Mild endoplasmic reticulum stress alleviates FB1-triggered intestinal pyroptosis via the Sec62-PERK pathway.

Fumonisin B1 (FB1), a water-soluble mycotoxin released by Fusarium moniliforme Sheld, is widely present in corn and its derivative products, and seriously endangers human life and health. Recent studies have reported that FB1 can lead to pyroptosis, however, the mechanisms by which FB1-induced pyroptosis remain indistinct. In the present study, we aim to investigate the mechanisms of pyroptosis in intestinal porcine epithelial cells (IPEC-J2) and the relationship between FB1-induced endoplasmic reticulum stress (ERS) and pyroptosis. Our experimental results showed that the pyroptosis protein indicators in IPEC-J2 were significantly increased after exposure to FB1. The ERS markers, including glucose-regulated Protein 78 (GRP78), PKR-like ER kinase protein (PERK), and preprotein translocation factor (Sec62) were also significantly increased. Using small interfering RNA silencing of PERK or Sec62, the results demonstrated that upregulation of Sec62 activates the PERK pathway, and activation of the PERK signaling pathway is upstream of FB1-induced pyroptosis. After using the ERS inhibitor 4-PBA reduced the FB1-triggered intestinal injury by the Sec62-PERK pathway. In conclusion, we found that FB1 induced pyroptosis by upregulating Sec62 to activate the PERK pathway, and mild ERS alleviates FB1-triggered damage. It all boils down to one fact, the study provides a new perspective for further, and improving the toxicological mechanism of FB1.

Baicalin mitigates nephropathogenic infectious bronchitis virus infection-induced spleen injury via modulation of mitophagy and macrophage polarization in Hy-Line chick.

Nephropathogenic infectious bronchitis virus (NIBV) infections continue to pose a significant hazard in the poultry industry. Baicalin is a natural flavonoid that has been reported to have antiviral activity, but its function in NIBV infection largely remains unclear. In this study, the antiviral mechanism of baicalin in the spleen of NIBV-infected chicks was mainly elucidated in mitophagy and macrophage polarization. 28-day-old Hy-Line brown chicks were randomly divided into four groups: the group of chicks was treated intranasally (in) with normal saline (0.2 mL) and subsequently divided into two groups: the Con group (basic diet), the Con+BA group (basic diet+10 mg/kg Baicalin); another group of chicks was intranasally infected with SX9 (10-5/0.2 mL) and subsequently divided into two groups: the Dis group (basic diet), the Dis+BA group (basic diet+10 mg/kg Baicalin). Spleen tissues were collected at 3, 7, and 11 days post infection (dpi). NIBV copy number was strikingly decreased in the spleens under BA treatment with infectious time. Histopathological examination showed enlarged and hemorrhagic white pulp and no clearly defined boundary between white pulp and red pulp in the Dis group, which could be improved by BA treatment. Meanwhile, the loss of cristae structure and vacuolization in mitochondria caused by NIBV infection was repaired in the Dis+BA group by ultrastructure observation. In addition, BA treatment inhibited the induction of mitophagy by NIBV infection. BA treatment also promoted innate immunity by enhancing type I IFN levels. Moreover, BA treatment up-regulated M1-related cytokines (iNOS, TNF-α, IL-1ß, IL-6) and inhibited M2-related cytokines (ARG2, IL-4, IL-10, Pparg) at the mRNA and protein levels. However, the results from the splenic tissues at 11 dpi are opposite results from 3 and 7 dpi. Immunofluorescence analysis for M1 macrophage marker iNOS and M2 macrophage marker CD163 further validated this result. Collectively, BA inhibited mitophagy and triggered IFN activation, and M1 polarization, which contributed to the inhibition of NIBV infection.

Risk factors of gastrointestinal bleeding after cardiopulmonary bypass in children: a retrospective study.

