A comprehensive review of the anticancer effects of decursin.

Cancer is a globally complex disease with a plethora of genetic, physiological, metabolic, and environmental variations. With the increasing resistance to current anticancer drugs, efforts have been made to develop effective cancer treatments. Currently, natural products are considered promising cancer therapeutic agents due to their potent anticancer activity and low intrinsic toxicity. Decursin, a coumarin analog mainly derived from the roots of the medicinal plant Angelica sinensis, has a wide range of biological activities, including anti-inflammatory, antioxidant, neuroprotective, and especially anticancer activities. Existing studies indicate that decursin affects cell proliferation, apoptosis, autophagy, angiogenesis, and metastasis. It also indirectly affects the immune microenvironment and can act as a potential anticancer agent. Decursin can exert synergistic antitumor effects when used in combination with a number of common clinical anticancer drugs, enhancing chemotherapy sensitivity and reversing drug resistance in cancer cells, suggesting that decursin is a good drug combination. Second, decursin is also a promising lead compound, and compounds modifying its structure and formulation form also have good anticancer effects. In addition, decursin is not only a key ingredient in several natural herbs and dietary supplements but is also available through a biosynthetic pathway, with anticancer properties and a high degree of safety in cells, animals, and humans. Thus, it is evident that decursin is a promising natural compound, and its great potential for cancer prevention and treatment needs to be studied and explored in greater depth to support its move from the laboratory to the clinic.

Targeting oxidative stress with natural products: A novel strategy for esophageal cancer therapy.

Esophageal cancer (ESC) is a malignant tumor that originates from the mucosal epithelium of the esophagus and is part of the digestive tract. Although the exact pathogenesis of ESC has not been fully elucidated, excessive oxidative stress is an important characteristic that leads to the development of many cancers. Abnormal expression of several proteins and transcription factors contributes to oxidative stress in ESCs, which alters the growth and proliferation of ESCs and promotes their metastasis. Natural compounds, including alkaloids, terpenes, polyphenols, and xanthine compounds, can inhibit reactive oxygen species production in ESCs. These compounds reduce oxidative stress levels and subsequently inhibit the occurrence and progression of ESC through the regulation of targets and pathways such as the cytokine interleukins 6 and 10, superoxide dismutase, the NF-+ACY-kappa+ADs-B/MAPK pathway, and the mammalian Nrf2/ARE target pathway. Thus, targeting tumor oxidative stress has become a key focus in anti-ESC therapy. This review discusses the potential of Natural products (NPs) for treating ESCs and summarizes the application prospects of oxidative stress as a new target for ESC treatment. The findings of this review provide a reference for drug development targeting ESCs. Nonetheless, further high-quality studies will be necessary to determine the clinical efficacy of these various NPs.

Abdominal massage for chronic constipation in the elderly: a systematic review and meta-analysis protocol.

INTRODUCTION: Chronic constipation (CC) is a highly prevalent health challenge that is particularly challenging to treat in elderly patients. Although lifestyle guidance and laxative therapy often yield positive outcomes, patients occasionally struggle with maintaining dietary control. Therefore, identifying an economical and safe alternative therapy to the existing treatment methods documented in the international literature is necessary. This systematic review and meta-analysis aims to evaluate the efficacy and safety of abdominal massage in elderly patients with CC to provide a basis for future mechanistic research. METHODS AND ANALYSIS: Electronic searches will be conducted to identify clinical randomised controlled trials in various databases, including Web of Science, PubMed, Cumulated Index to Nursing and Allied Health Literature, Cochrane Library, Embase, Airiti Library, Chinese National Knowledge Infrastructure Databases, Chinese Science and Technology Periodical Database (VIP), Chinese Biomedical Literature Database and Wan Fang Database. Relevant data will be extracted, and a meta-analysis will be conducted using Reviewer Manager V.5.4. Quality and risk assessments of the included studies will be performed, and the outcome indicators of the trials will be observed. This review will evaluate abdominal massage as a treatment option for relieving symptoms and improving quality of life in elderly patients with CC. Moreover, it will provide additional insights for clinical treatment and mechanistic studies. The search will be performed following the publication of this protocol (estimated to occur on 30 December 2023). ETHICS AND DISSEMINATION: As this is a literature review, ethics approval will not be required. We will disseminate the findings of this study to publications in peer-reviewed journals as well as presentations at relevant national and international conferences. PROSPERO REGISTRATION NUMBER: CRD42023408629.

