Intermittent fasting improves glucose homeostasis not entirely dependent on caloric restriction in db/db male mice.

Intermittent fasting (IF), which involves prolonged fasting intervals accompanied by caloric restriction, is an effective dietary treatment for obesity and diabetes. Although IF offers many benefits, it is difficult to determine whether these benefits are the consequences of caloric restriction. Every-other-day feeding (EODF) is a commonly used IF research model. This study was designed to identify other effectors of EODF, in addition to caloric restriction, and the possible underlying mechanisms. Diabetic db/db mice were divided into three groups: ad libitum (AL), meal-feeding (MF) and EODF. The MF model was employed to attain a level of caloric restriction comparable to EODF, with food distribution evenly divided between 10 AM and 6 PM, thereby minimizing the fasting interval. EODF yielded greater improvements in glucose homeostasis than MF in db/db mice by reducing fasting glucose levels and enhancing glucose tolerance. However, these effects on glucose metabolism were less pronounced in lean mice. Furthermore, ubiquitination of the liverspecific glucocorticoid receptor (GR) facilitated its degradation, and downregulating Kruppel-like factor 9 (KLF9), which ultimately suppressed liver gluconeogenesis in diabetic EODF mice. Although GR and KLF9 might mediate the metabolic benefits of EODF, the potential benefits of EODF might be limited by elevated serum glucocorticoid (GC) levels in diabetic EODF mice. Overall, this study suggests that the metabolic benefits of EODF in improving glucose homeostasis are independent of caloric restriction, possibly due to the downstream effects of liver-specific GR degradation.

LncRNA ZFAS1 Alleviated NLRP3 Inflammasome-Mediated Pyroptosis through Regulating miR-96-5p/Smad7 Signaling in Allergic Rhinitis.

INTRODUCTION: The NLR family pyrin domain containing 3 (NLRP3)-mediated pyroptosis was positively correlated with the allergic rhinitis progression and was reported to be regulated by SMAD family member 7 (Smad7). Bioinformatics analysis revealed that Smad7 might be targeted by miR-96-5p, and miR-96-5p might be targeted by long noncoding RNA zinc finger antisense 1 (ZFAS1). However, the effects and regulatory mechanisms of the ZFAS1/miR-96-5p/Smad7 functional axis in allergic rhinitis have not been investigated. METHODS: Human nasal mucosa epithelial cell line RPMI 2650 and C57BL/6 mice were obtained for in vitro and in vivo studies. Dual-luciferase reporter assay and RNA immunoprecipitation were implemented for detecting molecular interactions. Cell counting kit-8 and flow cytometry were used for measuring cell viability and pyroptosis. ELISA was obtained for monitoring cytokine secretion. RT-qPCR and Western blot were examined for determining RNA and protein expression. RESULTS: In vitro studies revealed that ZFAS1 was downregulated in interleukin (IL)-13-treated RPMI 2650 cells, while overexpression of ZFAS1 enhanced cell viability and inhibited NLRP3-mediated pyroptosis and inflammatory response. ZFAS1 directly inhibited miR-96-5p to suppress NLRP3-mediated pyroptosis in IL-13-treated RPMI 2650 cells. MiR-96-5p bound to the 3'-untranslated region of Smad7 and knockdown of Smad7 significantly reversed the effects of miR-96-5p depletion. Moreover, in vivo experiments further confirmed the findings of in vitro studies and showed ZFAS1 overexpression or miR-96-5p inhibition alleviated allergic rhinitis in vivo. CONCLUSION: ZFAS1 downregulated the expression of miR-96-5p to upregulate Smad7 level, which subsequently inhibited NLRP3-mediated pyroptosis and inflammatory response to ameliorate allergic rhinitis.

HDAC3-mediated lncRNA ZFAS1 inhibited IL-13-induced secretion of proinflammatory cytokines in nasal epithelial cells by regulating the miR-7-5p/SIRT1 pathway.

