Objective: Moderate-to-severe pain is the most common clinical symptom in patients with hepatocellular carcinoma (HCC).This trial aimed to analyze the clinical efficacy of Transcutaneous electrical acupoint stimulation (TEAS) in patients of HCC with severe pain and provide a reliable reference for optimizing the clinical diagnostic and therapeutic strategies of HCC. Methods: A total of 104 eligible patients were randomly allocated to experimental and control groups in a ratio of 1:1.The treatment was administered for 1 week continuously. Patients in both groups were followed up 1 week after the end of the treatment.The primary outcome measure was the Numerical Rating Scale (NRS) score, whereas the secondary outcome measures included Brief Pain Inventory BPI-Q3, Q4, Q5 scores, analgesic dose, frequency of opioid-induced gastrointestinal side effects, Karnofsky Performance Status (KPS), Quality of Life Scale - Liver Cancer (QOL-LC), and Brief Fatigue Inventory (BFI) scores. Results: The NRS scores of experimental group was significantly lower after treatment and at the follow-up than baseline (average P<0.01), there were also statistical differences between the groups at the above time points (average P<0.01). BPI-Q3, -Q4, and -Q5 scores in the experimental group were decreased after treatment when compared with those before treatment (average P<0.01). Furthermore, there were significant improvements of gastrointestinal side effects, KPS, QOL-LC and BPI in the experimental group after treatment, and the above results were statistically significant compared to the control group. Conclusion: 7-day TEAS treatment can significantly enhance the analgesic effect and maintain for the following week, also reduce the incidence of gastrointestinal side effects caused by opioids, and improve the quality of life of patients with moderate-to-severe HCC-related pain, which has reliable safety and certain clinical promotion value.
Mitosis is a key step of eukaryote proliferation.Endosomal sorting complex required for transport, a protein complex closely associated with membrane shearing, is involved in endosome maturation, virus budding, and autophagy.The structural and functional abnormalities of the complex are associated with the occurrence and progression of cancer and other diseases.In this paper, we summarized the roles of the endosomal sorting complex required for transport in different stages of mitosis and reviewed the studies about the role of the complex in regulating mitosis in diseases.
Background: Motor disturbances and non-motor disturbances such as constipation are the main factors affecting the quality of life in patients with Parkinson's disease (PD). We investigated the efficacy and safety of electroacupuncture combined with conventional pharmacological treatment on motor dysfunction and constipation in PD. Methods: In this multi-centre randomised controlled trial, we enrolled 166 eligible participants between September 19, 2018 and September 25, 2019 in four hospitals in China. Participants were randomly assigned (1:1) to the electroacupuncture (EA) group and the waitlist control group. Each participant in both groups received the conventional pharmacological treatment, EA group received 3 sessions of electroacupuncture per week for 12 weeks. The primary outcome was the change in the Unified Parkinson's Disease Rating Scale (UPDRS) score from baseline to week 12. The secondary outcomes included the evaluation of functional disability in motor symptoms and constipation, the adherence and adverse events were also recorded. Registered with Chictr.org.cn, ChiCTR1800019517. Findings: At week 12, the change in the UPDRS score of the EA group was significantly higher than that of the control group, with a difference of -9.1 points (95% CI, -11.8 to -6.4), and this difference continued into weeks 16 and 24. From baseline to week 12, the 39-item Parkinson Disease Question (PDQ-39) decreased by 10 points (interquartile range, IQR -26.0 to 0.0) in the EA group and 2.5 points (IQR: -11.0 to 4.0) in the control group, the difference was statistically significant. The time and steps for the 20-m walk at week 12, as well as the changes from baseline in the EA group, were comparable with that in the control group. But the EA group had a greater decrease than the control group from baseline in the times for 20-m walks at weeks 16 and 24. From week 4 to week 24, the median values of spontaneous bowel movements (SBMs) per week in the EA group were higher than that in the control group, the differences were all statistically significant. The incidence of EA-related adverse events during treatment was low, and they are mild and transient. Interpretation: The findings of our study suggested that compared with conventional pharmacological treatment, conventional pharmacological treatment combined with electroacupuncture significantly enhances motor function and increased bowel movements in patients with PD, electroacupuncture is a safe and effective treatment for PD. Funding: Shanghai "Science and Technology Innovation Action Plan" Clinical Medicine Field Project (18401970700), Shanghai Special Project on Aging and Women's and Children's Health Research (020YJZX0134), Shanghai Clinical Research Centre for Acupuncture and Moxibustion (20MC1920500).
BACKGROUND: Chronic atrophic gastritis (CAG) is a pathological stage in the Correa's cascade, whereby Helicobacter pylori (H. pylori) infection is the primary cause. Cellular senescence is an inducing factor for cancer occurrence and cellular senescence is an obvious phenomenon in gastric mucosal tissues of H. pylori-positive CAG patients. METHODS: In this review, we collated the information on cellular senescence and H. pylori-positive CAG. RESULTS: At present, only a few studies have observed the effect of cellular senescence on precancerous lesions. In combination with the latest research, this review has collated the information on cellular senescence and H. pylori-positive CAG from four aspects- telomere shortening, DNA methylation, increased reacive oxygen species (ROS) production, and failure of autophagy. CONCLUSION: This is expected to be helpful for exploring the relevant mechanisms underlying inflammatory cancerous transformation and formulating appropriate treatment strategies.
Gastritis, Atrophic , Helicobacter Infections , Helicobacter pylori , Stomach Neoplasms , Humans , Gastritis, Atrophic/pathology , Helicobacter Infections/complications , Helicobacter Infections/pathology , Gastric Mucosa/pathology , Cellular Senescence , Stomach Neoplasms/pathology
Currently colorectal cancer (CRC) is the third most prevalent cancer worldwide. Body mass index (BMI) is frequently used in CRC screening and risk assessment to quantitatively evaluate weight. However, the impact of BMI on clinical strategies for CRC has received little attention. Within the framework of the predictive, preventive, and personalized medicine (3PM/PPPM), we hypothesized that BMI stratification would affect the primary, secondary, and tertiary care options for CRC and we conducted a critical evidence-based review. BMI dynamically influences CRC outcomes, which helps avoiding adverse treatment effects. The outcome of surgical and radiation treatment is adversely affected by overweight (BMI ≥ 30) or underweight (BMI < 20). A number of interventions, such as enhanced recovery after surgery and robotic surgery, can be applied to CRC at all levels of BMI. BMI-controlling modalities such as exercise, diet control, nutritional therapy, and medications may be potentially beneficial for patients with CRC. Patients with overweight are advised to lose weight through diet, medication, and physical activity while patients suffering of underweight require more focus on nutrition. BMI assists patients with CRC in better managing their weight, which decreases the incidence of adverse prognostic events during treatment. BMI is accessible, noninvasive, and highly predictive of clinical outcomes in CRC. The cost-benefit of the PPPM paradigm in developing countries can be advanced, and the clinical benefit for patients can be improved with the promotion of BMI-based clinical strategy models for CRC.
Constipation is one of the most common nonmotor symptoms in patients with Parkinson's disease (PD) and often occurs before motor symptoms. Electroacupuncture effectively improves the symptoms of constipation in patients with PD. In the present study, we used thymus cell antigen 1-α-synuclein (Thy1-αSyn) transgenic mice as a model of intestinal motility disorders in PD to determine the therapeutic effect of electroacupuncture and the underlying mechanisms. Electroacupuncture significantly improved fecal excretion and accelerated the rate of small-intestinal propulsion in Thy1-αSyn mice by upregulating the serotonin concentration and the expression of the serotonin 4 receptor. Consequently, the downstream cyclic AMP/protein kinase A (cAMP/PKA) pathway was affected, and to upregulate and downregulate, the expression of substance P was upregulated, and the expression of calcitonin gene-related peptide was downregulated. In summary, electroacupuncture improved intestinal motility in PD mice by affecting serotonin levels, serotonin 4 receptor expression, and the cAMP/PKA pathway, providing a potentially effective and promising complementary and alternative therapy for relieving constipation symptoms in patients with PD.
The 5-methylcytosine (m5C) RNA methyltransferase NOP2/Sun RNA methyltransferase 5 (NSUN5) has been reported to serve important roles in numerous diseases. However, the functions and clinical significance of NSUN5 in hepatocellular carcinoma (HCC) remain unknown. Clinical information and NSUN5 mRNA sequencing data for 374 patients with HCC were downloaded from The Cancer Genome Atlas (TCGA) database, and NSUN5 mRNA and protein expression levels in 120 patients with HCC (present study cohorts) were assessed using reverse transcription-quantitative PCR, western blotting or immunohistochemistry. The association between NSUN5 mRNA and protein expression levels and the clinical characteristics (or prognosis) of patients with HCC was analyzed using the χ2 or log-rank test. The functions of NSUN5 in HCC were evaluated using in vitro and in vivo experiments, and the mechanism by which NSUN5 affected the progression of HCC was assessed using bioinformatics analysis using LinkedOmics. NSUN5 was significantly upregulated and predicted poor prognosis in HCC according to data from both TCGA database and present study cohorts. NSUN5 significantly promoted HCC proliferation and migration in vitro and significantly induced HCC tumor growth in vivo. Bioinformatics analysis demonstrated that NSUN5 was positively correlated with genes associated with translation in HCC. It was hypothesized that overexpression of NSUN5 strengthened ribosome functions and global protein translation, which may promote the proliferation and migration of HCC. In conclusion, NSUN5 may promote the progression of HCC by enhancing translation, thus making it a potential target for HCC treatment.