Corynoline inhibits esophageal squamous cell carcinoma growth via targeting Pim-3.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is an aggressive and deadly malignancy characterized by late-stage diagnosis, therapy resistance, and a poor 5-year survival rate. Finding novel therapeutic targets and their inhibitors for ESCC prevention and therapy is urgently needed. METHODS: We investigated the proviral integration site for maloney murine leukemia virus 3 (Pim-3) protein levels using immunohistochemistry. Using Methyl Thiazolyl Tetrazolium and clone formation assay, we verified the function of Pim-3 in cell proliferation. The binding and inhibition of Pim-3 by corynoline were verified by computer docking, pull-down assay, cellular thermal shift assay, and kinase assay. Cell proliferation, Western blot, and a patient-derived xenograft tumor model were performed to elucidate the mechanism of corynoline inhibiting ESCC growth. RESULTS: Pim-3 was highly expressed in ESCC and played an oncogenic role. The augmentation of Pim-3 enhanced cell proliferation and tumor development by phosphorylating mitogen-activated protein kinase 1 (MAPK1) at T185 and Y187. The deletion of Pim-3 induced apoptosis with upregulated cleaved caspase-9 and lower Bcl2 associated agonist of cell death (BAD) phosphorylation at S112. Additionally, binding assays demonstrated corynoline directly bound with Pim-3, inhibiting its activity, and suppressing ESCC growth. CONCLUSIONS: Our findings suggest that Pim-3 promotes ESCC progression. Corynoline inhibits ESCC progression through targeting Pim-3.

Genome-Wide Identification of the NPR1-like Gene Family in Solanum tuberosum and Functional Characterization of StNPR1 in Resistance to Ralstonia solanacearum.

The NPR1 (nonexpressor of pathogenesis-related genes 1) gene is an activator of the systemic acquisition of resistance (SAR) in plants and is one of the central factors in their response to pathogenic bacterial infestation, playing an important role in plant disease resistance. Potato (Solanum tuberosum) is a crucial non-grain crop that has been extensively studied. However, the identification and analysis of the NPR1-like gene within potato have not been understood well. In this study, a total of six NPR1-like proteins were identified in potato, and phylogenetic analysis showed that the six NPR1-like proteins in Solanum tuberosum could be divided into three major groups with NPR1-related proteins from Arabidopsis thaliana and other plants. Analysis of the exon-intron patterns and protein domains of the six NPR1-like genes from potato showed that the exon-intron patterns and protein domains of the NPR1-like genes belonging to the same Arabidopsis thaliana subfamily were similar. By performing quantitative real-time PCR (qRT-PCR) analysis, we found that six NPR1-like proteins have different expression patterns in different potato tissues. In addition, the expression of three StNPR1 genes was significantly downregulated after being infected by Ralstonia solanacearum (RS), while the difference in the expression of StNPR2/3 was insignificant. We also established potato StNPR1 overexpression lines that showed a significantly increased resistance to R. solanacearum and elevated activities of chitinase, ß-1,3-glucanase, and phenylalanine deaminase. Increased peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) activities, as well as decreased hydrogen peroxide, regulated the dynamic balance of reactive oxygen species (ROS) in the StNPR1 overexpression lines. The transgenic plants activated the expression of the genes associated with the Salicylic acid (SA) defense response but suppressed the expression of the genes associated with Jasmonic acid (JA) signaling. This resulted in resistance to Ralstonia solanacearum.

Tripterygium wilfordii Hook.f. ameliorates paraquat-induced lung injury by reducing oxidative stress and ferroptosis via Nrf2/HO-1 pathway.

