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1.
J Biol Chem ; : 100426, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33609526

RESUMO

Birt-Hogg-Dubé (BHD) syndrome is a multiorgan disorder caused by inactivation of the folliculin (FLCN) protein. Previously, we identified FLCN as a binding protein of Rab11A, a key regulator of the endocytic recycling pathway. This finding implies that the abnormal localization of specific proteins whose transport requires the FLCN-Rab11A complex may contribute to BHD. Here, we used human kidney-derived HEK293 cells as a model, and we report that FLCN promotes the binding of Rab11A with transferrin receptor 1 (TfR1), which is required for iron uptake through continuous trafficking between the cell surface and the cytoplasm. Loss of FLCN attenuated the Rab11A-TfR1 interaction, resulting in delayed recycling transport of TfR1. This delay caused an iron deficiency condition that induced hypoxia-inducible factor (HIF) activity, which was reversed by iron supplementation. In a Drosophila model of BHD syndrome, we further demonstrated that the phenotype of BHD mutant larvae was substantially rescued by an iron-rich diet. These findings reveal a conserved function of FLCN in iron metabolism and may help to elucidate the mechanisms driving BHD syndrome.

2.
Proc Natl Acad Sci U S A ; 118(6)2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33547233

RESUMO

Intracellular delivery of messenger RNA (mRNA)-based cancer vaccine has shown great potential to elicit antitumor immunity. To achieve robust antitumor efficacy, mRNA encoding tumor antigens needs to be efficiently delivered and translated in dendritic cells with concurrent innate immune stimulation to promote antigen presentation. Here, by screening a group of cationic lipid-like materials, we developed a minimalist nanovaccine with C1 lipid nanoparticle (LNP) that could efficiently deliver mRNA in antigen presenting cells with simultaneous Toll-like receptor 4 (TLR4) activation and induced robust T cell activation. The C1 nanovaccine entered cells via phagocytosis and showed efficient mRNA-encoded antigen expression and presentation. Furthermore, the C1 lipid nanoparticle itself induced the expression of inflammatory cytokines such as IL-12 via stimulating TLR4 signal pathway in dendritic cells. Importantly, the C1 mRNA nanovaccine exhibited significant antitumor efficacy in both tumor prevention and therapeutic vaccine settings. Overall, our work presents a C1 LNP-based mRNA cancer nanovaccine with efficient antigen expression as well as self-adjuvant property, which may provide a platform for developing cancer immunotherapy for a wide range of tumor types.

3.
BMC Cardiovasc Disord ; 21(1): 51, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33526034

RESUMO

BACKGROUND: Atherosclerosis (AS) is a chronic inflammatory disorder. The aim of our study was to explore the role of circular RNA (circRNA) transmembrane 7 superfamily member 3 (circTM7SF3) in AS progression. METHODS: Experiments were conducted using oxidized low-density lipoprotein (ox-LDL)-induced THP-1-derived macrophages and differentiated human monocyte-derived macrophages (hMDMs). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of circTM7SF3, its linear form TM7SF3, microRNA-206 (miR-206) and aspartyl (asparaginyl) ß-hydroxylase (ASPH) messenger RNA (mRNA). Cell viability and apoptosis were examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. Cell inflammation was analyzed by measuring the production of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) using enzyme-linked immunosorbent assay (ELISA) kits. Cell oxidative stress was assessed through analyzing the levels of oxidative stress markers using their corresponding commercial kits. Dual-luciferase reporter assay and RNA-pull down assay were used to confirm the interaction between miR-206 and circTM7SF3 or ASPH. The protein level of ASPH was examined by Western blot assay. RESULTS: CircTM7SF3 level was markedly increased in the serum samples of AS patients and ox-LDL-induced THP-1-derived macrophages compared with their matching counterparts. ox-LDL induced-damage in THP-1 cells was partly attenuated by the interference of circTM7SF3. MiR-206 was a downstream molecular target of circTM7SF3. Si-circTM7SF3-mediated effects in ox-LDL-induced THP-1-derived macrophages were partly ameliorated by the addition of anti-miR-206. MiR-206 directly interacted with ASPH mRNA. CircTM7SF3 silencing reduced the expression of ASPH partly through up-regulating miR-206 in THP-1-derived macrophages. ASPH overexpression partly counteracted the effects induced by miR-206 overexpression in ox-LDL-induced THP-1-derived macrophages. CONCLUSION: CircTM7SF3 contributed to ox-LDL-induced injury in AS cell model through up-regulating the expression of ASPH via targeting miR-206.

