SESN1 functions as a new tumor suppressor gene via Toll-like receptor signaling pathway in neuroblastoma.

AIMS: Neuroblastoma (NB) is the most common extracranial solid tumor in children, with a 5-year survival rate of <50% in high-risk patients. MYCN amplification is an important factor that influences the survival rate of high-risk patients. Our results indicated MYCN regulates the expression of SESN1. Therefore, this study aimed to investigate the role and mechanisms of SESN1 in NB. METHODS: siRNAs or overexpression plasmids were used to change MYCN, SESN1, or MyD88's expression. The role of SESN1 in NB cell proliferation, migration, and invasion was elucidated. Xenograft mice models were built to evaluate SESN1's effect in vivo. The correlation between SESN1 expression and clinicopathological data of patients with NB was analyzed. RNA-Seq was done to explore SESN1's downstream targets. RESULTS: SESN1 was regulated by MYCN in NB cells. Knockdown SESN1 promoted NB cell proliferation, cell migration, and cell invasion, and overexpressing SESN1 had opposite functions. Knockdown SESN1 promoted tumor growth and shortened tumor-bearing mice survival time. Low expression of SESN1 had a positive correlation with poor prognosis in patients with NB. RNA-Seq showed that Toll-like receptor (TLR) signaling pathway, and PD-L1 expression and PD-1 checkpoint pathway in cancer were potential downstream targets of SESN1. Knockdown MyD88 or TLRs inhibitor HCQ reversed the effect of knockdown SESN1 in NB cells. High expression of SESN1 was significantly associated with a higher immune score and indicated an active immune microenvironment for patients with NB. CONCLUSIONS: SESN1 functions as a new tumor suppressor gene via TLR signaling pathway in NB.

Unveiling a Virulence-Regulating Mechanism in Aeromonas hydrophila: a Quantitative Exoproteomic Analysis of an AraC-Like Protein.

Bacterial AraC is a transcription factor family that initiates transcription by recruiting RNA polymerase to the promoter and directly regulating various bacterial phenotypes. It also directly regulates various bacterial phenotypes. However, how this transcription factor regulates bacterial virulence and affects host immunity is still largely unknown. In this study, deleting the orf02889 (AraC-like transcription factor) gene in virulent Aeromonas hydrophila LP-2 affected several important phenotypes, such as increasing biofilm formation and siderophore production abilities. Moreover, Δorf02889 also significantly decreased the virulence of A. hydrophila and has promising attenuated vaccine potential. To better understand the effects of orf02889 on biological functions, a data independent acquisition (DIA)-based quantitative proteomics method was performed to compare the differentially expressed proteins between Δorf02889 and the wild-type strain in extracellular fractions. The following bioinformatics analysis suggested that ORF02889 may regulate various metabolic pathways, such as quorum sensing and ATP binding cassette (ABC) transporter metabolism. Moreover, 10 selected genes from the top 10 decreasing abundances in proteomics data were deleted, and their virulence to zebrafish was evaluated, respectively. The results showed that ΔcorC, Δorf00906, and Δorf04042 significantly reduced bacterial virulence. Finally, the following chromatin immunoprecipitation and polymerase chain reaction (ChIP-PCR) assay validated that the promoter of corC was directly regulated by ORF02889. Overall, these results provide insight into the biological function of ORF02889 and demonstrate its inherent regulatory mechanism for the virulence of A. hydrophila.

Experiences of nurses working in nurse-led clinics in Traditional Chinese Medicine hospitals: A focused ethnographic study.

BACKGROUND: Traditional Chinese Medicine (TCM) nurse-led clinics (NLC) is an innovative working model in China, representing the specialization and extension of nurses' role. However, as a pioneer in TCM nursing, this new model of working is facing both opportunities and challenges because it is known little about the operational status of NLCs. AIMS: To explore the experiences of nurses who work in NLC in TCM hospitals. MATERIALS & METHODS: A focused ethnographic study was conducted in three TCM hospitals affiliated with Guangzhou University of Chinese Medicine. We interviewed eleven nurses in those hospitals and observed seven of them working with patients. We used snowball sampling for data collection including interview, non-participant observation and documents from medical records. All the data were processed as following steps: (a) coding for descriptive labels; (b) sorting for patterns; (c) identifying outliers or negative cases; (d) generalizing with construction and theories and (e) noting reflective remarks. RESULTS: Nurse-led clinics help nurses develop their skills and knowledge that are highly recognized by public since they meet the growing needs of patients and also relieve the workload of physicians in the hospitals. However, lack of specialization is still a major challenge in NLCs due to insufficiency of full-time staff with specialized education, nurse-led practice without standardized guidelines, restrictions on prescription right of nurses, and also inadequate support from hospitals. DISCUSSIONS: As a revolutionary innovation of working model for nurses in TCM hospitals, NLCs could improve quality of care and lead to a comprehensive promotion of nursing career. However, there are several challenges on providing high quality care for patients whilst improving educational development of nurses. This study suggests that nurses, hospital administration and the government should cooperate with each other to develop standard nursing programs for NLCs. CONCLUSIONS: It is imperative to identify nursing roles, collect available resources, and develop supportive policies and training programs to enhance the quality of NLCs.

