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Myo-Inositol (MI) has been shown to alleviate aging in Caenorhabditis (C). elegans. However, the mechanism by which MI alleviates aging remains unclear. In this study, we investigate whether MI can modulate the PI3K so as to attenuate the insulin/IGF-1 signaling (IIS) pathway and exert the longevity effect. The wild-type C. elegans and two mutants of AKT-1 and DAF-16 were used to explore the mechanism of MI so as to extend the lifespan, as well as to improve the health indexes of pharyngeal pumping and body bend, and an aging marker of autofluorescence in the C. elegans. We confirmed that MI could significantly extend the lifespan of C. elegans. MI also ameliorated the pharyngeal pumping and body bend and decreased autofluorescence. We further adopted the approach to reveal the loss-of-function mutants to find the signaling mechanism of MI. The functions of the lifespan-extending, health-improving, and autofluorescence-decreasing effects of MI disappeared in the AKT-1 and DAF-16 mutants. MI could also induce the nuclear localization of the DAF-16. Importantly, we found that MI could dramatically inhibit the phosphoinositide 3-kinase (PI3K) activity in a dose-dependent manner with an IC50 of 90.2 μM for the p110α isoform of the PI3K and 21.7 μM for the p110β. In addition, the downregulation of the PI3K expression and the inhibition of the AKT phosphorylation by MI was also obtained. All these results demonstrate that MI can inhibit the PI3K activity and downregulate the PI3K expression, and the attenuation of the IIS pathway plays a crucial role for MI in alleviating aging in C. elegans. [ABSTRACT FROM AUTHOR]

A water stable Eu3+-organic framework (1-Eu), [Eu(HL)(H2L)]·7.5H2O (H3L = 3-(3,5-dicarboxylphenyl)-4-carboxylpyridine) was constructed through solvothermal synthesis and studied by structural analyses and luminescence sensing. Crystallographic studies revealed that 1-Eu was a 3D framework in which two adjacent Eu3+ ions with a single isophthalate bridge were interlinked by organic ligands HL or H2L and contained uncoordinated carboxylate groups. 1-Eu represents the (3,3,6,6)-connected (42·10)(42·10)(43·85·105·122)(44·82·104·125) topology. As expected, 1-Eu exhibits a strong red-light emission at room temperature. And 1-Eu also shows good thermal stability and high chemical stability in common solvents and even in acidic or basic solutions (pH = 3 to 12). Therefore, the strong luminescence, good stability and presence of free carboxylate oxygen atoms in the framework allow 1-Eu to serve as an excellent luminescence sensor for probing Fe3+ and Cr2O72− ions in water with quenching constant (KSV) values of 3.38 × 104 M−1 and 2.23 × 104 M−1, respectively. In addition, 1-Eu can be further used as a sensor for amines with high (KSV) values and relatively low limit of detection (LOD), e.g. the KSV and LOD values of ethylenediamine (EN) are 6.25 × 106 M−1 and 0.23 μM, respectively. Meanwhile, the luminescence intensity of the quenched 1-Eu samples will be recovered after washing with water, indicating that 1-Eu can act as a multiresponsive luminescence sensor for Fe3+, Cr2O72− and amines with high selectivity, sensitivity and recyclability. Moreover, the luminescence sensing mechanisms for the above different analytes were proposed. [ABSTRACT FROM AUTHOR]

A new flavanol, named songarin A (1), was isolated from Cynomorium songaricum Rupr. The structure was established on the basis of spectroscopic methods including 2D NMR techniques. Compound 1 displayed the protective effect against d-galactosamine-induced HepG2 damage and reduced the damage from 58.64% to 22.26%. [ABSTRACT FROM AUTHOR]

From November 1973 to June 1992, cryosurgery with liquid nitrogen (−196°C) was performed on 113 patients with hepatic cancer, including 107 patients with primary liver cancer (PLC) and 6 patients with secondary liver cancer (SLC). Of the 107 PLC patients, the subclinical stage constituted 30.8% (33/107), the moderate stage 61.7% (66/107), and the late stage 7.5% (8/107). There were 32 cases with small PLC (up to 5 cm). Liver cirrhosis was observed in 86.0% (92/107). We designed flat cryoprobes for freezing surface tumors, and single and multiple trocar cryoprobes for freezing tumors deep within the hepatic parenchyma. Intraoperative ultrasound was used for monitoring hepatic cryolesions. There were no operative mortalities and complications, such as rupture of a tumor, delayed bleeding, or bile leakage. The 5-year and 10-year survival rates were 22.0% and 8.2%, respectively, for the 107 PLC patients and 48.8% and 17.1%, respectively, for the 32 patients with small PLC. Of the 6 SLC patients, survival ranged from 2 months to 90 months (average, 23.2 months). One SLC patient has been well for 7 years and 6 months after cryosurgery. These results indicate that cryosurgery, the in situ freezing of cancer, is a safe and effective treatment for unresectable hepatic cancer. [ABSTRACT FROM AUTHOR]