4.
Anal Chem ; 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33599499

RESUMO

Accurate counting of single molecules at nanoscale resolution is essential for the study of molecular interactions and distribution in subcellular fractions. By using small-sized carbon dots (CDs), we have now developed a quantitative single-molecule localization microscopy technique (qSMLM) based on spontaneous blinking to count single molecules with a localization precision of 10 nm, which can be accomplished on conventional microscopes without sophisticated laser control. We explore and adapt the blinking of CDs with diverse structures and demonstrate a counting accuracy of >97% at a molecular density of 500 per µm2. When applied to G-protein coupled receptors on a cell membrane, we discriminated receptor oligomerization and clustering and revealed ligand-regulated receptor distribution patterns. This is the first example of adapting nanoparticle self-blinking for molecular counting, and this demonstrates the power of CDs as SMLM probes to reliably decipher sub-diffraction structures that mediate crucial biological functions.

5.
BMC Geriatr ; 21(1): 113, 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33563232

RESUMO

BACKGROUND: Community-acquired pneumonia (CAP) and acute myocardial infarction cardiovascular (AMI) are two important health issues in older patients. Little is known regarding characteristics of AMI in older patients hospitalized for CAP. Therefore, we investigated the prevalence, characteristics compared with younger patients, impact on clinical outcomes and risk factors of AMI during hospitalization for CAP in geriatric patients. METHODS: Eleven thousand nine adult inpatients consisted of 5111 patients≥65 years and 5898 patients< 65 years in respiratory ward diagnosed with CAP were retrospectively analyzed by electronic medical records. RESULTS: 159 (3.1%) older patients in respiratory ward experienced AMI during hospitalization for CAP. AMI were more frequently seen in patients≥65 years compared with patients< 65 years (3.1% vs. 1.0%). Patients≥65 years who experienced AMI during hospitalization for CAP had higher percentage of respiratory failure (P = 0.001), hypertension (P = 0.008), dyspnea (P = 0.046), blood urea nitrogen (BUN) ≥7 mmol/L (P < 0.001), serum sodium< 130 mmol/L (P = 0.005) and had higher in-hospital mortality compared to patients< 65 years (10.1% vs. 6.6%). AMI was associated with increased in-hospital mortality (odds ratio, OR, with 95% confidence interval: 1.49 [1.24-1.82]; P < 0.01). Respiratory failure (OR, 1.34 [1.15-1.54]; P < 0.01), preexisting coronary artery disease (OR, 1.31[1.07-1.59]; P = 0.02), diabetes (OR, 1.26 [1.11-1.42]; P = 0.02) and BUN (OR, 1.23 [1.01-1.49]; P = 0.04) were correlated with the occurrence of AMI in the older patients after hospitalization with CAP. CONCLUSIONS: The incidence of AMI during CAP hospitalization in geriatric patients is notable and have an impact on in-hospital mortality. Respiratory failure, preexisting coronary artery disease, diabetes and BUN was associated with the occurrence of AMI in the older patients after hospitalization with CAP. Particular attention should be paid to older patients with risk factors for AMI.

