Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 85
Filter
1.
Comput Methods Programs Biomed ; 257: 108450, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39369587

ABSTRACT

BACKGROUND AND OBJECTIVES: The higher clinical significance of central aortic blood pressure (CABP) compared to peripheral blood pressures has been extensively demonstrated. Accordingly, many methods for noninvasively estimating CABP have been proposed. However, there still lacks a systematic comparison of existing methods, especially in terms of how they differ in the ability to tolerate individual differences or measurement errors. The present study was designed to address this gap. METHODS: A large-scale 'virtual subject' dataset (n = 600) was created using a computational model of the cardiovascular system, and applied to examine several classical CABP estimation methods, including the direct method, generalized transfer function (GTF) method, n-point moving average (NPMA) method, second systolic pressure of periphery (SBP2) method, physical model-based wave analysis (MBWA) method, and suprasystolic cuff-based waveform reconstruction (SCWR) method. The errors of CABP estimation were analyzed and compared among methods with respect to the magnitude/distribution, correlations with physiological/hemodynamic factors, and sensitivities to noninvasive measurement errors. RESULTS: The errors of CABP estimation exhibited evident inter-method differences in terms of the mean and standard deviation (SD). Relatively, the estimation errors of the methods adopting pre-trained algorithms (i.e., the GTF and SCWR methods) were overall smaller and less sensitive to variations in physiological/hemodynamic conditions and random errors in noninvasive measurement of brachial arterial blood pressure (used for calibrating peripheral pulse wave). The performances of all the methods worsened following the introduction of random errors to peripheral pulse wave (used for deriving CABP), as characterized by the enlarged SD and/or increased mean of the estimation errors. Notably, the GTF and SCWR methods did not exhibit a better capability of tolerating pulse wave errors in comparison with other methods. CONCLUSIONS: Classical noninvasive methods for estimating CABP were found to differ considerably in both the accuracy and error source, which provided theoretical evidence for understanding the specific advantages and disadvantages of each method. Knowledge about the method-specific error source and sensitivities of errors to different physiological/hemodynamic factors may contribute as theoretical references for interpreting clinical observations and exploring factors underlying large estimation errors, or provide guidance for optimizing existing methods or developing new methods.

2.
J Immunol ; 213(5): 730-742, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38984862

ABSTRACT

Teleost IgM+ B cells can phagocytose, like mammalian B1 cells, and secrete Ag-specific IgM, like mammalian B2 cells. Therefore, teleost IgM+ B cells may have the functions of both mammalian B1 and B2 cells. To support this view, we initially found that grass carp (Ctenopharyngodon idella) IgM+ plasma cells (PCs) exhibit robust phagocytic ability, akin to IgM+ naive B cells. Subsequently, we sorted grass carp IgM+ PCs into two subpopulations: nonphagocytic (Pha-IgM+ PCs) and phagocytic IgM+ PCs (Pha+IgM+ PCs), both of which demonstrated the capacity to secrete natural IgM with LPS and peptidoglycan binding capacity. Remarkably, following immunization of grass carp with an Ag, we observed that both Pha-IgM+ PCs and Pha+IgM+ PCs could secrete Ag-specific IgM. Furthermore, in vitro concatenated phagocytosis experiments in which Pha-IgM+ PCs from an initial phagocytosis experiment were sorted and exposed again to beads confirmed that these cells also have phagocytic capabilities, thereby suggesting that all teleost IgM+ B cells have phagocytic potential. Additionally, we found that grass carp IgM+ PCs display classical phenotypic features of macrophages, providing support for the hypothesis that vertebrate B cells evolved from ancient phagocytes. These findings together reveal that teleost B cells are a primitive B cell type with functions reminiscent of both mammalian B1 and B2 cells, providing insights into the origin and evolution of B cells in vertebrates.