Paraquat (PQ) poisoning can induce acute lung injury and fibrosis and has an extremely high mortality rate. However, no effective treatments for PQ poisoning have been established. In this study, the potential efficacy of Tripterygium wilfordii Hook.f. (TwHF) in alleviating PQ-induced lung injury and fibrosis was investigated in a mouse model. Mice were randomly assigned to the control, PQ, PQ + TwHF1 (pretreatment before inducing poisoning), and PQ + TwHF2 (treatment after poisoning) groups. The mice in the PQ + TwHF1 group were pretreated with TwHF for 5 days before receiving one dose of PQ (120 mg/kg) and then received a daily oral gavage of the indicated dosages of TwHF until sacrifice. The mice in the PQ + TwHF2 group were treated with TwHF 2 h after PQ exposure until sacrifice. The pathological analysis and Fapi PET/CT showed that treatment with TwHF attenuated lung injury. And TwHF reduced pulmonary oxidative stress, as indicated by the reduction in, malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS) levels, as well as by the increase in superoxide dismutase (SOD) levels. Accordingly, the Perls DAB staining showed increased iron concentrations and western blotting revealed a decreased GPX4 expression after PQ exposure, as well as the mitigation of the overexpression of Nrf2 and HO-1 induced by PQ. In conclusion, our study demonstrated the potential of TwHF as a treatment for PQ-induced lung injury and fibrosis. The protective mechanism of this medicinal herb may involve the regulation of ferroptosis.

Combined Deflection Angle Classification: A Novel Typing System of Adult Femoral Neck Fracture.

OBJECTIVE: Femoral neck fracture (FNF) is a common clinical trauma with high mortality and disability rates. Furthermore, its incidence increases exponentially with increasing age. Existing classifications have some disadvantages. Thus, this study aimed to establish a novel typing system for FNF. METHODS: We retrospectively analyzed all adult patients with FNF admitted to our hospital between December 2015 and November 2017 for cannulated screw internal fixation. The study population was divided into the femoral varus offset group (VAR) and the valgus offset group (VAL). The data collected included sex, age, affected side, injury mode, body mass index, complications, pelvic incidence (PI), hip deflection angle (HDA), combined deflection angle (CDA), and neck shaft angle. Statistical analysis was conducted to determine the correlation between complications and deviation angles. A novel typing system was developed and compared with the Garden classification to detect its superiority. RESULTS: A total of 108 patients were recruited, with 59 patients in the VAR and 49 patients in the VAL groups. The incidence of complications in the VAR group was significantly higher than that in the VAL group (P < 0.05). Moreover, there were more male participants in the VAR group. Compared with the VAL group, the VAR group had significantly higher PI, HDA, and CDA (P < 0.05). The CDA classification (CDAC) was defined, with CDA as the main criterion and HDA as the supplementary criterion. Furthermore, there was a hierarchical correlation between the actual incidence of complications and the typing level, which was increased in CDAC but not in the Garden classification. This showed that CDAC was more accurate. CONCLUSION: A novel typing system, CDAC, for FNF was established, which was more accurate than the Garden classification. We suggest combining CDAC and Garden classifications for the preoperative diagnosis, treatment selection, and prognostic evaluation for patients with FNF.

Manual Therapy and Related Interventions for Carpal Tunnel Syndrome: A Systematic Review and Meta-Analysis.

Objective: Systematic review and meta-analysis to assess the efficacy of Manual therapy and related interventions in the treatment of carpal tunnel syndrome (CTS) based on Boston carpal tunnel questionnaire. Design: Systematic review and meta-analysis. Subjects: Carpal tunnel syndrome. Interventions: Manual therapy and related interventions versus other therapies or manual therapy and related interventions plus other therapies versus other therapies. Outcomes measures: Boston carpal tunnel questionnaire. Results: A total of 6 studies were included, including 211 cases in the manual therapy group and 211 cases in the control group. The quality of the included articles was high, and the results of meta-analysis showed that manual therapy and related interventions were superior in terms of improving the Boston carpal tunnel questionnaire Symptom Severity score in patients with CTS (standardised mean difference [SMD] -1.13, 95% CI -1.40 to -0.87), were superior to control groups in terms of improving the Boston carpal tunnel questionnaire functional capacity scale in patients with CTS (SMD -1.01,95% CI -1.24 to -0.77). Conclusion: The results of this meta-analysis suggested that manual therapy and related interventions were better than control groups in treating CTS. Manual therapy and related interventions could relieve the symptoms of patients with CTS and promote the recovery of hand function. Manual therapy and related interventions should be considered clinically effective methods for treating CTS. Registration: The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO; No. CRD 42020201389). Contribution of the Article: Manual therapy and related interventions could relieve the symptoms of patients with CTS and promote the recovery of hand function. Manual therapy and related interventions should be considered clinically effective methods for treating CTS.

