Recent investigations indicate that schistosome infection is closely associated with aberrant glycolipid metabolism. However, the actual glycolipid metabolism gene expression, as well as the possible ...pathways that regulate glycolipid metabolism in the schistosome-infected liver, has not been extensively explored.
In this study, we evaluated the dynamic expression of glycolipid metabolism-associated genes and proteins in the livers from mice infected with Schistosoma japonicum at the indicated time points using real-time PCR and immunofluorescence. Then, cultures of macrophages were treated with schistosome soluble egg antigen (SEA) to detect the expression levels of genes associated with glucose and lipid metabolism in order to identify macrophages metabolic characteristics in response to these antigens. Furthermore, SEA-stimulated macrophages were co-cultures with hepatocytes and detected the effects of macrophages on the gene expression of hepatocytes metabolism.
The expression of glycolysis-related genes (Ldha, Glut4, Pkm2, Glut1, Pfkfb3, Aldoc, HK2, Pfk) in the liver were upregulated but the gluconeogenesis gene (G6pc) was downregulated during S. japonicum infection. In addition, the mRNA levels of fatty acid (FA) oxidation-related genes (Ucp2, Atp5b, Pparg) in the liver were significantly upregulated; however, the FA synthesis genes (Fas, Acc, Scd1, Srebp1c) and lipid uptake gene (Cd36) were downregulated post-S. japonicum-infection. In consistence with these data, stimulation with SEA in vitro significantly enhanced the gene expression that involved in glycolysis and FA oxidation, but decreased genes related to gluconeogenesis, FA synthesis and lipid uptake in macrophages. The levels of phosphorylated AMPK, AKT and mTORC1 were increased in macrophages after SEA stimulation. Inhibition of phosphorylated AMPK, AKT and mTORC1 promoted SEA-treated macrophages to produce glucose. In addition, suppression of phosphorylated-AMPK, but not phosphorylated-AKT and phosphorylated-mTOR, induced the lipid accumulation in SEA-stimulated macrophages. Furthermore, SEA-treated macrophages significantly reduced the expression of Acc mRNA in hepatocytes in vitro.
These findings reveal S. japonicum infection induces dynamic changes in the expression levels of genes involved in catabolism (glucose uptake, glycolysis and fatty acid oxidation) and suppressing anabolism (glycogen synthesis) in the liver, which could occur via macrophages' metabolic states, particularly those involved in the AMPK, AKT and mTORC1 pathways.
The ladybird beetle
Cheilomenes sexmaculata
(family Coccinellidae, order Coleoptera) is a common insect predator of agricultural pests. In this study, the full genome sequence of a novel picorna-like ...virus, tentatively named “Cheilomenes sexmaculata picorna-like virus 1” (CSPLV1), was identified in
C. sexmaculata
. The full-length sequence of CSPLV1 is 11,384 nucleotides (nt) in length (excluding the polyA tail), with one predicted open reading frame (ORF) encoding a polyprotein of 3727 amino acids, a 13-nt 5' untranslated region (UTR), and a 187-nt 3' UTR. The ORF of CSPLV1 consists of four distinct domains, including an RNA virus helicase domain (nt 3029-3319), a peptidase domain (nt 5555-6121), an RNA-dependent RNA polymerase domain (nt 7154-8101), and a picorna-like coat protein domain (nt 8606-9283). Phylogenetic analysis based on the conserved RdRP sequence showed that CSPLV1, together with Wuhan house centipede virus 3, Hypera postica associated virus 1, and Diabrotica undecimpunctata virus 1, forms an unclassified group that is closely related to members of the family
Solinviviridae
. To the best of our knowledge, CSPLV1 is the first picorna-like virus discovered in
C. sexmaculata
.
Panax species are the most popular medicinal herbs. The root of these plants contains pharmacologically active triterpene saponins, also known as ginsenosides, compounds that are divided into ...dammarane- and oleanane-type triterpenes. Two CYP716A subfamily genes (CYP716A47 and CYP716A53v2) were recently characterized, encoding an enzyme catalyzing the hydroxylation of dammarane-type triterpenes in Panax ginseng. Herein, we report that one CYP716A subfamily gene (CYP716A52v2) isolated from P. ginseng encodes a β-amyrin 28-oxidase, which is suggested to modify β-amyrin into oleanolic acid, a precursor of an oleanane-type saponin (mainly ginsenoside Ro) in P. ginseng. The ectopic expression of both PNY1 and CYP716A52v2 in recombinant yeast resulted in erythrodiol and oleanolic acid production, respectively. In vitro enzymatic activity assays biochemically confirmed that CYP716A52v2 catalyzed the oxidation of β-amyrin to produce oleanolic acid, and the chemical structure of the oleanolic acid product was confirmed using gas chromatography-mass spectrometry (GC/MS). Transgenic P. ginseng plants were generated via Agrobacterium tumefaciens-mediated transformation: the overexpression of CYP716A52v2 greatly increased the content of oleanane-type ginsenoside (ginsenoside Ro), whereas RNA interference against CYP716A52v2 markedly reduced it. Furthermore, the levels of other dammarene-type ginsenosides were not affected in these transgenic lines. These results indicate that CYP716A52v2 is a β-amyrin 28-oxidase that plays a key role in the biosynthesis of oleanane-type triterpenes in P. ginseng.
