[Determination of plasma protein binding rate of Shuganning Injection using equilibrium dialysis and UPLC-MS/MS].

Traditional Chinese medicine(TCM) compound preparations have complex compositions. As a widely used TCM injection, Shuganning Injection, its in vivo processes are not yet fully understood. Determining the plasma protein binding rate is of great significance for pharmacokinetic and pharmacodynamic studies. In this experiment, the equilibrium dialysis method combined with UPLC-MS/MS technology was used to determine the plasma protein binding rates of 10 components, including p-hydroxyacetophenone, caffeic acid, baicalein, oroxylin A, geniposide, baicalin, cynaroside, oroxylin A-7-O-ß-D-glucuronide, scutellarin, and hyperoside, in Shuganning Injection in rat and human plasma to provide a theoretical basis for further elucidating the in vivo processes of Shuganning Injection and guiding clinical medication. The results showed that, except for baicalein and geniposide, the plasma protein binding rates of the other eight components were higher in human plasma than in rat plasma, and there were interspecies differences. In human plasma, except for geniposide, caffeic acid, and baicalin, the plasma protein binding rates of the remaining seven components were above 80%, with baicalein and oroxylin A exceeding 90%. All components exhibit a high level of binding to plasma proteins, with the exception of geniposide.

Optimization of water washing for mitigation of 3-monochloropropane 1,2 diol ester in palm oil physical refining process.

The presence of 3-monochloropropane-1,2 diol ester (3-MCPDE) and glycidyl ester (GE) in processed palm oils is of concern, as these oils are widely used for edible purposes. The mitigation method studied here optimizes the removal of chloride through water washing of crude palm oil (CPO), to limit the formation of 3-MCPDE. The contaminant removal obtained via washing CPO supports the quantitative findings. By utilizing 5% water in the washing step, water-soluble chlorides in CPO are removed by up to 76%, resulting in a 71% reduction of 3-MCPDE to within statutory limits. In this study, a linear correlation was developed between the chloride and the corresponding 3-MCPDE with a correlation coefficient (R2) of 0.99. Using the correlations, 1.0 mg/kg of 3-MCPDE in refined, bleached and deodorized palm oil (RBDPO) will be obtained from CPO with 1.2 mg/kg chloride with 7% wash water usage. The study also showed minor GE reduction between 7 and 11% was attained after water washing.

Metal-coding assisted serological multi-omics profiling deciphers the role of selenium in COVID-19 immunity.

Uncovering how host metal(loid)s mediate the immune response against invading pathogens is critical for better understanding the pathogenesis mechanism of infectious disease. Clinical data show that imbalance of host metal(loid)s is closely associated with the severity and mortality of COVID-19. However, it remains elusive how metal(loid)s, which are essential elements for all forms of life and closely associated with multiple diseases if dysregulated, are involved in COVID-19 pathophysiology and immunopathology. Herein, we built up a metal-coding assisted multiplexed serological metallome and immunoproteome profiling system to characterize the links of metallome with COVID-19 pathogenesis and immunity. We found distinct metallome features in COVID-19 patients compared with non-infected control subjects, which may serve as a biomarker for disease diagnosis. Moreover, we generated the first correlation network between the host metallome and immunity mediators, and unbiasedly uncovered a strong association of selenium with interleukin-10 (IL-10). Supplementation of selenium to immune cells resulted in enhanced IL-10 expression in B cells and reduced induction of proinflammatory cytokines in B and CD4+ T cells. The selenium-enhanced IL-10 production in B cells was confirmed to be attributable to the activation of ERK and Akt pathways. We further validated our cellular data in SARS-CoV-2-infected K18-hACE2 mice, and found that selenium supplementation alleviated SARS-CoV-2-induced lung damage characterized by decreased alveolar inflammatory infiltrates through restoration of virus-repressed selenoproteins to alleviate oxidative stress. Our approach can be readily extended to other diseases to understand how the host defends against invading pathogens through regulation of metallome.

Aggressive variant prostate cancer: A case report and literature review.

