Fire acupuncture for plaque psoriasis case series.

OBJECTIVE: To investigate the clinical efficacy of fire acupuncture (FA) on plaque psoriasis (PP), exploring its suitable syndrome types, in order to achieve better therapeutic effects, accelerate the possibility of psoriasis skin lesion recovery, and provide assistance for clinical treatment. METHODS: A total of 8 patients with PP aged between 18 and 60 years were recruited and treated with FA once a week, and the lesion area and severity index (PASI), visual analog scale and pruritus were measured before, 2, 4 and 8 weeks after treatment and at the follow-up period (week 12), respectively. Visual analog scale, and dermoscopy were used for assessment. RESULTS: All patients showed improvement in pruritus after 1 FA treatment, and lesions were reduced to varying degrees after 2 weeks. Except for patients 5 and 8, who only achieved effective results due to severe disease, all other patients with psoriasis achieved significant results at 8 weeks after treatment. CONCLUSION: FA can significantly control the development of lesions, reduce the symptoms of PP lesions and pruritus, and help prevent psoriasis recurrence.

Activation of NRF2 by celastrol increases antioxidant functions and prevents the progression of osteoarthritis in mice.

Excessive oxidative stress impairs cartilage matrix metabolism balance, significantly contributing to osteoarthritis (OA) development. Celastrol (CSL), a drug derived from Tripterygium wilfordii, has recognized applications in the treatment of cancer and immune system disorders, yet its antioxidative stress mechanisms in OA remain underexplored. This study aimed to substantiate CSL's chondroprotective effects and unravel its underlying mechanisms. We investigated CSL's impact on chondrocytes under both normal and inflammatory conditions. In vitro, CSL mitigated interleukin (IL)-1ß-induced activation of proteinases and promoted cartilage extracellular matrix (ECM) synthesis. In vivo, intra-articular injection of CSL ameliorated cartilage degeneration and mitigated subchondral bone lesions in OA mice. Mechanistically, it was found that inhibiting nuclear factor erythroid 2-related factor 2 (NRF2) abrogated CSL-mediated antioxidative functions and exacerbated the progression of OA. This study is the first to elucidate the role of CSL in the treatment of OA through the activation of NRF2, offering a novel therapeutic avenue for arthritis therapy.

Traditional Chinese Exercises for Cardiovascular Diseases: A Bibliometric Analysis.

Traditional Chinese exercises (TCEs) have great value in the prevention and effective treatment of cardiovascular diseases (CVD). Our purpose in this study was to summarize present research trends and future directions regarding the link between TCEs and CVD by bibliometrics analysis. We searched the Web of Science Core Collection (WoSCC) for all original articles and reviews on TCEs for CVD published in English before August 7, 2022 using CiteSpace 5.8.R3 and Microsoft Excel 2019 software, and we displayed the results in the form of network maps, line graphs, and tables. We initially obtained 725 articles. Our results showed that the United States was the most influential country in this line of research, with Harvard University the most prolific institution in the field, and, Evidence-Based Complementary and Alternative Medicine was the most productive journal for these articles. The highest-frequency keywords in this research area were Tai Chi, exercise, blood pressure, quality of life, and older adult. Additionally, important research topics included heart rate variability, quality of life, meta-analysis, Baduanjin exercise, and breathing exercise. In addition, our results revealed that among all the TCEs, Tai Chi, Baduanjin, and Qigong emerged as the most extensively studied. However, it's important to note our exclusive focus on literature published in English may have led to our missing important results. Future investigators should broaden their search to include other databases and languages to present a still more comprehensive overview of this field.

Analysis of the Current Situation and Factors Influencing the Clinical Thinking Ability of Nursing Undergraduates.