Objective
Dual‐specificity phosphatase 5 (DUSP‐5) is a phosphatase that specifically dephosphorylates both phosphoserine and phosphotyrosine residues of MAPK. The dysregulated activation of MAPK ...contributes to the pathogenesis of rheumatoid arthritis. This study was undertaken to investigate the therapeutic potential of DUSP‐5 in preventing the development of autoimmune arthritis in an animal model.
Methods
Autoimmune arthritis was induced in DBA/1J mice by immunization with type II collagen (CII). Eight days after CII immunization, the mice were injected intravenously with pcDNA–DUSP5 or mock vector, and electroporation was performed. The serum concentration of anti‐CII antibodies was measured by enzyme‐linked immunosorbent assay. Histologic analysis of the joints was performed using Safranin O, toluidine blue, and immunohistochemical staining. The expression of transcription factors was analyzed by immunostaining and Western blotting. The frequencies of interleukin‐17–producing CD4+ Th17 cells and CD4+CD25+Foxp3+ Treg cells were analyzed by flow cytometry.
Results
In DUSP5‐overexpressing mice, the severity of arthritis, as indicated by the clinical arthritis score and the extent of histologic inflammation and cartilage damage, was attenuated. The pcDNA–DUSP5–injected mice had lower circulating levels of total and CII‐specific IgG, IgG1, and IgG2a. The Th17 cell population frequency was decreased and the Treg cell frequency was increased in the spleens of the DUSP5‐treated group. The reciprocal regulation of Th17 and Treg cells in vivo was associated with attenuated activity of pSTAT‐3 and pERK, and with increased activity of pSTAT‐5. DUSP5 overexpression suppressed joint damage through down‐regulation of pro‐osteoclastogenic molecules.
Conclusion
The antiarthritic properties of DUSP‐5 are associated with its reciprocal regulation of Th17 and Treg cells and its inhibition of ERK activity.
In this systematic review and meta‐analyses, we sought to determine sex‐disparities in treatment abandonment in children with cancer in low‐ and middle‐income countries (LMICs) and identify the ...characteristics of children and their families most disadvantaged by such abandonment. Sex‐disaggregated data on treatment abandonment were collated from the available literature and a random‐effects meta‐analysis was conducted to compare the rates in girls with those in boys. Subgroup analyses were conducted in which studies were stratified by design, cancer type and the Gender Inequality Index of the country of study. Eighteen studies were included in the systematic review and of these studies, 16 qualified for the meta‐analysis, representing 10 754 children. The pooled rate of treatment abandonment overall was 30%. We observed no difference in the proportion of treatment abandonment in girls relative to estimates observed in boys (rate ratio RR 0.95, 95% CI: 0.79‐1.15; P = .61). There was significant heterogeneity across the included studies and in the pooled estimate of RR for girls vs boys (both I2 > 98%). Subgroup analyses did not reveal any effect on abandonment risk. Risk factors for abandonment observed fell into three main categories: socio‐demographic; geographic; and travel‐related. In conclusion, a high rate of treatment abandonment (30%) was observed overall for children with cancer in included studies in LMICs, although this was variable and context specific. No evidence of gender bias in childhood cancer treatment abandonment rates across LMICs was found. Given that the risk factors for abandonment are context specific, in‐depth country‐level analyses may provide further insights into the role of a child's gender in treatment abandonment decisions.
What's new?
Treatment abandonment is a major cause of treatment failure in children with cancer in resource poor settings. Multiple factors potentially influence rates of treatment abandonment in childhood cancers, although very few studies have examined the influence of a child's gender. Here, analyses of treatment abandonment rates among boys and girls with cancer in low‐ and middle‐income countries uncovered no evidence to support gender bias. Treatment abandonment, however, was significantly linked to sociodemographic factors, including socioeconomic status and rural residence, indicating that risk factors for abandonment are context specific. Future in‐depth studies are needed to better understand treatment abandonment decisions.
