Publications by authors named "Jianhua Zhu"

330 Publications

Serum albumin was negatively associated with diabetic peripheral neuropathy in Chinese population: a cross-sectional study.

Diabetol Metab Syndr 2021 Sep 15;13(1):100. Epub 2021 Sep 15.

Department of Endocrinology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China.

Background: Previous studies that explored the relationship of serum albumin with diabetic peripheral neuropathy (DPN) have indicated inconsistent results. Thus, the present study aimed to evaluated the association between serum albumin and DPN, defined as vibration perception threshold (VPT) values ≥ 25 V and/or inability to feel the monofilament, in Chinese patients with type 2 diabetes mellitus (T2DM).

Methods: 1465 T2DM patients aged ≥ 16 years, who completed the measurement of serum albumin and DPN screening between 2012 and 2015, were included in the cross-sectional study. Correlation and multivariate logistic regression analysis models were used to evaluate the possible relationship between serum albumin and DPN.

Results: Patients with higher quartiles of serum albumin had significantly lower VPT values and prevalence of DPN compared with those with lower quartiles (P for trend < 0.01), and there was an inverse relationship between serum albumin and VPT values and prevalence of DPN (all P < 0.01). Multivariate logistic regression analysis demonstrated that the risk of DPN was progressively decreased across serum albumin quartiles (P for trend < 0.01), and participants in the highest quartile of serum albumin were at a significantly decreased risk of DPN compared to those in the lowest quartile (odds rate: 0.311, 95% confidence intervals 0.134-0.724, P < 0.01). ROC analysis revealed that the optimal cutoff point of serum albumin for the prevalence of DPN was 39.95 g/L in patients with T2DM, with a sensitivity of 65.88% and a specificity of 66.7%.

Conclusions: Decreased levels of serum albumin might be correlated with increased risk of DPN in Chinese patients with T2DM. Future longitudinal studies with large samples are warranted to confirm our findings, and elucidate putative mechanisms for the association.
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http://dx.doi.org/10.1186/s13098-021-00718-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444578PMC
September 2021

[Protective effect and mechanism of Baicalin on acute kidney injury in septic mice].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 Jul;33(7):866-870

Department of Intensive Care Unit, Ningbo First Hospital, Ningbo 315010, Zhejiang, China. Corresponding author: Zhu Jianhua, Email:

Objective: To observe the protective effect and mechanism of different doses of Baicalin (BAI) on acute kidney injury (AKI) in septic mice.

Methods: According to the random number table, 100 mice were divided into sham operation group (Sham group), cecal ligation and perforation (CLP) induced sepsis model group (CLP group) and BAI pretreatment groups. The mice in BAI pretreatment groups were divided into low-, medium- and high-dose groups (BAI-L+CLP, BAI-M+CLP, BAI-H+CLP groups), with 20 mice in each group. A murine sepsis associated-acute kidney injury (SA-AKI) model was reproduced using CLP. The mice in the Sham group were only opened and closed the abdomen, without ligating or perforating the cecum. The mice in the BAI pretreatment groups were given BAI 25, 50 and 100 mg/kg daily for 3 days, and CLP was performed at 6 hours after administration of BAI at the 3rd day to reproduce sepsis model. The mice in the Sham group and CLP group were given the same amount of distilled water as control. Ten mice were sacrificed at 24 hours after operation to collect orbital blood for renal function determination [serum creatinine (SCr), blood urea nitrogen (BUN), plasma neutrophil gelatinase-associated lipocalin (pNGAL) and plasma kidney injury molecule-1 (pKIM-1)] by enzyme linked immunosorbent assay (ELISA). The kidney tissue was collected to observe the kidney tissue injury under light microscope after hematoxylin-eosin (HE) staining. The TdT-mediated dUTP nick-end labeling (TUNEL) was used to detect the apoptosis of renal tubular epithelial cells. Western blotting was used to detect the expression of cell FLICE like inhibitory protein (c-FLIP) in renal tissue. The remaining 10 mice in each group were used to calculate the survival rate of 7 days after operation.

Results: The renal tubular epithelial cells in the CLP group were massively degenerated with necrosis, the renal tubular lumen was significantly expanded, and inflammatory cells were widely infiltrated in the renal interstitium. Furthermore, the renal function deteriorated rapidly. Compared with the CLP group, the renal function of mice pretreated with low dose of BAI was improved, but the difference was not significant. Compared with the CLP group, the renal function in the mice pretreated with medium and high doses of BAI was significantly improved, the SCr, BUN, pNGAL and pKIM-1 were significantly reduced [SCr (μmol/L): 135.16±5.18, 125.70±5.26 vs. 170.42±5.42; BUN (mmol/L): 33.59±1.77, 27.29±1.61 vs. 45.68±1.39; pNGAL (μg/L): 91.29±4.68, 73.40±3.77 vs. 131.50±6.55; pKIM-1 (μg/L): 6.34±0.30, 5.51±0.35 vs. 8.03±0.29; all P < 0.01], the pathological injury of renal tissue was significantly decreased, the apoptotic number of renal tubular epithelial cells was significantly reduced (cells/HP: 16.20±0.49, 13.10±0.66 vs. 29.60±0.49, both P < 0.01), and the expression of c-FLIP protein in renal tissue was significantly increased [c-FLIP protein (c-FLIP/GAPDH): 0.35±0.02, 0.46±0.02 vs. 0.21±0.01, both P < 0.01]. No mouse in the Sham group died within 7 days. Compared with the CLP group, the average survival time of the mice within 7 days in the BAI-L+CLP, BAI-M+CLP and BAI-H+CLP groups was significantly prolonged with a dose-dependent manner (days: 3.5±2.5, 5.4±2.2, 5.9±1.9 vs. 2.1±1.2; Log-Rank test: χ = 73.410, P < 0.001).

Conclusions: Pretreatment with medium and high doses of BAI can significantly improve the renal function in mice with SA-AKI, decrease the pathological damage and increase the survival of mice, and its mechanism may be related to promoting the increase of c-FLIP protein expression and inhibiting cell apoptosis.
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http://dx.doi.org/10.3760/cma.j.cn121430-20201204-00756DOI Listing
July 2021

KCNMB2-AS1 Promotes Bladder Cancer Progression Through Sponging miR-374a-3p to Upregulate S100A10.

Front Genet 2021 22;12:655569. Epub 2021 Jul 22.

