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International Endodontic Journal Jul 2024In this study, we investigated the systemic implications of chronic apical periodontitis (CAP). CAP may contribute to the nonalcoholic fatty liver disease (NAFLD)...
AIM
In this study, we investigated the systemic implications of chronic apical periodontitis (CAP). CAP may contribute to the nonalcoholic fatty liver disease (NAFLD) progression through the gut microbiota and its metabolites, which are related to the degree of fibrosis.
METHODOLOGY
Sixteen 7-week-old male apolipoprotein E knockout (apoE) mice were randomly divided into two groups: the CAP and Con groups. A CAP model was established by sealing the first- and second-maxillary molars with bacterium-containing cotton balls. Apical lesions were evaluated by micro-CT. Histological evaluations of NAFLD were performed using second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) assays. Additionally, we comprehensively analyzed the gut microbiota using 16S rRNA gene sequencing and explored metabolic profiles by liquid chromatography-mass spectrometry (LC-MS). Immunofluorescence analysis was used to examine the impact of CAP on tight junction proteins and mucin expression. Transcriptome assays have elucidated gene expression alterations in liver tissues.
RESULTS
Micro-CT scans revealed an evident periapical bone loss in the CAP group, and the total collagen percentage was increased (Con, 0.0361 ± 0.00510%, CAP, 0.0589 ± 0.00731%, p < .05). 16S rRNA sequencing revealed reduced diversity and distinct taxonomic enrichment in the CAP group. Metabolomic assessments revealed that differentially enriched metabolites, including D-galactosamine, were enriched and that 16-hydroxyhexadecanoic acid and 3-methylindole were depleted in the CAP group. Immunofluorescence analyses revealed disruptions in tight junction proteins and mucin production, indicating intestinal barrier integrity disruption. Liver transcriptome analysis revealed upregulation of Lpin-1 expression in the CAP group.
CONCLUSION
This study provides comprehensive evidence of the systemic effects of CAP on liver fibrosis in NAFLD patients by elucidating alterations in the gut microbiota composition and metabolism.
PubMed: 38958220
DOI: 10.1111/iej.14119 -
Journal of Biomaterials Science.... Jul 2024Cancer is ranked among the top causes of mortality throughout the world. Conventional therapies are associated with toxicity and undesirable side effects, rendering them... (Review)
Review
Cancer is ranked among the top causes of mortality throughout the world. Conventional therapies are associated with toxicity and undesirable side effects, rendering them unsuitable for prolonged use. Additionally, there is a high occurrence of resistance to anticancer drugs and recurrence in certain circumstances. Hence, it is essential to discover potent anticancer drugs that exhibit specificity and minimal unwanted effects. Curcumin, a polyphenol derivative, is present in the turmeric plant ( L.) and has chemopreventive, anticancer, radio-, and chemo-sensitizing activities. Curcumin exerts its anti-tumor effects on cancer cells by modulating the disrupted cell cycle through p53-dependent, p53-independent, and cyclin-dependent mechanisms. This review provides a summary of the formulations of curcumin based on nanospheres, since there is increasing interest in its medicinal usage for treating malignancies and tumors. Nanospheres are composed of a dense polymeric matrix, and have a size ranging from 10 to 200 nm. Lactic acid polymers, glycolic acid polymers, or mixtures of them, together with poly (methyl methacrylate), are primarily used as matrices in nanospheres. Nanospheres are suitable for local, oral, and systemic delivery due to their minuscule particle size. The majority of nanospheres are created using polymers that are both biocompatible and biodegradable. Previous investigations have shown that the use of a nanosphere delivery method can enhance tumor targeting, therapeutic efficacy, and biocompatibility of different anticancer agents. Moreover, these nanospheres can be easily taken up by mammalian cells. This review discusses the many curcumin nanosphere formulations used in cancer treatment.
PubMed: 38958210
DOI: 10.1080/09205063.2024.2371186 -
Journal of the American Chemical Society Jul 2024Water microdroplets promote unusual chemical reactions at the air-water interface. However, the interfacial structure of water microdroplets and its potential influence...