Background: During cardiac surgery that involved cardiopulmonary bypass (CPB) procedure, gastrointestinal (GI) system was known to be vulnerable to complications such as GI bleeding. Our study aimed to determine the incidence and risk factors associated with GI bleeding in children who received CPB as part of cardiac surgery. Methods: This retrospective study enrolled patients aged <18 years who underwent cardiac surgery with CPB from 2013 to 2019 at Shanghai Children's Medical Center. The primary outcome was the incidence of postoperative GI bleeding in children, and the associated risk factors with postoperative GI bleeding episodes were evaluated. Results: A total of 21,893 children who underwent cardiac surgery with CPB from 2013 to 2019 were included in this study. For age distribution, 636 (2.9%) were neonates, 10,984 (50.2%) were infants, and 10,273 (46.9%) were children. Among the 410 (1.9%) patients with GI bleeding, 345 (84.2%) survived to hospital discharge. Incidence of GI bleeding in neonates, infants and children were 22.6% (144/636), 2.0% (217/10,984) and 0.5% (49/10,273), respectively. The neonates (22.6%) group was associated with highest risk of GI bleeding. Patients with GI bleeding showed longer length of hospital stays (25.8 ± 15.9 vs. 12.5 ± 8.9, P < 0.001) and higher mortality (15.9% vs. 1.8%, P < 0.001). Multivariate logistic regression analysis showed that age, weight, complicated surgery, operation time, use of extracorporeal membrane oxygenation (ECMO), low cardiac output syndrome (LCOS), hepatic injury, artery lactate level, and postoperative platelet counts were significantly associated with increased risk of GI bleeding in children with congenital heart disease (CHD) pediatric patients that underwent CPB procedure during cardiac surgery. Conclusion: The study results suggest that young age, low weight, long operation time, complicated surgery, use of ECMO, LCOS, hepatic injury, high arterial lactate level, and low postoperative platelet counts are independently associated with GI bleeding after CPB in children.

A new method for evaluating the heat leak of cryogenic vessels without exhaust gas.

The thermal insulation performance of cryogenic vessels is evaluated by the boil-off gas (BOG) rate and heat leak as a reference standard; however, it consumes considerable testing time and working medium. In this study, we proposed a method of evaluating the thermal insulation performance of cryogenic vessels from the heat leak in the self-pressurization process, which can minimize the testing time and preserve the working medium. To improve the accuracy of heat leak calculation, the vapor temperature distribution of cryogenic vessels is analyzed and considered in the calculation of heat leak. However, it is ignored in the current standard test method. In this study, the energy equations of cryogenic vessels in the self-pressurization process were established by considering the vapor temperature distribution. Then, based on the experimental data, the heat leak was calculated for demonstrating the thermal insulation performance of cryogenic vessels depending on the new method. The results indicate that the vapor temperature should be seriously considered when the liquid level ratio is less than 50 %.

Celastrol attenuates hepatitis C virus translation and inflammatory response in mice by suppressing heat shock protein 90ß.