Subject(s)
B-Lymphocytes , Carps , Immunoglobulin M , Phagocytosis , Plasma Cells , Animals , Carps/immunology , Immunoglobulin M/immunology , Phagocytosis/immunology , Plasma Cells/immunology , B-Lymphocytes/immunology , Phagocytes/immunology , Biological Evolution
3.
Fish Shellfish Immunol ; 150: 109649, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38797336

ABSTRACT

In mammals, CD4 is found to be expressed on T cells and innate immune cells, however, teleost cells bearing CD4 have not been well identified and characterized. In this study, we identified two different CD4-1+ cell subsets in grass carp (Ctenopharyngodon idella): CD4-1+ lymphocytes (Lym) and CD4-1+ myeloid cells (Mye), both of which had the highest proportions in the head kidney. The mRNA expression analysis showed that CD4-1, CD4-2, TCRß, CD3γ/δ, and LCK1 are highly expressed in CD4-1+ Lym and also expressed in CD4-1+ Mye. Furthermore, we found that CD4-1+ Lym have a Lym morphology and highly express T-cell cytokines, suggesting that they are CD4+ T cells equivalent to mammalian Th cells. On the other hand, CD4-1+ Mye were found to have a morphology of macrophage and highly express macrophage marker gene MCSFR, indicating that they are macrophages. In addition, functional analysis revealed that CD4-1+ Mye possess phagocytic ability and great antigen-processing ability. Taken together, our study sheds further light on the composition and function of CD4+ cells in teleost fish.


Subject(s)
Carps , Fish Proteins , Animals , Carps/immunology , Carps/genetics , Fish Proteins/genetics , Fish Proteins/immunology , CD4-Positive T-Lymphocytes/immunology , CD4 Antigens/genetics , CD4 Antigens/immunology , CD4 Antigens/metabolism , Head Kidney/immunology , Head Kidney/cytology , Myeloid Cells/immunology , Immunity, Innate/genetics
4.
J Pain Res ; 17: 1393-1400, 2024.
Article in English | MEDLINE | ID: mdl-38618295

ABSTRACT

Objective: We aimed to understand the commonly used acupoints and the acupoint combination rules in Guasha therapy for primary headaches using data mining technology, providing a reference for the clinical application of Guasha therapy for primary headaches. Methods: Literature related to Guasha therapy for primary headaches in PubMed, Web of Science, Chinese National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and Chinese Biomedical Literature Database were searched, up until May 12, 2023. A database of acupoints for Guasha therapy for primary headaches was established in Excel. The frequency of the acupoints used for Guasha in therapy of primary headaches were calculated by SPSS 25.0. The association rules between the acupoints were further described using SPSS Modeler 18.0. Results: A total of 67 papers were included, involving 51 acupoints for Guasha against primary headaches. The most commonly used acupoints were Fengchi, Baihui, Taiyang, Shuaigu, Tianzhu, and Hegu. The common acupoint combinations for Guasha therapy for primary headaches were Fengchi-Taiyang, Fengchi-Baihui, Fengchi-Taiyang-Baihui, Fengchi-Tianzhu-Baihui, and Fengchi-Shuaigu-Taiyang-Baihui. Conclusion: Data mining can effectively analyze the commonly used acupoints and the acupoint combination rules in Guasha therapy for primary headaches, providing a reliable basis for clinical acupoint selection.

5.
Chem Sci ; 15(11): 4068-4074, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38487215

ABSTRACT

In the case of covalent polymers, immiscible polymers can be integrated by covalently linking them together, but such a strategy is not possible in supramolecular polymers. Here we report the supramolecular copolymerization of two porphyrin-based monomers, C10P2H and TEGPCu with side chains bearing cyanobiphenyl (CB) groups at the ends of hydrophobic alkyl or hydrophilic tetraethylene glycol chains, respectively. These monomers undergo self-sorting supramolecular polymerization in highly diluted solutions ([monomer] = 3.4 × 10-9 mol% (2.0 × 10-8 mol L-1)) in nonpolar media due to the incompatibility of the side chains. Surprisingly, these monomers undergo supramolecular copolymerization under high concentration conditions ([monomer] = 7.7 mol%) in the medium of 4-cyano-4'-pentyloxybiphenyl (5OCB) to form a columnar liquid crystalline phase under thermodynamic conditions, where the individual columns are composed of supramolecular block copolymers. The combination of CB ends of both monomers and the 5OCB medium is essential for the two monomers to form an integrated structure in a condensed system without phase separation.