Excess levels of chemical hepatotoxicants (alcohol, aflatoxin B1), oxidative drugs (acetaminophen) and some cytokines (ET-1, TGF-β1) can induce chronic or acute liver injury. After these, the severe hepatic disease, especially the liver fibrosis (LF) occurs without taking measures, which brings threat to human health. The dibenzocyclooctadiene lignans of S. chinensis (SCDLs) were found to act as the hepatoprotective components via blocking endothelin B receptor (ETBR). While study on its anti-LF mechanisms especially for its refined compound of schisantherin D (SC-D) is still a lack. So this study aims to investigate the anti-fibrosis effect of SC-D with in vitro and in vivo assays. Bioinformatics analysis revealed the close relations of ETBR to Smad2, Smad3, Nrf2, etc. in LF-related signaling pathways (such as TGF-β/Smad and Nrf2/ARE). Histopathological staining on livers showed the recovery trend in SC-D treated LF mice. SC-D also modulated expressions of ETBR and fibrosis or anti-oxidative related proteins (such as TIMP1, p-Smad2/3, Nrf2, Smad7, etc.) in LF mice livers. Serum levels of TNF-α, COL I, ALT, AST and LDH in SC-D treated mice were also downregulated compared with LF mice, and upregulated expression of GSH. In vitro studies, SC-D also modulated expressions of LF-related proteins to the normal tendency in LX-2 cell, while weakened its anti- LX-2 proliferation effect by transfections of si-Smad7 or si-Nrf2. Accordingly the anti-LF approach of SC-D showed relations with modulating ETBR linked fibrosis and anti-oxidative related signaling. Also, Smad7 and Nrf2 might be the key factors for SC-D mediated anti-LF effect. [Display omitted] • Dysfunction of ETBR mainly interferes expressions of TGF-β/Smad and Nrf2/ARE thus mediating liver fibrosis. • Schisantherin D mediated anti-liver fibrosis by blocking ETBR was confirmed with in vitro and in vivo studies. • Smad7 and Nrf2 were found to be key factors for Schisantherin D to exert its anti-liver fibrosis effect. [ABSTRACT FROM AUTHOR]

The intracellular protozoan parasite Babesia gibsoni infects canine erythrocytes and causes babesiosis. The hazards to animal health have increased due to the rise of B. gibsoni infections and medication resistance. However, the lack of high-quality full-genome sequencing sets has expanded the obstacles to the development of pathogeneses, drugs, and vaccines. In this study, the whole genome of B. gibsoni was sequenced, assembled, and annotated. The genomic size of B. gibsoni was 7.94 Mbp in total. Four chromosomes with the size of 0.69 Mb, 2.10 Mb, 2.77 Mb, and 2.38 Mb, respectively, 1 apicoplast (28.4 Kb), and 1 mitochondrion (5.9 Kb) were confirmed. KEGG analysis revealed 2,641 putative proteins enriched on 316 pathways, and GO analysis showed 7,571 annotations of the nuclear genome in total. Synteny analysis showed a high correlation between B. gibsoni and B. bovis. A new divergent point of B. gibsoni occurred around 297.7 million years ago, which was earlier than that of B. bovis , B. ovata, and B. bigemina. Orthology analysis revealed 22 and 32 unique genes compared to several Babesia spp. and apicomplexan species. The metabolic pathways of B.gibsoni were characterized, pointing to a minimal size of the genome. A species-specific secretory protein SA1 and 19 homologous genes were identified. Selected specific proteins, including apetala 2 (AP2) factor, invasion-related proteins BgAMA-1 and BgRON2, and rhoptry function proteins BgWH_04g00700 were predicted, visualized, and modeled. Overall, whole-genome sequencing provided molecular-level support for the diagnosis, prevention, clinical treatment, and further research of B. gibsoni . IMPORTANCE The whole genome of B. gibsoni was first sequenced, annotated, and disclosed. The key part of genome composition, four chromosomes, was comparatively analyzed for the first time. A full-scale phylogeny evolution analysis based on the whole-genome-wide data of B. gibsoni was performed, and a new divergent point on the evolutionary path was revealed. In previous reports, molecular studies were often limited by incomplete genomic data, especially in key areas like life cycle regulation, metabolism, and host-pathogen interaction. With the whole-genome sequencing of B. gibsoni , we provide useful genetic data to encourage the exploration of new terrain and make it feasible to resolve the theoretical and practical problems of babesiosis., Competing Interests: The authors declare no conflict of interest.

