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1.
J Asian Nat Prod Res ; : 1-14, 2022 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-36151896

RESUMO

Oleanolic acid (OA) is a five-ring triterpenoid compound, which is widely present in plants. Due to a wide range of pharmacological activities, oleanolic acid has attracted more and more attention. However, oleanolic acid is insoluble in water and has low bioavailability, which limits its clinical application. In this review, we focus on summarizing the anti-cancer activity and mechanism of the A ring or C-28 carboxyl modified derivatives of OA since 2015, to determine the strength of its anti-cancer effectiveness and evaluate whether it could be used as a clinical anti-cancer drug.

3.
Biomolecules ; 12(9)2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36139149

RESUMO

Cognitive impairment (CI) is one of the major clinical features of many neurodegenerative diseases. It can be aging-related or even appear in non-central nerve system (CNS) diseases. CI has a wide spectrum that ranges from the cognitive complaint with normal screening tests to mild CI and, at its end, dementia. Ginsenosides, agents extracted from a key Chinese herbal medicine (ginseng), show great promise as a new therapeutic option for treating CI. This review covered both clinical trials and preclinical studies to summarize the possible mechanisms of how ginsenosides affect CI in different diseases. It shows that ginsenosides can modulate signaling pathways associated with oxidative stress, apoptosis, inflammation, synaptic plasticity, and neurogenesis. The involved signaling pathways mainly include the PI3K/Akt, CREB/BDNF, Keap1/Nrf2 signaling, and NF-κB/NLRP3 inflammasome pathways. We hope to provide a theoretical basis for the treatment of CI for related diseases by ginsenosides.

4.
Antioxidants (Basel) ; 11(9)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36139821

RESUMO

Cerebrovascular disease is highly prevalent and has a complex etiology and variable pathophysiological activities. It thus poses a serious threat to human life and health. Currently, pathophysiological research on cerebrovascular diseases is gradually improving, and oxidative stress and autophagy have been identified as important pathophysiological activities that are gradually attracting increasing attention. Many studies have found some effects of oxidative stress and autophagy on cerebrovascular diseases, and studies on the crosstalk between the two in cerebrovascular diseases have made modest progress. However, further, more detailed studies are needed to determine the specific mechanisms. This review discusses nuclear factor erythroid 2-related factor 2 (Nrf2) molecules, which are closely associated with oxidative stress and autophagy, and the crosstalk between them, with the aim of providing clues for studying the two important pathophysiological changes and their crosstalk in cerebrovascular diseases as well as exploring new target treatments.

5.
Environ Res ; : 114395, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36150443

RESUMO

Type 2 diabetes (T2DM) as a non-communicable disease imposes heavy disease burdens on society. Limited studies have been conducted to assess the effects of short-term air pollution exposure on T2DM, especially in Asian regions. Our research aimed to determine the association between short-term exposure to ambient nitrogen dioxide (NO2) and outpatient visits for T2DM in Chongqing, the largest city in western China, based on the data collected from November 28, 2013 to December 31, 2019. A generalized additive model (GAM) was applied, and stratified analyses were performed to investigate the potential modifying effects by age, gender, and season. Meanwhile, the disease burden was revealed from attributable risk. Positive associations between short-term NO2 and daily T2DM outpatient visits were observed. The strongest association was observed at lag 04, with per 10 µg/m3 increase of NO2 corresponded to increased T2DM outpatient visits at 1.57% [95% confidence interval (CI): 0.48%, 2.65%]. Stronger associations were presented in middle-aged group (35-64 years old), male group, and cool seasons (October to March). Moreover, there were 1.553% (8664.535 cases) of T2DM outpatient visits attributable to NO2. Middle-aged adults, males, and patients who visited in cool seasons suffered heavier burdens. Conclusively, short-term exposure to NO2 was associated with increased outpatient visits for T2DM. Attention should be paid to the impact of NO2 on the burden of T2DM, especially for those vulnerable groups.

