Biodegradable microspheres have been widely used in the field of medicine due to their ability to deliver drug molecules of various properties through multiple pathways and their advantages of low ...dose and low side effects. Poly (lactic-co-glycolic acid) copolymer (PLGA) is one of the most widely used biodegradable material currently and has good biocompatibility. In application, PLGA with a specific monomer ratio (lactic acid and glycolic acid) can be selected according to the properties of drug molecules and the requirements of the drug release rate. PLGA-based biodegradable microspheres have been studied in the field of drug delivery, including the delivery of various anticancer drugs, protein or peptide drugs, bacterial or viral DNA, etc. This review describes the basic knowledge and current situation of PLGA biodegradable microspheres and discusses the selection of PLGA polymer materials. Then, the preparation methods of PLGA microspheres are introduced, including emulsification, microfluidic technology, electrospray, and spray drying. Finally, this review summarizes the application of PLGA microspheres in drug delivery and the treatment of pulmonary and ocular-related diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The fungicides epoxiconazole and pyraclostrobin have been widely used to control wheat fusarium head blight. This study was designed to investigate the dissipation behaviors in different climate ...regions and provide data for the modification of maximum residue limits of the two fungicides. Wheat samples were collected from field sites in twelve different regions, China and analyzed with an HPLC-MS/MS method for simultaneous detection of epoxiconazole and pyraclostrobin in wheat. The average recoveries of epoxiconazole and pyraclostrobin in wheat matrix were 87–112% and 85–102%, respectively, with the relative standard deviations ≤8.1%. The limits of quantification of epoxiconazole and pyraclostrobin in grain and straw were both 0.01 mg/kg. The dissipations of epoxiconazole and pyraclostrobin followed first-order kinetics, with the half-lives of 10.3 days and 7.6 days, respectively. The terminal residues of epoxiconazole and pyraclostrobin in grain were below 0.034 and 0.028 mg/kg, separately, both lower than the maximum residue limits recommended by China. Based on Chinese dietary pattern and terminal residue distributions, the risk quotients of epoxiconazole and pyraclostrobin were 13.9% and 65.9%, respectively, revealing the evaluated wheat exhibited an acceptably low dietary risk to consumers.
Display omitted
•A Fast and effective method was established to detect epoxiconazole and pyraclostrobin residues in wheat simultaneously in 12 different regions..•Dissipation kinetics of epoxiconazole and pyraclostrobin in wheat were fitted and studied.•Half-lives and other dissipation kinetic parameters were calculated.•Dietary risk assessments and safety use were evaluated.
This study explores the relationship between waist circumference and morbidity of cardiovascular diseases (CVD) and all-cause mortality in metabolically healthy individuals.BackgroundThis study ...explores the relationship between waist circumference and morbidity of cardiovascular diseases (CVD) and all-cause mortality in metabolically healthy individuals.A cohort of 5775 metabolically healthy participants from the 2001-2014 US National Health and Nutrition Examination Survey and National Death Index database was tracked over a median period of 81 months. These participants were divided into quartiles (Q1, Q2, Q3, Q4) based on increasing waist circumference. To compensate for missing covariates, multivariate multiple imputation methods were used. Adjusted logistic regression models were employed to examine the correlation between waist circumference and cardiovascular disease prevalence. Furthermore, Kaplan-Meier curves and multivariable Cox regression analysis were utilized to evaluate the association between waist circumference and all-cause mortality, both qualitatively and quantitatively.MethodsA cohort of 5775 metabolically healthy participants from the 2001-2014 US National Health and Nutrition Examination Survey and National Death Index database was tracked over a median period of 81 months. These participants were