Valorization and protection of anthocyanins from strawberries (Fragaria×ananassa Duch.) by acidified natural deep eutectic solvent based on intermolecular interaction.

This study introduces an innovative approach for the valorization and protection of anthocyanins from 'Benihoppe' strawberry (Fragaria × ananassa Duch.) based on acidified natural deep eutectic solvent (NADES). Choline chloride-citric acid (ChCl-CA, 1:1) was selected and acidified to enhance the valorization and protection of anthocyanins through hydrogen bond. The optimal conditions (ultrasonic power of 318 W, extraction temperature of 61 °C, liquid-to-solid ratio of 33 mL/g, ultrasonic time of 19 min), yielded the highest anthocyanins of 1428.34 µg CGE/g DW. UPLC-Triple-TOF/MS identified six anthocyanins in acidified ChCl-CA extract. Stability tests indicated that acidified ChCl-CA significantly increased storage stability of anthocyanins in high temperature and light treatments. Molecular dynamics results showed that acidified ChCl-CA system possessed a larger diffusion coefficient (0.05 m2/s), hydrogen bond number (145) and hydrogen bond lifetime (4.38 ps) with a reduced intermolecular interaction energy (-1329.74 kcal/mol), thereby efficiently valorizing and protecting anthocyanins from strawberries.

Cytotoxic and anti-inflammatory constituents from roots of Hypericum beanii and the antitumor potential under the view of cancer-related inflammation.

Hypericum beanii, a traditional folk medicine plant, has been employed in the treatment of various inflammation-related diseases and has demonstrated promising potential as an herbal remedy for cancer. In this study, we isolated 29 compounds from the roots of H. beanii. We evaluated their cytotoxic effects on five human cancer cell lines, which revealed that the ethanol extract, along with compounds 4 and 14, exhibited significant cytotoxic activity. Additionally, we assessed their anti-inflammatory properties by measuring the inhibition of nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages. Our findings showed that the ethanol extract (IC50 = 7.41 ± 0.38 µg/mL), compound 4 (IC50 = 7.82 ± 0.42 µM), and compound 14 (IC50 = 3.05 ± 0.06 µM) displayed substantial anti-inflammatory activity. ELISA assays and qPCR analysis revealed that compounds 4 and 14 may exert their anti-inflammatory and antitumor effects by inhibiting the expression of iNOS, TNF-α, IL-1ß, and IL-6 mRNA, shedding light on their role in cancer-related inflammation.

Extracts of Thesium chinense inhibit SARS-CoV-2 and inflammation in vitro.

CONTEXT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still spreading rapidly. Relevant research based on the antiviral effects of Thesium chinense Turcz (Santalaceae) was not found. OBJECTIVE: To investigate the antiviral and anti-inflammatory effects of extracts of T. chinense. MATERIALS AND METHODS: To investigate the anti-entry and replication effect of the ethanol extract of T. chinense (drug concentration 80, 160, 320, 640, 960 µg/mL) against the SARS-CoV-2. Remdesivir (20.74 µM) was used as positive control, and Vero cells were used as host cells to detect the expression level of nucleocapsid protein (NP) in the virus by real-time quantitative polymerase chain reaction (RT-PCR) and Western blotting. RAW264.7 cells were used as an anti-inflammatory experimental model under lipopolysaccharide (LPS) induction, and the expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: The ethanol extract of T. chinense significantly inhibited the replication (half maximal effective concentration, EC50: 259.3 µg/mL) and entry (EC50: 359.1 µg/mL) of SARS-CoV-2 into Vero cells, and significantly reduced the levels of IL-6 and TNF-α produced by LPS-stimulated RAW264.7 cells. Petroleum ether (EC50: 163.6 µg/mL), ethyl acetate (EC50: 22.92 µg/mL) and n-butanol (EC50: 56.8 µg/mL) extracts showed weak inhibition of SARS-CoV-2 replication in Vero cells, and reduced the levels of IL-6 and TNF-α produced by LPS-stimulated RAW264.7 cells. CONCLUSION: T. chinense can be a potential candidate to fight SARS-CoV-2, and is becoming a traditional Chinese medicine candidate for treating COVID-19.

Patient Preferences for Preventive Healthcare During the COVID-19 Pandemic in a Large Integrated Health System.