6.
ISME J ; 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36151458

RESUMO

A debate is currently ongoing as to whether intensive livestock farms may constitute reservoirs of clinically relevant antimicrobial resistance (AMR), thus posing a threat to surrounding communities. Here, combining shotgun metagenome sequencing, machine learning (ML), and culture-based methods, we focused on a poultry farm and connected slaughterhouse in China, investigating the gut microbiome of livestock, workers and their households, and microbial communities in carcasses and soil. For both the microbiome and resistomes in this study, differences are observed across environments and hosts. However, at a finer scale, several similar clinically relevant antimicrobial resistance genes (ARGs) and similar associated mobile genetic elements were found in both human and broiler chicken samples. Next, we focused on Escherichia coli, an important indicator for the surveillance of AMR on the farm. Strains of E. coli were found intermixed between humans and chickens. We observed that several ARGs present in the chicken faecal resistome showed correlation to resistance/susceptibility profiles of E. coli isolates cultured from the same samples. Finally, by using environmental sensing these ARGs were found to be correlated to variations in environmental temperature and humidity. Our results show the importance of adopting a multi-domain and multi-scale approach when studying microbial communities and AMR in complex, interconnected environments.

7.
Hum Genet ; 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36098810

RESUMO

The craniovertebral junction (CVJ) is an anatomically complex region of the axial skeleton that provides protection of the brainstem and the upper cervical spinal cord. Structural malformation of the CVJ gives rise to life-threatening neurological deficits, such as quadriplegia and dyspnea. Unfortunately, genetic studies on human subjects with CVJ malformation are limited and the pathogenesis remains largely elusive. In this study, we recruited 93 individuals with CVJ malformation and performed exome sequencing. Manual interpretation of the data identified three pathogenic variants in genes associated with Mendelian diseases, including CSNK2A1, MSX2, and DDX3X. In addition, the contribution of copy number variations (CNVs) to CVJ malformation was investigated and three pathogenic CNVs were identified in three affected individuals. To further dissect the complex mutational architecture of CVJ malformation, we performed a gene-based rare variant association analysis utilizing 4371 in-house exomes as control. Rare variants in LGI4 (carrier rate = 3.26%, p = 3.3 × 10-5) and BEST1 (carrier rate = 5.43%, p = 5.77 × 10-6) were identified to be associated with CVJ malformation. Furthermore, gene set analyses revealed that extracellular matrix- and RHO GTPase-associated biological pathways were found to be involved in the etiology of CVJ malformation. Overall, we comprehensively dissected the genetic underpinnings of CVJ malformation and identified several novel disease-associated genes and biological pathways.

8.
Artigo em Inglês | MEDLINE | ID: mdl-36099079

RESUMO

BACKGROUND: Ultraviolet radiation can aggravate facial erythema in atopic dermatitis (AD) patients. OBJECTIVE: To investigate the photobiological testing results of Chinese AD patients with refractory facial erythema. METHODS: We conducted a retrospective analysis of 82 AD patients with refractory facial erythema who visited our department during 2004-2021. All of them completed phototesting and photopatch testing. RESULTS: 82 patients were enrolled in the study, and 53 (64.6%) were between 18 and 30 years old. 51.2% (42/82) had positive phototesting results and were considered photosensitive AD (PhAD) patients. One-third of them were both allergic to ultraviolet A and ultraviolet B. 65.9% (54/82) suffered from photoallergic contact dermatitis. Chlorpromazine (50.7%), potassium dichromate (13.2%), and thimerosal (11.8%) were the top three common photoallergens. Overall, 86.3% of AD patients with refractory facial erythema had direct photoallergy or photocontact allergy. PhAD patients had fewer allergic comorbidities than the other group(P=0.007). More non-PhAD patients (55.0%) suffered from AD at 2-14 years old (P=0.015). CONCLUSIONS: Photosensitivity contributes a lot to the facial lesions of AD patients, especially in their 20s. 86.3% of these patients had direct photoallergy or photocontact allergy. Therefore, AD patients with facial erythema should undergo phototesting and photopatch testing routinely.

