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1.
Ecotoxicol Environ Saf ; 269: 115751, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38042132

ABSTRACT

There is growing evidence that prenatal exposure to Per- and polyfluoroalkyl substances (PFAS) was associated with childhood obesity, but evidence on multiple adiposity measures including arm circumference (AC), and waist circumference (WC) among Chinese children is limited. We investigated the associations of prenatal exposure to PFAS with adiposity measures of children at 4 and 6 years of age in the Shanghai-Minhang Birth Cohort Study. A total of 573 mother-child pairs with maternal PFAS concentrations and at least one measurement of adiposity measures of children were included in the present study. Eleven PFAS were assessed in maternal fasting blood samples. Information on children's weight, height, AC, and WC was collected at follow-ups. Weight for age Z score (WAZ), body mass index for age Z score (BMIz), and children overweight were calculated based on the World Health Organization Child Growth Standards. Multivariate linear regression, Poisson regression with robust error variance, and Bayesian Kernel Machine Regression (BKMR) models were used to examine the associations of prenatal exposure to PFAS with children's adiposity measures. Eight PFAS with detection rates above 85 % were included in the analyses. In the multivariate linear regression models, maternal PFNA concentrations were associated with a greater AC (ß = 0.29, 95 % Confidence Interval (CI): 0.04-0.55) in 4-year-old children and with an increase in WAZ (ß = 0.26, 95 % CI: 0.06-0.46), BMIz (ß = 0.31, 95 % CI: 0.09-0.53), AC (ß = 0.49, 95 % CI: 0.08-0.90), and WC (ß = 1.47, 95 % CI: 0.41-2.52) in 6-year-old children. We also observed the associations of maternal concentrations of PFOS, PFNA, PFUdA, and PFTrDA with the increased risk of children overweight in 6-year-old children. BKMR models further supported the findings from multivariate linear regression and Poisson regression models, and identified PFNA as the most important contributor. Moreover, the associations described above were generally more pronounced in girls. In conclusion, prenatal exposure to PFAS was associated with an increased risk of children's adiposity with a sex-specific manner, and PFNA contributed most to the associations after controlling for the effect of co-exposure to other PFAS compounds, especially among girls at 6 years of age.


Subject(s)
Alkanesulfonic Acids , Environmental Pollutants , Fluorocarbons , Pediatric Obesity , Prenatal Exposure Delayed Effects , Child , Male , Pregnancy , Female , Humans , Child, Preschool , Cohort Studies , Adiposity , Prenatal Exposure Delayed Effects/epidemiology , Prenatal Exposure Delayed Effects/chemically induced , Prospective Studies , Birth Cohort , Overweight/chemically induced , Bayes Theorem , Pediatric Obesity/epidemiology , Pediatric Obesity/chemically induced , China , Fluorocarbons/toxicity
2.
Int J Mol Sci ; 25(10)2024 May 17.
Article in English | MEDLINE | ID: mdl-38791528

ABSTRACT

An immune checkpoint is a signaling pathway that regulates the recognition of antigens by T-cell receptors (TCRs) during an immune response. These checkpoints play a pivotal role in suppressing excessive immune responses and maintaining immune homeostasis against viral or microbial infections. There are several FDA-approved immune checkpoint inhibitors (ICIs), including ipilimumab, pembrolizumab, and avelumab. These ICIs target cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed death ligand 1 (PD-L1). Furthermore, ongoing efforts are focused on developing new ICIs with emerging potential. In comparison to conventional treatments, ICIs offer the advantages of reduced side effects and durable responses. There is growing interest in the potential of combining different ICIs with chemotherapy, radiation therapy, or targeted therapies. This article comprehensively reviews the classification, mechanism of action, application, and combination strategies of ICIs in various cancers and discusses their current limitations. Our objective is to contribute to the future development of more effective anticancer drugs targeting immune checkpoints.


