Publications by authors named "Jia Song"

637 Publications

Discovery and identification of a novel small molecule BCL-2 inhibitor that binds to the BH4 domain.

Acta Pharmacol Sin 2022 Aug 2. Epub 2022 Aug 2.

Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China.

The B-cell lymphoma 2 (BCL-2) protein family plays a pivotal role in regulating the apoptosis process. BCL-2, as an antiapoptotic protein in this family, mediates apoptosis resistance and is an ideal target for cell death strategies in cancer therapy. Traditional treatment modalities target BCL-2 by occupying the hydrophobic pocket formed by BCL-2 homology (BH) domains 1-3, while in recent years, the BH4 domain of BCL-2 has also been considered an attractive novel target. Herein, we describe the discovery and identification of DC-B01, a novel BCL-2 inhibitor targeting the BH4 domain, through virtual screening combined with biophysical and biochemical methods. Our results from surface plasmon resonance and cellular thermal shift assay confirmed that the BH4 domain is responsible for the interaction between BCL-2 and DC-B01. As evidenced by further cell-based experiments, DC-B01 induced cell killing in a BCL-2-dependent manner and triggered apoptosis via the mitochondria-mediated pathway. DC-B01 disrupted the BCL-2/c-Myc interaction and consequently suppressed the transcriptional activity of c-Myc. Moreover, DC-B01 inhibited tumor growth in vivo in a BCL‑2‑dependent manner. Collectively, these results indicate that DC-B01 is a promising BCL-2 BH4 domain inhibitor with the potential for further development.
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http://dx.doi.org/10.1038/s41401-022-00936-0DOI Listing
August 2022

Damage of brown planthopper (BPH) and rice leaf folder (LF) in parent plants lead to distinct resistance in ratoon rice.

Plant Signal Behav 2022 Dec;17(1):2096790

The Provincial Key Laboratory for Agricultural Pest Management of the Mountainous Region, Institute of Entomology, Guizhou University, Guiyang, China.

Herbivore-induced defense responses are often specific, whereas plants could induce distinct defense responses corresponding to infestation by different herbivorous insects. Brown plant hopper (BPH) , a phloem-feeding insect, and rice leaf folder (LF) , a chewing insect, are both specialist herbivores on rice. To characterize the distinct resistance primed by prior damage to these two specialist herbivores, we challenged rice plants with two herbivores during vegetative growth of parent plants and assessed plant resistance in subsequent ratoons. Here, we show that LF and BPH induce different suites of defense responses in parent rice plants, LF induced higher level of JA accumulation and transcripts, while BPH induced higher accumulation of SA and transcripts. Moreover, an apparent loss of LF resistance was observed in RNAi lines. Ratoon plants generated from parents receiving prior LF infestation exhibited higher jasmonic acid (JA) levels and elevated levels of transcripts of defense-related genes associated with JA signaling, while ratoon generated from parents receiving prior BPH infestation exhibited higher salicylic acid (SA) levels and elevated levels of transcripts of defense-related genes associated with SA signaling. Moreover, previous LF infestation obviously elevated ratoons resistance to LF, while previous infestation by BPH led to enhanced resistance in ratoons to BPH. Pre-priming of ratoons defense to LF was significantly reduced in and RNAi plant, but silencing and did not attenuate ratoons resistance to BPH. These results suggest that infestation of two specialist herbivores with different feeding styles in parent crop led to distinct defense responses in subsequent rations, and the acquired resistance to LF in ratoons is associated with priming of jasmonic acid-dependent defense responses.
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http://dx.doi.org/10.1080/15592324.2022.2096790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318313PMC
December 2022

Afterglow-Suppressed LuO:Eu Nanoscintillators for High-Resolution and Dynamic Digital Radiographic Imaging.

Inorg Chem 2022 Jul 12;61(29):11293-11305. Epub 2022 Jul 12.

School of Physics, Northeast Normal University, 5268 Renmin Street, Changchun 130024, China.

LuEuO nanoscintillators ( = 0.005, 0.01, 0.03, 0.05, 0.07, and 0.10) with red emission were synthesized by a coprecipitation method. It is found that their photo- and radioluminescence intensities increase with increasing Eu concentration until = 0.05. According to their concentration-dependent luminescence intensity ratios ((C)/(S)), the existing energy transfer from Eu(S) (occupying S sites) to Eu(C) (occupying C sites) can be confirmed. Based on the spectral data and density functional theory (DFT) calculations, the origin of LuO:Eu persistent luminescence at low concentration might be related to the tunneling processes between Eu (occupying C and S sites) and oxygen interstitials (O). After dispersing afterglow-suppressed LuO:Eu nanoscintillators into polymethyl methacrylate (PMMA) polymer-acetone solution, flexible PMMA-LuO:Eu composite films with high thermal stability and radiation resistance were fabricated by a doctor blade method. As the flexible composite film was used as an imaging plate, static X-ray images with high spatial resolution (5.5 lp/mm) under an extremely low dose of ∼1.1 μGy can be acquired. When a watch with a moving second hand was used as an object, the dynamic X-ray imaging can be realized under a dose rate of 55 μGy·s. Our results demonstrate that LuO:Eu nanoscintillators can be regarded as candidate materials for dynamic digital radiographic imaging.
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http://dx.doi.org/10.1021/acs.inorgchem.2c01417DOI Listing
July 2022

[Analysis of a pedigree with distal hereditary motor neuropathy type 2A caused by mutation in HSPB8 gene].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2022 Jun;39(6):621-624

Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, China.

Objective: To explore phenotypic and mutational characteristics of a pedigree with distal hereditary motor neuropathy (dHMN).

Methods: Clinical data of the proband and her family members was collected. Electrophysiology, muscle biopsy and whole exome sequencing were carried out for the proband.

Results: Patients of the family mainly presented with distal lower limb weakness. Electrophysiological test of the proband revealed distal motor neuropathy and sensory nerves were normal. Muscle biopsy suggested neurogenic atrophy of muscle fibers. Genetic analysis revealed a heterozygous c.421A>G (p.K141E) mutation in exon 2 of the HSPB8 gene, which was a hot spot mutation.