6.
Neurol Sci ; 45(7): 3093-3105, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38381393

ABSTRACT

Post-sepsis psychiatric disorder, encompassing anxiety, depression, post-traumatic stress disorder and delirium, is a highly prevalent complication secondary to sepsis, resulting in a marked increase in long-term mortality among affected patients. Regrettably, psychiatric impairment associated with sepsis is frequently disregarded by clinicians. This review aims to summarize recent advancements in the understanding of the pathophysiology, prevention, and treatment of post-sepsis mental disorder, including coronavirus disease 2019-related psychiatric impairment. The pathophysiology of post-sepsis psychiatric disorder is complex and is known to involve blood-brain barrier disruption, overactivation of the hypothalamic-pituitary-adrenal axis, neuroinflammation, oxidative stress, neurotransmitter dysfunction, programmed cell death, and impaired neuroplasticity. No unified diagnostic criteria for this disorder are currently available; however, screening scales are often applied in its assessment. Modifiable risk factors for psychiatric impairment post-sepsis include the number of experienced traumatic memories, the length of ICU stay, level of albumin, the use of vasopressors or inotropes, daily activity function after sepsis, and the cumulative dose of dobutamine. To contribute to the prevention of post-sepsis psychiatric disorder, it may be beneficial to implement targeted interventions for these modifiable risk factors. Specific therapies for this condition remain scarce. Nevertheless, non-pharmacological approaches, such as comprehensive nursing care, may provide a promising avenue for treating psychiatric disorder following sepsis. In addition, although several therapeutic drugs have shown preliminary efficacy in animal models, further confirmation of their potential is required through follow-up clinical studies.


Subject(s)
Mental Disorders , Sepsis , Humans , COVID-19/complications , Delirium/etiology , Delirium/therapy , Delirium/prevention & control , Delirium/physiopathology , Mental Disorders/etiology , Mental Disorders/therapy , SARS-CoV-2 , Sepsis/complications , Sepsis/physiopathology , Sepsis/therapy , Stress Disorders, Post-Traumatic/therapy , Stress Disorders, Post-Traumatic/physiopathology , Stress Disorders, Post-Traumatic/etiology
7.
Int J Numer Method Biomed Eng ; 40(3): e3806, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38281742

ABSTRACT

Clinical studies have extensively demonstrated that central aortic blood pressure (CABP) has greater clinical significance in comparison with peripheral blood pressure. Despite the existence of various techniques for noninvasively measuring CABP, the clinical applications of most techniques are hampered by the unsatisfactory accuracy or large variability in measurement errors. In this study, we proposed a new method for noninvasively estimating CABP with improved accuracy and reduced uncertain errors. The main idea was to optimize the estimation of the pulse wave transit time from the aorta to the occluded lumen of the brachial artery under a suprasystolic cuff by identifying and utilizing the characteristic information of the cuff oscillation wave, thereby improving the accuracy and stability of the CABP estimation algorithms under various physiological conditions. The method was firstly developed and verified based on large-scale virtual subject data (n = 800) generated by a computational model of the cardiovascular system coupled to a brachial cuff, and then validated with small-scale in vivo data (n = 34). The estimation errors for the aortic systolic pressure were -0.05 ± 0.63 mmHg in the test group of the virtual subjects and -1.09 ± 3.70 mmHg in the test group of the patients, both demonstrating a good performance. In particular, the estimation errors were found to be insensitive to variations in hemodynamic conditions and cardiovascular properties, manifesting the high robustness of the method. The method may have promising clinical applicability, although further validation studies with larger-scale clinical data remain necessary.


