The causal association between artificial sweeteners and the risk of cancer: a Mendelian randomization study.

Artificial sweeteners (ASs) have been widely added to food and beverages because of their properties of low calories and sweet taste. However, whether the consumption of ASs is causally associated with cancer risk is not clear. Here, we utilized the two-sample Mendelian randomization (MR) method to study the potential causal association. Genetic variants like single-nucleotide polymorphisms (SNPs) associated with exposure (AS consumption) were extracted from a genome-wide association study (GWAS) database including 64 949 Europeans and the influence of confounding was removed. The outcome was from 98 GWAS data and included several types of cancers like lung cancer, colorectal cancer, stomach cancer, breast cancer, and so on. The exposure-outcome SNPs were harmonized and then MR analysis was performed. The inverse-variance weighted (IVW) with random effects was used as the main analytical method accompanied by four complementary methods: MR Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses consisted of heterogeneity, pleiotropy, and leave-one-out analysis. Our results demonstrated that ASs added to coffee had a positive association with high-grade and low-grade serous ovarian cancer; ASs added to tea had a positive association with oral cavity and pharyngeal cancers, but a negative association with malignant neoplasm of the bronchus and lungs. No other cancers had a genetic causal association with AS consumption. Our MR study revealed that AS consumption had no genetic causal association with major cancers. Larger MR studies or RCTs are needed to investigate small effects and support this conclusion.

Protective Mechanism of Electroacupuncture on Peripheral Neurotoxicity Induced by Oxaliplatin in Rats.

OBJECTIVE: To study the effect of electroacupuncture (EA) on oxaliplatin-induced peripheral neuropathy (OIPN) in rats. METHODS: Male Sprague-Dawley rats were equally divided into 3 groups using a random number table: the control group, the OIPN group, and the EA (OIPN + EA) group, with 10 rats in each. The time courses of mechanical, cold sensitivity, and microcirculation blood flow intensity were determined. The morphology of the dorsal root ganglion (DRG) was observed by electron microscopic examination. The protein levels of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and the transient receptor potential (TRP) protein family in DRGs were assayed by Western blot. RESULTS: EA treatment significantly reduced mechanical allodynia and cold allodynia in OIPN rats (P<0.01). Notably, oxaliplatin treatment resulted in impaired microcirculatory blood flow and pathomorphological defects in DRGs (P<0.01). EA treatment increased the microcirculation blood flow and attenuated the pathological changes induced by oxaliplatin (P<0.01). In addition, the expression levels of Nrf2 and HO-1 were down-regulated, and the TRP protein family was over-expressed in the DRGs of OIPN rats (P<0.01). EA increased the expression levels of Nrf2 and HO-1 and decreased the level of TRP protein family in DRG (P<0.05 or P<0.01). CONCLUSION: EA may be a potential alternative therapy for OIPN, and its mechanism may be mainly mediated by restoring the Nrf2/HO-1 signaling pathway.

[Therapeutic effect of Fanzhen Jieci needling on discogenic sciatica: a randomized controlled trial].

OBJECTIVE: To compare the therapeutic effect between Fanzhen Jieci (warming acupuncture plus fast needling) combined with conventional acupuncture and simple conventional acupuncture on discogenic sciatica. METHODS: A total of 76 patients with discogenic sciatica were randomized into a Fanzhen Jieci group and a conventional acupuncture group, 38 cases in each one. Conventional acupuncture was applied at Shenshu (BL 23), Dachangshu (BL 25), L1-L5 Jiaji (EX-B 2) and Huantiao (GB 30) on the affected side, etc. in the conventional acupuncture group. On the basis of the treatment in the conventional acupuncture group, Fanzhen Jieci was applied at L1-L5 Jiaji (EX-B 2) and Huantiao (GB 30) on the affected side in the Fanzhen Jieci group, i.e. warming acupuncture was applied at L1-L5 Jiaji (EX-B 2), and fast needling was applied at Huantiao (GB 30) on the affected side for a depth of 40-60 mm, so as to introduce a sensation of electric shock transmitting to lower limb, and then the needle was immediately withdrawn. The treatment was given once every other day, 3 times a week for 3 weeks in both groups. The visual analogue scale (VAS) score of leg and low back pain, the Oswestry disability index (ODI) score and the 36-item short form health survey (SF-36) score before and after treatment were compared between the two groups. RESULTS: Compared before treatment, the VAS scores of leg and low back pain and the ODI scores after treatment were decreased in both groups (P<0.001), the changes of the VAS scores of leg and low back pain in the Fanzhen Jieci group were larger than those in the conventional acupuncture group (P<0.05). After treatment, except for the role emotional and health transition scores, the various scores of SF-36 were increased compared before treatment in the Fanzhen Jieci group (P<0.01); except for the role physical, role emotional and health transition scores, the various scores of SF-36 were increased compared before treatment in the conventional acupuncture group (P<0.01). After treatment, the physical functioning, role physical, bodily pain, mental health and general health scores of SF-36 in the Fanzhen Jieci group were higher than those in the conventional acupuncture group (P<0.05). CONCLUSION: Fanzhen Jieci combined with conventional acupuncture can effectively relieve the pain and improve the mental state in patients with discogenic sciatica, its therapeutic effect is superior to simple conventional acupuncture.

High-quality Chlorella vulgaris biomass harvesting through chitosan and polyacrylamid2e.

Microalgal biomass is an emerging source of renewable energy and health-related compounds. However, harvesting of microalgae is a techno-economic hinder. In this research, chitosan and polyacrylamide were optimized harvesting condition for Chlorella vulgaris. Stirring at 300 rpm for 2 min is optimum for chitosan and polyacrylamide. Low-dose (10 mg/L) chitosan (flocculation efficiency (FE), 98.10 ± 1.06%) is more efficient than high-dose (25 mg/L) polyacrylamide (FE 94.57 ± 0.55%) for harvesting C. vulgaris. Chitosan resulted flocs settled more quickly than polyacrylamide, while polyacrylamide keep > 90% FE in a wider pH range (7-10) than chitosan (7-8). Chitosan and polyacrylamide both have no negative effect on biomass composition, including protein, carbohydrate, and carotenoid. C. vulgaris in flocs could successfully regrow in fresh culture media. The residual culture media was recycled with little impact on cell growth. All the results suggested that chitosan and polyacrylamide could harvest high-quality microalgal biomass.

Cancer CRC: A Comprehensive Cancer Core Transcriptional Regulatory Circuit Resource and Analysis Platform.

A core transcriptional regulatory circuit (CRC) is a group of interconnected auto-regulating transcription factors (TFs) that form loops and can be identified by super-enhancers (SEs). Studies have indicated that CRCs play an important role in defining cellular identity and determining cellular fate. Additionally, core TFs in CRCs are regulators of cell-type-specific transcriptional regulation. However, a global view of CRC properties across various cancer types has not been generated. Thus, we integrated paired cancer ATAC-seq and H3K27ac ChIP-seq data for specific cell lines to develop the Cancer CRC (http://bio.liclab.net/Cancer_crc/index.html). This platform documented 94,108 cancer CRCs, including 325 core TFs. The cancer CRC also provided the "SE active core TFs analysis" and "TF enrichment analysis" tools to identify potentially key TFs in cancer. In addition, we performed a comprehensive analysis of core TFs in various cancer types to reveal conserved and cancer-specific TFs.

Electroacupuncture Attenuates Neuropathic Pain and Comorbid Negative Behavior: The Involvement of the Dopamine System in the Amygdala.