Water microdroplets promote unusual chemical reactions at the air-water interface. However, the interfacial structure of water microdroplets and its potential influence on chemical processes are still enigmatic. Here, we present evidence of in-droplet fractionation of water isotopologues. Employing a sonic spray, we atomized the heavy water (DO, 99.9 atom % D) solution of three classes of organic compounds (basic, acidic, and neutral). The analytes were predominantly desorbed from the resulting droplet surface in protonated form rather than deuterated form, as detected by mass spectrometry. This result remained unaltered upon adding formic acid- (DCOOD) to the droplet. Monitoring Dakin oxidation of benzaldehyde at the surface of binary microdroplets composed of 1:1 (/) DO/HO revealed the preferred formation of phenolate-O over phenolate-O. Atmospheric pressure chemical ionization mass spectrometric analysis of the vapor composition in the sprayed aerosol revealed the preferential evaporation of lighter water isotopologue impurities from the surface of heavy water microdroplets. These results indicate the enrichment of lighter water isotopologue impurities (HOD/HO) on the surface of heavy water microdroplets, implying possible future developments for water isotopologue fractionation using microdroplets.
PubMed: 38958201
DOI: 10.1021/jacs.4c03315 -
Chemistry & Biodiversity Jul 2024In this study, the bioactive components, enzyme inhibitory, antioxidant and anticancer potentials of edible (L. sativa) and a new species (L. anatolica) of Lactuca were...
Comparison of Anticancer, Antioxidant, Enzyme Inhibitory Effects and Phytochemical Contents between Edible Lettuce (Lactuca sativa) and A New Wild Species (Lactuca anatolica).
In this study, the bioactive components, enzyme inhibitory, antioxidant and anticancer potentials of edible (L. sativa) and a new species (L. anatolica) of Lactuca were evaluated and compared. The quantitative analyzes of the bioactive components of L. sativa (LS) and L. anatolica (LA) were analyzed quantitatively by GC-MS and Orbitrab HPLC-HRMS. Antioxidant, enzyme inhibitory and anticancer properties were analyzed by various assays. In general, LA exhibited more stronger antioxidant properties compared to LS. The extracts showed similar inhibitory effects on these enzymes. It was determined that LS was dominant in terms of linoleic acid (23.71%), while LA contained a high level of α-linolenic acid (31.70%). LA and LS inhibited the viability of A549 and MCF-7 cells in a dose-dependent manner. IC50 values for LA, LS and cisplatin were determined as 120.3, 197.5, 4.3 µg/mL in A549 cell line and 286.2, 472.8, 7.2 µg/mL in MCF-7 cell line, respectively. It was revealed that LA and LS treatment at 50 µg/mL concentrations in A549 cells completely suppressed the colony forming capacity, and treatment with IC50 doses inhibited cell migration, and triggered apoptosis by regulating caspase-3, cPARP, p53 and p21. The findings of this study suggested that these species have significant pharmacological potential.
PubMed: 38958194
DOI: 10.1002/cbdv.202400552 -
ACS Nano Jul 2024Collagen is the most abundant protein in tissue scaffolds in live organisms. Collagen can self-assemble in vitro, which has led to a number of biotechnological and...
Collagen is the most abundant protein in tissue scaffolds in live organisms. Collagen can self-assemble in vitro, which has led to a number of biotechnological and biomedical applications. To understand the dominant factors that participate in the formation of collagen nanostructures, here we study in real time and with nanoscale resolution the disassembly and reassembly of collagens. We implement a high-speed force microscope, which provides in situ high spatiotemporal resolution images of collagen nanostructures under changing pH conditions. The disassembly and reassembly are dominated by the electrostatic interactions among amino-acid residues of different molecules. Acidic conditions favor disassembly by neutralizing negatively charged residues. The process sets a net repulsive force between collagen molecules. A neutral pH favors the presence of negative and positively charged residues along the collagen molecules, which promotes their electrostatic attraction. Molecular dynamics simulations reproduce the experimental behavior and validate the electrostatic-based model of the disassembly and reassembly processes.
PubMed: 38958189
DOI: 10.1021/acsnano.4c03839 -
Acta Crystallographica. Section F,... Jul 2024The third complementary-determining regions of the heavy-chain (CDR3H) variable regions (VH) of some cattle antibodies are highly extended, consisting of 48 or more...
