Publications by authors named "Bo Liang"

486 Publications

Traditional Chinese Medicine Intervenes Ventricular Remodeling Following Acute Myocardial Infarction: Evidence From 40 Random Controlled Trials With 3,659 Subjects.

Front Pharmacol 2021 31;12:707394. Epub 2021 Aug 31.

Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China.

We intend to conduct a meta-analysis on the systematic evaluation of traditional Chinese medicine (TCM) in the treatment of ventricular remodeling following acute myocardial infarction (AMI). Our findings may provide certain references for the clinical treatment of ventricular remodeling. A systematic literature search was conducted in PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wanfang Data, CQVIP, and CBM before 20 July 2020. Data were analyzed using a random/fixed-effect model. Primary outcomes included the effectiveness and TCM syndrome score (TCMSS). Secondary outcomes included 1) echocardiography data, including the left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic volume index (LVEDVi), left ventricular end-systolic volume index (LVESVi), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular ejection fraction (LVEF), E/A, stroke volume (SV), and wall motion score (WMS); 2) serum indicators, including the B-type natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP), and C-reactive protein (CRP) or high sensitivity CRP (hs-CRP); (3) major adverse cardiovascular events (MACE) and other adverse events Forty RCTs involving 3,659 subjects were recruited. Our findings proved that a combination of TCM or TCM preparations with conventional Western medicine for preventing and reversing ventricular remodeling at post-AMI could remarkably enhance the total effectiveness and reduced TCMSS. Moreover, myocardial functions (LVEF, E/A, and SV), ventricular remodeling (LVEDVi, LVESVi, LVEDV, LVESV, LVEDD, LVESD, LVPWT, and WMS), serum levels of BNP and CRP, and MACE were significantly improved by the combination of TCM or TCM preparations with conventional Western medicine. Nevertheless, IVST and the incidence of other adverse events were comparable between control and experimental groups The combination of TCM or TCM preparations and conventional Western medicine can alleviate the process of ventricular remodeling, enhance cardiac function, and reduce the incidence of MACE in AMI patients.
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http://dx.doi.org/10.3389/fphar.2021.707394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438202PMC
August 2021

Exosomal circular RNA circ_0074673 regulates the proliferation, migration, and angiogenesis of human umbilical vein endothelial cells via the microRNA-1200/MEOX2 axis.

Bioengineered 2021 12;12(1):6782-6792

Obstetrics and Gynecology Department, Shenzhen University General Hospital, Shenzhen, Guangdong, China.

Circular RNAs (circRNAs) are implicated in the pathogenesis of gestational diabetes mellitus (GDM). The aim of this study was to investigate the roles and molecular mechanism underlying the effects of circ_0074673 in GDM. Exosomal morphology was visualized by transmission electron microscopy (TEM), while exosomal size and concentration were determined by nanoparticle tracking analysis (NTA). The expression of CD9 and CD63 was measured by western blotting. The levels of circ_0074673, miR-1200 and mesenchyme homeobox 2 (MEOX2) were determined by quantitative real-time polymerase chain reaction (qPCR). Cellular proliferation, migration, and angiogenesis were measured by Cell Counting Kit-8 (CCK-8), transwell, and tube formation assays, respectively. The binding relationship between circ_0074673 or MEOX2 and miR-1200 was evaluated by luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and RNA-pull-down assay. The results showed that exosomal size and concentration were greater in the umbilical cord blood of patients with GDM than in that of the healthy controls. The expression of circ_0074673 was upregulated in exosomes from GDM and in human umbilical vein endothelial cells (HUVECs) co-cultured with exosomes. High glucose (HG) treatment suppressed cellular proliferation, migration, and angiogenesis. Circ_0074673 knockdown enhanced the proliferation, migration, and angiogenesis of HG treated HUVECs (HG-HUVECs). As circ_0074673 and MEOX2 directly bind to miR-1200, circ_0074673 silencing promoted the biological functions of HG-HUVECs by sponging miR-1200 and further targeting MEOX2. Altogether, the loss of exosomal circ_0074673 facilitated the proliferation, migration, and angiogenesis of HG-HUVECs via the miR-1200/MEOX2 axis, suggesting that circ_0074673 is a potential therapeutic target for GDM.
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http://dx.doi.org/10.1080/21655979.2021.1967077DOI Listing
December 2021

Photo-irradiation tunes highly active sites over β-Ni(OH) nanosheets for the electrocatalytic oxygen evolution reaction.

Chem Commun (Camb) 2021 Sep 9;57(72):9060-9063. Epub 2021 Sep 9.

International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.

A facile photo-irradiation method is developed to tune active sites over β-Ni(OH) nanosheets. Photo-irradiated β-Ni(OH) nanosheets possess disordered surface atoms and preferred growth of highly active crystal facets, which exhibit enhanced performance for the electrocatalytic oxygen evolution reaction.
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http://dx.doi.org/10.1039/d1cc03410cDOI Listing
September 2021

Evaluation of the Safety and Efficacy of Coronary Intravascular Lithotripsy for Treatment of Severely Calcified Coronary Stenoses: Evidence From the Serial Disrupt CAD Trials.

Authors:
Bo Liang Ning Gu

Front Cardiovasc Med 2021 19;8:724481. Epub 2021 Aug 19.

Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China.

Previous understanding holds that rotational atherectomy and modified balloons remain the default strategy for severely calcified coronary stenoses. In recent years, coronary intravascular lithotripsy (IVL) provides new ideas. This study was conducted to evaluate the safety and efficacy of IVL for the treatment of severely calcified coronary stenoses. The serial Disrupt CAD trials (Disrupt CAD I, Disrupt CAD II, Disrupt CAD III, and Disrupt CAD IV) were included in this study. The safety endpoint was freedom from major adverse cardiovascular events (MACE) in hospital, at 30 days, and at 6 months following the index procedure. The efficacy endpoints included procedural success and angiographic success. Optical coherence tomography (OCT) was used to evaluate the mechanism of action of IVL quantifying the coronary artery calcification (CAC) characteristics and calcium plaque fracture. We enrolled a total of 628 patients with a mean age of 71.8 years, 77.1% males. In these patients, the left anterior descending artery and right coronary artery were the most vulnerable vessels. The diameter stenosis was 64.6 ± 11.6% and the lesion length was 24.2 ± 11.4 mm. IVL had a favorable efficacy (93.0% procedural success, 97.5% angiographic success, and 100.0% stent delivery). Among the 628 patients, 568, 568, and 60 reported MACE endpoints in hospital, at 30 days, and at 6 months, respectively. The results showed that 528, 514, and 55 patients were free from MACE in hospital, at 30 days, and at 6 months, respectively. OCT measurements demonstrated that calcium fracture was the underlying mechanism of action for coronary IVL. IVL is safe and efficient for severely calcified coronary stenoses, and, importantly, calcium fracture facilitated increased vessel compliance and favorable stent expansion.
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http://dx.doi.org/10.3389/fcvm.2021.724481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416910PMC
August 2021

Low-impedance high-power pulsed generator based on forming line with built-in Tesla transformer.