Neuropathic pain (NeuP) is an important clinical problem accompanying negative mood symptoms. Neuroinflammation in the amygdala is critically involved in NeuP, and the dopamine (DA) system acts as an important endogenous anti-inflammatory pathway. Electroacupuncture (EA) can improve the clinical outcomes in NeuP, but the underlying mechanisms have not been fully elucidated. This study was designed to assess the effectiveness of EA on pain and pain-related depressive-like and anxiety-like behaviors and explore the role of the DA system in the effects of EA. Male Sprague-Dawley rats were subjected to the chronic constrictive injury (CCI) model to induce NeuP. EA treatment was carried out for 30 min once every other day for 3 weeks. The results showed that CCI caused mechanical hyperalgesia and depressive and anxiety-like behaviors in rats and neuroinflammation in the amygdala, such as an increased protein level of TNFα and IL-1ß and activation of astrocytes. EA treatment significantly improved mechanical allodynia and the emotional dysfunction induced by CCI. The effects of EA were accompanied by markedly decreased expression of TNFα, IL-1ß, and glial fibrillary acid protein (GFAP) in the amygdala. Moreover, EA treatment reversed CCI-induced down-regulation of DA concentration, tyrosine hydroxylase (TH) expression, and DRD1 and DRD2 receptors. These results suggest that EA-ameliorated NeuP may possibly be associated with the DA system to inhibit the neuroinflammation in the amygdala.

Resveratrol inhibits bile acid-induced gastric intestinal metaplasia via the PI3K/AKT/p-FoxO4 signalling pathway.

Gastric intestinal metaplasia (GIM) is the essential pre-malignancy of gastric cancer. Chronic inflammation and bile acid reflux are major contributing factors. As an intestinal development transcription factor, caudal-related homeobox 2 (CDX2) is key in GIM. Resveratrol has potential chemopreventive and anti-tumour effects. The aim of the study is to probe the effect of resveratrol in bile acid-induced GIM. We demonstrated that resveratrol could reduce CDX2 expression in a time- and dose-dependent manner in gastric cell lines. A Cignal Finder 45-Pathway Reporter Array and TranSignal Protein/DNA Array Kit verified that resveratrol could increase Forkhead box O4 (FoxO4) activity and that Chenodeoxycholic acid (CDCA) could reduce FoxO4 activity. Furthermore, bioinformatics analysis showed that FoxO4 could bind to the CDX2 promoter, and these conjectures were supported by chromatin-immunoprecipitation (ChIP) assays. Resveratrol can activate FoxO4 and decrease CDX2 expression by increasing phospho-FoxO4 nucleus trans-location. Resveratrol could increase FoxO4 phosphorylation through the PI3K/AKT pathway. Ectopic FoxO4 expression can up-regulate FoxO4 phosphorylation and suppress CDCA-induced GIM marker expression. Finally, we found a reverse correlation between p-FoxO4 and CDX2 in tissue arrays. This study validates that resveratrol could reduce bile acid-induced GIM through the PI3K/AKT/p-FoxO4 signalling pathway and has a potential reversing effect on GIM, especially that caused by bile acid reflux.

"Fan-zhen Jie-ci" acupuncture therapy for treatment of discogenic sciatica: protocol for a single-blind, randomized controlled clinical trial.

BACKGROUND: Curative medical treatment for patients with discogenic sciatica is limited. Acupuncture is an important non-pharmacological therapy reported to have positive therapeutic effects on discogenic sciatica. According to traditional Chinese acupuncture theory, discogenic sciatica is a channel tendon disease which can be treated by a special "Fan-zhen Jie-ci (FZJC)" method. Our recent preliminary clinical evidence indicated that the FZJC method had a positive treatment effect on the disease. This study will further evaluate the efficacy and safety of FZJC on patients with discogenic sciatica. METHODS: A single-blind randomized controlled clinical trial will be conducted, assigning 76 participants with discogenic sciatica to a randomly assigned FZJC group or a control group. Acupuncture treatment combined with the FZJC method will be applied in the FZJC group while routine acupuncture treatment only will be applied in the control group. Treatments will be administered three times a week for a total of 3 consecutive weeks. The primary outcome of this trial is change in the visual analogue scale of leg pain (VAS-LP), and the secondary outcomes are changes in the visual analogue scale of back pain (VAS-BP), the Brief Pain Inventory (BPI), the Oswestry Disability Index (ODI), the 36-Item Short Form Health Survey (SF-36), and serum concentrations of mitochondrial DNA (mtDNA) and high sensitivity C reactive protein (hsCRP). DISCUSSION: The results of this study will provide insight into the efficacy and safety of FZJC acupuncture as a treatment for discogenic sciatica. TRIAL REGISTRAION: The trial has been registered at the Chinese Clinical Trial Registry (ChiCTR1900026272) and the Acupuncture-Moxibustion Clinical Trial Registry (AMCTR-IOR-19000275).

[Research advances in the limbic system involved in acupuncture treatment of chronic pain].

Pain, especially chronic pain, can cause multiple changes including sensory-discriminative, emotional-affective, and cognitive-behavior changes and thus greatly affects patients' physical and mental health and quality of life. Therefore, multi-dimensional regulation of paralgesia, cognitive impairment, and negative emotion in patients with chronic pain has become a hot spot in recent studies. The brain regions in the limbic system are involved in the formation and expression of "pain sensation-emotion-cognition". Existing evidence suggests that acupuncture has a multi-dimensional comprehensive regulatory effect on chronic pain, and the brain regions in the limbic system also mediate the analgesic effect of acupuncture. However, further studies are still needed to explore the role and mechanism of action of these brain regions in the multi-dimensional regulation of chronic pain by acupuncture. This article reviews the research advances in the neural mechanism of the limbic system in chronic pain and the role of the limbic system in mediating acupuncture analgesia and mainly elaborates on the mechanism of action of the brain regions in the limbic system in the multi-dimensional regulation of chronic pain.

Cardioprotective effect of electroacupuncture in cardiopulmonary bypass through apelin/APJ signaling.

Aim Acupuncture, particularly electroacupuncture (EA), can improve the clinical outcomes of cardiopulmonary bypass (CPB) patients; however, the mechanisms remain unclear. This study aimed to examine the effects of EA pre-treatment on myocardial injury after CPB and investigate its potential mechanisms. MAIN METHODS: Male Sprague-Dawley rats were subjected to CPB and divided into Control (sham-operated), CPB, and EA (CPB + EA) groups. In the EA group, rats were treated with EA at the "PC6" acupoint for 30 min before being subjected to CPB. At 0.5, 1, and 2 h after CPB, the expression levels of plasma cardiac troponin I (cTnI) and lactate dehydrogenase (LDH), and myeloperoxidase (MPO) activity, TNFα, IL-1ß, reduced glutathione (GSH), oxidized glutathione (GSSH), and the ratio of GSH/GSSH in the myocardial tissue were measured. Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining. The expression of cleaved caspase-3 was detected by immunofluorescence. The expression of apelin, APJ, AKT, p-Akt, ERK1/2, and p-ERK1/2 was determined using western blotting. KEY FINDINGS: Decreased myocardial injury marker levels, myocardial apoptosis, oxidative stress, and the inflammatory response were found in the EA group compared with the CPB group. The expression levels of apelin, APJ, and p-Akt/AKT were increased in the EA group, and the p-ERK1/2/ERK1/2 level was decreased. SIGNIFICANCE: This study showed that EA pre-treatment can protect the heart from damage following CPB, which might be mainly mediated by restoring the apelin/APJ signaling pathway.

Therapeutic potential of IL-15 in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, destructive inflammatory autoimmune disease. Cytokine-mediated immunity has been found to play an important role in the pathogenesis of autoimmune diseases including RA. Recently, much attention has been paid on the role of IL-15, which is a member of the 4 α-helix bundle cytokine family. IL-15 was detected in serum and synovial fluid from RA patients and arthritis mice models. Moreover, administration of IL-15 leads to the development of severe inflammatory arthritis, suggesting that IL-15 may be therapeutically relevant in RA. Therefore, targeting IL-15 may be significantly important and valuable. In this article, we discuss the biological features and effects of IL-15 and summarize recent advances on the pathological roles of IL-15 in RA and treatment for RA.