Conclusion: This family was the first reported HSPB8 related dHMN2A in Chinese population, and p.K141E was the causative mutation, which enriched the mutational spectrum of dHMN in China.
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http://dx.doi.org/10.3760/cma.j.cn511374-20210528-00450DOI Listing
June 2022

The state of therapy modalities in clinic for biliary tract cancer.

Front Biosci (Landmark Ed) 2022 Jun;27(6):185

Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, Hubei, China.

Biliary tract cancers (BTCs) include intrahepatic cholangiocarcinoma (iCCA), perihilar and distal cholangiocarcinoma (pCCA and dCCA), and gallbladder carcinoma based on the epithelial site of origin. BTCs are highly aggressive tumors associated with poor prognosis due to widespread metastasis and high recurrence. Surgery is the typical curative-intent treatment, yet the cornerstone of cure depends on the anatomical site of the primary tumor, and only a minority of patients (approximately 30%) has an indication necessitating surgery. Similarly, only a small subset of carefully selected patients with early iCCA who are not candidates for liver resection can opt for liver transplantation. Chemotherapy, target therapy, and immunotherapy are the main treatment options for patients who have advanced stage or unresectable disease. The genetic background of each cholangiocarcinoma subtype has been accurately described based on whole gene exome and transcriptome sequencing. Accordingly, precision medicine in targeted therapies has been identified to be aimed at distinct patient subgroups harboring unique molecular alterations. Immunotherapy such as immune checkpoint inhibitors (ICIs) was identified as antitumor responses in a minority of select patients. Current studies indicate that immunotherapy of adoptive cell therapy represents a promising approach in hematological and solid tumor malignancies, yet clinical trials are needed to validate its effectiveness in BTC. Herein, we review the progress of BTC treatment, stratified patients according to the anatomic subtypes of cholangiocarcinoma and the gene drivers of cholangiocarcinoma progression, and compare the efficacy and safety of chemotherapy, targeted therapy, and immunotherapy, which will be conducive to the design of individualized therapies.
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http://dx.doi.org/10.31083/j.fbl2706185DOI Listing
June 2022

Salicylic acid-based hypoxia-responsive chemodynamic nanomedicines boost antitumor immunotherapy by modulating immunosuppressive tumor microenvironment.

Acta Biomater 2022 08 17;148:230-243. Epub 2022 Jun 17.

School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China. Electronic address:

The delivery of salicylic acid or its derivatives to tumor tissue in the form of nanomedicine is critical for the studies on their potential synergistic mechanism in tumor therapy and chemoprevention considering the dangerous bleeding in the high-dose oral administration. To deepen the understanding of their role in adjusting immunosuppressive tumor microenvironment (ITM), herein, we firstly developed a hypoxia-sensitive Fe-5,5'-azosalicylic acid nanoscale coordination polymer nanomedicines (FeNCPs) via a "old drugs new tricks" strategy for synergistic chemodynamic therapy (CDT) and remodulation of ITM to elevate antitumor immunotherapy effect. PEGylated FeNCPs could be reductively cleaved to release 5-aminosalicylic acid (5-ASA) and ferric ions by azo-reductase under hypoxic conditions, which could induce tumor cell death by Fenton reaction-catalysis enhanced CDT and 5-ASA-converted carboxylquinone to promote the production of •OH. Meanwhile, cyclooxygenase-2 (COX-2) and its enzymatic product prostaglandin E (PGE), as immune negative regulatory molecules, can promote tumor progression and immune tolerance. The released 5-ASA as a COX inhibitor could suppress the expression of PGE, and Fe was employed to reeducate M2-like tumor-associated macrophages (TAMs) to M1-like phenotype, which could initiate antitumor immune response to reach better antitumor immunotherapy. This work broadens the application of salicylic acid derivatives in antitumor immunotherapy, and provides a new strategy for their "old drugs new tricks". STATEMENT OF SIGNIFICANCE: Cyclooxygenase-2 (COX-2) and its enzymatic product prostaglandin E2 (PGE), as immune negative regulatory molecules, facilitate the differentiation of immune cells into immunosuppressive cells to build the immunosuppressive tumor microenvironment, which can promote tumor progression and immune tolerance. Thus, down-regulation of COX-2/PGE expression may be a key approach to tumor treatments. Meanwhile, as a class of inhibitors of COX-2/PGE, the potential mechanism of aspirin or 5-aminosalicylic acid has been a mystery in tumor therapy and chemoprevention. To expand the application of aspirin family nanomedicine in biomedicine, herein, we firstly developed a hypoxia-sensitive Fe-5,5'-azosalicylic acid nanoscale coordination polymer nanomedicines via a "old drugs new tricks" strategy for synergistic chemodynamic therapy and remodulation of immunosuppressive tumor microenvironment to elevate antitumor immunotherapy effect.
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http://dx.doi.org/10.1016/j.actbio.2022.06.026DOI Listing
August 2022

Long noncoding RNA TNFRSF10A-AS1 promotes colorectal cancer through upregulation of HuR.

World J Gastroenterol 2022 May;28(20):2184-2200

Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China.

Background: Recent studies have emphasized the emerging importance of long noncoding RNAs (lncRNAs) in colorectal cancer (CRC). However, the functions and regulatory mechanisms of numerous lncRNAs in CRC have not been fully elucidated.

Aim: To explore the functional role and underlying molecular mechanisms of lncRNA TNFRSF10A-AS1 in CRC.

Methods: TNFRSF10A-AS1 expression was measured by quantitative real-time polymerase chain reaction in CRC, and the relationship between TNFRSF10A-AS1 levels and the clinicopathological features of CRC patients was analyzed. The effect of TNFRSF10A-AS1 expression on CRC proliferation and metastasis was examined and . Mechanistically, we investigated how TNFRSF10A-AS1 is involved in CRC as a competitive endogenous RNA.

Results: TNFRSF10A-AS1 was expressed at a high level in CRC and the upregulation of TNFRSF10A-AS1 was associated with advanced T grade and tumor size in CRC patients. A functional investigation revealed that TNFRSF10A-AS1 enhanced the proliferation, migration ability and invasion ability of colon cancer cells and . A mechanistic analysis demonstrated that TNFRSF10A-AS1 acted as a miR-3121-3p molecular sponge to regulate HuR expression, ultimately promoting colorectal tumorigenesis and progression.