BACKGROUND: Aggressive variant prostate cancer (AVPC) is a rare disease that progresses rapidly. The first-line treatment for AVPC is currently unknown. We examined a rare case of AVPC with rare brain and bladder metastases. A summary review of the mechanism of development, clinicopathological manifestations, associated treatments and prognosis of this disease is presented. CASE SUMMARY: The patient was diagnosed with prostate cancer (PCA), and was actively treated with endocrine therapy, radiotherapy, chemotherapy, and traditional Chinese medicine. Unfortunately, he was insensitive to treatment, and the disease progressed rapidly. He died five years after being diagnosed with PCA. CONCLUSION: We should reach consensus definitions of the AVPC and other androgen receptor-independent subtypes of PCA and develop new biomarkers to identify groups of high-risk variants. It is crucial to complete a puncture biopsy of the tumor or metastatic lesion as soon as possible in patients with advanced PCA who exhibit clinical features such as low Prostate-specific antigen levels, high carcinoembryonic antigen levels, and insensitivity to hormones to determine the pathological histological type and to create a more aggressive monitoring and treatment regimens.

Simultaneous mitigation of 3-monochloropropane 1,2 diol ester and glycidyl ester in edible oils: a review.

The rising concern about the presence of 3-monochloropropane 1,2 diol ester (3-MCPDE) and glycidyl ester (GE) in food has prompted much research to be conducted. Some process modifications and the use of specific chemicals have been employed to mitigate both 3-MCPDE and GE. Alkalisation using NaOH, KOH, alkali metals or alkaline earth metals and post sparging with steam or ethanol and short path distillation have shown simultaneous mitigation of 51-91% in 3-MCPDE and of 13-99% in GE, both contaminants achieved below 1000 µg/kg. Some of the mitigation methods have resulted in undesirable deterioration in other parameters of the refined oil. When the processed oil is used in food processing, it results in changes to 3-MCPDE and GE. Repeated deep frying above 170 °C in the presence of NaCl and baking at 200 °C with flavouring (dried garlic and onion), resulted in increased 3-MCPDE. Repeated frying in the presence of antioxidants (TBHQ, rosemary and phenolics) decreased 3-MCPDE in processed food. The GE content in foods tends to decline with time, indicating instability of GE's epoxide ring.

Biancaea decapetala (Roth) O.Deg. extract exerts an anti-inflammatory effect by regulating the TNF/Akt/NF-κB pathway.

BACKGROUND: Biancaea decapetala (Roth) O.Deg. (Fabaceae) is used to treat colds, fever, and rheumatic pain caused by inflammation. However, the mechanism underlying its anti-inflammatory properties remains unclear. PURPOSE: This study aimed to evaluate the anti-inflammatory activity of Biancaea decapetala extract (BDE) in vitro and in vivo and explore the possible underlying mechanism and potential targets. METHODS: The release of nitric oxide (NO) and inflammatory cytokines in LPS-stimulated RAW264.7 cells and rats were measured using Griess reagent and enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (H&E) staining was employed to examine the pathology of animal tissues. Transcriptome analysis was performed to screen the pathways related to BDE-mediated inhibition of inflammation, and the expression of related proteins was measured using real-time quantitative polymerase chain reaction (RT-qPCR), western blotting, ELISA, and immunofluorescence methods. Surface Plasmon Resonance (SPR) and the Drug Affinity Reaction Target Stability (DARTS) method were used to verify whether BDE binds to TNF-α target protein, while a L929 cell model and NF-κB gene reporter systematic method were used to investigate the inhibitory effect of BDE on the activity of TNF-α protein. RESULTS: BDE inhibited the expression of TNF-α, IL-1ß, IL-6, and NO in RAW264.7 cells and rats, and improved the pathological changes in lung tissue. RNA-seq showed that BDE may regulate the TNF/Akt/NF-κB pathway to inhibit inflammation onset. BDE significantly downregulated the mRNA expression of TNF-α, IL-6, IL-1ß, and that of relevant proteins, including TNF-α, p-p65, p-Akt, p-IκBα. Furthermore, BDE inhibited the nuclear translocation of NF-κB (p65) and the activation of the Akt pathway by SC79. The L929 cell model, luciferase reporter gene analysis, DARTS, and SPR experiments showed that BDE may bind to TNF-α and inhibit the TNF-α-NF-κB pathway. CONCLUSION: BDE may target TNF-α to inhibit the TNF/Akt/NF-κB pathway, thereby attenuating inflammation. These findings reveal the anti-inflammatory effects and mechanisms of BDE and provide a theoretical basis for the further development and utilization of BDE.

