Locating sources of Szegedy's quantum network.

Source location in quantum networks is a critical area of research with profound implications for cutting-edge fields such as quantum state tomography, quantum computing, and quantum communication. In this study, we present groundbreaking research on the technique and theory of source location in Szegedy's quantum networks. We develop a linear system evolution model for a Szegedy's quantum network system using matrix vectorization techniques. Subsequently, we propose a highly precise and robust source-location algorithm based on compressed sensing specifically tailored for Szegedy's quantum network. To validate the effectiveness and feasibility of our algorithm, we conduct numerical simulations on various model and real networks, yielding compelling results. These findings underscore the potential of our approach in practical applications.

Electroacupuncture for mild-to-moderate dry eye: study protocol for a multicentre, randomised, single-blind, sham-controlled trial.

INTRODUCTION: Dry eye (DE) is a multifactorial ocular surface disease causing considerable medical, social and financial implications. Currently, there is no recognised long-term, effective treatment to alleviate DE. Clinical evidence shows that electroacupuncture (EA) can improve DE symptoms, tear secretion and tear film stability, but it remains controversial whether it is just a placebo effect. We aim to provide solid clinical evidence for the EA treatment of DE. METHODS AND ANALYSIS: This is a multicentre, randomised, sham-controlled trial. A total of 168 patients with DE will be enrolled and randomly assigned to EA or sham EA groups to receive 4-week consecutive treatments and follow-up for 24 weeks. The primary outcome is the change in the non-invasive tear break-up time (NIBUT) from baseline to week 4. The secondary outcomes include tear meniscus height, the Schirmer I test, corneal and conjunctival sensation, the ocular surface disease index, corneal fluorescein staining, the numerical rating scale and the Chinese DE-related quality of life scale. ETHICS AND DISSEMINATION: The trial protocol and informed consent were approved by the Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine (identifier: 2021-119), Shanghai Eye Disease Prevention and Treatment Center (identifier: 2022SQ003) and Eye and ENT Hospital of Fudan University (identifier: 2022014). TRIAL REGISTRATION NUMBER: NCT05552820.

NLSI: An innovative method to locate epidemic sources on the SEIR propagation model.

Epidemics pose a significant threat to societal development. Accurately and swiftly identifying the source of an outbreak is crucial for controlling the spread of an epidemic and minimizing its impact. However, existing research on locating epidemic sources often overlooks the fact that epidemics have an incubation period and fails to consider social behaviors like self-isolation during the spread of the epidemic. In this study, we first take into account isolation behavior and introduce the Susceptible-Exposed-Infected-Recovered (SEIR) propagation model to simulate the spread of epidemics. As the epidemic reaches a certain threshold, government agencies or hospitals will report the IDs of some infected individuals and the time when symptoms first appear. The reported individuals, along with their first and second-order neighbors, are then isolated. Using the moment of symptom onset reported by the isolated individuals, we propose a node-level classification method and subsequently develop the node-level-based source identification (NLSI) algorithm. Extensive experiments demonstrate that the NLSI algorithm is capable of solving the source identification problem for single and multiple sources under the SEIR propagation model. We find that the source identification accuracy is higher when the infection rate is lower, and a sparse network structure is beneficial to source localization. Furthermore, we discover that the length of the isolation period has little impact on source localization, while the length of the incubation period significantly affects the accuracy of source localization. This research offers a novel approach for identifying the origin of the epidemic associated with our defined SEIR model.

Sedative-sparing effect of acupuncture in gastrointestinal endoscopy: systematic review and meta-analysis.

Objective: This study aimed to perform a systematic review and meta-analysis to identify the efficacy of acupuncture therapy (including manual acupuncture and electroacupuncture) performed before or during gastrointestinal endoscopy with propofol as the main sedative, compared with placebo, sham acupuncture, or no additional treatment other than the same sedation. Methods: A systematic search was performed through PubMed, Embase, Web of Science, Cochrane Library, Chinese Biomedical Databases (CBM), Wanfang database, China National Knowledge Infrastructure (CNKI), SinoMed, and Chinese Scientific Journal Database (VIP) to collect randomized controlled trials published before 5 November 2022. Bias assessment of the included RCTs was performed according to Version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). Stata16.0 software was used to perform statistical analysis, sensitivity analysis, and publication bias analysis. The primary outcome was sedative consumption, and the secondary outcomes included the incidence of adverse events and wake-up time. Results: A total of 10 studies with 1331 participants were included. The results showed that sedative consumption [mean difference (MD) = -29.32, 95% CI (-36.13, -22.50), P < 0.001], wake-up time [MD = -3.87, 95% CI (-5.43, -2.31), P < 0.001] and the incidence of adverse events including hypotension, nausea and vomiting, and coughing (P < 0.05) were significantly lower in the intervention group than in the control group. Conclusion: Acupuncture combined with sedation reduces sedative consumption and wake-up time compared with sedation alone in gastrointestinal endoscopy; this combined approach allows patients to regain consciousness more quickly after examination and lower the risk of adverse effects. However, with the limited quantity and quality of relevant clinical studies, caution must be applied until more high-quality clinical studies verify and refine the conclusions. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?, identifier: CRD42022370422.

