Effect of Bushen yixue decoction on follicular development in experimental androgen-sterilized anovulatory rats and its possible mechanism of action

Purpose: To explore the activities of Bushen yixue decoction (BSY) against follicular development in anovulatory rats.Methods: Rats were divided into normal, normal control, clomifene citrate (positive control, orally, 5 mg/kg), and BSY (orally, 50, 100, 200 mg/kg) groups. Anovulatory rats were prepared by testosterone propionate injection (1.5 mg/rat). After 70 days, daily vaginal smears were performed for 10 days until no obvious sexual cycle was observed, indicating that androgen-sterilized anovulatory rats were successfully established. High performance liquid chromatography (HPLC) was used to analyse BSY chemical composition. Levels of follicular stimulating hormone (FSH), luteinizing hormone (LH), oestradiol (E2), progesterone (P), prolactin (PRL), inhibin (INH), activin (ACT) and follistatin (FS) were determined by radioimmunoassay or enzyme linked immunosorbent assay (ELISA). Western blotting was used to determine Bcl-2, cleaved-caspase-3, Bax, MMP-9 and VEGF in ovarian tissues.Results: BSY increased (p < 0.05) the levels of FSH, LH, E2 (p < 0.05) and ACT, but decreased (p < 0.05) the levels of PRL, INH and FS, relative to control rats. Expressions of VEGF (p < 0.01), MMP-9 (p < 0.05) and Bcl-2 (p < 0.01) were up-regulated by BSY, whereas Bax (p < 0.01) and C-caspase-3 (p < 0.01) were down-regulated.Conclusion: BSY promotes follicular development of anovulatory rats via regulating INH-ACT-FS hormones, VEGF, MMP-9, Caspase-3, Bax, and Bcl-2. Thus, BSY may have the potential to be developed for clinical management of infertility.Keywords: Bushen yixue decoction, Follicular development, Inhibin-Activin-Follistatin (INH-ACT-FS) system, Androgen-sterilized anovulatory rat

A new odorous frog species of Odorrana (Amphibia, Anura, Ranidae) from Guizhou Province, China

The frog genus Odorrana is distributed across east and southeastern Asia. Based on morphological differences and molecular phylogenetics, a new species of the genus occurring from Leigong Mountain in Guizhou Province, China is described. Phylogenetic analyses based on DNA sequences of the mitochondrial 12S rRNA, 16S rRNA, and ND2 genes supported the new species as an independent lineage. The uncorrected genetic distances between the 12S rRNA, 16S rRNA, and ND2 genes between the new species and its closest congener were 5.0%, 4.9%, and 16.3%, respectively. The new species is distinguished from its congeners by a combination of the following characters: body size moderate (SVL 39.1–49.4 mm in males, 49.7 mm in female); head width larger than head length; tympanum distinctly visible; small rounded granules scattered all over dorsal body and limbs; dorsolateral folds absent; heels overlapping when thighs are positioned at right angles to the body; tibiotarsal articulation reaching the level between eye to nostril when leg stretched forward; vocal sacs absent in male and nuptial pads present on the base of finger I

Therapeutic effects of Jiaotai pill on rat insomnia via regulation of GABA signal pathway

Purpose: To investigate the therapeutic effects of Jiaotai pill (JTP) on rats with insomnia induced by pchlorophenylalanine (PCPA).Methods: Rats with PCPA-induced insomnia were divided into 5 groups (n = 10), made up of control group, positive treatment group (estazolam 0.1 mg/kg), and 3 JTP treatment groups (0.6, 1.2 and 2.4 g/kg). Another group of 10 rats were treated as normal group. Rats in normal and control groups were treated with normal saline (10 mL/kg). After 14 days of drug treatment, the rats were injected intraperitoneally with sodium pentobarbital (45 mg/kg) and thereafter, latent period and sleeping time were recorded, while contents of γ-aminobutyric acid (GABA) and glutamic acid (Glu) in hypothalamus were determined by high performance liquid chromatography (HPLC). Furthermore, the expressions of glutamate decarboxylase 65 (GAD-65), glutamate decarboxylase 67 (GAD-67), GABAaminotransferase (GABA)-T, anti-GABA transporter 1 (GAT)-1, anti-GABA transporter (GAT)-3, and GABA receptors (GABA-A and GABA-B) in the hypothalamus were analyzed by western blotting assay.Results: The results showed that JTP (0.6, 1.2 and 2.4 g/kg) significantly shortened latent period and prolonged sleeping time (p < 0.01). JTP also increased GABA level (p < 0.01), but decreased Glu contents of the rat hypothalamus (p < 0.01). Western blotting data indicate that JTP significantly upregulated the levels of GAD-65 (p < 0.01), GAD-67 (p < 0.05), GAT-1 (p < 0.01), GAT-3 (p < 0.01), GABA-A (p < 0.01) and GABA-B (p < 0.01), while the level of GABA-T was down-regulated.Conclusion: The results demonstrate that JTP possesses significant sedative effects on insomnia in rats, most probably through a mechanism involving GABA signal pathway.Keywords: Jiaotai pill, Insomnia, GABA, Glutamate, Estazolam, GABA signal pathwa