Department of Pathology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Long non-coding RNAs (lncRNAs) have been reported to play a crucial role in the pathogenesis of numerous cancers. However, the function of lncRNA KCNMB2-AS1 in bladder cancer (BC) remains unclear. In the present study, we aimed to explore the role and underlying mechanisms of KCNMB2-AS1 in bladder cancer progression. We found that lncRNA KCNMB2-AS1 was significantly upregulated both in BC tissues and cell lines, the expression level was highly correlated with pathological TNM stage. Functionally, knockdown of lncRNA KCNMB2-AS1 dramatically inhibited the proliferation, migration, and invasion and of BC cells , and suppressed tumor growth . Mechanistically, lncRNA KCNMB2-AS1 could function as a competitive endogenous RNA (ceRNA) through direct sponging miR-374a-3p, which regulated the expression of S100A10. In conclusion, our results demonstrated that lncRNA KCNMB2-AS1 can promote the progression of bladder cancer through regulation of miR-374a-3p/S100A10.
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http://dx.doi.org/10.3389/fgene.2021.655569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339911PMC
July 2021

Mass spectrometry-based chemical mapping and profiling toward molecular understanding of diseases in precision medicine.

Chem Sci 2021 Jun 25;12(23):7993-8009. Epub 2021 May 25.

School of Pharmacy, Nanjing Medical University Nanjing 211166 China

Precision medicine has been strongly promoted in recent years. It is used in clinical management for classifying diseases at the molecular level and for selecting the most appropriate drugs or treatments to maximize efficacy and minimize adverse effects. In precision medicine, an in-depth molecular understanding of diseases is of great importance. Therefore, in the last few years, much attention has been given to translating data generated at the molecular level into clinically relevant information. However, current developments in this field lack orderly implementation. For example, high-quality chemical research is not well integrated into clinical practice, especially in the early phase, leading to a lack of understanding in the clinic of the chemistry underlying diseases. In recent years, mass spectrometry (MS) has enabled significant innovations and advances in chemical research. As reported, this technique has shown promise in chemical mapping and profiling for answering "what", "where", "how many" and "whose" chemicals underlie the clinical phenotypes, which are assessed by biochemical profiling, MS imaging, molecular targeting and probing, biomarker grading disease classification, These features can potentially enhance the precision of disease diagnosis, monitoring and treatment and thus further transform medicine. For instance, comprehensive MS-based biochemical profiling of ovarian tumors was performed, and the results revealed a number of molecular insights into the pathways and processes that drive ovarian cancer biology and the ways that these pathways are altered in correspondence with clinical phenotypes. Another study demonstrated that quantitative biomarker mapping can be predictive of responses to immunotherapy and of survival in the supposedly homogeneous group of breast cancer patients, allowing for stratification of patients. In this context, our article attempts to provide an overview of MS-based chemical mapping and profiling, and a perspective on their clinical utility to improve the molecular understanding of diseases for advancing precision medicine.
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http://dx.doi.org/10.1039/d1sc00271fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230026PMC
June 2021

[Analysis of nine antioxidants in vegetable oils by high performance liquid chromatography].

Se Pu 2020 Jul;38(7):841-846

Chinese Academy of Inspection and Quarantine, Beijing 100176, China.

A method was developed for the determination of nine antioxidants in vegetable oils by high performance liquid chromatography (HPLC). The samples were extracted with methanol, and the fat in the samples was degreased by freezing. Separation of the targeted compounds was performed on an XBridge C column in gradient elution mode using methanol-0.1% (v/v) formic acid aqueous solution as the mobile phase. The analytes were detected using a diode-array detector by the external standard method. The stability and storage conditions for the nine antioxidants were systematically investigated. Ascorbyl palmitate (AP) was introduced into the preparation and pre-treatment of the targets. The concentration of AP was optimized to improve the stability and recovery of the targets. The effects of different extraction solvents and purification methods on the extraction efficiencies were discussed. The results showed that the nine antioxidants could be separated well under the optimized conditions. Good linear relationships in the linear range were obtained, and the correlation coefficients () were greater than 0.999. The average recoveries of the nine antioxidants ranged from 85.3% to 104.1%, with RSDs of the method ≤5.0%. The limits of quantitation (LOQs) for the nine synthetic antioxidants were in the range of 0.6-3.0 mg/kg. The method is simple, rapid, sensitive, and it shows good recovery and reproducibility.
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http://dx.doi.org/10.3724/SP.J.1123.2019.11023DOI Listing
July 2020

[Determination of diazepam in aquatic products by ultra performance liquid chromatography-tandem mass spectrometry with pass-through solid phase extraction].

Se Pu 2020 Jul;38(7):791-797

Institute of Food Safety, Chinese Academy of Inspection and Quarantine, Beijing 100123, China.

A method was developed for the determination of diazepam in aquatic products by pass-through solid phase extraction-ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The analyte was extracted with acetonitrile directly and purified on a Prime HLB solid phase extraction column (60 mg/3 mL). The separation was performed on an Acquity UPLC BEH C column (100 mm×2.1 mm, 1.7 μm)using methanol-0.1% (v/v) formic acid aqueous solution as the mobile phase in gradient elution mode. Qualitative analysis was performed in the multiple reaction monitoring (MRM) mode. The analyte was quantified by matrix-matched external standard curves. The results showed good linear relationship in the range of 0.1-10 ng/mL, and the correlation coefficient () was greater than 0.99. The spiked recoveries of diazepam were 88.2%-101.1% at the spiked levels of 1.5, 3.0 and 15.0 μg/kg, and both the intra-and inter-day precisions were less than 10%. The developed method is simple, rapid and accurate, and it can meet the requirements for diazepam determination in aquatic product samples.
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http://dx.doi.org/10.3724/SP.J.1123.2019.11028DOI Listing
July 2020

Dynamic Modeling and Chaos Control of Informatization Development in Manufacturing Enterprises.

Entropy (Basel) 2021 May 28;23(6). Epub 2021 May 28.

School of Business Administration, University of Guangzhou, Guangzhou 510006, China.

To explore the cooperative evolutionary mechanism among top management support, employees' technical ability, and informatization performance in the process of the "integration of informatization and industrialization (IOII)" in manufacturing enterprises, this study established a three-dimensional dynamic model of informatization development, obtained the model parameters by the expert scoring method of case companies, and analyzed the time series of the dynamic model. After adjusting those parameters of the evolutionary process that do not meet the expectations of the enterprise, combined with management practice, the dynamic system is finally stable at the expected value. For a special state in the evolutionary process, the maximum Lyapunov exponent is used to identify the chaotic characteristics of the system, and a linear controller is designed to manage and control the chaotic system so that it evolves toward the expected value. The results of the case analysis verify the rationality of the model and the effectiveness of the control method, reveal the internal evolutionary mechanism of the informatization development of manufacturing enterprises, and explain the influence of chaos on enterprise management so as to help managers to use and control chaos.
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http://dx.doi.org/10.3390/e23060681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227066PMC
May 2021

The association between intracompartmental pressure and skeletal muscle recovery after tibial diaphyseal fractures: an ambispective cohort study.

