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In the vibration-assisted milling process, the cutting force as a very important parameter can reflect the cutting characteristics of this machining method. In this study, a three-dimensional vibration-assisted milling system was utilized to focus on the changing law of the cutting forces and the topography of the structured surface during machining. Firstly, the kinematic analysis proves that the trajectory of the tool relative to the workpiece under the excitation of the vibration device is a complex spatial spiral curve. Then, many vibration-assisted milling experiments were carried out to investigate the effect of the process variables, such as the spindle speed, feed rate, amplitude of vibration, vibration frequency, and tool radius, on the cutting forces (average and maximum cutting forces) and the topographical characteristics of the structured surfaces. The experimental results sufficiently confirmed that the amplitude of vibration is the most important process variable associated with the cutting forces, followed by spindle speed and vibration frequency; for the topographic features of the structured surface, the amplitude of vibration also has an important effect on the three-dimensional dimensions of each structural unit; by contrast, the vibration frequency and the feed rate do have a significant effect on the topography of structured surfaces. The results of the research provide critical guidance for 3D vibration-assisted milling to fabricate a variety of structured surfaces. [ABSTRACT FROM AUTHOR]

Ganlanye (GLY), the leaf of Canarium album (Lour.) DC., is a traditional Chinese medicinal herb for warm disease treatment. We found that its aqueous extract could inhibit the influenza A virus. To find and characterize anti-influenza virus phytochemicals from GLY, we performed (1) bioassay-guided isolation, (2) a cell and animal assay, and (3) a mechanism study. Bioassay-guided isolation was used to identify the effective components. Influenza virus-infected MDCK cell and BALB/c mouse models were employed to evaluate the anti-influenza virus activities. A MUNANA assay was performed to find the NA inhibitory effect. As a result, urolithin M5 was obtained from the crude extract of GLY. It inhibited influenza virus activities in vitro and in vivo by suppressing the viral NA activity. In the MDCK cell model, urolithin M5 could inhibit an oseltamivir-resistant strain. In a PR8-infected mouse model, 200 mg/kg/d urolithin M5 protected 50% of mice from death and improved lung edema conditions. GLY was recorded as a major traditional herb for warm disease treatment. Our study identified GLY as a potent anti-influenza herb and showed urolithin M5 as the active component. We first report the in vivo activity of urolithin M5 and support the anti-influenza application of GLY. [ABSTRACT FROM AUTHOR]

Aims: Obese patients are highly sensitive to adriamycin (ADR)-induced cardiotoxicity. However, the potential mechanism of superimposed toxicity remains to be elucidated. Sestrin 2 (SESN2), a potential antioxidant, could attenuate stress-induced cardiomyopathy; therefore, this study aims to explore whether SESN2 enhances cardiac resistance to ADR-induced oxidative damage in high-fat diet (HFD)–induced obese mice. Results: The results revealed that obesity decreased SESN2 expression in ADR-exposed heart. And, HFD mice may predispose to ADR-induced cardiotoxicity, which was probably associated with inhibiting protein kinase B (AKT), glycogen synthase kinase-3 beta (GSK-3β) phosphorylation and subsequently blocking nuclear localization of nuclear factor erythroid-2 related factor 2 (NRF2), ultimately resulting in cardiac oxidative damage. However, these destructive cascades and cardiac oxidative damage effects induced by HFD/sodium palmitate combined with ADR were blocked by overexpression of SESN2. Moreover, the antioxidant effect of SESN2 could be largely abolished by sh-Nrf2 or wortmannin. And sulforaphane, an NRF2 agonist, could remarkably reverse cardiac pathological and functional abnormalities caused by ADR in obese mice. Innovation and Conclusion: This study demonstrated that SESN2 might be a promising therapeutic target for improving anthracycline-related cardiotoxicity in obesity by upregulating activity of NRF2 via AKT/GSK-3β/Src family tyrosine kinase signaling pathway. Antioxid. Redox Signal. 40, 598–615. [ABSTRACT FROM AUTHOR]

Abstract: Functionalization of the indole benzene ring was achieved by using an organocatalytic enantioselective Friedel–Crafts alkylation/lactonization reaction of hydroxyindoles with a variety of substituted methyleneoxindoles. This reaction was applicable to indoles substituted with the hydroxy group at different positions of the benzene ring, and the corresponding pyrrolodihydrocoumarins were obtained in moderate to high yields (37–99%) with high stereoselectivities (up to 99% ee and >20:1 dr) in most cases. A scale‐up reaction and derivatization of the representative products were also carried out to investigate the usefulness of this protocol. [ABSTRACT FROM AUTHOR]