Rev Sci Instrum 2021 Aug;92(8):084705

College of Advanced Interdisciplinary Studies, National University of Defense Technology, Changsha 410073, China.

In order to meet the application needs of gyromagnetic nonlinear transmission lines, a pulsed power generator is required to output short duration pulses with a fast rising edge in high repetitive-rate mode. In this paper, a low-impedance high-power pulsed generator based on the forming line with a built-in Tesla transformer is explored and developed. The generator includes a 14 Ω coaxial forming line, a SF/N gas switch, and a resistive dummy load, which can steadily operate in 100 Hz mode and suits the needs above. The pulsed forming line adopts transformer oil as the insulation medium and has a large shell radius and short length to reduce impedance. It has been verified by CST simulation that a relatively high coupling coefficient (0.93) can be achieved when the length-radius ratio is 3.2. The maximum forming line charging voltage is -600 kV in single-shot mode, while the charging voltage is -520 kV in repetitive-rate mode. The output pulse duration is 13 ns with a 4 ns rising edge, and its amplitude for a 10 Ω load is -220 kV at a repetition rate of 100 Hz. The experimental results showed the feasibility of the low-impedance nanosecond periodically pulsed generator based on an oil forming line charged from the high-coupling Tesla transformer. These efforts expand the technical route of the pulse forming line with a built-in Tesla transformer and set a good foundation for its application in the future.
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http://dx.doi.org/10.1063/5.0055075DOI Listing
August 2021

Traditional Chinese Medicine for Coronary Artery Disease Treatment: Clinical Evidence From Randomized Controlled Trials.

Authors:
Bo Liang Ning Gu

Front Cardiovasc Med 2021 6;8:702110. Epub 2021 Aug 6.

Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China.

Traditional Chinese medicine has a history of more than 2,000 years and has been widely used in clinical practice. However, due to the lack of a reliable scientific basis, the role of traditional Chinese medicine in the prevention and treatment of coronary artery disease is not clear. At present, the existing randomized controlled trials about traditional Chinese medicine for coronary artery disease have defects, small sample sizes, and different results, so it is difficult to make a clear conclusion on the actual advantages and disadvantages of traditional Chinese medicine. In this review, the efficacy and safety of traditional Chinese medicine in the prevention and treatment of coronary artery disease were systematically evaluated through randomized controlled trials, most of which were double-blind trials. We reviewed 17 randomized controlled trials that included a total of 11,726 coronary artery disease patients. The methodological quality of the trials was generally high, with nine (52.94%) having a modified Jadad score of 7 and only three (17.65%) having a modified Jadad score of <3. There are 16 trials (94.12%) reporting safety; the safety of traditional Chinese medicine seems not to be inferior to that of mimetic, placebo, or western medications. Moreover, the results from 17 randomized controlled trials (100.00%) showed that traditional Chinese medicine can be applied as a complementary and alternative method to the primary and secondary prevention of coronary artery disease, and only six trials (35.29%) described adverse cardiovascular events specifically. However, it is necessary to assess the safety and efficacy of traditional Chinese medicine in treating coronary artery disease with long-term hard endpoints.
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http://dx.doi.org/10.3389/fcvm.2021.702110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377193PMC
August 2021

Development of bacterial biosensor for sensitive and selective detection of acetaldehyde.

Biosens Bioelectron 2021 Aug 13;193:113566. Epub 2021 Aug 13.

Energy-rich Compounds Production by Photosynthetic Carbon Fixation Research Center, Qingdao Agricultural University, Qingdao, China; Shandong Key Lab of Applied Mycology, College of Life Sciences, Qingdao Agricultural University, Qingdao, China. Electronic address:

Acetaldehyde is a human carcinogen and widely existed in alcoholic beverages and polluted air. In this study, a simple, fast, convenient and sensitive acetaldehyde biosensor was developed based on an acetaldehyde dehydrogenase (AldDH) bacteria surface display system. The whole-cell catalyst facilitated the dehydrogenation of acetaldehyde, while coenzyme NAD was reduced and the resultant NADH can be detected spectrometrically at 340 nm. The correct location of AldDH on the bacteria surface was confirmed by the subcellular fraction and immunofluorescence analysis. By comparing the fusion protein expression level and whole-cell activity, the proper display system for anchoring AldDH on the cell surface was obtained. The results of kinetics analysis towards both surface-displayed AldDH and intracellular expressed AldDH demonstrated that the mass-transport resistance was dramatically alleviated by cell-surface display strategy. Under optimal conditions, AldDH-surface display strain with the highest whole-cell activity (3.41 ± 0.3 mU/OD) was applied to spectrophotometry acetaldehyde detection system. An excellent linear relationship between the increases of absorbance at 340 nm and acetaldehyde concentration over the range from 1 μM to 300 μM was reached. The proposed approach offered adequate sensitivity for the detection of acetaldehyde at 0.33 μM. Most importantly, the developed biosensor showed the narrowest substrate specificity towards acetaldehyde, which has been employed for quick determination of acetaldehyde in real samples with good accuracy. The total detection time was within 20 min. The method reported here provided a simple, rapid, and low-cost strategy for the sensitive and selective measurement of acetaldehyde. Therefore, genetically engineered cells may find broad application in biosensors and biocatalysts.
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http://dx.doi.org/10.1016/j.bios.2021.113566DOI Listing
August 2021

Generation and Assembly of Virus-Specific Nucleocapsids of the Respiratory Syncytial Virus.

J Vis Exp 2021 Jul 27(173). Epub 2021 Jul 27.