J Orthop Traumatol 2021 May 6;22(1):18. Epub 2021 May 6.

Department of Radiology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, 201318, China.

Background: Due to the special anatomy of the lower leg, tibial diaphyseal fracture causes increased intracompartmental pressure (ICP). Not only is this increased ICP the manifestation of skeletal muscle injury, but it induces further deterioration of the injury. The aim of this study was to assess the association between short-term ICP elevation and long-term skeletal muscle recovery after severe limb trauma.

Methods: In this single-center ambispective cohort study, we retrospectively screened and recruited a cohort of tibial diaphyseal fracture patients with integrated ICP data during the early post-traumatic period, and performed a prospective observational study to evaluate their skeletal muscle recovery through long-term follow-up and MR imaging after the removal of the implants. We analyzed the association between ICP elevation and skeletal muscle recovery using statistical methods.

Results: A total of 46 patients with healed fractures underwent intramedullary nail removal and MR imaging. The absolute values of the Pearson product-moment correlation coefficients between various ICP parameters and the cross-sectional area ratio (CSAR) ranged from 0.588 to 0.793, and the correlation coefficients between the ICP parameters and the average T2-weighted signal intensity ratio (T2SIR) varied from 0.566 to 0.775. Statistically significant associations were observed between the ICP parameters and the MR imaging parameters when simple linear regression analysis was performed. Among the ICP parameters, the accumulated ΔP (ΔP = diastolic blood pressure minus ICP) had the highest determination coefficient and explained 62.1% and 59.1% of the variance in CSAR and T2SIR, respectively.

Conclusions: Short-term ICP elevation was associated with long-term skeletal muscle recovery following tibial diaphyseal fracture, especially for ICP data that integrated time factors.

Level Of Evidence: Level 3.
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http://dx.doi.org/10.1186/s10195-021-00579-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102659PMC
May 2021

Depleting long noncoding RNA HOTAIR attenuates chronic myelocytic leukemia progression by binding to DNA methyltransferase 1 and inhibiting PTEN gene promoter methylation.

Cell Death Dis 2021 05 3;12(5):440. Epub 2021 May 3.

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Long noncoding RNAs (lncRNAs) are known to play a key role in chronic myelocytic leukemia (CML) development, and we aimed to identify the involvement of the lncRNA HOX antisense intergenic RNA (HOTAIR) in CML via binding to DNA methyltransferase 1 (DNMT1) to accelerate methylation of the phosphatase and tensin homolog (PTEN) gene promoter. Bone marrow samples from CML patients and normal bone marrow samples from healthy controls were collected. HOTAIR, DNMT1, DNMT3A, DNMT3B, and PTEN expression was detected. The biological characteristics of CML cells were detected. The relationship among HOTAIR, DNMT1, and PTEN was verified. Tumor volume and weight in mice injected with CML cells were tested. We found that HOTAIR and DNMT1 expression was increased and PTEN expression was decreased in CML. We also investigated whether downregulated HOTAIR or DNMT1 reduced proliferation, colony formation, invasion, and migration and increased the apoptosis rate of CML cells. Moreover, we tested whether low expression of HOTAIR or DNMT1 reduced the volume and weight of tumors in mice with CML. Collectively, the results of this studied showed that depleted HOTAIR demonstrated reduced binding to DNMT1 to suppress CML progression, which may be related to methylation of the PTEN promoter.
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http://dx.doi.org/10.1038/s41419-021-03637-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093289PMC
May 2021

microRNA-1246-containing extracellular vesicles from acute myeloid leukemia cells promote the survival of leukemia stem cells via the LRIG1-meditated STAT3 pathway.

Aging (Albany NY) 2021 04 23;13(10):13644-13662. Epub 2021 Apr 23.

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Cancer cells-secreted extracellular vesicles (EVs) have emerged as important mediators of intercellular communication in local and distant microenvironment. Our initial GEO database analysis identified the presence of differentially-expressed microRNA-1246 (miR-1246) in acute myeloid leukemia (AML) cell-derived EVs. Consequently, the current study set out to investigate the role of AML-derived EVs-packaged miR-1246 in leukemia stem cells (LSCs) bioactivities. The predicted binding between miR-1246 and LRIG1 was verified using dual luciferase reporter assay. Then, gain- and loss-of-function assays were performed in LSCs, where LSCs were co-cultured with AML cell-derived EVs to characterize the effects of miR-1246-containing EVs, miR-1246, LRIG1 and STAT3 pathway in LSCs. Our findings revealed, in AML cell-derived EVs, miR-1246 was highly-expressed and directly-targeted LRIG1 to activate the STAT3 pathway. MiR-1246 inhibitor or EV-encapsulated miR-1246 inhibitor was found to suppress the viability and colony formation abilities but promoted the apoptosis and differentiation of LSCs through inactivation of STAT3 pathway by up-regulating LRIG1. In addition, the inhibitory effects of AML cell-derived EVs carrying miR-1246 inhibitor on LSCs were substantiated by experiments. Collectively, our findings reveal that the repression of AML cell-derived EVs containing miR-1246 inhibitor alters the survival of LSCs by inactivating the LRIG1-mediated STAT3 pathway.
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http://dx.doi.org/10.18632/aging.202893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202884PMC
April 2021

Structural characterization and immunomodulatory mechanisms of two novel glucans from Morchella importuna fruiting bodies.

Int J Biol Macromol 2021 Jul 18;183:145-157. Epub 2021 Apr 18.

Biotechnological Institute of Chinese Materia Medica, College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China; Department of Natural Products Chemistry, College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China. Electronic address:

Two novel glucans named MIPB50-W and MIPB50-S-1 were obtained from edible Morchella importuna with molecular weights (M) of 939.2 kDa and 444.5 kDa, respectively. MIPB50-W has a backbone of α-(1 → 4)-d-glucan, which was substituted at O-6 position by α-d-Glcp-(1→. Moreover, MIPB50-S-1 has a backbone of α-(1 → 4)-d-glucan, which was substituted at O-6 position by α-d-Glcp-(1 → 6)-α-d-Glcp-(1→. This is the first report about glucan found in Morchella mushrooms. Furthermore, MIPB50-W and MIPB50-S-1 strengthened the phagocytosis function and the promoted secretion of interleukins (IL)-6/tumor necrosis factor-alpha (TNF-α) and nitric oxide (NO), which induced the activation of Toll-like receptor 2 (TLR2), TLR4 as well as mitogen activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways. Interestingly, MIPB50-S-1 performed the better immunomodulatory activity than that of MIPB50-W in almost all tests. Therefore, MIPB50-W and MIPB50-S-1 are potential immune-enhancing components of functional foods.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.04.084DOI Listing
July 2021

Novel Magnetic FeO/α-FeOOH Nanocomposites and Their Enhanced Mechanism for Tetracycline Hydrochloride Removal in the Visible Photo-Fenton Process.