Subject(s)
Immune Checkpoint Inhibitors , Neoplasms , Humans , Neoplasms/drug therapy , Neoplasms/immunology , Immune Checkpoint Inhibitors/therapeutic use , Animals , CTLA-4 Antigen/antagonists & inhibitors , Immunotherapy/methods , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Immunomodulation/drug effects
3.
Int J Mol Sci ; 25(7)2024 Apr 07.
Article in English | MEDLINE | ID: mdl-38612904

ABSTRACT

Cardiovascular diseases (CVDs) pose a significant global health threat due to their complex pathogenesis and high incidence, imposing a substantial burden on global healthcare systems. Integrins, a group of heterodimers consisting of α and ß subunits that are located on the cell membrane, have emerged as key players in mediating the occurrence and progression of CVDs by regulating the physiological activities of endothelial cells, vascular smooth muscle cells, platelets, fibroblasts, cardiomyocytes, and various immune cells. The crucial role of integrins in the progression of CVDs has valuable implications for targeted therapies. In this context, the development and application of various integrin antibodies and antagonists have been explored for antiplatelet therapy and anti-inflammatory-mediated tissue damage. Additionally, the rise of nanomedicine has enhanced the specificity and bioavailability of precision therapy targeting integrins. Nevertheless, the complexity of the pathogenesis of CVDs presents tremendous challenges for monoclonal targeted treatment. This paper reviews the mechanisms of integrins in the development of atherosclerosis, cardiac fibrosis, hypertension, and arrhythmias, which may pave the way for future innovations in the diagnosis and treatment of CVDs.


Subject(s)
Cardiovascular Diseases , Hypertension , Humans , Integrins , Endothelial Cells , Cell Membrane
4.
Anal Chem ; 95(9): 4344-4352, 2023 03 07.
Article in English | MEDLINE | ID: mdl-36815760

ABSTRACT

Analysis of volatile organic compounds (VOCs) in exhaled breath (EB) has shown great potential for disease detection including lung cancer, infectious respiratory diseases, and chronic obstructive pulmonary disease. Although many breath sample collection and analytical methods have been developed for breath analysis, analysis of metabolic VOCs in exhaled breath is still a challenge for clinical application. Many carbonyl compounds in exhaled breath are related to the metabolic processes of diseases. This work reports a method of ultrahigh-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-MS) for the analysis of a broad range of carbonyl metabolites in exhaled breath. Carbonyl compounds in the exhaled breath were captured by a fabricated silicon microreactor with a micropillar array coated with 2-(aminooxy)ethyl-N,N,N-trimethylammonium (ATM) triflate. A total of six subgroups consisting of saturated aldehydes and ketones, hydroxy-aldehydes, and hydroxy-ketones, unsaturated 2-alkenals, and 4-hydroxy-2-alkenals were identified in the exhaled breath. The combination of a silicon microreactor for the selective capture of carbonyl compounds with UHPLC-MS analysis may provide a quantitative method for the analysis of carbonyls to identify disease markers in exhaled breath.


Subject(s)
Silicon , Volatile Organic Compounds , Chromatography, High Pressure Liquid , Volatile Organic Compounds/analysis , Aldehydes/analysis , Ketones/analysis , Breath Tests/methods
5.
Mol Pharm ; 20(9): 4574-4586, 2023 09 04.
Article in English | MEDLINE | ID: mdl-37307591