Subject(s)
Arterial Pressure , Blood Pressure Determination , Humans , Blood Pressure Determination/methods , Blood Pressure/physiology , Aorta/physiology , Brachial Artery/physiology
8.
J Immunol ; 212(1): 81-95, 2024 01 01.
Article in English | MEDLINE | ID: mdl-38038392

ABSTRACT

Antimicrobial peptides/proteins (AMPs) constitute a critical component of gut immunity in animals, protecting the gut from pathogenic bacteria. However, the interactions between AMPs and gut microbiota remain elusive. In this study, we show that leukocyte-derived chemotaxin-2 (LECT2)-b, a recently discovered AMP, helps maintain gut homeostasis in grass carp (Ctenopharyngodon idella), one of the major farmed fish species globally, by directly regulating the gut microbiota. Knockdown of LECT2-b resulted in dysregulation of the gut microbiota. Specifically, LECT2-b deficiency led to the dominance of Proteobacteria, consisting of proinflammatory bacterial species, over Firmicutes, which includes anti-inflammatory bacteria. In addition, the opportunistic pathogenic bacteria genus Aeromonas became the dominant genus replacing the probiotic bacteria Lactobacillus and Bacillus. Further analysis revealed that this effect was due to the direct and selective inhibition of certain pathogenic bacterial species by LECT2-b. Moreover, LECT2-b knockdown promoted biofilm formation by gut microbiota, resulting in tissue damage and inflammation. Importantly, LECT2-b treatment alleviated the negative effects induced by LECT2-b knockdown. These findings highlight the crucial role of LECT2-b in maintaining the gut microbiota homeostasis and mucosal health. Overall, our study provides important data for understanding the roles of AMPs in the regulation of gut homeostasis in animals.


Subject(s)
Anti-Infective Agents , Gastrointestinal Microbiome , Probiotics , Animals , Bacteria , Homeostasis
9.
Sci Total Environ ; 912: 169013, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38040345

ABSTRACT

Non-aerated bacteria-algae system gaining O2 through photosynthesis presents an alternative for costly mechanical aeration. This study investigated oxygen supply and performance of nutrients removal at low and high light intensity (LL and HL). The results showed that P removal was high and robust (LL 97 ± 1.8 %, HL 95 % ± 2.9 %), while NH4+-N removal fluctuated dramatically (LL 66 ± 14.7 %, HL 84 ± 8.6 %). Oxygen generated at illumination of 200 µmol m-2 s-1, 6 h was sufficient to sustain aerobic phase for 2.25 g/L MLSS. However, O2 produced by algae was preferentially captured in the order of heterotrophic bacteria (HB), ammonia oxidizing bacteria (AOB), nitrite oxidizing bacteria (NOB). Oxygen affinity coupled with light intensity led to NOB suppression with stable nitrite accumulation ratio of 57 %. Free nitrous acid (FNA) and light stimulated the abundance of denitrifying polyphosphate accumulating organism (DPAO) of Flavobacterium, but with declined P-accumulating metabolism (PAM) of P release, P/C, K/P and Mg/P ratios. Flavobacterium and cyanobacteria Leptolyngbya, along with biologically induced CaP in extracellular polymeric substances was the key to robust P removal. AOB of Ellin6067 and DPAO of Flavobacteria offer a promising scenario for partial nitrification-denitrifying phosphorus removal.


Subject(s)
Ammonia , Nitrites , Nitrites/metabolism , Ammonia/metabolism , Sewage/microbiology , Phosphorus/metabolism , Bioreactors/microbiology , Bacteria/metabolism , Nitrification , Oxygen/metabolism , Nitrogen/analysis
10.
J Med Chem ; 66(23): 16303-16329, 2023 12 14.
Article in English | MEDLINE | ID: mdl-38054267

ABSTRACT

Optimization of compound 11L led to the identification of novel HIV capsid modulators, quinazolin-4-one-bearing phenylalanine derivatives, displaying potent antiviral activities against both HIV-1 and HIV-2. Notably, derivatives 12a2 and 21a2 showed significant improvements, with 2.5-fold over 11L and 7.3-fold over PF74 for HIV-1, and approximately 40-fold over PF74 for HIV-2. The X-ray co-crystal structures confirmed the multiple pocket occupation of 12a2 and 21a2 in the binding site. Mechanistic studies revealed a dual-stage inhibition profile, where the compounds disrupted capsid-host factor interactions at the early stage and promoted capsid misassembly at the late stage. Remarkably, 12a2 and 21a2 significantly promoted capsid misassembly, outperforming 11L, PF74, and LEN. The substitution of easily metabolized amide bond with quinolin-4-one marginally enhanced the stability of 12a2 in human liver microsomes compared to controls. Overall, 12a2 and 21a2 highlight their potential as potent HIV capsid modulators, paving the way for future advancements in anti-HIV drug design.