Fu Rong Ye (FRY), the leaf of Hibiscus mutabilis L., is a Chinese medicinal herb used to treat coughs and respiratory diseases. FRY is the major herbal component of the patent medicine Fupo Ganmao Granules for treating common cold. However, its anti-influenza active components and mechanism were not identified. Here, we aim to a) isolate the anti-influenza phytochemicals from FRY extract and b) explore its anti-flu mechanism. Bioassay guided isolation was performed to get anti-influenza virus components. Influenza virus infected cells and mouse model were employed for efficacy evaluation. Using bioassay-guided isolation, the flavonoid tiliroside was obtained, which inhibited four IAV strains in MDCK cells with EC 50 ranging from 3.87 to 27.61 μM by suppressing the viral ribonucleoprotein activity. Tiliroside also significantly downregulated the expression of cytokines/chemokines in A549 cells, and protected 50% of PR8-infected BALB/c mice from death and at 800 mg/kg/day, improved lung edema conditions. Tiliroside is effective for influenza virus infection treatment and promising for further drug development. This study is the first to demonstrate that tiliroside in FRY acts against influenza virus. [Display omitted] • Tiliroside was isolated from leaves of Hibiscus mutabilis L.. • Tiliroside inhibited ribonucleoprotein (RNP) activity. • Tiliroside exhibited antiviral activities in mice. • This study supports the clinical application of FRY in influenza treatment. [ABSTRACT FROM AUTHOR]

Canarium album (Lour.) DC. belongs to the Burseraceae family. Its leaf, named as Ganlanye (GLY), was recorded to treat warm disease symptoms via clearing lung heat and toxicants in medical classics. Its aqueous extract had anti-influenza activity in our previous phenotypic screening. However, its active components and mechanism were not identified. We aim to isolate the anti-influenza phytochemicals from GLY extract and explore its anti-flu mechanism. Influenza A virus infected MDCK cells were used to test the compounds and fractions. Structural analyses of new compounds were performed via NMR calculation with the combination of DP4plus probability method and computed electronic circular dichroism (ECD). Hemagglutination inhibitory assay and neuraminidase inhibitory assay were performed to find the target protein. Molecular docking and recombinant virus were used to confirm the action site of the three new canaroleosides. Three new phenolic glycosides, canaroleosides A−C (1 – 3), and three known flavonoids (4 – 6), were isolated from the GLY aqueous extract and their anti-influenza virus mechanism was revealed. The absolute configurations of 1 − 3 were determined by ECD method, with the structure of the 2,5-dihydroxybenzoic acid moiety in 1 assigned by NMR calculation. Compound 1 was found to suppress both hemagglutinin and neuraminidase activities. Compounds 2 , 3 4 and 6 inhibited neuraminidase, while compound 5 inhibited hemagglutinin. 1 – 3 could interact with Arg152 of the viral neuraminidase based on the result of molecular docking and reverse genetics. Six phytochemicals were isolated from GLY aqueous extract and found to inhibit influenza A strains. They were found to interact with hemagglutinin or neuraminidase and canaroleosides 1 – 3 could interact with Arg152 of the viral neuraminidase. This study provided more evidence on the anti-influenza effect of Ganlan and laid the foundation for further generation of potent NA inhibitors. [Display omitted] [ABSTRACT FROM AUTHOR]

Fibroblast growth factor 1 (FGF1) has a critical regulatory role in the development of the cardiovascular system (CVS) and is strongly associated with the progression or treatment of cardiovascular diseases (CVDs). However, the regulatory mechanisms of FGF1 in CVS and CVDs have not yet been fully elucidated. Therefore, this review article summarized the existing literature reports on the role of FGF1 in CVS under physiological and pathological conditions. First, the expression and physiological functions of endogenous FGF1 is fully demonstrated. Then, we analyzed the role of exogenous FGF1 in normal CVS and related pathological processes. Specifically, the potential signaling pathways might be mediated by FGF1 in CVDs treatment is discussed in detail. In addition, the barriers and feasible solutions for the application of FGF1 are further analyzed. Finally, we highlight therapeutic considerations of FGF1 for CVDs in the future. Thus, this article may be as a reference to provide some ideas for the follow-up research. [Display omitted] [ABSTRACT FROM AUTHOR]