Conclusion: TNFRSF10A-AS1 exerts a tumor-promoting function through the miR-3121-3p/HuR axis in CRC, indicating that it may be a novel target for CRC therapy.
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http://dx.doi.org/10.3748/wjg.v28.i20.2184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157619PMC
May 2022

Adipocyte-derived kynurenine promotes obesity and insulin resistance by activating the AhR/STAT3/IL-6 signaling.

Nat Commun 2022 06 17;13(1):3489. Epub 2022 Jun 17.

Department of Respiratory and Critical Care Medicine, the Center for Biomedical Research, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Aberrant amino acid metabolism is a common event in obesity. Particularly, subjects with obesity are characterized by the excessive plasma kynurenine (Kyn). However, the primary source of Kyn and its impact on metabolic syndrome are yet to be fully addressed. Herein, we show that the overexpressed indoleamine 2,3-dioxygenase 1 (IDO1) in adipocytes predominantly contributes to the excessive Kyn, indicating a central role of adipocytes in Kyn metabolism. Depletion of Ido1 in adipocytes abrogates Kyn accumulation, protecting mice against obesity. Mechanistically, Kyn impairs lipid homeostasis in adipocytes via activating the aryl hydrocarbon receptor (AhR)/Signal transducer and activator of transcription 3 /interleukin-6 signaling. Genetic ablation of AhR in adipocytes abolishes the effect of Kyn. Moreover, supplementation of vitamin B6 ameliorated Kyn accumulation, protecting mice from obesity. Collectively, our data support that adipocytes are the primary source of increased circulating Kyn, while elimination of accumulated Kyn could be a viable strategy against obesity.
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http://dx.doi.org/10.1038/s41467-022-31126-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205899PMC
June 2022

Calpain2 Upregulation Regulates EMT-Mediated Pancreatic Cancer Metastasis the Wnt/β-Catenin Signaling Pathway.

Front Med (Lausanne) 2022 30;9:783592. Epub 2022 May 30.

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China.

Calpains2 (CAPN2) is a calcium-dependent, non-lysosomal cysteine protease that plays critical roles in normal cellular functions and pathological processes, including tumorigenesis, cancer progression, and metastasis. However, the role and underlying regulatory mechanisms of CAPN2 in pancreatic cancer (PC) are still unknown. We found that CAPN2 is highly expressed in PC tissues and associated with poor PC prognosis by using The Cancer Genome Atlas (TCGA) datasets, Gene Expression Omnibus (GEO) datasets, and PC tissue arrays. CAPN2 downregulation significantly inhibited cell proliferation, migration, and invasion and regulated Wnt/β-catenin signaling pathway-mediated epithelial-mesenchymal transition (EMT) in PC cells. Our findings highlight the significance of CAPN2 in tumor regression and, thus, indicate that CAPN2 could be a promising target for PC treatment.
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http://dx.doi.org/10.3389/fmed.2022.783592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9189366PMC
May 2022

A novel rapid web investigation method for ecological agriculture patterns in China.

Sci Total Environ 2022 Jun 10;842:156653. Epub 2022 Jun 10.

State Key Laboratory of Resources and Environmental Information System, Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China. Electronic address:

The investigation of Ecological Agriculture (EA) patterns can reveal the differences, aggregation, and diversity of agricultural development, providing specific paths in agricultural development and environmental protection to achieve the Sustainable Development Goals. Although field surveys, literature analysis, and the method using administrative statistics can be employed to investigate EA records and determine EA distributions comprehensively, they still rely on manual operations that are generally unable to support the rapid and large-scale identification of EA patterns required by current agricultural sustainable researches. To address this issue, this paper proposes a novel and rapid approach for Ecological Agriculture Pattern Investigation Based on Web-text (WEAPI), with the ability to automatically acquire EA pattern records, including pattern type, occurrence time, precise location, and other relevant information. The proposed method is employed in a national-scale case study to investigate trends in Chinese Ecological Agriculture (CEA). Results of the study reveal WEAPI's ability to detect new trends in CEA via the latest news and the corresponding distributions. The WEAPI method can also exhibit the unknown patterns of the current Chinese agricultural development. Further validation experiments demonstrate that the proposed method achieves over 95 % precision in the pattern parse processes and an 87 % coverage rate at the town level of the official CEA pattern list. Moreover, WEAPI can provide dynamic changing analyses on the annual evolution of the EA patterns in each type. Despite limitations under sparse records in partial classes, the results reveal WEAPI as a promising and powerful tool for agricultural research and agricultural development planning.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156653DOI Listing
June 2022

sp. nov., a novel ligninase-producing Actinobacterium isolated from soil.

Int J Syst Evol Microbiol 2022 Jun;72(6)

Key Laboratory of Agricultural Microbiology of Heilongjiang Province, Northeast Agricultural University, Harbin 150030, PR China.

A novel ligninase-producing actinomycete, designated strain NEAU-G4, was isolated from a soil sample and subjected to a polyphasic taxonomic study to establish its status. According to 16S rRNA gene sequence comparisons, the isolate was identified as a member of the genus , with the highest sequence similarity to DSM 44496 (99.2 %). The whole-cell sugars contained galactose and arabinose. The amino acid of the cell wall was determined to be -diaminopimelic acid. The major fatty acids (>10 %) were C, C 9, C and C 7. The predominant menaquinone was identified as MK-8(H, ω-cycl). The major polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositol. Strain NEAU-G4 had a draft genome size of 6 405 167 bp, annotated with 5815 protein-coding genes. The DNA G+C content was 67.6 mol%. Phylogenetic analysis using the 16S rRNA gene and whole-genome sequences showed that strain NEAU-G4 formed a stable phyletic line with DSM 44496. The digital DNA-DNA hybridization and average nucleotide identity values between them were 63.7 % (60.8-66.5 %) and 95.5 %, respectively. Moreover, genomic analysis indicated that strain NEAU-G4 had the potential to degrade lignin and produce bioactive compounds. On the basis of genotypic analysis, physiological data, as well as phenotypic and chemotaxonomic characterizations, it is concluded that the organism be classified as representing a novel species of the genus , for which the name sp. nov. is proposed. The type strain is NEAU-G4 (=CCTCC AA 2020038=DSM 111936).
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http://dx.doi.org/10.1099/ijsem.0.005416DOI Listing
June 2022

Research letter: The impact of elexacaftor/tezacaftor/ivacaftor on adherence to nebulized maintenance therapies in people with cystic fibrosis.

