/Th2 balance, and improving cellular metabolism.

19.
Sci Rep ; 11(1): 14822, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34285333

RESUMO

To develop a predictive model and a nomogram for predicting postoperative hemorrhage in preoperative patients undergoing laparoscopic pancreaticoduodenectomy (LPD). A total of 409 LPD patients that underwent LPD by the same surgical team between January 2014 and December 2020 were included as the training cohort. The preoperative data of patients were statistically compared and analyzed for exploring factors correlated with postoperative hemorrhage. The predictive model was developed by multivariate logistic regression and stepwise (stepAIC) selection. A nomogram based on the predictive model was developed. The discriminatory ability of the predictive model was validated using the receiver operating characteristic (ROC) curve and leave-one-out method. The statistical analysis was performed using R 3.5.1 ( www.r-project.org ). The predictive model including the risk-associated factors of postoperative hemorrhage was as follows: 2.695843 - 0.63056 × (Jaundice = 1) - 1.08368 × (DM = 1) - 2.10445 × (Hepatitis = 1) + 1.152354 × (Pancreatic tumor = 1) + 1.071354 × (Bile duct tumor = 1) - 0.01185 × CA125 - 0.04929 × TT - 0.08826 × APTT + 26.03383 × INR - 1.9442 × PT + 1.979563 × WBC - 2.26868 × NEU - 2.0789 × LYM - 0.02038 × CREA + 0.00459 × AST. A practical nomogram based on the model was obtained. The internal validation of ROC curve was statistically significant (AUC = 0.7758). The validation by leave-one-out method showed that the accuracy of the model and the F measure was 0.887 and 0.939, respectively. The predictive model and nomogram based on the preoperative data of patients undergoing LPD can be useful for predicting the risk degree of postoperative hemorrhage.

20.
Anal Chem ; 93(31): 10850-10861, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34320311

RESUMO

We describe a mass spectrometry (MS) analytical platform resulting from the novel integration of acoustic droplet ejection (ADE) technology, an open-port interface (OPI), and electrospray ionization (ESI)-MS that creates a transformative system enabling high-speed sampling and label-free analysis. The ADE technology delivers nanoliter droplets in a touchless manner with high speed, precision, and accuracy. Subsequent sample dilution within the OPI, in concert with the capabilities of modern ESI-MS, eliminates the laborious sample preparation and method development required in current approaches. This platform is applied to a variety of experiments, including high-throughput (HT) pharmacology screening, label-free in situ enzyme kinetics, in vitro absorption, distribution, metabolism, elimination, pharmacokinetic and biomarker analysis, and HT parallel medicinal chemistry.


Assuntos
Ensaios de Triagem em Larga Escala , Espectrometria de Massas por Ionização por Electrospray , Acústica
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