Mitigation of 3-monochloropropane 1,2 diol ester and glycidyl ester in refined oil - A review.

The 3-Monochloropropane-1, 2-diol ester (3-MCPDE) and glycidyl ester (GE) are formed at high processing temperatures with the presence of respective precursors. Both are potentially harmful to humans, causing adverse health impacts including kidney damage, reproductive problems, and increased risk of cancer. The presence of 3-MCPDE and GE in palm oil is of particular concern because of its widespread use by the food industry. There are a variety of methods for reducing 3-MCPDE and GE. For example, water washing eliminates mostly inorganic chlorides that, in turn, reduce the formation of 3-MCPDE. 3-MCPDE has also been reduced by up to 99% using combinations of methods and replacing stripping steam with alcohol-based media. Activated carbon, clay, antioxidants, potassium-based salts, and other post-refining steps have positively lowered GE, ranging from 10 to 99%. Several approaches have been successful in reducing these process contaminants without affecting other quality metrics.

[Simultaneous determination of eleven volatile components in Cinnamomi Oleum by GC-MS].

A gas chromatography-triple quadrupole mass spectrometry(GC-MS) method was established for the simultaneous determination of eleven volatile components in Cinnamomi Oleum and the chemical pattern recognition was utilized to evaluate the quality of essential oil obtained from Cinnamomi Fructus medicinal materials in various habitats. The Cinnamomi Fructus medicinal materials were treated by water distillation, analyzed using GC-MS, and detected by selective ion monitoring(SIM), and the internal standards were used for quantification. The content results of Cinnamomi Oleum from various batches were analyzed by hierarchical clustering analysis(HCA), principal component analysis(PCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) for the statistic analysis. Eleven components showed good linear relationships within their respective concentration ranges(R~2>0.999 7), with average recoveries of 92.41%-102.1% and RSD of 1.2%-3.2%(n=6). The samples were classified into three categories by HCA and PCA, and 2-nonanone was screened as a marker of variability between batches in combination with OPLS-DA. This method is specific, sensitive, simple, and accurate, and the screened components can be utilized as a basis for the quality control of Cinnamomi Oleum.

Quantification of six volatile oil constituents of Oleum Cinnamomi in rat plasma and multiple tissues using GC-MS and its application to pharmacokinetic and tissue distribution studies.

Oleum Cinnamomi is the essential oil obtained from the herb Fructus Cinnamomi which is used by the Hmong people in traditional medicine for the treatment of various diseases. At present, there are a variety of marketed preparations with it as the main medicine on the market. Information regarding the in vivo process of it is lacking, which has become a bottleneck restricting its development and utilization. In view of this, a GC-MS SIM analysis method was established for the simultaneous determination of six main volatile components [eucalyptol, p-cymene, 4-carvomenthenol, 4-isopropyl-2-cyclohexenone, α-terpineol, and 2-(4-Methylphenyl)-propan-2-ol] in plasma and ten tissues of rats to study their pharmacokinetic and distribution characteristics in vivo. The pharmacokinetic results showed that the t1/2 of each index was 0.41-1.66 h, Tmax was 0.16-0.68 h, Cmax was 13.66-2015.02 ng/mL, AUC0-t was 12.84-4299.00 h·ng/mL, CLZ/F was 1750.93-107013.11 mL/h/kg. This meant that the six components could be absorbed quickly, had a short residence time, and be eliminated quickly in the body. Among them, eucalyptol has the highest degree of absorption and a larger amount of entering the body. Moreover, the Cmax and AUC0-t of the six components increased correspondingly with the increase of the dose, indicating that the concentration of Oleum Cinnamomi in the rat plasma was dose-dependent. At different time points, the six components were widely distributed with uneven characteristics in the body. The six components mainly tend to be distributed in stomach, small intestine, and liver, followed by kidney, spleen, heart, and brain, and to a lesser extent in lung, skin, and muscle. And the six components were eliminated quickly in each tissue. The pharmacokinetic process and tissue distribution characteristics of Oleum Cinnamomi were expounded in this study, which can provide scientific theory for the in-depth development and guidance of clinical drug use of Oleum Cinnamomi, and at the same time provide a medicinal material basis for the in-depth development and utilization of Oleum Cinnamomi.

