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1.
Toxicol Mech Methods ; : 1-15, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38872277

ABSTRACT

In biomedical research, the fruit fly (Drosophila melanogaster) is among the most effective and flexible model organisms. Through the use of the Drosophila model, molecular mechanisms of human diseases can be investigated and candidate pharmaceuticals can be screened. White rot fungus Inonotus obliquus is a member of the family Hymenochaetaceae. Due to its multifaceted pharmacological effects, this fungus has been the subject of scientific investigation. Nevertheless, the precise mechanisms by which Inonotus obliquus treats diseases remain unclear. In this study, we prepared an aqueous extract derived from Inonotus obliquus and demonstrated that it effectively prevented the negative impacts of inflammatory agents on flies, including overproliferation and overdifferentiation of intestinal progenitor cells and decreased survival rate. Furthermore, elevated reactive oxygen species levels and cell death were alleviated by Inonotus obliquus aqueous extract, suggesting that this extract inhibited intestinal inflammation. Additionally, Inonotus obliquus aqueous extract had an impact on the insulin pathway, as it alleviated growth defects in flies that were fed a high-sugar diet and in chico mutants. In addition, we determined the composition of Inonotus obliquus aqueous extract and conducted a network pharmacology analysis in order to identify prospective key compounds and targets. In brief, Inonotus obliquus aqueous extract exhibited considerable potential as a therapeutic intervention for human diseases. Our research has established a foundational framework that supports the potential clinical implementation of Inonotus obliquus.

2.
Environ Sci Pollut Res Int ; 31(27): 39439-39453, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38819511

ABSTRACT

Red mud (RM) is a typical bulk solid waste with Fe/Al/Si/Ca-rich characteristics that has been used to prepare various heterogeneous catalysts such as iron-based catalysts and supported catalysts. Prussian blue analogues (PBA) is a low-cost, environmentally friendly, and active site rich iron-based metal organic framework, but its catalytic properties are adversely affected by their easy aggregation. In this study, nickel-doped RM-based PBA (RM-Ni PBA) was synthesized by acid dissolution-coprecipitation method for the degradation of ciprofloxacin (CIP). The characterization showed that RM-Ni PBA was a material with excellent dispersibility, large specific surface area, and abundant active sites. The degradation results showed that the removal efficiency of CIP in the RM-Ni PBA/H2O2 system was 16.63, 1.78, and 1.81 times that of RM, RM-PB, and Ni PBA, respectively. It was found that 1O2 was the main reactive oxygen species (ROS) dominated the degradation process, and its formation was accompanied by the mutual conversion of Ni(II)/Fe(II) and Ni(III)/Fe(III). Notably, the degradation process maintained a satisfactory efficiency over a wide pH range (3-9) and exhibited strong anti-interference ability against impurities such as Cl-, SO42-, and NO3-. The components and contents of RM-Ni PBA remained relatively stable during the degradation process. In addition, the degradation intermediates of CIP were identified, and possible degradation pathways were proposed. This study is expected to provide theoretical basis and technical guidance for the application of RM-based heterogeneous catalyst in the treatment of antibiotic wastewater.


Subject(s)
Ciprofloxacin , Ferrocyanides , Hydrogen Peroxide , Nickel , Ciprofloxacin/chemistry , Nickel/chemistry , Hydrogen Peroxide/chemistry , Ferrocyanides/chemistry , Catalysis , Solid Waste
3.
Water Res ; 252: 121221, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38324985

ABSTRACT

This study proposes a novel method by forming biogenic K-jarosite coatings on pyrite surfaces driven by Acidithiobacillus ferrooxidans (A. ferrooxidans) to reduce heavy metal release and prevent acid mine drainage (AMD) production. Different thicknesses of K-jarosite coatings (0.7 to 1.1 µm) were able to form on pyrite surfaces in the presence of A. ferrooxidans, which positively correlated with the initial addition of Fe2+ and K+ concentrations. The inhibiting effect of K-jarosite coatings on pyrite oxidation was studied by electrochemical measurements, chemical oxidation tests, and bio-oxidation tests. The experimental results showed that the best passivation performance was achieved when 20 mM Fe2+ and 6.7 mM K+ were initially introduced with a bacterial concentration of 4 × 108 cells·mL-1, reducing chemical and biological oxidation by 70 % and 98 %, respectively (based on the concentration of total iron dissolved into the solution by pyrite oxidation). Similarly, bio-oxidation tests of two mine waste samples also showed sound inhibition effects, which offers a preliminary demonstration of the potential applicability of this method to actual waste rock. This study presents a new perspective on passivating the oxidation of metal sulfide tailings or waste and preventing AMD.