Allergic rhinitis (AR) is a disease that is difficult to cure and accompanies the patient's life. Proinflammatory cytokines (GM-CSF and eotaxin) and MUC5AC are key mediators promoting AR progression. Herein, the function of lncRNA ZFAS1 in AR was investigated. Nasal epithelial cells (NECs) were subjected to 50 ng/mL IL-13 for 24 h to construct an AR cell model. The mRNA and protein expressions were assessed using qRT-PCR and western blot. The levels of GM-CSF, eotaxin, IL-1ß, IL-6, TNF-α and MUC5AC in cell supernatant were examined by ELISA. The binding relationships between HDAC3, ZFAS1, miR-7-5p and SIRT1 were analysed using dual luciferase reporter or ChIP assays. Herein, our results displayed that ZFAS1 and SIRT1 were lowly expressed in AR, while miR-7-5p and HDAC3 were highly expressed. Functional experiments displayed that ZFAS1 overexpression suppressed IL-13-induced proinflammatory cytokines and mucin production in NECs. The highly expressed HDAC3 in AR inhibited ZFAS1 expression by binding with ZFAS1 promoter. In addition, our experiments revealed that ZFAS1 targeted miR-7-5p, and miR-7-5p targeted SIRT1. As expected, miR-7-5p overexpression or SIRT1 silencing abrogated ZFAS1 upregulation's repression on IL-13-induced proinflammatory cytokines and MUC5AC secretory levels in NECs. ZFAS1 suppressed proinflammatory cytokines, inflammatory cytokines, and MUC5AC secretory levels in AR by regulating the miR-7-5p/SIRT1 axis. Thus, our work suggested that ZFAS1 might serve as a novel target for AR treatment and prevention.

Protection of propofol on liver ischemia reperfusion injury by regulating Cyp2b10/ Cyp3a25 pathway.

To verify whether propofol alleviates liver ischemia-reperfusion injury (IRI) in mice by regulating Cyp2b10/ Cyp3a25 pathway. The liver I/R injury in vivo and in vitro model was constructed. The serum level of AST, ALT, ALP and ALB was detected using ELISA. The mRNA and protein expression of Cyp2b10 and Cyp3a25 were determined by qRT-PCR and western blot, respectively. The liver cell activity was assessed by MTT assay. The binding between Cyp2b10 and Cyp3a25 was evaluated by online website prediction, CoIP, and cell transfection with Cyp2b10 siRNA and pcDNA3.1-Cyp3a25. The hepatocyte apoptosis was examined using flow cytometry assay. The serum level of AST, ALT, ALP was increased and that of ALB was decreased in liver I/R injury in vivo model. Also, the mRNA and protein expression of Cyp2b10 and Cyp3a25 were enhanced and reduced in liver I/R injury in vivo and vitro model respectively. The liver cell activity was markedly reduced in H/R cell model. However, these changes were all reversed with propofol treatment. Furthermore, Cyp2b10 could directly bind to Cyp3a25 to regulate the H/R-induced hepatocyte apoptosis. Propofol plays an effect of on liver I/R injury by regulating Cyp2b10/ Cyp3a25 pathway.

The hepatoprotective effect from ischemia-reperfusion injury of remote ischemic preconditioning in the liver related surgery: a meta-analysis.

BACKGROUND: This study aimed to assess the hepatoprotective effect of remote ischemic preconditioning (RIPC) in the liver related surgery. METHODS: Published articles in PubMed, Embase and Cochrane clinical trial databases were searched from the inception to May 2021. Randomized control trials (RCTs) comparing the RIPC with control or other conditionings were included for analysis. The postoperative liver synthetic function was used as the primary outcome. RESULTS: A total of six RCTs were included the present meta-analysis. There were 216 patients underwent RIPC and 212 patients in the control group. The RIPC group had a significantly lower level of postoperative alanine transaminase and aspartate transaminase (p<0.001). The postoperative bilirubin level was also significant lower in the RIPC group than the control group (MD = -9.0, 95%CI, -13.94 to -4.03; p<0.001). ICG clearance was reduced in controls versus RIPC (p<0.001). There was no significant difference between the RIPC and control group in terms of the complication rate. CONCLUSION: The RIPC was evaluated to have a strong hepatoprotective effect from ischemia-reperfusion injury in the liver related surgery.

Towards Holistic Governance of China's E-Waste Recycling: Evolution of Networked Policies.

Electronic products are being updated and replaced much faster and there is therefore an increasing growth in electronic waste (e-waste). In order to promote professional recycling of e-waste, the relevant government departments of China have published a series of policies. This paper aims to unearth the evolution tendency of the networked policies towards holistic governance of China's e-waste recycling. Content analysis, quantitative text analysis and network analysis are applied to analyze relevant policy documents from 2001 to 2016. This paper illustrates evolution of policy themes, evolution of intergovernmental relationships, and evolution of policy relations. This study reveals policy intentions, maps policy progress, and unearths governance philosophy, providing an overall understanding of the policy ways by which the Chinese government has deployed its guiding strategies on professional recycling of e-waste. This paper illustrates how to approach holistic governance from perspective of networked policies, contributing to answering the central question of holistic governance about how to achieve it.

Beyond Just Giving Care: Exploring the Role of Culture in Chinese American Personal Care Aides' Work.

As the number of older Chinese Americans with immigration background increases, there is a growing need for Chinese American personal care aides (CA-PCAs) to assist them with aging at home by providing culturally congruent and linguistically competent service. However, little is known about how culture factors into the caregiving process and influences CA-PCAs' well-being. In this study, two focus groups were conducted with ten immigrant CA-PCAs and conventional content analysis was used to analyze the qualitative data. Seven cultural themes were identified, including guanxi (relationship), renqing (favor), mianzi/lian (face), hierarchy and authority, communication, harmony, and elder respect. By drawing attention to the idiosyncratic cultural landscape and entailed challenges faced by underrepresented CA-PCAs, the investigators corroborate the importance of cultural sensitivity for working with ethnic minority non-familial caregivers. The findings shed light on cultural factors that can be targeted by culturally sensitive direct practices, programs, and policies.

Long Noncoding RNA SNHG5 Knockdown Alleviates Neuropathic Pain by Targeting the miR-154-5p/CXCL13 Axis.

Neuropathic pain is an unneglectable pain condition with limited treatment options owing to its enigmatic underlying mechanisms. Long noncoding RNA small nucleolar RNA host gene 5 (SNHG5) is involved in the progression of a spectrum of human cancers. However, its role in neuropathic pain remains undiscovered. In the present study, we established a mouse spinal nerve ligation (SNL) model, and a significant upregulation of SNHG5 was observed. Then we knocked down SNHG5 level in mouse L5 dorsal root ganglion (DRG) by delivering specific short hairpin RNA against SNHG5 with adenovirus vehicle. Mouse paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in response to mechanical stimuli was increased after SNHG5 knockdown, accompanied with decreased protein levels of glial fibrillary acidic protein (GFAP) and ionized calcium binding adapter molecule 1 (IBA-1). Besides, SNHG5 directly modulated the expression of miR-154-5p, which was downregulated in SNL mice. MiR-154-5p inhibition abolished the effect of SNHG5 knockdown on mouse behavioral tests and GFAP and IBA-1 levels. In addition, we validated that C-X-C motif chemokine 13 (CXCL13) was a novel downstream target of miR-154-5p, and CXCL13 level was positively related to that of SNHG5 in SNL mice. In conclusion, our study demonstrated that SNHG5 knockdown alleviated neuropathic pain and inhibited the activation of astrocytes and microglia by targeting the miR-154-5p/CXCL13 axis, which might be a novel therapeutic target for neuropathic treatment clinically.