Subject(s)
Anti-HIV Agents , HIV Infections , Humans , Capsid/metabolism , Phenylalanine , Capsid Proteins/metabolism , Anti-HIV Agents/chemistry , HIV Infections/drug therapy
11.
J Enzyme Inhib Med Chem ; 38(1): 2277135, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37955306

ABSTRACT

Our previous studies have shown that the introduction of structurally diverse benzyl side chains at the C5-NH2 position of oseltamivir to occupy 150-cavity contributes to the binding affinity with neuraminidase and anti-influenza activity. To obtain broad-spectrum neuraminidase inhibitors, we designed and synthesised a series of novel oseltamivir derivatives bearing different N-heterocycles substituents that have been proved to induce opening of the 150-loop of group-2 neuraminidases. Among them, compound 6k bearing 4-((r)-2-methylpyrrolidin-1-yl) benzyl group exhibited antiviral activities similar to or weaker than those of oseltamivir carboxylate against H1N1, H3N2, H5N1, H5N6 and H5N1-H274Y mutant neuraminidases. More encouragingly, 6k displayed nearly 3-fold activity enhancement against H3N2 virus over oseltamivir carboxylate and 2-fold activity enhancement over zanamivir. Molecular docking studies provided insights into the explanation of its broad-spectrum potency against wild-type neuraminidases. Overall, as a promising lead compound, 6k deserves further optimisation by fully considering the ligand induced flexibility of the 150-loop.


Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza A Virus, H5N1 Subtype , Oseltamivir/pharmacology , Oseltamivir/chemistry , Neuraminidase , Molecular Docking Simulation , Influenza A Virus, H5N1 Subtype/metabolism , Influenza A Virus, H3N2 Subtype/metabolism , Glycoside Hydrolases
12.
Front Pharmacol ; 14: 1282090, 2023.
Article in English | MEDLINE | ID: mdl-37936907

ABSTRACT

Background: Acquired immunodeficiency syndrome (AIDS) has seriously endangered human life and health, the main pathogenic agent is human immunodeficiency virus type 1 (HIV-1). The combination antiretroviral therapy (cART) has shown serious drug resistance and side effects, and the discovery of HIV-1 capsid inhibitors is an effective way to solve the problem. Recent studies have shown significant progress in the research of HIV-1 capsid inhibitors. However, there is still a lack of comprehensive overview of bibliometric analysis in this field. This study aimed to provide the research trends and hotspots of HIV-1 capsid inhibitors. Method: Publications related to HIV-1 capsid inhibitors from 2000 to 2022 were searched on the Web of Science Core Collection (WoSCC) database and screened according to inclusion criteria. VOSviewer was conducted to evaluate the results. Results: 96 publications from 25 countries were finally included, and the number of annual publications related to HIV-1 capsid inhibitors showed an increasing trend. The United States was the most productive country with the most publication number, H-index, and total citation number, as well as the widest international cooperation. The most popular journal in this field was Journal of Virology. Drexel University was the most productive institution, and Simon Cocklin participated in the most publications. Keywords co-occurrence analysis exhibited that studying the molecular mechanism of capsid protein, discovering drug candidates, and improving antiretroviral therapy are the main and hot topics in this field. Conclusion: This is the first bibliometric study in the field of HIV-1 capsid inhibitors, which comprehensively analyzed the research trends and hotspots in this direction. This work is expected to provide the scientific community with new insights to promote the research of HIV-1 capsid inhibitors.