Hepatitis C virus (HCV) infection is one of the major factors to trigger a sustained hepatic inflammatory response and hence hepatocellular carcinoma (HCC), but direct-acting-antiviral (DAAs) was not efficient to suppress HCC development. Heat shock protein 90 kDa (HSP90) is highly abundant in different types of cancers, and especially controls protein translation, endoplasmic reticulum stress, and viral replication. In this study we investigated the correlation between the expression levels of HSP90 isoforms and inflammatory response marker NLRP3 in different types of HCC patients as well as the effect of a natural product celastrol in suppression of HCV translation and associated inflammatory response in vivo. We identified that the expression level of HSP90ß isoform was correlated with that of NLRP3 in the liver tissues of HCV positive HCC patients (R2 = 0.3867, P < 0.0101), but not in hepatitis B virus-associated HCC or cirrhosis patients. We demonstrated that celastrol (3, 10, 30 µM) dose-dependently suppressed the ATPase activity of both HSP90α and HSP90ß, while its anti-HCV activity was dependent on the Ala47 residue in the ATPase pocket of HSP90ß. Celastrol (200 nM) halted HCV internal ribosomal entry site (IRES)-mediated translation at the initial step by disrupting the association between HSP90ß and 4EBP1. The inhibitory activity of celastrol on HCV RNA-dependent RNA polymerase (RdRp)-triggered inflammatory response also depended on the Ala47 residue of HSP90ß. Intravenous injection of adenovirus expressing HCV NS5B (pAde-NS5B) in mice induced severe hepatic inflammatory response characterized by significantly increased infiltration of immune cells and hepatic expression level of Nlrp3, which was dose-dependently ameliorated by pretreatment with celastrol (0.2, 0.5 mg/kg, i.p.). This study reveals a fundamental role of HSP90ß in governing HCV IRES-mediated translation as well as hepatic inflammation, and celastrol as a novel inhibitor of HCV translation and associated inflammation by specifically targeting HSP90ß, which could be developed as a lead for the treatment of HSP90ß positive HCV-associated HCC.

On-demand targeting nanotheranostics with stimuli-responsive releasing property to improve delivery efficiency to cancer.

Nanocarriers have great potential to enhance drug delivery efficiency and therapeutic effect for various cancers. However, premature drug leakage and non-specific targeting still limit the delivery efficiency. Here, we present a smart on-demand targeting nanotheranostic system (PO-PB@SPIOs) with stimuli-responsive releasing property to improve the delivery efficiency for ovarian cancer. This delivery system prevents premature drug leakage via boronate ester linkages and shields the targeting moieties (phenylboronic acid) from non-specific binding when circulating in the blood. The PO-PB@SPIOs would release the tumor-targeting payload (PB) in response to the tumor microenvironment. Then, PB was able to target the overexpressed sialic acids on tumor cells. The significant improvement of delivery efficiency was demonstrated in vivo by a significantly enhanced signal in near-infrared-fluorescence (NIRF)/magnetic-resonance (MR) imaging (5-fold higher) and a remarkable photo-thermal therapeutic effect (complete cure rate (CCR) up to 80%). Furthermore, due to the on-demand targeting and stimuli-responsive releasing strategy, this nanotheranostic system shows a greater delivery efficiency even than the active-targeting small molecules or control nanoformulations. We believe this delicate design has great potential to develop novel drug nanoformulation.

Association between IL1RL1 gene polymorphisms and allergic rhinitis risk in the Chinese Han population.

BACKGROUND: Although it has been confirmed that IL1RL1 is involved in the occurrence of allergic rhinitis (AR), the role of IL1RL1 gene single nucleotide polymorphisms (SNPs) in AR is still unclear. METHODS: We performed a case-control study including 1000 AR patients and 1000 healthy controls. The four SNPs rs72823628 G > A, rs950881 G > T, rs72823641 T > A and rs3771175 T > A in IL1RL1 were chosen and genotyped using Agena MassARRAY platform. The relationship between IL1RL1 SNPs and AR risk was analyzed by logistic regression and assessed with odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs). RESULTS: Overall analysis revealed that IL1RL1 gene rs72823628, rs950881 and rs3771175 were associated with a reduced AR risk. Stratified analysis showed that the three SNPs (rs72823628, rs950881 and rs3771175) were obviously linked to a reduced risk of AR in males. Moreover, no correlation was observed between haplotypes and reduced AR risk after the false discovery rate (FDR) correction. The false positive report probability (FPRP) analysis was used to further validate significant findings. CONCLUSION: Our study is the first to indicate that IL1RL1 gene polymorphisms (rs72823628, rs950881 and rs3771175) may be correlated with decreased risk of AR in the Chinese Han population.

Effects of N-Acetyl-L-Cysteine on Serum Indices and Hypothalamic AMPK-Related Gene Expression Under Chronic Heat Stress.