Towards Better Dermoscopic Image Feature Representation Learning for Melanoma Classification

Deep learning-based melanoma classification with dermoscopic images has recently shown great potential in automatic early-stage melanoma diagnosis. However, limited by the significant data imbalance and obvious extraneous artifacts, i.e., the hair and ruler markings, discriminative feature extraction from dermoscopic images is very challenging. In this study, we seek to resolve these problems respectively towards better representation learning for lesion features. Specifically, a GAN-based data augmentation (GDA) strategy is adapted to generate synthetic melanoma-positive images, in conjunction with the proposed implicit hair denoising (IHD) strategy. Wherein the hair-related representations are implicitly disentangled via an auxiliary classifier network and reversely sent to the melanoma-feature extraction backbone for better melanoma-specific representation learning. Furthermore, to train the IHD module, the hair noises are additionally labeled on the ISIC2020 dataset, making it the first large-scale dermoscopic dataset with annotation of hair-like artifacts. Extensive experiments demonstrate the superiority of the proposed framework as well as the effectiveness of each component. The improved dataset publicly avaliable at https://github.com/kirtsy/DermoscopicDataset.Comment: ICONIP 2021 conferenc

A double‐edged sword: Complement component 3 in toxoplasma gondii infection

Sprague Dawley rats and Kunming (KM) mice are artificially infected with type II Toxoplasma gondii strain Prugniaud (Pru) to generate toxoplasmosis, which is a fatal disease mediated by T. gondii invasion of the central nervous system (CNS) by unknown mechanisms. The aim is to explore the mechanism of differential susceptibility of mice and rats to T. gondii infection. Therefore, a strategy of isobaric tags for relative and absolute quantitation (iTRAQ) is established to identify differentially expressed proteins (DEPs) in the rats’ and the mice's brains compared to the healthy groups. In KM mice, which is susceptible to T. gondii infection, complement component 3 (C3) is upregulated and the tight junction (TJ) pathway shows a disorder. It is presumed that T. gondii‐stimulated C3 disrupts the TJ of the blood–brain barrier in the CNS. This effect allows more T. gondii passing to the brain through the intercellular space.info:eu-repo/semantics/acceptedVersio

Combination of G-CSF and AMD3100 Improves the Anti-inflammatory Effect of Mesenchymal Stem Cells on Inducing M2 Polarization of Macrophages Through NF-κB-IL1RA Signaling Pathway

Mobilized peripheral blood-derived mesenchymal stem cells (PB-MSCs) mainly derived from bone marrow-derived MSCs (BM-MSCs) exert a similar anti-inflammatory effect. However, the mechanism of anti-inflammatory effect of mobilized PB-MSCs by a combination of G-CSF and AMD3100 remains unclear. Cultured rat PB-MSCs mobilized by G-CSF/AMD3100 have shown typical surface markers and potential for multiple differentiations, similar to non-mobilized BM-MSCs. In a co-culture system, rat M0-type macrophages co-cultured with PB-MSCs have shown higher expression of M2 markers including CD206, Arg-1, IL-10, and CCL-22 than BM-MSCs, indicating that PB-MSCs induced greater M0 polarization to M2. Furthermore, compared with BM-MSCs, PB-MSCs in a co-culture system with lipopolysaccharide-induced M1-type macrophages more efficiently promoted M1 polarization to M2, accompanied by increasing expression of CD206, Arg-1, IL-10, and CCL-22 while decreasing expression of M1 markers including iNOS, TNF-α, IL-1β and IL-6, indicating that PB-MSCs triggered greater M1 polarization to M2. Subsequently, polymerase chain reaction arrays showed higher expressions of both IL1rn and Tnfrsf11b in PB-MSCs versus BM-MSCs. In response to an inflammatory niche, such as TNF-α, PB-MSCs have shown higher expression and release of IL1RA, causing greater M2 polarization of macrophages, and the special effects may be almost entirely abolished through the neutralization antibody of IL1RA. Mechanistic studies determined that PB-MSCs showed higher levels NF-κBp65 and NF-κBp-p65 than BM-MSCs, which could be obviously enhanced by TNF-α. And the increased IL1RA expression by TNF-α in PB-MSCs could be markedly canceled by an NF-κB inhibitor PDTC. Interestingly, mimicking the mobilized PB-MSCs by a combination of G-CSF and AMD3100 in vivo, BM-MSCs were treated with G-CSF and/or AMD3100 in vitro, showing the increased expressions of NF-κBp65 and IL1RA, which could be prominently abolished by PDTC. Therefore, targeting IL1rn, gene modification or drug intervention for MSCs may provide a novel therapeutic strategy for human diseases, especially inflammatory diseases