Efficacy of Acupuncture Treatment for Postprandial Distress Syndrome: A Systematic Review and Meta-Analysis.

Objective: This systematic review and meta-analysis was conducted to assess the efficacy of acupuncture treatment for postprandial distress syndrome (PDS). Methods: Search the Web of Science, the Cochrane Library, PubMed, and Embase databases with acupuncture randomized controlled trials for the treatment of patients with PDS. Strictly according to inclusion and exclusion quality assessment standards, the qualified ones are used to study the optimum extraction and data by two independent reviewers. Stata 15.0 software was used for meta-analysis. Result: We initially identified 63 studies, of which five (1253 participants) were eventually included in our analysis. There were 643 cases in the experimental group and 610 cases in the control group. Acupuncture had a significant effect on the total therapeutic effect (OTE) at week 4 (OR 4.74, 95% CI 02.88-7.83, Z = 6.10, P = 0 < 0.05). Significantly improved NDI (Nepean dyspepsia index) scores of PDS patients at week 4 (SMD 0.61, 95% CI 0.48 to 0.74). Significantly improved NDI scores in PDS patients at week 16 (SMD 0.49, 95% CI 0.27 to 0.71). After acupuncture treatment, the SID (dyspepsia symptom index) score of PDS patients decreased significantly at week 4 (SMD-0.52, 95% CI -0.73 to -0.32) and week 16 (SMD-0.59, 95% CI -0.81 to -0.36). Postprandial satiety scores (SMD-0.63, 95% CI -0.76 to -0.50) and early satiety scores (SMD-0.51, 95% CI -0.64 to -0.37) were also significantly lower at week 4 after acupuncture. Conclusion: This study highlighted that the acupuncture could significantly improve the overall therapeutic effect of PDS patients, alleviate the symptoms of postprandial fullness and early satiety, and improve the quality of life of patients. Our results supported that acupuncture was an effective therapeutic strategy for postprandial distress syndrome.

Green tea-derived theabrownin suppresses human non-small cell lung carcinoma in xenograft model through activation of not only p53 signaling but also MAPK/JNK signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: According to the theory and practice of traditional Chinese medicine (TCM), the pathogenesis of lung carcinoma is associated with many syndromes, such as "sputum stasis", "cough", "lung fever", "lung toxin", and "hemoptysis", which should be removed for therapeutic purpose. Tea is not only a world-wide beverage, but also a TCM herb, possessing activities against the above syndromes. Recently, green tea extract exerted inhibitory effects on a variety of tumor cells. As a pigment active substance of green tea, theabrownin (TB) has been found to inhibit many cancer cells. AIM OF THE STUDY: This study focused on the efficacy and mechanism of TB on non-small cell lung cancer (NSCLC) cell lines. The in vivo efficacy of TB on p53-deficient NSCLC (H1299) cells and p53-wild type NSCLC (A549) cells NSCLC cells were determined, and its mechanism of action was explored. MATERIALS AND METHODS: In vivo, two lung cancer cell lines, H1299 (p53-deficient) and A549 (p53-wild type) were selected to establish xenograft models of larval zebrafish, respectively. For in vitro experiments, wound healing assay, DAPI staining, TUNEL assay, immunofluorescence assay, and flow cytometry were conducted in these two cell lines. RNA sequencing (RNAseq), real time PCR (qPCR) and Western blot (WB) were performed for the mechanism study. RESULTS: The in vivo results showed that TB significantly inhibited the H1299 and the A549 xenograft tumor growth in larval zebrafish (dosage ranged from 2.13 to 21.3 µg/ml). Wound healing assay results showed that TB suppressed the migration of H1299 cells. DAPI staining, TUNEL assay, and immunofluorescence assay results showed that TB inhibited the growth of H1299 cells by inducing apoptosis. RNAseq, qPCR and WB data showed that TB significantly up-regulated the MAPK/JNK pathway-related proteins (ASK-1, JNK and c-JUN) through phosphorylation activation, accompanying with down-regulation of the epithelial-mesenchymal transition (EMT)-associated genes (N-CADHERIN, SLUG, FIBROWNECTIN and ZEB1) and anti-apoptotic molecules (BCL-2), and up-regulation of the metastasis-related gene HSPA6 and the pro-apoptotic molecules (BIM, BAX, PARP, c-PARP, γ-H2A.X, c-CASP3, c-CASP8, c-CASP9, DDIT3 and DUSP8). CONCLUSION: This study determined the in vivo efficacy of green tea-derived TB on p53-deficient NSCLC (H1299) cells and p53-wild type NSCLC (A549) cells and clarified its p53-independent mechanism mediated by the activation of MAPK/JNK signaling pathway.