13.
RSC Med Chem ; 14(11): 2380-2400, 2023 Nov 15.
Article in English | MEDLINE | ID: mdl-37974964

ABSTRACT

Interfering with the assembly of hepatitis B virus (HBV) capsid is a promising approach for treating chronic hepatitis B (CHB). In order to enhance the metabolic stability and reduce the strong hERG inhibitory effect of HBV capsid assembly modulator (CAM) GLS4, we rationally designed a series of carboxyl-containing heteroaryldihydropyrimidine (HAP) derivatives based on structural biology information combined with medicinal chemistry strategies. The results from biological evaluation demonstrated that compound 6a-25 (EC50 = 0.020 µM) exhibited greater potency than the positive drug lamivudine (EC50 = 0.09 µM), and was comparable to the lead compound GLS4 (EC50 = 0.007 µM). Furthermore, it was observed that 6a-25 reduced levels of core protein (Cp) and capsid in cells. Preliminary assessment of drug-likeness revealed that 6a-25 exhibited superior water solubility (pH 2.0: 374.81 µg mL-1; pH 7.0: 6.85 µg mL-1; pH 7.4: 25.48 µg mL-1), liver microsomal metabolic stability (t1/2 = 108.2 min), and lower hERG toxicity (10 µM inhibition rate was 72.66%) compared to the lead compound GLS4. Overall, compound 6a-25 holds promise for further investigation.

14.
J Immunol ; 211(6): 964-980, 2023 09 15.
Article in English | MEDLINE | ID: mdl-37578390

ABSTRACT

Teleost B cells are primitive lymphocytes with both innate and adaptive immune functions. However, the heterogeneity and differentiation trajectory of teleost B cells remain largely unknown. In this study, the landscape of grass carp IgM+ (gcIgM+) B cells was revealed by single-cell RNA sequencing. The results showed that gcIgM+ B cells mainly comprise six populations: (im)mature B cells, innate B cells, proliferating B cells, plasma cells, CD22+ cells, and CD34+ cells, among which innate B cells and proliferating B cells were uncommon B cell subsets with, to our knowledge, new characteristics. Remarkably, three functional IgMs were discovered in grass carp, and a significant percentage of gcIgM+ B cells, especially plasma cells, expressed multiple Igµ genes (Igµ1, Igµ2, and/or Igµ3). More importantly, through single-cell sorting combined with Sanger sequencing, we found that distinct VHDJH recombination patterns of Igµ genes were present in single IgM+ B cells, indicating that individual teleost B cells might produce multiple Abs by coexpressing rearranged IgM subclass genes. Moreover, the percentage of IgM1highIgM2highIgM3high plasma cells increased significantly after bacterial infection, suggesting that individual plasma cells might tend to produce multiple IgMs to resist the infection in teleost fish. In summary, to our knowledge, this study not only helps to uncover the unique heterogeneity of B cells in early vertebrates but also provided significant new evidence supporting the recently proposed "one cell-multiple Abs" paradigm, challenging the classical rule of "one cell-one Ab."


Subject(s)
Bacterial Infections , Carps , Fish Diseases , Animals , Immunity, Innate/genetics , Fish Proteins/genetics , Immunoglobulin M , Homeostasis
15.
RSC Med Chem ; 14(7): 1272-1295, 2023 Jul 20.
Article in English | MEDLINE | ID: mdl-37484571

ABSTRACT

HIV-1 capsid (CA) is an attractive target for its indispensable roles in the viral life cycle. We report the design, synthesis, and mechanistic study of a novel series of 2-piperazineone peptidomimetics as HIV capsid modulators by mimicking the structure of host factors binding to CA. F-Id-3o was the most potent compound from the synthesized series, with an anti-HIV-1 EC50 value of 6.0 µM. However, this series of compounds showed a preference for HIV-2 inhibitory activity, in which Id-3o revealed an EC50 value of 2.5 µM (anti-HIV-2 potency), an improvement over PF74. Interestingly, F-Id-3o did bind HIV-1 CA monomers and hexamers with comparable affinity, unlike PF74, consequently showing antiviral activity in the early and late stages of the HIV-1 lifecycle. Molecular dynamics simulations shed light on F-Id-3o and Id-3o binding modes within the HIV-1/2 CA protein and provide a possible explanation for the increased anti-HIV-2 potency. Metabolic stability assays in human plasma and human liver microsomes indicated that although F-Id-3o has enhanced metabolic stability over PF74, further optimization is necessary. Moreover, we utilized computational prediction of drug-like properties and metabolic stability of F-Id-3o and PF74, which correlated well with experimentally derived metabolic stability, providing an efficient computational pipeline for future preselection based on metabolic stability prediction. Overall, the 2-piperazineone-bearing peptidomimetics are a promising new chemotype in the CA modulators class with considerable optimization potential.