6.
Biomater Sci ; 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33595569

RESUMO

In this study, UiO-66-NH2 metal-organic framework (MOF) nanoparticles with peroxidase and oxidase mimetic activities were incorporated into a chitosan (CS) matrix by a simple and environmentally friendly method. The UiO-66-NH2/CS composite membrane possesses the peroxidase mimicking activity in the presence of traces of H2O2, thus resulting in good antibacterial properties. Intriguingly, 30 min of UV pre-irradiation of the UiO-66-NH2/CS composite membrane, in the absence of H2O2, still leads to a good antibacterial activity. This was attributed to the oxidase mimetic activity and the peroxidase mimicking activity of UiO-66-NH2. In such a way, the side effects of direct exposure to UV irradiation and H2O2 can be avoided for wound-healing treatments. The antibacterial mechanism was further proved by antibacterial experiments, TMB·2HCl color development experiments, reactive oxygen species generation tests and electron spin resonance tests. As a potential medical antibacterial dressing, in vitro membranes were also investigated.

7.
J Nat Prod ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33606538

RESUMO

Nine new glucosyloxybenzyl 2-hydroxy-2-isobutylsuccinates, pleionosides M-U (1-9), and 12 known compounds (10-21) were isolated from the pseudobulbs of Pleione yunnanensis. Their structures and absolute configurations were established through a combination of HRESIMS and NMR data and supported by physical and chemical methods. Compounds 5, 6, 10, and 15 showed significant in vitro hepatoprotective activity against d-galactosamine (d-GalN)-induced toxicity in HL-7702 cells with increasing cell viability by 27%, 22%, 19%, and 31% compared to the model group (cf. bicyclol, 14%) at 10 µM, respectively. Compounds 4, 9, and 11 exhibited moderate hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced toxicity in HepG2 cells with increasing cell viability by 9%, 16%, and 12% compared to the model group (cf. bicyclol, 9%) at 10 µM, respectively.

8.
J Gynecol Obstet Hum Reprod ; 50(8): 102068, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33484932

RESUMO

OBJECTIVE: Many women experience pelvic floor dysfunction (PFD) during the perinatal period. Knowledge of PFD among women is poor, which may reflect inadequate provision of information by healthcare workers. The aim of this study was to explore obstetrical healthcare workers' knowledge, attitude, and practice regarding PFD. MATERIAL AND METHODS: This study had a cross-sectional design. We developed a 65-question survey to explore obstetrical healthcare workers' knowledge, attitude, and practice regarding PFD. An electronic version of the questionnaire was distributed to healthcare workers from 31 provinces in the People's Republic of China by convenience sampling in July and August 2019. This research complied with the guidelines of the Strengthening of the Reporting of Observational Studies in Epidemiology checklist. RESULTS: In total, 1545 valid questionnaires were collected. The mean scores for the knowledge, attitude, and practice of obstetrical healthcare workers were 23.67 ± 4.70 out of 30, 31.91 ± 6.68 out of 40, and 47.88 ± 9.17 out of 65, respectively. Approximately 50 % of the respondents reported providing practical pelvic floor muscle training (PFMT) guidance and evaluation of its correct performance only "sometimes" or even "never". Nearly 30 % of respondents denied asking patients about PFD-related symptoms. Respondents' PFD-related practice were affected not only by their knowledge and attitude but also by their age, treatment or nursing experience of PFD, own PFD history and that of relatives or friends, and the PFD-related departmental setup of their hospital (P < 0.001). CONCLUSION: Most obstetrical healthcare workers have knowledge of PFD and hold a positive attitude but fail to routinely provide PFD counseling and mentoring to patients. Many factors affect the respondents' PFD-related practice.