Manual Acupuncture at LI11, Local Points and Both for Knee Osteoarthritis: A Pilot Randomized Controlled Trial.

Objective: Knee osteoarthritis (KOA) is a common chronic degenerative joint disease, and acupuncture is an alternative therapy for KOA. This study aims to detect the effectiveness of acupuncture at LI11 in improving pain and function for KOA patients. Methods: A total of 108 patients with KOA were randomly allocated to Control Group (local points), Treatment Group A (LI11), and Treatment Group B (local points and LI11) with a treatment phase of 4 weeks and a follow-up phase of 4 weeks. Primary outcome was response rate. Secondary outcomes included Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and recurrence rate. Study was registered on Chinese Clinical Trial Registry (Registered number: ChiCTR2000034926). Results: The response rate in Treatment Group A, Treatment Group B, and Control Group was 71.43%, 85.29%, and 51.53%, respectively, at Week 4, and Treatment Group B was significantly higher than Control Group (difference[98.3% CI]: 33.86[0.135,0.543], P = 0.003). Although no significant difference was found, Treatment Group A had a better response rate compared with Control Group (difference[98.3% CI]: 20.00 [-0.072, 0.472], P = 0.086). For VAS and WOMAC, there were significant differences within 3 groups at Week 4 compared with the baseline. There was a significant improvement in VAS scores and WOMAC function and pain subscales at Week 4 in Treatment Group B compared with Control Group and Treatment Group A. Conclusion: LI11 is an effective point for patients with KOA, and it could be a selection for young acupuncturists and acupuncturists who work in rural areas; however, large-sample studies are necessary to further verify results in the future.

A study of the effect of reactive oxygen species induced by violet and blue light from oxytetracycline on the deactivation of Escherichia coli.

Oxytetracycline (OTC), a tetracycline antibiotic, is a broad-spectrum antibacterial agent. In this investigation, liquid chromatography-mass spectrometry (LC-MS) is utilized to determine the effects of blue light (λ = 448 nm) illumination (BLIA) and violet light (λ = 403 nm) illumination (VLIA) on conformational changes in OTC at pH 7.8. The photochemical effect of OTC that is exposed to BLIA and VLIA on the deactivation of Escherichia coli (E. coli) is studied. The deactivation of E. coli has an insignificant effect on treatment with OTC alone. OTC is relatively unstable under BLIA and VLIA illumination in an alkaline solution, and OTC has been shown to inactivate E. coli by generating reactive oxygen species (ROS). Less anionic superoxide radicals (O2•-) are generated from OTC that is treated with BLIA than that from VLIA treatment, so OTC is more efficient in inactivating E. coli under VLIA. Inactivation of reduction rates of 0.51 and 3.65 logs in E. coli are achieved using 0.1 mM OTC under BLIA for 120 min and VLIA for 30 min, respectively, under the same illumination intensity (20 W/m2). Two photolytic products of OTC (PPOs) are produced when OTC is exposed to BLIA and VLIA, with molecular ions at m/z 447 and 431, molecular formulae C21H22N2O9 and C21H22N2O8, and masses of 446.44 and 430.44 g/mol, respectively. The results show that when exposed to VLIA, OTC exhibits enhanced inactivation of E. coli, suggesting that the photochemical treatment of OTC is a potential supplement in a hygienic process.

A Web-Based Health Application to Translate Nutrition Therapy for Cardiovascular Risk Reduction in Primary Care (PortfolioDiet.app): Quality Improvement and Usability Testing Study.