The locatability of Pearson algorithm for multi-source location in complex networks.

We study locating propagation sources in complex networks. We proposed an multi-source location algorithm for different propagation dynamics by using sparse observations. Without knowing the propagation dynamics and any dynamic parameters, we can calculate node centrality based on the character that positive correlation between inform time of nodes and geodesic distance between nodes and sources. The algorithm is robust and have high location accuracy for any number of sources. We study locatability of the proposed source location algorithm and present a corresponding strategy to select observer nodes based on greedy algorithm. All simulations on both model and real-world networks proved the feasibility and validity of this algorithm.

Suppression of microRNA-222-3p ameliorates ulcerative colitis and colitis-associated colorectal cancer to protect against oxidative stress via targeting BRG1 to activate Nrf2/HO-1 signaling pathway.

Oxidative stress is an important pathogenic factor in ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC), further impairing the entire colon. Intestinal epithelial cells (IECs) are crucial components of innate immunity and play an important role in maintaining intestinal barrier function. Recent studies have indicated that microRNA-222-3p (miR-222-3p) is increased in colon of UC and colorectal cancer (CRC) patients, and miR-222-3p is a crucial regulator of oxidative stress. However, whether miR-222-3p influences IEC oxidative stress in UC and CAC remains unknown. This study investigated the effect of miR-222-3p on the regulation of IEC oxidative stress in UC and CAC. An in vitro inflammation model was established in NCM460 colonic cells, mouse UC and CAC models were established in vivo, and IECs were isolated. The biological role and mechanism of miR-222-3p-mediated oxidative stress in UC and CAC were determined. We demonstrated that miR-222-3p expression was notably increased in dextran sulfate sodium (DSS)-induced NCM460 cells and IECs from UC and CAC mice. In vitro, these results showed that the downregulation of miR-222-3p reduced oxidative stress, caspase-3 activity, IL-1ß and TNF-α in DSS-induced NCM460 cells. We further identified BRG1 as the target gene of miR-222-3p, and downregulating miR-222-3p alleviated DSS-induced oxidative injury via promoting BRG1-mediated activation Nrf2/HO-1 signaling in NCM460 cells. The in vivo results demonstrated that inhibiting miR-222-3p in IECs significantly relieved oxidative stress and inflammation in the damaged colons of UC and CAC mice, as evidenced by decreases in ROS, MDA, IL-1ß and TNF-α levels and increases in GSH-Px levels. Our study further demonstrated that inhibiting miR-222-3p in IECs attenuated oxidative damage by targeting BRG1 to activate the Nrf2/HO-1 signaling. In summary, inhibiting miR-222-3p in IECs attenuates oxidative stress by targeting BRG1 to activate the Nrf2/HO-1 signaling, thereby reducing colonic inflammation and tumorigenesis.

Effects of electroacupuncture on dry eye: A pilot randomized controlled trial.

PURPOSE: The purpose of the study was to assess the efficacy of electroacupuncture on dry eye (DE). METHODS: Eighty-four DE patients were randomly assigned to receive electroacupuncture (EAG) three times a week or 0.1% sodium hyaluronate artificial tears (ATG) four times per day for 4 weeks. The primary outcomes were non-invasive tear film breakup time (NIBUT) and tear meniscus height (TMH). The secondary outcomes included the ocular surface disease index (OSDI), Schirmer I test (SIT), corneal sodium fluorescein staining (CFS) score, corneal topography descriptors surface asymmetry index (SAI) and surface regularity index (SRI), corneal sensitivity, 36-item Short-form Health Survey (SF-36) score and Hospital Anxiety and Depression Scale (HADS) score. All outcomes were assessed at Week 0 (baseline), Week 4 (after-treatment) and Week 8 (follow-up). RESULTS: Between-group comparisons showed significant differences in the changes in NIBUT (Week 4, p = 0.003; Week 8, p = 0.008), TMH (Week 4, p = 0.014; Week 8, p = 0.009), OSDI (Week 4, p = 0.029; Week 8, p = 0.022), CFS score (Week 8, p = 0.036) and SF-36 role-physical score (Week 4, p = 0.010), favouring EAG. Mean changes in SIT, SAI, SRI, corneal sensitivity and HADS scores were statistically equal between the two groups (all p > 0.05). Treatment with electroacupuncture was well-tolerated and showed minimal adverse events. CONCLUSIONS: Compared with artificial tears, electroacupuncture shows superior efficacy in improving tear film stability and symptoms of DE.

LncRNA-miRNA-mRNA Network Analysis Reveals the Potential Biomarkers in Crohn's Disease Rats Treated with Herb-Partitioned Moxibustion.

Background: Long noncoding RNA (lncRNA) is receiving growing attention in Crohn's disease (CD). However, the mechanism by which herb-partitioned moxibustion (HPM) regulates the expression and functions of lncRNAs in CD rats is still unclear. The aim of our study is to identify lncRNA-miRNA-mRNA network potential biological functions in CD. Methods: RNA sequencing and microRNA (miRNA) sequencing were carried out to analyze lncRNA, miRNA and mRNA expression profiles among the CD rats, normal control rats, and CD rats after HPM treatment and constructed the potential related lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) networks. Then, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, protein-protein interaction (PPI) analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to explore potentially important genes in ceRNA networks. Results: A total of 189 lncRNAs, 32 miRNAs and 463 mRNAs were determined as differentially expressed (DE) genes in CD rats compared to normal control rats, and 161 lncRNAs, 12 miRNAs and 130 mRNAs were identified as remarkably DE genes in CD rats after HPM treatment compared to CD rats. GO analysis indicated that the target genes were most enriched in cAMP and in KEGG pathway analysis the main pathways included adipocytokine, PPAR, AMPK, FoxO and PI3K-Akt signaling pathway. Finally, qRT-PCR results confirmed that lncRNA LOC102550026 sponged miRNA-34c-5p to regulate the intestinal immune inflammatory response by targeting Pck1. Conclusion: By constructing a ceRNA network with lncRNA-miRNA-mRNA, PCR verification, and KEGG analysis, we revealed that LOC102550026/miRNA-34c-5p/Pck1 axis and adipocytokine, PPAR, AMPK, FoxO, and PI3K-Akt signaling pathways might regulate the intestinal immune-inflammatory response, and HPM may regulate the lncRNA LOC102550026/miR-34c-5p/Pck1 axis and adipocytokine, PPAR, AMPK, FoxO, and PI3K-Akt signaling pathways, thus improving intestinal inflammation in CD. These findings may be novel potential targets in CD.

Electroacupuncture inhibits the corneal ROS/TXNIP/NLRP3 signaling pathway in a rat model of dry eye syndrome.

BACKGROUND: Electroacupuncture (EA) treatment has been found to ameliorate clinical symptoms in patients with dry eye, but its mechanisms are still not entirely clear. OBJECTIVE: To study the regulation of EA on ocular surface function and the corneal reactive oxygen species (ROS)/thioredoxin-interacting protein (TXNIP)/Nod-like receptor protein 3 (NLRP3) inflammatory signaling pathway in dry eye syndrome (DES) model rats. METHODS: Male Sprague-Dawley (SD) rats were randomly divided into five groups: Normal, Model, Model + EA, Model + NAC (N-actetylcysteine) and Model + NS (normal saline). The DES model was developed by subcutaneous injection of scopolamine hydrobromide with exposure to an air draft in the latter four groups. After intervention, the Schirmer I test (SIT), tear film break-up time (BUT) and ROS content were measured, the histopathological changes of corneal tissues were observed, and the mRNA and protein expression levels of TXNIP, NLRP3, apoptosis-associated Speck-like protein containing CARD (ASC), caspase-1, interleukin (IL)-1ß and IL-18 were detected. RESULTS: Compared with the Model group, the SIT and BUT increased significantly in the Model + EA group after intervention (p < 0.05), and the corneal injury was improved. Corneal ROS content declined in both Model + EA and Model + NAC groups (p < 0.05), and mRNA expression of TXNIP, NLRP3, ASC and caspase-1 also decreased (p < 0.01). Corneal protein expression of TXNIP, NLRP3, IL-1ß and IL-18 decreased significantly in the Model + EA group (p < 0.01). CONCLUSION: Inhibiting the ROS/TXNIP/NLRP3 signaling pathway may be the mechanism underlying the role of EA in improving corneal injury in DES model rats.

Moxibustion Inhibits the Expression of Colonic NLRP3 through miR7/RNF183/NF-κB Signaling Pathway in UC Rats.

BACKGROUND: Moxibustion has been recognized as an effective approach for ulcerative colitis, yet its mechanism is not clear. The research aimed to investigate the influence of moxibustion on the activation of NLRP3 inflammasome and its mechanism in treating ulcerative colitis by observing miR7/RNF183 inducing IκB α ubiquitination to regulate NF-κB signaling pathway in an ulcerative colitis rat model. METHODS: An ulcerative colitis rat model was established by unlimited access to self-administration of 3.5% (w/v) dextran sulfate sodium solution. Mild moxibustion was applied to bilateral Tianshu points (ST25) in the moxa-stick moxibustion group; rats in the control group were intervened by intraperitoneal injection of ubiquitination inhibitor, MG132. The disease activity index was determined at the end of the intervention; colon injury was observed and scored after hematoxylin-eosin staining; the immunohistochemical method was adopted to detect the expressions of colonic IL-1ß and NLRP3 proteins; Western blot determined the expressions of RNF183, IκB α, and NF-κB p65 proteins in the colon; the immunofluorescence test was used to observe the coexpression of IκB α/ubiquitin and IκB α/RNF183 proteins in the colon; immunoprecipitation assay was adopted to observe the interaction between IκB α and RNF183 proteins; and quantitative real-time polymerase chain reaction determined the expression of colonic miR7. RESULTS: Moxibustion lowered the disease activity index, manifesting as restored colonic tissue and reduced inflammatory reaction, and decreased expression levels of NLRP3 and IL-1ß proteins, compared with the model group. It also reduced colonic expression of NF-κB p65 protein, together with the increased level of IκB α protein and weaker expression levels of ubiquitin and RNF183 proteins and mRNAs and stronger expression of miR7. There were no significant differences between the moxa-stick moxibustion group and the control group except the expressions of RNF183 protein and mRNA and miR7. CONCLUSION: Moxibustion encourages the recovery of colon injury probably by regulating the expression of NLRP3 protein in ulcerative colitis rats through miR7/RNF183/NF-κB signaling pathway.

Auricular acupressure for myopia prevention and control in children and its effect on choroid and retina: a randomized controlled trial protocol.

BACKGROUND: Nowadays, because of the increasing incidence, the prevention and control of myopia has become an urgent issue. In China, auricular acupressure has been commonly used in the clinical treatment of myopia in children, but the exact effectiveness remains unproven. The purpose of this trial is to observe the efficacy of auricular acupressure in myopia prevention and control, as well as its effect on the choroidal and retinal thickness. METHOD/DESIGN: A total of 480 subjects at 8-9 years old will be randomized in a 1:1 ratio to an intervention group versus a control group. The intervention group will receive auricular acupressure for 12 months, while the control group will be taken as a blank control. The primary and secondary outcomes will be measured at baseline, and again at 3, 6, 9, and 12 months after recruitment. The myopia incidence (spherical equivalent ≤ - 0.50 D) and the mean change of spherical equivalent will be taken as the primary variables; the secondary outcome measures include axial length, uncorrected visual acuity, and choroidal and retinal thickness. DISCUSSION: This trial aims to evaluate the effectiveness of auricular acupressure for myopia prevention and control with objective evidence and to preliminarily explore the plausible mechanism and provide reference for adopting this approach to retard the onset and control the progression of myopia. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000038456 . Registered on September 23, 2020.

Herb-partitioned moxibustion alleviates colonic inflammation in Crohn's disease rats by inhibiting hyperactivation of the NLRP3 inflammasome via regulation of the P2X7R-Pannexin-1 signaling pathway.