Subject(s)
Acidithiobacillus , Iron , Sulfates , Ferric Compounds , Sulfides , Oxidation-Reduction
4.
Ecotoxicol Environ Saf ; 269: 115794, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38061084

ABSTRACT

The massive accumulation of red mud (RM) and the abuse of antibiotics pose a threat to environment safety and human health. In this study, we synthesized RM-based Prussian blue (RM-PB) by acid solution-coprecipitation method to activate H2O2 to degrade norfloxacin, which reached about 90% degradation efficiency at pH 5 within 60 min and maintained excellent catalytic performance over a wide pH range (3-11). Due to better dispersion and unique pore properties, RM-PB exposed more active sites, thus the RM-PB/H2O2 system produced more reactive oxygen species. As a result, the removal rate of norfloxacin by RM-PB/H2O2 system was 8.58 times and 2.62 times of that by RM/H2O2 system and PB/H2O2 system, respectively. The reactive oxygen species (ROS) produced in the degradation process included ·OH, ·O2- and 1O2, with 1O2 playing a dominant role. The formation and transformation of these ROS was accompanied by the Fe(III)/Fe(II) cycle, which was conducive for the sustained production of ROS. The RM-PB/H2O2 system maintained a higher degradation efficiency after five cycles, and the material exhibited strong stability, with a low iron leaching concentration. Further research showed the degradation process was less affected by Cl-, SO42-, NO3-, and humic acids, but was inhibited by HCO3- and HPO42-. In addition, we also proposed the possible degradation pathway of norfloxacin. This work is expected to improve the resource utilization rate of RM and achieve treating waste with waste.


Subject(s)
Ferrocyanides , Hydrogen Peroxide , Norfloxacin , Humans , Hydrogen Peroxide/chemistry , Reactive Oxygen Species , Ferric Compounds , Oxidation-Reduction
5.
Insects ; 14(8)2023 Aug 14.
Article in English | MEDLINE | ID: mdl-37623416

ABSTRACT

Autophagy is a process that promotes the lysosomal degradation of cytoplasmic proteins and is highly conserved in eukaryotic organisms. Autophagy maintains homeostasis in organisms and regulates multiple developmental processes, and autophagy disruption is related to human diseases. However, the functional roles of autophagy in mediating innate immune responses are largely unknown. In this study, we sought to understand how Atg2, an autophagy-related gene, functions in the innate immunity of Drosophila melanogaster. The results showed that a large number of melanotic nodules were produced upon inhibition of Atg2. In addition, inhibiting Atg2 suppressed the phagocytosis of latex beads, Staphylococcus aureus and Escherichia coli; the proportion of Nimrod C1 (one of the phagocytosis receptors)-positive hemocytes also decreased. Moreover, inhibiting Atg2 altered actin cytoskeleton patterns, showing longer filopodia but with decreased numbers of filopodia. The expression of AMP-encoding genes was altered by inhibiting Atg2. Drosomycin was upregulated, and the transcript levels of Attacin-A, Diptericin and Metchnikowin were decreased. Finally, the above alterations caused by the inhibition of Atg2 prevented flies from resisting invading pathogens, showing that flies with low expression of Atg2 were highly susceptible to Staphylococcus aureus and Erwinia carotovora carotovora 15 infections. In conclusion, Atg2 regulated both cellular and humoral innate immunity in Drosophila. We have identified Atg2 as a crucial regulator in mediating the homeostasis of immunity, which further established the interactions between autophagy and innate immunity.