With the continuous development of information technology, new teaching resources "micro-video class" and teaching model "flipped classroom" have gradually attracted the attention of teachers. Whether and how they can be applied in pharmacology teaching has already become the focus of medical education research in recent years. This paper explores the application and evaluation of the flipped classroom based on micro-video class in pharmacology teaching in our college. Students in Class 1 and Class 2 majoring in clinical medicine of 2018 in Chengdu Medical College were randomly divided into experimental group and control group. The teaching model of flipped classroom based on micro-video class was used in the experimental group, while the traditional teaching model was used in the control group. Theory tests and questionnaires were carried out at the end of the course. The average scores of theoretical knowledge in experimental group were significantly higher than those in control group ( P < 0.05). In addition, the results of the feedback questionnaire showed that the overall satisfaction of students participating in flipped classroom based on micro-video class was higher ( P < 0.05), and students thought that their learning enthusiasm, learning efficiency, and abilities of autonomous learning and problem-solving were greatly improved compared with those of students taught applying the traditional teaching model. Flipped classroom based on micro-video class model successfully improved the outcome of pharmacology teaching. It is supposed to provide reference for the reform of pharmacology teaching in medical college., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Liu, Man, Luo, Zheng, Yang, Ming and Zhang.)

Until now, the dopamine (DA) precursor, L-3,4-dihydroxyphenylalanine (L-DOPA), remains the gold standard effective drug therapy for Parkinson's disease (PD) patients. Nevertheless, long-term chronic L-DOPA administration leads to the drug efficacy loss and severe adverse effects, such as L-DOPA-induced dyskinesia (LID). Icariin (ICA), a flavonoid that is extracted from Epimedium, has been proved to evoke neuroprotection against DA neuronal loss in PD animal models. Here, the present study detected the effects of ICA combined with L-DOPA on 6-hydroxydopamine (6-OHDA)-elicited DA neurotoxicity and L-DOPA-induced motor dysfunction as well. PC12 cells were applied to investigate the combination treatment of ICA and L-DOPA against 6-OHDA-lesioned neurotoxicity. In addition, rat substantia nigral stereotaxic injection of 6-OHDA-induced DA neuronal injury was performed to explore the neuroprotective effects mediated by ICA combined with L-DOPA. The pathological movement triggered by L-DOPA was determined by the abnormal involuntary movements (AIM) scores analysis. In PC12 cells, ICA combined with L-DOPA produced better neuroprotection from 6-OHDA-induced neurotoxicity than ICA or L-DOPA alone treatment. In parkinsonian 6-OHDA lesioned rats, ICA conferred DA neuroprotection as monotherapy and an enhancement benefit of L-DOPA treatment after daily administration of L-DOPA and ICA for 21 days. Moreover, ICA ameliorated the development of LID as evidenced by the lowered AIM scores without affecting L-DOPA-mediated efficacy. Furtherly, ICA attenuated neuroinflammation in 6-OHDA-induced DA neuronal loss and the development of LID in vivo . In conclusion, these findings suggest ICA might be a potential promising adjuvant to enhance L-DOPA efficacy and attenuate L-DOPA-produced adverse effects in PD.

This study aimed at investigating the possible mechanisms of hepatic protective activity of Cichorium intybus L. (chicory) in acute liver injury. Pathological observation, reactive oxygen species (ROS) detection and measurements of biochemical indexes on mouse models proved hepatic protective effect of Cichorium intybus L. Identification of active compounds in Cichorium intybus L. was executed through several methods including ultra performance liquid chromatography/time of flight mass spectrometry (UPLC-TOF-MS). Similarity ensemble approach (SEA) docking, molecular modeling, molecular docking, and molecular dynamics (MD) simulation were applied in this study to explore possible mechanisms of the hepato-protective potential of Cichorium intybus L. We then analyzed the chemical composition of Cichorium intybus L., and found their key targets. Furthermore, in vitro cytological examination and western blot were used for validating the efficacy of the selected compounds. In silico analysis and western blot together demonstrated that selected compound 10 in Cichorium intybus L. targeted Akt-1 in hepatocytes. Besides, compound 13 targeted both caspase-1 and Akt-1. These small compounds may ameliorate liver injury by acting on their targets, which are related to apoptosis or autophagy. The conclusions above may shed light on the complex molecular mechanisms of Cichorium intybus L. acting on hepatocytes and ameliorating liver injury.

