Publications by authors named "Hui-Min Liu"

149 Publications

High Glucose Reduces the Paracellular Permeability of the Submandibular Gland Epithelium via the MiR-22-3p/Sp1/Claudin Pathway.

Cells 2021 Nov 19;10(11). Epub 2021 Nov 19.

National Engineering Laboratory for Digital and Material Technology of Stomatology and Beijing Key Laboratory of Digital Stomatology, National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, China.

Tight junctions (TJs) play an important role in water, ion, and solute transport through the paracellular pathway of epithelial cells; however, their role in diabetes-induced salivary gland dysfunction remains unknown. Here, we found that the TJ proteins claudin-1 and claudin-3 were significantly increased in the submandibular glands (SMGs) of db/db mice and high glucose (HG)-treated human SMGs. HG decreased paracellular permeability and increased claudin-1 and claudin-3 expression in SMG-C6 cells. Knockdown of claudin-1 or claudin-3 reversed the HG-induced decrease in paracellular permeability. MiR-22-3p was significantly downregulated in diabetic SMGs and HG-treated SMG-C6 cells. A miR-22-3p mimic suppressed claudin-1 and claudin-3 expression and abolished the HG-induced increases in claudin-1 and claudin-3 levels in SMG-C6 cells, whereas a miR-22-3p inhibitor produced the opposite effects. Specificity protein-1 (Sp1) was enhanced in diabetic SMGs and HG-treated SMG-C6 cells, which promoted claudin-1 and claudin-3 transcription through binding to the corresponding promoters. A luciferase reporter assay confirmed that miR-22-3p repressed Sp1 by directly targeting the Sp1 mRNA 3'-untranslated region (3'-UTR). Consistently, the miR-22-3p mimic suppressed, whereas the miR-22-3p inhibitor enhanced, the effects of HG on Sp1 expression. Taken together, our results demonstrate a new regulatory pathway through which HG decreases the paracellular permeability of SMG cells by inhibiting miR-22-3p/Sp1-mediated claudin-1 and claudin-3 expression.
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http://dx.doi.org/10.3390/cells10113230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8617860PMC
November 2021

Development and Validation of a Prognostic Model for One-year Survival of Cirrhosis Patients with First-ever Spontaneous Bacterial Peritonitis.

J Clin Transl Hepatol 2021 Oct 24;9(5):647-654. Epub 2021 May 24.

Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Background And Aims: Spontaneous bacterial peritonitis (SBP) is one of the leading causes of death in patients with liver cirrhosis. We aimed to establish a prognostic model to evaluate the 1-year survival of cirrhosis patients after the first episode of SBP.

Methods: A prognostic model was developed based on a retrospective derivation cohort of 309 cirrhosis patients with first-ever SBP and was validated in a separate validation cohort of 141 patients. We used Uno's concordance, calibration curve, and decision curve (DCA) analysis to evaluate the discrimination, calibration, and clinical net benefit of the model.

Results: A total of 59 (19.1%) patients in the derivation cohort and 42 (29.8%) patients in the validation cohort died over the course of 1 year. A prognostic model in nomogram form was developed with predictors including age [hazard ratio (HR): 1.25; 95% confidence interval (CI): 0.92-1.71], total serum bilirubin (HR: 1.66; 95% CI: 1.28-2.14), serum sodium (HR: 0.94; 95% CI: 0.90-0.98), history of hypertension (HR: 2.52; 95% CI: 1.44-4.41) and hepatic encephalopathy (HR: 2.06; 95% CI: 1.13-3.73). The nomogram had a higher concordance (0.79) compared with the model end-stage liver disease (0.67) or Child-Turcotte-Pugh (0.71) score. The nomogram also showed acceptable calibration (calibration slope, 1.12; Bier score, 0.15±0.21) and optimal clinical net benefit in the validation cohort.

Conclusions: This prediction model developed based on characteristics of first-ever SBP patients may benefit the prediction of patients' 1-year survival.
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http://dx.doi.org/10.14218/JCTH.2021.00031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516845PMC
October 2021

Efficacy of acupuncture based on acupoint combination theory for irritable bowel syndrome: a study protocol for a multicenter randomized controlled trial.

Trials 2021 Oct 19;22(1):719. Epub 2021 Oct 19.

School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China.

Background: Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain, diarrhea or constipation, and changes in defecation patterns. No organic disease is found to explain these symptoms by routine clinical examination. This study aims to investigate the efficacy and safety of acupuncture therapy for IBS patients compared with those of conventional treatments. We also aim to identify the optimal acupoint combination recommended for IBS and to clarify the clinical advantage of the "multiacupoint co-effect and synergistic effect."

Methods And Analysis: A total of 204 eligible patients who meet the Rome IV criteria for IBS will be randomly stratified into acupuncture group A, acupuncture group B, or the control group in a 1:1:1 ratio with a central web-based randomization system. The prespecified acupoints used in the control group will include bilateral Tianshu (ST25), Shangjuxu (ST37), Neiguan (PC6), and Zusanli (ST36). The prespecified acupoints used in experimental group A will include bilateral Tianshu (ST25), Shangjuxu (ST37), and Neiguan (PC6). The prespecified acupoints used in experimental group B will include bilateral Tianshu (ST25), Shangjuxu (ST37), and Zusanli (ST36). Each patient will receive 12 acupuncture treatments over 4 weeks and will be followed up for 4 weeks. The primary outcome is the IBS-Symptom Severity Scale (IBS-SSS) score. The secondary outcomes include the Bristol Stool Form Scale (BSFS), Work and Social Adjustment Score (WSAS), IBS-Quality of Life (IBS-QOL), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) scores. Both the primary outcome and the secondary outcome measures will be collected at baseline, at 2 and 4 weeks during the intervention, and at 6 weeks and 8 weeks after the intervention.

Ethics And Dissemination: The entire project has been approved by the ethics committee of the Beijing University of Chinese Medicine (2020BZYLL0903).

Discussion: This is a multicenter randomized controlled trial for IBS in China. The findings may shed light on the efficacy of acupuncture as an alternative to conventional IBS treatment. The results of the trial will be disseminated in peer-reviewed publications.

Trial Registration: Chinese Clinical Trials Register ChiCTR2000041215 . First registered on 12 December 2020. http://www.chictr.org.cn/ .
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http://dx.doi.org/10.1186/s13063-021-05432-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525000PMC
October 2021

hsa‑miR‑429 targets CBX8 to promote cell apoptosis in diffuse large B‑cell lymphoma.

Mol Med Rep 2021 12 15;24(6). Epub 2021 Oct 15.

Department of Hematology, Jingzhou Central Hospital, Institute of Hematology, Yangtze University, Jingzhou, Hubei 434020, P.R. China.