ABSTRACT

SLC16A1 and SLC16A3 (SLC16A1/3) are highly expressed in cervical cancers and associated with the malignant biological behavior of cancer. SLC16A1/3 is the critical hub for regulating the internal and external environment, glycolysis, and redox homeostasis in cervical cancer cells. Inhibiting SLC16A1/3 provides a new thought to eliminate cervical cancer effectively. There are few reports on effective treatment strategies to eliminate cervical cancer by simultaneously targeting SLC16A1/3. GEO database analysis and quantitative reverse transcription polymerase chain reaction experiment were used to confirm the high expression of SLC16A1/3. The potential inhibitor of SLC16A1/3 was screened from Siwu Decoction by using network pharmacology and molecular docking technology. The mRNA levels and protein levels of SLC16A1/3 in SiHa and HeLa cells treated by Embelin (EMB) were clarified, respectively. Furthermore, the Gallic acid-iron (GA-Fe) drug delivery system was used to improve its anti-cancer performance. Compared with normal cervical cells, SLC16A1/3 mRNA was over-expressed in SiHa and HeLa cells. Through the analysis of Siwu Decoction, a simultaneously targeted SLC16A1/3 inhibitor EMB was discovered. It was found for the first time that EMB promoted lactic acid accumulation and further induced redox dyshomeostasis and glycolysis disorder by simultaneously inhibiting SLC16A1/3. The gallic acid-iron-Embelin (GA-Fe@EMB) drug delivery system delivered EMB, which had a synergistic anti-cervical cancer effect. Under the irradiation of a near-infrared laser, the GA-Fe@EMB could elevate the temperature of the tumor area effectively. Subsequently, EMB was released and mediated the lactic acid accumulation and the GA-Fe nanoparticle synergistic Fenton reaction to promote ROS accumulation, thereby increasing the lethality of the nanoparticles on cervical cancer cells. GA-Fe@EMB can target cervical cancer marker SLC16A1/3 to regulate glycolysis and redox pathways, synergistically with photothermal therapy, which provides a new avenue for the synergistic treatment of malignant cervical cancer.


Subject(s)
Nanoparticles , Uterine Cervical Neoplasms , Female , Humans , HeLa Cells , Iron , Gallic Acid , Molecular Docking Simulation , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/genetics , Oxidation-Reduction , Glycolysis
6.
Environ Sci Technol ; 57(42): 15869-15881, 2023 10 24.
Article in English | MEDLINE | ID: mdl-37821457

ABSTRACT

Alterations in bile acid (BA) profiles are closely associated with adverse outcomes in pregnant women and their offspring and may be one potential pathway underlying the related metabolic effects of per- and poly-fluoroalkyl substances (PFAS) exposure. However, evidence of associations between PFAS exposure and BA profiles in pregnant women is scarce. This study examined the associations of individual PFAS and PFAS mixture with BA profiles of pregnant women. We obtained quantitative data on the plasma concentrations of 13 PFAS and 15 BAs in 645 pregnant women from the Jiashan birth cohort. In Bayesian kernel machine regression models, the PFAS mixture was associated with increased plasma CA, TCA, TCDCA, and GLCA levels but with decreased GCA and LCA concentrations. Furthermore, the PFAS mixture was associated with increased concentrations of total BAs and the secondary/primary BA ratio but with decreased conjugated/unconjugated and glycine/taurine-conjugated BA ratios. PFHxS, PFUdA, PFOS, PFNA, and PFDA were the dominant contributors. The results of the linear regression analysis of individual PFAS were generally similar. Our findings provide the first epidemiological evidence for the associations of a PFAS mixture with BA profiles in pregnant women and may provide explanatory insights into the biological pathways underlying the related metabolic effects of PFAS exposure.


Subject(s)
Alkanesulfonic Acids , Environmental Pollutants , Fluorocarbons , Humans , Female , Pregnancy , Pregnant Women , Bile Acids and Salts , Bayes Theorem
7.
Environ Sci Technol ; 57(22): 8213-8224, 2023 06 06.
Article in English | MEDLINE | ID: mdl-37216669

ABSTRACT

Epidemiological evidence regarding the effects of prenatal exposure to perfluoroalkyl substances (PFASs) on neurodevelopment in children is inconclusive. In 449 mother-child pairs from the Shanghai-Minhang Birth Cohort Study, we measured the concentrations of 11 PFASs in maternal plasma samples obtained at 12-16 weeks of gestation. We assessed children's neurodevelopment at 6 years of age by the fourth edition of the Chinese Wechsler Intelligence Scale for Children and Child Behavior Checklist for ages 6-18. We evaluated the association between prenatal exposure to PFASs and children's neurodevelopment and the effect modification of maternal dietary factors during pregnancy and the child's sex. We found that prenatal exposure to multiple PFASs was associated with increased scores for attention problems, and the individual effect of perfluorooctanoic acid (PFOA) was statistically significant. However, no statistically significant association between PFASs and cognitive development was observed. Additionally, we found the effect modification of maternal nut intake and child's sex. In conclusion, this study suggests that prenatal exposure to PFASs was associated with more attention problems, and maternal nut intake during pregnancy may alter the potential effect of PFASs. However, these findings were exploratory because of multiple testing and the relatively small sample size.