9.
J Ethnopharmacol ; 300: 115690, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36075274

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Xianglian Pill (XLP) is a classical Chinese medicine prescription applied for controlling ulcerative colitis (UC). Whereas, the underlying mechanism remains unclear. AIM OF THE STUDY: The present work was aimed to investigate the mechanism of XLP in dextran sulfate sodium (DSS)-induced UC via the Toll Like Receptor 4 (TLR4)/Myeloid Differentiation factor 88 (MyD88)/Nuclear Factor kappa-B (NF-κB) signaling in mice. MATERIALS AND METHODS: The major components of XLP were detected by high-performance liquid chromatography-diode array detection (HPLC-DAD). The ulcerative colitis model was induced by DSS in mice. 5-Amino Salicylic Acid (5-ASA) group and XLP group were intragastrically treated. Disease activity index (DAI) and colon length were monitored and hematoxylin-eosin (HE) staining was conducted. Gasdermin D (GSDMD)-N and TLR4 expressions in colon tissues were visualized by immunofluorescence. TLR4 mRNA was measured by Real Time Quantitative PCR (RT-qPCR). The expressions of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), active-caspase-1, GSDMD-N, TLR4, MYD88, NF-κB, p-NF-κB, and the ubiquitination of TLR4 in colon tissues were detected by Western blot. Myeloperoxidase (MPO) enzyme activity was examined and serum inflammatory factors Interleukin (IL)-1ß, IL-6, Tumor Necrosis Factor-α (TNF-α), and IL-18 were determined by Enzyme-linked Immunosorbent Assay (ELISA). TLR4-/- mice were applied for verifying the mechanism of XLP attenuated DSS symptoms. RESULTS: The XLP treatment extended colon length, reduced DAI, and attenuated histopathological alteration in DSS-induced mice. XLP administration suppressed MPO activity and reduced the content of IL-1ß, IL-6, TNF-α and IL-18 in serum. XLP also inhibited the expression levels of GSDMD-N, TLR4, NLRP3, active-caspase-1, MyD88, p-NF-κB/NF-κB in colon tissues of DSS-induced mice. TLR4-/- mice proved that TLR4 was involved in XLP-mediated beneficial effect on DSS-induced ulcerative colitis. CONCLUSIONS: XLP might treat ulcerative colitis by regulating the TLR4/MyD88/NF-κB signaling pathway.

10.
CNS Neurosci Ther ; 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36052650

RESUMO

AIMS: Stroke has a high incidence and is a disabling condition that can lead to severe cognitive, motor, and sensory dysfunction. In this study, we employed a drug repurposing strategy to investigate the neuroprotective effect of lomitapide on focal ischemic brain injury and explore its potential mechanism of action. METHODS: Experimental cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in adult male C57BL/6 mice and simulated by oxygen-glucose deprivation in N2a-BV2 cells in co-cultivation. RESULTS: Lomitapide significantly increased the survival rate, reduced the neuronal tissue loss, and improved the neurological function after MCAO. Furthermore, lomitapide could increase the expression of LC3-II, reduce the expression of P62 and LAMP2, promote autophagic flux, and inhibit apoptosis by increasing and inhibiting the expression of the apoptosis-associated proteins Bcl-2 and Bax, respectively. In addition, lomitapide inhibited the migration of pro-inflammatory microglia. CONCLUSION: Lomitapide is a lipid-lowering drug, and this is the first study to explore its protective effect on ischemic nerve injury in vitro and in vivo. Our results suggest that lomitapide can be repositioned as a potential therapeutic drug for the treatment of stroke.