Polymeric micelles based on poly(ethylene glycol) block poly(racemic amino acids) hybrid polypeptides: conformation-facilitated drug-loading behavior and potential application as effective anticancer drug carriers

In this work, racemic hybrid polypeptides poly(ethylene glycol) (PEG)-b-poly(racemic-leucine) (PRL) copolymers with different leucine residues have been synthesized and characterized. Using docetaxel as a model molecule, the high drug-loaded spherical micelles based on PEG-PRL were prepared successfully using dialysis, with a tunable particle size from 170 nm to 250 nm obtained by changing the length of the hydrophobic blocks. Facilitated drug-loading behavior (higher drug-loading ability and easier drug-loading process) of PEG-PRL compared with their corresponding levo forms (PEG-b-poly[levo leucine]) was observed and clarified for the first time. With this facilitation, the highest drug-loading content and efficiency of PEG-PRL micelles can achieve 11.2% ± 0.4% and 67.2% ± 2.4%, respectively. All drug-loaded PEG-PRL micelles exhibit a similar release behavior with a sustained release up to 72 hours. The PEG-PRL was shown to be nontoxic against MCF-7 and human umbilical vein endothelial cells up to a concentration of 100 μg/mL, displaying a good biocompatibility. Also, the docetaxel-loaded PEG-PRL micelles were more toxic than the free drug against MCF-7 human breast cancer cells – both dose and time dependent. Therefore, these high docetaxel-loaded micelles based on racemic hybrid polypeptides appear to be a novel promising nanomedicine for anticancer therapy

Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis in Multi-Ethnic Region, Xinjiang Uygur Autonomous Region, China

<div><h3>Background</h3><p>The multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) has emerged as a global threat. Xinjiang is a multi-ethnic region and suffered second highest incidence of TB in China. However, epidemiological information on MDR and XDR TB is scarcely investigated.</p> <h3>Methodology/Principal Findings</h3><p>A prospective study was conducted to analyze the prevalence of MDR and XDR TB and the differences of drug resistance TB between Chinese Han and other nationalities population at Chest Hospital of Xinjiang Uygur Autonomous Region, China. We performed in vitro drug susceptibility testing of <em>Mycobacterium tuberculosis</em> to first- and second-line anti-tuberculosis drugs for all 1893 culture confirmed positive TB cases that were diagnosed between June 2009 and June 2011. Totally 1117 (59.0%, 95% CI, 56.8%–61.2%) clinical isolates were resistant to ≥1 first-line drugs; the prevalence of MDR TB was 13.2% (95% CI, 11.7%–14.7%), of which, 77 (30.8%; 95% CI, 25.0%–36.6%) and 31 (12.8%; 95% CI, 8.6%–17.0%) isolates were pre-XDR and XDR TB respectively. Among the MDR/XDR TB, Chinese Han patients were significantly less likely to be younger with an odds ratio 0.42 for age 20–29 years and 0.52 for age 40–49 years; <em>P</em>_trend = 0.004), and Chinese Han patients has a lower prevalence of XDR TB (9.6%) than all the other nationality (14.9%).</p> <h3>Conclusions/Significance</h3><p>The burden of drug resistance TB cases is sizeable, which highlights an urgent need to reinforce the control, detection and treatment strategies for drug resistance TB. However, the difference of MDR and XDR TB between Chinese Han and other nationalities was not observed.</p> </div