Subject(s)
Alkanesulfonic Acids , Environmental Pollutants , Fluorocarbons , Prenatal Exposure Delayed Effects , Female , Pregnancy , Humans , Prenatal Exposure Delayed Effects/epidemiology , Cohort Studies , China , Cognition , Alkanesulfonic Acids/pharmacology , Maternal Exposure
8.
Int J Mol Sci ; 24(7)2023 Mar 24.
Article in English | MEDLINE | ID: mdl-37047140

ABSTRACT

Integrins are a group of heterodimers consisting of α and ß subunits that mediate a variety of physiological activities of immune cells, including cell migration, adhesion, proliferation, survival, and immunotolerance. Multiple types of integrins act differently on the same immune cells, while the same integrin may exert various effects on different immune cells. In the development of cancer, integrins are involved in the regulation of cancer cell proliferation, invasion, migration, and angiogenesis; conversely, integrins promote immune cell aggregation to mediate the elimination of tumors. The important roles of integrins in cancer progression have provided valuable clues for the diagnosis and targeted treatment of cancer. Furthermore, many integrin inhibitors have been investigated in clinical trials to explore effective regimens and reduce side effects. Due to the complexity of the mechanism of integrin-mediated cancer progression, challenges remain in the research and development of cancer immunotherapies (CITs). This review enumerates the effects of integrins on four types of immune cells and the potential mechanisms involved in the progression of cancer, which will provide ideas for more optimal CIT in the future.


Subject(s)
Disease Progression , Immune System , Immunotherapy , Integrins , Neoplasms , Animals , Humans , B-Lymphocytes/immunology , Dendritic Cells/immunology , Integrins/antagonists & inhibitors , Integrins/metabolism , Killer Cells, Natural/immunology , Macrophages/immunology , Neoplasms/immunology , Neoplasms/metabolism , Neoplasms/pathology , Neoplasms/therapy , Neutrophils/immunology , T-Lymphocytes/immunology , Immune System/cytology , Immune System/immunology
9.
J Org Chem ; 87(2): 974-984, 2022 01 21.
Article in English | MEDLINE | ID: mdl-34985275

ABSTRACT

A phosphine-mediated, well-designed Morita-Baylis-Hillman-type/Wittig cascade for the rapid assembly of a quinolinone framework from benzaldehyde derivatives is developed for the first time. By rationally combining I2/NIS-mediated cyclization, biologically relevant 3-(benzopyrrole/furan-2-yl) quinolinones were facilely synthesized in a one-pot process by starting from 3-styryl-quinolinones bearing an o-hydroxy/amino group, significantly expanding the chemical space of this privileged skeleton. Further utility of this protocol is illustrated by successfully performing this transformation in a catalytic manner through in situ reduction of phosphine oxide by phenylsilane.


Subject(s)
Phosphines , Quinolones , Cyclization , Furans
10.
Org Biomol Chem ; 20(21): 4415-4420, 2022 Jun 01.
Article in English | MEDLINE | ID: mdl-35583213

ABSTRACT

The mechanism of the phosphine-catalysed domino sequence of alkynoates and activated methylenes has been computationally studied. The computational results revealed that the [3 + 2] annulation sequence could be ruled out, due to a difficult Knoevenagel condensation of aromatic aldehydes and active methylenes. The reaction proceeds through a [4 + 1] annulation pathway, which involves a phosphine-catalysed MBH-type reaction followed by a [1,5]-proton shift and dehydration to afford vinyl phosphonium intermediates as four-carbon synthons in the annulation reaction. Then 1,3-dicarbonyls act as nucleophiles to attack vinyl phosphonium intermediates, subsequently leading to a stepwise [1,3]-proton shift and an intramolecular nucleophilic attack to close the five-member ring.