BACKGROUND: Ulcerative colitis (UC) is a chronic, nonspecific intestinal inflammatory disease. Acupuncture and moxibustion is proved effective in treating UC, but the mechanism has not been clarified. Proteomic technology has revealed a variety of biological markers related to immunity and inflammation in UC, which provide new insights and directions for the study of mechanism of acupuncture and moxibustion treatment of UC. AIM: To investigate the mechanism of electroacupuncture (EA) and herb-partitioned moxibustion (HM) on UC rats by using proteomics technology. METHODS: Male Sprague-Dawley rats were randomly divided into the normal (N) group, the dextran sulfate sodium (DSS)-induced UC model (M) group, the HM group, and the EA group. UC rat model was prepared with 3% DSS, and HM and EA interventions at the bilateral Tianshu and Qihai acupoints were performed in HM or EA group. Haematoxylin and eosin staining was used for morphological evaluation of colon tissues. Isotope-labeled relative and absolute quantification (iTRAQ) and liquid chromatography-tandem mass spectrometry were performed for proteome analysis of the colon tissues, followed by bioinformatics analysis and protein-protein interaction networks establishment of differentially expressed proteins (DEPs) between groups. Then western blot was used for verification of selected DEPs. RESULTS: The macroscopic colon injury scores and histopathology scores in the HM and EA groups were significantly decreased compared to the rats in the M group (P < 0.01). Compared with the N group, a total of 202 DEPs were identified in the M group, including 111 up-regulated proteins and 91 down-regulated proteins, of which 25 and 15 proteins were reversed after HM and EA interventions, respectively. The DEPs were involved in various biological processes such as biological regulation, immune system progression and in multiple pathways including natural killer cell mediated cytotoxicity, intestinal immune network for immunoglobulin A (IgA) production, and FcγR-mediated phagocytosis. The Kyoto Encyclopedia of Genes and Genomes pathways of DEPs between HM and M groups, EA and M groups both included immune-associated and oxidative phosphorylation. Network analysis revealed that multiple pathways for the DEPs of each group were involved in protein-protein interactions, and the expression of oxidative phosphorylation pathway-related proteins, including ATP synthase subunit g (ATP5L), ATP synthase beta subunit precursor (Atp5f), cytochrome c oxidase subunit 4 isoform 1 (Cox4i1) were down-regulated after HM and EA interventions. Subsequent verification of selected DEPs (Synaptic vesicle glycoprotein 2A; nuclear cap binding protein subunit 1; carbamoyl phosphate synthetase 1; Cox4i1; ATP synthase subunit b, Atp5f1; doublecortin like kinase 3) by western blot confirmed the reliability of the iTRAQ data, HM and EA interventions can significantly down-regulate the expression of oxidative phosphorylation-associated proteins (Cox4i1, Atp5f1) (P < 0.01). CONCLUSION: EA and HM could regulate the expression of ATP5L, Atp5f1, Cox4i1 that associated with oxidative phosphorylation, then might regulate immune-related pathways of intestinal immune network for IgA production, FcγR-mediated phagocytosis, thereby alleviating colonic inflammation of DSS-induced UC rats.
