Blueberry Anthocyanin-Enriched Extracts Attenuate Fine Particulate Matter (PM_2.5)‑Induced Cardiovascular Dysfunction

Blueberry anthocyanin-enriched extracts (BAE) at three doses (0.5, 1.0, and 2.0 g/kg) were administered by oral gavage to rats exposed to 10 mg/kg fine particulate matter (PM_2.5) three times a week. A positive control group was exposed to PM_2.5 without BAE treatment. We analyzed heart rate (HR), electrocardiogram (ECG), and histopathology, and biomarkers of cardiovascular system injuries, systemic inflammation, oxidative stress, endothelial function, and apoptosis. Results indicated that BAE, particularly at 1.0 g/kg, improved ECG and decreased cytokine levels in PM_2.5-exposed rats. These changes were accompanied by an increase in interleukin 10 levels and superoxide dismutase activity in heart tissue and Bcl-2 protein expression, as well as a decrease in interleukin 6, malondialdehyde, endothelin 1, and angiotensin II levels and a reduction in Bax protein expression. This study demonstrates that BAE at certain doses can protect the cardiovascular system from PM_2.5-induced damage

Salinity Regulation of the Interaction of Halovirus SNJ1 with Its Host and Alteration of the Halovirus Replication Strategy to Adapt to the Variable Ecosystem

<div><p>Halovirus is a major force that affects the evolution of extreme halophiles and the biogeochemistry of hypersaline environments. However, until now, the systematic studies on the halovirus ecology and the effects of salt concentration on virus-host systems are lacking. To provide more valuable information for understanding ecological strategies of a virus-host system in the hypersaline ecosystem, we studied the interaction between halovirus SNJ1 and its host <i>Natrinema</i> sp.J7-2 under various NaCl concentrations. We found that the adsorption rate and lytic rate increased with salt concentration, demonstrating that a higher salt concentration promoted viral adsorption and proliferation. Contrary to the lytic rate, the lysogenic rate decreased as the salt concentration increased. Our results also demonstrated that cells incubated at a high salt concentration prior to infection increased the ability of the virus to adsorb and lyse its host cells; therefore, the physiological status of host cells also affected the virus-host interaction. In conclusion, SNJ1 acted as a predator, lysing host cells and releasing progeny viruses in hypersaline environments; in low salt environments, viruses lysogenized host cells to escape the damage from low salinity.</p></div

Identification of natural products with neuronal and metabolic benefits through autophagy induction

<p>Autophagy is a housekeeping lysosomal degradation pathway important for cellular survival, homeostasis and function. Various disease models have shown that upregulation of autophagy may be beneficial to combat disease pathogenesis. However, despite several recently reported small-molecule screens for synthetic autophagy inducers, natural chemicals of diverse structures and functions have not been included in the synthetic libraries, and characterization of their roles in autophagy has been lacking. To discover novel autophagy-regulating compounds and study their therapeutic mechanisms, we used analytic chemistry approaches to isolate natural phytochemicals from a reservoir of medicinal plants used in traditional remedies. From this pilot plant metabolite library, we identified several novel autophagy-inducing phytochemicals, including Rg2. Rg2 is a steroid glycoside chemical that activates autophagy in an AMPK-ULK1-dependent and MTOR-independent manner. Induction of autophagy by Rg2 enhances the clearance of protein aggregates in a cell-based model, improves cognitive behaviors in a mouse model of Alzheimer disease, and prevents high-fat diet-induced insulin resistance. Thus, we discovered a series of autophagy-inducing phytochemicals from medicinal plants, and found that one of the compounds Rg2 mediates metabolic and neurotrophic effects dependent on activation of the autophagy pathway. These findings may help explain how medicinal plants exert the therapeutic functions against metabolic diseases.</p

Thin section electron micrographs of <i>Natrinema</i> sp. J7-2 for cells incubated in media with different salinity.

<p>(A) cells incubated in 18% medium; (B) cells incubated in 25% medium; (C) cells incubated in 30% medium. The scale bars represent 500 nm.</p

Single-step growth curves of halovirus SNJ1 incubated in media with differing salinity.

<p>(A) cells incubated in 18% medium; (B) cells incubated in 25% medium; (C) cells incubated in 30% medium. ●, extracellular and mature intracellular phage; ○, extracellular phage and infective centers.</p

Adsorption efficiency of SNJ1 under different salt concentrations.

<p>Adsorption efficiency of SNJ1 under different salt concentrations.</p

The effect of salinity on the infective activity of halovirus SNJ1 and the growth of its host cells.

<p>(A) the remaining infective activity of halovirus SNJ1 under different NaCl concentrations at indicative time; ■,●,▲,▼, and ○ represent the remaining infective activity in 12%, 15%, 18%, 25%, and 30% NaCl, respectively. (B) the growth curves of <i>Natrinema</i> sp. J7-2 under different NaCl concentrations at indicative time; the symbols △, ■, ●, ▲, and ▼ denote the growth of the host cells in 12%, 15%, 18%, 25%, and 30% NaCl, respectively.</p

Regulation of the replication cycles of halovirus SNJ1by salinity (w/v, %).

<p>Regulation of the replication cycles of halovirus SNJ1by salinity (w/v, %).</p

SNAPIN is critical for lysosomal acidification and autophagosome maturation in macrophages

<p>We previously observed that SNAPIN, which is an adaptor protein in the SNARE core complex, was highly expressed in rheumatoid arthritis synovial tissue macrophages, but its role in macrophages and autoimmunity is unknown. To identify SNAPIN's role in these cells, we employed siRNA to silence the expression of SNAPIN in primary human macrophages. Silencing SNAPIN resulted in swollen lysosomes with impaired CTSD (cathepsin D) activation, although total CTSD was not reduced. Neither endosome cargo delivery nor lysosomal fusion with endosomes or autophagosomes was inhibited following the forced silencing of SNAPIN. The acidification of lysosomes and accumulation of autolysosomes in SNAPIN-silenced cells was inhibited, resulting in incomplete lysosomal hydrolysis and impaired macroautophagy/autophagy flux. Mechanistic studies employing ratiometric color fluorescence on living cells demonstrated that the reduction of SNAPIN resulted in a modest reduction of H⁺ pump activity; however, the more critical mechanism was a lysosomal proton leak. Overall, our results demonstrate that SNAPIN is critical in the maintenance of healthy lysosomes and autophagy through its role in lysosome acidification and autophagosome maturation in macrophages largely through preventing proton leak. These observations suggest an important role for SNAPIN and autophagy in the homeostasis of macrophages, particularly long-lived tissue resident macrophages.</p

Characteristics of the underground brines.

<p>Characteristics of the underground brines.</p