11.
J Acquir Immune Defic Syndr ; 91(S1): S42-S50, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36094514

RESUMO

BACKGROUND: Results from both clinical trials and real-world observational studies suggest that lamivudine plus dolutegravir (3TC + DTG) dual therapy has excellent virological efficacy and safety in HIV-1-infected patients. However, there is still no relevant study related to this dual therapy reported in China. METHODS: In this multicenter, retrospective, observational study that included HIV-1-infected patients in China, baseline and follow-up data were collected to analyze the virological suppression rate, immune restoration, and adverse events during follow-up in HIV-1-infected patients who switched to the 3TC + DTG dual therapy. RESULTS: This study recruited 112 HIV-1-infected patients, including 101 men (90.2%), with a median age of 44.0 years (IQR: 33.00-57.75) and median CD4+ T-cell count of 432.13 cells/µL (IQR: 237.75-578.50). The overall virological suppression rate was 94.5% at the 24-week follow-up. However, the virological suppression rates of men who have sex with men patients and patients with CD4+ T-cell count of <350 cells/µL were higher than the baseline value (P < 0.05) at week 24. The results of Cox regression analysis showed that the baseline CD4+ T-cell count was an independent determinant of immune restoration in patients, and patients with baseline CD4+ T-cell count of 350-500 cells/µL outperformed patients with baseline CD4+ T-cell count of <350 cells/µL in immune restoration (hazard ratio: 4.469, 95% confidence interval: 1.801 to 11.091, P = 0.001). Adverse events were reported in 5 patients (incidence rate of 4.5%); among them, 3 patients developed neuropsychiatric symptoms. Results from the laboratory data analysis showed that patients with grade 1 and 2 adverse events had elevated levels of low-density lipoprotein cholesterol and total bilirubin. Furthermore, grade 3 and 4 adverse events were associated with the elevation of blood glucose level in 4 patients. CONCLUSIONS: Thus, the 3TC + DTG dual therapy displayed an excellent virological efficacy against HIV-1 infections and had an acceptable safety profile, with predominantly mild adverse events in HIV-1-infected patients in China.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Soropositividade para HIV , HIV-1 , Minorias Sexuais e de Gênero , Adulto , Fármacos Anti-HIV/efeitos adversos , Estudos de Coortes , Infecções por HIV/tratamento farmacológico , Soropositividade para HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis , Homossexualidade Masculina , Humanos , Lamivudina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Oxazinas , Piperazinas , Piridonas , Estudos Retrospectivos
12.
Int J Part Ther ; 9(2): 49-58, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060413

RESUMO

Purpose: Finite proton range affords improved dose conformality of radiation therapy when patient regions-of-interest geometries are well characterized. Substantial changes in patient anatomy necessitate re-planning (RP) to maintain effective, safe treatment. Regularly planned verification scanning (VS) is performed to ensure consistent treatment quality. Substantial resources, however, are required to conduct an effective proton plan verification program, which includes but is not limited to, additional computed tomography (CT) scanner time and dedicated personnel: radiation therapists, medical physicists, physicians, and medical dosimetrists. Materials and Methods: Verification scans (VSs) and re-plans (RPs) of 711 patients treated with proton therapy between June 2015 and June 2018 were studied. All treatment RP was performed with the intent to maintain original plan integrity and coverage. The treatments were classified by anatomic site: brain, craniospinal, bone, spine, head and neck (H&N), lung or chest, breast, prostate, rectum, anus, pelvis, esophagus, liver, abdomen, and extremity. Within each group, the dates of initial simulation scan, number of VSs, number of fractions completed at the time of VS, and the frequency of RP were collected. Data were analyzed in terms of rate of RP and individual likelihood of RP. Results: A total of 2196 VSs and 201 RPs were performed across all treatment sites. H&N and lung or chest disease sites represented the largest proportion of plan modifications in terms of rate of re-plan (RoR: 54% and 58%, respectively) and individual likelihood of RP on a per patient basis (likelihood of RP [RP%]: 46% and 39%, respectively). These sites required RP beyond 4 weeks of treatment, suggesting continued benefit for frequent, periodic VS. Disease sites in the lower pelvis demonstrated a low yield for RP per VS (0.01-0.02), suggesting that decreasing VS frequency, particularly late in treatment, may be reasonable. Conclusions: A large degree of variation in RoR and individual RP% was observed between anatomic treatment sites. The present retrospective analysis provides data to help develop anatomic site-based VS protocols.