This study aims to investigate the effect of heat stress on the physiological metabolism of young laying hens and whether N-acetyl-l-cysteine (NAC) can effectively alleviate heat stress. 120 Hy-Line Brown laying hens aged 12 weeks were randomly divided into four groups: the control group (fed on basal diet under thermal neutral condition), HS group (fed on basal diet under heat stress condition), CN group (fed on the basic meal supplemented with 1,000 mg NAC per kg under thermal neutral condition), and HS+N group (fed on the basic meal was supplemented with 1000 mg NAC per kg under heat stress condition). The HS and HS+N groups were exposed to 36 ± 1°C for 10 h/day. The effects of NAC on the changes of serum concentrations of T3, T4, and CORT and hypothalamic gene and protein expressions induced by heat stress were measured. Results showed that heat stress upregulated the contents of T3, T4, and CORT, while NAC reduced the contents of T3, T4, and CORT. In addition, NAC downregulated AgRP expression, while upregulated the expression of POMC. Moreover, the expressions of AMPKα1, LKB1, and CPT1 were inhibited by NAC, while the expressions of AKT1, ACC, GPAT, and PPARα were increased after NAC treatment, and HMGR did not change significantly. Western blot and comprehensive immunofluorescence section of AMPK in the hypothalamus showed that NAC attenuated the activity of AMPK. In conclusion, NAC can enhance the resistance of laying hens to heat stress by alleviating the metabolic disorders of serum T3, T4, and CORT induced by heat stress, inhibiting the activation of the AMPK pathway and regulating the expression of appetite-related genes in the hypothalamus.

Nephropathogenic Infectious Bronchitis Virus Mediates Kidney Injury in Chickens via the TLR7/NF-κB Signaling Axis.

Nephropathogenic infectious bronchitis virus (NIBV) is one of the most important viral pathogens in the world poultry industry. Here, we used RT-qPCR, WB and immunofluorescence to explore the interaction between NIBV and the host innate immune system of the kidney. Multiple virions were found in the kidney tissues of the disease group under electron microscopy, and pathological changes such as structural damage of renal tubules and bleeding were observed by HE staining. In addition, we found that the mRNA levels of TLR7, TRAF6, and IKKß were upregulated after NIBV infection. IRF7 mRNA levels decreased significantly at 5 dpi and increased significantly at 11 to 18 dpi. The NF-κB P65 mRNA level increased significantly at 5 to 18 dpi and decreased at 28 dpi. However, NIBV infection-induced NF-κB P65 protein levels were downregulated at multiple time points. Moreover, we demonstrated that the cytokine (IFN-γ, IL-8, and IL-6) mRNA and protein expression levels were increased significantly at multiple time points after NIBV infection. Furthermore, immunofluorescence analysis showed that NF-κB P65 and IFN-γ were mainly located in the nuclear or perinuclear region. The positive signal intensity of NF-κB P65 was significantly lower than that of the normal group at 1 to 5 dpi, and there was no significant change in the subsequent time period. The positive signal intensity of IFN-γ decreased significantly at 5 dpi, and increased significantly at 11 to 28 dpi. In conclusion, we found that NIBV promoted cytokine release through the TLR7/NF-κB signaling axis, thus causing kidney injury.

The role of immunoglobulin E and mast cells in hypertension.