6.
Front Physiol ; 14: 1266635, 2023.
Article in English | MEDLINE | ID: mdl-38187130

ABSTRACT

Background: Liver transplantation (LTx) is the most effective treatment for end-stage liver diseases. Gut microorganisms influence the host physiology. We aim to profile the dynamics of gut microbiota in the perioperative period and a 1-year follow-up of LTx recipients in Northeast China. Methods: A total of 257 fecal samples were longitudinally collected from 85 LTx patients using anal swabs from pre-LTx to 1-year post-LTx. A total of 48 fecal samples from end-stage liver disease patients without LTx served as the control. 16S rRNA sequencing was used to analyze gut microbiota diversity, bacterial genera, phenotype classification, and metabolic pathways. Results: The diversity of gut microbiota decreased significantly after transplantation, accompanied by a profound change in the microbial structure, which is characterized by increased abundance of facultative anaerobic bacteria dominated by g_Enterococcus and reduced anaerobic bacteria composition. Predicted functional analysis also revealed disturbances in the metabolic pathway of the gut microbiota. After LTx, the diversity of microbiota gradually recovered but to a less preoperative level after 1 year of recovery. Compared with pre-transplantation, the microbiome structure was characterized by an increase in Acidaminococcus and Acidithiobacillus after 1 year of transplantation. Conclusion: LTx and perioperative treatment triggered gut microbial dysbiosis. The gut microbiota was restructured after LTx to near to but significantly differed from that of pre-LTx.

7.
Sci Total Environ ; 851(Pt 2): 158200, 2022 Dec 10.
Article in English | MEDLINE | ID: mdl-36049690

ABSTRACT

Humic acid has the advantages of wide source, easy availability and environmental friendliness, which may be a good choice for inhibiting chalcopyrite biooxidation and alleviating copper pollution. However, there are few researches on the inhibitory effect and mechanism of humic acid on the biooxidation of chalcopyrite. In order to fill this knowledge gap, this study proposed and validated a novel method for inhibiting chalcopyrite biooxidation by means of humic acid. The results showed that the biooxidation of chalcopyrite could be effectively inhibited by humic acid, which consequently decreased the release of copper ions. Humic acid with a concentration of 120 ppm had the best inhibitory effect, which reduced the biooxidation efficiency of chalcopyrite from 40.7 ± 0.5 % to 29.3 ± 0.8 %. This in turn suggested that humic acid could effectively suppress the pollution of copper under these conditions. The analysis results of solution parameters, mineral surface morphology, mineral phases and element composition showed that humic acid inhibited the growth of Acidithiobacillus ferrooxidans, promoted the formation of jarosite and intensified the passivation of chalcopyrite, which effectively hindered the biooxidation of chalcopyrite, and would help to alleviate the pollution of copper.


Subject(s)
Copper , Humic Substances , Environmental Pollution
8.
Chem Biol Interact ; 366: 110137, 2022 Oct 01.
Article in English | MEDLINE | ID: mdl-36055377

ABSTRACT

Accumulating evidence have indicated that ferroptosis plays a crucial role in cerebral ischemia-reperfusion (I/R) injury which is the most serious treatment complication of ischemic stroke. Baicalein (5,6,7-trihydroxyflavone) is a main bioactive ingredient isolated from a traditional Chinese medicine named Baikal Skullcap, which is the root of Scutellaria baicalensis Georgi. This study investigated the potential role of baicalein in cerebral I/R injury using oxygen-glucose deprivation and reoxygenation (OGD/R) HT22 cells, transient middle cerebral artery occlusion (tMCAO) mice and RSL3-sitmulated HT22 cells. Baicalein improved the viability of OGD/R cells and significantly ameliorated cerebral I/R injury in tMCAO mice. Baicalein decreased the iron levels, lipid peroxidation production and morphology features of ferroptosis of the brain tissues in tMCAO mice, which indicated that baicalein ameliorated cerebral I/R injury by inhibiting ferroptosis in vivo and in vitro. We further confirmed that baicalein had the activity of inhibiting ferroptosis in RSL3-stimulated HT22 cells. Western blot revealed that baicalein inhibited the ferroptosis by regulating on the expression levels of GPX4, ACSL4 and ACSL3 in OGD/R cells, tMCAO mice and RSL3-stimulated HT22 cells. Our findings demonstrated that baicalein reversed the cerebral I/R injury via anti-ferroptosis, which was regulated by GPX4/ACSL4/ACSL3 axis. The results suggested that baicalein has therapeutic potential as a drug for cerebral I/R injury.