9.
Medicine (Baltimore) ; 100(2): e23888, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33466132

RESUMO

BACKGROUND: Microvascular angina has become a clinical and frequent cardiovascular disease in recent years, which is complicated and there is no clear treatment. Today, Western medicine still deals with microvascular angina with standardized treatment based on the stable angina. Firstly, it is to control the risk factors of atherosclerosis, and the second is to reduce the oxygen consumption of the patient's heart muscle. In the previous randomized controlled clinical trials, it has shown that nicorandil can improve the symptoms of angina for the treatment of microvascular angina, but there is a lack of high-quality randomized controlled trials on the clinical effectiveness and safety of nicorandil in the treatment of microvascular angina, and the lack of evaluation of its effectiveness and safety. Therefore, this paper aims to understand whether nicorandil can further improve the prognosis of patients with microvascular angina and the safety of the drug through the method of systematic evaluation. METHODS: Retrieval of relevant network electronic databases by computer: SinoMed, CNKI, WanFang Data, VIP, PubMed, EMbase and The Cochrane Library, the retrieval time is from the establishment of each database to December 2017, to collect randomized controlled studies of nicorandil in the treatment of microvascular angina. At the same time, it is supplemented by manual search of the included literature references, as far as possible to increase the included literature imformation. Two researchers independently browse the topics and abstracts, and select, find, read the full text of the relevant literature, and screen the literature according to the criteria for inclusion and exclusion established in advance, then extract the data, and cross-check, and resolve the differences through multi-person discussion. Data analysis of collected information is performed by using RevMan 5.3 software. RESULTS: The data of the included literature are statistically analyzed by meta-analysis, and the key outcome indicators are used to determine whether nicorandil can further improve the prognosis of patients with microvascular angina and the safety of the drug. CONCLUSION: Through the method of evidence-based medicine, this study finds the existing problems and defects in the current research, which will provide high-quality evidence-based medical evidence for nicorandil's treatment of microvascular angina, and it help the clinical treatment and further research. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/DSQG9.


Assuntos
Angina Microvascular/tratamento farmacológico , Nicorandil/uso terapêutico , Vasodilatadores/uso terapêutico , Humanos , Nicorandil/administração & dosagem , Nicorandil/efeitos adversos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Vasodilatadores/administração & dosagem , Vasodilatadores/efeitos adversos
10.
Artigo em Inglês | MEDLINE | ID: mdl-33403738

RESUMO

AIM: To investigate the safety and feasibility of taking low-concentration carbohydrate solution at 2 h before induction of anesthesia for gestational diabetes mellitus (GDM) patients. METHODS: GDM patients undergoing cesarean section were randomly assigned to experimental group (n = 43) and control group (n = 42). Two hours before induction of anesthesia, participants in experimental group orally received 300 mL low-concentration carbohydrate solution, while those in control group received equivalent warm water. Blood glucose and serum insulin were measured at 2 h before induction of anesthesia, right before induction of anesthesia, and the morning of postoperative day 1. Neonatal blood glucose level was monitored at birth. Maternal gastrointestinal function and well-being were assessed perioperatively. RESULTS: The levels of blood glucose and serum insulin right before induction of anesthesia in the experimental group were significantly higher than those in the control group. There were four cases with hypoglycemia in the experimental group and 19 cases in the control group right before induction of anesthesia (9.3% vs 45.2%, p < 0.001). The incidence of neonatal hypoglycemia was 2.3% in the experimental group and 7.1% in the control group with no significance. Hunger score of the participants between the two groups right before induction of anesthesia was significantly different. No aspiration, nausea, and vomiting occurred in both groups before, during, and after surgery. No significant difference was found in the time to the first flatus and abdominal distension between the two groups. CONCLUSION: Taking low-concentration carbohydrate solution is safe and feasible for patients with GDM undergoing elective cesarean section.

11.
Spectrochim Acta A Mol Biomol Spectrosc ; 250: 119378, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33401180

RESUMO

Supramolecular hydrogels are attracting soft materials with potential applications. In this study, we synthesized a facile gelator (named 2-QF) based on phenylalanine derivative with a Quinoline group. 2-QF can assemble to form hydrogels at room temperature in different colors under low pH values. Moreover, 2-QF was triggered to form a yellow metallohydrogel (2-QF-Zn) at high pH by the coordination between 2-QF and Zn2+. 2-QF-Zn metallohydrogel showed excellent multi-stimuli responsiveness, especially the reversible "on-off" luminescence switching, as induced by base/acid. In addition, at a low concentration, 2-QF can selectively and visibly identify Zn2+ through fluorescence enhancement, and can detect Zn2+ at physiological pH as a chemosensor. Remarkably, 2-QF and 2-QF-Zn exhibited an excellent biocompatibility without cell cytotoxicity, and 2-QF is able to penetrate live HeLa cells and image intracellular Zn2+ by a turn-on fluorescent response, which makes it a potential candidate for biomedical applications.