J Cyst Fibros 2022 May 15. Epub 2022 May 15.

Centre for Heart Lung Innovation, University of British Columbia and St. Paul's Hospital, Vancouver, BC, Canada; Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.jcf.2022.05.005DOI Listing
May 2022

Noncoding RNAs related to the hedgehog pathway in cancer: clinical implications and future perspectives.

Mol Cancer 2022 05 17;21(1):115. Epub 2022 May 17.

Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, 110122, People's Republic of China.

Cancer is a type of malignant affliction threatening human health worldwide; however, the molecular mechanism of cancer pathogenesis remains to be elusive. The oncogenic hedgehog (Hh) pathway is a highly evolutionarily conserved signaling pathway in which the hedgehog-Patched complex is internalized to cellular lysosomes for degradation, resulting in the release of Smoothened inhibition and producing downstream intracellular signals. Noncoding RNAs (ncRNAs) with diversified regulatory functions have the potency of controlling cellular processes. Compelling evidence reveals that Hh pathway, ncRNAs, or their crosstalk play complicated roles in the initiation, metastasis, apoptosis and drug resistance of cancer, allowing ncRNAs related to the Hh pathway to serve as clinical biomarkers for targeted cancer therapy. In this review, we attempt to depict the multiple patterns of ncRNAs in the progression of malignant tumors via interactions with the Hh crucial elements in order to better understand the complex regulatory mechanism, and focus on Hh associated ncRNA therapeutics aimed at boosting their application in the clinical setting.
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http://dx.doi.org/10.1186/s12943-022-01591-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9112456PMC
May 2022

lncRNA PRADX is a Mesenchymal Glioblastoma Biomarker for Cellular Metabolism Targeted Therapy.

Front Oncol 2022 29;12:888922. Epub 2022 Apr 29.

School of Clinical Medicine, Hebei University, Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding, China.

Glioblastoma (GBM) is the most common and lethal type of primary malignant central nervous system (CNS) tumor with an extremely poor prognosis, and the mesenchymal subtype of GBM has the worst prognosis. Here, we found that lncRNA PRADX was overexpressed in the mesenchymal GBM and was transcriptionally regulated by RUNX1-CBFβ complex, overexpressed PRADX suppressed BLCAP expression interacting with EZH2 and catalyzing trimethylation of lysine 27 on histone H3 (H3K27me3). Moreover, we showed that BLCAP interacted with STAT3 and reduced STAT3 phosphorylation, overexpressed PRADX activated STAT3 phosphorylation, and promoted ACSL1 expression suppressing BLCAP expression, accelerating tumor metabolism. Finally, we determined that combined of ACSL1 and CPT1 inhibitors could reverse the accelerated cellular metabolism and tumor growth induced by PRADX overexpression and . Collectively, PRADX/PRC2 complex activated the STAT3 pathway and energy metabolism in relation to mesenchymal GBM progression. Furthermore, our findings provided a novel therapeutic strategy targeting the energy metabolism activity of GBM.
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http://dx.doi.org/10.3389/fonc.2022.888922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9106305PMC
April 2022

miRNA-320 inhibits colitis-associated colorectal cancer by regulating the IL-6R/STAT3 pathway in mice.

J Gastrointest Oncol 2022 Apr;13(2):695-709

Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Hebei Medical University, Shijiazhuang, China.

Background: Colitis-associated colorectal cancer (CAC) is a serious complication of inflammatory bowel disease (IBD). microRNA-320 (miRNA-320) promotes intestinal mucosal barrier repair in IBD and inhibits tumor progression. However, the role of miRNA-320 in the progression of CAC remains to be defined. We studied the mechanisms of miRNA-320 in the progression of CAC in mice.

Methods: CAC was induced in mice (C57BL/B6) by the administration of azoxymethane (AOM) and dextran sulfate sodium (DSS), and the mice were given a lentiviral vector (LV) overexpressing mmu-miRNA-320. The level of miRNA-320 was analyzed by quantitative real-time polymerase chain reaction (qPCR). Colonic inflammation, histological analysis, and tumorigenesis were evaluated. Ki-67 in colonic tissues was examined by immunohistochemistry. B-cell lymphoma-extra large (BCL-xl) and proliferating cell nuclear antigen (PCNA) expression was examined by Western blot. Furthermore, the proliferation, migration, and invasion of colorectal cancer (CRC) cells were evaluated. The levels of interleukin-6 receptor (IL-6R), signal transducer and activator of transcription 3 (STAT3), and phosphorylated-signal transducer and activator of transcription 3 (p-STAT3) were examined by Western blot and qPCR.

Results: miRNA-320 was downregulated in CAC mice (0.57±0.13 1.00±0.12, =-5.95, P<0.001). miRNA-320 decreased the disease activity index (DAI) scores, improved colonic inflammation, and inhibited tumor formation (tumor number: 8.00±2.90 13.67±2.73, =-3.49, P<0.01) in mice with CAC. miRNA-320 suppressed the expression of BCL-xl, PCNA, and Ki-67 (0.38±0.07 0.69±0.08, =-7.30, P<0.001). miRNA-320 inhibited colon cancer cell proliferation, migration, and invasion. miRNA-320 significantly inhibited the levels of IL-6R [colon tissue messenger RNA (mRNA): 4.06±1.44 10.05±1.55, =-6.94, P<0.001], STAT3, and p-STAT3 and . Silencing IL-6R expression partially reversed the IL-6R/STAT3-suppressing and tumor-inhibiting effect of miRNA-320.

Conclusions: miRNA-320 inhibits tumorigenesis in mice with CAC by suppressing IL-6R/STAT3 expression, and IL-6R is a target gene of miRNA-320.
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http://dx.doi.org/10.21037/jgo-22-237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086045PMC
April 2022

Well-Paired-Seq: A Size-Exclusion and Locally Quasi-Static Hydrodynamic Microwell Chip for Single-Cell RNA-Seq.

