Baduanjin exercise intervention trial: research protocol of a randomised controlled trial for frail kidney transplant recipients.

INTRODUCTION: Frailty is one of the most common comorbidities in kidney transplant recipients (KTRs). Physical, psychological and social frailty could be improved by exercise intervention. Baduanjin, also known as Eight-section Brocades, is a type of traditional Chinese medicine exercise characterised by the interplay between physical postures and movements, breathing and mind. It can help frail patients strengthen their upper and lower body muscles, improve their mood, quality of life and frailty. However, the effectiveness of Baduanjin on frail KTRs remains unknown. Therefore, we will conduct a randomised controlled trial (RCT) to evaluate the effectiveness of Baduanjin on frail KTRs. METHODS AND ANALYSIS: This protocol describes an assessor and analyst blinded, parallel RCT for frail KTRs comparing Baduanjin group (n=72) with care-as-usual group (n=72). The primary outcomes are frailty assessed by Frailty Phenotype scale and Tilburg Frailty Indicator scale, and muscle strength assessed by a grip strength metre. The secondary outcomes are quality of life assessed by Medical Outcomes Study 36-Item Short-Form Health Survey (MOS SF-36) and depression assessed by the Hospital Anxiety and Depression Scale. All these data will be collected at the baseline, after 3, 6, 9 and 12 months, respectively. Two-way mixed analysis of variance (ANOVA) will be used to test the effectiveness of Baduanjin exercise. Qualitative interviews with participants in the intervention group will also be performed after 6 months. Themes will be extracted from interview transcripts using NVivo software. ETHICS AND DISSEMINATION: The Ethics Committees of Beijing University of Chinese Medicine (2022BZYLL1018) and China-Japan Friendship Hospital (2022-KY-250) had approved the study. The organ donors were all from China-Japan Friendship Hospital. They provided informed consent and they were not executed prisoners. We have provided BMJ Open with documentation from the hospital that indicates that the organs will be harvested ethically. The findings of this study will be disseminated through peer-reviewed journals, international conferences, media reports and briefings. TRIAL REGISTRATION NUMBER: ChiCTR2100041730.

Simultaneous production of aromatics-rich bio-oil and carbon nanomaterials from catalytic co-pyrolysis of biomass/plastic wastes and in-line catalytic upgrading of pyrolysis gas.

An integrated process that includes catalytic co-pyrolysis of biomass/plastic wastes and in-line catalytic upgrading of pyrolysis gas were conducted to simultaneously produce aromatics-rich bio-oil and carbon nanotubes (CNTs). The influences of feedstocks blending ratio on the characteristics of bio-oil and CNTs were established. The reaction mechanism of carbon deposition during the system was also probed. The results showed that co-feeding plastic to biomass siginificantly enhanced the selectivity of monoaromatics (benzene, toluene, and xylene) from 5.6% for pure biomass to the maximum yield of 44.4% for 75.0% plastic ratio, and decreased naphthalene and its derivates from 85.9 to 41.7% correspondingly. The most synergistic effect on BTX selectivity occurred at 25% of plastic ratio. The multi-walled CNTs were successfully synethsized on Ni catalyst by utilizing prolysis gas as feedstocks. For pure biomass, the least CNTs yield with ultrafine diameters of 3.9-8.5 nm was generated via disproportionation reaction of CO which was derived from decarboxylation and decarbonylation of oxygenates on the ZSM-5 acid sites. With the rise of plastic ratio, sufficient hydrocarbons were produced for CNTs growth, endowing CNTs with long and straight tube walls, along with uniform diameters (~16 nm). The CNTs yield increased as high as 139 mg/g-cata. In addition, the decreased CO2 inhibited dry reforming with C1-C4 hydrocarbons and deposited carbon, avoiding excessive etching of CNTs. Thereby, high-purity CNTs with less defects were fabricated when plastic ratio was beyond 50% in the feedstock. The strategy is expected to improve the sustainability and economic viability of biomass pyrolysis.

Lysosome-Targeted Gold Nanotheranostics for In Situ SERS Monitoring pH and Multimodal Imaging-Guided Phototherapy.