Formation mechanism of the quarantine hotel booking intention of potential consumers.

In this paper, we investigated the quarantine hotel (QH) booking intention (BI) of potential consumers from a corporate social responsibility (CSR) perspective. Mixed methods were adopted to explore the formation mechanisms of QH BI of potential consumers when the COVID-19 pandemic recedes. In Study 1, we constructed a theoretical model of QH BI of potential consumers based on grounded theory and put forward research propositions. In Study 2, we tested the robustness of the model and identified the mediating effect through two situational experiments. The research results showed that: (1) Potential customers are more willing to book QHs than normal hotels (NHs). (2) Multiple mediating mechanisms are involved in the effect of the operation as a quarantine facility on BI of potential consumers, including "QH-corporate social responsibility (CSR)-customer trust (CT)-BI" and "QH-CSR-customer gratitude (CG)-BI." This research not only has theoretical significance for deepening and expanding social exchange theory and hotel CSR theories but also provides guidance for the participation of the hotel industry in the prevention and control of the COVID-19 pandemic and hotel marketing after the pandemic ends.

Metaphorical or Straightforward? Comparing the Effectiveness of Different Types of Social Media Advertising.

The existing studies have analyzed the advertising effects of metaphorical advertisements and straightforward adverts in traditional advertising media. However, their advertising effects on social media are still unclear. To address this issue, this study uses eye-tracking and questionnaires to examine two types of social media tourism advertising-metaphorical and straightforward in posts with both high and low popularity. This within-subject (n = 55) experiment was designed to examine the effects of social media tourism advertising types on visual attention and tourism intention and to identify the moderating role of post popularity based on the elaboration likelihood model (ELM). We found that advertising types had no significant effect on visual attention, but metaphorical advertisements increased tourism intention compared with straightforward adverts. Furthermore, we found that the level of post popularity moderated the effect of advertising types on visual attention. Specifically, metaphorical adverts in highly popular posts attracted more visual attention in the advertising text area and in the whole advert. Straightforward adverts in posts with low popularity attracted more visual attention in the advertising text area. This research advances the current literature by exploring the effects of social media tourism advertising types and has implications for managers deciding on strategies for social media tourism marketing.

An improved CUT&RUN method for regulation network reconstruction of low abundance transcription factor.

By improving the previous method of CUT&RUN, we developed D-CUT&RUN (DSP fixed CUT&RUN) for under-expressed transcription factor. High-quality data could be obtained for low expressed transcription factors using chemical crosslinkers (DSP) and reducing agent (DTT). We applied our D-CUT&RUN to detection of Bcl11b and Mycn binding sites in mammary epithelial progenitor cells. Pathway enrichment analysis results of Bcl11b target genes showed that Bcl11b was a regulatory factor involved in breast cancer and it could negatively regulate Wnt signaling pathway. Furthermore, the role of Bcl11b in breast cancer was mediated by catabolic process and stress-related pathway. Our research suggested that D-CUT&RUN could be used for low abundance transcription factor binding sites detection and Bcl11b could be a target for breast cancer treatment in the future.

Effectiveness of Aromatherapy on Ameliorating Fatigue in Adults: A Meta-Analysis.

Background: Fatigue is a common symptom in adults that may cause physical and psychological problems and reduce quality of life. Aromatherapy could possibly provide relief for those suffering from fatigue. Here, we evaluated the effect of aromatherapy on fatigue in adults. Methods: We searched the PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature, SinoMed, Wanfang, and Chinese Scientific Journal Database databases for randomized controlled trials of aromatherapy treatment for fatigue in adults from their inception to June 2021. Two reviewers searched independently, extracted the characteristics of the studies, and assessed the risk of bias using the Cochrane risk-of-bias tool and Stata v. 14.0. Results: Nineteen studies were included in this systematic review. Aromatherapy had a significant effect on fatigue (standardized mean difference -0.64, 95% confidence interval-1.14, -0.15, I2 94.4%, P < 0.001). Subgroup analysis according to aromatic type, substance, frequency, treatment duration, intervention, outcomes measurement, and population type showed that aromatherapy had a significantly greater effect in the intervention group, compared to the control group. Funnel plots and Egger's test indicated no significant publication bias. Conclusion: Our results suggest that aromatherapy ameliorates fatigue in adults who suffer from chronic diseases. A rigorous intervention program and larger randomized controlled trials are needed.