Subject(s)
Reperfusion Injury , Animals , Coenzyme A Ligases , Flavanones , Glucose , Iron/metabolism , Mice , Oxygen/therapeutic use , Reperfusion Injury/drug therapy , Reperfusion Injury/metabolism
9.
Front Immunol ; 13: 905370, 2022.
Article in English | MEDLINE | ID: mdl-35911716

ABSTRACT

The innate immune response provides the first line of defense against invading pathogens, and immune disorders cause a variety of diseases. The fruit fly Drosophila melanogaster employs multiple innate immune reactions to resist infection. First, epithelial tissues function as physical barriers to prevent pathogen invasion. In addition, macrophage-like plasmatocytes eliminate intruders through phagocytosis, and lamellocytes encapsulate large particles, such as wasp eggs, that cannot be phagocytosed. Regarding humoral immune responses, the fat body, equivalent to the mammalian liver, secretes antimicrobial peptides into hemolymph, killing bacteria and fungi. Drosophila has been shown to be a powerful in vivo model for studying the mechanism of innate immunity and host-pathogen interactions because Drosophila and higher organisms share conserved signaling pathways and factors. Moreover, the ease with which Drosophila genetic and physiological characteristics can be manipulated prevents interference by adaptive immunity. In this review, we discuss the signaling pathways activated in Drosophila innate immunity, namely, the Toll, Imd, JNK, JAK/STAT pathways, and other factors, as well as relevant regulatory networks. We also review the mechanisms by which different tissues, including hemocytes, the fat body, the lymph gland, muscles, the gut and the brain coordinate innate immune responses. Furthermore, the latest studies in this field are outlined in this review. In summary, understanding the mechanism underlying innate immunity orchestration in Drosophila will help us better study human innate immunity-related diseases.


Subject(s)
Drosophila melanogaster , Drosophila , Animals , Hemocytes , Humans , Immunity, Innate , Mammals , Signal Transduction
10.
Transl Androl Urol ; 11(2): 228-237, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35280653

ABSTRACT

Background: The occurrence of systemic inflammatory response syndrome (SIRS) is an early alert for sepsis after flexible ureteroscopy (fURS). Once sepsis occurs, it often leads to severe or fatal consequences. We aimed to identify SIRS patients preoperatively by developing and validating a feasible prognostic nomogram model based on retrospective cohort analysis. Methods: A total of 311 patients who underwent fURS in Dongguan Kanghua Hospital (Dongguan, China) between 2016 and 2020 were included and randomly divided into a primary cohort (n=219) and validation cohort (n=92). Single factor regression analysis was used to identify the primary cohort's meaningful characters between SIRS and non-SIRS groups. Factors of the primary cohort were then identified by least absolute shrinkage and selection operator (LASSO) regression analysis, and a nomogram was built to execute the subsequent analysis using these factors. Finally, we analyzed and drew the calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) curve to validate the prognostic value of the nomogram in calibration and discrimination. Results: Review of the single regression analysis of characters in the primary cohort showed gender, stone burden, diabetes, neutrophil (N), lymphocyte (L), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocytes ratio (LMR), urine-WBC, nitrite (Nit), urine culture, and surgery time as significant factors between the SIRS and non-SIRS groups (P<0.05). The LASSO regression analysis suggested NLR, PLR, and urine culture were substantial factors in predicting SIRS postoperatively, lambda.min and lambda.1se (standard error, SE) were 0.01491 and 0.0796. A nomogram built with the three factors showed good calibration and discrimination, with the Brier values 0.064 and 0.034 and the area under curve (AUC) values 0.897 (95% CI: 0.837-0.957) and 0.976 (95% CI: 0.947-1.000) in the primary and validation cohort, respectively. DCA demonstrated the nomogram was clinically useful, and the predict probability of SIRS's occurrence was very close to the actual rate as the risk threshold increased by higher than 60% in clinical impact curve analysis. Conclusions: NLR, PLR, and urine culture were significantly related to the occurrence of SIRS's after fURS. The nomogram with these three factors showed excellent calibration, discrimination, and clinical usefulness.