ACS Omega 2021 Apr 26;6(13):9095-9103. Epub 2021 Mar 26.

Anhui Province Key Laboratory of Metallurgical Emission Reduction, Anhui University of Technology, Maanshan 243002, Anhui, P. R. China.

Magnetic FeO/α-FeOOH heterojunction nanocomposites (denoted as Fe-NCs) have been synthesized by a fast one-pot hydrothermal method. The obtained Fe-NCs contain rich micropores with a high surface area of 135.15 m/g. The different phases in the composites can efficiently enhance the visible-light absorption, improving the separation and transfer of photogenerated electron-hole pairs during the photocatalytic reaction. Thus, they show excellent degradation and mineralization of tetracycline (TC) over a wide pH range (5-9) in the visible photo-Fenton reaction. Especially, the catalyst exhibits the highest adsorption capacity toward TC at a neutral pH, which facilitates the surface reactions of TC with active species. Experiments evidence that the high production of photogenerated holes and superoxide radicals (O ) in Fe-NCs are favorable to the high catalytic efficiency. Combined with liquid chromatography-mass spectrometry, the possible pathway toward TC degradation was proposed.
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http://dx.doi.org/10.1021/acsomega.1c00204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028166PMC
April 2021

Purification and characterization of a novel mixed-linkage α,β-d-glucan from Arca subcrenata and its immunoregulatory activity.

Int J Biol Macromol 2021 Jul 5;182:207-216. Epub 2021 Apr 5.

Biotechnological Institute of Chinese Materia Medica, Jinan University, Guangzhou 510632, China. Electronic address:

Arca subcrenata Lischke is a seafood with high nutritional value. In this study, we purified and characterized a novel water-soluble polysaccharide (ASPG-2) from Arca subcrenata with significant immunoregulatory effects and no apparent cell toxicity. ASPG-2 is a class of mixed-linkage α,β-d-glucan backbones with α-linked side chains with a molecular weight of 4.39 × 10 Da. Its structure was characterized as a repeating unit consisting of (1 → 3)-β-d-Glcp, (1 → 4)-α-d-Glcp, (1 → 4,6)-α-d-Glcp and (1 → 6)-α-d-Glcp. Using mouse RAW264.7 macrophages, we demonstrated that ASPG-2 exerted marked immunoregulatory effects by promoting the secretion of NO and increasing the phagocytosis of RAW264.7 cells in vitro. Moreover, flow cytometry analysis of the expression of the cell surface molecule CD86 revealed that ASPG-2 could polarize RAW264.7 cells into the M1 type. The immunomodulatory mechanism of ASPG-2 in macrophages was associated with the activation of the TLR4-MAPK/Akt-NF-κB signalling pathways. These results indicated that ASPG-2 might be researched and developed as a potential immunomodulatory agent or health product from marine organisms.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.03.196DOI Listing
July 2021

The Inflammatory Factors Associated with Disease Severity to Predict COVID-19 Progression.

J Immunol 2021 04 12;206(7):1597-1608. Epub 2021 Feb 12.

Department of Clinical Laboratory, Wuhan Fourth Hospital; Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430033, People's Republic of China

Coronavirus disease 2019 (COVID-19) is associated with immune dysregulation and cytokine storm. Exploring the immune-inflammatory characteristics of COVID-19 patients is essential to reveal pathogenesis and predict progression. In this study, COVID-19 patients showed decreased CD3, CD4, and CD8 T cells but increased neutrophils in circulation, exhibiting upregulated neutrophil-to-lymphocyte and neutrophil-to-CD8 T cell ratio. IL-6, TNF-α, IL-1β, IL-18, IL-12/IL-23p40, IL-10, Tim-3, IL-8, neutrophil extracellular trap-related proteinase 3, and S100A8/A9 were elevated, whereas IFN-γ and C-type lectin domain family 9 member A (clec9A) were decreased in COVID-19 patients compared with healthy controls. When compared with influenza patients, the expressions of TNF-α, IL-18, IL-12/IL-23p40, IL-8, S100A8/A9 and Tim-3 were significantly increased in critical COVID-19 patients, and carcinoembryonic Ag, IL-8, and S100A8/A9 could serve as clinically available hematologic indexes for identifying COVID-19 from influenza. Moreover, IL-6, IL-8, IL-1β, TNF-α, proteinase 3, and S100A8/A9 were increased in bronchoalveolar lavage fluid of severe/critical patients compared with moderate patients, despite decreased CD4 T cells, CD8 T cells, B cells, and NK cells. Interestingly, bronchoalveolar IL-6, carcinoembryonic Ag, IL-8, S100A8/A9, and proteinase 3 were found to be predictive of COVID-19 severity and may serve as potential biomarkers for predicting COVID-19 progression and potential targets in therapeutic intervention of COVID-19.
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http://dx.doi.org/10.4049/jimmunol.2001327DOI Listing
April 2021

Long non-coding RNA OTUD6B-AS1 overexpression inhibits the proliferation, invasion and migration of colorectal cancer cells via downregulation of microRNA-3171.

Oncol Lett 2021 Mar 8;21(3):193. Epub 2021 Jan 8.

Department of Emergency Traumatic Surgery, Shanghai Pudong New District Zhoupu Hospital (Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital), Shanghai 201318, P.R. China.

Colorectal cancer (CRC) is a common digestive system malignancy and a major cause of cancer-associated mortality worldwide. Aberrant expression of long non-coding RNAs has been reported in several types of cancer. The aim of the present study was to investigate the role of ovarian tumor domain containing 6B antisense RNA1 (OTUD6B-AS1) in CRC and its underlying mechanisms. OTUD6B-AS1 expression in CRC cell lines was examined using reverse transcription-quantitative PCR. Furthermore, The Cancer Genome Atlas database was utilized to examine the expression levels of OTUD6B-AS1 in CRC tissues. Following OTUD6B-AS1 overexpression, Cell Counting Kit-8 and colony formation assays were used to detect the proliferation ability of HCT116 cells. The expression levels of proliferation-related protein Ki67 were determined using immunofluorescence staining. Subsequently, Transwell and wound healing assays were used to evaluate the invasion and migration of HCT116 cells, respectively. The expression levels of migration-related proteins (MMP2 and MMP9) were measured using western blotting. Additionally, a luciferase reporter assay was used to verify the potential interaction between OTUD6B-AS1 and microRNA-3171 (miR-3171). Subsequently, rescue assays were performed to clarify the regulatory effects of OTUD6B-AS1 and miR-3171 on CRC development. The results demonstrated that OTUD6B-AS1 expression was low in CRC cells and tissues. Overexpression of OTUD6B-AS1 inhibited the proliferation, invasion and migration of HCT116 cells. Furthermore, miR-3171 was demonstrated to be a direct target of OTUD6B-AS1 using a luciferase reporter assay. The rescue assays revealed that miR-3171 mimics markedly reversed the inhibitory effects of OTUD6B-AS1 overexpression on proliferation, invasion and migration of CRC cells. Overall, these findings demonstrated that OTUD6B-AS1 overexpression inhibited the proliferation, invasion and migration of HCT116 cells via downregulation of miR-3171, suggesting that OTUD6B-AS1 may serve as a novel biomarker for CRC treatment.
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http://dx.doi.org/10.3892/ol.2021.12454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816294PMC
March 2021

Identification, Classification, and Expression Analysis of the () Gene Family Related to Abiotic Stresses in Tomato.

Int J Mol Sci 2021 Jan 30;22(3). Epub 2021 Jan 30.

State Key Laboratory of Crop Stress Biology for Arid Areas, College of Horticulture, Northwest A&F University, Yangling 712100, China.

Triacylglycerol Lipases (TGLs) are the major enzymes involved in triacylglycerol catabolism. TGLs hydrolyze long-chain fatty acid triglycerides, which are involved in plant development and abiotic stress responses. Whereas most studies of TGLs have focused on seed oil metabolism and biofuel in plants, limited information is available regarding the genome-wide identification and characterization of the gene family in tomato ( L.). Based on the latest published tomato genome annotation ITAG4.0, 129 genes were identified and classified into 5 categories according to their structural characteristics. Most genes were distributed on 3 of 12 chromosomes. Segment duplication appeared to be the driving force underlying expansion of the gene family in tomato. The promoter analysis revealed that the promoters of s contained many stress responsiveness -elements, such as ARE, LTR, MBS, WRE3, and WUN-motifs. Expression of the majority of genes was suppressed following exposure to chilling and heat, while it was induced under drought stress, such as , and . These results provide valuable insights into the roles of the genes family and lay a foundation for further functional studies on the linkage between triacylglycerol catabolism and abiotic stress responses in tomato.
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http://dx.doi.org/10.3390/ijms22031387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866549PMC
January 2021

[Relationship between the timing of initiation of continuous renal replacement therapy and the prognosis of patients with sepsis-associated acute kidney injury].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2020 Nov;32(11):1352-1355

Department of Critical Care Medicine, Ningbo First Hospital, Ningbo 315010, Zhejiang, China. Corresponding author: Zhu Jianhua, Email:

Objective: To investigate the relationship between the timing of initiation of continuous renal replacement therapy (CRRT) and the prognosis of patients with sepsis associated-acute kidney injury (SA-AKI).

Methods: The clinical data of SA-AKI patients undergoing CRRT in intensive care unit (ICU) of Ningbo First Hospital from January 2017 to November 2019 were retrospectively analyzed. According to the guidelines for Kidney Disease: Improving Global Outcomes (KDIGO), patients with AKI who started CRRT in stage 1 or 2 were included in the early treatment group, and those started CRRT in stage 3 were included in the late treatment group. The general clinical data, length of ICU stay, total length of hospital stay, 28-day and 90-day mortality, CRRT duration, 28-day and 90-day renal replacement therapy (RRT) disengagement rate, 28-day and 90-day RRT dependence rate in the survival patients were compared between the two groups. Kaplan-Meier survival analysis was performed to assess the 90-day cumulative survival rate of patients with SA-AKI between two groups.

Results: A total of 244 SA-AKI patients were enrolled in this study, including 71 patients in the early treatment group and 173 patients in the late treatment group. There were no significant differences in age, gender composition, acute physiology and chronic health evaluation II (APACHE II), proportion of surgical patients, infection site and anticoagulation program between the two groups. The CRRT duration in the early group was significantly shorter than that in the late group [hours: 26.0 (12.0, 49.0) vs. 41.0 (20.8, 87.0), P < 0.01], but there were no significant differences in the length of ICU stay [days: 9.0 (4.0, 15.0) vs. 10.0 (4.5, 18.0)], total length of hospital stay [days: 17.0 (10.0, 30.0) vs. 18.0 (10.0, 32.0)], 28-day mortality (45.1% vs. 48.0%), 90-day mortality (46.4% vs. 51.4%), 28-day RRT disengagement rate (49.3% vs. 45.1%) and 90-day RRT disengagement rate (52.1% vs. 47.4%) between the early treatment group and late treatment group (all P > 0.05). There were also no significant differences in 28-day RRT dependence rate [10.3% (4/39) vs. 13.3% (12/90)] and 90-day RRT dependence rate [2.6% (1/38) vs. 2.4% (2/84)] between early treatment group and late treatment group (both P > 0.05). Kaplan-Meier survival analysis suggested that there was no significant difference in the 90-day cumulative survival rate between two groups (Log-Rank test: χ = 0.791, P = 0.374).

Conclusions: Early initiation of CRRT treatment in SA-AKI patients can reduce the duration of CRRT, but has no effect on length of ICU stay, total length of hospital stay, renal function recovery and mortality. At present, the optimal timing for initiation of CRRT in patients with SA-AKI remains unknown.
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http://dx.doi.org/10.3760/cma.j.cn121430-20200304-00206DOI Listing
November 2020

RNF185-AS1 promotes hepatocellular carcinoma progression through targeting miR-221-5p/integrin β5 axis.

Life Sci 2021 Feb 31;267:118928. Epub 2020 Dec 31.

Department of Gastroenterology, Wuhan No.1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. Electronic address:

Aims: Recently, long noncoding RNAs (lncRNAs) have been reported to play important role in the pathogenesis of various cancers. However, the functions of RNF185-AS1 in hepatocellular carcinoma (HCC) remain unknown.

Materials And Methods: The RNF185-AS1 expression in HCC cells and tissues was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of RNF185-AS1 on tumor cell proliferation, migration and invasion were assessed by Cell Counting Kit-8 (CCK8) assay, colony formation assay, transwell assay. The luciferase reporter assay, RNA-binding protein immunoprecipitation assay, qRT-PCR and Western blot were performed to explore and confirm the interaction between RNF185-AS1 and miR-221-5p and integrin β5. The role of RNF185-AS1 in tumor progression was explored through in vivo experiments.

Key Findings: RNF185-AS1 was highly expressed in HCC tissues and cell lines. High levels of RNF185-AS1 were correlated with advanced TNM stage, distant metastasis and a poorer overall survival rate. RNF185-AS1 knockdown inhibited cell proliferation, migration and invasion. Additionally, RNF185-AS1 acted as a sponge for miR-221-5p and integrin β5 was identified as a target gene of miR-221-5p. Rescue assays showed that miR-221-5p inhibitor or integrin β5 overexpression rescued the function of RNF185-AS1 knockdown on cell proliferation, migration, and invasion. Moreover, we found that RNF185-AS1 knockdown inhibited tumor growth and metastasis.

Significance: Our study demonstrates that RNF185-AS1 is a new oncogenic lncRNA in HCC and suggests that the RNF185-AS1/miR-221-5p/integrin β5 axis might be a potential therapeutic target for HCC.
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http://dx.doi.org/10.1016/j.lfs.2020.118928DOI Listing
February 2021

Association of Circulating Omentin-1 with Osteoporosis in a Chinese Type 2 Diabetic Population.

Mediators Inflamm 2020 15;2020:9389720. Epub 2020 Oct 15.

Department of Endocrinology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.

Aims: Omentin-1, a newly identified adipokine, has been demonstrated to be associated with bone metabolism, but the results have been inconsistent. Moreover, the potential relationship of circulating omentin-1 with diabetic osteoporosis has never been reported. This study is intended for studying the association between circulating omentin-1, bone mineral density (BMD), prior fragility fractures, and other bone metabolic-related parameters.

Methods: Circulating omentin-1 levels were measured in 172 patients with type 2 diabetes mellitus (T2DM), and participants were divided into the normal BMD group ( = 52), the osteopenia group ( = 66), and the osteoporosis group ( = 54). The relationship between circulating omentin-1 and diabetic osteoporosis and other parameters was analyzed.

Results: Circulating omentin-1 was significantly higher in the osteoporosis group than in the normal group and in the osteopenia group (both < 0.05). Circulating omentin-1 levels were correlated significantly and positively with sex; high-density lipoprotein cholesterol; apolipoprotein A; and prevalence of prior fragility fractures, diabetic nephropathy, and retinopathy; they were correlated negatively with diastolic blood pressure, triglyceride, hemoglobin, atherogenic index of plasma, osteoporosis self-assessment tool for Asians, BMD at different skeletal sites, and corresponding scores, irrespective of age, sex, and body mass index ( < 0.01 or < 0.05). Moreover, circulating omentin-1 was an independent decisive factor for the presence of osteoporosis only in women after multivariate adjustment (odds ratio: 1.069; 95% confidence interval: 1.003-1.139; < 0.05). Lastly, the analysis of receiver operating characteristic curves revealed that the best cutoff value for circulating omentin-1 to predict diabetic osteoporosis was 15.37 ng/mL (sensitivity: 71.7%; specificity: 58.5%) in female subjects.

Conclusions: High levels of circulating omentin-1 may be associated with the development of osteoporosis in female diabetic subjects and may be a potential biomarker for diabetic osteoporosis in women.
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http://dx.doi.org/10.1155/2020/9389720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603618PMC
October 2020

Oleate acid-stimulated HMMR expression by CEBPα is associated with nonalcoholic steatohepatitis and hepatocellular carcinoma.

Int J Biol Sci 2020 27;16(15):2812-2827. Epub 2020 Aug 27.

Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing 100850, China.

Non-alcoholic steatohepatitis (NASH) is a type of nonalcoholic fatty liver disease and has become a major risk factor for hepatocellular carcinoma (HCC). However, the underlying pathophysiological mechanisms are still elusive. Here, we identify hyaluronan-mediated motility receptor (HMMR) as a critical gene associated with NASH/HCC by combination of bioinformatic analysis and functional experiments. Analysis of differentially expressed genes (DEGs) between normal controls and NASH/HCC identified 5 hub genes (HMMR, UBE2T, TYMS, PTTG1 and GINS2). Based on the common DEGs, analyses of univariate and multivariate Cox regression and the area under the curve (AUC) value of the receiver operating characteristic (ROC) indicate that HMMR is the most significant gene associated with NASH/HCC among five hub genes. Oleate acid (OA), one of fatty acids that induce cellular adipogenesis, stimulates HMMR expression via CCAAT/enhancer-binding protein α (CEBPα). CEBPα increases the expression of HMMR through binding to its promoter. HMMR promotes HCC cell proliferation via activation of G1/S and G2/M checkpoint transitions, concomitant with a marked increase of the positive cell cycle regulators, including cyclin D1, cyclin E, and cyclin B1. Knockdown of HMMR suppresses HCC tumor growth in nude mice. Our study identifies an important role of HMMR in NASH/HCC, and suggests that HMMR may be a useful target for therapy and prognostic prediction of NASH/HCC patients.
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http://dx.doi.org/10.7150/ijbs.49785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545721PMC
August 2020

Corrigendum to "Angiotensin II promotes differentiation of mouse embryonic stem cells to smooth muscle cells through PI3-kinase signaling pathway and NF-κB" [Differentiation (2013) 41-54].

Differentiation 2020 Nov - Dec;116:39. Epub 2020 Sep 26.

Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.diff.2020.09.001DOI Listing
September 2020

-Inspired Electrode with Polyaniline Decorated on Porous Heteroatom-Doped Carbon Nanofibers for Flexible Supercapacitors.

ACS Appl Mater Interfaces 2020 Sep 21;12(39):43634-43645. Epub 2020 Sep 21.

Innovation Center for Textile Science and Technology, Donghua University, Shanghai 201620, China.

Carbon nanofibers are promising as primary electrode materials for supercapacitors on account of high specific surface area, lightweight, superior physicochemical stability, rich resource, and renewability. However, constructing porous and flexible carbon electrode materials with high capacitance for practical applications remains challenging. Here, heteroatom-decorated hierarchical porous carbon nanofiber composites containing phosphazene [NP(-OCH--CHO), HAPCP], polymethyl methacrylate (PMMA), and graphene oxide (GO) are prepared through one-step electrospinning and subsequent thermal treatment. The alternant phosphorus-nitrogen structure links to the carbon backbones to improve flexibility and electrochemical performance. Inspired by a biomimetic -like structure, the polyaniline (PANI)-decorated porous hybrid electrodes are prepared. The [email protected]/PMMA/HAPCP/PAN carbon nanofibers ([email protected]) covered by PANI nanofibers as a novel free-standing flexible electrode exhibit an excellent electrochemical performance of 680.8 F g at 0.5 A g with a good capacitance retention of 93.5% after 3000 cycles. Moreover, the symmetric flexible all-solid-state supercapacitor assembled by the novel and delicate electrodes exhibits a high energy density of 27.70 W h kg (at a power density of 231.08 W kg) and favorable cycling stability (84.50% retention of the capacitance after 1000 charge-discharge cycles), which indicates that the [email protected] have great potential as a high-performance flexible supercapacitor electrode.
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http://dx.doi.org/10.1021/acsami.0c10933DOI Listing
September 2020

Purification and Characterization of a New CRISP-Related Protein from and Its Immunomodulatory Activity.

Mar Drugs 2020 Jun 4;18(6). Epub 2020 Jun 4.

Biotechnological Institute of Chinese Materia Medica, Jinan University, Guangzhou 510632, China.

More and more attention has been paid to bioactive compounds isolated from marine organisms or microorganisms in recent years. At the present study, a new protein coded as HPCG2, was purified from by stepwise chromatography methods. The molecular weight of HPCG2 was determined to be 30.71 kDa by MALDI-TOF-MS. The complete amino acid sequence of HPCG2 was obtained by tandem mass spectrometry combined with transcriptome database analysis, and its secondary structure was analyzed using circular dichroism. HPCG2 comprised 251 amino acids and contained 28.4% α-helix, 26% β-sheet, 18.6% β-turn, and 29.9% random coil. HPCG2 was predicted to be a cysteine-rich secretory protein-related (CRISP-related) protein by domain prediction. Moreover, HPCG2 was proved to possess the immunomodulatory effect on the murine immune cells. MTT assay showed that HPCG2 promoted the proliferation of splenic lymphocytes and the cytotoxicity of NK cells against YAC-1 cells. Flow cytometry test revealed that HPCG2 enhanced the phagocytic function of macrophages and polarized them into M1 type in RAW264.7 cells. In particular, Western blot analysis indicated that the immunomodulatory mechanism of HPCG2 was associated with the regulation on TLR4/JNK/ERK and STAT3 signaling pathways in RAW 264.7 cells. These results suggested that HPCG2 might be developed as a potential immunomodulatory agent or new functional product from marine organisms.
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http://dx.doi.org/10.3390/md18060299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344751PMC
June 2020

Changes of circulating neuregulin 4 and its relationship with 25-hydroxy vitamin D and other diabetic vascular complications in patients with diabetic peripheral neuropathy.

Diabetol Metab Syndr 2020 19;12:42. Epub 2020 May 19.

1Department of Endocrinology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000 China.

Background: Neuregulin 4 (Nrg4) is a novel neurotrophic adipokine associated with the development of diabetic peripheral neuropathy (DPN), however, the pathological mechanism remains poorly understood. The purpose of our study was to investigate the association of circulating Nrg4 with DPN and 25-hydroxy vitamin D [25(OH)D], a multifunctional secosteroid hormone that regulates other neurotrophic factors and adipokines gene expression, and other diabetic vascular complications.

Methods: Circulating Nrg4 levels were measured with an ELISA kit in 164 newly diagnosed type 2 diabetes mellitus (nT2DM) patients. The relationship between circulating Nrg4 and DPN and other parameters was analyzed.

Results: Circulating Nrg4 levels were significantly lower in nT2DM patients with DPN than those without, and subjects in the highest quartile of circulating Nrg4 had significantly lower vibration perception threshold (VPT), the prevalence of DPN, the proportion of persons with VPT > 25 V, and significantly higher circulating 25(OH)D (all < 0.01). Moreover, circulating Nrg4 was positively and independently associated with 25(OH)D, and was negatively with VPT (< 0.01 or < 0.05), but showed no associations with the prevalence of peripheral arterial disease, diabetic nephropathy, and diabetic retinopathy (all > 0.05). Additionally,the prevalence of DPN and risk of DPN development were progressively decreased with increasing circulating Nrg4 quartiles, independently of potential confounding factors.

Conclusions: These data demonstrate that decreased levels of circulating Nrg4 might lead to the development of DPN through its close interaction with circulating 25(OH)D not with other diabetic vascular complications. Further prospective studies are needed to identify our findings in these populations.
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http://dx.doi.org/10.1186/s13098-020-00550-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236347PMC
May 2020

Delayed-phase thrombocytopenia in patients with coronavirus disease 2019 (COVID-19).

Br J Haematol 2020 07 18;190(2):179-184. Epub 2020 Jun 18.

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Coronavirus disease 2019 (COVID-19) can affect the haematopoietic system. Thrombocytopenia at admission was prevalent, while late-phase or delayed-phase thrombocytopenia (occurred 14 days after symptom onset) is rare. This retrospective, single-centre study screened 450 COVID-19 patients and enrolled 271 patients at the Union Hospital, Wuhan, China, from January 25 to March 9, 2020. COVID-19-associated delayed-phase thrombocytopenia occurred in 11·8% of enrolling patients. The delayed-phase thrombocytopenia in COVID-19 is prone to develop in elderly patients or patients with low lymphocyte count on admission. The delayed-phase thrombocytopenia is significantly associated with increased length of hospital stay and higher mortality rate. Delayed-phase nadir platelet counts demonstrated a significantly negative correlation with B cell percentages. We also provided and described bone marrow aspiration pathology of three patients with delayed-phase thrombocytopenia, showing impaired maturation of megakaryocytes. We speculated that immune-mediated platelet destruction might account for the delayed-phase thrombocytopenia in a group of patients. In addition, clinicians need to pay attention to the delayed-phase thrombocytopenia especially at 3-4 weeks after symptom onset.
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http://dx.doi.org/10.1111/bjh.16885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283673PMC
July 2020

Structural characterization and biological activities of a novel polysaccharide containing N-acetylglucosamine from Ganoderma sinense.

Int J Biol Macromol 2020 May 6. Epub 2020 May 6.

Biotechnological Institute of Chinese Materia Medica, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China; Department of Natural Product Chemistry, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China. Electronic address:

A novel homogeneous heteropolysaccharide (GSPB70-S) with a molecular weight of 2.87 kDa was isolated from Ganoderma sinense. Structural analysis showed that GSPB70-S was composed of glucose, glucosamine, mannose, and galactose with a molar ratio of 12.90:3.70:2.26:1.00. The repeating structure units of GSPB70-S were characterized by the combined application of chemical methods and nuclear magnetic resonance. GSPB70-S contains a backbone of →3)-β-D-Glcp-(1 → 4)-α-D-GlcpNAc-(1 → 4)-α-D-Manp-(1 → 3)-β-D-Glcp-(1→, with branches of β-D-Glcp-(1→, α-D-GlcpNAc-(1 → and →4)-α-D-Galp-(1→. Scanning electron microscope (SEM) showed that GSPB70-S presented a long strip shape with different thicknesses, and there were many lamellar substances on the surface. Biological research showed that GSPB70-S inhibited the activity of α-glucosidase in vitro, increased the viability of RAW 264.7 macrophages, and promoted the release of NO. In addition, GSPB70-S showed good abilities to scavenge free radicals.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.05.028DOI Listing
May 2020

Celastrol mitigates high glucose-induced inflammation and apoptosis in rat H9c2 cardiomyocytes via miR-345-5p/growth arrest-specific 6.