Department of Biochemistry, Emory University School of Medicine;

The use of an authentic RNA template is critical to advance the fundamental knowledge of viral RNA synthesis that can guide both mechanistic discovery and assay development in virology. The RNA template of nonsegmented negative-sense (NNS) RNA viruses, such as the respiratory syncytial virus (RSV), is not an RNA molecule alone but rather a nucleoprotein (N) encapsidated ribonucleoprotein complex. Despite the importance of the authentic RNA template, the generation and assembly of such a ribonucleoprotein complex remain sophisticated and require in-depth elucidation. The main challenge is that the overexpressed RSV N binds non-specifically to cellular RNAs to form random nucleocapsid-like particles (NCLPs). Here, we established a protocol to obtain RNA-free N (N) first by co-expressing N with a chaperone phosphoprotein (P), then assembling N with RNA oligos with the RSV-specific RNA sequence to obtain virus-specific nucleocapsids (NCs). This protocol shows how to overcome the difficulty in the preparation of this traditionally challenging viral ribonucleoprotein complex.
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http://dx.doi.org/10.3791/62010DOI Listing
July 2021

Receptor Tyrosine Kinase Inhibitor Sunitinib as Novel Immunotherapy to Inhibit Myeloid-Derived Suppressor Cells for Treatment of Endometriosis.

Front Immunol 2021 22;12:641206. Epub 2021 Jul 22.

Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong, Hong Kong, SAR China.

Endometriosis is a common, benign, and hormone-dependent gynaecological disorder that displays altered immunoinflammatory profiles. Myeloid-derived suppressor cells (MDSCs) suppressed immunosurveillance in endometriosis in human and mouse model. Receptor tyrosine kinase inhibitor Sunitinib can induce MDSC apoptosis and suppress the progression of cancer. However, the effects of Sunitinib on MDSCs in endometriosis and the underlying mechanism are not clear. In this study, we employed an animal study of the endometriosis model in mice for treatment of Sunitinib. After syngeneic endometrium transplantation and treatment, endometriotic lesion volume, weight, and histology were compared. Peritoneal fluid, peripheral blood, and bone marrow MDSC subsets and their molecular signaling were monitored by flow cytometry. Peritoneal cytokines were assayed by ELISA. The gene expression profiles of isolated CD11b+Ly6G+Ly6C cells were studied by RNA sequencing. We found that Sunitinib significantly decreased the endometriotic lesion size and weight after 1 and 3 weeks, and decreased p-STAT3 activation in MDSCs after 1 week of treatment. In the first week, Sunitinib specifically increased the G-MDSC population in peritoneal fluid but the isolated CD11b+Ly6G+Ly6C MDSCs after Sunitinib treatment were presented as mature polynuclear MDSCs, while the control group had immature mononuclear MDSCs. Importantly, we found Sunitinib differentially suppressed gene expressions of immunosuppressive function and differentiation in peritoneal G-MDSCs. Apelin signaling pathway associated genes and inflammation related genes were upregulated, and amino acid metabolism regulator genes were downregulated in bone marrow G-MDSCs. For endometriotic lesions, the PPARG gene governing glucose metabolism and fatty acid storage, which is important for the development of endometriosis was upregulated. In conclusion, Sunitinib inhibited endometriotic lesions, by promoting peritoneal fluid MDSCs maturation and inhibiting the immunosuppressive function. These findings suggest that Sunitinib changed the immune microenvironment and inhibited the development of endometriosis, which has potential therapeutic effects as novel immunotherapy to promote MDSCs maturation, differentiation, and metabolism for the treatment of endometriosis.
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http://dx.doi.org/10.3389/fimmu.2021.641206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340010PMC
September 2021

E3 ubiquitin ligase TRIM29 promotes pancreatic cancer growth and progression via stabilizing Yes-associated protein 1.

J Transl Med 2021 08 5;19(1):332. Epub 2021 Aug 5.

Jiangxi Province Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang, 330006, Jiangxi, China.

Background: Pancreatic cancer (PC) is one of the most fatal digestive system cancers. tripartite motif-29 (TRIM29) has been reported as oncogene in several human cancers. However, the precise role and underlying signal cascade of TRIM29 in PC progression remain unclear.

Methods: Western blot, qRT-PCR and immunohistochemistry were used to analyze TRIM29 and Yes-associated protein 1 (YAP1) levels. CCK8 assays, EdU assays and flow cytometry were designed to explore the function and potential mechanism of TRIM29 and YAP1 in the proliferation of PC. Next, a nude mouse model of PC was established for validating the roles of TRIM29 and YAP1 in vivo. The relationship among TRIM29 and YAP1 was explored by co-immunoprecipitation and in vitro ubiquitination assay.

Results: TRIM29 and YAP1 was significantly upregulated in PC patient samples, and TRIM29 expression was closely related to a malignant phenotype and poorer overall survival (OS) of PC patients. Functional assays revealed that TRIM29 knockdown suppresses cell growth, arrests cell cycle progression and promotes cell apoptosis of PC cells in vivo and in vitro. Furthermore, the rescue experiments demonstrated that TRIM29-induced proliferation is dependent on YAP1 in PC cells. Mechanistically, TRIM29 regulates YAP1 expression by directly binding to YAP1, and reduced its ubiquitination and degradation.

Conclusion: Taken together, these results identify a novel mechanism used by PC growth, and provide insight regarding the role of TRIM29 in PC.
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http://dx.doi.org/10.1186/s12967-021-03007-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340474PMC
August 2021

An in-depth analysis reveals two new genetic variants on 22q11.2 associated with vitiligo in the Chinese Han population.

Mol Biol Rep 2021 Aug 4;48(8):5955-5964. Epub 2021 Aug 4.

Department of Dermatology and Institute of Dermatology at No. 1 Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, China.

Background: Vitiligo is a complex disease in which patchy depigmentation is the result of an autoimmune-induced loss of melanocytes in affected regions. On the basis of a genome-wide linkage analysis of vitiligo in the Chinese Han population, we previously showed significant evidence of a linkage between 22q12 and vitiligo. Our aim in the current study was to identify vitiligo susceptibility variants within an expanded region of the 22q12 locus.

Methods And Results: An in-depth analysis of the expanded region of the 22q12 locus was performed by imputation using a large GWAS dataset consisting of 1117 cases and 1701 controls. Eight nominal SNPs were selected and genotyped in an independent cohort of Chinese Han individuals (2069 patients and 1370 control individuals) by using the Sequenom MassArray iPLEX1 system. The data were analyzed with PLINK 1.07 software. The C allele of rs730669 located in ZDHHC8/RTN4R showed a strong association with vitiligo (P = 3.25 × 10, OR = 0.81). The C allele of rs4820338 located in VPREB1 and the A allele of rs2051582 (a SNP reported in our previous study) located in IL2RB showed a suggestive association with vitiligo (P = 1.04 × 10, OR = 0.86; P = 1.78 × 10, OR = 1.27). The three identified SNPs showed independent associations with vitiligo in a conditional logistic regression analysis (all P < 1.0 × 10; all D' < 0.05 and r < 1.0 × 10).