11.
Med Sci Monit ; 28: e934100, 2022 Jan 11.
Article in English | MEDLINE | ID: mdl-35013090

ABSTRACT

BACKGROUND Hyperhomocysteinemia (HHcy) and metabolic syndrome (MS) are established cardiovascular risk factors of stroke and are frequently associated with hypertension. However, studies on the association between HHcy combined with MS and stroke risk in hypertensive patients were absent. MATERIAL AND METHODS In 14 059 selected participants with elevated blood pressure, we assessed the prevalence of the MS and stroke. We defined HHcy as plasma total homocysteine >15 µmol/L. MS was defined according to the Chinese Diabetes Society (CDS) criterion. Multivariable analysis was used to examine the association of HHcy or (and) MS with stroke risk in different models. RESULTS The prevalence rates of HHcy and MS were 49.96% and 42.21%, respectively. Patients with stroke had higher plasma total homocysteine levels and a higher prevalence of MS (P<0.001). Multivariable analyses indicated that HHcy and MS are independently associated with higher prevalence of stroke (adjusted-odds ratio (OR): 1.36, 95% CI 1.17 to 1.58, P<0.001; adjusted-OR: 1.68, 95% CI 1.44 to 1.96, P<0.001, respectively). Those with combined HHcy and MS had higher odds of stroke than those with isolated HHcy or MS (adjusted-OR: 1.78, 95% CI 1.47 to 2.15, P<0.001; adjusted-OR: 1.39, 95% CI 1.13 to 1.70, P=0.002, respectively). CONCLUSIONS HHcy combined with MS was associated with higher prevalence of stroke in Chinese adults with elevated blood pressure.


Subject(s)
Homocysteine/blood , Hyperhomocysteinemia , Hypertension , Metabolic Syndrome , Stroke , Aged , Biomarkers/blood , Blood Pressure Determination/methods , Blood Pressure Determination/statistics & numerical data , China/epidemiology , Comorbidity , Correlation of Data , Female , Heart Disease Risk Factors , Humans , Hyperhomocysteinemia/blood , Hyperhomocysteinemia/diagnosis , Hyperhomocysteinemia/epidemiology , Hypertension/diagnosis , Hypertension/epidemiology , Hypertension/metabolism , Male , Metabolic Syndrome/blood , Metabolic Syndrome/diagnosis , Metabolic Syndrome/epidemiology , Prevalence , Risk Assessment/methods , Stroke/diagnosis , Stroke/epidemiology , Stroke/metabolism , Stroke/physiopathology
12.
Int J Gen Med ; 14: 3627-3634, 2021.
Article in English | MEDLINE | ID: mdl-34321908

ABSTRACT

BACKGROUND: High body mass index (BMI) is a well-recognized risk factor for cardiovascular diseases. But its role in peripheral artery disease (PAD) remains perplexing. Our study aims to evaluate the association of BMI with PAD in the Chinese hypertensive population. METHODS: This is a cross-sectional study with enrollment data from the Chinese H-type Hypertension Registry.10896 hypertensive patients aged ≥18 years were included in the final analysis. RESULTS: The prevalence of PAD diagnosed by ABI in this study was 3.2% (n=351). A U-shaped association between BMI and PAD was found. Per SD increment (3.6 kg/m2) on the left side of the BMI threshold (BMI < 25.7 kg/m2) was associated with a 27% decrease in the adjusted risk of PAD [OR, 0.73; 95% confidence interval (CI) 0.60, 0.89; P=0.002]; BMI was significantly positively associated with the risk of PAD (OR, 1.52; 95% CI 1.52, 1.93; P=0.001) in those with BMI ≥25.7 kg/m2. CONCLUSION: In summary, a U-shaped association between BMI and the risk of PAD in the Chinese hypertensive population was found. BMI with the lowest risk of PAD was estimated to be 25.7 kg/m2.

13.
Chemosphere ; 279: 130516, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33878694

ABSTRACT

Chalcopyrite is a crucial contributor causing acid mine drainage (AMD). Silver and pyrite are commonly co-existed with chalcopyrite, and can significantly affect the copper release from chalcopyrite bio-dissolution process. However, the combined effect of them on chalcopyrite bio-dissolution has not been illustrated up to now. To fill this knowledge gap, the combined effect of silver and pyrite on chalcopyrite dissolution with Acidithiobacillus ferrooxidans was investigated in this study. The copper extraction reached the maximum value (62.3 ± 0.1%) with the presence of silver and pyrite, which was 43.8 ± 0.1% higher than the control group (without addition). This suggested more copper ions and acids were released under this circumstance. According to bio-dissolution results, SEM, XRD and XPS analyses, the promotion effect of silver and pyrite on chalcopyrite bio-dissolution was mainly attributed to the increase of ferric ions in solution and the reduction of passivation layer (Sn2-/S0) on chalcopyrite surface. The investigation into the bio-dissolution of chalcopyrite is important for controlling the generation of copper ions and acids. Silver or pyrite bearing chalcopyrite should be carefully treated to avoid the pollution of heavy metal copper and acid in the mining environment.


