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1.
Zhongguo Zhen Jiu ; 44(4): 400-404, 2024 Apr 12.
Article in English, Chinese | MEDLINE | ID: mdl-38621726

ABSTRACT

OBJECTIVES: To observe the effect of penetrating-moxibustion therapy on postpartum uterine involution. METHODS: Eighty puerpera were randomized into an observation group and a control group, 40 cases in each one. In the control group, oxytocin injection was administered by intravenous drip, 20 U each time, once daily. In the observation group, on the base of the treatment as the control group, the penetrating-moxibustion therapy was used at Shenque (GV 8), Qihai (CV 6) and Guanyuan (CV 4), 30 min to 40 min each time, twice a day. The intervention of each group started from the first day after childbirth and lasted 3 days. The uterine volume before and after treatment, and in 42 days of postpartum, the height decrease of the fundus of the uterus, the score of visual analogue scale (VAS) for uterine contraction, the volume of lochia rubra in 1 to 3 days of treatment, and lochia duration were compared between the two groups; and the clinical effect was evaluated. RESULTS: The uterine volume in the observation group was smaller than that of the control group after treatment (P<0.01). In 1 to 3 days of treatment, the height decrease of the fundus of the uterus in the observation group was larger (P<0.01), VAS scores of uterine contraction were lower (P<0.05, P<0.01), the lochia rubra volume was less (P<0.01) than those in the control group. The duration of lochia rubra and lochia was shorter (P<0.01) in the observation group when compared with that of the control group. The favorable rate of uterine involution in the observation group was 95.0% (38/40), higher than that of the control group (75.0%, 30/40, P<0.05). CONCLUSIONS: Penetrating-moxibustion therapy accelerates the recovery of the uterine volume, relieves uterine contraction, shortens the duration of lochia, reduces the lochia volume and promotes the postpartum uterine involution.


Subject(s)
Body Fluids , Moxibustion , Pregnancy , Female , Humans , Postpartum Period , Uterus , Delivery, Obstetric , Acupuncture Points
2.
Funct Plant Biol ; 512024 Jan.
Article in English | MEDLINE | ID: mdl-38228091

ABSTRACT

The fatty acyl-acyl carrier protein thioesterase B (FATB ) gene, involved in the synthesis of saturated fatty acids, plays an important role in the content of fatty acid and composition of seed storage lipids. However, the role of FATB in soybeans (Glycine max ) has been poorly characterised. This paper presents a preliminary bioinformatics and molecular biological investigation of 10 hypothetical FATB members. The results revealed that GmFATB1B , GmFATB2A and GmFATB2B contain many response elements involved in defense and stress responses and meristem tissue expression. Moreover, the coding sequences of GmFATB1A and GmFATB1B were significantly longer than those of the other genes. Their expression varied in different organs of soybean plants during growth, with GmFATB2A and GmFATB2B showing higher relative expression. In addition, subcellular localisation analysis revealed that they were mainly present in chloroplasts. Overexpression of GmFATB1A , GmFATB1B , GmFATB2A and GmFATB2B in transgenic Arabidopsis thaliana plants increased the seed oil content by 10.3%, 12.5%, 7.5% and 8.4%, respectively, compared to that in the wild-type and led to significant increases in palmitic and stearic acid content. Thus, this research has increased our understanding of the FATB family in soybeans and provides a theoretical basis for subsequent improvements in soybean quality.


Subject(s)
Arabidopsis , Fatty Acids , Thiolester Hydrolases , Fatty Acids/metabolism , Arabidopsis/genetics , Glycine max/genetics , Seeds/genetics
3.
Bioinspir Biomim ; 18(6)2023 10 17.
Article in English | MEDLINE | ID: mdl-37846869

ABSTRACT

We propose a method for extending the virtual aperture of the small aperture high-frequency surface wave radar multielement array inspired by a fly namedOrmia ochracea. Despite the tremendous incompatibility between its ear and the incoming wavelength,Ormiacan accurately local the sound of its host cricket. This ability benefits from the coupled structure ofOrmia's ears which have been modelled as a mechanical vibration system. In this paper, we first design a two-degree of freedom biologically inspired coupled system by mimickingOrmia's coupled ears. We quantitatively analyze its extension capability to the array aperture and construct the received signal model of the virtual array. We then analyze its response characteristic and available frequency band. To achieve the applications of arbitrary desired frequencies, we propose a frequency conversion algorithm. Moreover, we design two multi-degree of freedom biologically inspired coupled systems for the multielement array We summarize the criteria for extending the degree of freedom and optimize these two systems to address their respective shortcomings. Numerical results give the optimal system parameters for our desired frequency and validate the frequency conversion algorithm. By comparing the radiation pattern of the inspired arrays (arrays with the proposed systems) with that of an ordinary array, we demonstrate the virtual aperture extension capability of our proposed method. We also verify the effectiveness of proposed method by processing the actual received signals of the array.


Subject(s)
Radar , Vibration , Equipment Design , Sound , Algorithms
4.
Genes Dis ; 10(4): 1429-1444, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37397521

ABSTRACT

DNA is highly vulnerable to spontaneous and environmental timely damage in living cells. DNA damage may cause genetic instability and increase cancer risk if the damages are not repaired timely and efficiently. Human cells possess several DNA damage response (DDR) mechanisms to protect the integrity of their genome. Clarification of the mechanisms underlying the DNA damage response following lethal damage will facilitate the identification of therapeutic targets for cancers. Histone post-translational modifications (PTMs) have been indicated to play different roles in the repair of DNA damage. In this context, histone PTMs regulate recruitment of downstream effectors, and facilitate appropriate repair response. This review outlines the current understanding of different histone PTMs in response to DNA damage repair, besides, enumerates the role of new type PTMs such as histone succinylation and crotonylation in regulating DNA damage repair processes.

5.
Int J Mol Sci ; 24(10)2023 May 16.
Article in English | MEDLINE | ID: mdl-37240164

ABSTRACT

Male infertility is a global issue that seriously affects reproductive health. This study aimed to understand the underlying causes of idiopathic non-obstructive azoospermia (iNOA), which is a type of male infertility with unknown origins that accounts for 10-15% of cases. By using single-cell analysis techniques, we aimed to uncover the mechanisms of iNOA and gain insight into the cellular and molecular changes in the testicular environment. In this study, we performed bioinformatics analysis using scRNA-seq and microarray data obtained from the GEO database. The analysis included techniques such as pseudotime analysis, cell-cell communication, and hdWGCNA. Our study showed a significant difference between the iNOA and the normal groups, indicating a disorder in the spermatogenic microenvironment in iNOA. We observed a reduction in the proportion of Sertoli cells and blocked germ cell differentiation. Additionally, we found evidence of testicular inflammation related to macrophages and identified ODF2 and CABYR as potential biomarkers for iNOA.


Subject(s)
Azoospermia , Infertility, Male , Orchitis , Humans , Male , Azoospermia/genetics , Testis , Spermatogenesis , Inflammation , Single-Cell Analysis , Heat-Shock Proteins
6.
PeerJ ; 11: e14941, 2023.
Article in English | MEDLINE | ID: mdl-36968000

ABSTRACT

Background: Soybean (Glycine max) is a major protein and vegetable oil source. In plants, diacylglycerol acyltransferase (DGAT) can exert strong flux control, which is rate-limiting for triacylglycerol biosynthesis in seed oil formation. Methods: Here, we identified soybean DGAT genes via a bioinformatics method, thereby laying a solid foundation for further research on their function. Based on our bioinformatics analyses, including gene structure, protein domain characteristics, and phylogenetic analysis, 26 DGAT putative gene family members unevenly distributed on 12 of the 20 soybean chromosomes were identified and divided into the following four groups: DGAT1, DGAT2, WS/DGAT, and cytoplasmic DGAT. Results: The Ka/Ks ratio of most of these genes indicated a significant positive selection pressure. DGAT genes exhibited characteristic expression patterns in soybean tissues. The differences in the structure and expression of soybean DGAT genes revealed the diversity of their functions and the complexity of soybean fatty acid metabolism. Our findings provide important information for research on the fatty acid metabolism pathway in soybean. Furthermore, our results will help identify candidate genes for potential fatty acid-profile modifications to improve soybean seed oil content. Conclusions: This is the first time that in silico studies have been used to report the genomic and proteomic characteristics of DGAT in soybean and the effect of its specific expression on organs, age, and stages.


Subject(s)
Diacylglycerol O-Acyltransferase , Glycine max , Diacylglycerol O-Acyltransferase/genetics , Glycine max/genetics , Phylogeny , Proteomics , Plant Oils/metabolism , Fatty Acids/metabolism
7.
J Plant Physiol ; 284: 153961, 2023 May.
Article in English | MEDLINE | ID: mdl-36933340

ABSTRACT

The tubers of the widely distributed Cyperus esculentus are rich in oil, and therefore, the plant is considered to have a high utilization value in the vegetable oil industry. Oleosins and caleosins are lipid-associated proteins found in oil bodies of seeds; however oleosins and caleosins genes have not been identified in C. esculentus. In this study, we performed transcriptome sequencing and lipid metabolome analysis of C. esculentus tubers at four developmental stages to obtain the information on their genetic profile, expression trends, and metabolites in oil accumulation pathways. Overall, 120,881 non-redundant unigenes and 255 lipids were detected; 18 genes belonged to the acetyl-CoA carboxylase (ACC), malonyl-CoA:ACP transacylase (MCAT), ß-ketoacyl-ACP synthase (KAS), and fatty acyl-ACP thioesterase (FAT) gene families involved in fatty acid biosynthesis, and 16 genes belonged to the glycerol-3-phosphate acyltransferase (GPAT), diacylglycerol acyltransferase 3 (DGAT3), phospholipid:diacylglycerol acyltransferase (PDAT), FAD2, and lysophosphatidic acid acyltransferase (LPAAT) gene families playing important roles in triacylglycerol synthesis. We also identified 9 oleosin- and 21 caleosin-encoding genes in C. esculentus tubers. These results provide detailed information on the C. esculentus transcriptional and metabolic profiles, which can be used as reference for the development of strategies to increase oil content in C. esculentus tubers.


Subject(s)
Cyperus , Diacylglycerol O-Acyltransferase , Diacylglycerol O-Acyltransferase/genetics , Cyperus/genetics , Cyperus/metabolism , Plant Proteins/metabolism , Seeds/metabolism , Plant Oils/metabolism
8.
J Oncol ; 2022: 7319641, 2022.
Article in English | MEDLINE | ID: mdl-35847360

ABSTRACT

Aim: To explore the role of Rac1 on sorafenib resistance in hepatocellular carcinoma. Methods: CCK-8, wound healing assay, Transwell, and cell cycle assay were used to detect the tumor cells development. Cell viability was assessed by MTT. The glycolytic pathway was revealed by cellular metabolism assays. Result: We recovered that Rac1 upregulation was related to HCC patients' poorer prognosis. Forced expression of Rac1 promoted cell development and sorafenib chemoresistance in HCC cells. Rac1 inhibitor EHop-016 and sorafenib combination markedly prevented cell viability, G2/M phase cycle arrest, and apoptosis than single therapy. Furthermore, combination therapy decreased glycolysis in HCC cells. In vivo, the tumor growth was significantly prevented by combination therapy single therapy. Conclusion: Our research declares that Rac1 inhibition could block sorafenib resistance in HCC by decreasing glycolysis, which would provide an underlying target for HCC therapy.

9.
Trials ; 23(1): 574, 2022 Jul 19.
Article in English | MEDLINE | ID: mdl-35854329

ABSTRACT

BACKGROUND: Migraine is a highly prevalent neurological disorder. It is the third most prevalent disorder and the seventh highest cause of disability worldwide. Acupuncture may be a viable prophylactic treatment option for frequent or uncontrolled migraine. Clinical studies comparing acupuncture and placebo acupuncture have not reached a consistent conclusion in confirming whether acupuncture is effective in migraine prophylaxis. The effect of acupuncture mainly depends on acupoints and needles operation. We found that the design of the placebo acupuncture in previous studies included shallow needling at sham acupoints, non-penetrating needling at sham acupoints, and needling at inactive acupuncture points to achieve the inert effect of control group, but the non-penetrating needling at true acupoints was ignored. This randomized controlled trial aims to use true acupoints for non-penetrating acupuncture as control to evaluate the efficacy of manual acupuncture for the prophylaxis of migraine without aura (MWoA). METHODS/DESIGN: This is a single-blinded, randomized, controlled, prospective, multi-center trial with two parallel treatment groups. A total of 198 eligible patients with MWoA will be randomly divided into two groups (1:1 allocation ratio). The intervention group will receive manual acupuncture and the control group will receive placebo acupuncture (non-penetrating). Patients will receive three acupuncture treatment sessions per week for 4 consecutive weeks. All patients will then receive a 12-week follow-up. DISCUSSION: In this study, we are evaluating the efficacy and safety of manual acupuncture in the prophylaxis of MWoA. The placebo control is using non-penetrating needling verum acupoints. It is essential to determine an appropriate control method to ensure the methodological quality of a randomized controlled trial. TRIAL REGISTRATION: The trial has been registered in the Chinese Clinical Trial Registry (approval no. ChiCTR2000032308 ) in April 2020.


Subject(s)
Acupuncture Therapy , Migraine without Aura , Acupuncture Points , Acupuncture Therapy/adverse effects , Acupuncture Therapy/methods , Humans , Migraine without Aura/etiology , Multicenter Studies as Topic , Prospective Studies , Randomized Controlled Trials as Topic , Treatment Outcome
10.
Proc Natl Acad Sci U S A ; 119(29): e2205574119, 2022 07 19.
Article in English | MEDLINE | ID: mdl-35858331

ABSTRACT

Intestinal barrier immunity is essential for controlling gut microbiota without eliciting harmful immune responses, while its defect contributes to the breakdown of intestinal homeostasis and colitis development. Chemerin, which is abundantly expressed in barrier tissues, has been demonstrated to regulate tissue inflammation via CMKLR1, its functional receptor. Several studies have reported the association between increased expression of chemerin-CMKLR1 and disease severity and immunotherapy resistance in inflammatory bowel disease (IBD) patients. However, the pathophysiological role of endogenous chemerin-CMKLR1 signaling in intestinal homeostasis remains elusive. We herein demonstrated that deficiency of chemerin or intestinal epithelial cell (IEC)-specific CMKLR1 conferred high susceptibility to microbiota-driven neutrophilic colon inflammation and subsequent tumorigenesis in mice following epithelial injury. Unexpectedly, we found that lack of chemerin-CMKLR1 signaling specifically reduced expression of lactoperoxidase (LPO), a peroxidase that is predominantly expressed in colonic ECs and utilizes H2O2 to oxidize thiocyanates to the antibiotic compound, thereby leading to the outgrowth and mucosal invasion of gram-negative bacteria and dysregulated CXCL1/2-mediated neutrophilia. Importantly, decreased LPO expression was causally linked to aggravated microbiota-driven colitis and associated tumorigenesis, as LPO supplementation could completely rescue such phenotypes in mice deficient in epithelial chemerin-CMKLR1 signaling. Moreover, epithelial chemerin-CMKLR1 signaling is necessary for early host defense against bacterial infection in an LPO-dependent manner. Collectively, our study reveals that the chemerin-CMKLR1/LPO axis represents an unrecognized immune mechanism that potentiates epithelial antimicrobial defense and restricts harmful colonic neutrophilia and suggests that LPO supplementation may be beneficial for microbiota dysbiosis in IBD patients with a defective innate antimicrobial mechanism.


Subject(s)
Carcinogenesis , Chemokines , Colitis , Colon , Gastrointestinal Microbiome , Intercellular Signaling Peptides and Proteins , Lactoperoxidase , Receptors, Chemokine , Animals , Carcinogenesis/immunology , Cell Transformation, Neoplastic , Chemokines/genetics , Chemokines/metabolism , Colitis/immunology , Colitis/microbiology , Colon/immunology , Colon/microbiology , Hydrogen Peroxide/metabolism , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Intestinal Mucosa/metabolism , Intestinal Mucosa/microbiology , Lactoperoxidase/metabolism , Mice , Neutrophils/immunology , Receptors, Chemokine/genetics , Receptors, Chemokine/metabolism
11.
Chin Med ; 17(1): 67, 2022 Jun 08.
Article in English | MEDLINE | ID: mdl-35676697

ABSTRACT

BACKGROUND: The acupoint selections impact the effects of acupuncture, and preliminary evidence showed potential connection between pain threshold (PT) and acupuncture response. This study examined whether acupuncture at acupoints with lower PT versus higher PT would yield different effects in patients with knee osteoarthritis (KOA). METHODS: In this multicenter randomized clinical trial, patients were randomly assigned (1:1:1) to receive acupuncture at acupoints with lower PT (LPT group), acupuncture at acupoints with higher PT (HPT group), and no acupuncture (waiting-list group). PT was measured with electronic von Frey detector. The primary outcome was the change in WOMAC total score from baseline to 16 weeks, and the secondary outcomes were SF-12 score, and active knee range of motion (ROM). Intention-to-treat analysis was conducted with linear mixed-effect model. RESULTS: Among 666 randomized patients, 625 (93.84%) completed the study. From baseline to 16 weeks, patients in the LPT group versus HPT group had similar effects in reducing WOMAC total score (adjusted mean difference (MD) 2.21, 95% confidence interval (CI) -2.51 to 6.92, P = 0.36), while a greater reduction in WOMAC total score was observed in LPT group (-9.77, 95% CI -14.47 to -5.07, P < 0.001) and HPT group (-11.97, 95% CI -16.71 to -7.24, P < 0.001) compared with waiting-list group. There were no differences in SF-12 score and knee ROM between LPT versus HPT groups. CONCLUSION: Our findings found that the effects of acupuncture at acupoints with lower versus higher PT were similar, both were effective for patients with KOA. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03299439. Registered 3 October 2017, https://clinicaltrials.gov/ct2/show/NCT03299439.

12.
Immunity ; 55(7): 1185-1199.e8, 2022 07 12.
Article in English | MEDLINE | ID: mdl-35738281

ABSTRACT

Lipoprotein disorder is a common feature of chronic pancreatitis (CP); however, the relationship between lipoprotein disorder and pancreatic fibrotic environment is unclear. Here, we investigated the occurrence and mechanism of pancreatic stellate cell (PSC) activation by lipoprotein metabolites and the subsequent regulation of type 2 immune responses, as well as the driving force of fibrotic aggressiveness in CP. Single-cell RNA sequencing revealed the heterogeneity of PSCs and identified very-low-density lipoprotein receptor (VLDLR)+ PSCs that were characterized by a higher lipid metabolism. VLDLR promoted intracellular lipid accumulation, followed by interleukin-33 (IL-33) expression and release in PSCs. PSC-derived IL-33 strongly induced pancreatic group 2 innate lymphoid cells (ILC2s) to trigger a type 2 immune response accompanied by the activation of PSCs, eventually leading to fibrosis during pancreatitis. Our findings indicate that VLDLR-enhanced lipoprotein metabolism in PSCs promotes pancreatic fibrosis and highlight a dominant role of IL-33 in this pro-fibrotic cascade.


Subject(s)
Pancreatic Stellate Cells , Pancreatitis, Chronic , Receptors, LDL/metabolism , Cells, Cultured , Fibrosis , Humans , Immunity, Innate , Interleukin-33/metabolism , Lipid Metabolism , Lipoproteins, VLDL/metabolism , Lymphocytes/metabolism , Pancreas/pathology , Pancreatic Stellate Cells/metabolism , Pancreatic Stellate Cells/pathology , Pancreatitis, Chronic/metabolism , Pancreatitis, Chronic/pathology
13.
Hepatology ; 75(1): 28-42, 2022 01.
Article in English | MEDLINE | ID: mdl-34387870

ABSTRACT

BACKGROUND AND AIMS: We previously demonstrated that cancer-associated fibroblasts (CAFs) promote tumor growth through recruitment of myeloid-derived suppressor cells (MDSCs). 5-lipoxygenase (5-LO) is highly expressed in myeloid cells and is critical for synthesizing leukotriene B4 (LTB4), which is involved in tumor progression by activating its receptor leukotriene B4 receptor type 2 (BLT2). In this study, we investigated whether and how CAFs regulate MDSC function to enhance cancer stemness, the driving force of the cancer aggressiveness and chemotherapy refractoriness, in highly desmoplastic intrahepatic cholangiocarcinoma (ICC). APPROACH AND RESULTS: RNA-sequencing analysis revealed enriched metabolic pathways but decreased inflammatory pathways in cancer MDSCs compared with blood MDSCs from patients with ICC. Co-injection of ICC patient-derived CAFs promoted cancer stemness in an orthotopic ICC model, which was blunted by MDSC depletion. Conditioned media (CM) from CAF-educated MDSCs drastically promoted tumorsphere formation efficiency and stemness marker gene expression in ICC cells. CAF-CM stimulation increased expression and activity of 5-LO in MDSCs, while 5-LO inhibitor impaired the stemness-enhancing capacity of MDSCs in vitro and in vivo. Furthermore, IL-6 and IL-33 primarily expressed by CAFs mediated hyperactivated 5-LO metabolism in MDSCs. We identified the LTB4-BLT2 axis as the critical downstream metabolite signaling of 5-LO in promoting cancer stemness, as treatment with LTB4 was elevated in CAF-educated MDSCs, or blockade of BLT2 (which was preferentially expressed in stem-like ICC cells) significantly reduced stemness-enhancing effects of CAF-educated MDSCs. Finally, BLT2 blockade augmented chemotherapeutic efficacy in ICC patient-derived xenograft models. CONCLUSIONS: Our study reveals a role for CAFs in orchestrating the optimal cancer stemness-enhancing microenvironment by educating MDSCs, and suggests the 5-LO/LTB4-BLT2 axis as promising therapeutic targets for ICC chemoresistance by targeting cancer stemness.


Subject(s)
Arachidonate 5-Lipoxygenase/metabolism , Bile Duct Neoplasms/pathology , Cancer-Associated Fibroblasts/metabolism , Cholangiocarcinoma/pathology , Neoplastic Stem Cells/pathology , Animals , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bile Duct Neoplasms/drug therapy , Bile Ducts, Intrahepatic/pathology , Cell Communication , Cell Line, Tumor , Cell Proliferation/drug effects , Cholangiocarcinoma/drug therapy , Culture Media, Conditioned/metabolism , Drug Resistance, Neoplasm , Humans , Lipoxygenase Inhibitors/pharmacology , Male , Mice , Myeloid-Derived Suppressor Cells/metabolism , Neoplastic Stem Cells/drug effects , Receptors, Leukotriene B4/antagonists & inhibitors , Receptors, Leukotriene B4/metabolism , Tumor Microenvironment/drug effects , Xenograft Model Antitumor Assays
15.
J Leukoc Biol ; 110(2): 293-300, 2021 08.
Article in English | MEDLINE | ID: mdl-34184320

ABSTRACT

Chronic pancreatitis (CP) is a continuing or relapsing inflammatory disease of the pancreas, characterized by fibrosis of the whole tissue. The regulatory mechanisms of the immune microenvironment in the pathogenesis of CP are still not clear. Immune cells, especially myeloid cells, play an important role in the pathogenesis of pancreatitis. Understanding the regulatory mechanisms of immune infiltration has a significant impact on CP intervention. Here, we demonstrated that transcription factor STAT5 was involved in and critical for the progression of CP. Inflammatory stress could significantly increase the expression and activation of STAT5 during CP. STAT5 deficiency or inhibition contributed to alleviating pancreatic inflammation and fibrosis in CP mice. The increased neutrophil infiltration, mediated by up-regulated GM-CSF, was responsible for the pancreatitis-promoting activity of STAT5. Our investigation highlighted the importance of STAT5 in regulating the immune microenvironment of CP. Targeting STAT5 may hold distinct promise for clinical treatment to alleviate CP.


Subject(s)
Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Neutrophils/immunology , Neutrophils/metabolism , Pancreatitis, Chronic/etiology , Pancreatitis, Chronic/metabolism , STAT5 Transcription Factor/metabolism , Animals , Biomarkers , Disease Susceptibility , Fibrosis , Humans , Pancreatitis, Chronic/pathology , Stress, Physiological
16.
Cell Death Dis ; 12(3): 273, 2021 03 15.
Article in English | MEDLINE | ID: mdl-33723230