Omeprazole inhibits α-glucosidase activity and the formation of nonenzymatic glycation products: Activity and mechanism.

In this study, the inhibitory effect and mechanism of omeprazole on α-glucosidase and nonenzymatic glycation were investigated in vitro by using multi-spectroscopic methods and molecular docking. Enzyme kinetic results showed that omeprazole inhibited α-glucosidase in a reversible and noncompetitive manner (IC50= 0.595 ± 0.003 mM). The results from fluorescence quenching and thermomechanical analyses signified that omeprazole reduced the fluorescence intensity of α-glucosidase by forming an omeprazole-α-glucosidase complex primarily driven by hydrogen bonds. Molecular docking further confirmed that hydrogen bonds and hydrophobic forces were the major driving forces for omeprazole binding to α-glucosidase. The nonenzymatic glycation assays revealed that omeprazole had a moderate inhibition against the formation of fructosamine, dicarbonyl compounds, and advanced glycation end products (AGEs). This study provides a new inhibitor of both α-glucosidase and nonenzymatic glycation and provides a practicable candidate for treating diabetes and its complications.

The Beneficial Role of Auricular Point Pressure in Insomnia and Anxiety in Isolated COVID-19 Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) causes psychological distress and can have a negative impact on the general mental health and rehabilitation in affected patients under currently implemented isolation guidelines. Auricular point pressure (APP) as well-established technique in traditional Chinese medicine may help to relieve sleep disturbance and anxiety in COVID-19 patients. METHODS: During the early phase of the epidemic/pandemic, patients were enrolled in this study (02/2020 until 03/2020 n = 84). They were strictly isolated on specific wards at the Hubei Provincial Hospital of Integrated Chinese and Western Medicine in Hubei. The retrospective cohort study design included two groups. Group A patients were treated with an auricular point pressure (APP) in addition to standard intensive care medicine while Group B participants (No-APP) received routine nursing measures alone. Treatment outcome was measured using the St. Mary's Hospital Sleep Questionnaire (SMH) Score and the 7-Item Generalized Anxiety Disorder Scale (GAD-7). Both scores were measured in each patient at baseline and on the discharge day. RESULTS: The SMH score and sleep status changed in APP patients at the end of the treatment period when compared with No-APP patients (P < 0.01). APP-treated patients demonstrated lower GAD-7 scores than No-APP controls (P < 0.01). Further, no significant differences in safety or adverse events between the APP and No-APP groups were observed. CONCLUSION: The results from our snapshot study during the early phase of the SARS-CoV-2 epidemic/pandemic suggest that auricular point pressure could be a simple and effective tool to relieve insomnia and situational anxiety in hospitalized patients suffering from COVID-19 and kept under disconcerting conditions of isolation.

5-Methoxy-2-mercaptobenzimidazole as an efficient inhibitor on tyrosinase: Inhibitory activity and mechanism.

In this study, 5-methoxy-2-mercaptobenzimidazole (5-M-2-MB) was confirmed as an efficient tyrosinase inhibitor by methods of enzyme kinetic, fluorescence quenching, ANS-binding, thermodynamics, energy transfer, and molecular docking in combination. The results proved that 5-M-2-MB significantly inhibited the tyrosinase (IC50 = 60 ± 2 nM) in a reversible and competitive way with the Ki value of 80 ± 1 nM. It quenched the intrinsic fluorescence of tyrosinase through a static mechanism, and caused conformational change of the enzyme by increasing the hydrophobic region. Moreover, this compound could bind to tyrosinase and form 5-M-2-MB-tyrosinase complex by hydrogen bond and hydrophobic interaction. The interactions were generated between 5-M-2-MB and specific amino acid residues (Trp-358, Thr-308, Glu-356, and Asp-357) located on the A chain of tyrosinase. Therefore, this study would offer a theoretical foundation for developing the new tyrosinase inhibitor.

Topical therapy with rhubarb navel plasters in patients with chronic constipation: Results from a prospective randomized multicenter study.