J Gene Med 2020 09 8;22(9):e3201. Epub 2020 May 8.

Department of Cardiology, the First Affiliated Hospital of Zhejiang University, Hangzhou, China.

Background: Celastrol (Cel) has been corroborated as an anti-inflammatory and anti-apoptotic agent in multiple cell damage models. However, the protective effect of Cel in high glucose (HG)-induced cardiomyocyte injury is still unclear. The present study aimed to determine whether Cel can mitigate HG-stimulated cardiomyocyte injury via regulating the miR-345-5p/growth arrest-specific 6 (Gas6) signaling pathway.

Methods: Cardiomyocytes were exposed to normal glucose (NG; 5 mmol/l) or HG (30 mmol/l) and then administered with Cel. Cell counting kit-8 and flow cytometry assays were used to detect cell proliferative activity and apoptosis. mRNA and protein expression were analyzed using a quantitative reverse transcriptase-polymerase chain reaction and western blotting, respectively. A bioinformatics algorithm and a luciferase reporter gene assay were used to determine whether Gas6 is a direct target of miR-345-5p.

Results: The present study confirmed the inhibitory effects of Cel in HG-induced inflammation in cardiomyocytes. Moreover, Cel exhibited the ability to antagonize HG-induced cardiomyocyte apoptosis and suppress the elevated Bax/Bcl-2 ratio elicited by HG stimulation. Intriguingly, Cel treatment revoked the HG-triggered repression of Gas6 protein expression, and Gas6 loss-of-function accelerated HG-induced cardiomyocyte apoptosis. HG-triggered up-regulation of miR-345-5p expression was depressed following Cel treatment. Importantly, we validated that Gas6 is a direct target of miR-345-5p. Transfection with miR-345-5p inhibitors restrained HG-induced release of pro-inflammatory cytokines and cell apoptosis.

Conclusions: The findings of the present study demonstrate that Cel administration antagonized HG-induced cardiomyocyte apoptosis and inflammation through up-regulating Gas6 expression by restraining miR-345-5p.
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http://dx.doi.org/10.1002/jgm.3201DOI Listing
September 2020

LncRNA SNHG1 regulates vascular endothelial cell proliferation and angiogenesis via miR-196a.

J Mol Histol 2020 Apr 15;51(2):117-124. Epub 2020 Apr 15.

Department of Cardiology, The First Affiliated Hospital of Zhejiang University, Number 79, Qingchun Road, Hangzhou, 310003, Zhejiang, China.

Inflammatory cytokines are important protagonists in the formation of atherosclerotic plaques, triggering effects throughout the atherosclerotic vessels due to the destruction in proliferation, migration and angiogenesis of endothelial cells. In this study, we found SNHG1 is upregulated in TNF-α-treated HUVECs. We silenced SNHG1 and found it inhibited vascular endothelial cell proliferation and angiogenesis. In the other hand, exogenetic overexpression of SNHG1 promotes proliferation, migration and angiogenesis. Then we demonstrated that SNHG1 may interact directly with miR-196a to act as a miR-196a sponge. Further, MAPK6 were predicted to be the target of miR-196a. So we blocked miR-196a, which increased expression level of MAPK6, enhanced cell proliferation, migration and angiogenesis. These data indicated that SNHG1/miR-196a/MAPK6 axis may take a part in autophagy regulation in TNF-α-treated HUVECs. The subsequent rescue experiments come to the results ascertained the specificity of SNHG1/miR-196a/MAPK6 axis in regulating MAPK6. Overall, our findings demonstrate a novel mechanism by which SNHG1 overexpression protects the function of HUVECs, which may delay the progression of AS. SNHG1/miR-196a/MAPK6 axis may be of therapeutic significance in AS.
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http://dx.doi.org/10.1007/s10735-020-09862-zDOI Listing
April 2020

The identification of a CD47-blocking "hotspot" and design of a CD47/PD-L1 dual-specific antibody with limited hemagglutination.

Signal Transduct Target Ther 2020 03 6;5(1):16. Epub 2020 Mar 6.

CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, 100101, Beijing, China.

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http://dx.doi.org/10.1038/s41392-020-0121-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058617PMC
March 2020

RBM4 regulates M1 macrophages polarization through targeting STAT1-mediated glycolysis.

Int Immunopharmacol 2020 Jun 2;83:106432. Epub 2020 Apr 2.

Department of Cardiology, The First Affiliated Hospital, Zhejiang University, Hangzhou 310003, China. Electronic address:

M1/M2 macrophages polarization play important roles in regulating tissue homeostasis. Recently, RNA-binding motif 4 (RBM4) has been reported to modulate the proliferation and expression of inflammatory factors in HeLa cells. However, whether RBM4 is involved in regulating macrophage polarization and inflammatory factor expression are still unknown. In this study, RAW264.7, a mouse macrophage cell line, were stimulated with interferon γ (IFN-γ) or interleukin-4 (IL-4) to induce M1/M2 macrophages polarization. We found that IFN-γ, but not IL-4, stimulation decreased RBM4 expression in macrophages, and RBM4 overexpression inhibits IFN-γ-induced M1 macrophage polarization. Furthermore, RNA-Sequencing, protein immunoprecipitation accompanied with mass spectrometry, and extracellular acidification rate analysis showed that RBM4 suppresses IFN-γ-induced M1 macrophage polarization though inhibiting glycolysis. Moreover, RBM4 knockdown promoted IFN-γ-induced signal transducer and activator of transcription 1 (STAT1) activation via increasing STAT1 mRNA stability, leading to the increase of glycolysis-related gene transcripts regulated by STAT1. Finally, we find that RBM4 interacts with YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) to degrade m6A modified STAT1 mRNA, thereby regulating glycolysis and M1 macrophage polarization. Collectively, the current study firstly reports that RBM4 regulates M1 macrophages polarization through targeting STAT1-mediated glycolysis and shows that RBM4 is a possible candidate for regulating macrophage M1 polarization and inflammatory responses.
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http://dx.doi.org/10.1016/j.intimp.2020.106432DOI Listing
June 2020
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