The integration of surface-enhanced Raman spectrum (SERS) and fluorescence-photoacoustic multimodal imaging in near-infrared photothermal therapy is highly desirable for cancer theranostic. However, typically, gold nanotheranostics usually require an additional modification of fluorophores and complex design refinements. In this work, by integrating surface-modified cysteine-hydroxyl merocyanine (CyHMC) molecules onto AuNRs, a novel lysosome-targeted gold-based nanotheranostics AuNRs-CyHMC that combines the specificity of Raman spectrum, the speed of fluorescence imaging, and deep penetration of photoacoustic imaging was successfully fabricated. Interestingly, fluorescence and Raman signals in this AuNRs-CyHMC system do not interfere, but it has pH-sensitive Raman signals and self-fluorescence localization ability under different excitation wavelengths. Fluorescence co-localization experiments further confirmed the lysosome-targeting ability of AuNRs-CyHMC. Typically, the proposed nanotheranostics were capable of SERS monitoring pH changes in both phosphate-buffered saline and living cells. Meanwhile, in vitro and in vivo experiments revealed that AuNRs-CyHMC possessed excellent fluorescence-photoacoustic performance and could be used for multimodal imaging-guided photothermal therapy. Furthermore, our work implied that gold nanotheranostics can provide great potential for cancer diagnosis and treatment.

Effects of spore powder of ganoderma lucidum on CaSR and apoptosis-related proteins in hippocampus tissue of epilepsy following dementia: A protocol of systematic review.

BACKGROUND: This study will investigate the effects of Spore Powder of Ganoderma Lucidum (SPGL) on CaSR and apoptosis-related proteins (ARP) in hippocampus tissue of epilepsy following dementia. METHODS: This study will retrieve all potential studies from both electronic databases (Cochrane Library, EMBASE, MEDLINE, CINAHL, AMED, and CNKI) and other literature sources to assess the effects of SPGL on CaSR and ARP in hippocampus tissue of epilepsy following dementia. We will search all literature sources from the inception to the present. All eligible case-control studies will be included in this study. Two authors will independently carry out literature selection, data collection, and study quality evaluation. Any divergence will be resolved by another author through discussion. RevMan 5.3 software will be employed for data analysis. RESULTS: This study will summarize existing evidence to assess the effects of SPGL on CaSR and ARP in hippocampus tissue of epilepsy following dementia. CONCLUSIONS: The findings of this study may provide helpful evidence of SPGL on CaSR and ARP in hippocampus tissue of epilepsy following dementia. SYSTEMATIC REVIEW REGISTRATION: INPLASY202070041.

Oceanivirga miroungae sp. nov., isolated from oral cavity of northern elephant seal (Mirounga angustirostris).

Two independent strains of a Leptotrichia species (ES3154-GLUT and ES2714_GLU) were isolated from the oral cavity of northern elephant seals (Mirounga angustirostris) that were admitted to The Marine Mammal Centre facilities in California, USA. The strains were isolated from oral swabs by cultivation in PPLO broth supplemented with serum, penicillin and colistin in anaerobic conditions. The strains were Gram-negative, pleomorphic, indole-, oxidase- and catalase-negative, non-spore-forming, non-motile rods/coccobacilli in short chains. The 16S rRNA gene sequence of these strains shared 94.42 % nucleotide similarity with Oceanivirga salmonicida AVG 2115T but demonstrated ≤86.00-92.50 % nucleotide similarity to the 16S rRNA genes of other species of the family Leptotrichiaceae. The genome was sequenced for strain ES3154-GLUT. Average nucleotide identity values between strain ES3154-GLUT and 15 type strain genomes from the family Leptotrichiaceae ranged from 66.74 % vs. Sebaldella termitidis to 73.35 % vs. O. salmonicida. The whole genome phylogeny revealed that the novel species was most closely related to O. salmonicida AVG 2115T. This relationship was also confirmed by nucleotide similarity and multilocus phylogenetic analyses employing various housekeeping genes (partial 23S rRNA, rpoB, rpoC, rpoD, polC, adh, gyrA and gyrB genes). Chemotaxonomic and phenotypical features of strain ES3154-GLUT were in congruence with closely related members of the family Leptotrichiaceae, represented by similar enzyme profiles and fatty acid patterns. MALDI-TOF MS analysis was capable to clearly discriminate strain ES3154-GLUT from all currently described taxa of the family Leptotrichiaceae. Based on these data, we propose a novel species of the genus Oceanivirga, for which the name Oceanivirga miroungae sp. nov. is proposed with the type strain ES3154-GLUT (=DSM 109740T=CCUG 73653T=ATCC TSD-189T=NCTC 14411T) and one representative strain ES2714_GLU. The G+C content is 26.82 %, genome size is 1 356 983 bp.