Small Methods 2022 07 6;6(7):e2200341. Epub 2022 May 6.

State Key Laboratory of Physical Chemistry of Solid Surfaces, The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Key Laboratory for Chemical Biology of Fujian Province, Collaborative Innovation Center of Chemistry for Energy Materials, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, P. R. China.

Single-cell RNA sequencing (scRNA-seq) is a powerful technology for revealing the heterogeneity of cellular states. However, existing scRNA-seq platforms that utilize bead-based technologies suffer from a large number of empty microreactors and a low cell/bead capture efficiency. Here, Well-paired-seq is presented, which consists of thousands of size exclusion and quasi-static hydrodynamic dual wells to address these limitations. The size-exclusion principle allows one cell and one bead to be trapped in the bottom well (cell-capture-well) and the top well (bead-capture-well), respectively, while the quasi-static hydrodynamic principle ensures that the trapped cells are difficult to escape from cell-capture-wells, achieving cumulative capture of cells and effective buffer exchange. By the integration of quasi-static hydrodynamic and size-exclusion principles, the dual wells ensure single cells/beads pairing with high density, achieving excellent efficiency of cell capture (≈91%), cell/bead pairing (≈82%), and cell-free RNA removal. The high utilization of microreactors and single cells/beads enable to achieve a high throughput (≈10 cells) with low collision rates. The technical performance of Well-paired-seq is demonstrated by collecting transcriptome data from around 200 000 cells across 21 samples, successfully revealing the heterogeneity of single cells and showing the wide applicability of Well-paired-seq for basic and clinical research.
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http://dx.doi.org/10.1002/smtd.202200341DOI Listing
July 2022

EIF4A3-induced circTOLLIP promotes the progression of hepatocellular carcinoma via the miR-516a-5p/PBX3/EMT pathway.

J Exp Clin Cancer Res 2022 May 5;41(1):164. Epub 2022 May 5.

Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, 430030, Wuhan, Hubei, People's Republic of China.

Background: Circular RNAs (circRNAs) function as crucial regulators in multiple cancers, including hepatocellular carcinoma (HCC). However, the roles of circRNAs in HCC remains largely unknown.

Methods: circTOLLIP was identified in HCC by screening of two public circRNA microarray datasets and detected in HCC cells and tissues through quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH). Gain- and loss-of-function assays were performed to confirm the biological effects of circTOLLIP on HCC in vitro and in vivo. Mechanistically, bioinformatics analysis of online databases, MS2-RNA pulldown, biotin-labeled circTOLLIP/miR-516a-5p RNA pulldown, RNA immunoprecipitation (RIP), luciferase reporter assay, fluorescence in situ hybridization assay (FISH) and RNA sequencing were used to confirm the regulation of Eukaryotic initiation factor 4A3 (EIF4A3) on circTOLLIP and the interaction among circTOLLIP, miR-516a-5p and PBX homeobox 3 (PBX3).

Results: circTOLLIP was significantly upregulated in HCC cells and tissues. High circTOLLIP expression was correlated with poor overall survival (OS) and disease-free survival (DFS) in patients. circTOLLIP promoted the proliferation and metastasis of HCC cells in vitro and in vivo. Mechanistically, EIF4A3 promoted the biogenesis of circTOLLIP without affecting its stability. Moreover, circTOLLIP sponged miR-516a-5p to elevate the expression of PBX3, thereby activating the epithelial-to-mesenchymal transition (EMT) pathway and facilitating tumor progression in HCC.

Conclusions: Our findings indicate that EIF4A3-induced circTOLLIP promotes the progression of HCC through the circTOLLIP/miR-516a-5p/PBX3/EMT axis.
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http://dx.doi.org/10.1186/s13046-022-02378-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9069765PMC
May 2022

Sarcopenic Obesity with Normal Body Size May Have Higher Insulin Resistance in Elderly Patients with Type 2 Diabetes Mellitus.

Diabetes Metab Syndr Obes 2022 19;15:1197-1206. Epub 2022 Apr 19.

Department of Geriatrics, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, People's Republic of China.

Objective: Data are limited regarding how body composition is linked to insulin resistance in elderly patients with type 2 diabetes mellitus (T2DM). We examined the association between body composition and insulin resistance in elderly T2DM patients.

Methods: The cross-sectional study included 488 Chinese elderly patients wth T2DM. Subjects were classified into four groups based on body composition: normal body composition (NBC), low muscle mass alone (LMM), high body fat alone (HBF), both low muscle mass and high body fat (LMMHBF).

Results: The percentage of subjects with LMMHBF was 14.5% (11.9% in men and 17.7% in women). Homeostasis model assessment of insulin resistance (HOMA2-IR) was higher in the LMMHBF group than in the HBF group (p = 0.045), and was also significantly higher in the LMMHBF or HBF group than in the NBC or LMM group. The HBF group showed the highest body mass index (BMI) of the four groups of different body compositions, and the LMMHBF group showed lower BMI than the HBF group; however, there was no significant difference in BMI or waist to hip ratio (WHR) between the LMMHBF group and the NBC group. The LMMHBF and HBF groups were significantly associated with increased risk of insulin resistance compared to the NBC group, with odds ratios (ORs) of 4.47 [95% confidence interval (CI) 2.06-9.68, p < 0.001] and 1.76 (95% CI 1.02-3.02, p = 0.041) respectively, even after the adjustment for covariates.

Conclusion: In China, though elderly T2DM patients with the body composition of sarcopenic obesity (as defined by coexistence of low muscle mass and high body fat) seemed to have normal body size, they exhibited the most severe degree and the highest risk of insulin resistance.
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http://dx.doi.org/10.2147/DMSO.S360942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9034890PMC
April 2022

Cilo-seq: highly sensitive cell-in-library-out single-cell transcriptome sequencing with digital microfluidics.

Lab Chip 2022 05 17;22(10):1971-1979. Epub 2022 May 17.

The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials, Department of Chemical Biology, Department of Chemical Engineering, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.