ETHNOPHARMACOLOGICAL RELEVANCE: Constipation is a functional gastrointestinal disorder and one of the most prevalent conditions encountered in primary care settings. Rhubarb navel dressings have been used for more than 2,000 years in Chinese medicine to treat constipation. However, the effect of topical rhubarb administration has still not been well recognized and this strategy is not yet established as an evidence-based approach. AIM OF THE STUDY: In this study, we performed a prospective multicentric randomized controlled trial to evaluate the efficacy and safety of rhubarb navel plasters for patients with chronic constipation. MATERIALS AND METHODS: A total of 374 patients from six teaching hospitals were prospectively included between 09/2016 and 10/2017 in the study based on Rome III criteria. All participants were randomly assigned (1:1) into verum/placebo group and given either Rheum officinale rhubarb powder or a placebo flour stick on the navel for 6 h/day/8 days. Primary outcome measures were the Cleveland Constipation Score (CCS) for the feces condition and Bristol Stool Scale (BSS) for stool consistency and 24 h defecation frequency. RESULTS: The groups demonstrated no statistical differences in demographic data, clinical diagnoses and concomitant medication at baseline. In patients treated with the verum CCS was 5.61 (day 8, 95% CI 5.15-6.07) compared to 8.62 (95% CI 8.07-9.18) in placebo-treated controls (P < 0.001). The mean change of CCS at the end of treatment (day 8 versus [vs] day 0) was 6.04 in verum-treated vs 2.73 in placebo-treated controls (P < 0.001). Also 24 h defecation frequency (BSS) showed superior results (day 5: 0.84 vs 0.62, 95% CI 0.67-0.80, P < 0.001; day 6: 0.82 vs 0.60, 95% CI 0.64-0.78, P < 0.01 and day 8: 0.82 vs 0.60, 95% CI 0.64-0.78, P < 0.01) and better BSS type classification during treatment than controls (P < 0.05). No significant differences in adverse events between both groups became obvious. CONCLUSION: Rhubarb navel plaster administration over an 8-day-treatment period resulted in significantly improved bowel function as demonstrated by the CCS, 24 h defecating frequency and BSS. Our results suggest that rhubarb navel plasters represent a feasible, safe and efficient application route for the treatment of patients suffering from chronic constipation.

Efficacy of empowerment strategies for patients with hypertension: A systematic review and meta-analysis.

BACKGROUND: Cardiovascular disease has caused heavy health care burdens in many countries, and hypertension (HTN) is a well-known independent cardiovascular risk factor. OBJECTIVE: To assess the efficacy of empowerment strategies that affect systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), quality of life, and self-management behaviours for patients with hypertension. METHODS: A literature search of the Cochrane Library, PubMed, MEDLINE, Embase, Web of Science, and several Chinese medical databases was performed. Study screening, quality assessment, data extraction, and meta-analysis were conducted according to Cochrane standards. RESULTS: Eleven randomised controlled trials with 988 subjects were identified. Relative to control groups, the empowerment strategies showed significant decreases in SBP (the mean difference [MD] = 9.46, 95 % confidence interval [CI] = 6.36-12.55, p <  0.00001) and DBP (MD = 6.68, 95 % CI = 3.07-10.29, p =  0.0003). However, no significant difference was found in BMI (p = 0.05). Subgroup analysis showed significant differences in the improvement of both SBP and DBP among the various groups, regardless of the duration and type of interventions. DISCUSSION: Empowerment strategies can decrease both SBP and DBP in hypertension patients. However, its influence on patients' BMI, quality of life, and self-management behaviour remains unclear. PRACTICAL VALUE: Empowerment strategies are useful for controlling the blood pressure of hypertension patients.

Assessing differences in the response of forest aboveground biomass and composition under climate change in subtropical forest transition zone.

The subtropical forest transition zone in southern China is a typical transition zone with high coverage and diverse vegetation. Projected climate change will affect physiological processes of trees, which would consequently alter the forest aboveground biomass (AGB) and composition at broad spatial scales. However, spatially heterogeneous responses may also be shaped by climate change, succession, and harvesting in different forest habitats. The objectives of this study were to assess the changes in subtropical forest AGB and composition in response to climate change, while comparing the responses of two similar forest landscapes: Taihe County (TH) and Longnan County (LN). We used a loose-coupling of PnET-II with LANDIS-II to simulate changes in forest AGB and composition under climate change scenarios (Current climate, RCP2.6, RCP4.5, RCP6.0, and RCP8.5) with harvest disturbances. Our simulation results demonstrated that forest AGB and composition were significantly affected by climate change in both landscapes. Changes in forest AGB was mostly driven by succession and harvest, but climate change also greatly contribute to the variation in AGB of deciduous broad-leaved forests (DBF), and coniferous forests (CF). Moreover, a larger area of LN experienced biomass reduction compared to TH, specifically under the RCP8.5 scenario. Given our estimates of the response in forest AGB and composition under climate change scenarios across different periods, we recommend that the regional forest management should be localized and should consider the effects of climate change through time in their planning schemes.