Depriving Iron Supply to the Virus Represents a Promising Adjuvant Therapeutic Against Viral Survival.

PURPOSE OF THE REVIEW: The ongoing outbreak of novel coronavirus pneumonia (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) in China is lifting widespread concerns. Thus, therapeutic options are urgently needed, and will be discussed in this review. RECENT FINDINGS: Iron-containing enzymes are required for viruses most likely including coronaviruses (CoVs) to complete their replication process. Moreover, poor prognosis occurred in the conditions of iron overload for patients upon infections of viruses. Thus, limiting iron represents a promising adjuvant strategy in treating viral infection through oral uptake or venous injection of iron chelators, or through the manipulation of the key iron regulators. For example, treatment with iron chelator deferiprone has been shown to prolong the survival of acquired immunodeficiency syndrome (AIDS) patients. Increasing intracellular iron efflux via increasing iron exporter ferroportin expression also exhibits antiviral effect on human immunodeficiency virus (HIV). The implications of other metals besides iron are also briefly discussed. SUMMARY: For even though we know little about iron regulation in COVID-19 patients thus far, it could be deduced from other viral infections that iron chelation might be an alternative beneficial adjuvant in treating COVID-19.

A green route for pyrolysis poly-generation of typical high ash biomass, rice husk: Effects on simultaneous production of carbonic oxide-rich syngas, phenol-abundant bio-oil, high-adsorption porous carbon and amorphous silicon dioxide.

Rice husk is a widespread agriculture waste in rice-farming country. High silica content in rice husk prevent its efficient utilization. So in this work, concept of poly-generation was introduced to improve its utilization value. This study provided CO-rich syngas, phenol-abundant bio-oil, high-adsorption porous carbon and amorphous SiO2 as four end products for first time via combination of acid washing and activated carbon catalyst. Specifically, acid washing effectively decreasedsoluble ash, which altered pyrolysis paths, increased volatiles release and reduced impurities in bio-char. After catalytic pyrolysis, phenol content of 65.56% and CO of 56.09 vol% were detected in bio-oil and syngas from AWRH. For solid products, acid washing benefited both bio-char and silica. A low-cost porous carbon with developed pores and rich surface functional groups was prepared for water absorption. And high purity amorphous SiO2 was recycled from alkali etching solution. Finally, a green process with no waste emission was proposed.

Roles of mtDNA damage and disordered Ca2+ homeostasis in the joint toxicities of cadmium and BDE209.

Cadmium, a typical heavy metal, causes serious toxicities on many organs and tissues. As the last partially controlled class of polybrominated diphenyl ethers (PBDEs), BDE209 can also induce various health issues. Although apoptosis mediated by mitochondria has been known to be a key player in inducing toxicities by cadmium, the detailed mechanisms are incompletely understood. Moreover, co-existence of cadmium and PBDEs has been found in various environment context and human body. However, studies on the joint toxicity of cadmium and PBDEs are still limited with largely unknown mechanisms. In the present study, we investigated the adverse effects and mechanisms of single or combined treatment of CdCl2 and BDE209 on hepatocytes. We observed that apoptosis were significantly induced by CdCl2, and the combined treatment of CdCl2 and BDE209 greatly promoted the progression of apoptosis. BDE209 induced mild apoptosis. Mitochondria was the pivot of several mechanisms to induce apoptosis, including ROS production, decreased mitochondrial membrane potential (MMP), mtDNA damage and disordered calcium (Ca2+) homeostasis. However, we found that mtDNA damage and disordered Ca2+ homeostasis were the main mechanisms for CdCl2-induced apoptosis while ROS production played important roles in BDE209-induced apoptosis. Less mtDNA damage occurred in BDE209-treated cells. In the cells with combined treatment, CdCl2 and BDE209 exhibited a complementary pattern for the underlying mechanisms of apoptosis, leading to the joint toxicities, in which CdCl2 showed more contributions. In a conclusion, our results demonstrated that combined exposure to cadmium and BDE209 causes joint adverse effects on hepatocytes through diverse mechanisms as mediated by mitochondria.

The Influence of Hyperlipidemia on Endothelial Function of FPN1 Tek-Cre Mice and the Intervention Effect of Tetramethylpyrazine.