AIMS: Hypertension is the major cause of cardiovascular diseases and global mortality. Immunoglobulin E (IgE), which plays crucial roles in allergic diseases, has been implicated in the pathogenesis of vascular and cardiac remodelling via its receptor (FcεR1). In this study, we aimed to reveal the role of IgE and FcεR1 in hypertension. METHODS AND RESULTS: Herein, we reported that IgE levels were significantly increased in hypertensive patients as well as in hypertensive mice induced by angiotensin II (Ang II). Ang II-induced vascular remodelling and hypertension were significantly alleviated in FcεR1 genetic knockout mice or in mice treated with anti-IgE monoclonal antibody. Similarly, treatment with omalizumab (a clinical IgE antagonist) also markedly inhibited Ang II-induced hypertension. Furthermore, the cellular contribution of IgE-FcεR1 in hypertension was evaluated in mice with FcεR1 conditional knockout in mast cell (MC), smooth muscle cell (SMC), or endothelial cell (EC). Our data revealed that IgE-mediated hypertension is largely dependent on FcεR1 in MCs but not SMCs and ECs. Finally, RNA-seq and signalling pathway analyses of mouse bone marrow-derived MCs suggested that interleukin 6 (IL-6) is one of critical mediators in IgE-mediated hypertension. IL-6 derived from IgE-stimulated MCs promoted reactive oxygen species production and decreased the levels of phosphorylated endothelial nitric oxide synthase in ECs, leading to endothelial dysfunction. CONCLUSION: Our findings reveal that IgE contributes to the pathogenesis of hypertension, at least partially through activating the IgE-FcεR1 signalling in MCs. Thus, IgE may represent a new therapeutic target for IgE-mediated hypertension.

CLEC16A variants conferred a decreased risk to allergic rhinitis in the Chinese population.

Background: Allergic rhinitis (AR) is a chronic respiratory disease. Hereditary factors played a key role in the pathogenesis of the AR. This study investigated the association between CLEC16A variants and AR risk in the Chinese population. Methods: We applied Agena MassARRAY technology platform to genotype five single nucleotide polymorphisms (SNPs) located in CLEC16A in 1004 controls and 995 cases. The association between CLEC16A SNPs (rs2286973, rs887864, rs12935657, rs11645657 and rs36045143) and AR risk were calculated by logistic regression analysis, with odds ratio (OR) and 95% confidence interval (CI). False-positive report probability (FPRP) was also used to assess the significant results to reduce false positives. Multifactor dimensionality reduction (MDR) was completed to assess the interaction between CLEC16A variants to predict AR risk. Results: Totally, CLEC16A (rs887864, rs12935657, rs2286973, rs11645657 and rs36045143) were significantly associated with AR risk. Therein, rs2286973, rs11645657 and rs36045143 were related to a decreased risk of AR in the people ≤ 43 years old, females and the people with BMI≤24, respectively. And rs887864 and rs12935657 were also associated with a decreased susceptibility of AR in the people >43 years old. Meanwhile, in the results of region stratification, rs887864 conferred a reduced risk to AR in the people from loess hilly area. Conclusion: CLEC16A variants conferred a decreased risk to AR in the Chinese population.

Andrographolide derivative as antagonist of vitamin D receptor to induce lipidation of microtubule associate protein 1 light chain 3 (LC3).

Lipidation of microtubule associated protein 1 light chain 3 (LC3) is the critical step in autophagosome formation, numerous efforts have been made to design and develop small molecules that trigger LC3 lipidation to activate autophagy. In this study, we discovered a series of andrographolide derivatives as potent antagonists of vitamin D receptor (VDR) by luciferase reporter assay. Structure-activity-relationship study revealed that andrographolide derivative ZAV-12 specifically inhibited VDR signaling but not NF-κB or STAT3 activation. Western blot analysis indicates that ZAV-12 markedly triggered lipidation of LC3 in MPP+-induced Parkinsonism in vitro in an mTOR-independent manner. The ZAV-12 triggered lipidation was mediated through SREBP2 activation instead of changing expression levels of lipid synthesis genes. Furthermore, ZAV-12 treatment increased the ratio of LC3-II/LC3-I and oligomerization of A53T α-synuclein (SNCA) in SNCA triggered neurotoxicity. Taken together, these results demonstrate the therapeutic potential of VDR antagonist as novel drug candidate for neurodegenerative diseases.