Context: Clinical thinking encompasses the critical analysis, judgment, and decision-making pertaining to the existing or potential nursing problems of patients. It plays a pivotal role in effectively executing clinical nursing work in alignment with the prescribed nursing procedures. Proficient clinical thinking empowers nurses with the capability to identify, analyze, and resolve problems. Objective: The study intended to investigate the current situation of clinical thinking ability of nursing students and its influencing factors, so as to improve their clinical thinking ability. Methods: This was a cross-sectional study and the research took place at Taizhou University in Taizhou, Zhejiang province, China in the Faculty of Nursing. 143 full-time undergraduate nursing students at the University were selected for the cross-sectional survey, including a general questionnaire and a clinical thinking ability questionnaire for undergraduate nursing students. The respondents included nursing students in their sophomore, junior and senior years. Results: The survey results obtained between the first and the third year of study were included. Age of the participants ranged from 18 to 24 years, with an average age of 21.58 ± 2.45 years. The professional knowledge score of undergraduate nursing students in this survey was found to be 52.59 ± 13.93; ​the score of professional emotion was 14.21 ± 2.40; ​the score of professional will was 19.51 ± 2.15; ​the score of professional values was 14.40 ± 2.31; ​the professional skill score was 18.52 ± 2.06; the professional expectation was found to be 12.73 ± 1.30; and ​the total score was (99.26 ± 7.96). All dimensions and total scores of clinical ability of thinking among undergraduate nursing students in this survey were found to be average. Conclusions: Clinical thinking of undergraduate nursing students is found to be of a medium level, and the main influencing factors are grade and the satisfaction of teachers. Nursing colleges and practice hospitals should unite to adopt various ways to help nursing undergraduates cultivate and improve their clinical thinking ability.

Chemical compositions of Souliea vaginata (Maxim) Franch rhizome and their potential therapeutic effects on collagen-induced arthritis in rats.

ETHNOPHARMACOLOGICAL REVEVANCE: Rheumatoid arthritis (RA) is a global prevalent chronic autoimmune inflammatory disease and acceptable safety drugs are lack for its treatment. The rhizomes of Souliea vaginata (Maxim) Franch (SV) possess anti-inflammatory functions and are used as substitution of Coptis chinensis Franch. SV is also traditional Chinese medicine and Tibetan medicine for the treatment of conjunctivitis, enteritis and rheumatic. For searching complementary and alternative anti-RA drugs, it is necessary to characterize the potential anti-arthritic activity of SV and underlying mechanism involved. AIM OF THE STUDY: The aim of the study was to test the chemical compositions, evaluate the anti-arthritic effects and underlying mechanisms of SV. MATERIALS AND METHODS: The chemical compositions of SV were analyzed using liquid chromatography-ion trap-time of flight tandem mass spectrometry (LCMS-IT-TOF). From day 11 to day 31, SV (0.5, 1.0 and 1.5 g/kg body weight) and Tripterygium glycosidorum (TG, 10 mg/kg body weight) were administered orally to the CIA model rats once a day. Thickness of paw and body weights were measured once every two days from day 1 to day 31. Histopathological changes were measured using hematoxylin-eosin (HE) staining. Effects of SV on the levels of IL-2, TNF-α, IFN-γ, IL-4 and IL-10 in serum of CIA rats were measured by enzyme-linked immunosorbent assay (ELISA) kits. CD3+, CD4+, CD8+ and CD4+CD25+ T cells populations were measured using flow cytometric analysis. To evaluate the possible hepatotoxicity and nephrotoxicity, the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea (UREA) and creatinine (CREA) in CIA rats were also tested using blood auto analyzer. RESULTS: 34 compounds were identified from SV based on LCMS-IT-TOF, and triterpenoids are major anti-arthritic compositions. SV significantly relieved CIA rats' paw swelling without obvious influence on the body weight growth. SV decreased the serum levels of IL-2, TNF-α and IFN-γ in CIA rat, and increased the serum levels of IL-4 and IL-10. SV significantly increased and decreased the percentages of CD4+ and CD8+, with no significant effects on CD3+ in lymphocytes of CIA model rats. Moreover, SV simultaneously decreased thymus and spleen indexes and no hepatotoxicity and nephrotoxicity was observed after short-term treatment. CONCLUSION: These findings suggest that SV possesses preventive and therapeutic effect on RA by modulating the inflammatory cytokines, T-lymphocyte, thymus and spleen indexes and shows no hepatotoxicity and nephrotoxicity.

Effects of Zishen Yutai Pills on in vitro Fertilization-Embryo Transfer Outcomes in Patients with Diminished Ovarian Reserve: A Prospective, Open-Labeled, Randomized and Controlled Study.