13.
Research (Wash D C) ; 2022: 9789657, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061819

RESUMO

Durable dropwise condensation of saturated vapor is of significance for heat transfer and energy saving in extensive industrial applications. While numerous superhydrophobic surfaces can promote steam condensation, maintaining discrete microdroplets on surfaces without the formation of a flooded filmwise condensation at high subcooling remains challenging. Here, we report the development of carbon nanotube array-embedded hierarchical composite surfaces that enable ultra-durable dropwise condensation under a wide range of subcooling (ΔT sub = 8 K-38 K), which outperforms existing nanowire surfaces. This performance stems from the combined strategies of the hydrophobic nanostructures that allow efficient surface renewal and the patterned hydrophilic micro frames that protect the nanostructures and also accelerate droplet nucleation. The synergistic effects of the composite design ensure sustained Cassie wetting mode and capillarity-governed droplet mobility (Bond number < 0.055) as well as the large specific volume of condensed droplets, which contributes to the enhanced condensation heat transfer. Our design provides a feasible alternative for efficiently transferring heat in a vapor environment with relatively high temperatures through the tunable multiscale morphology.

14.
J Oral Pathol Med ; 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36053880

RESUMO

BACKGROUND: Previous studies on oral submucous fibrosis (OSF) mostly focused on the activation of fibroblasts and collagen metabolism, while little involved in the epithelium. As we have reported the role of differentiated embryo-chondrocyte expressed gene 1 (DEC1) in oral cancer and other precancerous lesions, this research aimed to explore its role in the OSF epithelium. METHODS: Expression of DEC1 and other proteins were investigated in tissue array constructed with 33 OSF and 14 normal oral mucosa (NOM) tissues. Human oral keratinocytes treated with arecoline and/or hypoxia were used to simulate OSF epithelium and detected for morphological and protein alterations. Inhibition of DEC1 was used to explore its mediating role. Finally, animal models of OSF constructed by locally arecoline injecting in buccal mucosa were used to verify our findings. RESULTS: DEC1 overexpression could be detected in the epithelium of OSF compared with that in NOM followed by phosphorylated FAK and Akt, and DEC1 showed a significant positive correlation with them. Cytology experiment revealed that OSF-like treatment could upregulate DEC1 expression followed by phosphorylated FAK, Akt, but inhibit E-cadherin, while knockdown of DEC1 could suppress the effects. In addition, OSF mice revealed higher expression of DEC1 in the epithelium of buccal mucosa, along with synchronized alterations of phosphorylated FAK and Akt. CONCLUSION: In the epithelium of OSF, overexpression of DEC1 induced activation of FAK/Akt signal axis, caused mesenchymal transition in epithelial cells, and may promote malignant transformation of OSF. Targeting DEC1 in OSF could be promising a new target for the diagnosis and treatment of this process.

15.
Epilepsy Behav ; 135: 108902, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36081241

RESUMO

The incidence of epileptic spasms (ES) that begin after the first year of life is much lower than that before 1 year of age. The aim of this study was to identify clinical and electroencephalography (EEG) characteristics, etiologies, treatments, and prognoses in pediatric patients with ES onset after 1 year of age. Forty-one children were retrospectively identified in Children's Hospital of Chongqing Medical University between January 1, 2020 and December 1, 2021. ES onset after 1 year of age have diverse presentations. Although most occur in clusters, are symmetrical and flexional, and occur frequently during awakening, some are characterized as isolated and asymmetrical, have a tonic component, and can also occur during sleep. The hypsarrhythmia variants and focal or multifocal discharges occur alternately in the interictal period, and the focal spikes and slow waves predominated in the unilateral temporal or frontotemporal areas. These patients had diverse etiologies, including structural (51.2 % of patients) and genetic (22.0 %) ones, and 11 patients (26.8 %) had an unknown etiology. No patients in our study had an infectious or immune-mediated etiology. Forty-eight percent of patients responded to hydrocortisone and/or adrenocorticotropic hormone. The efficacy of antiepileptic drug therapy was lower in patients who did not receive concurrent steroid therapy. However, ES onset after 1 year of age caused by a tumor, brain malformation, or other focal lesions, may be cured by focal cortical resection despite a lack of clearly localized EEG surface anomalies. Delays in motor, language, and cognitive development, or behavioral problems were observed in all but three patients.