Colitis, Ulcerative , Electroacupuncture , Moxibustion , Acupuncture Points , Adenosine Triphosphate , Animals , Carbamyl Phosphate , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/therapy , Dextran Sulfate/toxicity , Doublecortin Domain Proteins , Electron Transport Complex IV , Eosine Yellowish-(YS) , Glycoproteins , Immunoglobulin A , Inflammation , Ligases , Male , Proteome , Proteomics , RNA Cap-Binding Proteins , Rats , Rats, Sprague-Dawley , Receptors, IgG , Reproducibility of Results
OBJECTIVE: To investigate the mechanism of action of herb-partitioned moxibustion on CD from the perspective of autophagy and immunity. METHODS: The expression of microtubule-associated protein LC3II and SQSTM1/p62 in the colon tissues was detected by immunohistochemistry. Western blot was used to detect the expression of autophagic and immune-related proteins in the colon, such as LC3II, SQSTM1/p62, Beclin1, ATG16L1, NOD2, IRGM, IL-1ß, IL-17, and TNF-ß. mRNA levels of immune factors, such as IL-1ß, IL-17, and TNF-ß, and autophagy signaling molecules, such as PI3KC, AKT1, LKB1, and mTOR, were detected by RT-qPCR. RESULTS: Herb-partitioned moxibustion reduced the protein levels of ATG16L1, NOD2, IRGM, LC3II, and Beclin1 (P < 0.01) and both the protein and mRNA levels of IL-1ß, IL-17, and TNF-ß in CD rats (P < 0.01 or P < 0.05), and it also increased the expression of SQSTM1/p62 protein (P < 0.01). The modulatory effects of herb-partitioned moxibustion on ATG16L1, NOD2, IRGM, LC3II, TNF-ß, and IL-17 protein and IL-1ß protein and mRNA were better than those of mesalazine (P < 0.01 or P < 0.05). Herb-partitioned moxibustion also reduced colon PI3KC, AKT1, and LKB1 mRNA expressions in CD rats (P < 0.01 or P < 0.05) and increased mTOR protein expression (P < 0.05). And the modulatory effect of herb-partitioned moxibustion on AKT1 mRNA was better than that of mesalazine (P < 0.05). CONCLUSION: Herb-partitioned moxibustion may inhibit excessively activated autophagy and modulate the expression of immune-related factors by regulating the LKB1-mTOR-PI3KC signal transduction networks, thereby alleviating intestinal inflammation in CD rats.
BACKGROUND: The pathogenesis of ulcerative colitis (UC) is closely related to the gut microbiota. Moxibustion has been used to improve the inflammation and gastrointestinal dysfunctions in gastrointestinal disorders such as UC. In this study, we investigated whether moxibustion could improve the gut microbial dysbiosis induced by dextran sulphate sodium. METHODS: Twenty-five male rats were randomly assigned into five groups. The UC rat model was established by administering DSS solution. The rats in the moxibustion and normal rats with moxibustion groups were treated with moxibustion at Tianshu (bilateral, ST25) points, and the mesalazine group rats were treated with mesalazine once daily for 7 consecutive days. Disease activity index (DAI) and haematoxylin and eosin staining were used to evaluate the effect of moxibustion. Gut microbiota profiling was conducted by metagenomic high throughput sequencing technology. The gut microbiota composition, diversity and function were analyzed and compared using metagenomics methodologies. RESULTS: The DAI scores and histopathology scores in the moxibustion and mesalazine groups were significantly decreased compared with the UC group (P < 0.01). Moxibustion treatment increased abundance levels of Bacteroidetes, Actinobacteria, Ascomycota, Synergistetes and decreased abundance of Firmicutes, Proteobacteria. At the genus level, the abundance of Bacteroides, Bacteroides_bacterium_M7, Prevotella, Bacteroidales_bacterium_H2, were increased and Bacteroides_bacterium_H3, Parabacteroides, Porphyromonas, Alistipes, Parasutterella were decreased in the UC group in comparsion with those in the NG group. Moxibustion increased the abundance of Bacteroides and Bacteroides_bacterium_H3 and decreased Bacteroides_bacterium_M7, Prevotella, Bacteroidales_bacterium_H2. In UC group, the specie Bacteroides_massiliensis was negatively (P < 0.05) correlated with IL-23, Bacteroides_eggerthii_CAG109 and Bacteroides_eggerthii were negatively (P < 0.05) correlated with TGF-ß. And the species Prevotella_sp_CAG1031 and Bacteroides_bacterium_H2 were significant positively (P < 0.05) correlated with IL-23. In addition, compare with the normal group, genes involved in certain metabolic pathways, such as energy production and conversion, amino acid transport and metabolism, carbohydrate transport and metabolism, were under-represented in the UC group, and these changes in the metabolic pathways could be reversed by moxibustion treatment and mesalazine treatment. CONCLUSIONS: Our findings suggest that moxibustion treatment may protect the host from mucosal inflammation by modulating the intestinal microbiota community.
Colitis, Ulcerative , Colitis , Gastrointestinal Microbiome , Moxibustion , Acupuncture Points , Animals , Colitis/chemically induced , Colitis/therapy , Colitis, Ulcerative/therapy , Dextran Sulfate , Disease Models, Animal , Male , Rats
BACKGROUND: The efficacy and mechanisms of acupuncture for Crohn's disease (CD) are not well understood. We investigated its effects on symptoms, intestinal microbiota, and circulating inflammatory markers in CD patients. METHODS: This 48-week, randomized, sham controlled, parallel-group clinical trial was performed at a tertiary outpatient clinic in China. From April 2015 to November 2019, 66 patients (mean age 40·4, 62·1% were male, all were Han Chinese) with mild to moderate active CD and unresponsive to drug treatment were enrolled and randomly assigned equally to an acupuncture group or a sham group. The treatment group received 3 sessions of acupuncture plus moxibustion per week for 12 weeks and a follow-up of 36 weeks. Clinicaltrials.gov: NCT02559037. FINDINGS: At week 12, the clinical remission rate (the primary outcome) and clinical response rate of acupuncture group were significantly higher than that of sham group, with a difference of 42·4% (95% CI: 20·1%-64·0%) and 45·5% (95% CI: 24·0%-66·9%), respectively, both of which maintained at week 48. The acupuncture group had significantly lower CD activity index and C-reactive protein level at week 12, which maintained at 36-week follow-up. The CD endoscopic index of severity, histopathological score, and recurrence rate at week 48 were significantly lower in acupuncture group. The number of operational taxonomic unit of intestinal microbiota and relative abundance of Faecalibacterium prausnitzii and Roseburia faecis were increased. Plasma diamine oxidase, lipopolysaccharide, and Th1/Th17 related cytokines were decreased in 12-week after acupuncture. INTERPRETATION: Acupuncture was effective in inducing and maintaining remission in patients with active CD, which was associated with increased abundance of intestinal anti-inflammatory bacteria, enhanced intestinal barrier, and regulation of circulating Th1/Th17-related cytokines. FUNDING: National Key Basic Research Program of China (2015CB554500 and 2009CB522900), Shanghai Rising-Star Program (19QA1408100).
BACKGROUND: Moxibustion is increasingly used for treatment of irritable bowel syndrome (IBS). This study investigated the long-term effects of moxibustion for IBS with diarrhea (IBS-D). METHODS: Patients with IBS-D were assigned to receive moxibustion or sham moxibustion (52 each, 3× per week, 6 weeks) and were followed up to 24 weeks. The acupoints were bilateral ST25 and ST36, body surface temperatures at acupoints were 43°C ± 1°C and 37°C ± 1°C for the moxibustion and sham groups, respectively. Primary outcome was changes in IBS Adequate Relief (IBS-AR) from baseline to 6 weeks. Secondary outcomes included the following: IBS symptom severity scale (IBS-SSS), Bristol stool form scale (BSS), IBS quality of life (IBS-QOL), and Hospital Anxiety and Depression Scale (HADS). RESULTS: Based on an intention-to-treat analysis, the rate of IBS-AR in the moxibustion group was significantly higher than the sham group at 6 weeks (76.9% versus 42.3%; p < 0.001); the mean decrease of total IBS-BSS score in the moxibustion group was lower than that of the sham group (-116.9 versus -61.5; p < 0.001), both of which maintained throughout the follow-up period. Five specific domains of the IBS-SSS were lower in the moxibustion group than the sham, throughout (p < 0.001). At week 6, the rate of reduction >50 points in IBS-SSS of the treatment group was significantly higher than that of the sham (p < 0.001), which persisted throughout the follow-up period. Similar long-lasting improvements were observed in BSS, stool frequency, and stool urgency (p < 0.001). Improvements of IBS-QOL and HADS were comparable between the groups. CONCLUSIONS: Moxibustion treatment benefits the long-term relief of symptoms in IBS-D patients. TRIAL REGISTRATION: Clinical trials.gov (NCT02421627). Registered on 20 April 2015.