Subject(s)
Acidithiobacillus , Copper , Iron , Silver , Solubility , Sulfides
14.
Elife ; 102021 02 09.
Article in English | MEDLINE | ID: mdl-33560224

ABSTRACT

The hematopoietic system of Drosophila is a powerful genetic model for studying hematopoiesis, and vesicle trafficking is important for signal transduction during various developmental processes; however, its interaction with hematopoiesis is currently largely unknown. In this article, we selected three endosome markers, Rab5, Rab7, and Rab11, that play a key role in membrane trafficking and determined whether they participate in hematopoiesis. Inhibiting Rab5 or Rab11 in hemocytes or the cortical zone (CZ) significantly induced cell overproliferation and lamellocyte formation in circulating hemocytes and lymph glands and disrupted blood cell progenitor maintenance. Lamellocyte formation involves the JNK, Toll, and Ras/EGFR signaling pathways. Notably, lamellocyte formation was also associated with JNK-dependent autophagy. In conclusion, we identified Rab5 and Rab11 as novel regulators of hematopoiesis, and our results advance the understanding of the mechanisms underlying the maintenance of hematopoietic homeostasis as well as the pathology of blood disorders such as leukemia.


Subject(s)
Drosophila Proteins/genetics , Drosophila melanogaster/genetics , Hematopoiesis/genetics , Homeostasis/genetics , Signal Transduction , rab GTP-Binding Proteins/genetics , rab5 GTP-Binding Proteins/genetics , Animals , Drosophila Proteins/metabolism , Drosophila melanogaster/growth & development , Drosophila melanogaster/metabolism , Larva/genetics , Larva/growth & development , Larva/metabolism , rab GTP-Binding Proteins/metabolism , rab5 GTP-Binding Proteins/metabolism
15.
Front Aging Neurosci ; 13: 706928, 2021.
Article in English | MEDLINE | ID: mdl-35250530

ABSTRACT

BACKGROUND: Increasing studies have focused on the predictive value of high estimated glomerular filtration rate (eGFR) on cardiovascular diseases and mortality; however, the association between high eGFR with cognitive function is still not established. Thus, this study aimed to determine the co-relationship between high eGFR and cognitive performance in the hypertensive population. METHODS: We conducted a baseline cross-sectional study using data from the China H-type Hypertension Registry study. Mini-Mental State Examination (MMSE) assessment was performed to evaluate the cognitive function scale, and serum creatinine was collected to estimate eGFR level. Different MMSE cutoff values were applied in participants with the various educational background to define dementia: <24 in participants with secondary school and above education setting, <20 in those with primary school, and <17 in illiterate participants. RESULTS: A total of 9,527 hypertensive adults with mean age 63.7 ± 9.8 years and 67% female gender were analyzed. The eGFR cutoff value of 71.52 ml/min/1.73 m2 was found after adjusting for potential covariates in a threshold effect analysis. The MMSE increased significantly with the increment of eGFR (ß, 0.27; 95% CI: 0.12-0.41) in participants with eGFR < 71.52 ml/min/1.73 m2 and decreased (ß, -0.28; 95% CI: -0.39 to -0.17) in participants with eGFR ≥ 71.52 ml/min/1.73 m2. Individuals with eGFR ≥ 85 ml/min/1.73 m2 have an elevated risk of cognitive impairment than those with eGFR of 65-75 ml/min/1.73 m2. Subgroup analysis showed that a greater reduction degree of MMSE was observed in female individuals and those who had body mass index (BMI) ≥ 24 kg/m2 among participants with eGFR ≥ 71.52 ml/min/1.73 m2. CONCLUSION: Our findings observed an inverted U-shaped relationship between eGFR and cognitive function. Both the low and high levels of eGFR were independently associated with worse cognitive assessment in the hypertensive population.