Crohn's disease is a chronic inflammatory bowel disease and the NLRP3 inflammasome plays an important role in Crohn's disease. Previous studies have shown that Herb-partitioned moxibustion treating (at Qihai (CV 6) and Tianshu (ST 25)) prevented the excessive activation of the NLRP3 inflammasome and repaired damaged colonic mucosa in Crohn's disease. However, the mechanism by which Herb-partitioned moxibustion (at CV 6 and ST 25) regulates NLRP3 remains unclear. In this study, we treated Crohn's disease rats with herb-partitioned moxibustion (at CV 6 and ST 25) to investigate the mechanism by which Herb-partitioned moxibustion regulates the colonic NLRP3 inflammasome by observing colon length, the colon macroscopic damage indexes, and the expression of ATP, P2X7R, Pannexin-1, NF-κBp65, NLRP3, ASC, caspase-1, IL-1ß and IL-18 in the colon in Crohn's disease. Here, this study shows that herb-partitioned moxibustion (at CV 6 and ST 25) can reduce colon macroscopic damage indexes and colon histopathological scores, alleviate colon shortening and block the abnormal activation of the NLRP3 inflammasome by inhibiting the ATP content and the expression of P2X7R, Pannexin-1 and NF-κBp65, thereby reducing the release of the downstream inflammatory cytokine IL-1ß and ultimately suppressing colonic inflammation in Crohn's disease rats. This study for the first time identifies the mechanism by which herb-partitioned moxibustion (at CV 6 and ST 25) may inhibit the abnormal activation of the NLRP3 inflammasome by inhibiting the P2X7R-Pannexin-1 signaling pathway in Crohn's disease rats.

A Mechanism Study of Electroacupuncture for Dry Eye Syndrome by Targeting Conjunctival Cytokine Expressions.

Aim: To discuss the immunological mechanism in electroacupuncture (EA) treatment of dry eye syndrome (DES) by targeting the changes in conjunctival cytokine expression profile.Method: Eligible DES patients were randomized into an EA group (EAG) or an acupuncture group (AG). The ocular surface disease index (OSDI), amount of tear production, and tear film break-up time (BUT) were observed to evaluate the efficacy. Conjunctival cells were collected from both effective and invalid cases to observe the expressions of cytokines by protein microarray. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for functional cluster and signaling pathway analysis of the differentially expressed proteins. Enzyme-linked immunosorbent assay (ELISA) was used to verify the specific differential proteins.Result: After treatment, OSDI dropped and BUT extended in both groups, and the tear production increased only in the EAG (all P < .01). Compared with the AG, the improvement in tear production was more significant in the EAG (P < .01). There were 17 differentially expressed conjunctival cytokines between the effective and invalid cases in the EAG, and those expressed higher than the limit of detection (LOD) included monocyte chemoattractant protein 1 (MCP-1), macrophage colony-stimulating factor (M-CSF), regulated on activation in normal T-cell expressed and secreted (RANTES) and tissue inhibitor of metalloproteinases 1 (TIMP-1). GO analysis showed that the differential cytokines were mainly involved in cellular interaction, signaling pathways and reactions to stimuli. KEGG analysis revealed that the signaling pathways of these cytokines were mainly responsible for interactions between cytokines or between cytokines and their receptors, such as Jak-STAT signaling pathway, chemokine signaling pathway, and tumor necrosis factor signaling pathway.Conclusion: EA can effectively treat DES by improving the symptoms, increasing tear secretion and extending BUT, which is possibly related to its regulation on the conjunctival cytokine expressions.

Moxibustion Eases Chronic Inflammatory Visceral Pain In Rats Via MAPK Signaling Pathway In The Spinal Cord.

