Publications by authors named "Tian Lan"

312 Publications

Cellular fate of intersex differentiation.

Cell Death Dis 2021 Apr 12;12(4):388. Epub 2021 Apr 12.

Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Renmin Hospital of Wuhan University, Wuhan, China.

Infertile ovotestis (mixture of ovary and testis) often occurs in intersex individuals under certain pathological and physiological conditions. However, how ovotestis is formed remains largely unknown. Here, we report the first comprehensive single-cell developmental atlas of the model ovotestis. We provide an overview of cell identities and a roadmap of germline, niche, and stem cell development in ovotestis by cell lineage reconstruction and a uniform manifold approximation and projection. We identify common progenitors of germline stem cells with two states, which reveal their bipotential nature to differentiate into both spermatogonial stem cells and female germline stem cells. Moreover, we found that ovotestis infertility was caused by degradation of female germline cells via liquid-liquid phase separation of the proteasomes in the nucleus, and impaired histone-to-protamine replacement in spermatid differentiation. Notably, signaling pathways in gonadal niche cells and their interaction with germlines synergistically determined distinct cell fate of both male and female germlines. Overall, we reveal a cellular fate map of germline and niche cell development that shapes cell differentiation direction of ovotestis, and provide novel insights into ovotestis development.
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http://dx.doi.org/10.1038/s41419-021-03676-xDOI Listing
April 2021

A five-gene signature for predicting overall survival of esophagus adenocarcinoma.

Medicine (Baltimore) 2021 Apr;100(14):e25305

Department of Breast Surgery, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medicine University, Hangzhou Hospital of Traditional Chinese Medicine.

Abstract: Esophageal adenocarcinoma (EAC) is common and aggressive with increasing trend of incidence. Urgent need for an effective signature to assess EAC prognosis and facilitate tailored treatment is required.Differentially expressed mRNAs (DEMs) were identified by analyzing EAC tissues and adjacent normal samples from The Cancer Genome Atlas (TCGA). Then univariate regression analyses were performed to confirm prognostic DEMs. We used least absolute shrinkage and selection operator (LASSO) to build a prognostic mRNA signature whose performance was assessed by Kaplan-Meier curve, receiver operating characteristic (ROC). GSE72874 were used as an external test set. The performances of the signature were also validated in internal TCGA and external test sets. Gene set enrichment analysis (GSEA) and tumor immunity analysis were performed to decipher the biological mechanisms of the signature.A 5-mRNA signature consisted of SLC26A9, SINHCAF, MICB, KRT19, and MT1X was developed to predict prognosis of EAC. The 5-mRNA signature was promising as a biomarker for predicting 3-year survival rate of EAC in the internal test set, the entire TCGA set, and the external test set with areas under the curve (AUC) = 0.849, 0.924, and 0.747, respectively. Patients were divided into low- and high-risk groups based on risk scores of the signature. The high-risk group was mainly associated with cancer-related pathways and low levels of B cell infiltration.The 5-mRNA prognostic signature we identified can reliably predict prognosis and facilitate individualized treatment decisions for EAC patients.
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http://dx.doi.org/10.1097/MD.0000000000025305DOI Listing
April 2021

Low NLRP3 expression predicts a better prognosis of colorectal cancer.

Biosci Rep 2021 Apr 6. Epub 2021 Apr 6.

West China Hospital, Sichuan University, Chengdu, China.

Background: NOD-like receptor pyrin domain-3 (NLRP3) inflammasome activation is a double-edged sword in tumorigenesis. Whether NLRP3 is involved in the progression and prognosis of colorectal cancer (CRC) remains elucidated and is the focus of this study.

Methods: Immunohistochemistry (IHC) was applied on tissue microarray to determine the expression of NLRP3 in CRC patients. All 100 patients were divided into the low NLRP3 group and the high NLRP3 group according to their NLRP3 IHC scoring. Additionally, CRC xenografts were established by injecting HCT116 or RKO cells subcutaneously into nude mice. Cell proliferation and apoptosis were determined in HCT116 cells after treatment with NLRP3 inhibitor MCC950.