Diffuse large B‑cell lymphoma (DLBCL) is the most common type of non‑Hodgkin lymphoma worldwide. Several studies have indicated that (hsa)‑microRNA (miR)‑429 exerts a tumor‑suppressive effect on a variety of malignant tumors. To the best of our knowledge, the molecular function and mechanism of action of hsa‑miR‑429 in DLBCL have not been evaluated to date. The present study demonstrated that the expression of hsa‑miR‑429 in DLBCL cells was significantly reduced. hsa‑miR‑429 inhibited the proliferation of the DLBCL cell lines, SUDHL‑4 and DB, and promoted apoptosis. A dual luciferase reporter assay was used to demonstrate that chromobox 8 (CBX8) was the target gene of hsa‑miR‑429. Overexpression of CBX8 promoted the proliferation of SUDHL‑4 and DB cells and inhibited apoptosis, thereby playing a cancer‑promoting role. Transfection of hsa‑miR‑429 mimic into DB cells overexpressing CBX8 antagonized the effect of CBX8 on the proliferation of DB cells. Moreover, the apoptotic rate was increased in DB cells overexpressing CBX8 and transfected with hsa‑miR‑429 mimic, while the proportion of cells in the G/M phase was significantly reduced. These results demonstrated the antagonistic effect of hsa‑miR‑429 on the oncogenic function of CBX8. Therefore, in DLBCL, the tumor suppressor effect of hsa‑miR‑429 may be achieved by targeted downregulation of CBX8, suggesting that hsa‑miR‑429 may be used as a diagnostic marker and a potential nucleic acid drug for DLBCL. CBX8 may also represent an effective therapeutic target for DLBCL.
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http://dx.doi.org/10.3892/mmr.2021.12497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548936PMC
December 2021

Screening S protein - ACE2 blockers from natural products: Strategies and advances in the discovery of potential inhibitors of COVID-19.

Eur J Med Chem 2021 Dec 4;226:113857. Epub 2021 Oct 4.

State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China. Electronic address:

The Coronavirus disease, 2019 (COVID-19) is caused by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), which poses a major threat to human life and health. Given its continued development, limiting the spread of COVID-19 in the population remains a challenging task. Currently, multiple therapies are being tried around the world to deal with SARS-CoV-2 infection, and a variety of studies have shown that natural products have a significant effect on COVID-19 patients. The combination of SARS-CoV-2 S protein with Angiotensin converting enzyme II(ACE2) of host cell to promote membrane fusion is an initial critical step for SARS-CoV-2 infection. Therefore, screening natural products that inhibit the binding of SARS-CoV-2 S protein and ACE2 also provides a feasible strategy for the treatment of COVID-19. Establishment of high throughput screening model is an important basis and key technology for screening S protein-ACE2 blockers. Based on this, the molecular structures of SARS-CoV-2 and ACE2 and their processes in the life cycle of SARS-CoV-2 and host cell infection were firstly reviewed in this paper, with emphasis on the methods and techniques of screening S protein-ACE2 blockers, including Virtual Screening (VS), Surface Plasmon Resonance (SPR), Biochromatography, Biotin-avidin with Enzyme-linked Immunosorbent assay and Gene Chip Technology. Furthermore, the technical principle, advantages and disadvantages and application scope were further elaborated. Combined with the application of the above screening technologies in S protein-ACE2 blockers, a variety of natural products, such as flavonoids, terpenoids, phenols, alkaloids, were summarized, which could be used as S protein-ACE2 blockers, in order to provide ideas for the efficient discovery of S protein-ACE2 blockers from natural sources and contribute to the development of broad-spectrum anti coronavirus drugs.
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http://dx.doi.org/10.1016/j.ejmech.2021.113857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489279PMC
December 2021

Human gut microbiome impacts skeletal muscle mass via gut microbial synthesis of the short-chain fatty acid butyrate among healthy menopausal women.

J Cachexia Sarcopenia Muscle 2021 Sep 1. Epub 2021 Sep 1.

Center for System Biology, Data Sciences, and Reproductive Health, School of Basic Medical Science, Central South University, Changsha, Hunan, China.

Background: Increasing evidence suggests that human gut microbiome plays an important role in variation of skeletal muscle mass (SMM). However, specific causal mechanistic relationship of human gut microbiome with SMM remains largely unresolved. Understanding the causal mechanistic relationship may provide a basis for novel interventions for loss of SMM. This study investigated whether human gut microbiome has a causal effect on SMM among Chinese community-dwelling healthy menopausal women.

Methods: Estimated SMM was derived from whole-body dual-energy X-ray absorptiometry. We performed integrated analyses on whole-genome sequencing, shotgun metagenomic sequencing, and serum short-chain fatty acids (SCFAs), as well as available host SMM measurements among community-dwelling healthy menopausal women (N = 482). We combined the results with summary statistics from genome-wide association analyses for human gut microbiome (N = 952) and SMM traits (N = 28 330). As a prerequisite for causality, we used a computational protocol that was proposed to measure correlations among gut metagenome, metabolome, and the host trait to investigate the relationship between human gut microbiome and SMM. Causal inference methods were applied to assess the potential causal effects of gut microbial features on SMM, through one-sample and two-sample Mendelian randomization (MR) analyses, respectively.

Results: In metagenomic association analyses, the increased capacity for gut microbial synthesis of the SCFA butyrate was significantly associated with serum butyrate levels [Spearman correlation coefficient (SCC) = 0.13, P = 0.02] and skeletal muscle index (SCC = 0.084, P = 0.002). Of interest was the finding that two main butyrate-producing bacterial species were both positively associated with the increased capacity for gut microbial synthesis of butyrate [Faecalibacterium prausnitzii (SCC = 0.25, P = 6.6 × 10 ) and Butyricimonas virosa (SCC = 0.15, P = 0.001)] and for skeletal muscle index [F. prausnitzii (SCC = 0.16, P = 6.2 × 10 ) and B. virosa (SCC = 0.17, P = 2.4 × 10 )]. One-sample MR results showed a causal effect between gut microbial synthesis of the SCFA butyrate and appendicular lean mass (β = 0.04, 95% confidence interval 0.029 to 0.051, P = 0.003). Two-sample MR results further confirmed the causal effect between gut microbial synthesis of the SCFA butyrate and appendicular lean mass (β = 0.06, 95% confidence interval 0 to 0.13, P = 0.06).

Conclusions: Our results may help the future development of novel intervention approaches for preventing or alleviating loss of SMM.
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http://dx.doi.org/10.1002/jcsm.12788DOI Listing
September 2021

Calcifying pseudoneoplasms of the neuraxis (CAPNON). A case report.

Neuropathology 2021 Oct 9;41(5):371-375. Epub 2021 Aug 9.

Department of Pathology, Changzheng Hospital, Naval Medical University, Shanghai, China.