divided into quartiles (Q1, Q2, Q3, Q4) based on increasing waist circumference. To compensate for missing covariates, multivariate multiple imputation methods were used. Adjusted logistic regression models were employed to examine the correlation between waist circumference and cardiovascular disease prevalence. Furthermore, Kaplan-Meier curves and multivariable Cox regression analysis were utilized to evaluate the association between waist circumference and all-cause mortality, both qualitatively and quantitatively.The adjusted logistic regression model indicated that a 10 cm increase in waist circumference was associated with a 1.45 times higher prevalence of CVD. As a categorical variable, there was a significant upward trend in CVD incidence across quartiles of waist circumference. The adjusted odds ratios (95% confidence intervals) were 2.41 (1.13-5.53) for Q2, 2.65 (1.18-6.39) for Q3, and 2.53 (0.9-7.44) for Q4, compared to Q1. Notably, individuals with high waist circumference showed significantly poorer survival compared to those with low waist circumference (p = 0.008). The Cox regression analysis revealed that each 10 cm increase in waist circumference contributed to an ~8% increase in all-cause mortality.ResultsThe adjusted logistic regression model indicated that a 10 cm increase in waist circumference was associated with a 1.45 times higher prevalence of CVD. As a categorical variable, there was a significant upward trend in CVD incidence across quartiles of waist circumference. The adjusted odds ratios (95% confidence intervals) were 2.41 (1.13-5.53) for Q2, 2.65 (1.18-6.39) for Q3, and 2.53 (0.9-7.44) for Q4, compared to Q1. Notably, individuals with high waist circumference showed significantly poorer survival compared to those with low waist circumference (p = 0.008). The Cox regression analysis revealed that each 10 cm increase in waist circumference contributed to an ~8% increase in all-cause mortality.This study underscores a positive correlation between waist circumference and both CVD morbidity and all-cause mortality in metabolically healthy individuals. The findings highlight the significance of routinely monitoring waist circumference for effective CVD risk management, regardless of metabolic health status.ConclusionsThis study underscores a positive correlation between waist circumference and both CVD morbidity and all-cause mortality in metabolically healthy individuals. The findings highlight the significance of routinely monitoring waist circumference for effective CVD risk management, regardless of metabolic health status.
Hepatitis B virus (HBV) is considered highly prevalent in West Africa. However, major gaps in surveillance exist in Sierra Leone. Although healthcare workers (HCWs) are at high risk for HBV ...infection, little is known about the prevalence and knowledge of hepatitis B among HCWs in Sierra Leone.
A cross-sectional study of all HCWs at the No. 34 Military Hospital located in Freetown, Sierra Leone, was conducted from March 20 to April 10, 2017. Whole blood was collected and screened for HBV markers using a one-step rapid immunochromatographic test with positive samples tested for HBV DNA. Additionally, questionnaires assessing self-reported knowledge of HBV infections were administered to all participants. Data were processed and analyzed using SPSS (version 17.0) software.
A total of 211 HCWs were included in this study with a median age of 39.0 years (range: 18-59). Of the participating HCWs, 172 (81.5%) participants were susceptible (all markers negative), 21(10.0%) were current HBV (HBsAg positive) and nine (4.3%) were considered immune because of past infection (HBsAg negative and anti-HBc positive; anti-HBs positive). Additionally, nine (4.3%) participants displayed immunity to the virus as a result of prior hepatitis B vaccination (only anti-HBs positive). Of the 21 HCWs with positive HBsAg, 13 (61.9%) had detectable HBV DNA. There was a significantly lower risk for current HBV infection among HCWs older than 39 years (OR 0.337, p = 0.046). In addition, only 14 (6.6%), 73 (34.6%) and 82 (38.9%) participants in this survey had adequate knowledge about the clinical outcome, routes of transmission, and correct preventive measures of HBV infection, respectively.