12.
Mol Med Rep ; 23(1): 1, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33179093

RESUMO

The aim of the present study was to investigate the effects of the ginsenoside Rg1 on D­galactose (D­gal)­induced mouse models of premature ovarian insufficiency (POI) and the related mechanisms. C57BL/6 female mice were randomly grouped into the following: i) D­gal [subcutaneously (s.c.) 200 mg/kg/d D­gal for 42 days]; ii) Rg1 [intraperitoneally (i.p.) 20 mg/kg/d Rg1 for 28 days]; iii) D­gal + Rg1 (s.c. 200 mg/kg/d D­gal for 42 days followed by i.p. 20 mg/kg/d Rg1 for 28 days); and iv) saline groups (equivalent volume of saline s.c. and i.p.). Hematoxylin and eosin staining and electron microscopy were used to analyze uterine and ovarian morphology. Expression levels of senescence factors (p21, p53 and serine/threonine kinase), secretion of pro­inflammatory cytokines [interleukin (IL)­6, tumor necrosis factor (TNF)­α and IL­1ß] and the activities of oxidation biomarkers [superoxide dismutase (T­SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH­px)] were analyzed. The results showed that mice in the Rg1 + D­gal group had significantly higher uterine and ovarian weight compared with those in the D­gal group. Uterus morphology was also improved, based on the comparison between the D­gal group and the Rg1 + D­gal group. In addition, the Rg1 treatment after D­gal administration significantly decreased the expression of senescence­associated factors, enhanced the activities of anti­oxidant enzymes total T­SOD and GSH­px in addition to reducing TNF­α, IL­1ß, MDA and IL­6 (based on the comparison between the D­gal group and the Rg1 + D­gal group). In conclusion, the present study suggested that the ginsenoside Rg1 improved pathological damages in the ovary and uterus by increasing anti­oxidant and anti­inflammatory abilities whilst reducing the expression of senescence signaling pathways in POI mouse models.

13.
Sci Total Environ ; 753: 141746, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33207482

RESUMO

This study explored the effects of adding phosphogypsum (PPG), medical stone (MS), and both (PPM) during composting on nitrogen transformation, nitrogen functional genes, the bacterial community, and their relationships with NH3 and N2O emissions. Adding MS and PPM reduced NH3 emissions by 25.78-68.37% and N2O emissions by 19.00-42.86%. PPG reduced NH3 emissions by 59.74% but slightly increased N2O emissions by 8.15%. MS was strongly correlated with the amoA-dominated nitrification process. PPG and PPM had strong correlations with nirS- and nirK-dominated, and nosZ-dominated denitrification processes, respectively. PPM promoted nitrification and denitrification processes more than PPG and MS. Different functional bacteria had key roles in nitrification and denitrification during different composting stages. Firmicutes probably contributed to the conversion and release of nitrogen in the thermophilic period, whereas Proteobacteria, Chloroflexi, Bacteroidetes, and other phyla might have played important roles in the cooling and maturation periods. PPM obtained the greatest reductions in NH3 and N2O release via the regulation of environmental variables, nitrogen functional genes, and the bacterial community. Overall, these results provide insights at a molecular level into the effects of PPG and MS on nitrogen transformation and NH3 and N2O emissions during composting.