Tanshinol suppresses osteosarcoma by specifically inducing apoptosis of U2-OS cells through p53-mediated mechanism.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Salviae miltiorrhizae (also called Danshen in traditional Chinese medicine) is a famous herbal medicine, which has been frequently used to treat blood stasis syndrome including osteosarcoma (OS) in traditional Chinese medicine. Main components of Danshen have been assumed to exhibit anti-OS capacity. Nevertheless, tanshinol (TS, main component of Danshen)'s efficacy and mechanism in OS hasn't been clearly described ever since. This drew our attention, since OS is the most frequent primary bone carcinomas in children and adolescents, with a high incidence and fatality rate. Unfortunately, chemotherapy for OS has faced many clinical challenges due to the increasing chemoresistance and recurrence. This study was then designed to deeply explore TS's role in OS therapy. AIM OF THE STUDY: To explore the anti-OS efficacy and mechanism of TS, we conducted in vivo and in vitro experiments by using a zebrafish xenograft model and U2-OS cells. MATERIALS AND METHODS: CCK-8 assay, DAPI and γ-H2A.X immunofluorescence staining, and flow cytometry (apoptosis verification) were employed to determine the anti-proliferative and pro-apoptotic effects of TS. qPCR and Western blot were used to examine TS's molecular actions and mechanism on apoptosis of U2-OS cells. RESULTS: The in vivo data showed that TS significantly inhibited U2-OS tumor growth in larval zebrafish from 2 to 20 ng/mL. In vitro data indicated that TS exerted significant anti-proliferative and pro-apoptotic effects on U2-OS cells in a dose-dependent manner. Moreover, TS has no inhibitory effect on bMSCs, suggesting its safety on normal bone-forming cells. Molecular data illustrated that TS obviously activated the p53 signaling-related proteins (p-p53, Bax, CASP3, CASP9) and its upstream JNK (p-JNK, p-c-JUN) and ATM (p-ATM) signaling molecules through phosphorylation and cleavage, followed by up-regulation of the pro-apoptotic genes, NOXA, PUMA, TP53, BAX, and BIM, and down-regulation of Bcl-2 protein. CONCLUSION: In sum, TS specifically induced apoptosis of U2-OS cells by activating p53 signaling pathways, indicating TS as a promising candidate for OS treatment.

Demethylenetetrahydroberberine protects dopaminergic neurons in a mouse model of Parkinson's disease.