Single-cell RNA sequencing (scRNA-seq) plays a critical role in revealing genetic expression patterns at the single-cell level for cell type identification and rare transcript detection. Although there have been great advances in scRNA-seq methodologies, existing technologies still suffer from complexity and high cost, and an integrated platform for complete library construction is still lacking. Herein we describe Cilo-seq for high-performance scRNA-seq library construction in a single device with programmed and addressable droplet handling based on digital microfluidics. The platform is simultaneously accessible for convenient single-cell isolation, efficient nucleic acid amplification, low-loss nucleic acid purification and high-quality library preparation by leveraging specific interface design, tiny reaction volume, auxiliary magnetic field control and accurate droplet control. With a closed hydrophobic interface, the platform further reduces nucleic acid loss and exogenous background interference. Cilo-seq provides excellent detection sensitivity (1.4-fold improvement over tube-based methods), accuracy ( = 0.98) and cost efficiency (10-fold decrease in cost compared to tube-based methods), and holds great promise for studies of single-cell RNA biology.
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http://dx.doi.org/10.1039/d2lc00167eDOI Listing
May 2022

Identification of clinical and molecular features of recurrent serous borderline ovarian tumour.

EClinicalMedicine 2022 Apr 8;46:101377. Epub 2022 Apr 8.

State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Institute of Metabolism and Integrative Biology, Obstetrics and Gynecology Hospital of Fudan University, Fudan University, Shanghai 200438, China.

Background: Serous borderline ovarian tumour (SBOT) is the most common type of BOT. Fertility sparing surgery (FSS) is an option for patients with SBOT, though it may increase the risk of recurrence. The clinical and molecular features of its recurrence are important and need to be investigated in detail.

Methods: An internal cohort of 319 patients with SBOT was collected from Aug 1, 2009 to July 31, 2019 from the Obstetrics and Gynecology Hospital of Fudan University in China. An external cohort of 100 patients with SBOT was collected from Aug 1, 2009 to Nov 30, 2019 from the Shandong Provincial Hospital in China. The risk factors for the recurrence were identified by multivariate cox analysis. Several computational methods were tested to establish a prediction tool for recurrence. Whole genome sequencing, RNA-seq, metabolomics and lipidomics were used to understand the molecular characteristics of the recurrence of SBOT.

Findings: Five factors were significantly correlated with SBOT recurrence in a Han population: micropapillary pattern, advanced stage, FSS, microinvasion, and lymph node invasion. A random forest-based online recurrence prediction tool was established and validated using an internal cohort and an independent external cohort for patients with SBOT. The multi-omics analysis on the original SBOT samples revealed that recurrence is related to metabolic regulation of immunological suppression.

Interpretation: Our study identified several important clinical and molecular features of recurrent SBOT. The prediction tool we established could help physicians to estimate the prognosis of patients with SBOT. These findings will contribute to the development of personalised and targeted therapies to improve prognosis.

Funding: JL was funded by MOST 2020YFA0803600, 2018YFA0801300, NSFC 32071138, and SKLGE-2118 to Jin Li; JY was funded by the Initial Project for Young and Middle-aged Medical Talents of Wuhan City, Hubei Province ([2014] 41); HH was funded by MOST 2019YFA0801900 and 2020YF1402600 to He Huang; JS was funded by NSFC 22,104,080; CG was funded by Natural Science Foundation of Shanghai 20ZR1408800 and NSFC82171633; BL was funded by Natural Science Foundation of Shanghai 19ZR1406800.
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http://dx.doi.org/10.1016/j.eclinm.2022.101377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9011028PMC
April 2022

A polygenic risk score for nasopharyngeal carcinoma shows potential for risk stratification and personalized screening.

Nat Commun 2022 04 12;13(1):1966. Epub 2022 Apr 12.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.

Polygenic risk scores (PRS) have the potential to identify individuals at risk of diseases, optimizing treatment, and predicting survival outcomes. Here, we construct and validate a genome-wide association study (GWAS) derived PRS for nasopharyngeal carcinoma (NPC), using a multi-center study of six populations (6 059 NPC cases and 7 582 controls), and evaluate its utility in a nested case-control study. We show that the PRS enables effective identification of NPC high-risk individuals (AUC = 0.65) and improves the risk prediction with the PRS incremental deciles in each population (P ranging from 2.79 × 10 to 4.79 × 10). By incorporating the PRS into EBV-serology-based NPC screening, the test's positive predictive value (PPV) is increased from an average of 4.84% to 8.38% and 11.91% in the top 10% and 5% PRS, respectively. In summary, the GWAS-derived PRS, together with the EBV test, significantly improves NPC risk stratification and informs personalized screening.
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http://dx.doi.org/10.1038/s41467-022-29570-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9005522PMC
April 2022

Quantitative prediction error analysis to investigate predictive performance under predictor measurement heterogeneity at model implementation.

Diagn Progn Res 2022 Apr 7;6(1). Epub 2022 Apr 7.

Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.

Background: When a predictor variable is measured in similar ways at the derivation and validation setting of a prognostic prediction model, yet both differ from the intended use of the model in practice (i.e., "predictor measurement heterogeneity"), performance of the model at implementation needs to be inferred. This study proposed an analysis to quantify the impact of anticipated predictor measurement heterogeneity.

Methods: A simulation study was conducted to assess the impact of predictor measurement heterogeneity across validation and implementation setting in time-to-event outcome data. The use of the quantitative prediction error analysis was illustrated using an example of predicting the 6-year risk of developing type 2 diabetes with heterogeneity in measurement of the predictor body mass index.

Results: In the simulation study, calibration-in-the-large of prediction models was poor and overall accuracy was reduced in all scenarios of predictor measurement heterogeneity. Model discrimination decreased with increasing random predictor measurement heterogeneity.

Conclusions: Heterogeneity of predictor measurements across settings of validation and implementation reduced predictive performance at implementation of prognostic models with a time-to-event outcome. When validating a prognostic model, the targeted clinical setting needs to be considered and analyses can be conducted to quantify the impact of anticipated predictor measurement heterogeneity on model performance at implementation.
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http://dx.doi.org/10.1186/s41512-022-00121-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8988417PMC
April 2022

cGAS-STING mediates cytoplasmic mitochondrial-DNA-induced inflammatory signal transduction during accelerated senescence of pancreatic β-cells induced by metabolic stress.