16.
Front Cardiovasc Med ; 10: 1131962, 2023.
Article in English | MEDLINE | ID: mdl-37522090

ABSTRACT

Background: Arterial Velocity-pulse Index (AVI) and Arterial Pressure-volume Index (API), measured by a brachial cuff, have been demonstrated to be indicative of arterial stiffness and correlated with the risk of cardiovascular events. However, the threshold values of AVI and API for screening increased arterial stiffness in the general population are yet to be established. Methods: The study involved 860 subjects who underwent general physical examinations (M/F = 422/438, age 53.4 ± 12.7 years) and were considered to represent the general population in China. In addition to the measurements of AVI, API and brachial-ankle pulse wave velocity (baPWV), demographic information, arterial blood pressures, and data from blood and urine tests were collected. The threshold values of AVI and API were determined by receiver operating characteristic (ROC) analyses and covariate-adjusted ROC (AROC) analyses against baPWV, whose threshold for diagnosing high arterial stiffness was set at 18 m/s. Additional statistical analyses were performed to examine the correlations among AVI, API and baPWV and their correlations with other bio-indices. Results: The area under the curve (AUC) values in ROC analysis for the diagnosis with AVI/API were 0.745/0.819, 0.788/0.837, and 0.772/0.825 (95% CI) in males, females, and all subjects, respectively. Setting the threshold values of AVI and API to 21 and 27 resulted in optimal diagnosis performance in the total cohort, whereas the threshold values should be increased to 24 and 29, respectively, in order to improve the accuracy of diagnosis in the female group. The AROC analyses revealed that the threshold values of AVI and API increased markedly with age and pulse pressure (PP), respectively. Conclusions: With appropriate threshold values, AVI and API can be used to perform preliminary screening for individuals with increased arterial stiffness in the general population. On the other hand, the results of the AROC analyses imply that using threshold values adjusted for confounding factors may facilitate the refinement of diagnosis. Given the fact that the study is a cross-sectional one carried out in a single center, future multi-center or follow-up studies are required to further confirm the findings or examine the value of the threshold values for predicting cardiovascular events.

17.
RSC Adv ; 13(25): 17194-17201, 2023 Jun 05.
Article in English | MEDLINE | ID: mdl-37304779

ABSTRACT

Porous materials such as metal-organic frameworks (MOFs) are considered to be suitable materials for immobilizing enzymes to improve their stability. However, conventional MOFs reduce the enzymes' catalytic activity due to difficulties with mass transfer and diffusing reactants after their micropores are occupied by enzyme molecules. To address these issues, a novel hierarchically structured zeolitic imidazolate framework-8 (HZIF-8) was prepared to study the effects of different laccase immobilization approaches such as the post-synthesis (LAC@HZIF-8-P) and de novo (LAC@HZIF-8-D) immobilization of catalytic activities for removing 2,4-dichlorophenol (2,4-DCP). The results showed higher catalytic activity for the laccase-immobilized LAC@HZIF-8 prepared using different methods than for the LAC@MZIF-8 sample, with 80% of 2,4-DCP removed under optimal conditions. These results could be attributable to the multistage structure of HZIF-8. The LAC@HZIF-8-D sample was stable and superior to LAC@HZIF-8-P, maintaining a 2,4-DCP removal efficiency of 80% after three recycles and demonstrating superior laccase thermostability and storage stability. Moreover, after loading with copper nanoparticles, the LAC@HZIF-8-D approach exhibited a 2,4-DCP removal efficiency of 95%, a promising finding for its potential use in environmental purification.

