PDGFRß + cell HIF2α is dispensable for white adipose tissue metabolic remodeling and hepatic lipid accumulation in obese mice.

BACKGROUND: Obesity is associated with extensive white adipose tissue (WAT) expansion and remodeling. Healthy WAT expansion contributes to the maintenance of energy balance in the liver, thereby ameliorating obesity-related hepatic steatosis. Tissue-resident mesenchymal stromal cell populations, including PDGFRß + perivascular cells, are increasingly recognized pivotal as determinants of the manner in which WAT expands. However, the full array of regulatory factors controlling WAT stromal cell functions remains to be fully elucidated. Hypoxia-inducible factors (HIFs) are critical regulators in WAT stromal cell populations such as adipocyte precursor cells (APCs). It is revealed that HIF1α activation within PDGFRß + stromal cells results in the suppression of de novo adipogenesis and the promotion of a pro-fibrogenic cellular program in obese animals. However, the role of HIF2α in PDGFRß + cells remains undetermined in vivo. METHODS: New genetic models were employed in which HIF1α (encoded by the Hif1a gene) and HIF2α (encoded by the Epas1 gene) are selectively inactivated in PDGFRß + cells in an inducible manner using tamoxifen (TAM). With these models, both in vitro and in vivo functional analysis of PDGFRß + cells lacking HIF proteins were performed. Additionally, comprehensive metabolic phenotyping in diet-induced mouse models were performed to investigate the roles of PDGFRß + cell HIF proteins in WAT remodeling, liver energy balance and systemic metabolism. RESULTS: Unlike HIF1α inactivation, the new findings in this study suggest that inducible ablation of HIF2α in PDGFRß + cells does not cause apparent effects on WAT expansion induced by obesogenic diet. The adipogenic ability of PDGFRß + APCs is not significantly altered by genetic HIF2α ablation. Moreover, no difference of key parameters associated with healthy WAT remodeling such as improvements of WAT insulin sensitivity, reduction in metabolic inflammation, as well as changes in liver fat accumulation or systemic glucose metabolism, is detected in PDGFRß + cell Epas1-deficient mice. CONCLUSION: The new findings in this study support that, in contrast to HIF1α, PDGFRß + cell HIF2α appears dispensable for WAT metabolic remodeling and the resulting effects on liver metabolic homeostasis in diet-induced obesity, underscoring the isoform-specific roles of HIFα proteins in the regulation of adipose tissue biology.

[Rapid determination of nine components in the first extraction process of Xingnaojing injection by using ultraviolet spectroscopy].

In this study, an analytical method based on ultraviolet spectroscopy was established for the rapid determination of nine components including isophorone, 4-methylene-isophorone, curcumenone, curcumenol, curdione, curzerenone, furanodienone, curcumol and germacrone in the first extraction process of Xingnaojing injection. 166 distillate samples of Gardeniae Fructus and Radix Curcumae were collected in the first extraction process of Xingnaojing injection. The ultraviolet spectra of these samples were collected, and the contents of the nine components in these samples were determined by high performance liquid chromatography. Least squares support vector machine and radial basis function artificial neural network were used to establish the multivariate calibration models between the ultraviolet spectra and the contents of the nine components. The results showed that the established ultraviolet spectrum analysis method can determine the contents of the nine components in the distillates accurately, with root mean square error of prediction of 0.068, 0.147, 0.215, 0.319, 1.01, 1.27, 0.764, 0.147, 0.610 mg•L⁻¹, respectively. This proposed method is a rapid, simple and low-cost tool for the monitoring and endpoint determination of the extraction process of Xingnaojing injection to reduce quality defects and variations.

Synergistic remineralization of enamel white spot lesions using mesoporous bioactive glasses loaded with amorphous calcium phosphate.

Objectives: The purpose of this study was to create a new delivery system that can synergistically remineralize enamel white spot lesions (WSLs). Materials and methods: The delivery system (PAA-ACP@aMBG) was prepared by using aminated mesoporous bioactive glasses (aMBG) as the carrier loaded with polyacrylic-stabilized amorphous calcium phosphate (PAA-ACP). The materials were characterized by transmission electron microscopy (TEM), X-ray powder diffraction (XRD), inductively coupled plasma-optical emission spectrometry (ICP-OES), and so on. Forty-eight artificial WSLs enamel samples were randomized to four groups: artificial saliva (negative control, NC), casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), PAA-ACP@aMBG, and MBG. The effects of demineralization and remineralization of the enamel surface were compared by means of surface microhardness (SMH) measurements, surface color change measurements, fluorescence microscopy (FM), X-ray diffraction (XRD) analysis and scanning electron microscopy (SEM). Results: There was no significant difference in the surface microhardness recovery rate (SMHRR) or color recovery rate (CRR) among the CPP-ACP group, PAA-ACP@aMBG group and MBG group (P>0.05), but these values were significantly higher than those in the NC group (p < 0.01). FM demonstrated that the remineralization depth in the PAA-ACP@aMBG group was significantly greater than that of the remaining three groups (p < 0.01). SEM analysis indicated that the enamel demineralization marks in the PAA-ACP@aMBG group, CPP-ACP group, and MBG group were obscured by mineral deposition. Conclusions: PAA-ACP@aMBG showed good mineralization properties, implying its great potential for clinical application.