16.
Artigo em Inglês | MEDLINE | ID: mdl-36082749

RESUMO

BACKGROUND/PURPOSE: Chronic actinic dermatitis (CAD) is a spectrum of diseases with chronic photosensitivity occurring mostly among middle-aged and older men. We seek to explore the characteristics and pathogenesis of CAD among the Chinese population. METHODS: The medical records of 488 CAD cases diagnosed by phototesting at Huashan Hospital, Fudan University from January 2014 to December 2018 were analyzed retrospectively. RESULTS: Among the 488 patients, 344 were male and 144 were female. 84.8% of the cases were over 40 years old at the age of onset, while the remaining with an early age of onset had a prevalence of atopic history of 21.6%. Up to 45.0% of the patients reported excessive sun exposure and outdoor activities before the initiation of symptoms. The typical skin lesions were erythema, papules and plaques laid predominantly in sun-exposed areas. 42.8% of the cases showed sensitivity to UVB only, 20.7% were both sensitive to UVA and UVB, and 18.2% had UVA sensitivity only. The most predominant photoallergens were chlorpromazine (80.1%), thimerosal (17.2%), potassium dichromate (12.7%), etc. The most prevalent patch test allergens were potassium dichromate (24.4%), thimerosal (20.5%), formaldehyde (16.8%), etc. CONCLUSIONS: CAD was more commonly seen in males over 40 years old. The action spectrum of Chinese patients is primarily in the UVB range. Exposure to excessive sunlight or contact allergens and photoallergens are important risk factors. Photobiology tests are essential in detecting photosensitivity and recognizing potential photosensitizers. Early avoidance of confirmed photoallergens and sun exposure may prevent photosensitive reactions from progressing into persistent photosensitivity.

17.
Int J Mol Sci ; 23(17)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36077405

RESUMO

Brown adipose tissue (BAT) is functionally linked to skeletal muscle because both tissues originate from a common progenitor cell, but the precise mechanism controlling muscle-to-brown-fat communication is insufficiently understood. This report demonstrates that the immunoglobulin superfamily containing leucine-rich repeat (Islr), a marker of mesenchymal stromal/stem cells, is critical for the control of BAT mitochondrial function and whole-body energy homeostasis. The mice loss of Islr in BAT after cardiotoxin injury resulted in improved mitochondrial function, increased energy expenditure, and enhanced thermogenesis. Importantly, it was found that interleukin-6 (IL-6), as a myokine, participates in this process. Mechanistically, Islr interacts with NADH: Ubiquinone Oxidoreductase Core Subunit S2 (Ndufs2) to regulate IL-6 signaling; consequently, Islr functions as a brake that prevents IL-6 from promoting BAT activity. Together, these findings reveal a previously unrecognized mechanism for muscle-BAT cross talk driven by Islr, Ndufs2, and IL-6 to regulate energy homeostasis, which may be used as a potential therapeutic target in obesity.


Assuntos
Tecido Adiposo Marrom , Interleucina-6 , Tecido Adiposo Marrom/metabolismo , Animais , Diferenciação Celular , Metabolismo Energético , Homeostase , Imunoglobulinas/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Leucina/metabolismo , Camundongos , Músculo Esquelético/metabolismo , NADH Desidrogenase/metabolismo , Termogênese
18.
Bioresour Technol ; 363: 127961, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36113816

RESUMO

As a promising method for efficiently harvesting microalgae, electro-flotation's performance is related to various factors including electrode design and process operating parameters. In this paper, bubble generation behavior on stainless-steel cathodes, with wire diameters of 0.8 mm, 0.2 mm and 0.05 mm, was studied. The results show that the bubble size increased with the increasing diameter of the electrode wire. Over 90 % harvesting efficiency was achieved using non-sacrificial anode. Extracellular polymeric substance is the main reason keeping bubbles from bursting.