OBJECTIVE: To explore the effects of Zishen Yutai Pills (ZYPs) on the quality of oocytes and embryos, as well as pregnancy outcomes in patients with diminished ovarian reserve (DOR) receiving in vitro fertilization-embryo transfer (IVF-ET). The possible mechanisms, involving the regulation of bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9), were also investigated. METHODS: A total of 120 patients with DOR who underwent their IVF-ET cycle were randomly allocated to 2 groups in a 1:1 ratio. The patients in the treatment group (60 cases) received ZYPs from the mid-luteal phase of the former menstrual cycle by using gonadotropin-releasing hormone (GnRH) antagonist protocol. The patients in the control group (60 cases) received the same protocol but without ZYPs. The primary outcomes were the number of oocytes retrieved and high-quality embryos. Secondary outcomes included other oocyte or embryo indices as well as pregnancy outcomes. Adverse events were assessed by comparison of the incidence of ectopic pregnancy, pregnancy complications, pregnancy loss, and preterm birth. Contents of BMP15 and GDF9 in the follicle fluids (FF) were also quantified with enzyme-linked immunosorbent assay. RESULTS: Compared with the control group, the numbers of oocytes retrieved and high-quality embryos were significantly increased in the ZYPs group (both P<0.05). After treatment with ZYPs, a significant regulation of serum sex hormones was observed, including progesterone and estradiol. Both hormones were up-regulated compared with the control group (P=0.014 and 0.008), respectively. No significant differences were observed with regard to pregnancy outcomes including implantation rates, biochemical pregnancy rates, clinical pregnancy rates, live birth rates, and pregnancy loss rates (all P>0.05). The administration of ZYPs did not increase the incidence of adverse events. The expressions of BMP15 and GDF9 in the ZYPs group were significantly up-regulated compared with the control group (both P<0.05). CONCLUSIONS: ZYPs exhibited beneficial effects in DOR patients undergoing IVF-ET, resulting in increments of oocytes and embryos, and up-regulation of BMP15 and GDF9 expressions in the FF. However, the effects of ZYPs on pregnancy outcomes should be assessed in clinical trials with larger sample sizes (Trial reqistration No. ChiCTR2100048441).

[Effect of electroacupuncture at back-shu points of five zang on fatigue status and cortical excitability in chronic fatigue syndrome].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at back-shu points of five zang on fatigue status, quality of life and motor cortical excitability in patients with chronic fatigue syndrome (CFS), so as to explore the possible mechanism of EA for CFS. METHODS: A total of 72 patients with CFS were randomized into an EA group (36 cases, 4 cases dropped off) and a sham EA group (36 cases, 3 cases dropped off). In the EA group, EA at Ganshu (BL 18), Xinshu (BL 15), Pishu (BL 20), Feishu (BL 13) and Shenshu (BL 23) was adopted, with continuous wave, 2 Hz in frequency. In the sham EA group, sham EA at non-acupoints (1.5-2.0 cm lateral to back-shu points of five zang) was applied, with shallow needling, and no current was connected. The treatment in the both groups was 20 min each time, once every other day, 2 weeks as one course, 3 courses were required. Before and after treatment, the scores of fatigue scale-14 (FS-14) and the MOS 36-item short form health survey (SF-36) were observed, and cortical excitability (the resting motor threshold [RMT], amplitude of motor-evoked potential [MEP-A] and latency of motor-evoked potential [MEP-L]) was detected in the two groups. RESULTS: After treatment, the physical fatigue score, mental fatigue score and total score of FS-14, as well as RMT of motor cortex in the EA group were decreased compared with those before treatment (P<0.01), the physical fatigue score and total score of FS-14 in the sham EA group were decreased compared with those before treatment (P<0.05); each item score and total score of FS-14 and RMT of motor cortex in the EA group were lower than those in the sham EA group (P<0.01, P<0.05). After treatment, each item score and total score of SF-36 and MEP-A of motor cortex in the EA group were increased compared with those before treatment (P<0.01), which were higher than those in the sham EA group (P<0.01, P<0.05). CONCLUSION: EA at back-shu points of five zang can effectively improve the fatigue status and quality of life in patients with CFS, its mechanism may be related to the up-regulating excitability of cerebral motor cortex.

Effects and mechanisms of 6-hydroxykaempferol 3,6-di-O-glucoside-7-O-glucuronide from Safflower on endothelial injury in vitro and on thrombosis in vivo.