BACKGROUND/AIMS: Systemic iron homeostasis is strictly governed in mammals; however, disordered iron metabolism (such as excess iron burden) is recognized as a risk factor for various types of diseases including AS (Atherosclerosis). The hepcidin-ferroportin axis plays the key role in regulation of iron homeostasis and modulation of this signaling could be a potential therapeutic strategy in the treatment of these diseases. TMP (Tetramethylpyrazine) has been reported to have therapeutical effect on AS. Here, we aimed to investigate the effect of iron overload under hyperlipidemia condition on the endothelial injury, inflammation and oxidative stress by employing FPN1 Tek-cre mouse model with or without TMP intervention. METHODS: Subjects for this study were 80 FPN1 Tek-cre mice and 40 C57BL/6 mice and we randomly divided them into six groups: Group N: C57BL/6 mice with normal diet, Group M: C57BL/6 mice with high-fat diet, Group FN: FPN1 Tek-cre mice with normal diet, Group FNT: FPN1 Tek-cre mice with normal diet and TMP injection, Group FM: FPN1 Tek-cre mice with high-fat diet, Group FMT: FPN1 Tek-cre mice with high-fat diet and TMP injection. After seven days of treatment, blood samples were obtained to detect the levels of blood lipids, Hepcidin, NO, ET-1, ROS, MDA, SOD, IL-1, IL-6 and TNF-α respectively. The liver and aorta were used for testing the lipid deposition by using hematoxylin and eosin(HE). RESULTS: Hyperlipidemia could cause iron overload in the aorta and increased serum hepcidin level, particularly in FPN1 Tek-cre mice, and can be reversed by TMP intervention. Knockout of Fpn1 induced increase of serum hepcidin, exacerbated endothelial dysfunction, oxidative stress and inflammatory response, particularly under hyperlipidemia condition. TMP intervention attenuated these processes. CONCLUSIONS: Our study signifies the potential application of certain natural compounds to ameliorating iron disorders induced by hyperlipidemia and protecting on endothelial function through modulation of hepcidin-ferroportin signaling.

Neisseria zalophi sp. nov., isolated from oral cavity of California sea lions (Zalophus californianus).

Three independent strains of Neisseria sp. were isolated from the oral cavity of California sea lions (Zalophus californianus) that were admitted to The Marine Mammal Center facilities in California, USA. The strains were isolated from oral swabs by cultivation on Trypticase Soy agar with 5% sheep blood under aerobic conditions. The 16S rRNA gene sequence of these three strains shared 99% similarity, but demonstrated only 97-98% nucleotide similarity to the phylogenetically closest relatives such as N. canis, N. zoodegmatis, N. animaloris, and N. dumasiana. These three strains also shared 99% sequence similarity of their rplF, rpoB, and gyrB gene sequences. Based on the biochemical tests alone (i.e., without genetic analysis of housekeeping genes), it is difficult to discriminate this novel species from N. canis; however, it can be easily discriminated from all phylogenetically closely related species using the sequencing analysis of its housekeeping genes (e.g., rplF, rpoB, or gyrB genes). Thus, genetic testing is indispensable for accurate identification of this species in a routine laboratory practice. The species is an obligate aerobe and able to grow in Mueller-Hinton broth supplemented with 6% NaCl, but the phylogenetically closely related species (N. canis, N. zoodegmatis, N. animaloris, and N. dumasiana) were not. Based on these phenotypic and genotypic characteristics and phylogenetic data, we conclude that these new strains represent a novel species of the genus Neisseria, for which the name Neisseria zalophi sp. nov. is proposed. The type strain is CSL 7565T (= ATCC BAA2455T = DSM 102031T).

Resveratrol Attenuates Microglial Activation via SIRT1-SOCS1 Pathway.

Microglial activation is involved in a variety of neurological disorders, and overactivated microglial cells can secrete large amount of proinflammatory factors and induce neuron death. Therefore, reducing microglial activation is believed to be useful in treating the disorders. In this study, we used 10 ng/ml lipopolysaccharide plus 10 U/ml interferon γ (LPS/IFNγ) to induce N9 microglial activation and explored resveratrol- (RSV-) induced effects on microglial activation and the underlying mechanism. We found that LPS/IFNγ exposure for 24 h increased inducible nitric oxide synthase (iNOS) and nuclear factor κB (NF-κB) p65 subunit expressions in the cells and enhanced tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) releases from the cells. RSV of 25 µM reduced the iNOS and NF-κB p65 subunit expressions and the proinflammatory factors' releases; the knockdown of silent information regulator factor 2-related enzyme 1 (SIRT1) or suppressor of cytokine signaling 1 (SOCS1) by using the small interfering RNA, however, significantly abolished the RSV-induced effects on iNOS and NF-κB p65 subunit expressions and the proinflammatory factors' releases. These findings showed that microglial SIRT1-SOCS1 pathway may mediate the RSV-induced inhibition of microglial activation in the LPS/IFNγ-treated N9 microglia.