ABSTRACT

Chronic pancreatitis (CP) is characterized by a wide range of irreversible fibro-inflammatory diseases with largely ambiguous pathogenesis. Although neddylation pathway has been implicated in regulating immune responses, whether the dysregulation of neddylation is involved in the progression of CP and how neddylation regulates the inflammatory microenvironment of CP have not yet been reported. Here, we demonstrate that global inactivation of neddylation pathway by MLN4924 significantly exacerbates chronic pancreatitis. The increased M2 macrophage infiltration, mediated by the upregulated chemokine (C-C motif) ligand 5 (CCL5), is responsible for the enhanced pancreatitis-promoting activity of MLN4924. Both CCL5 blockade and macrophage depletion contribute to alleviating pancreatic fibrosis and inflammation in MLN4924-treated CP mice. Mechanistic investigation identifies that inactivation of Cullin-RING ligases (CRLs) stabilizes cellular levels of hypoxia-inducible factor 1α (HIF-1α), which increases CCL5 expression by promoting CCL5 transactivation. Clinically, UBE2M expression remarkably decreases in human CP tissues compared with normal specimens and the levels of CCL5 and M2 marker CD163 are negatively correlated with UBE2M intensity, suggesting that neddylation is involved in the pathogenesis of pancreatitis. Hence, our studies reveal a neddylation-associated immunopathogenesis of chronic pancreatitis and provide new ideas for the disease treatment.


Subject(s)
Chemokine CCL5/metabolism , Chemotaxis , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Macrophages/metabolism , Pancreas/metabolism , Pancreatitis, Chronic/metabolism , Ubiquitin-Activating Enzymes/metabolism , Animals , Cell Line , Chemokine CCL5/genetics , Chemotaxis/drug effects , Cyclopentanes/toxicity , Disease Models, Animal , Enzyme Inhibitors/toxicity , Female , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Macrophages/drug effects , Macrophages/pathology , Mice, Inbred C57BL , Pancreas/drug effects , Pancreas/pathology , Pancreatitis, Chronic/chemically induced , Pancreatitis, Chronic/genetics , Pancreatitis, Chronic/pathology , Phenotype , Pyrimidines/toxicity , Signal Transduction , Ubiquitin-Activating Enzymes/antagonists & inhibitors , Ubiquitination
17.
Medicine (Baltimore) ; 99(42): e22599, 2020 Oct 16.
Article in English | MEDLINE | ID: mdl-33080693

ABSTRACT

INTRODUCTION: Whether there is the long-term effect of acupuncture on patients with knee osteoarthritis (KOA) or not is controversial. According to the basic theory of traditional acupuncture, deqi is the key to the efficacy of acupuncture. This randomized controlled trial aims to evaluate the existence of long-term effects caused by deqi in patients with KOA. METHODS AND ANALYSIS: A three-armed, parallel-design, randomized controlled trial is underway in China.108 KOA patients recruited by the rehabilitation center of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine will be randomly assigned to the acupuncture with deqi group (A group), the acupuncture without deqi group (B group) and the waiting-list group (C group). Each patient will receive 5 30-minute sessions per week for 4 consecutive weeks and rest for 2 days between treatments, and undergo a 20-week follow-up. The primary outcome is the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC score). The secondary outcomes include Western Ontario and McMaster Universities Osteoarthritis index (WOMAC score), Knee Injury and Osteoarthritis Outcome Score (KOOS), arthritis quality of life measurement scale simplified scale (AIMS2-SF), emotional monitoring and expectation scale. The pain visual analogue scale (VAS) and the Chinese version of modified Massachusetts General Hospital Acupuncture Sensation Scale (C-MMASS) will be used to evaluate the deqi sensation after each acupuncture treatment. At the same time, adverse events (AEs) occurred in the whole process will be recorded and analyzed. We will perform an intention-to-treat analysis and protocol (PP) analysis to statistically analyze the results of the trial. DISCUSSION: This trial will be useful to study the long-term effect of acupuncture and the influence of the deqi sensation on the long-term in the treatment of KOA, and to provide a clinical basis for treatment of patients with mild to moderate knee osteoarthritis in clinic. TRIAL REGISTRATION: Chinese Clinical Trial Registry, IDF: ChiCTR2000029291. Registered on January 21, 2020.