PURPOSE: The purpose of this study was to explore the central analgesia mechanism of moxibustion for chronic inflammatory visceral pain (CIVP). METHODS: A CIVP rat model was established by 2,4,6-trinitrobenzene sulfonic acid (TNBS) plus 50% ethanol via enema. The analgesic effect of moxibustion was evaluated using the abdominal withdrawal reflex (AWR), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL). The expression profile of phosphorylated proteins of the mitogen-activated protein kinase (MAPK) signaling pathway in the spinal cord was assayed by protein microarray. The differentially expressed proteins were examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for functional clusters and corresponding signaling pathways. RESULTS: Moxibustion exerted a significant analgesic effect for CIVP rats, mainly presenting as a decrease in the AWR score (all P<0.01) under different levels of distending pressure and an increase in MWT and TWL thresholds (all P<0.05). Compared with the normal group, 76 proteins were upregulated while 15 were downregulated, and MAPK signaling pathway was activated in the model group. Compared with the model group, there were 53 downregulated and 38 upregulated proteins in the moxibustion group, and MAPK signaling pathway was inhibited. Fold change (FC)>1.3 or <0.77 was taken as the screening standard to define the differentially expressed proteins. Fifteen differentially expressed proteins upregulated in the model group were downregulated in the moxibustion group. GO analysis showed that the differentially expressed proteins mainly controlled cellular metabolism regulation, transportation, and stress reactions. KEGG analysis revealed that these differentially expressed proteins were mostly involved in the ERK, JNK, and p38 pathways, and the ERK pathway was predominant. CONCLUSION: Moxibustion mitigates CIVP in rats and inhibits the phosphorylation of proteins in the spinal MAPK signaling pathway. The analgesic effect of moxibustion may be associated with the regulation of the spinal MAPK signaling pathway.

Manual Acupuncture for Optic Atrophy: A Systematic Review and Meta-Analysis.

Objectives. This systematic review aims to critically evaluate the efficacy of manual acupuncture for optic atrophy. Eight English and Chinese databases, including Cochrane Library, EMbase, PubMed, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), and Chinese Biomedical Literature Database (CBM), as well as ongoing trials registered with the WHO International Clinical Trials Registry Platform, were searched to identify eligible randomized controlled trials (RCTs) studying manual acupuncture for optic atrophy compared to medication alone. The quality of evidence was assessed using Cochrane Collaboration's risk of bias tool. Meta-analysis was performed using Review Manager version 5.3. Nine studies were identified and included for meta-analysis. The meta-analysis showed significant differences in favor of manual acupuncture or manual acupuncture plus medication compared with medication alone in the following outcome measures: visual acuity (MD = 0.18, 95% CI [0.17, 0.20], P < 0.00001), mean sensitivity of visual field (MD = 2.11, 95% CI [1.90, 2.32], P < 0.00001), the latent period of P-VEP100 (MD = -6.80, 95% CI [-8.94, -4.66], P < 0.00001), the total effectiveness (264 eyes) (OR = 3.22, 95% CI [1.88, 5.51], P<0.0001), and the total effectiveness (344 participants) (OR = 4.29, 95% CI [2.56, 7.19], P < 0.00001). Despite statistical advantages of manual acupuncture in the literature, due to serious methodological flaws in study design, it cannot be concluded that manual acupuncture is more effective than medicine alone. It is essential that a properly controlled clinical trial is designed and controls are established to exclude placebo effects.

Herb-partitioned moxibustion alleviates colon injuries in ulcerative colitis rats.

AIM: To observe the effect of herb-partitioned moxibustion (HPM) on expression of colonic cytokines in ulcerative colitis (UC) rats. METHODS: A UC rat model was established by protein immunization in combination with topical chemical stimulation. Rats in the HPM group (n = 8) received HPM at bilateral Tianshu (ST25) points. The gross injury and pathological scores of the colon were recorded. The expression profile of colonic cytokines was assayed using the protein microarray technique. Specific differential cytokines were selected and verified by ELISA. The corresponding UniProt Accessions of the differentially expressed cytokines were retrieved in the UniProt database. The pathways involved were analyzed with the help of the KEGG PATHWAY database. The DAVID database was used for functional cluster and pathway analysis. RESULTS: HPM improved colon injuries in UC rats, manifested by accelerated repair of ulcers and alleviation of inflammation, and the gross injury and pathological scores both significantly decreased (P < 0.01). Fold change > 1.3 or < 0.77 was taken as the screening standard. There were 77 down-regulated and 9 up-regulated differentially expressed colonic cytokines in the HPM group compared with the model group, and expression of 20 differed significantly (P < 0.05). Twelve of the 20 significantly differentially expressed cytokines [ß-catenin, interleukin-1 receptor 6 (IL-1R6), IL-1ß, B7-1, nerve growth factor receptor, AMP-activated protein kinase-α1, neuropilin-2, orexin A, adipocyte differentiation-related protein, IL-2, Fas and FasL] were up-regulated in the model group (n = 3, compared with the normal group) but down-regulated in the HPM group (n = 3, compared with the model group). Functional cluster analysis showed that the differentially expressed colonic cytokines in the HPM group regulated apoptosis and protein phosphorylation. KEGG pathway analysis showed that 52 down-regulated and 7 up-regulated differentially expressed colonic cytokines in the HPM group had pathways. The pathways that interacted between the cytokines and their receptors accounted for the largest proportion (28 of the down-regulated and 5 of the up-regulated cytokines). CONCLUSION: HPM promotes the repair of colon injuries in UC rats, which is related to the regulation of several abnormally expressed cytokines.