18.
Korean J Physiol Pharmacol ; 27(3): 221-230, 2023 May 01.
Article in English | MEDLINE | ID: mdl-37078296

ABSTRACT

Diabetic kidney disease is one of the most serious complications of diabetes. Although diabetic kidney disease can be effectively controlled through strict blood glucose management and corresponding symptomatic treatment, these therapies cannot reduce its incidence in diabetic patients. The sodium-glucose cotransporter 2 (SGLT2) inhibitors and the traditional Chinese herb "Gegen" have been widely used in diabetes-related therapy. However, it remains unclear whether the combined use of these two kinds of medicines contributes to an increased curative effect on diabetic kidney disease. In this study, we examined this issue by evaluating the efficacy of the combination of puerarin, an active ingredient of Gegen, and canagliflozin, an SGLT2 inhibitor for a 12-week intervention using a mouse model of diabetes. The results indicated that the combination of puerarin and canagliflozin was superior to canagliflozin alone in improving the metabolic and renal function parameters of diabetic mice. Our findings suggested that the renoprotective effect of combined puerarin and canagliflozin in diabetic mice was achieved by reducing renal lipid accumulation. This study provides a new strategy for the clinical prevention and treatment of diabetic kidney disease. The puerarin and SGLT2 inhibitor combination therapy at the initial stage of diabetes may effectively delay the occurrence of diabetic kidney injury, and significantly alleviate the burden of renal lipotoxicity.

19.
Drug Discov Today ; 28(6): 103581, 2023 06.
Article in English | MEDLINE | ID: mdl-37030533

ABSTRACT

Approved or licensed antiviral drugs have limited applications because of their drug resistance and severe adverse effects. By contrast, by stabilizing or destroying the viral capsid, compounds known as capsid modulators prevent viral replication by acting on new targets and, therefore, overcoming the problem of clinical drug resistance. For example, computer-aided drug design (CADD) methods, using strategies based on structures of biological targets (structure-based drug design; SBDD), such as docking, molecular dynamics (MD) simulations, and virtual screening (VS), have provided opportunities for fast and effective development of viral capsid modulators. In this review, we summarize the application of CADD in the discovery, optimization, and mechanism prediction of capsid-targeting small molecules, providing new insights into antiviral drug discovery modalities.


Subject(s)
Capsid , Computer-Aided Design , Drug Design , Drug Discovery , Antiviral Agents/pharmacology , Antiviral Agents/chemistry
20.
Front Immunol ; 14: 1128138, 2023.
Article in English | MEDLINE | ID: mdl-36891317

ABSTRACT

Antimicrobial peptides are important components of the host innate immune system, forming the first line of defense against infectious microorganisms. Among them, liver-expressed antimicrobial peptides (LEAPs) are a family of antimicrobial peptides that widely exist in vertebrates. LEAPs include two types, named LEAP-1 and LEAP-2, and many teleost fish have two or more LEAP-2s. In this study, LEAP-2C from rainbow trout and grass carp were discovered, both of which are composed of 3 exons and 2 introns. The antibacterial functions of the multiple LEAPs were systematically compared in rainbow trout and grass carp. The gene expression pattern revealed that rainbow trout and grass carp LEAP-1, LEAP-2A, LEAP-2B and/or LEAP-2C were differentially expressed in various tissues/organs, mainly in liver. After bacterial infection, the expression levels of LEAP-1, LEAP-2A, LEAP-2B and/or LEAP-2C in the liver and gut of rainbow trout and grass carp increased to varying degrees. Moreover, the antibacterial assay and bacterial membrane permeability assay showed that rainbow trout and grass carp LEAP-1, LEAP-2A, LEAP-2B and LEAP-2C all have antibacterial activities against a variety of Gram-positive and Gram-negative bacteria with varying levels through membrane rupture. Furthermore, cell transfection assay showed that only rainbow trout LEAP-1, but not LEAP-2, can lead to the internalization of ferroportin, the only iron exporter on cell surface, indicating that only LEAP-1 possess iron metabolism regulation activity in teleost fish. Taken together, this study systematically compared the antibacterial function of LEAPs in teleost fish and the results suggest that multiple LEAPs can enhance the immunity of teleost fish through different expression patterns and different antibacterial activities to various bacteria.


Subject(s)
Anti-Bacterial Agents , Antimicrobial Peptides , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/metabolism , Gram-Negative Bacteria , Gram-Positive Bacteria , Liver/metabolism , Iron/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL