Shu-Xie decoction alleviates oxidative stress and colon injury in acute sleep-deprived mice by suppressing p62/KEAP1/NRF2/HO1/NQO1 signaling

Introduction: Sleep disorders are common clinical psychosomatic disorders that can co-exist with a variety of conditions. In humans and animal models, sleep deprivation (SD) is closely related with gastrointestinal diseases. Shu-Xie Decoction (SX) is a traditional Chinese medicine (TCM) with anti-nociceptive, anti-inflammatory, and antidepressant properties. SX is effective in the clinic for treating patients with abnormal sleep and/or gastrointestinal disorders, but the underlying mechanisms are not known. This study investigated the mechanisms by which SX alleviates SD-induced colon injury in vivo.Methods: C57BL/6 mice were placed on an automated sleep deprivation system for 72 h to generate an acute sleep deprivation (ASD) model, and low-dose SX (SXL), high-dose SX (SXH), or S-zopiclone (S-z) as a positive control using the oral gavage were given during the whole ASD-induced period for one time each day. The colon length was measured and the colon morphology was visualized using hematoxylin and eosin (H&E) staining. ROS and the redox biomarkers include reduced glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) were detected. Quantitative real-time PCR (qRT-PCR), molecular docking, immunofluorescence and western blotting assays were performed to detect the antioxidant signaling pathways.Results: ASD significantly increased FBG levels, decreased colon length, moderately increased the infiltration of inflammatory cells in the colon mucosa, altered the colon mucosal structure, increased the levels of ROS, GSH, MDA, and SOD activity compared with the controls. These adverse effects were significantly alleviated by SX treatment. ASD induced nuclear translocation of NRF2 in the colon mucosal cells and increased the expression levels of p62, NQO1, and HO1 transcripts and proteins, but these effects were reversed by SX treatment.Conclusion: SX decoction ameliorated ASD-induced oxidative stress and colon injury by suppressing the p62/KEAP1/NRF2/HO1/NQO1 signaling pathway. In conclusion, combined clinical experience, SX may be a promising drug for sleep disorder combined with colitis

Puerarin Alleviates Neuropathic Pain by Inhibiting Neuroinflammation in Spinal Cord

Neuropathic pain responds poorly to drug treatments, and partial relief is achieved in only about half of the patients. Puerarin, the main constituent of Puerariae Lobatae Radix, has been used extensively in China to treat hypertension and tumor. The current study examined the effects of puerarin on neuropathic pain using two most commonly used animal models: chronic constriction injury (CCI) and diabetic neuropathy. We found that consecutive intrathecal administration of puerarin (4–100 nM) for 7 days inhibited the mechanical and thermal nociceptive response induced by CCI and diabetes without interfering with the normal pain response. Meanwhile, in both models puerarin inhibited the activation of microglia and astroglia in the spinal dorsal horn. Puerarin also reduced the upregulated levels of nuclear factor-κB (NF-κB) and other proinflammatory cytokines, such as IL-6, IL-1β, and TNF-α, in the spinal cord. In summary, puerarin alleviated CCI- and diabetes-induced neuropathic pain, and its effectiveness might be due to the inhibition of neuroinflammation in the spinal cord. The anti-inflammation effect of puerarin might be related to the suppression of spinal NF-κB activation and/or cytokines upregulation. We conclude that puerarin has a significant effect on alleviating neuropathic pain and thus may serve as a therapeutic approach for neuropathic pain

Resting-State Functional Connectivity Within Medial Prefrontal Cortex Mediates Age Differences in Risk Taking

To investigate the association between age-related changes in risk taking and resting-state functional activity, we recorded resting-state scans from both young (n=26) and older adults (n=27). In addition, all participants completed two decision-making tasks: the Cambridge Gambling Task and the Balloon Analogue Risk Task. We found that older adults showed decreased functional connectivity within the medial prefrontal cortex, particularly between the ventromedial prefrontal cortex and the dorsal medial prefrontal cortex. Moreover, these changes in resting-state functional connectivity were associated with the individuals&#39; risk-taking behavior, and mediated the influence of age on risk taking.</p

The expression and significance of feces cyclooxygensae-2 mRNA in colorectal cancer and colorectal adenomas

Background/Aim: This study aims to explore the expression and significance of feces cyclooxygensae-2 (COX-2) mRNA in colorectal cancer and colorectal adenomas. Materials and Methods: The expression of feces COX-2 mRNA in colorectal cancer (n = 28), colorectal adenomas (n = 54), and normal control group (n = 11) were examined by reverse transcriptase polymerase chain reaction (RT-PCR). The positive rate of fecal occult blood test (FOBT) were detected in colorectal cancer (n = 30), colorectal adenomas (n = 56), and normal control group (n = 11); the sensitivity of the two methods was also compared. Results: The positive rate of feces COX-2 mRNA in colorectal cancer was 82.1% (25/28), which was significantly higher than colorectal adenomas 59.3% (32/54), and normal tissues 18.2% (2/11), the difference being significant between the three groups (χ2= 13.842,P= 0.001). The positive rate of FOBT in colorectal cancer was 73.3% (10/30), which was significantly higher than colorectal adenomas 10.7% (6/56) and normal tissues 9.1% (1/11), the difference being significant between these three groups (χ2= 7.525,P= 0.023). There was no significant association between feces COX-2 expression and various clinical pathological features of colorectal cancer and colorectal adenomas (P > 0.05). The sensitivity of the RT-PCR method is higher than FOBT, however, the specificity of FOBT is slightly higher than RT-PCR. Conclusions: High expression of feces COX-2 mRNA in colorectal adenomas and colorectal cancer is a common event; it is an early event in the development of colorectal adenomas to colorectal cancer. Feces COX-2 mRNA has a high sensitivity for detect colorectal cancer; combination with FOBT will be the best alternative. Feces COX-2 can be potentially used in the early diagnosis and screening of colorectal cancer