Assuntos
Compostagem , Bactérias/genética , Sulfato de Cálcio , Desnitrificação , Genes Bacterianos , Nitrificação , Nitrogênio , Óxido Nitroso/análise , Fósforo , Solo
14.
Sci Total Environ ; 752: 142162, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33207525

RESUMO

The present study compared the effects of adding shrimp shell powder (SSP) at four levels comprising 0% (CK), 5% (L), 10% (M), and 15% (H) on the abundance of antibiotic resistance genes (ARGs) and the bacterial community succession during swine manure composting. The relative abundances of 5/11 ARGs were reduced in CK, and 7/11 in H. Moreover, the removal rate was enhanced by adding SSP. Thus, H decreased the total abundance of ARGs by 32.68%, whereas CK increased it by 6.31%. Redundancy analysis indicated that mobile genetic elements (MGEs) (46.6%) and the bacterial community (31.1%) mainly explained the changes in ARGs. H enhanced the removal of MGEs, prolonged the thermophilic phase, stabilized copper and zinc, and retained nitrogen. LEfSe analysis and non-metric multidimensional scaling indicated that the bacterial community changed in the composting process, and it was optimized by H. The abundances of the potential bacterial co-hosts (such as Lactobacillus, Corynebacterium_1, and Ornithinicoccus) of ARGs and MGEs were lower and the decomposition of organic matter was higher in H compared with CK. Thus, composting with 15% SSP can reduce the risk of ARGs and improve the practical value for agronomic application.


Assuntos
Compostagem , Animais , Antibacterianos , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos , Esterco , Suínos
15.
J Hazard Mater ; 403: 123890, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33264956

RESUMO

Aerobic fermentation is a sustainable option for livestock waste treatment, but little is known about the microbial mechanism that allows oxytetracycline (OTC) and copper (Cu) to affect nitrogen metabolism during aerobic fermentation. In this study, contamination with OTC and Cu alone or in combination reduced the total nitrogen (TN) content of the fermentation products. Metagenomic analysis demonstrated that the contribution of microorganisms to nitrogen metabolism changed significantly in different stages of fermentation. OTC and Cu affected the formation and utilization pattern of NO2--N by microorganisms, which were mainly responsible for the reduced N2O emissions. In the presence of OTC and/or Cu, Myxococcus_stipitatus, Myxococcus_xanthus, and Gimesia_maris were evidently enriched at the end of fermentation, and their increased roles in the dissimilatory reduction of nitrite to ammonium were confirmed by network analysis. Ardenticatena_maritima was the main contributor to denitrification (NO3--N to NO). Furthermore, organic matter (OM) was the most important factor responsible for driving the variation in nitrogen-transforming microorganisms and controlling denitrification. OTC affected the formation of OM, which can directly affect TN (λ = -0.37, p < 0.001), and the adverse impact of Cu on nirK- and nifH-dominant microorganisms was validated (p < 0.05).

16.
Poult Sci ; 100(1): 235-245, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33357686

RESUMO

As one of the 3 main short-chain fatty acids, the role of propionate in chicken fat metabolism is largely unknown. In this study, we demonstrated that dietary supplementation of coated sodium propionate (SP) moderately inhibits fat deposition in broiler chickens, as evidenced by the decreased adipocyte mean area (P < 0.01), the lowered triglyceride content in abdominal fat tissue (P < 0.01), and the reduced transcription of several lipogenic genes in liver and abdominal fat tissues (P < 0.05). Surprisingly, the propionate content was not significantly elevated either in serum or in the cecal chyme by SP administration (P > 0.05). However, SP application significantly decreased the average daily feed intake of broilers (P < 0.05). In addition, the composition of the cecal microbial communities was altered, with the ratio of Firmicutes to Bacteroidetes decreasing in particular (P < 0.05). At the genus level, SP application increased the richness of Alistipes, Lactobacillus, and Bifidobacterium, while reduced the abundance of Lachnospiraceae and Helicobacter significantly (P < 0.05). Moreover, in vitro experiments indicated that, although physiological concentrations of propionate (0.01 to 0.1 mmol) upregulated or downregulated the transcription of some fat synthesis-associated genes (P < 0.05), they did not significantly affect the triglyceride accumulation in hepatocytes and adipocytes (P > 0.05). These results suggest that feed supplementation with SP inhibits fat deposition in broilers by reducing feed and caloric intake, but not via direct regulation on hepatic fat synthesis or adipocytic fat deposition. Alteration in the relative populations of the gut microflora suggests that SP may have gut health implications.