BACKGROUND AND AIMS: Intestinal fibrosis is one of the severe and common complications of Crohn's disease (CD), but the etiology and pathogenesis remain uncertain. The study intended to examine whether the effect of herb-partitioned moxibustion on rats with CD-associated intestinal fibrosis is associated with the RhoA/ROCK1/MLC pathway. METHODS: All experimental rats were randomly allocated into the normal control group (NC), model control group (MC), and herb-partitioned moxibustion group (HPM). Intestinal fibrosis was established in rats with CD by repeated rectal administrations of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Herb-partitioned moxibustion was applied at the Qihai (CV6) and Tianshu (ST25) acupoints once daily for 10 days in the HPM group. In this study, histological changes were examined by hematoxylin and eosin (HE) staining; then, Masson's trichrome staining was used to assess the degree of fibrosis in each group. Experimental methods of immunohistochemistry, western blotting, and real-time PCR were applied to detect the levels of α-SMA, collagen III, RhoA, ROCK1, and p-MLC. Moreover, the double immunofluorescent staining for the colocalization of both α-SMA and ROCK1 was performed. RESULTS: Contrasted with the normal controls, the collagen deposition and fibrosis scores were increased in colonic tissue of model rats, and HPM decreased the collagen deposition and fibrosis scores. The protein of α-SMA and collagen III in the MC group exceeds that of the NC group; HPM decreased the expression of α-SMA and collagen III in rats with intestinal fibrosis. Similarly, the expression of RhoA, ROCK1, and p-MLC in model rats was obviously increased compared with normal controls; the expression of RhoA, ROCK1, and p-MLC was decreased after HPM. The coexpression of α-SMA and ROCK1 in rats with intestinal fibrosis was higher than normal rats. CONCLUSION: HPM improves CD-associated intestinal fibrosis by suppressing the RhoA/ROCK1/MLC pathway.
Acupuncture and moxibustion have definite clinical effects on treating ulcerative colitis (UC), but their mechanism is still unclear. To investigate the molecular mechanisms, we applied herb-partitioned moxibustion or electroacupuncture at the Tianshu (ST25) points on UC rats and used RNA sequencing to identify molecular consequences. Male Sprague Dawley (SD) rats were divided into 6 groups randomly: the normal control (NC) group, the control + herb-partitioned moxibustion (NCHM) group, the control + electroacupuncture (NCEA) group, the model (UC) group, the model + herb-partitioned moxibustion (UCHM) group, and the model + electroacupuncture (UCEA) group. Compared to the UC group, HE staining in the UCHM group and UCEA group indicated that colitis was relieved, the histopathological score and MPO were both significantly reduced, and the serum hs-CRP concentration was decreased significantly. The results of RNA-seq suggested that, compared to the NC group, 206 upregulated genes and 167 downregulated genes were identified in colon tissues from the UC group; compared to the UC group, the expression levels of some genes were both affected in the UCHM group and the UCEA group (684 differentially expressed genes were identified in the UCHM group, and 1182 differentially expressed genes were identified in the UCEA group). KEGG signal pathway analysis indicated that the differentially expressed genes in the UCHM group were associated with the JAK-STAT signaling pathway and cell adhesion molecule (CAM); the differentially expressed genes in the UCEA group were associated with the NF-κB signaling pathway, the toll-like receptor signaling pathways, the PI3K-Akt signaling pathway, the MAPK signaling pathway, and the Wnt signaling pathway. This is the first study to reveal the gene expression characteristics of the anti-inflammatory effect of UC rats from the perspective of acupuncture and moxibustion control, which provide a clue for further investigation into the molecular mechanisms of UC treatment by acupuncture and moxibustion.
OBJECTIVE: To observe the effect of herb-partitioned moxibustion (HPM) on the miRNA expression profile of thyroid tissue in experimental autoimmune thyroiditis (EAT) rats. METHODS: Rats were randomly divided into normal control (NC) group, EAT model (EAT) group, HPM group and western medicine (Med) group. EAT model rats were prepared by a combined immunization with complete and incomplete Freund's adjuvant emulsified with porcine thyroglobulin and iodine. Rats in the HPM group were treated with HPM, while rats in the Med group were treated with levothyrocine (1 µg/2 mL) by gavage. HE staining was used to observe the pathological morphological changes of thyroid tissue, ELISAs was uaed to detect the serum concentrations of TGAb, TPOAb, FT3, FT4, TSH. We then performed high-throughput miRNA sequencing to analyse the miRNA expression profiles in the thyroid tissues, followed by a bioinformatics analysis. RT-qPCR was used to verify the identified differentially expressed miRNAs. RESULTS: HPM improved the thyroid tissue morphology and reduced serum TPOAb, TGAb, TSH concentration in EAT rats (P < 0.05), but with no obvious effect on FT3 and FT4 concentration. While the TSH, FT3 and FT4 concentration was significantly changed in the Med group (P < 0.01 or P < 0.05) compared with that of EAT group. Sequencing results showed that a total of 17 miRNAs were upregulated, and 4 were downregulated in the EAT rats, in which the expression levels of miR-346 and miR-331-5p were reversed by HPM. The target genes of the miRNAs that regulated by HPM were associated with a variety of immune factors and immune signals. RT-qPCR verification showed that the expression of miRNA-346 and miRNA-331-5p was consistent with the sequencing results. CONCLUSIONS: HPM could regulate the the expression of miRNA-346 and miRNA-331-5p, then act on their target genes to immune and inflammation-related pathways, which may be one of the mechanisms of HPM on EAT rats.