Investigation on the processing and improving the cleavage efficiency of furin cleavage sites in Pichia pastoris

Abstract Background Proprotein convertase furin is responsible for the processing of a wide variety of precursors consisted of signal peptide, propeptide and mature peptide in mammal. Many precursors processed by furin have important physiological functions and can be recombinantly expressed in Pichia pastoris expression system for research, pharmaceutical and vaccine applications. However, it is not clear whether the furin cleavage sites between the propeptide and mature peptide can be properly processed in P. pastoris, bringing uncertainty for proper expression of the coding DNA sequences of furin precursors containing the propeptides and mature peptides. Results In this study, we evaluated the ability of P. pastoris to process furin cleavage sites and how to improve the cleavage efficiencies of furin cleavage sites in P. pastoris. The results showed that P. pastoris can process furin cleavage sites but the cleavage efficiencies are not high. Arg residue at position P1 or P4 in furin cleavage sites significantly affect cleavage efficiency in P. pastoris. Kex2 protease, but not YPS1, in P. pastoris is responsible for processing furin cleavage sites. Heterologous expression of furin or overexpression of Kex2 in P. pastoris effectively increased cleavage efficiencies of furin cleavage sites. Conclusions Our investigation on the processing of furin cleavage sites provides important information for recombinant expression of furin precursors in P. pastoris. Furin or Kex2 overexpressing strains may be good choices for expressing precursors processed by furin in P. pastoris

The Roles of microRNAs in Regulating the Expression of PD-1/PD-L1 Immune Checkpoint

Engagement of programmed death-ligand 1 (PD-L1) with its receptor programmed death 1 (PD-1) on T cells has been speculated to play a major role in suppressing the immune system, which helps tumor cells evade anti-tumor immunity. With the development of whole genome sequencing technologies, microRNAs have gained more attention as an important new layer of molecular regulation. Recent studies have revealed that altered expression of microRNAs play a pivotal role in immune checkpoint and various cellular processes in cancer. In this review, we focused on the latest progress about microRNAs research which involves the regulation of PD-1/PD-L1 immune checkpoint

Meta-analysis of acupuncture for relieving non-organic dyspeptic symptoms suggestive of diabetic gastroparesis

Xiamen Science and Technology Bureau (Xiamen Research Platform for Systems Biology of Metabolic Disease) [3502Z20100001]; National Natural Science Foundation [30973912, 81073113, 81270901]Background: Acupuncture is widely used to treat diabetic patients with dyspeptic symptoms suggestive of gastroparesis in China. We conducted this systematic review of randomized controlled trials (RCTs) to evaluate the efficacy of acupuncture for diabetic gastroparesis (DGP). Methods: We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and four Chinese databases including China National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodicals, Chinese Biomedical Literature Database (CBM) and WanFang Data up to January 2013 without language restriction. Eligible RCTs were designed to examine the efficacy of acupuncture in improving dyspeptic symptoms and gastric emptying in DGP. Risk of bias, study design and outcomes were extracted from trials. Relative risk (RR) was calculated for dichotomous data. Mean difference (MD) and standardized mean difference (SMD) were selected for continuous data to pool the overall effect. Results: We searched 744 studies, among which 14 RCTs were considered eligible. Overall, acupuncture treatment had a higher response rate than controls (RR, 1.20 [95% confidence interval (CI), 1.12 to 1.29], P < 0.00001), and significantly improved dyspeptic symptoms compared with the control group. There was no difference in solid gastric emptying between acupuncture and control. Acupuncture improved single dyspeptic symptom such as nausea and vomiting, loss of appetite and stomach fullness. However, most studies were in unclear and high risk of bias and with small sample size (median = 62). The majority of the RCTs reported positive effect of acupuncture in improving dyspeptic symptoms. Conclusions: The results suggested that acupuncture might be effective to improve dyspeptic symptoms in DGP, while a definite conclusion about whether acupuncture was effective for DGP could not be drawn due to the low quality of trials and possibility of publication bias. Further large-scale, high-quality randomized clinical trials are needed to validate this claim and translate this result to clinical practice

An Aqueous Extract of Radix Astragali, Angelica sinensis, and Panax notoginseng Is Effective in Preventing Diabetic Retinopathy

Diabetic retinopathy (DR), in which inflammation has been implicated playing important roles, is one of the most common diabetes complications. Dang Gui Bu Xue Tang (DBT), an aqueous extract of Radix Astragali and Radix Angelica sinensis, is a classical prescription in Traditional Chinese Medicine for treating inflammation and ischemic diseases. Here, we investigated the effects of a modified recipe of DBT, with addition of Panax notoginseng, in treating diabetic retinopathy. An aqueous extract of Radix Astragali, Radix Angelica sinensis, and Panax notoginseng (RRP) was given to Goto-Kakizaki (GK) rats and streptozotocin-induced Sprague-Dawley (SD) rats. Leukostasis, vascular leakage, and acellular capillaries in retinal vasculature of animals were determined. Expression of retinal inflammatory biomarkers was assessed. We found that RRP reduced leukostasis, acellular capillaries, and vascular leakage compared to diabetic control rats. We also found that RRP decreased the expression of inflammatory factors including IL-1β, IL-6, TNF-α, NF-κB, MCP-1, ICAM-1, or VCAM-1 in the retinas of GK rats and reversed high glucose-induced inhibition of endothelial cell migration and proliferation in vitro. We conclude that RRP has a potent effect in preventing the pathogenesis and/or progression of DR and thus may serve as a promising nontoxic therapeutic approach of DR