11.
J Med Internet Res ; 24(9): e25959, 2022 09 14.
Article in English | MEDLINE | ID: mdl-36103227

ABSTRACT

BACKGROUND: Despite the great potential of eHealth, substantial costs are involved in its implementation, and it is essential to know whether these costs can be justified by its benefits. Such needs have led to an increased interest in measuring the benefits of eHealth, especially using the willingness to pay (WTP) metric as an accurate proxy for consumers' perceived benefits of eHealth. This offered us an opportunity to systematically review and synthesize evidence from the literature to better understand WTP for eHealth and its influencing factors. OBJECTIVE: This study aimed to provide a systematic review of WTP for eHealth and its influencing factors. METHODS: This study was performed and reported as per the Cochrane Collaboration and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. PubMed, CINAHL Plus, Cochrane Library, EconLit, and PsycINFO databases were searched from their inception to April 19, 2022. We conducted random-effects meta-analyses to calculate WTP values for eHealth (at 2021 US dollar rates) and meta-regression analyses to examine the factors affecting WTP. RESULTS: A total of 30 articles representing 35 studies were included in the review. We found that WTP for eHealth varied across studies; when expressed as a 1-time payment, it ranged from US $0.88 to US $191.84, and when expressed as a monthly payment, it ranged from US $5.25 to US $45.64. Meta-regression analyses showed that WTP for eHealth was negatively associated with the percentages of women (ß=-.76; P<.001) and positively associated with the percentages of college-educated respondents (ß=.63; P<.001) and a country's gross domestic product per capita (multiples of US $1000; ß=.03; P<.001). Compared with eHealth provided through websites, people reported a lower WTP for eHealth provided through asynchronous communication (ß=-1.43; P<.001) and a higher WTP for eHealth provided through medical devices (ß=.66; P<.001), health apps (ß=.25; P=.01), and synchronous communication (ß=.58; P<.001). As for the methods used to measure WTP, single-bounded dichotomous choice (ß=2.13; P<.001), double-bounded dichotomous choice (ß=2.20; P<.001), and payment scale (ß=1.11; P<.001) were shown to obtain higher WTP values than the open-ended format. Compared with ex ante evaluations, ex post evaluations were shown to obtain lower WTP values (ß=-.37; P<.001). CONCLUSIONS: WTP for eHealth varied significantly depending on the study population, modality used to provide eHealth, and methods used to measure it. WTP for eHealth was lower among certain population segments, suggesting that these segments may be at a disadvantage in terms of accessing and benefiting from eHealth. We also identified the modalities of eHealth that were highly valued by consumers and offered suggestions for the design of eHealth interventions. In addition, we found that different methods of measuring WTP led to significantly different WTP estimates, highlighting the need to undertake further methodological explorations of approaches to elicit WTP values.


Subject(s)
Telemedicine , Costs and Cost Analysis , Female , Humans , Publications , Regression Analysis
12.
Ecotoxicol Environ Saf ; 241: 113818, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35777342

ABSTRACT

Findings from epidemiological studies on the associations between prenatal perfluoroalkyl substances (PFASs) exposure and children's neurodevelopment were inconclusive, and most studies did not account for the co-exposure to multiple PFASs with strong inter-correlations. The present study aimed to assess the effects of prenatal multiple PFAS exposure on children's neurobehavioral development based on 614 mother-infant pairs in the Shanghai-Minhang Birth Cohort Study. Eight PFAS concentrations were measured in maternal plasma at 12-16 weeks of gestation. Children's neurobehavioral development at 2 and 4 years of age was assessed by the Child Behavior Checklist for Ages 1.5-5. In Bayesian kernel machine regression (BKMR) analyses that could address the inter-correlations between multiple PFASs, PFAS mixture appeared to be associated with fewer Somatic Complaints and more Externalizing Problems in boys, but more Somatic Complaints and Sleep Problems in girls. There were suggestive associations of PFNA and PFOS with decreased risk of Somatic Complaints and of PFUdA and PFTrDA with increased risk of Externalizing Problems in boys; trends of increased risk in girls were observed between PFUdA and Somatic Complaints and between PFTrDA and Sleep Problems. Overall, we found no clear evidence that prenatal exposure to PFASs had negative effects on neurobehavioral development in children. However, the modest associations still suggested the potential developmental neurotoxicity of prenatal PFAS exposure.