A pinanamine‐based analog, (1R,2R,3R,5S)‐N‐((3‐cyclopropylthiophen‐2‐yl)methyl)‐2,6,6‐trimethylbicyclo[3.1.1]heptan‐3‐amine (M090) was synthesized and demonstrated with anti‐influenza activity to overcome the multi‐drug resistance. Herein, a rapid and robust liquid chromatography‐tandem mass spectrometry method was developed and validated to quantify M090 in rat plasma. With simple protein precipitation by methanol, the separation of M090 was performed on a Waters BEH‐C18 column (2.1 × 100 mm, 1.7 μm) by gradient elution at 0.4 mL/min with mobile phases consisting of water containing 0.1 % formic acid (phase A) and methanol (phase B). M090 and clenbuterol (internal standard) were detected using multiple reaction monitoring in positive electrospray ionization mode with transitions of m/z 290.3→137.0 and m/z 277.0→203.0, respectively. The method was validated over a linear range of 1.0–2400 ng/mL with a regression coefficient of 0.9974 and no endogenous interference. The intra‐ and inter‐batch precisions were within 8.29% and accuracy ranged from 100.3% to 108.1% for M090. The validated method was utilized to evaluate the in vitro metabolic stability and in vivo pharmacokinetics of M090 in rats. [ABSTRACT FROM AUTHOR]

• A series of pinane oxime derivatives were designed and synthesized from scratch. • Compound 11h showed antiviral activity with EC 50 value at the low micromolar level. • Compound 11h was identified to be a M2-S31N inhibitor. • The plausible binding mode of compound 11h was also discussed. Parasitic characteristics, mutations and resistance of influenza A virus make it difficult for current influenza antiviral drugs to maintain long-term effectiveness. Currently, to design non-adamantane compounds targeting the S31N mutant of M2 proton channel is a promising direction for the development of novel anti-influenza drugs. In our previous research, a pinanamine-based antiviral M090 was discovered to target hemagglutinin instead of M2, with its structure being highly similar to reported M2-S31N inhibitors. Herein, a series of pinane oxime derivatives were designed from scratch and evaluated for anti-influenza activity and their cytotoxicity in vitro. Utilizing a combination of structure-activity relationship analysis, electrophysiological assay and molecular docking, the most potent compound 11h , as a M2-S31N blocker, exhibited excellent activity with EC 50 value at the low micromolar level against both H3N2 and H1N1. No significant toxicity of 11h was observed. In addition, compound 11h was located tightly in the pore of the drug-binding site with the thiophene moiety facing down toward the C-terminus, and did not adopt a similar position and orientation as the reference inhibitor. [ABSTRACT FROM AUTHOR]

Despite intensive studies for decades, the common mechanistic correlations among the underlying pathology of diabetes mellitus (DM), its complications, and effective clinical treatments remain poorly characterized. High-quality diets and nutrition therapy have played an indispensable role in the management of DM. More importantly, tribbles homolog 3 (TRIB3), a nutrient-sensing and glucose-responsive regulator, might be an important stress-regulatory switch, linking glucose homeostasis and insulin resistance. Therefore, this review aimed to introduce the latest research progress on the crosstalk between dietary nutrition intervention and TRIB3 in the development and treatment of DM. This study also summarized the possible mechanisms involved in the signaling pathways of TRIB3 action in DM, in order to gain an in-depth understanding of dietary nutrition intervention and TRIB3 in the pathogenesis of DM at the organism level. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is an anthracycline chemotherapy drug used in the treatment of various types of cancer. However, short-term and long-term cardiotoxicity limits the clinical application of DOX. Currently, dexrazoxane is the only approved treatment by the United States Food and Drug Administration to prevent DOX-induced cardiotoxicity. However, a recent study found that pre-treatment with dexrazoxane could not fully improve myocardial toxicity of DOX. Therefore, further targeted cardioprotective prophylaxis and treatment strategies are an urgent requirement for cancer patients receiving DOX treatment to reduce the occurrence of cardiotoxicity. Accumulating evidence manifested that Sirtuin 1 (SIRT1) could play a crucially protective role in heart diseases. Recently, numerous studies have concentrated on the role of SIRT1 in DOX-induced cardiotoxicity, which might be related to the activity and deacetylation of SIRT1 downstream targets. Therefore, the aim of this review was to summarize the recent advances related to the protective effects, mechanisms, and deficiencies in clinical application of SIRT1 in DOX-induced cardiotoxicity. Also, the pharmaceutical preparations that activate SIRT1 and affect DOX-induced cardiotoxicity have been listed in this review. [ABSTRACT FROM AUTHOR]