Conclusions: The study reveals that two novel variants rs730669 (ZDHHC8/RTN4R) and rs4820338 (VPREB1) on 22q11.2 might confer susceptibility to vitiligo and affect disease subphenotypes. The presence of multiple independent variants emphasizes their important roles in the genetic pathogenesis of disease.
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http://dx.doi.org/10.1007/s11033-021-06597-2DOI Listing
August 2021

Discovery of the first chemical tools to regulate MKK3-mediated MYC activation in cancer.

Bioorg Med Chem 2021 Sep 22;45:116324. Epub 2021 Jul 22.

Department of Pharmacology and Chemical Biology, Emory University School of Medicine, Emory University, Atlanta, GA, USA; Emory Chemical Biology Discovery Center, Emory University School of Medicine, Emory University, Atlanta, GA, USA; Winship Cancer Institute, Emory University, Atlanta, GA, USA. Electronic address:

The transcription master regulator MYC plays an essential role in regulating major cellular programs and is a well-established therapeutic target in cancer. However, MYC targeting for drug discovery is challenging. New therapeutic approaches to control MYC-dependent malignancy are urgently needed. The mitogen-activated protein kinase kinase 3 (MKK3) binds and activates MYC in different cell types, and disruption of MKK3-MYC protein-protein interaction may provide a new strategy to target MYC-driven programs. However, there is no perturbagen available to interrogate and control this signaling arm. In this study, we assessed the drugability of the MKK3-MYC complex and discovered the first chemical tool to regulate MKK3-mediated MYC activation. We have designed a short 44-residue inhibitory peptide and developed a cell lysate-based time-resolved fluorescence resonance energy transfer (TR-FRET) assay to discover the first small molecule MKK3-MYC PPI inhibitor. We have optimized and miniaturized the assay into an ultra-high-throughput screening (uHTS) 1536-well plate format. The pilot screen of ~6,000 compounds of a bioactive chemical library followed by multiple secondary and orthogonal assays revealed a quinoline derivative SGI-1027 as a potent inhibitor of MKK3-MYC PPI. We have shown that SGI-1027 disrupts the MKK3-MYC complex in cells and in vitro and inhibits MYC transcriptional activity in colon and breast cancer cells. In contrast, SGI-1027 does not inhibit MKK3 kinase activity and does not interfere with well-known MKK3-p38 and MYC-MAX complexes. Together, our studies demonstrate the drugability of MKK3-MYC PPI, provide the first chemical tool to interrogate its biological functions, and establish a new uHTS assay to enable future discovery of potent and selective inhibitors to regulate this oncogenic complex.
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http://dx.doi.org/10.1016/j.bmc.2021.116324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456368PMC
September 2021

Silencing of ATG4D suppressed proliferation and enhanced cisplatin-induced apoptosis in hepatocellular carcinoma through Akt/Caspase-3 pathway.

Mol Cell Biochem 2021 Jul 27. Epub 2021 Jul 27.

Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330000, China.

ATG4D, a member of autophagy-related protein 4 (ATG4) family, plays an interplay role between autophagy and apoptosis in cancers. However, the role of ATG4D in hepatocellular carcinoma (HCC) has not been defined. Herein, this study aimed to investigate the role and the underlying mechanism of ATG4D in regulating HCC cell apoptosis. ATG4D was silenced in MHCC-97L HCC cells, and then cell proliferation and apoptosis were examined. ATG4D expression was significantly upregulated in HCC tissues when compared with paired non-tumor tissues. In vitro assays revealed that silencing of ATG4D significantly suppressed cell proliferation, promoted cell apoptosis, and enhanced sensitivity to cisplatin of MHCC-97L cells. Furthermore, silencing of ATG4D decreased the phosphorylation of Akt and increased the protein level of caspase-3. Taken together, ATG4D may play an oncogenic role in HCC progression. These findings suggest that ATG4D may serve as a therapeutic target for HCC therapy.
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http://dx.doi.org/10.1007/s11010-021-04224-zDOI Listing
July 2021

Integrating systematic pharmacology-based strategy and experimental validation to explore the synergistic pharmacological mechanisms of Guanxin V in treating ventricular remodeling.

Bioorg Chem 2021 Oct 18;115:105187. Epub 2021 Jul 18.

Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China. Electronic address:

Background: Guanxin V (GXV) has been widely used to treat ventricular remodeling (VR) in clinical practice in China. However, the underlying mechanisms are currently still lack.

Methods: A systematic pharmacology-based strategy was utilized for predicting the synergistic pharmacological mechanisms of GXV in VR. The active compounds of GXV were selected and then the potential targets of these compounds contained in GXV and VR were successively identified. Then, after networks were constructed, DAVID was applied to functional enrichment. Moreover, the key findings were validated though molecular docking and molecular biology experiments.

Results: A total of 119 active components in GXV and 169 potential targets shared between GXV and VR were obtained. The results of functional enrichment indicated that several biological processes and signaling pathways, mainly cell apoptosis and fibrosis. Finally, we discovered GXV produced marked anti-apoptosis and anti-fibrosis effects in VR though Caspase-3 and TGF-β1.

Conclusion: GXV could relieve and reverse VR through anti-apoptosis and anti-fibrosis effects predicted by systematic pharmacology and validated by molecular docking and molecular experiments. Our study deepens the understanding of the molecular mechanisms of GXV in treating VR.
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http://dx.doi.org/10.1016/j.bioorg.2021.105187DOI Listing
October 2021

An integrated electrochemical POCT platform for ultrasensitive circRNA detection towards hepatocellular carcinoma diagnosis.

Biosens Bioelectron 2021 Nov 13;192:113500. Epub 2021 Jul 13.

Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China; Key Laboratory of Laparoscopic Technique Research of Zhejiang Province, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China; Zhejiang Minimal Invasive Diagnosis and Treantment Thechnology Research Center of Severe Hepatobiliary Disease, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China; Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China. Electronic address:

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death. Circ-CDYL, one of the circular RNAs (circRNAs), is recognized as an independent marker for HCC early diagnosis. Point-of-care testing (POCT) of circRNA is essential and in great demand for clinical applications. Herein, we report a fully integrated electrochemical POCT platform for circRNA detection based on Au nanoflowers (AuNFs)/peptide nucleic acid (PNA) modified carbon-fiber microelectrode (CFME). PNA is applied as the recognition element, highly specified for a back-splice junction of circRNA. AuNFs increased active site for PNA probes, improving target-capturing efficiency at an ultralow level. The platform provides a linear range of 10 fM to 1 μM, with a detection limit as low as 3.29 fM. This biosensor demonstrates high specificity towards one-base mismatch and is stable for up to 24 days. The analytical performance has also been verified in human serum samples, demonstrating the potential utility in clinical POCT applications for HCC.
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http://dx.doi.org/10.1016/j.bios.2021.113500DOI Listing
November 2021

Characterization of a Tumor-Microenvironment-Relevant Gene Set Based on Tumor Severity in Colon Cancer and Evaluation of Its Potential for Dihydroartemisinin Targeting.

Evid Based Complement Alternat Med 2021 17;2021:4812068. Epub 2021 Jun 17.

Department of Hepatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China.

Colon cancer (COAD) is a leading cause of cancer mortality in the world. Most patients with COAD die as a result of cancer cell metastasis. However, the mechanisms underlying the metastatic phenotype of COAD remain unclear. Instead, particular features of the tumor microenvironment (TME) could predict adverse outcomes including metastasis in patients with COAD, and the role of TME in governing COAD progression is undeniable. Therefore, exploring the role of TME in COAD may help us better understand the molecular mechanisms behind COAD progression which may improve clinical outcomes and quality of patients. Here, we identified a Specific TME Regulatory Network including AEBP1, BGN, POST, and FAP (STMERN) that is highly involved in clinical outcomes of patients with COAD. Comprehensive analysis of our study revealed that the STMERN is highly correlated with the severity of COAD. Meanwhile, our results reveal that the STMERN might be associated with immune infiltration in COAD. Importantly, we show that dihydroartemisinin (DHA) potentially interacts with the STMERN. We suggest that DHA might contribute to immune infiltration through regulating the STMERN in COAD. Taken together, our data provide a set of biomarkers of progression and poor prognosis in COAD. These findings could have potential prognostic and therapeutic implications in the progression of COAD.
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http://dx.doi.org/10.1155/2021/4812068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233087PMC
June 2021

LncRNA HCP5 : A Potential Biomarker for Diagnosing Gastric Cancer.

Front Oncol 2021 18;11:684531. Epub 2021 Jun 18.

Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China.

Background: It has been reported that long non-coding RNAs (lncRNAs) can be regarded as a biomarker and had particular clinical significance for early screening and gastric cancer (GC) diagnosis. Therefore, this study aimed to investigate whether serum HCP5 could be a new diagnostic biomarker.

Methods: Filtered out the HCP5 from the GEO database. The specificity of HCP5 was verified by real-time fluorescence quantitative PCR (qRT-PCR), and then the stability of HCP5 was verified by room temperature storage and repeated freeze-thaw experiments. Meanwhile, the accuracy of HCP5 was verified by agarose gel electrophoresis (AGE) and Sanger sequencing. Simultaneously, the expression level of serum HCP5 was detected by qRT-PCR in 98 patients with primary gastric cancer, 21 gastritis patients, 82 healthy donors, and multiple cancer types. Then, the methodology analysis was carried on. Moreover, receiver operating characteristic (ROC) was used to evaluate its diagnostic efficiency.

Results: qRT-PCR method had good repeatability and stability in detecting HCP5. The expression level of HCP5 in the serum of gastric cancer patients was remarkably higher than that of healthy controls, and it could distinguish gastritis patients from healthy donors. Besides, the expression of HCP5 was increased dramatically in MKN-45 and MGC-803. The FISH assay showed that HCP5 was mainly distributed in the cytoplasm of MKN-45 and BGC-823 cells. When HCP5 was combined with existing tumor markers, the diagnostic efficiency of HCP5 was the best, and the combined diagnosis of carcinoembryonic antigen (CEA), carbohydrate antigen199 (CA199), and HCP5 can significantly improve the diagnostic sensitivity. Besides, compared with the expression levels of thyroid cancer (THCA), colorectal cancer (CRC), and breast cancer (BRCA), serum HCP5 in gastric cancer was the most specific. Moreover, the high expression of serum HCP5 was related to differentiation, lymph node metastasis, and nerve invasion. The term of serum HCP5 after the operation was significantly lower than that of patients with primary gastric cancer.

Conclusion: Serum HCP5 can be used as a potential biomarker of non-invasive fluid biopsy, which had a unique value in the early diagnosis, development, and prognosis of gastric cancer.
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http://dx.doi.org/10.3389/fonc.2021.684531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252797PMC
June 2021

Measurement of size-segregated airborne particulate bound polycyclic aromatic compounds and assessment of their human health impacts - A case study in a megacity of southwest China.

Chemosphere 2021 Jun 28;284:131339. Epub 2021 Jun 28.

Chongqing Environmental Monitoring Center, Chongqing, 401147, China.

Particle size distribution of particulate polycyclic aromatic compounds (PACs) is one of the important factors controlling human exposure to PACs in air. In this study, size-segregated airborne particle samples were collected in a megacity in southwest China to analyze PACs concentrations and evaluate related health risks. Annual average concentrations of ΣPAHs (polycyclic aromatic hydrocarbons, 17.4 ng/m) and ΣOPAHs (oxygenated PAHs, 15.3 ng/m) were one order of magnitude higher than those of ΣMPAHs (methyl PAHs, 0.97 ng/m) and ΣNPAHs (nitrated PAHs, 1.54 ng/m). More than 55% of PACs masses were associated with fine particles (aerodynamic diameter D < 2.1 μm). Inhalation exposure assessment showed that less than 60% of particulate bound PACs could deposit in the respiratory tract, which implies that the traditional model using ambient concentration of PACs would overestimate the inhalation risk. On the other hand, incremental lifetime cancer risks from dermal absorption (ILCR) were comparable to those from inhalation (ILCR) exposure despite the much lower daily dermal absorption dose than the daily inhalation dose, which implies that the health impact might be underestimated if only considering inhalation exposure. Cancer risks from inhalation exposure were mainly attributed to fine particles while those from dermal exposure were mostly associated with coarse particles. Although neither ILCR nor ILCR exceeded the threshold value of 10 set by USEPA, the total ILCR exceeded this criterion, manifesting potential health risks from exposure to airborne particulate PACs in this region.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131339DOI Listing
June 2021

Effects of Traditional Chinese Medication-Based Bioactive Compounds on Cellular and Molecular Mechanisms of Oxidative Stress.