Background: Wnt-induced secreted protein-1 (WISP-1/CCN4) is a member of the CCN family growth factors, and its role in liver fibrosis is largely unknown., Methods: For in vitro, hepatic stellate cells (HSCs) were isolated from Sprague-Dawley rats. Expression of WISP-1 during progressive activation of cultured rat HSCs was analyzed by qRT-PCR. The effects of TNF-a and TGF-beta1 on WISP-1 expression were analyzed in stellate cell lines HSC-T6 and LX-2. The effect of exogenous WISP-1 protein on LX-2 proliferation was examined. For in vivo, expressions of WISP-1 in fibrotic liver of a carbon tetrachloride (CCl4)-induced fibrosis rat model were analyzed by qRT-PCR and immunohistochemistry., Results: In vitro, WISP-1 was increasingly expressed during progressive activation of cultured rat HSCs. WISP-1 was significantly induced in HSC-T6 cells by TNF-a and in LX-2 cells by TGF-beta1. Recombinant WISP-1 protein promoted LX-2 proliferation in a dose-dependent manner. In vivo, both mRNA and protein expression levels of WISP-1 were increased significantly in experimental hepatic fibrosis model., Conclusions: Our results showed the upregulation of WISP-1 in both in vitro and in vivo liver fibrosis models, and WISP-1 stimulated the proliferation of HSCs in vitro. These results may be helpful to elucidate the exact role of WISP-1 in liver fibrogenesis.

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Although much is known about both the cellular changes that lead to HCC and the etiological agents responsible for the majority of HCC cases, the molecule pathogenesis of HCC is still not well understood. We aimed to determine the effect of c-Myc gene expression on the proliferative, invasive, and migrative capabilities of hepatocellular carcinoma HepG2 cells., Methods: A plasmid- based polymerase III promoter system was used to deliver and express short interfering RNA targeting c-Myc to reduce its expression in HepG2 cells. Western blot analysis was used to measure the protein level of c-Myc in HepG2 cells. The effects of c-Myc silencing on the invasion, motility, and proliferation of HepG2 cells were assessed using a Transwell chamber cell migration assay system and a growth curve assay, respectively., Results: The data showed that plasmids expressing siRNA against c-Myc significantly decreased its expression in HepG2 cells by up to 85%. Importantly, pSilencer-c-Myc transfected cells showed a significantly reduced potential in migration, invasion, and proliferation., Conclusion: C-Myc plays an important role in the development of hepatocellular carcinoma. The data show that down-regulating the c-Myc protein level in HepG2 cells by RNAi could significantly inhibit migration, invasion and proliferation of HepG2 cells. Thus, c-Myc might be a potential therapeutic target for hepatocellular carcinoma.

Peliosis hepatis (PH) is a rare benign condition characterized by the presence of multiple, randomly distributed, blood filled cystic areas of variable size within the liver parenchyma. PH is difficult to recognize and may be mistaken for neoplasm, metastases or multiple abscesses. A 75-year-old female with a previous history of colon cancer was admitted when a liver mass in the right liver lobe was found 11 mo after surgery during the follow-up period. Computed tomography and magnetic resonance imaging scan of the abdomen were performed. The initial possible diagnosis was metastatic hepatocellular carcinoma. The patient underwent excision of the hepatic segment where the nodule was located. The pathological diagnosis of the surgical specimen was PH. PH should be considered in the differential diagnosis of new liver lesions in patients whose clinical settings do not clearly favor metastasization. Clinicians and radiologists must recognize these lesions to minimize the probability of misdiagnosis and inappropriate treatment.

Background: Hepatocellular carcinoma (HCC) has a dismal 5-year-survival rate of 10%, so novel strategies are warranted. IL-24 mediates anti-tumor activity reducing STAT3 expression, which suggests that interferon (IFN) alpha may augment tumor cell lysis and reduce angiogenesis. We investigated the antitumor activity of treatment with IFN-α, with the oncolytic adenovirus SG600-IL-24, or the combination of both in HCC in vitro and in vivo., Results: RT-PCR, ELISA assay and Western-blot confirmed that the exogenous IL-24 gene was highly expressed in HCC cells infected with SG600-IL-24. Treatment with combined IFN-α and SG600-IL-24 suppressed growth and promoted apoptosis of the HepG2, MHCC97L, and HCCLM3 cell lines compared with the normal cell line L02. The combined therapy increased STAT1 and SOCS1 and apoptosis, but decreased the expression of the metastatic and angiogenic proteins MMP-2, XIAP, OPN, and VEGF, which are regulated by STAT3 in HCC cells in vitro. To assess the effects in vivo, the HCC cell line HCCLM3 was transplanted subcutaneously into the right flanks of nude mice. Mice in the IFN-α group, the SG600-IL-24 group, or the combined therapy group had significantly suppressed growth of the HCC xenografted tumors compared to the PBS control group of mice. Among the mice treated with the combination of IFN-α and SG600-IL-24, three of those eight mice had long-term survival and no evidence of a tumor. These mice also had decreased expression of the metastatic and angiogenic proteins MMP-2, XIAP, OPN, and VEGF., Conclusions: The present study demonstrated for the first time the potential antitumor activity of IFN-α combined with the oncolytic adenovirus SG600-IL-24 in HCC both in vitro and in vivo, and suggests its further development as a potential candidate for HCC cancer gene therapy.