Calcifying pseudoneoplasms of the neuraxis (CAPNON) are rare, slow-growing, benign lesions occurring throughout the neuroaxis that are frequently misdiagnosed and overlooked by clinicians. Here, we report a case of a 56-year-old woman who presented with a history of recurrent headache for the previous six years. Magnetic resonance imaging (MRI) revealed a 2.3-cm-sized solid mass in the right frontal lobe that was surrounded by marked edematous areas. The lesion demonstrated dense calcification and avid enhancement. The lesion was initially diagnosed as oligodendroglioma, and then found to be CAPNON based on histopathology of a surgically resected tissue. Genetic analysis revealed a nonsense mutation in the CUL4B gene. The patient's condition appeared to reflect a reactive, rather than neoplastic, process. Clinicians should be prepared to detect such pseudotumors histopathologically in order to avoid unnecessary differential tests of neoplastic or infectious diseases, as well as potentially harmful therapies.
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http://dx.doi.org/10.1111/neup.12743DOI Listing
October 2021

Optimization of Fermentation Process of Pomegranate Peel and and the Biological Activities of Fermentation Broth: Antioxidant Activity and Protective Effect Against HO-induced Oxidative Damage in HaCaT Cells.

Molecules 2021 Jun 5;26(11). Epub 2021 Jun 5.

School of Perfume & Aroma and Cosmetics, Shanghai Institute of Technology, Shanghai 201418, China.

In this study, the lactobacillus fermentation process of pomegranate ( L.) peel and (Turcz.) Baill (PP&SC) was optimized by using the response surface method (RSM) coupled with a Box-Behnken design. The optimum fermentation condition with the maximal yield of ellagic acid (99.49 ± 0.47 mg/g) was as follows: 1:1 () ratio of pomegranate peel to , 1% () of strains with a 1:1 () ratio of to , a 37 °C fermentation temperature, 33 h of fermentation time, 1:20 (g:mL) of a solid-liquid ratio and 3 g/100 mL of a glucose dosage. Under these conditions, the achieved fermentation broth (FB) showed stronger free radical scavenging abilities than the water extract (WE) against the ABTS, DPPH, OH and O radicals. The cytotoxicity and the protective effect of FB on the intracellular ROS level in HaCaT cells were further detected by the Cell Counting Kit-8 (CCK-8) assay. The results showed that FB had no significant cytotoxicity toward HaCaT cells when its content was no more than 8 mg/mL. The FB with a concentration of 8 mg/mL had a good protective effect against oxidative damage, which can effectively reduce the ROS level to 125.94% ± 13.46% ( < 0.001) compared with 294.49% ± 11.54% of the control group in HO-damaged HaCaT cells. The outstanding antioxidant ability and protective effect against HO-induced oxidative damage in HaCaT cells promote the potential for the FB of PP&SC as a functional raw material of cosmetics.
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http://dx.doi.org/10.3390/molecules26113432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201020PMC
June 2021

Integrated analysis of lncRNA and mRNA expression profiles in the submandibular glands of DIO mice.

Oral Dis 2021 Jun 30. Epub 2021 Jun 30.

Department of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, Beijing, China.

Objective: Obesity contributes to the dysfunction of salivary gland. To explore the specific underlying mechanism for obesity-induced hyposalivation, a model for high-fat diet-induced obese (DIO) mice were constructed to analyze long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) expression profiles.

Methods: The DIO group and control group were fed a diet containing 60 kcal% fat and a normal chow diet for 16 weeks respectively. Microarray analyses were performed to detect the expression profiles of lncRNA and mRNA in submandibular gland tissues from control group mice and DIO mice. Gene ontology, kyoto encyclopedia of genes and genomes, protein-protein interaction, coding-non-coding gene co-expression, transcription factors and competing endogenous RNA analyses were performed to examine the function of differentially expressed genes.

Results: Microarray analyses identified that 624 lncRNAs, along with 297 mRNAs were differentially expressed. Bioinformatic analyses revealed that "complement and coagulation cascades," "glutathione metabolism," "cysteine and methionine metabolism," and "estrogen signaling pathway" were significantly associated with candidate lncRNAs. Transcription factors analysis on candidate lncRNAs revealed several genes such as tribbles pseudokinase 3 may play regulatory roles.

Conclusions: Our results revealed the expression profiles of lncRNAs and mRNAs and provided new insights into the mechanism of obesity-induced hyposalivation using bioinformatic analyses.
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http://dx.doi.org/10.1111/odi.13952DOI Listing
June 2021

Parotid mammary analogue secretory carcinoma: A case report and review of literature.

World J Clin Cases 2021 Jun;9(16):4052-4062

Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Jilin University, Changchun 130021, Jilin Province, China.

Background: Mammary analogue secretory carcinoma (MASC) is a rare low-grade malignant salivary gland tumor. The morphological and immunohistochemical features of MASC closely resemble those of breast secretory carcinoma. The key characteristics of the lesion are a lack of pain and slow growth. There is no obvious specificity in the clinical manifestations and imaging features. The diagnosis of the disease mainly depends on the detection of the MASC-specific fusion gene.

Case Summary: This report describes a rare case of a 32-year-old male patient who presented with a gradually growing lesion that was initially diagnosed as breast-like secretory carcinoma of the right parotid gland. Imaging and histological investigations were used to overcome the diagnostic difficulties. The lesion was managed with right parotidectomy, facial nerve preservation, biological patch implantation to restore the resulting defect, and postoperative radiotherapy. On postoperative follow-up, the patient reported a mild facial deformity with no complications, signs of facial paralysis, or Frey's syndrome.

Conclusion: The imaging and histological diagnostic challenges for MASC are discussed.
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http://dx.doi.org/10.12998/wjcc.v9.i16.4052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180236PMC
June 2021

[The Inhibiting Effect of Autophagy Inhibitor ROC-325 on Multiple Myeloma].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Jun;29(3):797-804

Institute of Hematology, Xuzhou Medical University; Department of Hematology, Xuzhou Medical University Affiliated Hospital, Xuzhou 221002, Jiangsu Province, China,E-mail:

Objective: To investigate the effects of autophagy inhibitor ROC-325 and its combination with bortezomib on the proliferation, apoptosis and autophagy of multiple myeloma cell lines.

Methods: Multiple myeloma cells were treated with ROC-325 at different concentration. The cell proliferation was detected by CCK-8. Apoptosis was determined by Caspase-3/7 and Caspase-9 activity assays. Autophagy was detected by monodansylcadaverine staining. The apoptosis-related proteins (PARP and Caspase-3) and autophagy-related proteins (P62, Beclin-1, and LC3A/B) were analyzed by Western blot. The combined effect with bortezomib on bortezomib-resistant cell line was detected by CCK-8.

Results: ROC-325 inhibited the proliferation of RPMI 8226, RPMI 8226-BTZ100, U266 and IM9 cells in a dose-dependent manner (r=-0.8275, r=-0.9079, r=-0.9422, r=-0.9305), the 72 h IC values were 2.795, 4.020, 5.432 and 4.755 μmol/L, respectively. The activity assays of Caspase-3/7 and Caspase-9 showed that their relative activity was increased gradually in proportion to the drug concentration with the statistically significant difference (r=0.9648, r=0.9377, r=0.9318; r=0.9087, r=0.9431, r=0.8914). MDC staining results showed that the number of autophagic vacuoles increased with the rise of ROC-325 concentration (r=0.9565, r=0.9373, r=0.9233). ROC-325 could increase the expression of apoptosis-related proteins (PARP and Caspase-3) and autophagy-related proteins (P62 and LC3-Ⅱ/LC3-Ⅰ), but decrease the expression of Beclin-1 detected by Western blot. The CCK-8 assay showed that ROC-325 combined with bortezomib had synergistic effect on the inhibition of drug resistant cell line RPMI 8226-BTZ100.