Yanning Syrup ameliorates the lipopolysaccharide-induced inflammation: Adjusting the gut microbiota, short-chain fatty acids, and the CD4+ T cell balance.

ETHNOPHARMACOLOGICAL RELEVANCE: As a commercial Chinese patent medicine, Yanning Syrup (YN) is used to treat acute upper respiratory tract infections and acute enteritis effectively in clinical practice. However, the underlying mechanism remains unclear. AIMS OF THE STUDY: To reveal the effect of YN on gut microbiota dysbiosis, and explore the potential role of the gut microecosystem and CD4+ T cell immune homeostasis in YN-treated respiratory and intestinal diseases in lipopolysaccharide (LPS)-induced inflammatory rats. METHODS: Inflammation in rat models was induced by intraperitoneal injection of LPS (8 mg/kg). Histological changes were observed by H & E staining. Changes in gut microbiota and short-chain fatty acid (SCFA) production were analysed using 16S rRNA gene sequencing and targeted metabolomics. A Luminex cytokine microarray and enzyme-linked immunosorbent assay (ELISA) were conducted to evaluate the serum and colon cytokine profiles. The frequencies of immune cells, including Th1, Th2, Th17 and Treg cells in the mesenteric lymph nodes (MLNs), bronchoalveolar lavage fluid (BALF) and whole blood were phenotyped using flow cytometry. RESULTS: The YN-treated rats showed less colon inflammation, as evidenced by the reduction in mortality rate and histology score. Notably, YN was found to improve the immunosuppressed state induced by LPS in rats, which not only upregulated the levels of the proinflammatory cytokine IL-17A and the immunosuppressive cytokines IL-4 and IL-10 in colon tissue but also increased the levels of IL-1α, IL-5, IL-7, IL-12 (p70), GM-CSF and VEGF in serum. The numbers of Th17 cells and Treg cells in the MLNs, blood, and BALF of model rats were regulated by YN, with the restoration of the Th17/Treg balance. Additionally, the Th1/Th2 balance in MLNs and whole blood of model rats was restored after YN administration. Sequencing of 16S rRNA gene indicated that YN-treated rats exhibited greater gut microbial diversity and flora composition, specifically inhibiting some harmful bacteria such as Enterobacter and Blautia and increasing Firmicutes and Actinobacteria. Targeted metabolomics analysis demonstrated an increase of SCFA (acetic acid, butyric acid, valeric acid, and hexanoic acid) production in YN-treated rats. Most of the dominant bacterial genera regulated by YN administration were correlated with the concentrations of SCFA and inflammatory cytokines. CONCLUSIONS: These results demonstrated that YN could ameliorate LPS-induced inflammation in rats by modifying gut microbiota, increasing microbiota-derived SCFA production and regulating the balance of Th1/Th2 and Treg/Th17 cells.

[In silico cloning, expression and bioinformatics analysis of NtODB from common tobacco].

It has been reported that ODB genes play an important role in homologous recombination-directed DNA repair, suggesting their potential applications in plant breeding. To analyze the expression characteristics of tobacco NtODB gene, the cDNA sequence of NtODB was obtained using in silico cloning technique. The physicochemical properties, signal peptide, and advanced structures of the predicted protein were analyzed using bioinformatics tools. The results showed that the NtODB gene has a 579-bp open reading frame which encodes a protein with 192 amino acid residues. The protein NtODB is predicted to be alkaline and hydrophilic. Real-time quantitative PCR showed that NtODB was constitutively expressed in different tissues. Subcellular localization showed that NtODB was mainly expressed in cell membrane and chloroplast. These results may help us to better understand and elucidate the roles of ODB genes in the homologous recombination-directed DNA repair.

Advancement in the chemical analysis of Paeoniae Radix (Shaoyao).

Paeoniae Radix Alba (baishao or white peony root) and Paeoniae Radix Rubra (chishao or red peony root) are two highly valuable traditional Chinese medicines (TCMs) usually indicated for painful conditions, menstrual disorders and viral infections. These two TCMs are collectively referred to as shaoyao (Paeoniae Radix) due to their close origins and similar chemical compositions. Modern research indicates that monoterpene glycosides, polyphenols and paeonols are the three main types of compounds related to the pharmacological activities of Paeoniae Radix. This review summarizes recent advances in the chemical analysis of Paeoniae Radix and the related traditional Chinese medicine formulas/preparations, including methods used for sample pretreatment, qualitative analysis, quantitative analysis and biological sample analysis. More than 120 papers are discussed in this review, focusing on the chemical analysis of Paeoniae Radix, and various analytical techniques (such as HPLC, LC-MS, IR, near IR and quantitative NMR), as well as their advantages/disadvantages, are described. It is our hope that this paper can provide necessary information for improving the quality evaluation methods currently available for Paeoniae Radix and offer a scientific basis for the future in-depth study of the pharmacokinetics and pharmacodynamics of Paeoniae Radix.