Oxid Med Cell Longev 2021 14;2021:3617498. Epub 2021 May 14.

Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China.

The oxidative stress reaction is the imbalance between oxidation and antioxidation in the body, resulting in excessive production of oxygen free radicals in the body that cannot be removed, leading to excessive oxidation of the body, and causing damage to cells and tissues. A large number of studies have shown that oxidative stress is involved in the pathological process of many diseases, so inhibiting oxidative stress, that is, antioxidation, is of great significance for the treatment of diseases. Studies have shown that many traditional Chinese medications contain antioxidant active bioactive compounds, but the mechanisms of those compounds are different and complicated. Therefore, by summarizing the literature on antioxidant activity of traditional Chinese medication-based bioactive compounds in recent years, our review systematically elaborates the main antioxidant bioactive compounds contained in traditional Chinese medication and their mechanisms, so as to provide references for the subsequent research.
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http://dx.doi.org/10.1155/2021/3617498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139859PMC
May 2021

Effect of renal denervation on long-term outcomes in patients with resistant hypertension.

Cardiovasc Diabetol 2021 06 5;20(1):117. Epub 2021 Jun 5.

Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China.

Increasing studies strongly prove that renal denervation, a minimally invasive surgery, is a promising new non-drug treatment method that can effectively control blood pressure in patients with resistant hypertension, but the evaluation of the long-term blood pressure control effect of renal denervation for resistant hypertension is still lacking. Here, we critically review current long-term follow-up data about the use of renal denervation for RH to comprehensively evaluate the effectiveness of renal denervation for RH, and to provide practical guidance for practitioners who are establishing a renal denervation service. Limited by the current research, many problems need to be solved before renal denervation is applied to RH. In addition, ambulatory blood pressure should be the first choice for the evaluation of blood pressure. Finally, the continuous antihypertensive effect of renal denervation in different renal denervation systems also needs to be strictly compared.
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http://dx.doi.org/10.1186/s12933-021-01309-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180124PMC
June 2021

Structural Insights into the Respiratory Syncytial Virus RNA Synthesis Complexes.

Viruses 2021 05 5;13(5). Epub 2021 May 5.

Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.

RNA synthesis in respiratory syncytial virus (RSV), a negative-sense (-) nonsegmented RNA virus, consists of viral gene transcription and genome replication. Gene transcription includes the positive-sense (+) viral mRNA synthesis, 5'-RNA capping and methylation, and 3' end polyadenylation. Genome replication includes (+) RNA antigenome and (-) RNA genome synthesis. RSV executes the viral RNA synthesis using an RNA synthesis ribonucleoprotein (RNP) complex, comprising four proteins, the nucleoprotein (N), the large protein (L), the phosphoprotein (P), and the M2-1 protein. We provide an overview of the RSV RNA synthesis and the structural insights into the RSV gene transcription and genome replication process. We propose a model of how the essential four proteins coordinate their activities in different RNA synthesis processes.
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http://dx.doi.org/10.3390/v13050834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147935PMC
May 2021

Application of single-sperm sequencing in a male with Marfan syndrome: a case report and a literature review.

J Genet 2021 ;100

Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, People's Republic of China.

Marfan syndrome (MFS) is caused by a mutation. Many organ systems are affected in patients with MFS, including the skeletal, ocular, cardiovascular and pulmonary systems. Cardiovascular manifestations are the main cause of mortality in patients with MFS. The mode of inheritance of MFS is autosomal dominant inheritance and the offspring are at great risk for the disease. Thus, the genetic testing for monogenic disease during preimplantation (PGT-M) is routinely advised for patients with MFS. PGT-M is a clinical genetic method to obtain normal embryos which are not affected by the monogenetic disorder. However, allele drop out (ADO) typically results in misdiagnosis during the PGT-M in the autosomal dominant disorder. Thus, a linkage analysis of polymorphic sites is used to identify ADO and improve the accuracy of PGT-M. However, when there are no family members affected, or the patients carry a mutation, a linkage analysis cannot be performed to position the abnormal chromatid. Here, we performed single-sperm sequencing of preimplantation genetic testing in a male patient with MFS with a mutation in . We constructed the chromosomal haplotype of the male patient by analysing information at the mutation site and at polymorphic sites. Next, the normal embryos were selected based on the results of high-throughput sequencing and haplotyping, and the one frozen embryo was transferred to the uterus. Finally, the preimplantation genetic testing results were confirmed by the prenatal genetic diagnosis during pregnancy, which showed that the foetus did not carry the pathogenic mutation. In conclusion, our research showed that single-sperm sequencing and haplotype analysis can be used in male patients with monogenetic disorders caused by mutations to improve the accuracy of the preimplantation genetic diagnosis.
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August 2021

Serum hsa_tsr016141 as a Kind of tRNA-Derived Fragments Is a Novel Biomarker in Gastric Cancer.

Front Oncol 2021 13;11:679366. Epub 2021 May 13.

Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China.

Background: Gastric cancer (GC) is one of the most common malignant tumors globally and the third leading cause of cancer-related death. Currently, the sensitivity and specificity of diagnostic markers for GC are low, so it is urgent to find new biomarkers with higher sensitivity and specificity. tRNA-derived small RNAs are a kind of small non-coding RNAs derived from tRNAs. It is abundant in cancer cells and body fluids. Our goal is to find the differentially expressed tRNA-derived small RNAs in GC to explore their potential as a GC biomarker.

Methods: Quantitative real-time PCR was used to detect the expression level of hsa_tsr016141. The molecular characteristics of hsa_tsr016141 were verified by agarose gel electrophoresis, Sanger sequencing, Actinomycin D Assay, and Nuclear and Cytoplasmic RNA Separation Assay. The diagnostic efficiency of hsa_tsr016141 was analyzed through receiver operating characteristic.

Results: The expression level of hsa_tsr016141 in GC tissues and serum was significantly increased. The serum expression level showed a gradient change between GC patients, gastritis patients, and healthy donors and was positively correlated with the degree of lymph node metastasis and tumor grade. ROC analysis showed that the serum expression level of hsa_tsr016141 could significantly distinguish GC patients from healthy donors or gastritis patients. Besides, the expression level of hsa_tsr016141 in GC patients decreased significantly after the operation (P<0.0001).

Conclusions: Serum hsa_tsr016141 has good stability and specificity and can be used for dynamic monitoring of GC patients, suggesting that serum hsa_tsr016141 can be a novel biomarker for GC diagnosis and postoperative monitoring.
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http://dx.doi.org/10.3389/fonc.2021.679366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155501PMC
May 2021

Glycolipid toxicity induces osteogenic dysfunction via the TLR4/S100B pathway.

Int Immunopharmacol 2021 Aug 26;97:107792. Epub 2021 May 26.

Department of Endocrinology, M.D. Candidate, The First Affiliated Hospital of Fujian Medical University, China; Diabetes Research Institute of Fujian Province, Fuzhou, Fujian, China. Electronic address:

Diabetes can cause bone metabolism disorders and osteoporosis. The occurrence of both diabetes mellitus and osteoporosis increases the disability and mortality of elderly individuals due to pathological fracture. Abnormal metabolism of nutrientsis considered to be one of the important mechanisms of diabetes mellitus-induced osteoporosis. This study preliminarily explored the roles of TLR4 (Toll-like receptor 4) and S100B in osteogenic dysfunction induced by glycolipid toxicity. In this study, a diabetic rat model and TLR4-knockdown diabetic rat model were used in vivo. MC3T3-E1 cells in a high glucose and palmitic acid environment were used as glycolipid toxicity cell models in vitro. We investigated the effects of TLR4 and S100B on osteogenesis by overexpression or inhibition of TLR4 and S100B in vitro. We found that when TLR4 or S100B was inhibited, ALP and OCN were significantly up-regulated and p-ERK was significantly down regulated in the glycolipid model. These results suggest that TLR4/S100B may play a role in reducing glycolipid toxicity by regulating ERK phosphorylation.
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http://dx.doi.org/10.1016/j.intimp.2021.107792DOI Listing
August 2021

Network Pharmacology-Based Systematic Analysis of Molecular Mechanisms of Dingji Fumai Decoction for Ventricular Arrhythmia.

Evid Based Complement Alternat Med 2021 8;2021:5535480. Epub 2021 May 8.

Hospital (T.C.M.) Affiliated to Southwest Medical University, Luzhou, China.

Background: Dingji Fumai Decoction (DFD), a traditional herbal mixture, has been widely used to ventricular arrhythmia (VA) in clinical practice in China. However, research on the bioactive components and underlying mechanisms of DFD in VA is still scarce.

Methods: Components of DFD were collected from TCMSP, ETCM, and literature. The chemical structures of each component were obtained from PubChem. Next, SwissADME and SwissTargetPrediction were applied for compounds screening and targets prediction of DFD; meanwhile, targets of VA were collected from DrugBank and Online Mendelian Inheritance in Man (OMIM). Then, the H-C-T-D network and the protein-protein interaction (PPI) network were constructed based on the data obtained above. CytoNCA was utilized to filter hub genes and VarElect was used to analyze the relationship between genes and diseases. At last, Metascape was employed for systematic analysis on the potential targets of herbals against VA, and AutoDock was applied for molecular docking to verify the results.

Results: A total of 434 components were collected, 168 of which were qualified, and there were 28 shared targets between DFD and VA. Three function modules of DFD were found from the PPI network. Further systematic analysis of shared genes and function modules explained the potential mechanism of DFD in the treatment of VA; molecular docking has verified the interactions.

Conclusions: DFD could be employed for VA through mechanisms, including complex interactions between related components and targets, as predicted by network pharmacology and molecular docking. This work confirmed that DFD could apply to the treatment of VA and promoted the explanation of DFD for VA in the molecular mechanisms.
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http://dx.doi.org/10.1155/2021/5535480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128550PMC
May 2021

Lack of CFTR alters the ferret pancreatic ductal epithelial secretome and cellular proteome: Implications for exocrine/endocrine signaling.

J Cyst Fibros 2021 May 17. Epub 2021 May 17.

Dept. of Anatomy and Cell Biology, The Univ. of Iowa, Iowa City, IA, USA; Dept. Biomedical Engineering, The Univ. of Iowa, Iowa City, IA, USA; Fraternal Order of Eagles Diabetes Research Center Roy J. and Lucille A. Carver College of Medicine. Electronic address:

Background: Cystic fibrosis (CF) related diabetes is the most common comorbidity for CF patients and associated with islet dysfunction. Exocrine pancreas remodeling in CF alters the microenvironment in which islets reside. Since CFTR is mainly expressed in pancreatic ductal epithelium, we hypothesized altered CF ductal secretions could impact islet function through paracrine signals.

Method: We evaluated the secretome and cellular proteome of polarized WT and CF ferret ductal epithelia using quantitative ratiometric mass spectrometry. Differentially secreted proteins (DSPs) or expressed cellular proteins were used to mine pathways, upstream regulators and the CFTR interactome to map candidate CF-associated alterations in ductal signaling and phenotype. Candidate DSPs were evaluated for their in vivo pancreatic expression patterns and their functional impact on islet hormone secretion.

Results: The secretome and cellular proteome of CF ductal epithelia was significantly altered relative to WT and implicated dysregulated TGFβ, WNT, and BMP signaling pathways. Cognate receptors of DSPs from CF epithelia were equally distributed among endocrine, exocrine, and stromal pancreatic cell types. IGFBP7 was a downregulated DSP in CF ductal epithelia in vitro and exhibited reduced CF ductal expression in vivo. IGFBP7 also altered WT islet insulin secretion in response to glucose. Many CFTR-associated proteins, including SLC9A3R1, were differentially expressed in the CF cellular proteome. Upstream regulators of the differential CF ductal proteome included TGFβ, PDX1, AKT/PTEN, and INSR signaling. Data is available via ProteomeXchange with identifier PXD025126.

Conclusion: These findings provide a proteomic roadmap for elucidating disturbances in autocrine and paracrine signals from CF pancreatic ducts and how they may alter islet function and maintenance.
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http://dx.doi.org/10.1016/j.jcf.2021.04.010DOI Listing
May 2021

Acute pancreatitis-induced islet dysfunction in ferrets.

Pancreatology 2021 Aug 11;21(5):839-847. Epub 2021 May 11.

Fraternal Order of Eagles Diabetes Research Center, Iowa City, IA, USA; Department of Pediatrics, lowa City, IA, USA; Department of Radiation Oncology; University of Iowa, Iowa City, IA, USA. Electronic address:

Background: /Objectives: The pathogenesis of hyperglycemia during acute pancreatitis (AP) remains unknown due to inaccessibility of human tissues and lack of animal models. We aimed to develop an animal model to study the mechanisms of hyperglycemia and impaired glucose tolerance in AP.