Sangbaipi Decoction (SBPD) is an effective treatment for lung diseases caused by phlegm-heat obstruction according to Jingyue Quanshu , and soothes panting by purging the lung meridian. It is composed of anti-pyretic herbs (e.g., Scutellaria baicalensis Georgi and Coptis chinensis Franch.) and antitussive herbs (e.g., Cortex Mori and Armeniacae Semen Amarum). Therefore, we hypothesized that SBPD has therapeutic effects on lung injury caused by influenza virus. This study aimed to explore anti-influenza activity, active components, and mechanisms of SBPD. The anti-influenza activities of SBPD were determined in 48 h drug-treated MDCK cell model using CPE and plaque reduction assays, and 24 h drug-treated A549 cells using qRT-PCR. The in vivo efficacy of SBPD (1.0 g/kg/day and 0.5 g/kg/day) was evaluated in PR8 infected BALB/c mice. The chemical component was assessed through HPLC-Q-TOF MS/MS analysis. Network pharmacology was built via TCMSP, GeneCards, DisgeNet, OMIM, DrugBank databases, and Cytoscape software. Additionally, TOA, HI and NAI assays were employed to investigate impact on the virus replication cycle with different concentrations of SBPD (2.5 mg/mL, 1.25 mg/mL, or 0.625 mg/mL). In MDCK infected with viruses A/PR/8/34, A/Hong Kong/1/68, or A/California/4/2009, the IC 50 values of SBPD were 0.80 mg/mL, 1.20 mg/mL, and 1.25 mg/mL. In A549 cells, SBPD treatment reduced cytokine expression (e.g., TNF-α, IL-6, IL-1β) (p < 0.05). In PR8 infected BALB/c mice, SBPD improved the survival rate of infected mice, reduced lung index (p < 0.05), protected lung tissue from pathological damage, and regulated cytokine overexpression (p < 0.05). 29 components of SBPD were identified in SBPD treated mouse serum including some phytochemicals targeting influenza proteins. HI and NAI assays suggested the potential antiviral mechanism of SBPD through inhibition of HA and NA. This study is the first to demonstrate the anti-influenza and the anti-inflammatory effects of SBPD in vitro and in vivo. Its major anti-influenza phytochemicals were explored and its inhibitory effects on HA and NA protein were proved. It provides more options for anti-influenza drug discovery. [Display omitted] • We provide evidence that SBPDs have an inhibitory effect on influenza in vivo and vitro. • We show that the material basis for SBPD play against influenza virus. • We demonstrate that SBPD inhibits influenza HA and NA. • 29 blood components of SBPD (including baicalin, wogonin, kaempferol, etc.) may be involved in the antiviral effect of SBPD. [ABSTRACT FROM AUTHOR]

Sestrin2 (Sesn2) is a powerful anti-oxidant that can prevent acute and chronic diseases. The role of Sesn2 has been thoroughly reviewed in liver, nervous system, and immune system diseases. However, there is a limited number of reviews that have summarized the effects of Sesn2 in heart and vascular diseases, and very less literature-based information is available on involvement of Sesn2 in renal and respiratory pathologies. This review summarizes the latest research on Sesn2 in multi-organ stress responses, with a particular focus on the protective role of Sesn2 in cardiovascular, respiratory, and renal diseases, emphasizing the potential therapeutic benefit of targeting Sesn2 in stress-related diseases. [ABSTRACT FROM AUTHOR]

Bai Shao (Radix Paeoniae Alba , BS), the root of Paeonia lactiflora Pall., in ancient China was used for Wen Bing (Warm Disease) treatment. Wen Bing has the symptoms of influenza. Ethanol extract of the root has recently been shown to possess anti-influenza activity. However, the active compounds have not yet been identified. We showed that BS aqueous extract was potent in inhibiting influenza A virus in infected cells. We aimed to isolate the bioactive compounds and characterize the anti-influenza mechanism. Plaque reduction assay was performed for fractions isolated from BS. Hemagglutination inhibition assay and neuraminidase inhibition assay were performed to find the target protein. Molecular docking and reverse genetics were used to confirm the action site of gallic acid on the neuraminidase protein. We identified three tannin compounds gallic acid (GA), methyl gallate (MG) and pentagalloylglucose (PGG) in BS aqueous extract that could inhibit the replication of influenza A virus in MDCK cells. While only PGG was found to inhibit the influenza virus-induced hemagglutination of chicken erythrocytes, all three compounds significantly reduced the activity of the neuraminidase. The results from molecular docking and reverse genetics showed that GA interacted with Arg152 of neuraminidase protein. Three compounds GA, MG and PGG isolated from BS were found to inhibit influenza A virus in MDCK cells. GA interacts with amino acid Arg152 of the viral neuraminidase. Our study identified anti-influenza compounds of BS and demonstrated their antiviral mechanism, thus providing scientific evidence for using this herb for clinical treatment. Image 1 [ABSTRACT FROM AUTHOR]