BACKGROUND: The Portfolio Diet, or Dietary Portfolio, is a therapeutic dietary pattern that combines cholesterol-lowering foods to manage dyslipidemia for the prevention of cardiovascular disease. To translate the Portfolio Diet for primary care, we developed the PortfolioDiet.app as a patient and physician educational and engagement tool for PCs and smartphones. The PortfolioDiet.app is currently being used as an add-on therapy to the standard of care (usual care) for the prevention of cardiovascular disease in primary care. To enhance the adoption of this tool, it is important to ensure that the PortfolioDiet.app meets the needs of its target end users. OBJECTIVE: The main objective of this project is to undertake user testing to inform modifications to the PortfolioDiet.app as part of ongoing engagement in quality improvement (QI). METHODS: We undertook a 2-phase QI project from February 2021 to September 2021. We recruited users by convenience sampling. Users included patients, family physicians, and dietitians, as well as nutrition and medical students. For both phases, users were asked to use the PortfolioDiet.app daily for 7 days. In phase 1, a mixed-form questionnaire was administered to evaluate the users' perceived acceptability, knowledge acquisition, and engagement with the PortfolioDiet.app. The questionnaire collected both quantitative and qualitative data, including 2 open-ended questions. The responses were used to inform modifications to the PortfolioDiet.app. In phase 2, the System Usability Scale was used to assess the usability of the updated PortfolioDiet.app, with a score higher than 70 being considered acceptable. RESULTS: A total of 30 and 19 users were recruited for phase 1 and phase 2, respectively. In phase 1, the PortfolioDiet.app increased users' perceived knowledge of the Portfolio Diet and influenced their perceived food choices. Limitations identified by users included challenges navigating to resources and profile settings, limited information on plant sterols, inaccuracies in points, timed-logout frustration, request for step-by-step pop-up windows, and request for a mobile app version; when looking at positive feedback, the recipe section was the most commonly praised feature. Between the project phases, 6 modifications were made to the PortfolioDiet.app to incorporate and address user feedback. At phase 2, the average System Usability Scale score was 85.39 (SD 11.47), with 100 being the best possible. CONCLUSIONS: By undertaking user testing of the PortfolioDiet.app, its limitations and strengths were able to be identified, informing modifications to the application, which resulted in a clinical tool that better meets users' needs. The PortfolioDiet.app educates users on the Portfolio Diet and is considered acceptable by users. Although further refinements to the PortfolioDiet.app will continue to be made before its evaluation in a clinical trial, the result of this QI project is an improved clinical tool.

From GWAS to drug screening: repurposing antipsychotics for glioblastoma.

BACKGROUND: Glioblastoma is currently an incurable cancer. Genome-wide association studies have demonstrated that 41 genetic variants are associated with glioblastoma and may provide an option for drug development. METHODS: We investigated FDA-approved antipsychotics for their potential treatment of glioblastoma based on genome-wide association studies data using a 'pathway/gene-set analysis' approach. RESULTS: The in-silico screening led to the discovery of 12 candidate drugs. DepMap portal revealed that 42 glioma cell lines show higher sensitivities to 12 candidate drugs than to Temozolomide, the current standard treatment for glioblastoma. CONCLUSION: In particular, cell lines showed significantly higher sensitivities to Norcyclobenzaprine and Protriptyline which were predicted to bind targets to disrupt a certain molecular function such as DNA repair, response to hormones, or DNA-templated transcription, and may lead to an effect on survival-related pathways including cell cycle arrest, response to ER stress, glucose transport, and regulation of autophagy. However, it is recommended that their mechanism of action and efficacy are further determined.

[Pharmacokinetics of three index components of Periploca forrestii in rats by microdialysis combined with UPLC-MS/MS].

The present study established a UPLC-MS/MS method for the content determination of Periploca forrestii microdialysis samples and investigated the pharmacokinetics of three index components of P. forrestii in rats. The effects of flow rate and concentration of perfusate on the recovery rate were investigated by the concentration difference method(increment method and decrement method). The microdialysis samples at different time points were collected, and the concentrations of three index components were determined by UPLC-MS/MS. The actual drug concentrations were corrected with the in vivo recovery rate, and the pharmacokinetic parameters were calculated by WinNonlin 8.2. In the in vitro recovery test, the recovery rate measured by the increment method and the decrement method was inversely proportional to the flow rate and independent of the concentration. The pharmacokinetic parameter AUC_(0-t) values of 3-O-caffeoyl quinic acid, 4-O-caffeoyl quinic acid, and 5-O-caffeoyl quinic acid were(23 911.23±5 679.67),(16 688.43±3 448.45), and(9 677.02±1 606.74) min·µg·L~(-1), respectively. C_(max) values were(170.66±58.02),(121.61±48.14), and(69.69±18.23) µg·L~(-1), respectively. The UPLC-MS/MS method has the advantages of specificity, rapidity, high sensitivity, and accurate quantification. It can simultaneously determine the concentration of 3-O-caffeoyl quinic acid and other two index components in microdialysis samples and is suitable for the pharmacokinetics study of the three index components of P. forrestii in normal rats.

