Cardio-Protection of Salvianolic Acid B through Inhibition of Apoptosis Network

Targeting cellular function as a system rather than on the level of the single target significantly increases therapeutic potency. In the present study, we detect the target pathway of salvianolic acid B (SalB) in vivo. Acute myocardial infarction (AMI) was induced in rats followed by the treatment with 10 mg/kg SalB. Hemodynamic detection and pathological stain, 2-dimensional electrophoresis, MALDI-TOF MS/MS, Western blot, pathway identification, apoptosis assay and transmission electron microscope were used to elucidate the effects and mechanism of SalB on cardioprotection. Higher SalB concentration was found in ischemic area compared to no-ischemic area of heart, correlating with improved heart function and histological structure. Thirty-three proteins regulated by SalB in AMI rats were identified by biochemical analysis and were classified as the components of metabolism and apoptosis networks. SalB protected cardiomyocytes from apoptosis, inhibited poly (ADP-ribose) polymerase-1 pathway, and improved the integrity of mitochondrial and nucleus of heart tissue during AMI. Furthermore, the protective effects of SalB against apoptosis were verified in H9c2 cells. Our results provide evidence that SalB regulates multi-targets involved in the apoptosis pathway during AMI and therefore may be a candidate for novel therapeutics of heart diseases

Comparison of radial endobronchial ultrasound-guided transbronchial lung biopsy with distance measurement versus with guide sheath in diagnosing peripheral pulmonary lesions with a diameter ≥3 cm by thin bronchoscope

OBJECTIVE: This study aims to explore the diagnostic values of radial endobronchial ultrasound-guided transbronchial lung biopsy with distance (rEBUS-D-TBLB) measurement and with guide sheath (rEBUS-GS-TBLB) for peripheral pulmonary lesions (PPLs) with a diameter ≥3 cm by thin bronchoscope. PATIENTS AND METHODS: Six hundred and three patients with PPL (diameter ≥3 cm) were enrolled in this study. The subjects were divided into the rEBUS-D-TBLB and rEBUS-GS-TBLB groups by the random number table method. Patients were assigned to undergo rEBUS-D-TBLB or rEBUS-GS-TBLB, respectively. The histopathology, positive diagnosis rates, duration of the procedure, and postoperative adverse effects between the two groups were examined. RESULTS: A total of 569 patients were included in this study according to the inclusion and exclusion criteria, with 282 cases in the rEBUS-D-TBLB group and 287 cases in the rEBUS-GS-TBLB group. For malignant diseases, the positive diagnosis rates of PPL in the outer/inner-middle lung bands and the right-upper/-lower lung lobes by rEBUS-D-TBLB were noninferior to those of rEBUS-GS-TBLB. The duration of the procedure of rEBUS-D-TBLB was longer than that of rEBUS-GS-TBLB. There were 14 cases of hemorrhage >50 mL, 1 case of postoperative chest pain in the rEBUS-D-TBLB group, and 3 cases of hemorrhage >50 mL in the rEBUS-GS-TBLB group. CONCLUSION: REBUS-D-TBLB by thin bronchoscope has a high diagnostic value for PPL with a diameter ≥3 cm, which may be considered a useful alternative for rEBUS-GS-TBLB in the clinic

RNA binding protein TIAR modulates HBV replication by tipping the balance of pgRNA translation

Abstract The pregenomic RNA (pgRNA) of hepatitis B virus (HBV) serves not only as a bicistronic message RNA to translate core protein (Cp) and DNA polymerase (Pol), but also as the template for reverse transcriptional replication of viral DNA upon packaging into nucleocapsid. Although it is well known that pgRNA translates much more Cp than Pol, the molecular mechanism underlying the regulation of Cp and Pol translation efficiency from pgRNA remains elusive. In this study, we systematically profiled HBV nucleocapsid- and pgRNA-associated cellular proteins by proteomic analysis and identified TIA-1-related protein (TIAR) as a novel cellular protein that binds pgRNA and promotes HBV DNA replication. Interestingly, loss- and gain-of-function genetic analyses showed that manipulation of TIAR expression did not alter the levels of HBV transcripts nor the secretion of HBsAg and HBeAg in human hepatoma cells supporting HBV replication. However, Ribo-seq and PRM-based mass spectrometry analyses demonstrated that TIAR increased the translation of Pol but decreased the translation of Cp from pgRNA. RNA immunoprecipitation (RIP) and pulldown assays further revealed that TIAR directly binds pgRNA at the 5’ stem-loop (ε). Moreover, HBV replication or Cp expression induced the increased expression and redistribution of TIAR from the nucleus to the cytoplasm of hepatocytes. Our results thus imply that TIAR is a novel cellular factor that regulates HBV replication by binding to the 5’ ε structure of pgRNA to tip the balance of Cp and Pol translation. Through induction of TIAR translocation from the nucleus to the cytoplasm, Cp indirectly regulates the Pol translation and balances Cp and Pol expression levels in infected hepatocytes to ensure efficient viral replication