A cation-exchange controlled core-shell MnS@Bi2S3 theranostic platform for multimodal imaging guided radiation therapy with hyperthermia boost.

Overtreatment as a crucial modern medicine issue needs to be urgently addressed. Theranostic agents supply a unique platform and integrate multiple diagnosis and therapies to deal with this issue. In this study, a core-shell MnS@Bi2S3 nanostructure was fabricated via two step reactions for tri-modal imaging guided thermo-radio synergistic therapy. The mass ratio between the core and shell of the constructed MnS@Bi2S3 can be precisely controlled via cation exchange reaction. After surface PEGylation, MnS@Bi2S3-PEG nanoparticles exhibited excellent aqueous medium dispersibility for bioapplications. Based on the r1 and r2 relaxivity obtained from the MnS core and the strong near-infrared absorption and X-ray attenuation abilities of the Bi2S3 shell, the intratumoral injected MnS@Bi2S3-PEG can realize in vivo magnetic resonance, computer tomography, and photoacoustic tumor imaging under a single injection dose. Hyperthermia significantly boosts the efficacy of radiation therapy, showing synergistic tumor treatment efficacy. No obvious toxicity is monitored for the treated mice. Our study not only provides a new way to precisely construct the core-shell nanocomposite, but also presents a unique theranostic platform and unifies the solutions for the challenges related with high injection dose and overtreatment.

Cornin increases angiogenesis and improves functional recovery after stroke via the Ang1/Tie2 axis and the Wnt/ß-catenin pathway.

We investigated whether cornin, an iridoid glycoside isolated from fruits of Verbena officinalis L., regulated angiogenesis and thereby improved functional outcomes after stroke and discovered a potential mechanism. The effects of cornin on proliferation of rat artery smooth muscle cell (RASMC) and signalling was investigated in vitro. Adult male rats were subjected to 1 h of middle cerebral artery occlusion (MCAO) and reperfusion and treated with or without 25 mg/kg of cornin, starting 24 h after ischemia and reperfusion, by continuous intravenous injection daily for 14 days. Neurological functional tests were performed and cerebral Evans blue extravasation was measured. Angiogenesis and angiogenic factor expressions were measured by immunohistochemistry and Western blotting, respectively. Cornin increased the proliferation of RASMC and enhanced the expression of Wnt5a, ß-catenin, cyclin D1 and angiopoietin-1 (Ang1). Cornin treatment promoted angiogenesis in the ischemic brain core and improved functional outcomes after stroke. Cornin-treated MCAO rats showed significant increase in vascularization and expression of vascular endothelial growth factor and Ang1 and phosphorylation of Tie2 and Akt compared with vehicle-treated MCAO rats. The Ang1/Tie2 axis and Wnt/ß-catenin pathways appear to mediate cornin-induced angiogenesis.

Astaxanthin induces angiogenesis through Wnt/ß-catenin signaling pathway.

OBJECTIVE: In the present study, we sought to elucidate whether astaxanthin contributes to induce angiogenesis and its mechanisms. MATERIALS AND METHODS: To this end, we examined the role of astaxanthin on human brain microvascular endothelial cell line (HBMEC) and rat aortic smooth muscle cell (RASMC) proliferation, invasion and tube formation in vitro. For study of mechanism, the Wnt/ß-catenin signaling pathway inhibitor IWR-1-endo was used. HMBECs and RASMCs proliferation were tested by cell counting. Scratch adhesion test was used to assess the ability of invasion. A matrigel tube formation assay was performed to test capillary tube formation ability. The Wnt/ß-catenin pathway activation in HMBECs and RASMCs were tested by Western blot. RESULTS: Our data suggested that astaxanthin induces angiogenesis by increasing proliferation, invasion and tube formation in vitro. Wnt and ß-catenin expression were increased by astaxanthin and counteracted by IWR-1-endo in HMBECs and RASMCs. Tube formation was increased by astaxanthin and counteracted by IWR-1-endo. CONCLUSIONS: It may be suggested that astaxanthin induces angiogenesis in vitro via a programmed Wnt/ß-catenin signaling pathway.