FASEB J 2022 05;36(5):e22266

Department of Endocrinology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Type 2 diabetes mellitus (T2DM) is an age-related disease characterized by impaired pancreatic β cell function and insulin resistance. Recent studies have shown that the accumulation of senescent β cells under metabolic stress conditions leads to the progression of T2DM, while senolysis can improve the prognosis. However, the specific mechanism of β cell senescence is still unclear. In this study, we found that the increased load of senescence pancreatic β cells in both older mice and obese mice induced by high-fat diet (HFD) (DIO mice) was accompanied by activation of the Cyclic GMP-AMP synthase (cGAS) - stimulator of interferon genes (STING) pathway and using cGAS or STING small interfering RNA or STING inhibitor C176 to downregulate this pathway reduced the senescence-associated secretion profile (SASP) and senescence of Min6 cells treated with palmitic acid or hydrogen peroxide. C176 intervention in DIO mice also significantly reduced the inflammation and senescence of the islets, thereby protecting the function of pancreatic β cell and glucose metabolism. Our study further revealed that mitochondrial DNA (mtDNA) leakage under metabolic stress conditions was critical for the activation of the cGAS-STING pathway, which can be reversed by the mtDNA depleting agent ethidium bromide. Consistently, mtDNA leakage was more severe in older mice and was accelerated by a chronic HFD. In conclusion, we demonstrate that cytoplasmic mtDNA activates the cGAS-STING pathway to mediate SASP during the accelerated senescence of pancreatic β-cells induced by metabolic stress, and this process can be downregulated by the STING inhibitor C176.
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http://dx.doi.org/10.1096/fj.202101988RDOI Listing
May 2022

Improving the Acetic Acid Fermentation of by Enhancing the Energy Metabolism.

Front Bioeng Biotechnol 2022 8;10:815614. Epub 2022 Mar 8.

State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, China.

Energy metabolism is important for cell growth and tolerance against environment stress. In acetic acid fermentation by , the correlation coefficients of acid production rate with energy charge and ATP content were 0.9981 and 0.9826, respectively. The main energy metabolism pathway, including glycolysis pathway, TCA cycle, ethanol oxidation, pentose phosphate pathway, and ATP production, was constructed by transcriptome analysis. The effects of fermentation conditions, including dissolved oxygen, initial acetic acid concentration, and total concentration, on acetic acid fermentation and energy metabolism of were analyzed by using the RT-PCR method. The results showed the high energy charge inhibited glucose catabolism, and associated with the high ethanol oxidation rate. Consequently, a virtuous circle of increased ethanol oxidation, increased energy generation, and acetic acid tolerance was important for improving acetic acid fermentation.
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http://dx.doi.org/10.3389/fbioe.2022.815614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8957916PMC
March 2022

Glioma-derived exosomes hijack the blood-brain barrier to facilitate nanocapsule delivery via LCN2.

J Control Release 2022 05 25;345:537-548. Epub 2022 Mar 25.

Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Department of Neurosurgery, Tianjin Medical University General Hospital and Key Laboratory of Neurotrauma, Variation, and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin 300052, China. Electronic address:

Exosomes are small extracellular vehicles which could transport genetic materials and proteins between cells. Although there are reports about exosomes crossing the blood-brain barrier (BBB), the underlying mechanisms still need further study. We found that exosomes from primary brain tumors could upregulate the expression of Lipocalin-2 (LCN2) in bEnd.3 brain microvascular endothelial cells (BMVECs). Furthermore, exosomes increased the membrane fluidity of bEnd.3 cells in an LCN2 dependent manner. Both intraperitoneal injection and caudal vein injection of LCN2 increased the number of nanocapsules crossing the BBB. Evans Blue staining revealed that LCN2 does not interrupt the integrity of the BBB, as observed in the traumatic brain injury model. Tandem mass tags quantitative proteomics and bioinformatics analysis revealed that LCN2 is upregulated by exosomes via the JAK-STAT3 pathway, but not delivered from exosomes. Knocking down LCN2 in bEnd.3 cells significantly abrogated the effect of exosomes on BMVEC membrane fluidity. Previously, we have reported that 2-methacryloyloxyethyl phosphorylcholine (MPC) and a peptide crosslinker could encapsulate mAbs to achieve nanocapsules. The nanocapsules containing choline analogs could effectively penetrate the BBB to deliver therapeutic monoclonal antibodies (tAbs) to the glioma. However, the delivered tAbs could be significantly reduced by blocking the release of exosomes from the gliomas. Application of tAb nanocapsules prior to treatment with MK2206, an AKT pathway inhibitor that has been shown to inhibit the production of exosomes, resulted in a better combination. Insights from this study provide a mechanistic framework with regard to how glioblastomas hijack BMVECs using exosomes. In addition, we provide a strategy for maximizing the effect of the choline-containing nanocapsules and MK2206 combination. These results also demonstrate the therapeutic role of tAbs in glioblastoma and brain tumor metastasis, by shedding new light on strategies that can be used for BBB-penetrating therapies.
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http://dx.doi.org/10.1016/j.jconrel.2022.03.038DOI Listing
May 2022

Relationship Between Muscle Cramps and Diabetic Retinopathy in Patients with Type 2 Diabetes.

Diabetes Metab Syndr Obes 2022 15;15:827-837. Epub 2022 Mar 15.

Department of Endocrinology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, People's Republic of China.

Aim: Patients with type 2 diabetes (T2DM) often suffer from muscle cramps of varying severity. Studies have shown that muscle cramp is closely related to local microcirculation perfusion disorders. Diabetic retinopathy can not only reflect the microcirculation perfusion in the eye but also the systemic microcirculation in patients with diabetes. The aims of this study were to investigate the relationship between muscle cramps and diabetic retinopathy in patients with type 2 diabetes.

Methods: A total of 150 adult patients with type 2 diabetes were enrolled and administered a questionnaire on muscle cramping, along with a visual analogue scale for pain. Diabetic retinopathy (DR) was determined by using fundus photography and graded as non-proliferative DR (NPDR) and proliferative DR (PDR). To assess whether there was an association between the muscle cramps and diabetic retinopathy, we conducted binomial logistic regression analysis.