Conclusion: ROC-325 can inhibit the proliferation, induce the apoptosis of myeloma cells through the mitochondrial pathway, inhibit the autophagy of myeloma cells by affecting the fusion of autophagosomes and lysosomes, and overcome bortezomib resistance by the combination of ROC-325 with bortezomib.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.03.023DOI Listing
June 2021

Leonurine-Repressed miR-18a-5p/SOCS5/JAK2/STAT3 Axis Activity Disrupts CML malignancy.

Front Pharmacol 2021 16;12:657724. Epub 2021 Apr 16.

Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, China.

Leonurine, an active natural alkaloid compound isolated from Herba leonuri, has been reported to exhibit promising anticancer activity in solid tumors. The aim of this study was to explore whether leonurine is able to inhibit chronic myeloid leukemia (CML) malignancy. Here, we found that leonurine dose dependently inhibited the proliferation, migration, colony formation and promoted apoptosis of CML cells. Furthermore, leonurine markedly reduced CML xenograft growth . Mechanically, leonurine upregulated SOCS5 expression, thus leading JAK2/STAT3 signaling suppression. Silencing of SOCS5 by its siRNA abrogated the effect of leonurine on CML cells, demonstrating that SOCS5 mediates the anti-leukemia effect of leonurine. Notably, we observed that miR-18a-5p was remarkably increased in CML cells. Treating CML cells with leonurine significantly decreased miR-18a-5p expression. Moreover, we found miR-18a-5p repressed SOCS5 by directly targeting its 3'-UTR. miR-18a-5p downregulation induced by leonurine reduced the biological activity of CML cells by relieving miR-18a-5p repression of SOCS5 expression. Taken together, leonurine exerts significant anti-leukemia efficacy in CML by regulating miR-18a-5p/SOCS5/JAK2/STAT3 axis.
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http://dx.doi.org/10.3389/fphar.2021.657724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087248PMC
April 2021

Optimization of Ultrasonic Cellulase-Assisted Extraction and Antioxidant Activity of Natural Polyphenols from Passion Fruit.

Molecules 2021 Apr 24;26(9). Epub 2021 Apr 24.

School of Perfume and Aroma Technology, Shanghai Institute of Technology, Shanghai 201418, China.

In this paper, ultrasonic cellulase extraction (UCE) was applied to extract polyphenols from passion fruit. The extraction conditions for total phenol content (TPC) and antioxidant activity were optimized using response surface methodology (RSM) coupled with a Box-Behnken design (BBD). The results showed that the liquid-to-solid ratio (X) was the most significant single factor and had a positive effect on all responses. The ANOVA analysis indicated quadratic models fitted well as TPC with R = 0.903, DPPH scavenging activity with R = 0.979, and ABTS scavenging activity with R = 0.981. The optimal extraction parameters of passion fruit were as follows: pH value of 5 at 30 °C for extraction temperature, 50:1 (/) liquid-to-solid ratio with extraction time for 47 min, the experimental values were found matched with those predicted. Infrared spectroscopy suggested that the extract contained the structure of polyphenols. Furthermore, three main polyphenols were identified and quantified by HPLC. The results showed the content of phenolic compounds and antioxidant activity of the optimized UCE were 1.5~2 times higher than that determined by the single extraction method and the Soxhlet extraction method, which indicates UCE is a competitive and effective extraction technique for natural passion fruit polyphenols.
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http://dx.doi.org/10.3390/molecules26092494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123174PMC
April 2021

Fever and Antipyretic Supported by Traditional Chinese Medicine: A Multi-Pathway Regulation.

Front Pharmacol 2021 22;12:583279. Epub 2021 Mar 22.

State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China.

The coronavirus disease, 2019 (COVID-19), has spread rapidly around the world and become a major public health problem facing the world. Traditional Chinese medicine (TCM) has been fully committed to treat COVID-19 in China. It improved the clinical symptoms of patients and reduced the mortality rate. In light of the fever was identified as one of leading clinical features of COVID-19, this paper will first analyze the material basis of fever, including pyrogenic cytokines and a variety of the mediators of fever. Then the humoral and neural pathways of fever signal transmission will be described. The scattered evidences about fever recorded in recent years are connected in series. On this basis, the understanding of fever is further deepened from the aspects of pathology and physiology. Finally, combining with the chemical composition and pharmacological action of available TCM, we analyzed the mechanisms of TCMs to play the antipyretic effect through multiple ways. So as to further provide the basis for the research of antipyretic compound preparations of TCMs and explore the potential medicines for the prevention and treatment of COVID-19.
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http://dx.doi.org/10.3389/fphar.2021.583279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020597PMC
March 2021

Long noncoding RNA SNHG9 facilitates growth of glioma stem-like cells via miR-326/SOX9 axis.

J Gene Med 2021 Mar 31:e3334. Epub 2021 Mar 31.

Department of Oncology, Henan Provincial People's Hospital, People's Hospital of Henan University, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Background: Glioma stem-like cells (GSCs) are greatly responsible for the progression of glioma. Long noncoding RNAs (lncRNAs) play an important role in glioma tumor progression. This study aims to explore the role and underlying mechanism of lncRNA SNHG9 in regulating GSC cell growth.

Methods: GSCs were obtained from glioma cells (U87 and U251) and referred to as GSC-87 and GSC-251, respectively. The interactions between miR-326 and SNHG9 or SOX9 were analyzed using luciferase reporter assay. Cell growth of GSCs was evaluated by EdU assay and sphere formation assay.

Results: SNHG9 expression was significantly higher in GSC-87 and GSC-251 cells than in U87 and U251 cells. SNHG9 overexpression promoted GSC cell growth, whereas SNHG9 knockdown inhibited GSC cell growth. Mechanistically, SNHG9 acted as a competitive endogenous RNA of miR-326 to elevate the expression of SOX9, a direct target of miR-326. Moreover, transfection with miR-326 inhibitor counteracted SNHG9 knockdown-mediated inhibition of GSC cell growth.

Conclusions: SNHG9 facilitates growth of GSCs via the miR-326/SOX9 axis. This study provides a promising therapeutic target for glioma treatment.
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http://dx.doi.org/10.1002/jgm.3334DOI Listing
March 2021

Integrated metagenome and metabolome analyses of blood pressure studies in early postmenopausal Chinese women.

J Hypertens 2021 09;39(9):1800-1809

Center for System Biology, Data Sciences, and Reproductive Health, School of Basic Medical Science, Central South University, Changsha, Hunan Province.

Objective: We carried out sensitivity analyses on gut microbiota metagenomic sequencing, untargeted metabolome, targeted metabolome for short-chain fatty acids (SCFAs) and human whole genome sequencing from 402 early postmenopausal Chinese women to search for early omics-biomarkers and gain novel insights into the potential mechanisms of BP regulation in postmenopausal women.

Methods: Clusters of co-abundant gut bacterial species and serum untargeted metabolites were identified by weighted gene co-expression network analysis (WGCNA). Partial least square analysis and joint analysis were performed to detect BP-associated omics-variables. Partial Pearson correlation was conducted to identify the interactions of microbe--host for host BP variation. Mendelian randomization analysis and causal inference test were used to examine causal relationships among gut microbiota, metabolites and BP variation.

Results: In the present study, 651 bacterial species and 296 metabolites were binned into 53 and 26 co-abundance clusters by WGCNA, respectively. Then, we totally identified four gut bacterial species, one host metabolites and two SCFAs that were significantly associated with both SBP and DBP. Moreover, we found that gut microbiota would play important roles in host metabolic activity. Finally, our results revealed that increased Bacteroides fragilis could elevate BP via decreased caproic acid, and phenylacetylglutamine mediated the causal relationships of both B. fragilis and Clostridium sp.CAG.226 on DBP variation.

Conclusion: Multi-omics datasets integration has the potential to capture complementary effect and their interactions for BP variation, revealed the potential pathogenesis of BP variation and may be useful for studying other complex diseases/traits.
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http://dx.doi.org/10.1097/HJH.0000000000002832DOI Listing
September 2021

Identification and Functional Characterization of Metabolites for Bone Mass in Peri- and Postmenopausal Chinese Women.

J Clin Endocrinol Metab 2021 07;106(8):e3159-e3177

Tulane Center for Biomedical Informatics and Genomics, School of Medicine, Tulane University, New Orleans, LA, USA.

Context: Although metabolic profiles appear to play an important role in menopausal bone loss, the functional mechanisms by which metabolites influence bone mineral density (BMD) during menopause are largely unknown.

Objective: We aimed to systematically identify metabolites associated with BMD variation and their potential functional mechanisms in peri- and postmenopausal women.

Design And Methods: We performed serum metabolomic profiling and whole-genome sequencing for 517 perimenopausal (16%) and early postmenopausal (84%) women aged 41 to 64 years in this cross-sectional study. Partial least squares regression and general linear regression analysis were applied to identify BMD-associated metabolites, and weighted gene co-expression network analysis was performed to construct co-functional metabolite modules. Furthermore, we performed Mendelian randomization analysis to identify causal relationships between BMD-associated metabolites and BMD variation. Finally, we explored the effects of a novel prominent BMD-associated metabolite on bone metabolism through both in vivo/in vitro experiments.

Results: Twenty metabolites and a co-functional metabolite module (consisting of fatty acids) were significantly associated with BMD variation. We found dodecanoic acid (DA), within the identified module causally decreased total hip BMD. Subsequently, the in vivo experiments might support that dietary supplementation with DA could promote bone loss, as well as increase the osteoblast and osteoclast numbers in normal/ovariectomized mice. Dodecanoic acid treatment differentially promoted osteoblast and osteoclast differentiation, especially for osteoclast differentiation at higher concentrations in vitro (eg,10, 100 μM).

Conclusions: This study sheds light on metabolomic profiles associated with postmenopausal osteoporosis risk, highlighting the potential importance of fatty acids, as exemplified by DA, in regulating BMD.
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http://dx.doi.org/10.1210/clinem/dgab146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277206PMC
July 2021

Diagnostic utility of circulating plasma microRNA-101a in severity of coronary heart disease.

Ir J Med Sci 2021 Nov 21;190(4):1391-1396. Epub 2021 Jan 21.

Department of Cardiology, The 2nd Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China.

Background: For evaluating the severity of coronary heart disease (CHD), coronary arteriography may not be available everywhere due to technical limitations. MicroRNA-101a (miR-101a) associated with inflammation and cholesterol homeostasis. However, whether it related to presence and stratification of CHD is still unknown.

Aim: We aim to evaluate the value of miR-101a in stratifying CHD patients.

Methods: We enrolled 200 CHD patients and 100 controls, and 200 CHD patients were divided into two groups of low and high SYNTAX score (SYNTAX score ≤ 22 versus SYNTAX score ≥ 33). Intergroup comparisons of miR-101a level were compared among the controls and two groups of low and high SYNTAX score. Correlation between miR-101a and blood lipid profiles was analyzed. The logistic regression analysis were conducted to evaluate the risk factors of CHD.

Results: Relative level of miR-101a in the controls, SYNTAX score ≤ 22 and SYNTAX score ≥ 33 group were 4.61 (1.24-8.91), 3.28 (0.58-6.75) and 2.29 (1.04-3.62), respectively (p < 0.001). All lipid profiles significantly associated with miR-101a expression (all p < 0.001). The odds ratio (OR) of miR-101a in univariate analysis was 0.41 (95% CI, 0.33-0.52). After adjusting for the traditional risk factors, such as blood profiles and history of smoking, the odds ratio of miR-101a was 0.63 (95% CI, 0.47-0.43), which closely associated with CHD (p = 0.002).

Conclusions: Circulating miR-101a may be considered as a novel biomarker for evaluating the presence and severity of CHD.
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http://dx.doi.org/10.1007/s11845-021-02512-7DOI Listing
November 2021

Long non-coding RNA and mRNA profile analysis in the parotid gland of mouse with type 2 diabetes.

Life Sci 2021 Mar 4;268:119009. Epub 2021 Jan 4.

Department of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, and Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, PR China. Electronic address:

Aims: Salivary gland dysfunction is a common complication of diabetes mellitus (DM). Long non-coding RNA (lncRNA) is evidenced to involve in the functional regulation of salivary gland, however, its role in DM-impaired gland is unknown. Therefore, this study aimed to investigate the expression profiles and functional networks of lncRNA in the parotid glands (PGs) of DM mice.

Main Methods: Microarray was used to detect lncRNA and messenger RNA (mRNA) expression profiles in the PGs from db/db and db/m mice. Eleven differently expressed (DE) lncRNAs validated by qRT-PCR were selected for coding-non-coding gene co-expression (CNC) and competing endogenous RNA (ceRNA) network analysis, as well as the following Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Pearson's coefficient correlation analysis was used to analyze the correlations between DE lncRNAs expression and DM pathology.

Key Findings: By using a 2-fold change and P < 0.05 as the cutoff criteria, 1650 DE lncRNAs (758 upregulated and 892 downregulated) and 1073 mRNAs (563 upregulated and 510 downregulated) were identified in the PGs of db/db mice compared to db/m mice. GO and KEGG analysis of DE mRNA suggested that activated inflammation response and downregulated ion transport might count for the dysfunction of diabetic PG. CNC and ceRNA networks analysis of 11 DE lncRNAs showed that the inflammation process and its related signaling pathways including advanced glycation end product (AGE)-receptor for AGE (RAGE) signaling pathway in diabetic complications, cytokine-cytokine receptor interaction, chemokine signaling pathway, apoptosis, and cell adhesion molecules were significantly enriched. The alterations of lncRNAs were closely correlated with higher blood glucose and serum insulin levels in mice.