16.
Int J Pharm ; 587: 119638, 2020 Sep 25.
Article in English | MEDLINE | ID: mdl-32659406

ABSTRACT

It is a great challenge to improve the oral bioavailability for BCS class IV drugs because they have low solubility and poor permeability. However, nanonization and intestinal transporter-targeted prodrugs can increase the solubility and permeability, respectively. Hence, an "increased solubility and improved permeability" cascade strategy was proposed to enhance the dissolution rate and permeability for BCS class IV drugs. In this study, acyclovir glutarate (AG), a prodrug of acyclovir, was synthesized to improve intestinal permeability by targeting monocarboxylate transporter 1 (MCT 1), an intestinal influx transporter. Then, AG was formulated as AG nanoneedles (AGNNs) to improve dissolution behavior. AG was demonstrated to exhibit greatly higher cellular uptake efficiency and permeability than acyclovir due to the MCT 1-mediated active transport. Furthermore, intact AGNNs were also demonstrated to be endocytosed by enterocytes and to be transcytosed potentially. In addition, oral pharmacokinetics showed that the AUC0-24h of AGNNs was 1.89-fold to that of acyclovir. Collectively, these results confirmed that nanonized MCT 1-targeted prodrugs enhanced the oral bioavailability of acyclovir in a cascade manner. Our findings propose a promising strategy to develop BCS class IV drugs and have significant implications for a wide range of such drugs for high oral delivery efficiency.


Subject(s)
Prodrugs , Acyclovir , Administration, Oral , Biological Availability , Biological Transport , Solubility
17.
Front Cell Dev Biol ; 8: 382, 2020.
Article in English | MEDLINE | ID: mdl-32509789

ABSTRACT

Hematopoiesis is a necessary process for development and immune defense in Drosophila from the embryonic period to adulthood. There are two main stages in this process: the first stage occurs in the head mesoderm during the embryonic stage, and the second occurs in a specialized hematopoietic organ along the dorsal vessel, the lymph gland, during the larval stage. The lymph gland consists of paired lobes, each of which has distinct regions: the cortical zone (CZ), which contains mature hemocytes; the medullary zone (MZ), which contains hematopoietic progenitors; and the posterior signaling center (PSC), which specifically expresses the early B-cell factor (EBF) transcription factor Collier (Col) and the HOX factor Antennapedia (Antp) to form a microenvironment similar to that of the mammalian bone marrow hematopoietic stem cell niche. The PSC plays a key role in regulating hematopoietic progenitor differentiation. Moreover, the PSC contributes to the cellular immune response to wasp parasitism triggered by elevated ROS levels. Two recent studies have revealed that hematopoietic progenitor maintenance is directly regulated by Col expressed in the MZ and is independent of the PSC, challenging the traditional model. In this review, we summarize the regulatory networks of PSC cell proliferation, the controversy regarding PSC-mediated regulation of hematopoietic progenitor differentiation, and the wasp egg infection response. In addition, we discuss why the PSC is an ideal model for investigating mammalian hematopoietic stem cell niches and leukemia.

18.
Sci Total Environ ; 737: 139485, 2020 Oct 01.
Article in English | MEDLINE | ID: mdl-32516660

ABSTRACT

Although chalcopyrite biodissolution plays an important role in the formation of acid mine drainage (AMD), the control of AMD through inhibiting the biodissolution of chalcopyrite has not been studied until now. In order to fill this knowledge gap, a novel method for inhibiting chalcopyrite biodissolution using biochar was proposed and verified. The effects of biochar pyrolysis temperature and biochar concentration on the inhibition of chalcopyrite biodissolution in the presence of Acidithiobacillus ferrooxidans (A. ferrooxidans) were studied. The results indicate that biochar significantly inhibited chalcopyrite biodissolution, thus reducing the number of copper and iron ions and quantity of acid released. In turn, this suggests that AMD generation was suppressed under these conditions. Biochar pyrolyzed at 300 °C (Biochar-300 °C) was the most effective at inhibiting chalcopyrite biodissolution and reduced its biodissolution rate by 17.7%. A suitable concentration of biochar-300 °C enhanced its inhibition of chalcopyrite biodissolution. The optimal concentration of biochar-300 °C for inhibiting chalcopyrite biodissolution was 3 g/L. Biodissolution results, cyclic voltammetry, mineral surface morphology, mineralogical phase, and elemental composition analyses reveal that biochar inhibited the biodissolution of chalcopyrite by promoting the formation of passivation layer (jarosite and Sn2-/S0) and adsorbing bacteria.