Subject(s)
Alkanesulfonic Acids , Environmental Pollutants , Fluorocarbons , Prenatal Exposure Delayed Effects , Sleep Wake Disorders , Bayes Theorem , Child , Child, Preschool , China , Cohort Studies , Environmental Pollutants/toxicity , Female , Fluorocarbons/toxicity , Humans , Infant , Male , Maternal Exposure/adverse effects , Pregnancy , Prenatal Exposure Delayed Effects/chemically induced , Prospective Studies
13.
Angew Chem Int Ed Engl ; 61(45): e202211035, 2022 11 07.
Article in English | MEDLINE | ID: mdl-36111983

ABSTRACT

An unprecedented photoredox-catalyzed phosphine-mediated deoxygenation of hexafluoroacetone hydrate was established to accomplish the hydroxylpolyfluoroalkylation of electron-deficient alkenes. A range of bis(trifluoromethyl)carbinols were facilely accessed by using readily available hexafluoroacetone hydrate, instead of toxic gaseous hexafluoroacetone. A range of electron-deficient alkenes are tolerated, giving the corresponding hydro-hydroxylpolyfluoroalkylated products in moderate to high yields. Remarkable features of this synthetic strategy include operational simplicity, mild reaction conditions, excellent regioselectivity, and broad functional group tolerance. The success of this strategy relies on the delicate utilization of aldehyde/ketone-gem-diol intrinsic equilibrium, which offers an innovated open-shell pathway for the assembly of synthetically challenging polyfluoroalkylated scaffolds.


Subject(s)
Alkenes , Fluorocarbons , Catalysis , Acetone
14.
Angew Chem Int Ed Engl ; 61(44): e202212292, 2022 Nov 02.
Article in English | MEDLINE | ID: mdl-36083417

ABSTRACT

A metal-free photosensitized protocol for regioselective diamination of alkene feedstocks over a single step was developed based on the rationally designed bifunctional diamination reagent, thus affording a range of differentially protected 1,2-diamines in moderate to high yields. Mechanistic studies reveal that the reaction is initiated with a triplet-triplet energy transfer between thioxanthone catalyst and diamination reagent, followed by fragmentation to simultaneously generate long-lived iminyl radical and transient amidyl radical. The excellent regioselectivity presumably stems from the large reactivity difference between two different N-centered radical species. This protocol is characterized by excellent regioselectivity, broad functional group tolerance, and mild reaction conditions, which would enrich the diversity and versatility of facilitate the diversity-oriented synthesis of 1,2-diamine-containing complex molecule scaffolds.

15.
Org Biomol Chem ; 19(32): 7074-7080, 2021 08 28.
Article in English | MEDLINE | ID: mdl-34342319

ABSTRACT

A novel phosphine-catalysed, one-pot domino approach for the annulation of 2-formylphenyl alkynoates with activated methylene compounds to construct various cyclopentene-fused dihydrocoumarins is reported. This developed strategy provides a facile and efficient approach for the synthesis of structurally complex coumarins from inexpensive and readily available alkynoates.