17.
Res Social Adm Pharm ; 17(1): 1853-1858, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33317764

RESUMO

BACKGROUND: The practical experiences of active pharmacists involved in managing critically ill patients with coronavirus disease 2019 (COVID-19) have been rarely reported. OBJECTIVE: This work aimed to share professional experiences on medication optimization and provide a feasible reference for the pharmaceutical care of critically ill patients with COVID-19. METHODS: This study was conducted in a COVID-19-designated hospital in China. A group of dedicated clinical pharmacists participated in multidisciplinary rounds to optimize the treatments for critically ill patients with COVID-19. Consensus on medication recommendations was reached by a multidisciplinary team through bi-daily discussion. Related drug, classification, cause, and adjustment content for recommendations were recorded and reviewed. RESULTS: A total of 111 medication recommendations were supplied for 22 out of 33 (56.7%) critically ill patients from 1 February 2020 to 18 March 2020, and 106 (95.5%) of these were accepted. Among these recommendations, 64 (67.7%), 32 (28.8%), and 15 (13.5%) were related to antibiotics and antifungals, antiviral agents, and other drugs, respectively. Recommendation types significantly differed for different anti-infectives (p < 0.05). For antibiotics and antifungals, treatment effectiveness accounted for 60.9% of recommendation types, with 15 (38.5%) cases related to untreated infections. For antiviral agents, adverse drug events were the most common recommendation types (84.4%), with 20 (74.1%) cases related to liver function dysfunction. Discontinuation of suspected antiviral agents (66.7%) was usually recommended after the occurrence of adverse events that may progress and bring poor outcomes. CONCLUSION: Forceful and extensive on-ward participation is recommended for clinical pharmacists in managing critically ill patients. Our experiences highlight the need for special attention toward untreated infections and adverse events related to antiviral agents.


Assuntos
/terapia , Unidades de Terapia Intensiva , Farmacêuticos/organização & administração , Serviço de Farmácia Hospitalar/organização & administração , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/administração & dosagem , Antivirais/efeitos adversos , China , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente/organização & administração , Papel Profissional , Estudos Retrospectivos
18.
Chemosphere ; 263: 128338, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33297264

RESUMO

The residues of tetracycline in environment have raised increasing concern for the deleterious impact on ecological and human health. Natural organic matter (NOM), ubiquitous in natural waters, is unavoidable to encounter tetracycline, which might affect the fate of tetracycline in aquatic environment. In this study, we investigated the effect of natural organic matter (NOM) on the photolytic fate of tetracycline (TC). The photolysis kinetics of TC were evaluated with two representative NOM, tannic acid (TA) and gallic acid (GA). The presence of TA and GA obviously inhibited the removal of TC under UV irradiation with photolysis rate constant at 0.067 h-1 and 0.071 h-1, respectively, which were 32.3% and 28.3% less than that without TA and GA (0.099 h-1). Furthermore, NOM exhibited different impacts on both indirect photolysis and direct photolysis. NOM promoted the formation of hydroxyl radical, induced the generation of triplet-excited state NOM and thus greatly enhanced the indirect photolysis of TC. However, direct photolysis was almost completely inhibited by NOM via inner filter effect and interacting with TC to form ground-state complex with low photoreactive. Moreover, similar intermediates were detected in the presence and absence of NOM, indicating that NOM exhibited limited influence on the degradation pathways of TC. This study reveals the multiple roles of NOM on tetracycline photolysis, contributing to better understand the photolytic fate of antibiotics in natural waters.