Background: The florets of Carthamus tinctorius L. (Safflower) is an important traditional medicine for promoting blood circulation and removing blood stasis. However, its bioactive compounds and mechanism of action need further clarification. Objective: This study aims to investigate the effect and possible mechanism of 6-hydroxykaempferol 3,6-di-O-glucoside-7-O-glucuronide (HGG) from Safflower on endothelial injury in vitro, and to verify its anti-thrombotic activity in vivo. Methods: The endothelial injury on human umbilical vein endothelial cells (HUVECs) was induced by oxygen-glucose deprivation followed by reoxygenation (OGD/R). The effect of HGG on the proliferation of HUVECs under OGD/R was evaluated by MTT, LDH release, Hoechst-33342 staining, and Annexin V-FITC apoptosis assay. RNA-seq, RT-qPCR, Enzyme-linked immunosorbent assay and Western blot experiments were performed to uncover the molecular mechanism. The anti-thrombotic effect of HGG in vivo was evaluated using phenylhydrazine (PHZ)-induced zebrafish thrombosis model. Results: HGG significantly protected OGD/R induced endothelial injury, and decreased HUVECs apoptosis by regulating expressions of hypoxia inducible factor-1 alpha (HIF-1α) and nuclear factor kappa B (NF-κB) at both transcriptome and protein levels. Moreover, HGG reversed the mRNA expression of pro-inflammatory cytokines including IL-1ß, IL-6, and TNF-α, and reduced the release of IL-6 after OGD/R. In addition, HGG exhibited protective effects against PHZ-induced zebrafish thrombosis and improved blood circulation. Conclusion: HGG regulates the expression of HIF-1α and NF-κB, protects OGD/R induced endothelial dysfunction in vitro and has anti-thrombotic activity in PHZ-induced thrombosis in vivo.

Chemical Constituents of Cyperus esculentus Leaves and the Protective Effect against Agricultural Fungicide-Induced Hepatotoxicity.

Cyperus esculentus is cultivated as a crop plant due to its edible and oily tubers (tiger nut). However, little is known about the phytochemicals and bioeffects of the leaves. This study was conducted to identify and quantify the chemical constituents of C. esculentus leaves and evaluate their bioactivities. By liquid chromatography-mass spectrometry, 30 compounds including flavan-3-ols, caffeic acid derivatives, and flavones, were identified from the leaves. The quantitative analysis revealed that gallocatechin (8), procyanidin B1 (15), catechin (16), chlorogenic acid (19), orientin (30), and luteolin 7-O-glucuronide (31) are the major chemical constituents of C. esculentus leaves. The contents of these six chemical constituents in the leaves collected in September in Hohhot, China, reached to 1460.85±7.66, 10178.77±302.65, 1048.35±17.37, 1722.15±26.13, 5318.62±277.16, and 1526.54±11.95 µg, respectively, in one gram of the dried leaves. The leaf extract (CELE) showed strong antioxidant activity in vitro, with compounds 8, 15, and 19 contributing the most. CELE showed significant protection against the agricultural fungicide tebuconazole-induced developmental toxicity and hepatotoxicity in zebrafish.

Extracting Total Anthocyanin from Purple Sweet Potato Using an Effective Ultrasound-Assisted Compound Enzymatic Extraction Technology.

This study aimed to develop an effective technique for extracting total anthocyanins from purple sweet potato (Mianzishu 9) (PSP9) by ultrasound-assisted compound enzymatic extraction (UAEE). Single-factor experiments, Plackett-Burman experimental design, and response surface methodology were utilized for optimizing extraction conditions, and the antioxidant activities were evaluated. Anthocyanins were also measured using an ultra-performance liquid chromatograph linked to a mass spectrometer (UPLC-MS). The maximum yield of total anthocyanins was 2.27 mg/g under the following conditions: the ethanol concentration was 78%, the material-to-liquid ratio was 1:15 g/mL, the enzyme ratio (cellulase: pectinase: papain) was 2:2:1 and its hydrolysis was at 41 °C, pH = 4.5, 1.5 h, the ultrasonication was at 48 °C and conducted twice for 20 min each time. In addition to higher yield, anthocyanins extracted from purple sweet potato by UAEE showed great ability to scavenge DPPH (IC50 of 0.089 µg/mL) and hydroxyl radicals (IC50 of 100.229 µg/mL). Five anthocyanins were found in the purple sweet potato extract from UAEE. Taken together, the ultrasound-assisted compound enzymatic method can rapidly and effectively extract anthocyanins with greater antioxidant capacity from purple sweet potato.