HCWs in Sierra Leone lacked adequate knowledge of the hepatitis B virus. Additionally, the low coverage rate of hepatitis B vaccination among HCWs fails to meet WHO recommendations, leaving many of the sampled HCWs susceptible to infection. This study reaffirms the need for more intensive training for HCWs in addition to strengthening vaccination programmes to protect HCWs against HBV in Sierra Leone.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
With the increased incidence and recognition, ulcerative colitis (UC) has become a global public health problem in the world. Although many immunosuppressant and biological drugs have been ...used for UC treatment, the cure rate is still very low. It is necessary to find some safe and long-term used medicine for UC cure. Recently, the Chinese traditional herb Danshen has been investigated in the treatment of UC. However, it is a limitation of Danshen that many of the active components in Danshen are not easily absorbed by the human body. Probiotics could convert macromolecules into smaller molecules to facilitate absorption. Thus,
Lactobacillus rhamnosus
(F-B4-1) and
Bacillus subtillis Natto
(F-A7-1) were screened to ferment Danshen in this study. The fermented Danshen products were gavaged in the dextran sulfate sodium (DSS)-induced UC model mice. Danshen had better results to attenuate symptoms of DSS-induced UC after fermented with F-B4-1 and F-A7-1. Loss of body weight and disease activity index (DAI) were reduced. The abnormally short colon lengths and colonic damage were recovered. And fermented Danshen had the better inhibitory effect than Danshen itself on pro-inflammatory cytokine expression during DSS-induced UC. The results indicated that compared with Danshen, fermented Danshen relieved DSS-induced UC in mice more effectively. Danshen fermented by probiotics might be an effective treatment to UC in clinic stage in the future.
Our previous study demonstrated that Ca2+ influx through the Orai1 store-operated Ca2+ channel in macrophages contributes to foam cell formation and atherosclerosis via the calcineurin-ASK1 pathway, ...not the classical calcineurin-nuclear factor of activated T-cell (NFAT) pathway. Moreover, up-regulation of NFATc3 in macrophages inhibits foam cell formation, suggesting that macrophage NFATc3 is a negative regulator of atherogenesis. Hence, this study investigated the precise role of macrophage NFATc3 in atherogenesis.
Macrophage-specific NFATc3 knockout mice were generated to determine the effect of NFATc3 on atherosclerosis in a mouse model of adeno-associated virus-mutant PCSK9-induced atherosclerosis. NFATc3 expression was decreased in macrophages within human and mouse atherosclerotic lesions. Moreover, NFATc3 levels in peripheral blood mononuclear cells from atherosclerotic patients were negatively associated with plaque instability. Furthermore, macrophage-specific ablation of NFATc3 in mice led to the atherosclerotic plaque formation, whereas macrophage-specific NFATc3 transgenic mice exhibited the opposite phenotype. NFATc3 deficiency in macrophages promoted foam cell formation by potentiating SR-A- and CD36-meditated lipid uptake. NFATc3 directly targeted and transcriptionally up-regulated miR-204 levels. Mature miR-204-5p suppressed SR-A expression via canonical regulation. Unexpectedly, miR-204-3p localized in the nucleus and inhibited CD36 transcription. Restoration of miR-204 abolished the proatherogenic phenotype observed in the macrophage-specific NFATc3 knockout mice, and blockade of miR-204 function reversed the beneficial effects of NFATc3 in macrophages.
Macrophage NFATc3 up-regulates miR-204 to reduce SR-A and CD36 levels, thereby preventing foam cell formation and atherosclerosis, indicating that the NFATc3/miR-204 axis may be a potential therapeutic target against atherosclerosis.
As a major cause of various cardiovascular diseases, the prevalence of hypertension has been increasing in the past 30 years, leading to significant socioeconomic and health burdens. Obesity is one ...of the major risk factors for hypertension. Body mass index (BMI) is the most used anthropometric index to measure obesity in clinical practice and to assess the risk of obesity-related diseases. However, obesity is a heterogeneous disease, and the accumulation of fat in different body regions leads to differences in cardiovascular and metabolic risks. BMI only reflects the overall obesity but does not consider the distribution of fat and muscle mass. The limitation of BMI makes it insufficient to assess the risk of hypertension attributed to obesity. In addition, waist circumference is an easily obtainable anthropometric index to evaluate abdominal fat distribution. High waist circumference is an independent risk factor for various cardiovascular diseases and all-cause mortality regardless of BMI. Preliminary data indicate that waist circumference is significantly associated with the risk of hypertension at different BMI levels. However, routine measurement of waist circumference is currently not required in current clinical guidelines or is only recommended for obese populations, indicating an insufficient understanding of waist circumference. In this review, we summarize the measurement methods and diagnostic thresholds of waist circumference for abdominal obesity, the trend of central obesity prevalence, the superiority of waist circumference over other anthropometric indices, and recent cross-sectional and longitudinal studies on the association between obesity and hypertension.