Involvement of Aquaporins in the Intense Pulsed Light-Enhanced Wound Healing in Diabetic Rats.

BACKGROUND AND OBJECTIVES: We previously demonstrated that intense pulsed light (IPL) irradiation prior to wounding improved the wound healing in rats with diabetes mellitus (DM). Also, we found that IPL upregulated the expression of aquaporin 3 (AQP3), a protein that is crucial for wound healing, in normal rats. This present study aimed to examine the involvement of AQPs in the IPL-enhanced wound healing in diabetic rats. STUDY DESIGN/MATERIALS AND METHODS: Streptozotocin was used to induce diabetes in Sprague-Dawley rats. Animals were divided into four groups: normal group, DM only group, DM rats with IPL treatment 2 weeks before wounding (DM + IPL-Pre group), and DM rats with concurrent IPL irradiation and wounding (DM + IPL-Con group). Wounds were created on the dorsal skin of rats. The expressions of AQP1, 3, 4, 7, and 9 in the pre-injured skin, periwound, and wound were determined. RESULTS: Among all the AQPs analyzed, only the expressions of AQP3 and AQP7 were significantly altered. Unirradiated diabetic rats showed much higher expression level of AQP3 in the regenerating skin compared with normal rats. IPL pretreatment, but not concurrent treatment, attenuated the expression toward the level detected in the normal wounds. In contrast, a lower expression level of AQP7 was noted in the regenerating skin of DM only rats and IPL pretreatment upregulated the expression to a level similar to that in the normal rats. CONCLUSION: The beneficial effect of IPL pretreatment on the wound healing in diabetic rats might involve a mechanism by which the expression of AQPs is regulated. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Effect of Foot Reflexology Intervention on Depression, Anxiety, and Sleep Quality in Adults: A Meta-Analysis and Metaregression of Randomized Controlled Trials.

OBJECTIVES: The aim of this study was to conduct a systematic review, meta-analysis, and metaregression to determine the current best available evidence of the efficacy and safety of foot reflexology for adult depression, anxiety, and sleep quality. METHODS: Electronic databases (PubMed, ClinicalKey, ScienceDirect, EMBASE, PsycINFO, and the Cochrane Library) were searched till August, 10, 2020, and the validity of the eligible studies was critically appraised. Randomized controlled trials comparing foot reflexology groups with control groups for adult depression, anxiety, and sleep quality were included. Twenty-six eligible studies were included to assess the effect of foot reflexology intervention on the reducing symptoms of depression and anxiety and improving quality of sleep, respectively, as the primary outcome. RESULTS: Twenty-six randomized controlled trials involving 2,366 participants met the inclusion criteria. The meta-analyses showed that foot reflexology intervention significantly improved adult depression (Hedges' g = -0.921; 95% CI: -1.246 to -0.595; P < 0.001), anxiety (Hedges' g = -1.237; 95% CI -1.682 to -0.791; P < 0.001), and sleep quality (Hedges' g = -1.665; 95% CI -2.361 to -0.970; P < 0.001). Metaregression reveals that an increase in total foot reflexology time (P = 0.002) and duration (P = 0.01) can significantly improve sleep quality. CONCLUSIONS: Foot reflexology may provide additional nonpharmacotherapy intervention for adults suffering from depression, anxiety, or sleep disturbance. However, high quality and rigorous design RCTs in specific population, along with an increase in participants, and a long-term follow-up are recommended in the future.

Separation of 3-Hydroxy-3-Methylglutaryl Flavonoid Glycosides from Oxytropis falcata Using 2D Preparative Chromatography.