Inhibitory kinetics and mechanism of rifampicin on α-glucosidase: Insights from spectroscopic and molecular docking analyses.

α-Glucosidase is a critical enzyme associated with diabetes mellitus, and the inhibitors of the enzyme play important roles in the treatment of the disease. In this study, the inhibitory effect and mechanism of rifampicin on α-glucosidase were investigated by multispectroscopic methods along with molecular docking technique. The results showed that rifampicin inhibited α-glucosidase activity prominently (IC50 = 135 ±â€¯1.2 µM) in a reversible and competitive-type manner. The fluorescence intensity of α-glucosidase was quenched by rifampicin through forming rifampicin-α-glucosidase complex in a static procedure. And the formation of the rifampicin-α-glucosidase complex was driven spontaneously by hydrophobic forces and hydrogen bonds. The results obtained from molecular docking further indicated that hydrophobic forces were formed between rifampicin and amino acid residues Phe 173, Pro151, and hydrogen bonds were generated by the interactions of rifampicin with residues Ser 180, Asn 414, Gly160, and Gly161 of α-glucosidase. Moreover, it was found that the binding of rifampicin to α-glucosidase could alter the conformation of the enzyme to make it steady, and the binding distance was estimated to be 1.02 nm. Therefore, this study confirmed a novel α-glucosidase inhibitor and possibly contributed to the improvement of newfangled anti-diabetic agent.

Changing rainfall frequency affects soil organic carbon concentrations by altering non-labile soil organic carbon concentrations in a tropical monsoon forest.

Soil stores a substantial proportion of carbon (C), making it the greatest terrestrial C pool and pivotal to stabilizing the global climate system. Rainfall amounts and regimes have been changing in many places, but effects of precipitation changes on soil organic C (SOC) stabilization are not completely understood. Considerable attention has been focused on the consequences of changes in rainfall amounts, with rainfall regimes having been less studied. This study was conducted in a tropical climax forest to clarify the effects of rainfall changes on SOC fractions, with permanganate oxidation and density fractionations employed to divide the labile and non-labile SOC fractions. Two rainfall manipulation treatments, i.e., increased rainfall frequency with the total rainfall amount unchanged (IRF) and decreased rainfall amount by 50% with rainfall frequency unaltered (DRA), were conducted for two years, with ambient rainfall (AR) as the control. As a result, the IRF treatment increased the SOC concentration that mainly originated from increases in the non-labile SOC content. Relative to the AR control, the DRA treatment did not change the total SOC concentration although the labile SOC concentration increased. This typically is due to a small proportion of the labile fraction to the total SOC content. Our results suggest that this water-rich mature forest is resistant to rainfall amount changes to a great extent (e.g., decrease of 50% as in the present study) from the SOC stabilization perspective, while changes in rainfall frequency could exert more notable effects.

Antityrosinase mechanism of omeprazole and its application on the preservation of fresh-cut Fuji apple.

Omeprazole was first evaluated for its antityrosinase activity and preservation of fresh-cut apples. The results obtained from enzymic analyses showed that the omeprazole inhibited tyrosinase activity (IC50 = 40 ±â€¯1.2 µM) with a reversible and competitive mechanism. Fluorescence quenching assays demonstrated that the interaction between omeprazole and tyrosinase was driven by hydrophobic forces and hydrogen bonds in a static procedure. Molecular docking further revealed that hydrogen bonds and hydrophobic forces were generated by omeprazole with the amino acid residues located in the A chain of tyrosinase. Moreover, the results from preservation assays showed that omeprazole could inhibit the activities of polyphenol oxidase (PPO) and peroxidase (POD), prevent the oxidation of total phenolics and flavonoid, thereby delay the browning of fresh-cut apples. Hence, this work identified a novel tyrosinase inhibitor and expands its feasible application as a food preservative.

Evaluation of the prognostic and physiological functions of death associated protein kinase 1 in breast cancer.