Synthesis and evolution of neuroprotective effects of oxymatrine derivatives as anti-Alzheimer's disease agents.

While screening for natural product scaffolds as potential anti-Alzheimer's disease (AD), oxymatrine (OMT) was found to relieve symptoms of AD through diminishing death of neuronal cells caused by microglia-induced inflammation. In this study, 13 derivatives of OMT were synthesized and their neuroprotective effects were evaluated on Aß1-42 -induced PC12 cells using MTT method. In addition, the best neuroprotective potencies were obtained with compounds 4, 6e, and 6f, which were selected for evaluation of decrease in IL-1ß and TNF-α in Aß1-42 -treated PC12 cells. Collectively, these data reveal that derivatives 6e and 6f possess the best ability of diminish IL-1ß production and reverse cell damage in all compounds, which are possible to develop as therapeutic agents for AD.

Small molecules targeting ubiquitination to control inflammatory diseases.

The ubiquitination and deubiquitination of proteins govern signal transduction in every aspect of physiology and pathology, especially in cancer, inflammation, and autoimmune diseases. Rapid progress has been made in obtaining an in-depth understanding of the ubiquitination system since its first discovery during the 1970s. Manipulation of ubiquitination by small molecules is considered a novel therapeutic avenue. In this review, we summarize key applications of small molecules targeting ubiquitination enzymes and currently available technologies applied to the discovery of small molecules that control ubiquitination.

Preparation of the peroxisome proliferator-activated receptor α polyclonal antibody: Its application in fatty liver hemorrhagic syndrome.

Peroxisome proliferator-activated receptor α (PPARα) play a key role in the regulation of metabolic homeostasis, inflammation, cellular growth, and differentiation. To further explore the potential role of PPARα in the energy homeostasis of fatty liver hemorrhagic syndrome (FLHS), we reported the prokaryotic expression and purification of chicken PPARα subunit protein, and successfully prepared a polyclonal antibody against PPARα recombinant protein. The 987 bp PPARα subunit genes were cloned into the pEASY-T3 clone vector. Then the plasmid PCR products encoding 329 amino acids were ligated to pEASY-Blunt E2 vector and transformed into BL21 to induce expression. The recombinant PPARα subunit protein, containing His-tag, was purified by affinity column chromatography using Ni-NTA affinity column. Rabbit antiserum was generated by using the concentration of recombinant PPARα subunit protein as the antigen. The results of western blotting showed that the antiserum can specifically recognize chicken endogenous PPARα protein. Immunohistochemistry and immunofluorescence showed that the PPARα mainly existed in the nucleus of hepatocytes, renal epithelial cells and hypothalamic endocrine nerve cells. More importantly, western blotting and real-time quantitative PCR indicated that FLHS significantly decreased the expression of PPARα.

Comparing immersiveness and perceptibility of spherical and curved displays.

Curved displays are believed to create a feeling of immersiveness similar to virtual reality. However systematic studies are needed to demonstrate that this is, in fact, true and under what conditions. In an experimental study 24 participants compared five different displays (concave, convex, hemisphere, sphere and a flat display) in terms of their immersiveness and perceptibility, and they also rated their overall preferences. Both immersiveness and perceptibility affected overall preference ratings. Participants gave higher preference ratings to the convex and concave displays, which were rated high in immersiveness and perceptibility, but gave lower preference ratings to the hemisphere/spherical display which had high ratings on immersiveness but low ratings on perceptibility. The study results imply that curved displays do indeed create a feeling of immersiveness. Concave and convex displays were rated highly favorably and should receive more attention for applications where visual experience and a feeling of immersiveness is particularly important.

Hepatoprotective activity assessment of amino acids derivatives of picroside I and II.

