Inhibition of visfatin alleviates sepsis-induced intestinal damage by inhibiting Hippo signaling pathway

Background

The aim of this study is to investigate role of Visfatin, one of the pro-inflammatory adipokines, in sepsis-induced intestinal injury and to clarify the potential mechanism.

Methods

C57BL/6 mice underwent cecal ligation and puncture (CLP) surgery to establish sepsis model in vivo. Intestinal epithelial cells were stimulated with LPS to mimic sepsis-induced intestinal injury in vitro. FK866 (the inhibitor of Visfatin) with or without XMU-MP-1 (the inhibitor of Hippo signaling) was applied for treatment. The expression levels of Visfatin, NF-κB and Hippo signaling pathways-related proteins were detected by western blot or immunohistochemistry. The intestinal cell apoptosis and intestinal injury were investigated by TUNEL staining and H&E staining, respectively. ELISA was used to determine the production of inflammatory cytokines.

Results

The expression of Visfatin increased in CLP mice. FK866 reduced intestinal pathological injury, inflammatory cytokines production, and intestinal cell apoptosis in sepsis mice. Meanwhile, FK866 affected NF-κB and Hippo signaling pathways. Additionally, the effects of FK866 on inflammatory response, apoptosis, Hippo signaling and NF-κB signaling were partly abolished by XMU-MP-1, the inhibitor of Hippo signaling. In vitro experiments also revealed that FK866 exhibited a protective role against LPS-induced inflammatory response and apoptosis in intestinal cells, as well as regulating NF-κB and Hippo signaling, whereas addition of XMU-MP-1 weakened the protective effects of FK866.

Conclusion

In short, this study demonstrated that inhibition of Visfatin might alleviate sepsis-induced intestinal injury through Hippo signaling pathway, supporting a further research on Visfatin as a therapeutic target.

     

Ursolic acid induces apoptosis and autophagy in oral cancer cells

Oral squamous cell carcinoma (OSCC) is the fifth common cause of cancer mortality in Taiwan with high incidence and recurrence and needs new therapeutic strategies. In this study, ursolic acid (UA), a triterpenoid, was examined the antitumor potency in OSCC cells. Our results showed that UA inhibited the proliferation of OSCC cells in a dose‐ and time‐dependent manner in both Ca922 and SCC2095 oral cancer cells. UA induced caspase‐dependent apoptosis accompanied with the modulation of various biological biomarkers including downregulating Akt/mTOR/NF‐κB signaling, ERK, and p38. In addition, UA inhibited angiogenesis as evidenced by abrogation of migration/invasion and blocking MMP‐2 secretion in Ca922 cells. Interestingly, UA induced autophagy in OSCC cells, as manifested by LC3B‐II conversion and increased p62 expression and accumulation of autophagosomes. Inhibition by autophagy inhibitor enhanced UA‐mediated apoptosis in Ca922 cells. The experiment provides a rationale for using triterpenoid in the treatment of OSCC.     

奥美定隆乳注射患者术后取出的手术方式分析

探讨奥美定隆乳注射患者术后取出的手术方式。对我科收治的奥美定注射患者,根据其临床表现、B超和MRI检查分成包膜硬结型、散在团块型、液态游走型及混合型,对不同类型的患者采取不同的手术方式。比较其愈合时间、术后并发症及复发情况。乳腔镜手术在伤口愈合时间上显著短于乳晕切口包块取出术。液态游走型或混合型患者行乳腔镜下包块取出术,术后伤口感染、疾病复发率显著高于乳腺切除组。包膜硬结型、散在团块型可行乳腔镜包块取出术、乳晕切口包块取出术或乳腺部分切除术,以尽量保留乳腺的完整,液态游走型或混合型应行乳腺全切术以彻底根治。     

Hierarchical structured Mn2O3 nanomaterials with excellent electrochemical properties for lithium ion batteries

A series of Mn₂O₃ nanomaterials with hierarchical porous structures was synthesized using three types of leaves as templates. In addition to their different morphologies, different porous nanostructures were achieved by choosing different leaves. The Mn₂O₃ nanomaterial prepared by using gingko leaves as a template provides a larger pore volume and a higher Brunauer–Emmett–Teller (BET) surface area. At the same time, this material also displays excellent electrochemical performance, that is, the specific capacities are 1274.6 mA h g⁻¹ after 300 cycles and 381.5 mA h g⁻¹ at current densities of 300 and 3000 mA g⁻¹, respectively.