Correction of the Over-resected Nose.

Overzealous reduction during rhinoplasty may result in manifold functional as well as aesthetic injuries to the nose and is a prevailing antecedent of revision rhinoplasty. Although challenges for the revision rhinoplasty surgeon abound, careful assessment of the anatomic deficiencies of the nose, accurate evaluation and management of a patient's expectations, and precise planning and execution of surgical technique serve to facilitate a successful result. Contemporary techniques for correction of the over-resected nose are discussed, with special attention directed toward costal cartilage grafting and diced cartilage fascia techniques.

Propofol inhibits hepatocellular carcinoma growth and invasion through the HMGA2-mediated Wnt/ß-catenin pathway.

Propofol is a commonly used intravenous anesthetic in tumor surgery. Recently, studies have confirmed that propofol has an antitumor effect on hepatocellular carcinoma (HCC); however, the molecular mechanism underlying this effect has not been elucidated until now. The present study aimed to investigate the mechanism of propofol on HepG2 cell proliferation, apoptosis and invasion, focusing on High Mobility Group AT-Hook 2 (HMGA2)-mediated Wnt/ß-catenin pathway. The HepG2 cells were treated with various concentrations of propofol for 24 h, the relative protein levels of HMGA2, Wnt3a, ß-catenin, Snail Family Zinc Finger 1 and c-myc were determined by western blot analysis. HMGA2-pcDNA3.1 plasmid was transfected into the HepG2 cells to overexpress HMGA2. Cell proliferation, apoptosis and invasion were examined by MTT assays, flow cytometry and Transwell-matrigel invasion assays, respectively. The results showed that propofol suppressed HMGA2 expression and Wnt/ß-catenin signaling in a dose-dependent manner. Propofol was able to inhibit cell proliferation and invasion, and induce cell apoptosis of HepG2 cells; however, these effects were attenuated by HMGA2 overexpression. The suppressed Wnt/ß-catenin signaling in HepG2 cells by treatment with propofol was also reversed by HMGA2 overexpression. In conclusion, this study provided a novel mechanism underlying the anti-tumor function of propofol on HCC. To the best of our knowledge, the present study is the first to demonstrate that propofol could downregulate the expression of HMGA2, which inhibited the Wnt/ß-catenin pathway, thus leading to the inhibition of cell proliferation and invasion, as well as the apoptosis of HepG2 cells.

Effect of dexmedetomidine on hippocampal neuron development and BDNF-TrkB signal expression in neonatal rats.

The study aimed to explore the effect of dexmedetomidine (DEX) on hippocampal neuron development process and on molecular expression of brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling pathway in neonatal rats. The hippocampal neuron cells were isolated from newborn neonatal rats and cultured in vitro. One control group and three treated groups with 1, 10, and 100 µmol/L DEX were used for the study. Cell activity and apoptosis were detected by the MTT and terminal deoxynucleotidyl transferase-mediated biotinylated uridine triphosphate (UTP) nick end labeling assays. The synaptophysin (SYN) and postsynaptic density 95 (PSD95) were detected by quantitative polymerase chain reaction. There was no difference in the viability of neuron cells among the different dose groups of DEX and the control group during days 2-10 (P>0.05). Compared to the control group, there was no significant difference (P>0.05) in the expressions of SYN and PSD95 in the groups treated with 1 and 10 µmol/L DEX, whereas significant difference in the expression was observed in the group treated with 100 µmol/L DEX (P<0.01). Compared with the control group, the expression of BDNF was significantly upregulated (P<0.05) in the group treated with 100 µmol/L DEX. There were no significant differences in TrkB expression among the four groups. The expression of p-N-methyl-D-aspartate receptor increased with an increase in the concentration of DEX; however, only the high dose revealed a significant upregulation compared with the control group. The neuroprotective effect of DEX may be achieved by upregulating the expression of BDNF and phosphorylation level of N-methyl-D-aspartate receptor.