Significance: We identified multiple lncRNAs/mRNAs and several signaling pathways that may involve in the pathogenesis of diabetic salivary injury, providing new insight into potential target of diabetic hyposalivation.
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http://dx.doi.org/10.1016/j.lfs.2020.119009DOI Listing
March 2021

Progress in research into the role of abnormal glycosylation modification in tumor immunity.

Immunol Lett 2021 01 10;229:8-17. Epub 2020 Nov 10.

Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China. Electronic address:

In abnormal glycosylation, molecules of glucose or other carbohydrates in living organisms are inappropriately attached to proteins, which causes protein denaturation. Abnormal glycosylation modification is known to directly or indirectly affect the tumor escape process, but very few studies have been performed on whether protein glycosylation changes the structure and function of immune cells and immune molecules and thereby regulates the occurrence and development of tumor escape. Therefore, this article summarizes the effect of the immune system on tumor escape in association with the abnormal glycosylation process from an immunological perspective.
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http://dx.doi.org/10.1016/j.imlet.2020.11.003DOI Listing
January 2021

[Network Meta-analysis of traditional Chinese medicine in treating drug-induced liver injury].

Zhongguo Zhong Yao Za Zhi 2020 Oct;45(19):4746-4755

First Clinical School of Medicine, Beijing University of Chinese Medicine Beijing 100700, China.

To systematically evaluate the efficacy and safety of Chinese medicine in the treatment of drug-induced liver injury(DILI). By searching the randomized controlled trials(RCTs) of the Chinese medicine published in CNKI, WanFang, VIP, PubMed, Web of Science, in a time limit from database establishment to May 1, 2020. The bias risk assessment and Meta-analysis were then conducted for the included studies. Seventeen studies were finally included, all of which were RCTs, including 1 407 patients. The experimental group was treated with Chinese herbal medicine decoction or Chinese patent medicine, involving a total of 11 kinds of drugs, and the control group was treated with conventional Western medicine. Meta-analysis results showed that, in terms of treatment effective rate, Yinlan Yigan Granules, Shuganning, Jiangmeiling Capsules, Baidan Shugan Recipe and Sini Shugan Decoction were all superior to Western medicine treatment. In terms of reducing alanine aminotransferase(ALT), Yinlan Yigan Granules, Shuganning, Hugan Jiedu Recipe, Wuzhi Tablets, Wucao Baogan Recipe and Liuwei Wuling Tablets were superior to Western medicine. In terms of reducing aspartate aminotransferase(AST), Shuganning, Hugan Jiedu Recipe, Wucao Baogan Recipe, Liuwei Wuling Tablets and Sini Shugan Decoction were all superior to Western medicine. In terms of reducing total bilirubin(TBiL), Yinlan Yigan Granules, Shuganning, Jiedu Hugan Yin, Wuzhi Tablets, Wucao Baogan Recipe, Baidan Shugan Recipe and Sini Shugan Decoction were all superior to Western medicine treatment. Combined with network Meta-analysis and probability ranking, it can be seen that, Jiangmeiling Capsules, Shuganning, Sini Shugan Decoction and Baidan Shugan Recipe were most likely to be the best drugs to improve the efficiency and reduce ALT, AST, TBiL, respectively, with certain advantages compared to conventional Western medicine treatment. Of the seventeen studies included, eight studies described safety issues, three of which involved the test group, all of which were minor adverse reactions that disappeared after drug withdrawal or symptomatic treatment. However, due to the low quality of the included studies, more high-quality clinical studies are needed for further verification, thus providing more evidence-based medical evidence for Chinese medicine intervention in DILI.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200727.501DOI Listing
October 2020

Review of Denonvilliers' fascia: the controversies and consensuses.

Gastroenterol Rep (Oxf) 2020 Oct 30;8(5):343-348. Epub 2020 Sep 30.

Department of Colorectal Surgery, Changhai Hospital, Shanghai, P. R. China.

The Denonvilliers' fascia (DVF) plays an important role in rectal surgery because of its anatomic position and its relationship to the surrounding organs. It affects the surgical plane anterior to the rectum in the procedure of total mesorectal excision (TME). Anatomical and embryological studies have helped us to understand this structure to some extent, but many controversies remain. In terms of its embryonical origin, there are three mainstream hypotheses: peritoneal fusion of the embryonic cul-de-sac, condensation of embryonic mesenchyme, and mechanical pressure. Regarding its architecture, the DVF may be a single, two, or multiple layers, or a composite single-layer structure. In women, most authors deem that this structure does exist but they are willing to call it the rectovaginal septum rather than the DVF. Operating behind the DVF is supported by most surgeons. This article will review those mainstream studies and opinions on the DVF and combine them with what we have observed during surgery to discuss those controversies and consensuses mentioned above. We hope this review may help young colorectal surgeons to have a better understanding of the DVF and provide a platform from which to guide future scientific research.
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http://dx.doi.org/10.1093/gastro/goaa053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603872PMC
October 2020

[Pollution and Source Analysis of Heavy Metal in Surface Dust from Xi'an University Campuses].

Huan Jing Ke Xue 2020 Aug;41(8):3556-3562

College of Geography and Tourism, Shaanxi Normal University, Xi'an 710119, China.

Surface dust samples were collected from university campuses in Xi'an, and X-ray fluorescent spectrometry was used to determine the contents of nine heavy metals (Mn, As, Pb, Cr, Co, Ni, Cu, V, and Zn). Enrichment factors were subsequently used to determine the enrichment degree of each element and the preliminary determination of the pollution sources. The R programming language and SPSS were used for cluster analysis and principal components analysis to identify the pollution sources. The results showed that the average concentrations of all nine heavy metal elements were higher than their surface soil background values in Shaanxi Province; however, Mn, Co, As, V, and Ni exhibited relatively little enrichment and were less affected by human interference. Cr and Cu were moderately enriched, whereas Zn and Pb were significantly enriched, and human activities played a major role in the enrichment of these four elements. The main sources of Mn, Co, As, V, and Ni in surface dust samples from the university campuses were natural sources, whereas the accumulation of Zn, Cr, and Pb were mainly due to traffic sources, and Cu originated both from the auto repair industry and from paint coatings.
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http://dx.doi.org/10.13227/j.hjkx.201912041DOI Listing
August 2020

MicroRNA-mRNA expression profiles and functional network of submandibular gland in type 2 diabetic db/db mice.

Arch Oral Biol 2020 Dec 15;120:104947. Epub 2020 Oct 15.

Department of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, Beijing, 100191, China. Electronic address:

Objective: Hyposalivation is a common symptom of diabetes. Although microRNAs (miRNAs) play a role in the pathogenesis of diabetes, the specific effects of miRNAs on diabetic salivary glands are not clear.