Bibliometric and visualized analysis of electroacupuncture in the past 10 years.

BACKGROUND: There are many studies that have interrogated the evolution and use of electroacupuncture (EA). We aimed to evaluate the research status, cooperation and development of EA in the past 10 years. METHODS: We obtained data on the EA from the Web of Science core collection database. CiteSpace 5.7. R1 software was used to assess research cooperation through analysis of authors, institutions and countries. In addition, keyword cluster analysis, references and burst detection were analyzed to explore research hotspots and trends in the field of EA. RESULTS: We included a total of 3019 citing literature and 78,235 cited literature for analysis. The data showed that there has been a rise in the global number of EA studies in the past decade. Besides, the data demonstrated that China has made outstanding contribution in the development of EA. Whereas there is inter-agency cooperation in China, there is less cooperation with other countries. In addition, we showed frequent use of keywords such as "expression", "stimulation", or "pain". Besides, neuroscience was the main research area, followed by general medicine and oncology. Furthermore, with the improved research methods and technologies, there is enhanced overall quality of the studies. CONCLUSION: Taken together, our findings demonstrate a steady increase in the studies involving EA. However, the studies are unevenly distributed among countries and thus there is need for closer international cooperation.

Effects of natural antioxidants on the oxidative stability of Eucommia ulmoides seed oil: Experimental and molecular simulation investigations.

Eucommia ulmoides seed oil with high health potential is prone to oxidative rancidity due to its rich unsaturated fatty acids. In this work, three natural antioxidants were selected for exploring the oxidation resistance of the oil compared with the common synthetic antioxidant BHT. Antioxidant activity and its dispersion and migration as well as oxygen barrier performance were predicted via the bond dissociation enthalpy (BDE), mean square displacement (MSD), binding energy (Ebinding) and permeability coefficient (S). The predicted comprehensive performance is as follows: myricetin > epicatechin > caffeic acid > BHT. Free radical scavenging assay and Rancimat assay confirmed the antioxidant activity and protective effect on oil. That is the protective effect of three natural antioxidants on Eucommia ulmoides seed oil is better than BHT and myricetin shows the optimal comprehensive performance. The induction period of myricetin/lipid system increased 164.5% compared with the control. The experimental results are in good consistent with the simulation predictions.

(-)-Naringenin 4',7-dimethyl Ether Isolated from Nardostachys jatamansi Relieves Pain through Inhibition of Multiple Channels.

(-)-Naringenin 4',7-dimethyl ether ((-)-NRG-DM) was isolated for the first time by our lab from Nardostachys jatamansi DC, a traditional medicinal plant frequently used to attenuate pain in Asia. As a natural derivative of analgesic, the current study was designed to test the potential analgesic activity of (-)-NRG-DM and its implicated mechanism. The analgesic activity of (-)-NRG-DM was assessed in a formalin-induced mouse inflammatory pain model and mustard oil-induced mouse colorectal pain model, in which the mice were intraperitoneally administrated with vehicle or (-)-NRG-DM (30 or 50 mg/kg) (n = 10 for each group). Our data showed that (-)-NRG-DM can dose dependently (30~50 mg/kg) relieve the pain behaviors. Notably, (-)-NRG-DM did not affect motor coordination in mice evaluated by the rotarod test, in which the animals were intraperitoneally injected with vehicle or (-)-NRG-DM (100, 200, or 400 mg/kg) (n = 10 for each group). In acutely isolated mouse dorsal root ganglion neurons, (-)-NRG-DM (1~30 µM) potently dampened the stimulated firing, reduced the action potential threshold and amplitude. In addition, the neuronal delayed rectifier potassium currents (IK) and voltage-gated sodium currents (INa) were significantly suppressed. Consistently, (-)-NRG-DM dramatically inhibited heterologously expressed Kv2.1 and Nav1.8 channels which represent the major components of the endogenous IK and INa. A pharmacokinetic study revealed the plasma concentration of (-)-NRG-DM is around 7 µM, which was higher than the effective concentrations for the IK and INa. Taken together, our study showed that (-)-NRG-DM is a potential analgesic candidate with inhibition of multiple neuronal channels (mediating IK and INa).

Optimal dose of meropenem for the treatment of neonatal sepsis: Dosing guideline variations and clinical practice deviations.