The third complementary-determining regions of the heavy-chain (CDR3H) variable regions (VH) of some cattle antibodies are highly extended, consisting of 48 or more residues. These `ultralong' CDR3Hs form β-ribbon stalks that protrude from the surface of the antibody with a disulfide cross-linked knob region at their apex that dominates antigen interactions over the other CDR loops. The structure of the Fab fragment of a naturally paired bovine ultralong antibody (D08), identified by single B-cell sequencing, has been determined to 1.6 Å resolution. By swapping the D08 native light chain with that of an unrelated antigen-unknown ultralong antibody, it is shown that interactions between the CDR3s of the variable domains potentially affect the fine positioning of the ultralong CDR3H; however, comparison with other crystallographic structures shows that crystalline packing is also a major contributor. It is concluded that, on balance, the exact positioning of ultralong CDR3H loops is most likely to be due to the constraints of crystal packing.
Topics: Animals; Cattle; Immunoglobulin Heavy Chains; Crystallography, X-Ray; Immunoglobulin Light Chains; Complementarity Determining Regions; Immunoglobulin Fab Fragments; Models, Molecular; Amino Acid Sequence; Protein Conformation
PubMed: 38958188
DOI: 10.1107/S2053230X2400606X -
Molecular Genetics & Genomic Medicine Jul 2024Pompe Disease (PD) is a metabolic myopathy caused by variants in the GAA gene, resulting in deficient enzymatic activity. We aimed to characterize the clinical features...
BACKGROUND
Pompe Disease (PD) is a metabolic myopathy caused by variants in the GAA gene, resulting in deficient enzymatic activity. We aimed to characterize the clinical features and related genetic variants in a series of Mexican patients.
METHODS
We performed a retrospective study of clinical records of patients diagnosed with LOPD, IOPD or pseudodeficiency.
RESULTS
Twenty-nine patients were included in the study, comprising these three forms. Overall, age of symptom onset was 0.1 to 43 years old. The most frequent variant identified was c.-32-13T>G, which was detected in 14 alleles. Among the 23 different variants identified in the GAA gene, 14 were classified as pathogenic, 5 were likely pathogenic, and 1 was a variant of uncertain significance. Two variants were inherited in cis arrangement and 2 were pseudodeficiency-related benign alleles. We identified two novel variants (c.1615 G>A and c.1076-20_1076-4delAAGTCGGCGTTGGCCTG).
CONCLUSION
To the best of our knowledge, this series represent the largest phenotypic and genotypic characterization of patients with PD in Mexico. Patients within our series exhibited a combination of LOPD and IOPD associated variants, which may be related to genetic diversity within Mexican population. Further population-wide studies are required to better characterize the incidence of this disease in Mexican population.
Topics: Humans; Glycogen Storage Disease Type II; Male; Female; Child, Preschool; Child; Adult; alpha-Glucosidases; Infant; Mexico; Adolescent; Mutation; Age of Onset; Phenotype; Retrospective Studies; Genetic Association Studies; Alleles; Young Adult
PubMed: 38958145
DOI: 10.1002/mgg3.2480 -
Journal of the American Heart... Jul 2024Endothelial cell (EC) dysfunction involves reduced nitric oxide (NO) bioavailability due to NO synthase uncoupling linked to increased oxidation and reduced cofactor...
BACKGROUND
Endothelial cell (EC) dysfunction involves reduced nitric oxide (NO) bioavailability due to NO synthase uncoupling linked to increased oxidation and reduced cofactor availability. Loss of endothelial function and NO bioavailability are associated with inflammation, including leukocyte activation. Eicosapentaenoic acid (EPA) administered as icosapent ethyl reduced cardiovascular events in REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial) in relation to on-treatment EPA blood levels. The mechanisms of cardiovascular protection for EPA remain incompletely elucidated but likely involve direct effects on the endothelium.