A series of Mn₂O₃ nanomaterials with hierarchical porous structures was synthesized using three types of leaves as templates.     

A UPLC-MS/MS application for comparisons of the hepatotoxicity of raw and processed Xanthii Fructus by energy metabolites

The ripe fruit of Xanthium strumarium L. (Xanthii Fructus) cannot be widely used as a Chinese herbal medicine (CHM) owing to its hepatotoxicity. However, Xanthii Fructus (XF) can be used effectively and safely after correct processing based on traditional experience, although a high hepatotoxicity risk remains owing to improper usage. Therefore, the processing methods used must be clarified to ensure safety. The adenosine-5′-triphosphate (ATP) level in tissues is an important indicator reflecting the functional status of liver cells. Therefore, this study aims to evaluate the hepatotoxicity of XF using UPLC-MS/MS. The hepatotoxicity of raw XF (RXF) and XF processed by intermediary energy metabolites (PXF) is compared. The method is evaluated for its analytical performance and successfully applied to the quantification of ATP, adenosine-5′-diphosphate (ADP), adenosine-5′-monophosphate (AMP), atractyloside, and carboxyatractyloside in mouse liver. The hepatotoxicity results also indicate that the toxicity of XF is decreased after processing, perhaps due to the decrease in atractyloside and carboxyatractyloside contents. Importantly, the experimental evidence provides a rationale for the reduction in toxicity. These data show that mouse livers are damaged between the days 20 and 30 of RXF oral administration, and that the ATP level is decreased. Importantly, no significant difference is observed between the PXF treatment group and control group, while the RXF treatment group is significantly different. Therefore, processing can reduce the toxicity of XF.

The ripe fruit of Xanthium strumarium L. (Xanthii Fructus) cannot be widely used as a Chinese herbal medicine (CHM) owing to its hepatotoxicity.     

Combinatorial synthesis and biological evaluations of (E)-β-trifluoromethyl vinylsulfones as antitumor agents

Combinatorial synthesis of (E)-β-trifluoromethyl vinylsulfones is accomplished through a reaction of alkynes, Togni reagent, and sodium benzenesulfinates in DMSO under metal-free conditions at room temperature. These compounds are evaluated in several assays against different tumor cells. Some hits are identified against ES-2, HO-8910, and K562.

(E)-β-Trifluoromethyl vinylsulfones is accomplished through a reaction of alkynes, Togni reagent, and sodium benzenesulfinates under metal-free conditions. p-Acetylphenyl in R¹ has the best activities against several tumor cells.     

Impacts of e-health on the outcomes of care in low- and middle-income countries: where do we go from here?

E-health encompasses a diverse set of informatics tools that have been designed to improve public health and health care. Little information is available on the impacts of e-health programmes, particularly in low- and middle-income countries. We therefore conducted a scoping review of the published and non-published literature to identify data on the effects of e-health on health outcomes and costs. The emphasis was on the identification of unanswered questions for future research, particularly on topics relevant to low- and middle-income countries. Although e-health tools supporting clinical practice have growing penetration globally, there is more evidence of benefits for tools that support clinical decisions and laboratory information systems than for those that support picture archiving and communication systems. Community information systems for disease surveillance have been implemented successfully in several low- and middle-income countries. Although information on outcomes is generally lacking, a large project in Brazil has documented notable impacts on health-system efficiency. Meta-analyses and rigorous trials have documented the benefits of text messaging for improving outcomes such as patients' self-care. Automated telephone monitoring and self-care support calls have been shown to improve some outcomes of chronic disease management, such as glycaemia and blood pressure control, in low- and middle-income countries. Although large programmes for e-health implementation and research are being conducted in many low- and middle-income countries, more information on the impacts of e-health on outcomes and costs in these settings is still needed.