[Efficacy of acupuncture on moderate and severe allergic rhinitis].

OBJECTIVE: To observe the efficacy and safety of acupuncture therapy on moderate and severe allergic rhinitis via the comparison evaluation of western medicine. METHODS: Sixty cases of moderate and severe allergic rhinitis were divided into an acupuncture group (30 cases) and a western medicine group (30 cases). In the acupuncture group, the main acupoints included Yingxiang (LI 20), Shangxing (GV 23), Fengchi (GB 20), Quchi (LI 11), Xuehai (SP 10), Feishu (BL 13), Geshu (BL 17), Pishu (BL 20), etc. The supplementary points were selected according to syndrome differentiation. In the western medicine group, budesonide nasal spray and cetirizine tablets were prescribed. All the cases were treated for 8 weeks in the two groups. Separately, before treatment, in 4 weeks and 8 weeks of treatment, the scores of clinical symptoms and physical signs were observed and the clinical efficacy and safety were compared between the two groups. RESULTS: In 4 weeks and 8 weeks of treatment, the scores of symptoms such as sneezing, nasal discharge, nasal obstruction, nasal itching, eye itching and turbinate hypertrophy, the score of physical signs and total score were all reduced apparently as compared with those before treatment (all P<0. 05). The differences were not significant between the acupuncture group and the western medicine group (all P>0. 05). The total effective rates were 90. 0% (27/30) and 93. 4% (28/30) in the acupuncture group after 4 and 8 weeks of treatment, and were 76. 6% (23/30) and 80. 0% (24/30) in the western medicine group separately, without significant difference in comparison (all P>0. 05). CONCLUSION: Acupuncture achieves the similar efficacy on moderate and severe allergic rhinitis as western medicine. It is the safe therapy and has no apparent adverse reactions.

Biosynthesis of catechin components is differentially regulated in dark-treated tea (Camellia sinensis L.).

Tea (Camellia sinensis L.) is a crop with both commercial and medicinal value with remarkably high polyphenol content in the form of catechins. To understand the molecular regulation of catechin biosynthesis in tea, we treated the tea plants with darkness. We used qRT-PCR to validate the expression of genes involved in catechin biosynthesis. It indicated that dark treatment displayed different effects on the genes participating in tea flavonoid (FL) pathway. The early genes of FL biosynthesis pathway, CHSI, F3H and DFR, remained at steady expression levels when treated by darkness. It is noteworthy that the expression level of LAR increased and the level of ANS decreased under dark conditions. The vanillin assay showed that the dark-treated plants contained lower levels of total catechins than those grown under normal conditions. The HPLC analysis further demonstrated the changes in biosynthesis of catechins under these conditions. In accordance with the gene expression pattern, the content of epicatechins (ECs) declined and that of catechins (Cs) was elevated in response to the darkness. Our study uncovered the molecular mechanisms and biochemical changes of shading in tea cultivation.

[Effect of safflor yellow B on vascular endothelial cells injury induced by angiotensin-II].

This study is to investigate protective effect of safflor yellow B (SYB) against vascular endothelial cells (VECs) injury induced by angiotensin-II (Ang-II). VECs were cultured and divided into six groups: control group, Ang-II group, Ang-II + SYB (1 micromolL(-1)) group, Ang-II + SYB (10 micromolL(-1)) group, Ang-II + SYB (100 micromolL(-1)) group and Ang- II + verapamil (10 micromolL(-1)) group. Except control group, all of VECs in other groups were treated with Ang- II at the final concentration of 0.1 micromolL(-1). Mitochondria membrane potential (MMP) and free calcium concentration ([Ca2+]i) were measured by laser scanning confocal microscopy, and mitochondria complex IV activity was detected by BCA method. The levels of reactive oxygen species (ROS) in VECs were analyzed by fluorescence detector and apoptosis of VECs was observed by flow cytometer. Caspase 3 was determined by Western blotting method. Comparing with control group, Ang-II was able to increase [Ca2+]i and ROS level, decrease MMP level, inhibit complex IV activity and enhance caspase 3 activity in VECs, as a result, enhance apoptosis of VECs. But SYB could significantly reduce the result induced by Ang- II relying on different dosages (P < 0.05 or P < 0.01). SYB was able to eliminate the effect of Ang-II on VECs via regulating [Ca2+]i, mitochondrial structure and function and inhibiting apoptosis.