Results: Our study revealed that 48% of patients with T2DM experienced muscle cramps in the past three months. Patients self-reported suffering from muscle cramps exhibited a higher prevalence of DR (61% vs 38%, P < 0.05) and PDR (22% vs 4%, P < 0.05) compared with patients without muscle cramps. Serum 25-(OH) vitamin D, calcium, and magnesium levels were not significantly different between patients with and without muscle cramps. After adjusting for age, duration of diabetes, HbA1c, vitamin D, potassium, calcium, and magnesium, we demonstrated that diabetic retinopathy (OR, 2.18; 95% CI, 1.01-4.69; P< 0.05) and albumin (OR, 0.90; 95% CI, 0.82-1.00; P< 0.05) were highly associated with muscle cramps. Binomial logistic regression analysis also indicated that severity of DR is associated with muscle cramps. In addition, DR and PDR were found to be associated with muscle cramp frequency (P for trend < 0.05), duration (P for trend < 0.05), and pain severity (P for trend < 0.05).

Conclusion: Muscle cramps occur frequently in diabetes and are correlated with diabetic retinopathy and albumin. Patients with PDR exhibited a higher frequency, severity, and longer duration relative to those with NPDR or without DR. Our findings suggested that muscle cramps in individuals with T2DM might be a result of microvascular dysfunction. Modulation of microvascular perfusion might thus provide a therapeutic target for alleviating muscle cramps.
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http://dx.doi.org/10.2147/DMSO.S352735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8934164PMC
March 2022

Identification of Down-Regulated ADH1C is Associated With Poor Prognosis in Colorectal Cancer Using Bioinformatics Analysis.

Front Mol Biosci 2022 1;9:791249. Epub 2022 Mar 1.

School of Basic Medical Sciences, Hebei University, Baoding, China.

Colorectal cancer (CRC) is the second most deadly cancer in the whole world, with the underlying mechanisms largely indistinct. Therefore, we aimed to identify significant pathways and genes involved in the initiation, formation and poor prognosis of CRC using bioinformatics methods. In this study, we compared gene expression profiles of CRC cases with those from normal colorectal tissues from three chip datasets (GSE33113, GSE23878 and GSE41328) to identify 105 differentially expressed genes (DEGs) that were common to the three datasets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that the highest proportion of up-regulated DEGs was involved in extracellular region and cytokine-cytokine receptor interaction pathways. Integral components of membrane and bile secretion pathways were identified as containing down-regulated DEGs. 13 hub DEGs were chosen and their expression were further validated by GEPIA. Only four DEGs (ADH1C, CLCA4, CXCL8 and GUCA2A) were associated with a significantly lower overall survival after the prognosis analysis. Lower ADH1C protein level and higher CXCL8 protein level were verified by immunohistochemical staining and western blot in clinical CRC and normal colorectal tissues. In conclusion, our study indicated that the extracellular tumor microenvironment and bile metabolism pathways play critical roles in the formation and progression of CRC. Furthermore, we confirmed ADH1C being down-regulated in CRC and reported ADH1C as a prognostic predictor for the first time.
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http://dx.doi.org/10.3389/fmolb.2022.791249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8921497PMC
March 2022

Neuroimaging outcomes for writing epilepsy with generalized tonic clonic seizure: a case description and literature analysis.

Quant Imaging Med Surg 2022 Mar;12(3):2170-2177

Department of Neurology, Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Cangzhou, China.

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http://dx.doi.org/10.21037/qims-21-533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899960PMC
March 2022

Ameliorative Effects of Malonyl Ginsenoside from on Glucose-Lipid Metabolism and Insulin Resistance via IRS1/PI3K/Akt and AMPK Signaling Pathways in Type 2 Diabetic Mice.

Am J Chin Med 2022 10;50(3):863-882. Epub 2022 Mar 10.

College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, P. R. China.

Our previous study has revealed that malonyl-ginsenosides from (PG-MGR) play a crucial role in the treatment of T2DM. However, its potential mechanism was still unclear. In this study, we investigated the anti-diabetic mechanisms of action of PG-MGR in high fat diet-fed (HFD) and streptozotocin-induced diabetic mice and determined the main constituents of PG-MGR responsible for its anti-diabetic effects. Our results showed that 16 malonyl ginsenosides were identified in PG-MGR by HPLC-ESI-MS/MS. PG-MGR treatment significantly reduced fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels and improved insulin resistance and glucose tolerance. Simultaneously, PG-MGR treatment improved liver injury by decreasing aspartate aminotransferase (AST) and alanine aminotransferase (ALT) expression. Furthermore, Western blot analysis demonstrated that the protein expression levels of p-PI3K/PI3K, p-AKT/AKT, p-AMPK/AMPK, p-ACC/ACC and GLUT4 in liver and skeletal muscle were significantly up-regulated after PG-MGR treatment, and the protein expression levels of p-IRS-1/IRS-1, Fas and SREBP-1c were significantly reduced. These findings revealed that PG-MGR has the potential to improve glucose and lipid metabolism and insulin resistance by activating the IRS-1/PI3K/AKT and AMPK signal pathways.
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http://dx.doi.org/10.1142/S0192415X22500367DOI Listing
April 2022

Near-infrared spectroscopy and machine learning-based technique to predict quality-related parameters in instant tea.

Sci Rep 2022 03 9;12(1):3833. Epub 2022 Mar 9.

State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, 300457, China.

The traditional method for analyzing the content of instant tea has disadvantages such as complicated operation and being time-consuming. In this study, a method for the rapid determination of instant tea components by near-infrared (NIR) spectroscopy was established and optimized. The NIR spectra of 118 instant tea samples were used to evaluate the modeling and prediction performance of a combination of binary particle swarm optimization (BPSO) with support vector regression (SVR), BPSO with partial least squares (PLS), and SVR and PLS without BPSO. Under optimal conditions, Rp for moisture, caffeine, tea polyphenols, and tea polysaccharides were 0.9678, 0.9757, 0.7569, and 0.8185, respectively. The values of SEP were less than 0.9302, and absolute values of Bias were less than 0.3667. These findings indicate that machine learning can be used to optimize the detection model of instant tea components based on NIR methods to improve prediction accuracy.
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http://dx.doi.org/10.1038/s41598-022-07652-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8907319PMC
March 2022
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