Efficacy of herb-partitioned moxibustion at Qihai (CV 6) and bilateral Tianshu (ST 25) on colonic damage and the TLR4/NF-κB signaling pathway in rats with Crohn's disease.

OBJECTIVE: To observe the effect of stimulating Qihai (CV 6) and bilateral Tianshu (ST 25) with herb-partitioned moxibustion (HPM) in rats with Crohn's disease (CD), and to investigate the possible anti-inflammatory mechanism of HPM. METHODS: Forty rats were randomly divided into four groups (n = 10 rats per group): normal control (NC), model control (MC), mesalamine (MES), and HPM. The CD rat model was established in the MC, MES, and HPM groups by administering a mixture of trinitrobenzenesulfonic acid and alcohol via enema. The HPM group received HPM on Qihai (CV 6) and bilateral Tianshu (ST 25), while the MES group received intragastric mesalamine. Colonic histomorphological scores, and serum concentrations of tumor necrosis factor ¦Á (TNF-¦Á) and interleukin 1¦Â (IL-1¦Â) were assessed to evaluate the effects of HPM on colonic reparation and anti-inflammation. The expressions of Toll-like receptor 4 (TLR-4), nuclear factor ¦ÊB inhibitor ¦Á (I¦ÊB-¦Á), I¦ÊB kinase ¦Á/¦Â (IKK¦Á/¦Â), and NF-¦ÊB p65 were further analyzed to investigate the regulatory effects of the interventions on the TLR4/NF-¦ÊB pathway. RESULTS: CD rats showed inflammatory colonic damage and increased serum concentrations of TNF-¦Á and IL-1¦Â. The expressions of TLR4, IKK¦Á/¦Â, and NF-¦ÊB p65 in the colons of CD rats were significantly increased compared with the NC group, while the expression of I¦ÊB¦Á (a key negative regulator of NF-¦ÊB p65) was decreased. HPM significantly mitigated colonic damage and reduced the serum concentrations of TNF-α and IL-1¦Â. HPM downregulated the expressions of TLR4, IKK¦Á/¦Â, and NF-¦ÊB p65 in the colon, and upregulated the expression of I¦ÊB¦Á. The effects of HPM in CD rats were similar to those of mesalamine. CONCLUSION: HPM alleviates colonic inflammation in CD rats. This may be achieved through regulation of TLR4, which induces NF-¦ÊB signal transduction.

Extracellular signal-regulated kinase, substance P and neurokinin-1 are involved in the analgesic mechanism of herb-partitioned moxibustion.

Herb-partitioned moxibustion can effectively mitigate visceral pain, a major symptom in inflammatory bowel disease, but the analgesic mechanism is still unclear. Moreover, extracellular signal-regulated kinase, substance P, and neurokinin-1 are involved in formation of central hyperalgesia. Thus, we postulated that the analgesic effect of herb-partitioned moxibustion may be associated with these factors. Accordingly, in this study, we established an inflammatory bowel disease visceral pain model in rat by enema with a mixed solution of 5% trinitrobenzenesulfonic acid and 50% ethanol. Bilateral Tianshu (ST25) and Qihai (CV6) points were selected for herb-partitioned moxibustion. Our results showed that herb-partitioned moxibustion improved visceral pain and down-regulated extracellular signal-regulated kinase, substance P, and neurokinin-1 protein and mRNA expression in dorsal root ganglia. These results indicate that down-regulation of extracellular signal-regulated kinase, substance P, and neurokinin-1 protein and mRNA may be a central mechanism for the analgesic effect of herb-partitioned moxibustion.

Moxibustion eases chronic inflammatory visceral pain through regulating MEK, ERK and CREB in rats.