16.
Bioorg Chem ; 110: 104749, 2021 05.
Article in English | MEDLINE | ID: mdl-33652341

ABSTRACT

Real-time monitoring of drug metabolism in vivo is of great significance to drug development and toxicology research. The purpose of this study is to establish a rapid and visual in vivo detection method for the detection of an intermediate metabolite of the gold (I) drug. Gold (I) drugs such as sodium aurothiomalate (AuTM) have anti-inflammatory effects in the treatment of rheumatoid arthritis. Gold(III) ions (Au3+) are the intermediate metabolite of gold medicine, and they are also the leading factor of side effects in the treatment of patients. However, the rapid reduction of Au3+ to Au+ by thiol proteins in organisms limits the in-depth study of metabolism of gold drugs in vivo. Here we describe a luminescence Au3+ probe (RA) based on ruthenium (II) complex for detecting Au3+ in vitro and in vivo. RA with large Stokes shift, good water solubility and biocompatibility was successfully applied to detect Au3+ in living cells and vivo by luminescence imaging, and to trap the fluctuation of Au3+ level produced by gold (I) medicine. More importantly, the luminescent probe was used to the detection of the intermediate metabolites of gold (I) drugs for the first time. Overall, this work offers a new detection tool/method for a deeper study of gold (I) drugs metabolite.


Subject(s)
Fluorescent Dyes/chemistry , Gold Sodium Thiomalate/chemistry , Gold Sodium Thiomalate/metabolism , Gold/chemistry , Ruthenium Compounds/chemistry , Animals , Cell Survival/drug effects , Hep G2 Cells , Humans , Lipopolysaccharides/toxicity , Mice , Molecular Structure , RAW 264.7 Cells , Single-Cell Analysis , Zebrafish
17.
Int J Mol Sci ; 22(21)2021 Nov 05.
Article in English | MEDLINE | ID: mdl-34769433

ABSTRACT

It is of significance to mine the structural genes related to the biosynthetic pathway of fatty acid (FA) and cellulose as well as explore the regulatory mechanism of alternative splicing (AS), microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in the biosynthesis of cannabinoids, FA and cellulose, which would enhance the knowledge of gene expression and regulation at post-transcriptional level in Cannabis sativa L. In this study, transcriptome, small RNA and degradome libraries of hemp 'Yunma No.1' were established, and comprehensive analysis was performed. As a result, a total of 154, 32 and 331 transcripts encoding key enzymes involved in the biosynthesis of cannabinoids, FA and cellulose were predicted, respectively, among which AS occurred in 368 transcripts. Moreover, 183 conserved miRNAs, 380 C. sativa-specific miRNAs and 7783 lncRNAs were predicted. Among them, 70 miRNAs and 17 lncRNAs potentially targeted 13 and 17 transcripts, respectively, encoding key enzymes or transporters involved in the biosynthesis of cannabinoids, cellulose or FA. Finally, the crosstalk between AS and miRNAs or lncRNAs involved in cannabinoids and cellulose was also predicted. In summary, all these results provided insights into the complicated network of gene expression and regulation in C. sativa.


Subject(s)
Cannabis/genetics , Plant Proteins/genetics , RNA, Long Noncoding/genetics , Alternative Splicing , Biosynthetic Pathways , Cannabinoids/metabolism , Cannabis/metabolism , Cellulose/metabolism , Fatty Acids/metabolism , Gene Expression Profiling/methods , Gene Expression Regulation, Plant , Gene Regulatory Networks , Genome, Plant , MicroRNAs/genetics , Plant Proteins/metabolism , Whole Genome Sequencing
18.
Biochem Biophys Res Commun ; 527(3): 799-804, 2020 06 30.
Article in English | MEDLINE | ID: mdl-32423809

ABSTRACT

When administrated orally, the vasodilating drug diltiazem can be metabolized into diacetyl diltiazem in the presence of Bacteroides thetaiotaomicron, a human gut microbe. The removal of acetyl group from the parent drug is carried out by the GDSL/SGNH-family hydrolase BT4096. Here the crystal structure of the enzyme was solved by mercury soaking and single-wavelength anomalous diffraction. The protein folds into two parts. The N-terminal part comprises the catalytic domain which is similar to other GDSL/SGNH hydrolases. The flanking C-terminal part is made up of a ß-barrel subdomain and an α-helical subdomain. Structural comparison shows that the catalytic domain is most akin to acetyl-xylooligosaccharide esterase and allows a plausible binding mode of diltiazem to be proposed. The ß-barrel subdomain is similar in topology to the immunoglobulin-like domains, including some carbohydrate-binding modules, of various bacterial glycoside hydrolases. Consequently, BT4096 might originally function as an oligosaccharide deacetylase with additional subdomains that could enhance substrate binding, and it acts on diltiazem just by accident.