Cardioprotection of Asperosaponin X on experimental myocardial ischemia injury.

BACKGROUND: Asperosaponin X was isolated from the roots of Dipsacus asper. In this study, we investigated the anti-myocardial ischemia and reperfusion (I/R) injury effects of Asperosaponin X in vivo and elucidated the potential mechanism in vitro. RESULTS: Asperosaponin X significantly attenuated hypoxia-induced cytotoxicity in a concentration-dependent manner in H9c2 cells. Treatment of H9c2 cells with Asperosaponin X 5 µM or 10 µM blocked TNF-α-induced nuclear factor kappaB (NF-κB) phosphorylation by blocking HMGB1 expression. Treatment of rats with Asperosaponin X 10mg/kg, (i.v.) protected the animals from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics and reduction of myocardial damage severity. Treatment with Asperosaponin X also lowered serum levels of pro-inflammatory factors and reduced High mobility group box-1 protein (HMGB1), phosphorylated IκB-α and NF-κB expression in ischemic myocardial tissue. Additionally, continuous i.v. of Asperosaponin X 14 days attenuated cardiac remodeling. CONCLUSIONS: These protective effects suggested that Asperosaponin X may be due to block of myocardial inflammatory cascades through an HMGB1-dependent NF-κB signaling pathway.

Effect of loganin on experimental diabetic nephropathy.

Connective tissue growth factor (CTGF) plays a pathogenic role in diabetic nephropathy (DN). Loganin, an iridoid glucoside compound was isolated from Cornus officinalis Sieb. et Zucc. This study was conducted to investigate the efficacy of loganin on DN and to elucidate the potential mechanism. High glucose (HG) stimulated cultured human renal proximal tubular epithelial cells (HK-2) analyzed CTGF expression by Western blotting and investigated whether extracellular signal-regulated kinase (ERK) signaling pathway was involved. Streptozotocin (STZ)-induced experimental DN, randomized to receive intragastric (i.g.) of loganin. Renal tissue, blood and urine samples were collected to determine and analyze. In vitro study, loganin reduced CTGF excretion in HG-induced HK-2 cells through the ERK signaling pathway. In vivo study, I.g. of loganin 5 mg/kg or 10 mg/kg significantly ameliorated renal function and increased body weight. Meanwhile, loganin reduced renal CTGF expression by immunohistochemical staining, reduced serum levels of CTGF. Besides, there were no significant differences in blood sugar levels between the loganin groups compared to the STZ-treated group. Furthermore, loganin ameliorated renal pathology. These results suggested that loganin exerts an early renal protective role to DN. Inhibition of CTGF may be a potential target in DN therapy, which highlights the possibility of using loganin to treat DN.

Forsythoside B protects against experimental sepsis by modulating inflammatory factors.

The present study investigated the effects of Forsythoside B on an experimental model of sepsis induced by caecal ligation and puncture (CLP) in rats and elucidated the potential mechanism in cultured RAW 264.7 cells. Results showed that Forsythoside B concentration-dependently down-regulated the levels of TNF-α, IL-6 and high-mobility group-box 1 protein (HMGB1) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, inhibited the IκB kinase (IKK) pathway and modulated nuclear factor (NF)- κB. Intravenous injection (i.v.) of Forsythoside B alone or plus Imipenem reduced serum levels of TNF-α, IL-6, HMGB1, triggering receptor expressed on myeloid cells (TREM-1) and endotoxin, while the serum level of IL-10 was up-regulated and myeloperoxidase (MPO) in lung, liver and small intestine was reduced. Meanwhile, i.v. of Forsythoside B alone or plus Imipenem reduced CLP-induced lethality in rats. These data indicated that the antisepsis effect of Forsythoside B is mediated by decreasing local and systemic levels of a wide spectrum of inflammatory mediators. Its antisepsis mechanism may be that Forsythoside B binds to LPS and reduces the biological activity of serum LPS, and inhibits NF-κB activition. Our studies enhance the case for the use of Forsythoside B in sepsis. Forsythoside B itself has promise as a therapy for the treatment of sepsis in humans.