Metabolomic Analysis of Anti-Hypoxia and Anti-anxiety Effects of Fu Fang Jin Jing Oral Liquid

<div><p>Background</p><p>Herba Rhodiolae is a traditional Chinese medicine used by the Tibetan people for treating hypoxia related diseases such as anxiety. Based on the previous work, we developed and patented an anti-anxiety herbal formula Fu Fang Jin Jing Oral Liquid (FJJOL) with Herba Rhodiolae as a chief ingredient. In this study, the anti-hypoxia and anti-anxiety effects of FJJOL in a high altitude forced-swimming mouse model with anxiety symptoms will be elucidated by NMR-based metabolomics.</p> <p>Methods</p><p>In our experiments, the mice were divided randomly into four groups as flatland group, high altitude saline-treated group, high altitude FJJOL-treated group, and high altitude diazepam-treated group. To cause anxiety effects and hypoxic defects, a combination use of oxygen level decreasing (hypobaric cabin) and oxygen consumption increasing (exhaustive swimming) were applied to mice. After a three-day experimental handling, aqueous metabolites of mouse brain tissues were extracted and then subjected to NMR analysis. The therapeutic effects of FJJOL on the hypobaric hypoxia mice with anxiety symptoms were verified.</p> <p>Results</p><p>Upon hypoxic exposure, both energy metabolism defects and disorders of functional metabolites in brain tissues of mice were observed. PCA, PLS-DA and OPLS-DA scatter plots revealed a clear group clustering for metabolic profiles in the hypoxia versus normoxia samples. After a three-day treatment with FJJOL, significant rescue effects on energy metabolism were detected, and levels of ATP, fumarate, malate and lactate in brain tissues of hypoxic mice recovered. Meanwhile, FJJOL also up-regulated the neurotransmitter GABA, and the improvement of anxiety symptoms was highly related to this effect.</p> <p>Conclusions</p><p>FJJOL ameliorated hypobaric hypoxia effects by regulating energy metabolism, choline metabolism, and improving the symptoms of anxiety. The anti-anxiety therapeutic effects of FJJOL were comparable to the conventional anti-anxiety drug diazepam on the hypobaric hypoxia mice. FJJOL might serve as an alternative therapy for the hypoxia and anxiety disorders.</p> </div

Engineering of Acid-Resistant d‑Allulose 3‑Epimerase for Functional Juice Production

d-Allulose, a rare sugar and functional sweetener, can be biosynthesized by d-allulose 3-isomerase (DAE). However, most of the reported DAEs exhibit poor resistance under acidic conditions, which severely limited their application. Here, surface charge engineering and random mutagenesis were used to construct a mutant library of CcDAE from Clostridium cellulolyticum H10, combined with high-throughput screening to identify mutants with high activity and resistance under acidic conditions. The mutant M3 (I114R/K123E/H209R) exhibited high activity (3.36-fold of wild-type) and acid resistance (10.6-fold of wild-type) at pH 4.5. The structure–function relationship was further analyzed by molecular dynamics (MD) simulations, which indicated that M3 had a higher number of hydrogen bonds and negative surface charges than the wild type. A multienzyme cascade system including M3 was used to convert high-calorie sugars in acidic juices, and functional juices containing 7.8–15.4 g/L d-allulose were obtained. Our study broadens the manufacture of functional foods containing d-allulose

The protective effects of ginsenoside Rg1 against hypertension target-organ damage in spontaneously hypertensive rats

Abstract Background Although a number of medicines are available for the management of hypertension, the organ damage induced by hypertension is not resolved. The aim of this study was to investigate the protection of ginsenoside Rg1 (Rg1) against vascular remodeling and organ damage in spontaneously hypertensive rats (SHR). Methods Male SHR were treated with 5, 10 or 20 mg/kg Rg1 through intraperitoneal injection per day for 1 month. SHR or Wistar-Kyoto rats (WKY) receiving vehicle (saline) was used as control. Blood pressure detection and pathological stain, transmission electron microscope, immunohistochemical assay were used to elucidate the protection of Rg1. Results Blood pressures were not different between control SHR rats and Rg1 treated SHR rats, but Rg1 improved the aortic outward remodeling by lowering the lumen diameter and reducing the media thickness according the histopathological and ultrastructural detections. Rg1 also protected the retinal vessels against inward remodeling detected by immunohistochemical assay. Furthermore, Rg1 attenuated the target heart and kidney damage with improvement on cardiac and glomerular structure. Conclusions These results suggested that Rg1 held beneficial effects on vascular structure and further protected against the organ-damage induced by hypertension. These findings also paved a novel and promising approach to the treatment of hypertensive complications.</p

500-MHz ¹H NMR NOESY spectra (δ 0.5-4.7, 5.0-9.6) of aqueous extracts from brain tissues of mice in groups HF (A), HS (B), and F (C).

<p>The abbreviations of metabolites were shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0078281#pone-0078281-t001" target="_blank">Table 1</a>.</p