AIMS: Meropenem is increasingly used to treat neonatal sepsis. There are several guidelines recommending different dosing regimens of meropenem in neonates. Furthermore, deviations from these guidelines regularly occur in daily clinical practice. Therefore, the current study aimed to evaluate the variations of meropenem dosing guidelines and compare the difference between guideline and clinical practice in terms of the probability of target attainment. METHODS: This study is based on a population pharmacokinetic model. After defining the predictive performance of the model, Monte Carlo simulations were used to calculate the probability of target attainment of the currently existing dosing guidelines of meropenem and their use in daily clinical practice. RESULTS: Two guidelines and two labels were included in the Monte Carlo simulations. For 70% fT>MIC (fraction of time when the free meropenem concentration exceeded the minimum inhibitory concentration during the dosing interval), the probability of target attainment of four recommended doses ranged from 59% to 88% (MIC = 2 mg·L-1 ) and from 17% to 47% (MIC = 8 mg·L-1 ). At the clinical practice evaluation, only 20% of patients attained target exposure for the MIC of 8 mg·L-1 with 70% fT>MIC , which was much less than those found in the Food and Drug Administration labels (40%). CONCLUSION: This model-based population pharmacokinetics simulation showed that improper guidelines and/or clinical practice deviations will result in low probability of target attainment for patients infected with resistant bacteria and critically ill patients. It is important to develop and adhere to evidence-based and clinically pragmatic guidelines.

Authentication of Three Source Spices of Arnebiae Radix Using DNA Barcoding and HPLC.

Arnebia decumbens (Vent.) Coss. et Kralik, A. euchroma (Royle) Johnst and A. guttata Bunge, three commonly used traditional Chinese medicinal plants have been widely used for the clinical treatment of inflammatory diseases caused by fungal, bacterial, oxidation, and other related pathogens. However, precise identification at the similar species level is usually challenging due to the influence of the source of medicinal materials, traditional ethnic medicine and medicinal habits. Here we developed a comprehensive and efficient identification system for three source spices of Arnebiae Radix based on DNA barcoding and HPLC fingerprinting. A total of 599 samples from thirty-five wild populations were collected and identified by using DNA barcodes of ITS2 regions, and the chemotypes of seven naphthoquinoneswere revealed by HPLC quantitative analysis including principal component analysis and hierarchical clustering analysis. Our results showed that the ITS2 sequences can distinguish three source spices of Arnebiae Radix from adulterants. However, it was difficult to identify them by HPLC-specific chromatograms combined with chemometric analysis. These results indicated that DNA barcoding was a more powerful method than HPLC fingerprinting for the identification of related species that were genetically similar. DNA barcoding analysis could be a promising and reliable tool to accurately confirm the identities of medicinal materials, especially for those whose sources are multiple and difficult to be identified by conventional chromatography.

Discovery of HN37 as a Potent and Chemically Stable Antiepileptic Drug Candidate.

We previously reported that P-retigabine (P-RTG), a retigabine (RTG) analogue bearing a propargyl group at the nitrogen atom in the linker of RTG, displayed moderate anticonvulsant efficacy. Recently, our further efforts led to the discovery of HN37 (pynegabine), which demonstrated satisfactory chemical stability upon deleting the ortho liable -NH2 group and installing two adjacent methyl groups to the carbamate motif. HN37 exhibited enhanced activation potency toward neuronal Kv7 channels and high in vivo efficacy in a range of pre-clinical seizure models, including the maximal electroshock test and a 6 Hz model of pharmacoresistant limbic seizures. With its improved chemical stability, strong efficacy, and better safety margin, HN37 has progressed to clinical trial in China for epilepsy treatment.

In vivo hepatoprotective activity and the underlying mechanism of chebulinic acid from Terminalia chebula fruit.