Picrorhiza kurroa has a long medicinal history as a traditional medicinal plant in China and India that is widely used in clinical treatments. It is a common treatment for liver diseases, fever, diarrhoea, indigestion, and some other diseases. Modern pharmacological studies proved that P. kurroa rhizomes have high levels of picroside I and II, which were identified as main constituents with anti-inflammatory and hepatoprotective activities. In our study, we used picroside I and II as the lead compounds to generate derivatives by reactions with Boc-valine or Boc-proline, which underwent dehydration and condensation with the hydroxyl groups in the lead compounds in the presence of coupling reagent N,N'-dicyclohexylcarbodiimide. We synthesized 11 derivatives and examined their hepatoprotective effects in vitro by assessing the proliferation rates of H2 O2 -exposed HepG2 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. We found that some derivatives promoted higher proliferation rates in HepG2 cells than the natural compounds before derivatization, suggesting that those derivatives possessed an improved hepatoprotective capacity. The novel derivatization strategy for picrosides had the additional benefit that the esterification of their hydroxyl groups created derivatives not only with increased stability but also with improved pharmacokinetic properties and potentially prolonged half-life.

Discovery of fused bicyclic derivatives of 1H-pyrrolo[1,2-c]imidazol-1-one as VDR signaling regulators.

The modulation of VDR signaling is important in regulating tumor-related signal transduction and protecting from microorganismal infection. In this study we discovered by luciferase reporter assay that several fused bicyclic derivatives of 1H-pyrrolo[1,2-c]imidazol-1-one with the assistance of calcitriol result in up to three-fold increases of VDR promoter activity. Preliminary SAR results from 20 compounds disclose that ideal VDR signaling regulators of these compounds are built up by the optimal combination of multiple factors. Western blot analysis indicates that compounds of ZD-3, ZD-4 and ZD-5 not only significantly upregulate p62 and LC3-II but also elevate the ratio of LC3-II/LC3-I, which possibly leads to activated autophagy. All of five compounds also significantly downregulate p65 and upregulate p-p65 and ZD-3 is the most active one to NF-κB signaling, suggesting a possible induction of apoptosis through the regulation of NF-κB signal transduction mediated by VDR signaling. Compounds of ZD-3, ZD-4 and ZD-5 significantly counteract the interference by VDR shRNA, in which ZD-3 gets the highest compensation of VDR expression and the highest ratio of LC3-II/LC3-I, indicating that ZD-3 very likely activates VDR-mediated autophagy. Taken together, these 1H-pyrrolo[1,2-c]imidazol-1-one derivatives can modulate VDR signaling, possibly resulting in the regulation of some signal pathways to induce autophagy and apoptosis.

Synthesis and biological evaluation of picroside derivatives as hepatoprotective agents.

Picrorhizae Rhizoma as a hepatoprotective herb, has been applied for thousands of years, and picroside was proved to be its active constituent. In this study, twelve derivatives of picroside were synthesized and the hepatoprotective activity of the derivatives was evaluated on SMMC-7721 cells. Six out of the derivatives had shown a better protective effect on H2O2-induced SMMC-7221 cells than picroside, and the activity of two derivatives (2 and 4) was stronger than that of the reference compound, silybin. Compound 2 shown the strongest protective effect (EC50 = 6.064 ± 1.295 µM).

Synthesis and Promotion of the Osteoblast Proliferation Effect of Morroniside Derivatives.

Sambucus williamsii Hance has been used in fractures for thousands of years, but research on its active components, such as morroniside, until now had not been carried out. In this study, morroniside was taken as the leading compound, and fourteen derivatives were synthesized. The promotion of osteoblast proliferation effect of the derivatives was evaluated on MC3T3-E1 cells. Five derivatives (2, 3, 4, 5, and 14) showed a good proliferation effect on MC3T3-E1 cells, and their promoted expression effects on OC (Osteocalcin) and ALP (Alkaline phosphatase) in MC3T3-E1 cells were measured. Compound 3 was shown to have the strongest proliferation effect (EC50 = 14.78 ± 1.17 µg/mL) and to significantly promote the expression of OC and ALP.