Parkinson's disease (PD) is a multifactorial disorder of the nervous system where a progressive loss of dopaminergic neurons exist. However, the pathogenesis of PD remains undefined, which becomes the main limitation for the development of clinical PD treatment. Demethylenetetrahydroberberine (DMTHB) is a novel derivative of natural product berberine. This study was aimed to explore the neuroprotective effects and pharmacological mechanism of DMTHB on Parkinson's disease using C57BL/6 mice. A PD model of mice was induced by administration of MPTP (20 mg·kg-1) and probenecid (200 mg·kg-1) twice per week for five weeks. The mice were administered with DMTHB daily by gavage at the dose of 5 and 50 mg·kg-1 for one- week prophylactic treatment and five-week theraputic treatment. The therapeutic effects of DMTHB were evaluated by behavior tests (the open field, rotarod and pole tests), immunohistochemical staining of tyrosine hydroxylase (TH), Nissl staining and biochemical assays. The molecular mechanisms of DMTHB on the key biomarkers of PD pathological states were analyzed by Western blot (WB) and qRT-PCR. DMTHB treatment alleviated the behavioral disorder induced by MPTP-probenecid. Nissl staining and TH staining showed that the damage of dopaminergic neurons in the substantia nigra was remarkably suppressed by DMTHB treatment. Western blot results showed that the ratio of Bcl-2/Bax and TH increased, but the level of α-synuclein (α-syn) was remarkably reduced, which indicated that the apoptosis of dopaminergic neurons in mice was significantly reduced. The protein phosphorylation of p-PI3K, p-AKT and p-mTOR also increased about 2-fold, compared with the model group. Furthermore, qRT-PCR results demonstrated that the mRNA levels of pro-inflammatory cytokines, IL-1ß and TNF-α, were reduced, but the level of anti-inflammatory cytokine IL-10 increased after DMTHB treatment. Finally, the cellular assay displayed that DMTHB was also a strong antioxidant to protect neuron cell line PC12 by scavenging ROS. In this study, we demonstrated DMTHB alleviates the behavioral disorder and protects dopaminergic neurons through multiple-target effects includubg anti-apoptotic, anti-inflammatory and antioxidant effects.

New diarylheptanoid dimers as GLP-1 secretagogues and multiple-enzyme inhibitors from Alpinia katsumadai.

Ten new diarylheptanoid dimers, katsumadainols C1 - C10 (1-10), were isolated from the seeds of Alpinia katsumada and elucidated by extensive spectroscopic methods, ECD calculations, and single-crystal X-ray diffraction. Their antidiabetic effects were evaluated by the stimulation of GLP-1 secretion in STC-1 cells and inhibition against four diabetes-related enzymes, GPa, α-glucosidase, PTP1B, and DPP4. Compounds 1-5 and 7-10 significantly stimulated GLP-1 secretion by 267.5-433.1% (25.0 µM) and 117.8-348.2% (12.5 µM). Compounds 1-4 exhibited significant inhibition on GPa with IC50 values of 18.0-31.3 µM; compounds 1-5 showed obvious inhibition on α-glucosidase with IC50 values of 6.9-18.2 µM; compounds 1-5 and 10 possessed PTP1B inhibitory activity with IC50 values ranging from 35.5 to 80.1 µM. This investigation first disclosed compounds 1-4 as intriguing GLP-1 secretagogues and GPa, α-glucosidase, and PTP1B inhibitors, which provided valuable clues for searching multiple-target antidiabetic candidates from Zingiberaceae plants.

Theoretical Exploring of a Molecular Mechanism for Melanin Inhibitory Activity of Calycosin in Zebrafish.

Tyrosinase is an oxidase that is the rate-limiting enzyme for controlling the production of melanin in the human body. Overproduction of melanin can lead to a variety of skin disorders. Calycosin is an isoflavone from Astragali Radix, which is a traditional Chinese medicine that exhibits several pharmacological activities including skin whitening. In our study, the inhibitory effect of calycosin on melanin production is confirmed in a zebrafish in vivo model by comparing with hydroquinone, kojic acid, and arbutin, known as tyrosinase inhibitors. Moreover, the inhibitory kinetics of calycosin on tyrosinase and their binding mechanisms are determined using molecular docking techniques, molecular dynamic simulations, and free energy analysis. The results indicate that calycosin has an obvious inhibitory effect on zebrafish pigmentation at the concentration of 7.5 µM, 15 µM, and 30 µM. The IC50 of calycosin is 30.35 µM, which is lower than hydroquinone (37.35 µM), kojic acid (6.51 × 103 µM), and arbutin (3.67 × 104 µM). Furthermore, all the results of molecular docking, molecular dynamics simulations, and free energy analysis suggest that calycosin can directly bind to the active site of tyrosinase with very good binding affinity. The study indicates that the combination of computer molecular modeling and zebrafish in vivo assay would be feasible in confirming the result of the in vitro test and illustrating the target-binding information.