The COVID-19 pandemic caused healthcare systems and patients to cancel or postpone healthcare services, particularly preventive care. Many patients still have not received these services raising concerns about the potential for preventable morbidity and mortality. At Sutter Health, a large integrated healthcare system in Northern California, we conducted a population-based email survey in August 2020 to evaluate perceptions and preferences about where, when, and how healthcare is delivered during the COVID-19 pandemic. In total, 3351 patients completed surveys, and 42.6% reported that they would "wait until they felt safe" before receiving a colonoscopy as compared to 22.4% for a mammogram. The doctor's office was the most common preferred location for receiving vaccines/shots (79.9%), though many also reported preferring an outdoor setting or in a car (63.7%). With over 40% of patients reporting that they would "wait until they feel safe" for a colonoscopy, healthcare systems could focus on promoting other evidence-based options such a fecal-occult blood test to ensure timely colon cancer screening.

Microbial and Nonvolatile Chemical Diversities of Chinese Dark Teas Are Differed by Latitude and Pile Fermentation.

Understanding the microbial and chemical diversities, as well as what affects these diversities, is important for modern manufacturing of traditional fermented foods. In this work, Chinese dark teas (CDTs) that are traditional microbial fermented beverages with relatively high sample diversity were collected. Microbial DNA amplicon sequencing and mass spectrometry-based untargeted metabolomics show that the CDT microbial ß diversity, as well as the nonvolatile chemical α and ß diversities, is determined by the primary impact factors of geography and manufacturing procedures, in particular, latitude and pile fermentation after blending. A large number of metabolites sharing between CDTs and fungi were discovered by Feature-based Molecular Networking (FBMN) on the Global Natural Products Social Molecular Networking (GNPS) web platform. These molecules, such as prenylated cyclic dipeptides and B-vitamins, are functionally important for nutrition, biofunctions, and flavor. Molecular networking has revealed patterns in metabolite profiles on a chemical family level in addition to individual structures.

Chronotherapy for morning blood pressure surge in hypertensive patients: a systematic review and meta-analysis.

BACKGROUND: The morning blood pressure surge (MBPS) is related to an exaggerated risk of cardiovascular diseases and mortality. With increasing attention on circadian change in blood pressure and extensive use of ambulatory blood pressure monitoring (ABPM), chronotherapy that administration of medication according to biological rhythm, is reported to improve cardiovascular outcomes. The aim of this study is to evaluate the influence of chronotherapy of antihypertensive drugs upon MBPS in hypertensive patients. METHODS: A search strategy was applied in Ovid MEDLINE, EMBASE, Cochrane (Wiley) CENTRAL Register of Controlled Trials, Cochrane Database of Systematic Reviews, and the Chinese Biomedical literature database. No language and date restrictions. Randomized controlled trials (RCT) assessing the efficacy of evening and morning administration of the same medications in adult patients with primary hypertension were included. RESULTS: A total of ten trials, comprising 1724 participants with a mean age of 61 and 51% female, were included in this study. Combined analysis observed significant reduction of MBPS (- 5.30 mmHg, 95% CI - 8.80 to - 1.80), night-time SBP (- 2.29 mmHg, 95% CI - 4.43 to - 0.15), night-time DBP (- 1.63 mmHg, 95 %CI - 3.23 to - 0.04) and increase in night blood pressure dipping (3.23%, 95% CI 5.37 to 1.10) in evening dosage compared with traditional morning dosage of blood pressure-lowering drugs. No significant difference was found in the incidence of overall adverse effects (RR 0.65, 95% CI 0.30 to 1.41) and withdrawal due to adverse effects (RR 0.95, 95% CI 0.53 to 1.71). CONCLUSIONS: Our study suggested that evening administration of antihypertensive medications exerted better blood pressure-lowering effect on MBPS compared with conventional morning dosage. Safety assessment also indicated that the evening regimen did not increase the risk of adverse events. However, endpoint studies need to be carried out to confirm the significance and feasibility of this treatment regimen in clinical practice.

Evaluation of thermally-modified calcium-rich attapulgite as a low-cost substrate for rapid phosphorus removal in constructed wetlands.