AIM: To investigate the effects of herb-partitioned moxibustion (HPM) on phosphorylation of mitogen-activated extracellular signal-regulated kinase (MEK)1, extracellular signal-regulated kinase (ERK)1/2 and cAMP response element binding protein (CREB) in spinal cord of rats with chronic inflammatory visceral pain (CIVP), and to explore the central mechanism of HPM in treating CIVP. METHODS: Male Sprague-Dawley rats were randomized into normal, model, HPM, sham-HPM, MEK-inhibitor and dimethyl sulfoxide (DMSO) groups. The CIVP model was established using an enema mixture of trinitrobenzene sulfonic acid and ethanol. HPM was applied at bilateral Tianshu (ST25) and Qihai (CV6) acupoints in the HPM group, while in the sham-HPM group, moxa cones and herb cakes were only placed on the same points but not ignited. The MEK-inhibitor and DMSO groups received L5-L6 intrathecal injection of U0126 and 30% DMSO, respectively. Abdominal withdrawal reflex (AWR), mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were applied for the assessment of pain behavior. The colonic tissue was observed under an optical microscope after hematoxylin-eosin staining. Expression of phosphor (p)MEK1, pERK1/2 and pCREB in rat spinal cord was detected using Western blotting. The levels of MEK, ERK and CREB mRNA in rat spinal cord were detected using real-time polymerase chain reaction. RESULTS: Compared with the normal group, the AWR scores were increased significantly (P < 0.01) and the MWT and TWL scores were decreased significantly (P < 0.05) in the model, sham-HPM and DMSO groups. Compared with the model group, the AWR scores were decreased significantly (P < 0.01) and the MWT and TWL scores were increased significantly in the HPM and MEK-inhibitor groups (P < 0.05). Compared with the sham-HPM and DMSO groups, the AWR scores were decreased significantly (P < 0.01) and the MWT and TWL scores were increased significantly (P < 0.05) in the HPM and MEK-inhibitor groups. Compared with the normal group, the expression of pMEK1, pERK1/2 and pCREB proteins and the levels of MEK, ERK and CREB mRNA in rat spinal cord were increased significantly in the model, sham-HPM and DMSO groups (P < 0.01 or < 0.05). Compared with the model group, the expression of pMEK1, pERK1/2 and pCREB proteins and the levels of MEK, ERK and CREB mRNA in rat spinal cord were reduced significantly in the HPM and MEK-inhibitor groups (P < 0.01 or < 0.05). Compared with the sham-HPM and DMSO groups, expression of pMEK1, pERK1/2 and pCREB proteins and the levels of MEK, ERK and CREB mRNA in rat spinal cord were reduced significantly in the HPM and MEK-inhibitor groups (P < 0.01 or < 0.05). CONCLUSION: HPM down-regulates protein phosphorylation of MEK1, ERK1/2 and CREB, and mRNA expression of MEK, ERK and CREB, inhibiting activation of the MEK/ERK/CREB signaling pathway in the spinal cord of CIVP rats, which is possibly a critical central mechanism of the analgesic effect of HPM.

Mutation of miR-21 targets endogenous lipoprotein receptor-related protein 6 and nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is a chronic disorder characterized by hepatic fat accumulation and abnormal lipid metabolism. Although miR-21 has been implicated in nonalcoholic fatty liver disease, it is unknown whether miR-21 could function as a therapeutic target. Here, we perform transfection analysis of miR-21 mimic or control mimic to evaluate the effects of miR-21 expression levels on human HepG2 nonalcoholic fatty liver cells. We used siRNA techniques to knock down miR-21 in HepG2 and control 293T cell lines, and then monitored lipid production and the expression levels of genes involved in lipid metabolism. The effects of miR-21 expression levels on LDL receptor-related protein 6 (LRP6) expression were evaluated using qRT-PCR and western blot analyses. Luciferase reporter assays were conducted to confirm the effects of miR-21 expression levels on LRP6. The results indicated that transfection of miR-21 mimic induced changes in the expression levels of lipogenic enzymes, including acetyl-CoA carboxylase 1 (ACC1), stearoyl CoA desaturase (1SCD1), sterol regulatory element-binding protein 1 (SREBP1), and liver X receptor alpha (LXRα). Transfection of miR-21 mimic suppressed the transcription and translation of LRP6 at the mRNA and protein levels, whereas miR-21 knockdown increased the expression levels of LRP6. Transfection of miR-21 mimic in HepG2 cells also induced lipid production and triggered the expression of critical lipid metabolic enzymes. These data suggest that mutation of miR-21 may be a new therapeutic strategy to treat nonalcoholic fatty liver diseases by targeting endogenous LRP6.