Death associated protein kinase 1 (DAPK1) is a notable serine/threonine kinase involved in the regulation of multiple cellular pathways, including apoptosis and autophagy. Although DAPK1 is usually considered to be a tumor suppressor, it was previously reported to promote the viability of p53 mutant cancer cell lines and possess physiological oncogenic functions in breast cancer. However, the ability of endogenous DAPK1 to suppress breast cancer cell mobility has not been assessed. In the present study, the prognostic function of DAPK1 in a Chinese patient cohort was evaluated, and no significant association was observed between DAPK1 expression and patient survival or lymph node metastasis. In order to investigate the physiological function of endogenous DAPK1, stable inducible DAPK1 knockdown MCF7 and MDA-MB-231 cell lines were established. Consistent with previous studies, endogenous DAPK1 only regulated cell viability in p53 mutant MDA-MB-231 cells. However, knockdown of DAPK1 did not significantly affect cell motility of either MCF7 or MDA-MB-231 cells. Altogether, these results further explored the function of endogenous DAPK1 in breast cancer and may shed light in understanding the molecular signaling pathways regulating the physiological function of DAPK1.

Antityrosinase and antioxidant properties of mung bean seed proanthocyanidins: Novel insights into the inhibitory mechanism.

This study investigated the structure, antioxidant activity, antityrosinase activity and mechanism of proanthocyanidins from mung bean seed [Vigna radiata (L.) Wilczek]. The structural composition were characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), electrospray ionization-full-mass spectrometry (ESI-Full-MS), and high-pressure liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS) techniques. The mung bean seed proanthocyanidins were composed of procyanidins, prodelphinidins, and their rhamnosides. According to enzyme kinetic analysis, these compounds were potent, reversible, and mixed-type inhibitors of tyrosinase. They inhibited the enzyme activity by interacting with enzyme as well as substrates. The results of molecular docking showed that the interaction between mung bean seed proanthocyanidins and tyrosinase was driven by hydrogen bond, hydrophobic and electrostatic interactions. In addition, mung bean seed proanthocyanidins were demonstrated as powerful antioxidants. Therefore, this study confirmed a novel tyrosinase inhibitor and would lay a scientific foundation for their utilization in pharmaceutical and food industries.

Condensed Tannins from Longan Bark as Inhibitor of Tyrosinase: Structure, Activity, and Mechanism.

In this study, the content, structure, antityrosinase activity, and mechanism of longan bark condensed tannins were evaluated. The findings obtained from mass spectrometry demonstrated that longan bark condensed tannins were mixtures of procyanidins, propelargonidins, prodelphinidins, and their acyl derivatives (galloyl and p-hydroxybenzoate). The enzyme analysis indicated that these mixtures were efficient, reversible, and mixed (competitive is dominant) inhibitor of tyrosinase. What's more, the mixtures showed good inhibitions on proliferation, intracellular enzyme activity and melanogenesis of mouse melanoma cells (B16). From molecular docking, the results showed the interactions between inhibitors and tyrosinase were driven by hydrogen bond, electrostatic, and hydrophobic interactions. In addition, high levels of total phenolic and extractable condensed tannins suggested that longan bark might be a good source of tyrosinase inhibitor. This study would offer theoretical basis for the development of longan bark condensed tannins as novel food preservatives and medicines of skin diseases.

Inhibition of tyrosinase by cherimoya pericarp proanthocyanidins: Structural characterization, inhibitory activity and mechanism.

In this study, the structure of proanthocyanidins purified from cherimoya (Annona squamosa) pericarp was analyzed by ESI-QTOF-MS and HPLC analyses. The result indicated that these compounds were procyanidin-type proanthocyanidins, consisting mainly of (epi)catechin units linked b y B-type interflavan bonds. The analyses of enzymology showed that the activities of monophenolase and diphenolase of tyrosinase could be powerfully inhibited by the proanthocyanidins. Further researches on the inhibition mechanism demonstrated that they were reversible and competitive inhibitors with the KI value of 27.1±3.1µg/mL. These inhibitors quenched the fluorescence of tyrosinase through a static quenching mechanism and spontaneously formed proanthocyanidins-enzyme complex. Fluorescence changes of proanthocyanidins in the presence of copper ion suggested that the interactions could reduce the fluorescence intensity of these polymers and the molecular docking analysis revealed that copper irons of the enzyme could be chelated by adjacent hydroxyl groups on the B ring of proanthocyanidins. Moreover, proanthocyanidins were proved to be efficient quencher of substrates. These results would lay scientific foundation for their farther application in food and medicine industry.