Congenital epulis in a newborn Kang, Min-Jun; Kang, Sang-Hoon
Journal of The Korean Association of Oral and Maxillofacial Surgeons,
12/2022, Letnik:
48, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Congenital epulis (CE) is an extremely rare benign tumor of the gingiva that is found on the alveolar ridge of newborns, and the main treatment option is simple excision. Postoperative prognosis is ...very good, and spontaneous regression may occur despite incomplete excision. This report presented a rare case of CE and its healing process after surgery under local anesthesia. The treatment plan was decided upon through consultation between a medical team and the patient's family, with surgical excision for the main lesion, which benefitted from surgery, and follow-up for a very small-sized lesion, which was thought to be appropriate for a newborn. No recurrence was found after its removal, and favorable healing was observed.
Whether combining changes in eGFR and urine albumin-to-creatinine ratio (UACR) is more strongly associated with outcomes compared with either change alone is unknown.
We analyzed 8766 patients with ...type 2 diabetes in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation Observational (ADVANCE-ON) study. Changes in eGFR and UACR (baseline to 2 years) were defined as ≥40% decrease, minor change, and ≥40% increase. The primary outcome was the composite of major macrovascular (nonfatal or fatal myocardial infarction, nonfatal or fatal stroke, or cardiovascular death), major kidney events (requirement for kidney replacement therapy or kidney death), and all-cause mortality.
Over a median of 7.7 years of follow-up, 2191 primary outcomes were recorded. Strong linear associations between eGFR and UACR changes and subsequent risk of the outcome were observed. For eGFR, the hazard ratios were 1.58 (95% confidence interval 95% CI, 1.27 to 1.95) for a decrease ≥40% and 0.82 for an increase ≥40% (95% CI, 0.64 to 1.04) compared with minor change. For UACR, the hazard ratios were 0.96 (95% CI, 0.85 to 1.07) for a decrease ≥40% and 1.32 (95% CI, 1.19 to 1.46) for ≥40% increase compared with minor change. Compared with dual minor changes, both an eGFR decrease ≥40% and a UACR increase ≥40% had 2.31 (95% CI, 1.67 to 3.18) times the risk of the outcome, with evidence of interaction between the two markers.
Clinically meaningful decreases in eGFR and increases in UACR over 2 years, independently and in combination, were significantly associated with higher risk of major clinical outcomes.
G-protein-coupled receptors play a crucial role in various signaling pathways and function as targets for treating a wide spectrum of diseases. Since the twentieth century, extensive research has ...been conducted on the Mu opioid receptor (MOR) as a drug target. We examined the MOR inactivation and activation processes using an enhanced sampling method (Gaussian accelerated molecular dynamics), the binding pocket site area method, the root mean square deviation method, and the free energy (potential of mean force) method. This study revealed two important intermediate MOR structures (intermediate and intermediate inactive), and the results suggest that the intermediate MOR structure is responsible for the selectivity of opioids.
In this study, MnFe2O4 nanoparticle (MFNP)‐decorated graphene oxide nanocomposites (MGONCs) are prepared through a simple mini‐emulsion and solvent evaporation process. It is demonstrated that the ...loading of magnetic nanocrystals can be tuned by varying the ratio of graphene oxide/magnetic nanoparticles. On top of that, the hydrodynamic size range of the obtained nanocomposites can be optimized by varying the sonication time during the emulsion process. By fine‐tuning the sonication time, MGONCs as small as 56.8 ± 1.1 nm, 55.0 ± 0.6 nm and 56.2 ± 0.4 nm loaded with 6 nm, 11 nm, and 14 nm MFNPs, respectively, are successfully fabricated. In order to improve the colloidal stability of MGONCs in physiological solutions (e.g., phosphate buffered saline or PBS solution), MGONCs are further conjugated with polyethylene glycol (PEG). Heating by exposing MGONCs samples to an alternating magnetic field (AMF) show that the obtained nanocomposites are efficient hyperthermia agents. At concentrations as low as 0.1 mg Fe mL−1 and under an 59.99 kA m−1 field, the highest specific absorption rate (SAR) recorded is 1588.83 W g−1 for MGONCs loaded with 14 nm MFNPs. It is also demonstrated that MGONCs are promising as magnetic resonance imaging (MRI) T2 contrast agents. A T2 relaxivity value (r2) as high as 256.2 (mM Fe)−1 s−1 could be achieved with MGONCs loaded with 14 nm MFNPs. The cytotoxicity results show that PEGylated MGONCs exhibit an excellent biocompatibility that is suitable for biomedical applications.
Manganese ferrite‐decorated graphene oxide nanocomposites are prepared by a simple mini‐emulsion/solvent evaporation technique. Such a process involves hydrophobic manganese ferrite nanocrystals and oleylamine‐modified graphene oxide. The as‐synthesized water soluble magnetic nanocomposites still retain the original manganese ferrite superparamagnetic properties, and therefore the composite is suitable for various biomedical applications.
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