Subject(s)
Bacterial Proteins/metabolism , Bacteroides thetaiotaomicron/enzymology , Diltiazem/metabolism , Gastrointestinal Microbiome , Hydrolases/metabolism , Vasodilator Agents/metabolism , Acetylation , Bacterial Proteins/chemistry , Bacteroides thetaiotaomicron/chemistry , Bacteroides thetaiotaomicron/metabolism , Catalytic Domain , Humans , Hydrolases/chemistry , Models, Molecular , Protein Conformation , Substrate Specificity
19.
Org Biomol Chem ; 18(43): 8916-8920, 2020 11 12.
Article in English | MEDLINE | ID: mdl-33118589

ABSTRACT

Chromanone is a privileged structure with a wide range of unique biological activities. A phosphine-promoted, three-component domino sequence of salicylaldehyde with but-3-yn-2-one was well designed for the construction of the chromanone skeleton under mild conditions. As a consequence, a series of novel chromanone analogues bearing an all-carbon quaternary center were facilely assembled from commercially available starting materials with moderate to good yields, which hold promising applications in pharmacological studies. Mechanistic experiments were conducted to confirm the proposed mechanism.

20.
BMC Public Health ; 20(1): 1227, 2020 Aug 12.
Article in English | MEDLINE | ID: mdl-32787809

ABSTRACT

BACKGROUND: Patients with coexisting type 2 diabetes and hypertension generally exhibit poor adherence to self-management, which adversely affects their disease control. Therefore, identification of the factors related to patient adherence is warranted. In this study, we aimed to examine (i) the socio-demographic correlates of patient adherence to a set of self-management behaviors relevant to type 2 diabetes and hypertension, namely, medication therapy, diet therapy, exercise, tobacco and alcohol avoidance, stress reduction, and self-monitoring/self-care, and (ii) whether health attitudes and self-efficacy in performing self-management mediated the associations between socio-demographic characteristics and adherence. METHODS: We performed a secondary analysis of data collected in a randomized controlled trial. The sample comprised 148 patients with coexisting type 2 diabetes mellitus and hypertension. Data were collected by a questionnaire and analyzed using logistic regression. RESULTS: Female patients were found to be less likely to exercise regularly (odds ratio [OR] = 0.49, P = 0.03) and more likely to avoid tobacco and alcohol (OR = 9.87, P < 0.001) than male patients. Older patients were found to be more likely to adhere to diet therapy (OR = 2.21, P = 0.01) and self-monitoring/self-care (OR = 2.17, P = 0.02). Patients living with family or others (e.g., caregivers) were found to be more likely to exercise regularly (OR = 3.44, P = 0.02) and less likely to avoid tobacco and alcohol (OR = 0.10, P = 0.04) than those living alone. Patients with better perceived health status were found to be more likely to adhere to medication therapy (OR = 2.02, P = 0.03). Patients with longer diabetes duration (OR = 2.33, P = 0.01) were found to be more likely to adhere to self-monitoring/self-care. Self-efficacy was found to mediate the association between older age and better adherence to diet therapy, while no significant mediating effects were found for health attitudes. CONCLUSIONS: Adherence to self-management was found to be associated with socio-demographic characteristics (sex, age, living status, perceived health status, and diabetes duration). Self-efficacy was an important mediator in some of these associations, suggesting that patient adherence may be improved by increasing patients' self-management efficacy, such as by patient empowerment, collaborative care, or enhanced patient-physician interactions.


Subject(s)
Diabetes Mellitus, Type 2/therapy , Health Knowledge, Attitudes, Practice , Hypertension/therapy , Patient Compliance/statistics & numerical data , Self-Management/psychology , Aged , Diabetes Mellitus, Type 2/epidemiology , Female , Humans , Hypertension/epidemiology , Male , Middle Aged , Self Efficacy , Socioeconomic Factors , Surveys and Questionnaires
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