Design: We used high-throughput technologies to screen differentially expressed (DE) miRNAs and mRNAs in submandibular gland (SMG) tissues from db/db mice and db/m mice. DE miRNAs and mRNAs were confirmed using quantitative real-time polymerase chain reaction (qRT-PCR).

Results: Twenty-eight DE miRNAs and 1146 DE mRNAs were identified between the SMG tissues of db/db mice and db/m mice. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that the DE miRNAs were highly associated with terms related to diverse biological processes and signalling pathways. Of the related pathways, the tight junction pathway, autophagy pathway and transforming growth factor-β (TGF-β) signalling pathway were notable. AKT serine/threonine kinase 3 (AKT3) and phosphoinositide-3 kinase catalytic subunit delta (PIK3CD) may also play important roles in the development of diabetes-mediated hyposalivation.

Conclusions: Our research described the miRNA-mRNA expression profiles and miRNA-mRNA network in the SMG tissues of db/db mice. These results provide possible molecular mechanisms of diabetes-induced hyposalivation and information for further studies.
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http://dx.doi.org/10.1016/j.archoralbio.2020.104947DOI Listing
December 2020

Research Progress on Main Symptoms of Novel Coronavirus Pneumonia Improved by Traditional Chinese Medicine.

Front Pharmacol 2020 11;11:556885. Epub 2020 Sep 11.

School of Pharmacy, State Key Laboratory of Characteristic Chinese Drug Resources in Southwest China, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Novel coronavirus (COVID-19) pneumonia has become a major threat to worldwide public health, having rapidly spread to more than 180 countries and infecting over 1.6 billion people. Fever, cough, and fatigue are the most common initial symptoms of COVID-19, while some patients experience diarrhea rather than fever in the early stage. Many herbal medicine and Chinese patent medicine can significantly improve these symptoms, cure the patients experiencing a mild 22form of the illness, reduce the rate of transition from mild to severe disease, and reduce mortality. Therefore, this paper summarizes the physiopathological mechanisms of fever, cough, fatigue and diarrhea, and introduces Chinese herbal medicines (Ephedrae Herba, Gypsum Fibrosum, Glycyrrhizae Radix et Rhizoma, Asteris Radix et Rhizoma, Ginseng Radix et Rhizoma, Codonopsis Radix, Atractylodis Rhizoma, ) and Chinese patent medicines (Shuang-huang-lian, Ma-xing-gan-shi-tang, ) with their corresponding therapeutic effects. Emphasis was placed on their material basis, mechanism of action, and clinical research. Most of these medicines possess the pharmacological activities of anti-inflammatory, antioxidant, antiviral, and immunity-enhancement, and may be promising medicines for the treatment or adjuvant treatment of COVID-19 patients.
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http://dx.doi.org/10.3389/fphar.2020.556885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516165PMC
September 2020

Candidate genes involved in the biosynthesis of lignan in Schisandra chinensis fruit based on transcriptome and metabolomes analysis.

Chin J Nat Med 2020 Sep;18(9):684-695

College of life Science, Jilin Agricultural University, Changchun 130118, China. Electronic address:

Schisandra chinensis Turcz. (Baill.) is a plant species with fruits that have been well known in Far Eastern medicine for a long time. It has traditionally been used as a stimulating and fortifying agent in cases of physical exhaustion and to inhibit fatigue. The major bioactive compounds found in S. chinensis are lignans with a dibenzocyclooctadiene skeleton, but little is known about their biosynthesis in plants. S. chinensis is the ideal medicinal plant for studying the biosynthesis of lignans, especially the dibenzocyclooctadiene skeleton. Genomic information for this important herbal plant is unavailable. To better understand the lignan biosynthesis pathway, we generated transcriptome sequences from the fruit during ripening and performed de novo sequence assembly, yielding 136 843 unique transcripts with N50 of 1778 bp. Putative functions could be assigned to 41 824 transcripts (51.57%) based on BLAST searches against annotation databases including GO (Gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes). Furthermore, 22 candidate cytochrome P450 genes and 15 candidate dirigent proteins genes that were most likely involved in the lignan biosynthesis pathway were discovered based on transcriptome sequencing of S. chinensis. The genomic data obtained from S. chinensis, especially the identification of putative genes involved in the lignan biosynthesis pathway, will facilitate our understanding of lignan biosynthesis at the molecular level. The lignan metabolite profiles were analyzed by metabolomes, the accumulation patterns of 30 metabolites involved in the lignan pathway were studied. Co-expression network of lignan contents and transcriptional changes showed 355 strong correlations (correlation coefficient, R > 0.9) between 21 compounds and 153 transcripts. Furthermore, the comprehensive analysis and characterization of the genes involved in lignan pathways and the metabolite profiles of lignans are expected to provide better insight regarding the diversity of the chemical composition, synthetic characteristics, and regulatory mechanisms of this medical herb.
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http://dx.doi.org/10.1016/S1875-5364(20)60007-3DOI Listing
September 2020

[Accurate positioning and analysis on health function of high frequency anti-fatigue herbal medicines].

Zhongguo Zhong Yao Za Zhi 2020 Aug;45(15):3608-3616

State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, College of Pharmacy,Chengdu University of Traditional Chinese Medicine Chengdu 611137, China.

Fatigue is a widespread and complex physiological phenomenon. Chronic fatigue can lead to cardiovascular dysfunction, mental disorders and other serious pathological reactions. Therefore, how to relieve fatigue accurately and effectively is an important proposition to implement the concept of "Healthy China" in the new era. As an important part of Chinese medicine health industry, Chinese medicine health food has been developing rapidly in recent years. At present, there are 1 157 kinds of anti-fatigue health food on the market in China, most of which are single Chinese medicine and its compound. However, their functions are generally labeled as "anti-fatigue", and their function positioning is too extensive and unclear. With the deepened understanding of fatigue classification and its physiological and pathological basis, it is urgent to be combined with the progress of modern chemical and pharmacological stu-dies to differentiate and precisely position the anti-fatigue health effects of traditional Chinese medicine. For this purpose, the classifications of fatigue were summarized in this paper, and the mechanism of fatigue was explained from the aspects of energy metabolism, accumulation of metabolites, oxidative stress, inflammation, hypothalamus pituitary adrenal axis and so on. We selected 10 traditional Chinese medicines which are most frequently used in health food, analyzed their anti-fatigue effect mechanisms, and summarized the best types of anti-fatigue food, so as to promote the scientific development of anti-fatigue health food industry, expand the market application scope of anti-fatigue health food, better respond to the construction of a healthy China and serve for people's health.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200113.403DOI Listing
August 2020

Anion exchange behavior of MAl layered double hydroxides: a molecular dynamics and DFT study.

Phys Chem Chem Phys 2020 Sep;22(35):19758-19768

State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing 100029, China.