METHODS AND RESULTS
In this study, human ECs were treated with EPA and challenged with the cytokine IL-6 (interleukin-6). Proinflammatory responses in the ECs were confirmed by ELISA capture of sICAM-1 (soluble intercellular adhesion molecule-1) and TNF-α (tumor necrosis factor-α). Global protein expression was determined using liquid chromatography-mass spectrometry tandem mass tag. Release kinetics of NO and peroxynitrite were monitored using porphyrinic nanosensors. IL-6 challenge induced proinflammatory responses from the ECs as evidenced by increased release of sICAM-1 and TNF-α, which correlated with a loss of NO bioavailability. ECs pretreated with EPA modulated expression of 327 proteins by >1-fold (<0.05), compared with IL-6 alone. EPA augmented expression of proteins involved in NO production, including heme oxygenase-1 and dimethylarginine dimethylaminohydrolase-1, and 34 proteins annotated as associated with neutrophil degranulation. EPA reversed the endothelial NO synthase uncoupling induced by IL-6 as evidenced by an increased [NO]/[peroxynitrite] release ratio (<0.05).
CONCLUSIONS
These direct actions of EPA on EC functions during inflammation may contribute to its distinct cardiovascular benefits.
PubMed: 38958135
DOI: 10.1161/JAHA.123.034076 -
Journal of Animal Physiology and Animal... Jul 2024This study investigated the effects of negative energy balance (NEB) on perinatal ewes, with a focus on changes in growth performance, serum biochemical parameters,...
This study investigated the effects of negative energy balance (NEB) on perinatal ewes, with a focus on changes in growth performance, serum biochemical parameters, rumen fermentation, ruminal bacteria composition, placental phenotype-related indicators, and expression levels of genes related to placental function. Twenty ewes at 130 days of gestation were randomly allocated to either the positive energy balance (PEB) or NEB groups. In the experiment, ewes in the PEB group were fed the same amount as their intake during the pre-feeding baseline period, while ewes in the NEB group were restricted to 70% of their individual baseline feed intake. The experiment was conducted until 42 days postpartum, and five double-lamb ewes per group were selected for slaughter. The results demonstrated that NEB led to a significant decrease in body weight, carcass weight, and the birth and weaning weights of lambs (P < 0.05). Additionally, NEB caused alterations in serum biochemical parameters, such as increased non-esterified fatty acids and β-hydroxybutyrate levels and decreased cholesterol and albumin levels (P < 0.05). Rumen fermentation and epithelial parameters were also affected, with a reduction in the concentrations of acetic acid, butyric acid, total acid and a decrease in the length of the rumen papilla (P < 0.05). Moreover, NEB induced changes in the structure and composition of ruminal bacteria, with significant differences in α-diversity indices and rumen microbial community composition (P < 0.05). Gene expression in rumen papilla and ewe placenta was also affected, impacting genes associated with glucose and amino acid transport, proliferation, apoptosis, and angiogenesis (P < 0.05). These findings screened the key microbiota in the rumen of ewes following NEB and highlighted the critical genes associated with rumen function. Furthermore, this study revealed the impact of NEB on placental function in ewes, providing a foundation for investigating how nutrition in ewes influences reproductive performance. This research demonstrates how nutrition regulates reproductive performance by considering the combined perspectives of rumen microbiota and placental function.
PubMed: 38958108
DOI: 10.1111/jpn.14009 -
Advanced Materials (Deerfield Beach,... Jul 2024Label-free proteomics is widely used to identify disease mechanism and potential therapeutic targets. However, deep proteomics with ultratrace clinical specimen remains...
Label-free proteomics is widely used to identify disease mechanism and potential therapeutic targets. However, deep proteomics with ultratrace clinical specimen remains a major technical challenge due to extensive contact loss during complex sample pretreatment. Here, a hybrid of four boronic acid-rich lanthanide metal-organic frameworks (MOFs) with high protein affinity is introduced to capture proteins in ultratrace samples jointly by nitrogen-boronate complexation, cation-π and ionic interactions. A MOFs Aided Sample Preparation (MASP) workflow that shrinks sample volume and integrates lysis, protein capture, protein digestion and peptide collection steps into a single PCR tube to minimize sample loss caused by non-specific absorption, is proposed further. MASP is validated to quantify ≈1800 proteins in 10 HEK-293T cells. MASP is applied to profile cerebrospinal fluid (CSF) proteome from cerebral stroke and brain damaged patients, and identified ≈3700 proteins in 1 µL CSF. MASP is further demonstrated to detect ≈9600 proteins in as few as 50 µg mouse brain tissues. MASP thus enables deep, scalable, and reproducible proteome on precious clinical samples with low abundant proteins.
PubMed: 38958107
DOI: 10.1002/adma.202401559