Methods: We injected ferrets with intraperitoneal cerulein (50 μg/kg, 9 hourly injections) or saline. Blood samples were collected for glucose (0, 4, 8, 12, 24h); TNF-α, IL-6 (6h); amylase, lipase, insulin, glucagon, pancreatic polypeptide (PP), glucagon-like peptide-1 (GLP-1), and gastric inhibitory polypeptide (GIP) (24h). Animals underwent oral glucose tolerance test (OGTT), mixed meal tolerance test (MMTT) at 24h or 3 months, followed by harvesting pancreas for histopathology and immunostaining.

Results: Cerulein-injected ferrets exhibited mild pancreatic edema, neutrophil infiltration, and elevations in serum amylase, lipase, TNF-α, IL-6, consistent with AP. Plasma glucose was significantly higher in ferrets with AP at all time points. Plasma glucagon, GLP-1 and PP were significantly higher in cerulein-injected animals, while plasma insulin was significantly lower compared to controls. OGTT and MMTT showed abnormal glycemic responses with higher area under the curve. The hypoglycemic response to insulin injection was completely lost, suggestive of insulin resistance. OGTT showed low plasma insulin; MMTT confirmed low insulin and GIP; abnormal OGTT and MMTT responses returned to normal 3 months after cerulein injection.

Conclusions: Acute cerulein injection causes mild acute pancreatitis in ferrets and hyperglycemia related to transient islet cell dysfunction and insulin resistance. The ferret cerulein model may contribute to the understanding of hyperglycemia in acute pancreatitis.
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http://dx.doi.org/10.1016/j.pan.2021.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355067PMC
August 2021

Copper-Catalyzed Three-Component Carboboronation of Allenes Using Highly Strained Cyclic Ketimines as Electrophiles.

Org Lett 2021 Jun 13;23(11):4431-4435. Epub 2021 May 13.

Department of Chemistry and Innovation Center of Pesticide Research, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, P. R. China.

A diastereoselective copper and NHC-ligand-catalyzed three-component difunctionalization of allenes with bis(pinacolato)diboron and 2-azirines to afford borylated allylaziridines is described. The reaction exhibits complete diastereoselectivity and good yields, and the further chlorination of the corresponding borylated products was also performed. It is believed that the high ring-strain force of 2-azirines facilitates the reaction. More chemical transformations of borylated allylaziridines are also reported.
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http://dx.doi.org/10.1021/acs.orglett.1c01372DOI Listing
June 2021

Radiomics Signature: A potential biomarker for the prediction of survival in Advanced Hepatocellular Carcinoma.

Int J Med Sci 2021 30;18(11):2276-2284. Epub 2021 Mar 30.

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

To develop and validate radiomics nomograms for the pretreatment predictions of overall survival (OS) and time to progression (TTP) in the patients with advanced hepatocellular carcinoma (HCC) treated with apatinib plus transarterial chemoembolization (TACE), and to assess the incremental value of the clinical-radiomics nomograms for estimating individual OS and TTP. A total of 60 patients with advanced HCC (BCLC stage C) treated with apatinib plus TACE were divided into a training set (n=48) and a validation set (n=12). The predictors identified from the clinical variables and the radiomics signature constructed from the computed tomography images, such as ɑ-fetoprotein level (AFP), formfactor, the grey level co-occurrence matrix, the gray level size zone matrix, and the gray level run-length matrix, were used to build the clinical-radiomics nomograms and the radiomics nomograms for the prediction of OS and TTP. Apatinib plus TACE benefited the patients with advanced HCC, with a 579-day median OS and a 270-day median TTP. The nomograms were built with the radiomics signature and AFP, and achieved favorable prediction efficacy with acceptable calibration curves. Decision curve analyses demonstrated that the clinical-radiomics nomograms outperformed the radiomics nomograms for the predictions of OS and TTP. Apatinib plus TACE may improve OS and prolonged TTP in the patients with advanced HCC. The clinical-radiomics nomograms, a noninvasive pretreatment prediction tool that incorporate radiomics signature and AFP, demonstrated good prediction accuracy for OS and TTP in these patients. These results indicate that the clinical-radiomics nomograms may provide novel insight for precise personalized medicine approaches in the patients with advanced HCC.
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http://dx.doi.org/10.7150/ijms.55510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100633PMC
March 2021

Identification of 15 lncRNAs Signature for Predicting Survival Benefit of Advanced Melanoma Patients Treated with Anti-PD-1 Monotherapy.

Cells 2021 04 22;10(5). Epub 2021 Apr 22.

Department of Radiation Oncology, Universitätsklinikum Erlangen, 91054 Erlangen, Germany.

The blockade of programmed cell death protein 1 (PD-1) as monotherapy has been widely used in melanoma, but to identify melanoma patients with survival benefit from anti-PD-1 monotherapy is still a big challenge. There is an urgent need for prognostic signatures improving the prediction of immunotherapy responses of these patients. We analyzed transcriptomic data of pre-treatment tumor biopsies and clinical profiles in advanced melanoma patients receiving only anti-PD-1 monotherapy (nivolumab or pembrolizumab) from the PRJNA356761 and PRJEB23709 data sets as the training and validation cohort, respectively. Weighted gene co-expression network analysis was used to identify the key module, then least absolute shrinkage and selection operator was conducted to determine prognostic-related long noncoding RNAs (lncRNAs). Subsequently, the differentially expressed genes between different clusters were identified, and their function and pathway annotation were performed. In this investigation, 92 melanoma patients with complete survival information (51 from training cohort and 41 from validation cohort) were included in our analyses. We initiallyidentified the key module (skyblue) by weighted gene co-expression network analysis, and then identified a 15 predictive lncRNAs (AC010904.2, LINC01126, AC012360.1, AC024933.1, AL442128.2, AC022211.4, AC022211.2, AC127496.5, NARF-AS1, AP000919.3, AP005329.2, AC023983.1, AC023983.2, AC139100.1, and AC012615.4) signature in melanoma patients treated with anti-PD-1 monotherapy by least absolute shrinkage and selection operator in the training cohort. These results were then validated in the validation cohort. Finally, enrichment analysis showed that the functions of differentially expressed genes between two consensus clusters were mainly related to the immune process and treatment. In summary, the 15 lncRNAs signature is a novel effective predictor for prognosis in advanced melanoma patients treated with anti-PD-1 monotherapy.
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http://dx.doi.org/10.3390/cells10050977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143567PMC
April 2021
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