The cost-effective and geographically available substrates are vital for the design of constructed wetlands (CWs), especially the saturated subsurface flow CWs, which are deemed as an efficient way to remove the inlet-lake phosphorus concentrations. In this study, phosphorus removal of thermally-treated calcium-rich attapulgite (TCAP) with varied particle sizes (0.2-0.5 mm, 0.5-1 mm and 1-2 mm) was assessed using batch and long-term column experiments to evaluate its feasibility as a CWs substrate. The phosphorus-bound mechanism in TCAP was identified in various initial phosphorus concentrations. Batch studies indicated that more than 95% of P can be rapidly (<1 h) removed by TCAP from solution with a concentration of 20 mg P/L, and P sorption can be well fitted by a pseudo-second-order equation. The maximum P sorption capacity of TCAP was in the range of 4.46-5.99 mg P/g, and the availability of Ca2+ concentration might limit the P removal capacity of TCAP at high phosphorus concentrations. Both the P removal rate and capacities decreased with the increase of TCAP particle sizes. Column P removal experiments indicated that hydraulic retention time (HRT) exerts great influence on P removal performance and longer HRTs favor the dissolution of CaO in TCAP, consequently increasing the P removal rate. In a 150-day P removal experiment, TCAP removed an average of 93.1%-95.4% of the influent P with a HRT of eight hours. Both the batch and chemical extraction of the P fraction of TCAP showed that the P removed by TCAP was mainly through formation of Ca phosphate precipitation. However, the species of Ca-P precipitation formed might be varied in different phosphorus concentrations. All results indicated that TCAP can be a suitable substrate when used in CWs, and field experiments should be carried out to test its real P removal performance in the future.

Atorvastatin inhibits CD68 expression in aortic root through a GRP78-involved pathway.

PURPOSE: Glucose-regulated protein 78 (GRP78) is a chaperone protein in the endoplasmic reticulum (ER). Previous studies have suggested that statins favorably affect ER stress by upregulating GRP78. This study was designed to investigate whether the anti-atherosclerotic effect of atorvastatin is modulated by a GRP78-involved pathway. METHODS: Hamsters were made diabetic and randomly divided into a diabetic control group (DMC), a diabetic group with low-dose atorvastatin (DML, 2.5 mg/kg/day), and a diabetic group with high-dose atorvastatin (DMH, 5 mg/kg/day). Pathological examinations of the aortic root were performed, and the level of GRP78 and CD68 expression in the aortic root was detected by immunohistochemistry and RT-PCR analysis. In vitro THP-1 macrophages were treated with glucose and atorvastatin, and their GRP78 and CD68 protein expression levels were measured by Western blot. Next, with and without co-incubation with the GRP78 inhibitor, deoxynivalenol (DON), CD68 protein expression was again analyzed. RESULTS: We found that in vivo atorvastatin prominently limited the area of macrophage infiltration in the subendothelial spaces of the aortic root in the DML and DMH groups, and significantly inhibited CD68 expression (DML or DMH vs. DMC, all p < 0.001) and increased GRP78 expression (DML or DMH vs. DMC, p < 0.05 ~ 0.001). In vitro Western blot results showed that atorvastatin decreased CD68 and increased GRP78 protein expression in glucose-treated THP-1 macrophages, and the suppressing effect of atorvastatin on CD68 expression was almost abolished by co-incubation with the GRP78 inhibitor. CONCLUSIONS: Our results clearly showed that atorvastatin inhibited CD68 expression through GRP78 regulation, and that GRP78 could exert a protective effect in the early stages of atherosclerosis beyond being a chaperone protein, providing a new perspective into the anti-atherosclerosis mechanism of atorvastatin.

Simultaneous determination of calycosin-7-O-beta-D-glucoside, ononin, astragaloside IV, astragaloside I and ferulic acid in rat plasma after oral administration of Danggui Buxue Tang extract for their pharmacokinetic studies by liquid chromatography-mass spectrometry.

A sensitive and reliable high-performance liquid chromatography-mass spectrometry (HPLC-MS) was developed and validated for simultaneous quantification of five main bioactive components, i.e., calycosin-7-O-beta-D-glucoside, ononin, astragaloside IV, astragaloside I and ferulic acid in rat plasma after oral administration of Danggui Buxue Tang (DBT) extract. Plasma samples were extracted with solid-phase extraction (SPE) separated on an Inertsil ZORBAX C(18) column and detected by MS with electrospray ionization (ESI) interface in negative selective ion monitoring (SIM) mode. Calibration curves offered linear ranges of two orders of magnitude with r(2)>0.99. The method had the lower limit quantification of 0.55, 0.46, 1.07, 1.12 and 4.6 ng/mL for calycosin-7-O-beta-D-glucoside, ononin, astragaloside IV, astragaloside I and ferulic acid, respectively, with precision less than 10%. The RSD of intra- and inter-day variations ranged from 2.10% to 6.19% and 2.37% to 6.72%. This developed method was subsequently applied to pharmacokinetic studies of the five compounds in rats successfully.