Assuntos
Poluentes Químicos da Água , Antibacterianos , Humanos , Cinética , Fotólise , Tetraciclina/análise , Poluentes Químicos da Água/análise
19.
Sci Total Environ ; : 143840, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33261869

RESUMO

In arsenic toxicity, activation of the erythroid 2-related factor 2 (NRF2) pathway is regarded as a driver of cancer development and progression; however, the mechanisms by which NRF2 gene expression regulates cell cycle progression and mediates pathways of cellular proliferation and apoptosis in arsenic-induced lung carcinogenesis are poorly understood. In this study, we explored the regulatory functions of NRF2 expression and its target genes in immortalized human bronchial epithelial (HBE) cells continuously exposed to 1.0 µM sodium arsenite over approximately 43 passages (22 weeks). The experimental treatment induced malignant transformation in HBE cells, characterized by increased cellular proliferation and soft agar clone formation, as well as cell migration, and accelerated cell cycle progression from G0/G1 to S phase with increased levels of cyclin E-CDK2 complex,decreased cellular apoptosis rate. Moreover, we observed a sustained increase in NRF2 protein levels and those of its target gene products (NQO1, BCL-2) with concurrently decreased expression of apoptosis-related proteins (BAX, Cleaved-caspase-3/Caspase-3 and CHOP) and increased expression of the anti-apoptotic protein MCL-1. Silencing NRF2 expression with small interfering RNA (siRNA) in arsenite-transformed (T-HBE) cells was shown to reverse the malignant phenotype. Further, siRNA silencing of NQO1 significantly decreased levels of the cyclin E-CDK2 complex, inhibiting G0/G1 to S phase cell cycle progression and transformation to the T-HBE phenotypes. This study demonstrated a novel role for the NRF2/NQO1 signaling pathway in mediating arsenite-induced cell transformation by increasing the expression of cyclin E-CDK2, and accelerating the cell cycle and cell proliferation. Arsenite promotes activation of the NRF2/BCL-2 signaling pathway inhibited CHOP increasing cellular resistance to apoptosis and further promoting malignant transformation.

20.
J Appl Microbiol ; 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33263216

RESUMO

AIMS: The aims of this study were to investigate the effects of probiotics and antibiotics on microbial composition, short chain fatty acids (SCFAs) concentration and free fatty acid receptor 2/3 (FFAR2/3) expression in boiler chickens. METHODS AND RESULTS: 150 one-day-old male broilers were randomly allocated into 3 groups, control (CON) group, probiotics (PB) group and antibiotics (ATB) group. Results indicated that PB improved the average body weight from 1 d to 21 d and feed intake from 21 d to 42 d (p< 0.05), while ATB improved the feed efficiency from 1 d to 42 d (p< 0.05). Based on 16s rRNA sequencing, PB treatment increased the amount of kingdom bacteria, and the relative abundance of the main bacteria including acetate and butyrate producing bacteria of phylum Firmicutes, family Ruminococcaceae and genus Faecalibacterium. ATB treatment also increased the relative abundance of phylum Firmicutes, family Ruminococcaceae and Lachnospiraceae, however it introduced some pathogenic bacteria, such as bacteria of family Rikenellaceae and Enterobacteriaceae. Gas chromatography and mass spectrometry (GC-MS) assay revealed PB increased acetate and butyrate concentrations at both 21 d and 42 d, and propionate at 42 d in the colorectum. Moreover, qRT-PCR analysis showed PB treatment significantly activated the FFAR2/3 mRNA expressions. On the contrast, ATB treatment lowered the colorectal propionate at 21 d, and decreased acetate, propionate, and butyrate concentrations at 42 d, accompanied with decreased FFAR2/3 mRNA expressions. CONCLUSIONS: Compare to the CON birds, an enriched SCFAs producing bacteria with higher SCFAs contents and activated FFAR2/3 expressions are prominent features of PB birds. However, antibiotics treatment plays the reverse effect compared to PB treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: This study brings a significant idea that less SCFAs concentration may be another reason why the antibiotics inhibit the immune system development and immunity of the body.

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