As a quinonemethide triterpenoid extracted from species of the
and
, pristimerin has been shown potent anti-cancer effects. Specifically, it was found that pristimerin can affect many tumor-related ...processes, such as apoptosis, autophagy, migration and invasion, vasculogenesis, and drug resistance. Various molecular targets or signaling pathways are also involved, such as cyclins, reactive oxygen species (ROS), microRNA, nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and PI3K/AKT/mammalian target of rapamycin (mTOR) pathways. In this review, we will focus on the research about pristimerin-induced anti-cancer activities to achieve a deeper understanding of the targets and mechanisms, which offer evidences suggesting that pristimerin can be a potent anti-cancer drug.
The emergence of pandrug-resistant bacteria breaks through the last line of defense and raises fear among people of incurable infections. In the post-antibiotic era, the pharmaceutical field turns to ...seek non-conventional anti-infective agents. Antimicrobial peptides are considered a prospective solution to the crisis of antimicrobial resistance. In this study, we evaluated the antimicrobial efficiency of an ApoE mimetic peptide, COG1410, which has been confirmed to exhibit strong neural protective activity and immunomodulatory function. COG1410 showed potent antimicrobial activity against pandrug-resistant
Acinetobacter baumannii
, even eliminating large inocula (10
8
CFU/ml) within 30 min. LC
99.9
in PBS and 50% pooled human plasma was 2 μg/ml (1.4 μM) and 8 μg/ml (5.6 μM), respectively. Moreover, COG1410 exhibited biofilm inhibition and eradication activity, excellent stability in human plasma, and a low propensity to induce resistance. Although COG1410 easily entered bacterial cytoplasm and bound to DNA nonspecifically, the major mechanism of COG1410 killing was to disrupt the integrity of cell membrane and lead to leakage of cytoplasmic contents, without causing obvious pores on the cell surface or cell lysis. Additionally, transcriptome analysis showed that treatment with COG1410-enriched genes involved a series of oxidation–reduction processes. DCFH-DA probe detected an increased ROS level in the presence of COG1410, indicating ROS was another hit of this AMP. Furthermore, the action of COG1410 did not depend on the electronic interaction with the LPS layer, in contrast to polymyxin B. The strong synergistic interaction between COG1410 and polymyxin B dramatically reduced the working concentration of COG1410, expanding the safety window of the application.
C. elegans
infection model showed that combined therapy of COG1410 and polymyxin B was capable of significantly rescuing the infected nematodes. Taken together, our study demonstrates that COG1410 is a promising drug candidate in the battle against pandrug-resistant
A. baumannii
.
Display omitted
•Methods with phase inversion were designed for intensifying reactive extraction.•With designed dispersion methods, the Murphree efficiency reached 90% within 2 s.•The effects of ...phase inversion on mass transfer were systematically studied.•Mathematical models were established for describing mass transfer characteristics.•The most effective dispersion methods for reactive extraction were recommended.
Reactive extraction is widely applied to wastewater treatment, hydrometallurgy, and other industries. In this study, process intensification in reactive extraction of formic acid at an aqueous-to-oil phase ratio of 75:1 was conducted, by developing microdispersed liquid/liquid and gas/liquid/liquid systems with phase inversion. In two of the gas/liquid/liquid modes, the Murphree efficiency reached 90% within 2.0 s, which was below 28% within 28.3 s when it was carried out with millimeter-dispersed emulsion systems. The effects of phase inversion and the addition of microbubbles were systematically studied. Uniform correlations were developed to investigate the intensification effect of microbubbles in mass transfer during the formation stage in six gas/liquid/liquid dispersion methods and mass transfer during the flowing stage in four (G + O)/W emulsion systems. The most effective modes were recommended by studying process intensification fundamentals in different gas/liquid/liquid modes. This study provided simple and effective methods for process intensification of reactive extraction.
PDF