The ion exchange reaction has been extensively used in the field of synthesis of functionalized supramolecular materials such as layered double hydroxides (LDHs), ion-embedded batteries, sewage disposal and so on. In this work, the factors influencing the anion exchange behavior in the LDH gallery, such as the exchange domain, the exchange order, the driving force, and the diffusion of the anions, are investigated systematically using molecular dynamics (MD) simulations and density functional theory (DFT) methods in view of both thermodynamics and dynamics. 159 models of MIIRAl-A-LDHs (MII = Mg, Ni, Zn; R = 1.4-8, A = OH-, Cl-, Br-, NO3-, HCOO-, C6H5SO3-, CO32-, SO42-, and PO43-, respectively) are calculated. The results reveal that the anion exchange domain (interlayer distance) in LDHs is determined not only by the size and their arrangement modes of the guest anions, but also by the charges the anions carry. The relative binding energies of different anions and the Gibbs free energy changes of the anion exchange reactions in LDHs decrease in the order of PO43- > CO32- > SO42- > OH- > Cl- > Br- > HCOO- > NO3- > C6H5SO3-, which is in accordance with the experimental anion exchange order. The stronger the hydrogen bonding between the anion and the host, the larger the charge transfer, and the smaller the electronegativity of the anion, the more difficult it is for the anion to be exchanged out from LDH interlayer. In addition, for the anions with the same charges, the relative binding energy is linearly well correlated with the interlayer spacing. By analyzing the contribution of each energetic item comprising the total potential energy, it is found that the major driving force of anion exchange is the electrostatic force. The diffusion coefficient (D) along the c direction is nearly equal to zero, suggesting that the diffusion of anions occurs mainly in the ab plane of the LDH cell. It also can be inferred that when the cell parameter c < 24.0 Å, the anion exchange order is mainly determined by the thermodynamic factors, whereas when c > 24.0 Å, both the thermodynamic and the dynamic factors cast the same effect on the anion exchange behavior. This work provides an in-depth understanding of the anion exchange behavior, and is helpful guidance for the design and synthesis of functionalized guest anion intercalated LDHs and related materials using the anion-exchange method.
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http://dx.doi.org/10.1039/d0cp02537bDOI Listing
September 2020

TOSO interacts with SYK and enhances BCR pathway activation in chronic lymphocytic leukemia.

Chin Med J (Engl) 2020 Sep;133(17):2090-2097

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.

Background: TOSO, also named Fas inhibitory molecule 3 (FAIM3), has recently been identified as an immunoglobulin M (IgM) Fc receptor (FcμR). Previous studies have shown that TOSO is specifically over-expressed in chronic lymphocytic leukemia (CLL). However, the functions of TOSO in CLL remain unknown. The B-cell receptor (BCR) signaling pathway has been reported to be constitutively activated in CLL. Here, we aimed to investigate the functions of TOSO in the BCR signaling pathway and the pathogenesis of CLL.

Methods: We over-expressed TOSO in B-cell lymphoma cell lines (Granta-519 and Z138) by lentiviral transduction and knocked down TOSO by siRNA in primary CLL cells. The over-expression and knockdown of TOSO were confirmed at the RNA level by polymerase chain reaction and protein level by Western blotting. Co-immunoprecipitation with TOSO antibody followed by liquid chromatography coupled with tandem mass spectrometry (IP/LCMS) was used to identify TOSO interacting proteins. Western blotting was performed to detect the activation status of BCR signaling pathways as well as B-cell lymphoma 2 (BCL-2). Flow cytometry was used to examine the apoptosis of TOSO-over-expressing B lymphoma cell lines and TOSO-down-regulated CLL cells via the staining of Annexin V and 7-AAD. One-way analyses of variance were used for intergroup comparisons, while independent samples t tests were used for two-sample comparisons.

Results: From IP/LCMS, we identified spleen tyrosine kinase (SYK) as a crucial candidate of TOSO-interacting protein and confirmed it by co-immunoprecipitation. After stimulation with anti-IgM, TOSO over-expression increased the phosphorylation of SYK, and subsequently activated the BCR signaling pathway, which could be reversed by a SYK inhibitor. TOSO knockdown in primary CLL cells resulted in reduced SYK phosphorylation as well as attenuated BCR signaling pathway. The apoptosis rates of the Granta-519 and Z138 cells expressing TOSO were (8.46 ± 2.90)% and (4.20 ± 1.21)%, respectively, significantly lower than the rates of the control groups, which were (25.20 ± 4.60)% and (19.72 ± 1.10)%, respectively (P < 0.05 for both). The apoptosis rate was reduced after knocking down TOSO in the primary CLL cells. In addition, we also found that TOSO down-regulation in primary cells from CLL patients led to decreased expression of BCL-2 as well as lower apoptosis, and vice versa in the cell line.

Conclusions: TOSO might be involved in the pathogenesis of CLL by interacting with SYK, enhancing the BCR signaling pathway, and inducing apoptosis resistance.
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http://dx.doi.org/10.1097/CM9.0000000000000999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478576PMC
September 2020

Aggravated intestinal ischemia‑reperfusion injury is associated with activated mitochondrial autophagy in a mouse model of diabetes.

Mol Med Rep 2020 09 24;22(3):1892-1900. Epub 2020 Jun 24.

Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.

Numerous studies have reported that diabetes is associated with an increased susceptibility to cardiac ischemia‑ reperfusion injury; however, the mechanism underlying the role of diabetes during intestinal ischemia‑reperfusion (IIR) has yet to be elucidated. The present study evaluated the intestinal pathological alterations and possible underlying mechanisms in a mouse model of type 1 diabetes mellitus with IIR. The effects of diabetes were investigated by assessing the histopathology, oxidative stress, inflammatory cytokine levels in intestine tissues and blood plasma, and protein expression levels of phosphatase and tensin homolog‑induced putative kinase (PINK1), Parkin and the ratio of light chain 3B (LC3B) II/I. The results demonstrated that diabetes increased the Chiu's intestinal injury score, concentration of interleukin (IL)‑1β, IL‑6 and tumor necrosis factor (TNF)‑α, and levels of oxidative stress. Furthermore, the alterations were more pronounced in the diabetes with IIR group. The expression levels of PINK1 and Parkin, as well as the ratio of LC3BII/I, were significantly upregulated in the IIR group compared with the Sham group. Diabetes activated PINK1 and Parkin, and increased the expression of LC3BII. Furthermore, transmission electron microscopy revealed that mitochondrial destruction and the number of autophagosomes was increased in the diabetic groups compared with the non‑diabetic groups. Collectively, the results of the present study suggest that diabetes increased intestinal vulnerability to IIR by enhancing inflammation and oxidative stress. Furthermore, IIR was associated with overactivation of mitochondrial autophagy; therefore, the increased vulnerability to IIR‑induced intestine damage due to diabetes may be associated with PINK1/Parkin‑regulated mitochondrial autophagy.
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http://dx.doi.org/10.3892/mmr.2020.11270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411361PMC
September 2020
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