19.
Oxid Med Cell Longev ; 2022: 3858500, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36124086

RESUMO

Background: Berberine (BER) is a natural isoquinoline alkaloid which extensively been applied to treat bacterial infection in TCM for a long time. Alginate is an important component of Pseudomonas aeruginosa biofilm. Herein, we investigated the effects of berberine and azithromycin (AZM) on alginate in the biofilm of P. aeruginosa PAO1. Methods: The MIC and synergistic activity of BER and AZM against PAO1 were determined using the micro broth dilution and checkerboard titration methods, respectively. The effect of BER on PAO1 growth was evaluated using a time-kill assay. Moreover, the effects of BER, AZM, and a combination of both on PAO1 biofilm formation, kinesis, and virulence factor expression were evaluated at subinhibitory concentrations. The alginate content in the biofilm was detected using ELISA, and the relative expression of alginate formation-related genes algD, algR, and algG was detected by qRT-PCR. Results: Simultaneous administration of berberine significantly reduced the MIC of azithromycin, and berberine at a certain concentration inhibited PAO1 growth. Moreover, combined berberine and azithromycin had synergistic effects against PAO1, significantly reducing biofilm formation, swarming, and twitching motility, and the production of virulence factors. The relative expression of alginate-related regulatory genes algG, algD, and algR of the combined treatment group was significantly lower than that of the control group. Conclusion: In summary, berberine and azithromycin in combination had a significant synergistic effect on the inhibition of alginate production by P. aeruginosa. Further molecular studies are in great need to reveal the mechanisms underlying the synergistic activity between berberine and azithromycin.


Assuntos
Berberina , Pseudomonas aeruginosa , Alginatos/metabolismo , Azitromicina/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Berberina/farmacologia , Isoquinolinas/farmacologia , Fatores de Virulência/genética , Fatores de Virulência/metabolismo , Fatores de Virulência/farmacologia
20.
ESC Heart Fail ; 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36130871

RESUMO

AIMS: Peripartum cardiomyopathy (PPCM) are more vulnerable to intracardiac thrombus than other types of cardiomyopathies, although explicit anticoagulant strategy is not sure. Too aggressive anticoagulation therapy can lead to severe bleeding events. Hence, we want to construct a risk stratification model for intracardiac thrombus in PPCM patients. METHODS AND RESULTS: A total of 159 suspected PPCM cases were initially screened, whereas 123 confirmed cases were enrolled in the final analysis. The study population was randomly assigned as derivation group (N = 83) and validation group (N = 40). The derivation cohort was utilized to develop the model, and the validation cohort was used to internal validate the discriminatory ability of the model. Formation of intracardiac thrombus was detected in 22 patients. After adjusted by multivariable logistic regression analysis, left ventricle ejection fraction (LVEF, OR 0.772, 95% CI 0.665-0.897, P = 0.001), haemoglobin levels (OR 1.050, 95% CI 1.003-1.099, P = 0.038), and thrombocyte counts (OR 1.018, 95% CI 1.006-1.029, P = 0.003) were identified as risk factors independently associated with intracardiac thrombus and were finally included in the tentative risk stratification model with a C-indexes of 0.916 (95% CI: 0.850-0.982, P < 0.001). A score of ≤7 was regarded as low risk, 8-10 defined intermediate risk, and ≥11 defined high risk in our model. Internal validation showed good discriminatory ability of the model with a C-indexes of 0.790 (95% CI: 0.644-0.936, P = 0.017). CONCLUSIONS: In our retrospective study, impaired LVEF, elevated haemoglobin levels, and high thrombocyte counts were regarded as independent risk factors for intracardiac thrombus in PPCM. A risk stratification model derived from these risk factors, which was economic and easily applicable in clinical practice, could rapidly and accurately identify PPCM patients with higher-risk of intracardiac thrombus.

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