MicroRNAs , Moxibustion , Thyroiditis, Autoimmune , Animals , MicroRNAs/genetics , Moxibustion/methods , Rats , Thyroiditis, Autoimmune/genetics , Thyroiditis, Autoimmune/therapy
Inflammatory bowel disease (IBD), which mainly includes ulcerative colitis (UC) and Crohn's disease (CD), is a group of chronic bowel diseases that are characterized by abdominal pain, diarrhea, and bloody stools. IBD is strongly associated with depression, and its patients have a higher incidence of depression than the general population. Depression also adversely affects the quality of life and disease prognosis of patients with IBD. The tryptophan-kynurenine metabolic pathway degrades more than 90% of tryptophan (TRP) throughout the body, with indoleamine 2,3-dioxygenase (IDO), the key metabolic enzyme, being activated in the inflammatory environment. A series of metabolites of the pathway are neurologically active, among which kynerunic acid (KYNA) and quinolinic acid (QUIN) are molecules of great interest in recent studies on the mechanisms of inflammation-induced depression. In this review, the relationship between depression in IBD and the tryptophan-kynurenine metabolic pathway is overviewed in the light of recent publications.
Brain-Gut Axis , Depression/complications , Depression/metabolism , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/metabolism , Kynurenine/metabolism , Tryptophan/metabolism , Animals , Brain-Gut Axis/physiology , Depression/physiopathology , Humans , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Inflammation/metabolism , Inflammatory Bowel Diseases/physiopathology , Prognosis , Quality of Life , Quinolinic Acid/metabolism , Signal Transduction
OBJECTIVE: To evaluate the efficacy of herb-partitioned moxibustion (HPM) at Qihai (CV6), Tianshu (ST25) and Shangjuxu (ST37) acupoints in relieving symptoms and the immune regulation of HPM on the toll-like receptors 4 (TLR4) signaling pathway in ulcerative colitis (UC) patients. METHODS: A randomized, single-blind study was conducted 63 patients to receive HPM or sham HPM treatment. The efficacy outcomes included scores of the Mayo, Baron, inflammatory bowel disease questionnaire (IBDQ), self-rating depression scale (SDS), self-rating anxiety scale (SAS). HE staining was used to observe the histopathological changes of the colon. The expression of inflammatory cytokines and TLR4 signaling pathway related molecules were determined by enzyme-linked immunosorbent assay and immunohistochemistry. RESULTS: Baron, SDS, SAS scores were significantly decreased in moxibustion group (P < 0.05), IBDQ score was significantly greater in the moxibustion group than in the sham moxibustion group (P < 0.05). Histopathology of mucosal biopsies showed that both two groups improved in mucosa after treatment. The expression levels of tumor necrosis factor-α, interleukin-2, interleukin-12, interferon-γ, and TLR4, lipopolysaccharide, myeloid differentiation factor 88, interleukin receptor associated kinase, tumor necrosis factor receptor associated factor 6 and nuclear factor kappa-B p65 were significantly lower in the moxibustion group than in the sham moxibustion group (P < 0.05). CONCLUSION: This study showed that HPM at Qihai?(CV6),?Tianshu?(ST25) and?Shangjuxu (ST37) acupoints is effective to relieve symptoms, anxiety, depression and improving life quality in UC patients, which may be related to the immune regulation of HPM on TLR4 signaling pathway.
Colitis, Ulcerative , Moxibustion , Acupuncture Points , Animals , Colitis, Ulcerative/therapy , Humans , Rats , Rats, Sprague-Dawley , Signal Transduction , Single-Blind Method
Cofilin is an actin-binding protein that regulates filament dynamics and depolymerization. The over-expression of cofilin is observed in various cancers, cofilin promotes cancer metastasis by regulating cytoskeletal reorganization, lamellipodium formation and epithelial-to-mesenchymal transition. Clinical treatment of cancer regarding cofilin has been explored in aspects of tumor cells apoptosis and cofilin related miRNAs. This review addresses the structure and phosphorylation of cofilin and describes recent findings regarding the function of cofilin in regulating cancer metastasis and apoptosis in tumor cells.