Oxytropis falcata Bunge, known as "the King of Herbs" in Tibetan medicine, is used for treatment of hyperpyrexia, pain, wounds, inflammation and anthrax. However, it is difficult to isolate compound with high-purity from O. falcata because of its complexity. In this work, an efficient method was successfully established for the separation of 3-hydroxy-3-methylglutaryl (HMG) flavonoid glycosides from O. falcata by 2D preparative chromatography (2D-HPLC). An ODS C18 preparative column was used for the first-dimension preparation, and the XCharge C18 preparative column with different separation selectivity to the ODS C18 stationary phase was used for the second-dimension preparation. Four HMG flavonoid glycosides (oxytroflavosides A-D) and two flavonoid glycosides (oxytroflavosides F and G) were separated with purities over 98%. Their structures were elucidated by nuclear magnetic resonance spectroscopy. The 2D-HPLC method used in this study is effective for preparative separation of HMG flavonoid glycosides from O. falcata. Additionally, this method shows great potential for the separation of flavonoid glycosides from other plant extracts.

Chrysin alleviates imiquimod-induced psoriasis-like skin inflammation and reduces the release of CCL20 and antimicrobial peptides.

Psoriasis is a common non-contagious chronic inflammatory skin lesion, with frequent recurrence. It mainly occurs due to aberrant regulation of the immune system leading to abnormal proliferation of skin cells. However, the pathogenic mechanisms of psoriasis are not fully understood. Although most of the current therapies are mostly efficient, the side effects can result in therapy stop, which makes the effectiveness of treatment strategies limited. Therefore, it is urgent and necessary to develop novel therapeutics. Here, we investigated the efficacy of chrysin, a plant flavonoid, which we previously reported to possess strong antioxidant and anti-inflammatory effects, against psoriasis-like inflammation. Our results revealed that chrysin significantly attenuated imiquimod-induced psoriasis-like skin lesions in mice, and improved imiquimod-induced disruption of skin barrier. Moreover, the TNF-α, IL-17A, and IL-22-induced phosphorylation of MAPK and JAK-STAT pathways, and activation of the NF-κB pathway were also attenuated by chrysin pretreatment of epidermal keratinocytes. Most importantly, chrysin reduced TNF-α-, IL-17A-, and IL-22-induced CCL20 and antimicrobial peptide release from epidermal keratinocytes. Thus, our findings indicate that chrysin may have therapeutic potential against inflammatory skin diseases. Our study provides a basis for further investigating chrysin as a novel pharmacologic agent and contributes to the academic advancement in the field of Chinese herbal medicine.

The effects of correction of vitamin D deficiency on arterial stiffness: A systematic review and updated meta-analysis of randomized controlled trials.

It is unclear whether nutritional vitamin D supplementation in vitamin d-deficient persons improves arterial stiffness. To conduct a meta-analysis of the effects of the nutritional vitamin D therapy on arterial stiffness in adults with vitamin D deficiency, the Scopus, PUBMED, EMBASE, and Cochrane databases were searched for systematic reviews conducted up to October 5, 2018. Randomized clinical trials that compared nutritional vitamin D therapy with placebo in adults with vitamin D deficiency were eligible. Two reviewers independently evaluated eligibility of all retrieved studies based on titles and abstracts. Meta-analysis was performed using random effect or fixed effects model and inverse variance method was used to calculate the effect using standardized mean difference (SMD) and weighted mean difference. A leave-one-out method was used for sensitivity analysis. The main outcome was arterial stiffness, indicated by the carotid-femoral pulse wave velocity (PWV). We identified 237 records, of which 9 satisfied the inclusion criteria of the study. Our meta-analysis included relatively high-quality placebo-controlled randomized trials. In a random-effects model, nutritional vitamin D was associated with significant reductions in the pooled difference of PWV [(SMD: -0.29; 95 % CI: -0.51 to -0.06), p = 0.01; Cochran's Q test: chi2 = 21.85; df = 9; p = 0.009; I2 = 59 %; n = 909 from 9 studies]. All sensitivity analyses yielded similar results. Nutritional vitamin D supplementation significantly improved arterial stiffness (PWV) in several subgroups by correcting vitamin D deficiency, for a study duration of ≥4 months and a daily dose of vitamin D3 ≥ 2000 IU. The study indicated that the correction of vitamin D deficiency by nutritional vitamin D supplementation may improve arterial stiffness in vitamin d-deficient persons, especially by the correction of vitamin D deficiency with a daily dose of vitamin D3 ≥ 2000 IU. However, further studies are required to confirm this.