Subject(s)
Acupuncture Therapy , Osteoarthritis, Knee/therapy , Humans , Randomized Controlled Trials as Topic
18.
Cancer Immunol Res ; 8(11): 1440-1451, 2020 11.
Article in English | MEDLINE | ID: mdl-32917658

ABSTRACT

The mechanisms responsible for radioresistance in pancreatic cancer have yet to be elucidated, and the suppressive tumor immune microenvironment must be considered. We investigated whether the radiotherapy-augmented Warburg effect helped myeloid cells acquire an immunosuppressive phenotype, resulting in limited treatment efficacy of pancreatic ductal adenocarcinoma (PDAC). Radiotherapy enhanced the tumor-promoting activity of myeloid-derived suppressor cells (MDSC) in pancreatic cancer. Sustained increase in lactate secretion, resulting from the radiation-augmented Warburg effect, was responsible for the enhanced immunosuppressive phenotype of MDSCs after radiotherapy. Hypoxia-inducible factor-1α (HIF-1α) was essential for tumor cell metabolism and lactate-regulated activation of MDSCs via the G protein-coupled receptor 81 (GPR81)/mTOR/HIF-1α/STAT3 pathway. Blocking lactate production in tumor cells or deleting Hif-1α in MDSCs reverted antitumor T-cell responses and effectively inhibited tumor progression after radiotherapy in pancreatic cancer. Our investigation highlighted the importance of radiation-induced lactate in regulating the inhibitory immune microenvironment of PDAC. Targeting lactate derived from tumor cells and the HIF-1α signaling in MDSCs may hold distinct promise for clinical therapies to alleviate radioresistance in PDAC.


Subject(s)
Immunosuppression Therapy/methods , Lactic Acid/metabolism , Myeloid-Derived Suppressor Cells/immunology , Pancreatic Neoplasms/immunology , Animals , Disease Models, Animal , Humans , Mice
19.
Immun Inflamm Dis ; 8(4): 782-792, 2020 12.
Article in English | MEDLINE | ID: mdl-32749072

ABSTRACT

INTRODUCTION: Protein neddylation, one of the most important posttranslational modifications that tagging neuronal precursor cell-expressed developmentally downregulated protein 8 onto substrate proteins, plays fundamental roles in the process of many cellular functions. A number of studies have demonstrated the critical roles of neddylation modification in multiple pathophysiological processes, but its regulatory role in the immune system has only been finitely unveiled. METHODS: In this review, the latest advances in the field of neddylation modification in regulating the immune responses are succinctly discussed. RESULTS: Neddylation modification acts as a crucial modulator of innate immune cells (neutrophils, macrophages, and dendritic cells) and lymphocytes. Dysregulation of neddylation alters characteristics and functions of those cells due to abnormal degradation of key signaling molecules involved in immunoregulation. Furthermore, the ectopic immune responses caused by the abnormal neddylation play pivotal roles in a variety of immune-related diseases, such as infection, inflammation, and cancer. CONCLUSIONS: The pivotal roles of neddylation pathway in immunoregulation are attracted more and more attention, which may provide new insights into the pathogenesis of a variety of immune-related diseases and help to indicate new therapeutic targets and potential treatment strategies.


Subject(s)
Immunity , Humans , NEDD8 Protein , Neoplasms , Signal Transduction
20.
Zhongguo Zhen Jiu ; 40(1): 103-5, 2020 Jan 12.
Article in Chinese | MEDLINE | ID: mdl-31930908

ABSTRACT

In this paper, the micro-video teaching mode was explored in the course construction of Characteristic Clinical Technology of Acupuncture and Moxibustion. The micro-video teaching contents include the academic thought, experience in diagnosis and treatment, characteristic technology and clinical manipulation of famous acupuncture experts in the Henan University of CM. Each micro-video film is designed within 15-18 min, including three sections of knowledge, i.e. basic theory, technological application and clinical manipulation. Each section is designed within 5-6 min. The construction of the teaching course of Characteristic Clinical Technology of Acupuncture and Moxibustion is the innovation of practice mode of TCM and the new approach to the inheritance of the experience of experts. The construction of micro-video teaching course propels the reform of teaching mode, improves the learning initiative of students and clinical manipulative ability so as to improve the teaching effect and quality.


Subject(s)
Acupuncture Therapy , Moxibustion , Humans , Learning , Students , Teaching
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