BACKGROUND: The fruit of Terminalia chebula Retz. is one of the most widely used herbal drug in Traditional medicine prescriptions including those for liver diseases. In the screening of bioactive constituents that have potential hepatoprotective activity, chebulinic acid (CA) which is a major chemical constituent of T. chebula fruit showed potent activity. PURPOSE: This work was conducted to investigate the hepatoprotective activity and mechanisms of CA. METHODS: The hepatoprotective effect of CA was examined on hepatotoxic models of cells, zebrafish larvae and mice caused by tert-butyl hydrogen peroxide (t-BHP), acetaminophen (APAP) and CCl4, respectively. RESULTS: Pretreatment with CA could prevent t-BHP-induced damage in L-02 hepatocytes by blocking the production of ROS, reducing LDH levels and enhancing HO-1 and NQO1 expression via MAPK/Nrf2 signaling pathway. In animal experiments, CA significantly protected mice from CCl4-induced liver injury, as demonstrated by reduced ALT, AST and MDA levels, enhanced SOD activity, improved liver histopathological changes, and the activation of the Nrf2/HO-1 signaling pathway. CA metabolized to chebulic acid isomers with DPPH radical scavenging activity. In a transgenic zebrafish line with liver specific expression of DsRed RFP, CA diminished the hepatotoxicity induced by 10 mM APAP. CONCLUSION: Experiments in cell and two animal models demonstrated consistent results and comprehensively expounded the hepatoprotective effects of CA.

Improved production of echinenone and canthaxanthin in transgenic Nostoc sp. PCC 7120 overexpressing a heterologous crtO gene from Nostoc flagelliforme.

Echinenone and canthaxanthin are important carotenoid pigments with food and industrial applications. Biosynthesis of echinenone and/or canthaxanthin is catalyzed by ß-carotene ketolase (CrtO), with ß-carotene as the substrate. In this study, we generated transgenic Nostoc sp. PCC 7120 overexpressing a heterologous crtO gene from Nostoc flagelliforme and evaluated the productivity of both pigments. Normal (BG11 medium, 30 °C) and osmotic stress (BG11 medium supplemented with 0.4 M mannitol, 30 °C) conditions were used for cultivation. As compared to control strain, production of echinenone and canthaxanthin in transgenic strain were respectively increased by more than 16 % and 80 %, under either normal or osmotic stress conditions. Especially upon the stress condition, higher proportion of echinenone and canthaxanthin in total pigments was achieved, which should be beneficial for downstream separation and purification. In addition, transgenic strain showed drought tolerance and could revive from desiccation treatment after rewetting. Thus, this study provided technical clues for production of both pigments in engineered cyanobacteria as well as for cyanobacterial anhydrobiotic engineering.

Iron oxide nanoparticles induce reversible endothelial-to-mesenchymal transition in vascular endothelial cells at acutely non-cytotoxic concentrations.

BACKGROUND: Iron oxide nanoparticles (IONPs) have been extensively studied in different biomedical fields. Recently, the non-cytotoxic concentration of IONPs induced cell-specific response raised concern of their safety. Endothelial cell exposure was unavoidable in their applications, while whether IONPs affect the phenotype of vascular endothelial cells is largely unknown. In this work, the effect of IONPs on endothelial-to-mesenchymal transition (EndMT) was investigated in vitro and in vivo. RESULTS: The incubation with γ-Fe2O3 nanoparticles modified with polyglucose sorbitol carboxymethyether (PSC-Fe2O3) at non-cytotoxic concentration induced morphological changes of human umbilical vein endothelial cells (HUVECs) from cobblestone-like to spindle mesenchymal-like morphology, while PSC-Fe2O3 mostly stay in the culture medium and intercellular space. At the same time, the endothelial marker CD31 and VE-cadherin was decreased along with the inhibitory of angiogenesis properties of HUVEC. Meanwhile, the mesenchymal marker α-smooth muscle actin (α-SMA) and fibroblast specific protein (FSP) was up regulated significantly, and the migration ability of the cells was enhanced. When ROS scavenger mannitol or AA was supplemented, the EndMT was rescued. Results from the in vivo study showed that, expression of CD31 was decreased and α-SMA increased in the liver, spleen and kidney of mice given PSC-Fe2O3, and the density of collagen fibers in the liver sinusoid of mice was increased. The supplementary mannitol or AA could reverse the degree of EndMT in the tissues. Mechanistic study in vitro indicated that the level of extracellular hydroxyl radicals (·OH) was up regulated significantly by PSC-Fe2O3, which induced the response of intracellular ROS and resulted in the EndMT effect on HUVECs. CONCLUSION: The PSC-Fe2O3 was capable of inducing EndMT in the endothelial cells at acutely non-cytotoxic dose due to its intrinsic peroxidase-like activity, though they were few taken up by endothelial cell. The EndMT effect on HUVEC can be rescued by ROS scavenger in vitro and in vivo.