Subject(s)
Acidithiobacillus , Copper , Charcoal
19.
Cell Commun Signal ; 16(1): 95, 2018 12 05.
Article in English | MEDLINE | ID: mdl-30518379

ABSTRACT

BACKGROUND: The regulatory mechanisms of hematopoiesis and cellular immunity show a high degree of similarity between insects and mammals, and Drosophila has become a good model for investigating cellular immune responses. Jumeau (Jumu) is a member of the winged-helix/forkhead (FKH) transcription factor family and is required for Drosophila development. Adult jumu mutant flies show defective hemocyte phagocytosis and a weaker defense capability against pathogen infection. Here, we further investigated the role of jumu in the regulation of larval hemocyte development and phagocytosis. METHODS: In vivo phagocytosis assays, immunohistochemistry, Real-time quantitative PCR and immunoblotting were performed to investigate the effect of Jumu on hemocyte phagocytosis. 5-Bromo-2-deoxyUridine (BrdU) labeling, phospho-histone H3 (PH3) and TdT-mediated dUTP Nick-End Labeling (TUNEL) staining were performed to analyze the proliferation and apoptosis of hemocyte; immunohistochemistry and Mosaic analysis with a repressible cell marker (MARCM) clone analysis were performed to investigate the role of Jumu in the activation of Toll pathway. RESULTS: Jumu indirectly controls hemocyte phagocytosis by regulating the expression of NimC1 and cytoskeleton reorganization. The loss of jumu also causes abnormal proliferation and differentiation in circulating hemocytes. Our results suggest that a severe deficiency of jumu leads to the generation of enlarged multinucleate hemocytes by affecting the normal cell mitosis process and induces numerous lamellocytes by activating the Toll pathway. CONCLUSIONS: Jumu regulates circulating hemocyte differentiation and phagocytosis in Drosophila. Our findings provide new insight into the mechanistic roles of cytoskeleton regulatory proteins in phagocytosis and establish a basis for further analyses of the regulatory mechanism of the mammalian ortholog of Jumu in mammalian innate immunity.


Subject(s)
Cell Differentiation , Drosophila Proteins/metabolism , Drosophila melanogaster/cytology , Drosophila melanogaster/metabolism , Hemocytes/cytology , Phagocytosis , Transcription Factors/metabolism , Animals , Drosophila Proteins/deficiency , Drosophila Proteins/genetics , Drosophila melanogaster/genetics , Gene Expression Regulation , Gene Knockdown Techniques , Pseudopodia/metabolism , Receptors, Immunologic/metabolism , Transcription Factors/deficiency , Transcription Factors/genetics
20.
Exp Cell Res ; 368(2): 215-224, 2018 07 15.
Article in English | MEDLINE | ID: mdl-29727694

ABSTRACT

A high-sugar diet (HSD) induces Type 2 diabetes (T2D) and obesity, which severely threaten human health. The Drosophila T2D model has been constructed to study the mechanisms of insulin resistance, diet-induced cardiovascular diseases and other conditions. Innate immunity is the first line of defense against invading pathogens and parasites. However, few studies have focused on the relationship between a HSD and the innate immune response in Drosophila. In this study, we fed flies a high-sucrose diet and observed defects in the phagocytosis of latex beads and B. bassiana spores. The actin cytoskeleton was also disrupted in hemocytes from HSD-fed larvae. Furthermore, HSD induced the differentiation of lamellocytes in the lymph gland and circulating hemolymph, which rarely occurs in healthy bodies, via JNK signaling. In addition, the Toll and JNK pathways were excessively activated in the fat bodies of HSD-fed larvae, and a large number of dead cells were observed. Finally, HSD induced the aberrant activation of the innate immune system, including inflammation. Our results have established a connection between T2D and the innate immune response.


Subject(s)
Diet/adverse effects , Drosophila melanogaster/immunology , Immunity, Cellular/immunology , Immunity, Humoral/immunology , Sugars/administration & dosage , Actin Cytoskeleton/immunology , Animals , Cell Differentiation/immunology , Diabetes Mellitus, Type 2/immunology , Disease Models, Animal , Hemocytes/immunology , Immunity, Innate/immunology , Inflammation/immunology , Larva/immunology , MAP Kinase Signaling System/immunology , Phagocytosis/immunology
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