Molecular Simulation Studies on the Interactions of Bilirubin at Different States with a Lipid Bilayer.

The unconjugated bilirubin (BR) may penetrate through the cell membrane and cause a severe cytotoxicity. However, the molecular mechanism underlying the penetration of BR into the cell membrane is still largely unknown. In this work, we systematically investigate the interaction of BR and a lipid bilayer under different conditions by using all-atom molecular dynamics simulations. It is found that BR at the Z,Z conformation can easily enter into the interior of the lipid bilayer due to its hydrophobicity. However, when BR transforms from the Z,Z conformation to the E,E conformation (after the blue-light emission), its penetration ability is greatly reduced (especially at its ionized state). This study may offer useful physical insights into the effect of phototherapy on the penetration behavior and the cytotoxicity of the unconjugated BR.

Polyoxygenated sesquiterpenoids from Salvia castanea and their potential anti-Alzheime's disease bioactivities.

Salvia castanea (Family Labiatae), a perennial fragrant herb with castaneous flowers, is mainly distributed in areas with an altitude of 2500-3750 m. The roots of this plant were used as a tea drink by local residents to strengthen physical health. The aim of present study was to acquire secondary metabolites of the ethanol extract obtained from the whole plant of S. castanea and to evaluate their potential anti-Alzheimer's disease. Six new sesquiterpene lactones, salcastanins A-F (1-6), together with three known guaiane-type sesquiterpenoids nubiol (7), nubdienolide (8), and nubenolide (9), were separated from the whole plant of S. castanea. The structures of these compounds were determined by HRESIMS and NMR experiments. The absolute configurations of 1-6 were ascertained by electronic circular dichroism (ECD) experiments. The humanized Caenorhabditis elegans AD pathological model was used to evaluate anti-Alzheimer's disease (AD) activities of 1-9. The results showed the compounds 1-3 and 7 significantly delayed AD-like symptoms of worm paralysis phenotype, which could be used as novel anti-AD candidates.

Nineteen New Flavanol-Fatty Alcohol Hybrids with α-Glucosidase and PTP1B Dual Inhibition: One Unusual Type of Antidiabetic Constituent from Amomum tsao-ko.

The dried fruits of Amomum tsao-ko were first revealed to have hypoglycemic effects on db/db mice at a concentration of 200 mg/kg. In order to clarify the antidiabetic constituents, 19 new flavanol-fatty alcohol hybrids, tsaokoflavanols A-S (1-19), were isolated and determined by extensive spectroscopic data and ECD calculations. Most of the compounds showed α-glucosidase and PTP1B dual inhibition, among which 1, 2, 6, 11, and 18 exhibited obvious activity against α-glucosidase with IC50 values of 5.2-9.0 µM, 20-35 times stronger than that of acarbose (IC50, 180.0 µM); meanwhile, 6, 10-12, and 19 were PTP1B/TCPTP-selective inhibitors with IC50 values of 56.4-80.4 µM, 2-4 times stronger than that of suramin sodium (IC50, 200.5 µM). Enzyme kinetics study indicated that compounds 1, 2, 6, and 11 were α-glucosidase and PTP1B mixed-type inhibitors with Ki values of 13.0, 11.7, 2.9, and 5.3 µM and 142.3, 88.9, 39.2, and 40.8 µM, respectively. Docking simulations proved the importance of hemiacetal hydroxy, the orientation of 3,4-dihydroxyphenyl, and the length of alkyl in binding with α-glucosidase and PTP1B.

External treatment of traditional Chinese medicine for COVID-19: A protocol for systematic review and meta-analysis.