Metastasis and relapse are major causes of cancer-related fatalities. The elucidation of relevant pathomechanisms and adoption of appropriate countermeasures are thus crucial for the development of clinical strategies that inhibit malignancy progression as well as metastasis. An integral component of the extracellular matrix, the type 1 transmembrane glycoprotein syndecan-1 (SDC-1) binds cytokines and growth factors involved in tumor microenvironment modulation. Alterations in its localization have been implicated in both cancer metastasis and drug resistance. In this review, available data regarding the structural characteristics, shedding process, and nuclear translocation of SDC-1 are detailed with the aim of highlighting strategies directly targeting SDC-1 as well as SDC-1-mediated carcinogenesis.
BACKGROUND: Autophagy is an evolutionarily conserved biological process in eukaryotic cells that involves lysosomal-mediated degradation and recycling of related cellular components. Recent studies have shown that autophagy plays an important role in the pathogenesis of Crohn's disease (CD). Herbal cake-partitioned moxibustion (HM) has been historically practiced to treat CD. However, the mechanism by which HM regulates colonic autophagy in CD remains unclear. AIM: To observe whether HM can alleviate CD by regulating colonic autophagy and to elucidate the underlying mechanism. METHODS: Rats were randomly divided into a normal control (NC) group, a CD group, an HM group, an insulin + CD (I + CD) group, an insulin + HM (I + HM) group, a rapamycin + CD (RA + CD) group, and a rapamycin + HM (RA + HM) group. 2,4,6-trinitrobenzenesulfonic acid was administered to establish a CD model. The morphology of the colonic mucosa was observed by hematoxylin-eosin staining, and the formation of autophagosomes was observed by electron microscopy. The expression of autophagy marker microtubule-associated protein 1 light chain 3 beta (LC3B) was observed by immunofluorescence staining. Insulin and rapamycin were used to inhibit and activate colonic autophagy, respectively. The mRNA expression levels of phosphatidylinositol 3-kinase class I (PI3KC1), Akt1, LC3B, sequestosome 1 (p62), and mammalian target of rapamycin (mTOR) were evaluated by RT-qPCR. The protein expression levels of interleukin 18 (IL-18), tumor necrosis factor-α (TNF-α), nuclear factor κB/p65 (NF-κB p65), LC3B, p62, coiled-coil myosin-like BCL2-interacting protein (Beclin-1), p-mTOR, PI3KC1, class III phosphatidylinositol 3-kinase (PI3KC3/Vps34), and p-Akt were evaluated by Western blot analysis. RESULTS: Compared with the NC group, the CD group showed severe damage to colon tissues and higher expression levels of IL-18 and NF-κB p65 in colon tissues (P < 0.01 for both). Compared with the CD group, the HM group showed significantly lower levels of these proteins (P IL-18 < 0.01 and P p65 < 0.05). There were no significant differences in the expression of TNF-α protein in colon tissue among the rat groups. Typical autophagic vesicles were found in both the CD and HM groups. The expression of the autophagy proteins LC3B and Beclin-1 was upregulated (P < 0.01 for both) in the colon tissues of rats in the CD group compared with the NC group, while the protein expression of p62 and p-mTOR was downregulated (P < 0.01 for both). However, these expression trends were significantly reversed in the HM group compared with the CD group (P LC3B < 0.01, P Beclin-1 < 0.05, P p62 < 0.05, and P m-TOR < 0.05). Compared with those in the RA + CD group, the mRNA expression levels of PI3KC1, Akt1, mTOR, and p62 in the RA + HM group were significantly higher (P PI3KC1 < 0.01 and P Akt1, mTOR, and p62 < 0.05), while those of LC3B were significantly lower (P < 0.05). Compared with the RA + CD group, the RA + HM group exhibited significantly higher PI3KC1, p-Akt1, and p-mTOR protein levels (P PI3KC1 < 0.01, P p-Akt1 < 0.05, and P p-mTOR < 0.01), a higher p62 protein level (P = 0.057), and significantly lower LC3B and Vps34 protein levels (P < 0.01 for both) in colon tissue. CONCLUSION: HM can activate PI3KC1/Akt1/mTOR signaling while inhibiting the PI3KC3 (Vps34)-Beclin-1 protein complex in the colon tissues of CD rats, thereby inhibiting overactivated autophagy and thus exerting a therapeutic effect.
Biological Phenomena , Crohn Disease , Moxibustion , Animals , Autophagy , Colon , Crohn Disease/therapy , Phosphatidylinositol 3-Kinases , Rats