BACKGROUND: There is a worldwide outbreak of COVID-19, as the number of patients increases. External treatment of traditional Chinese medicine includes acupuncture, massage, fire needle, cupping, and other alternative therapies. Currently, there are no relevant articles for systematic review. METHODS: We will search the randomized controlled trials related to the external treatment of traditional Chinese medicine (such as, acupuncture, massage, etc) and COVID-19 from inception to June 2020. The following database is our focus area: the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wan-Fang Database. All published randomized controlled trials in English or Chinese related to massage for COVID-19 will be included. Primary outcomes include the influence of external treatment of traditional Chinese medicine on the patients with COVID-19. Secondary outcomes include accompanying symptoms (such as myalgia, expectoration, stuffiness, runny nose, pharyngalgia, anhelation, chest distress, dyspnea, crackles, headache, nausea, vomiting, anorexia, diarrhea) disappear rate, negative COVID-19 results rate on 2 consecutive occasions (not on the same day), average hospitalization time, Clinical curative effect, and improved quality of life. RESULTS: The results will provide a high-quality synthesis of current evidence for researchers in this subject area. CONCLUSION: The conclusion of our study will provide evidence to judge whether external treatment of traditional Chinese medicine is an effective intervention on the patients with COVID-19. PROSPERO REGISTRATION NUMBER: CRD42020181336.

Acute generalized exanthematous pustulosis with airway mucosa involvement: A case report.

BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction characterized by sterile pustules on erythematous skin associated with fever and leukocytosis. The annual incidence of AGEP is estimated to be 1-5 cases per million. Cases of AGEP with oral mucosa involvement have been reported. However, reports of AGEP involving airway mucosa are limited. CASE SUMMARY: We report a 42-year-old woman with serious AGEP involving the airway mucosa. The patient initially developed fever and a small rash on her forehead and face. Over the next 2 d, she developed a diffuse, pustular rash over her trunk and legs. In addition, she complained of a cough with white foam-like sputum, chest tightness and dyspnea. Four days later, due to dyspnea, her mental status started to gradually deteriorate. She became more and more drowsy. Biopsies of the skin and airway mucosa suggested the diagnosis of AGEP. According to the European study of severe cutaneous adverse reactions group's scoring system, the patient scored +6 indicating a probable diagnosis of AGEP. She received intravenous methylprednisolone 120 mg/12 h for 3 d, and was eventually discharged in good condition. This patient had already experienced respiratory failure and airway mucosa involvement on admission; however, the clinicians had an insufficient understanding of AGEP. Glucocorticoid was administered for more than 10 d following onset of the disease, and her overall prognosis was satisfactory. CONCLUSION: This case represents a rare clinical feature of AGEP and an important finding for clinicians.

Clinical characteristics and outcomes of patients with hepatic veno-occlusive disease induced by Gynura segetum: A retrospective study.

OBJECTIVE: Hepatic veno-occlusive disease (HVOD) has attracted increasing attention in recent years due to its relationship with ingestion of Gynura segetum. The mortality of severe HVOD remains high due to the lack of specific therapies. The aim of the study was to delineate the clinical characteristics and outcomes and explore the potential prognostic factors of HVOD. METHODS: This was a single-center retrospective study. Eighty-nine HVOD patients were screened from the First Affiliated Hospital of Zhejiang University with an ingestion history of G. segetum before developing symptoms from January 2009 to May 2018. The enrolled patients were divided into the survivor and death groups according to the clinical follow-up that ended on September 1, 2019. The demographic variables and clinical data of the patients were recorded. A binary logistic regression analysis and receiver operating characteristic curve were conducted to identify the prognostic factors and assess the prognostic value for predicting death, and a survival analysis was performed to evaluate the clinical outcomes. RESULTS: Sixty-four patients were eligible for further analysis. Most patients showed abdominal distension and were positive for migrating dullness in the abdomen (P = 0.740 and P = 0.732, respectively). The patients who died had higher levels of model for end-stage liver disease score, and higher prothrombin time than those who survived (both P < 0.001). All HVOD patients in both the survival and death groups showed ascites with abnormal imaging presentations of the liver parenchyma and hepatic blood vessels. Unexpectedly, we found that hydrothorax was detected in 21 (65.63%) patients in the death group and 19 (59.38%) patients in the survivor group during hospitalization, which was rarely mentioned in previous studies. Furthermore, international normalized ratio (INR) and creatinine are found to be potential independent prognostic factors for predicting death. Six severe patients achieved clinical improvements and survived after liver transplantation. CONCLUSION: HVOD can be induced by the ingestion of G. segetum, and INR combined with creatinine has prognostic value for predicting death. Liver transplantation may be an effective treatment option for severe HVOD patients.