Results: NLRP3 expression was up-regulated in colon adenocarcinoma tissues compared with that in paracancerous tissues in CRC patients, HCT116 xenograft, and RKO xenograft. High NLRP3 level correlated with the advanced TNM classification of malignant tumors, the occurrence of distant metastasis, vascular invasion, and positive lymph nodes. Furthermore, Kaplan-Meier survival analysis revealed that a high NLRP3 level was associated with a low 5-year survival rate and even a low 10-year survival rate. Moreover, the multivariable Cox proportional hazards regression model implied that NLRP3 expression level was an independent risk factor for CRC prognosis. Inhibition of NLRP3 by MCC950 suppressed cell proliferation, induced cell apoptosis, and decreased mRNA levels of interleukin 1β and interleukin 18 in HCT116 cells.

Conclusions: High level of NLRP3 predicts poor survival in CRC patients. NLRP3 is a putative prognostic biomarker and a potential therapeutic target in CRC treatments.
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http://dx.doi.org/10.1042/BSR20210280DOI Listing
April 2021

Current Regulation and Property Study of Porous Anodic Alumina Films with a Periodic Pore Structure.

ACS Omega 2021 Mar 17;6(12):7988-7993. Epub 2021 Mar 17.

Department of Applied Physics, Hebei University of Technology, Tianjin 300401, China.

Porous anodic alumina (PAA) films with periodically modulated pore diameters are prepared by cyclic anodization of Al in a 0.6 M HPO solution at room temperature. Studies have demonstrated that the oscillating current signals have an important effect on the structures of PAA films. Scanning electron microscopy (SEM) images of the PAA film show that when the positive triangle wave current signal is applied, with the increase in the maximum current value, PAA gradually exhibits a symmetrically modulated pore diameter structure, and part of the pores generates slub-like branches. When the maximum current value is 60 mA, the effect of modulation on the pore diameter is the most obvious and the UV reflectance spectrum shows the lowest reflectivity. A sawtooth wave current signal will cause the generation of a V-shaped structure at the junction of adjacent oxide layers. This work provides important guidance for regulating the structure of PAA by changing the current signal.
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http://dx.doi.org/10.1021/acsomega.0c04452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014930PMC
March 2021

Bayesian analysis of coupled cellular and nuclear trajectories for cell migration.

Biometrics 2021 Apr 4. Epub 2021 Apr 4.

Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, ON, Canada.

Cell migration, the process by which cells move from one location to another, plays crucial roles in many biological events. While much research has been devoted to understand the process, most statistical cell migration models rely on using time-lapse microscopy data from cell trajectories alone. However, the cell and its associated nucleus work together to orchestrate cell movement, which motivates a joint analysis of coupled cell-nucleus trajectories. In this paper we propose a Bayesian hierarchical model for analyzing cell migration. We incorporate a bivariate angular distribution to handle the coupled cell-nucleus trajectories, and introduce latent motility status indicators to model a cell's motility as a time-dependent characteristic. An MCMC algorithm is provided for practical implementation of our model, which is used on real experimental data from MDA-MB-231 and NIH 3T3 cells. Through the fitted models, deeper insights into the migratory patterns of these experimental cell populations are gained, and their differences are quantified. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/biom.13468DOI Listing
April 2021

Towards Improving the Quality of Electrophysiological Signal Recordings by Using Microneedle Electrode Arrays.

IEEE Trans Biomed Eng 2021 Apr 2;PP. Epub 2021 Apr 2.

Electrophysiological signals are recorded generally by metal electrodes placed on body surface. For long term use, the signal quality may decay with the change of interface impedance between electrodes and skin due to the conductive hydrogel dehydration. Besides, electrodes may shift during body movements, which causes unstable signal recordings. To improve the quality of electrophysiological signal recordings on human body surface, in this work, a type of microneedle electrode array (MEA) with microneedles around 550 m in length was fabricated with a magnetization-induce self-assembly method. The experiments showed that compared with the commonly used dry electrode array, the MEA has lower and more stable interface impedance, especially when the electrode-skin interface is under unstable pressures. For electrophysiological signal recording, the MEA can acquire electromyography (EMG) with significantly lower noise energy, higher signal-to-noise ratio, and higher motion-classification accuracy based on the EMG pattern-recognition method. Additionally, high quality electrocardiography (ECG) can be recorded by using the MEA, where more accurate R-peaks are extracted in different scenarios. Besides, there was no report about any discomfort like bleeding or inflammation by all the subjects. These findings suggest that the microneedles on the MEA can penetrate through the corneum and reach the epidermis of the subjects, which could avoid the influence of corneum and fix the electrode on the body surface for high-quality signal recording especially during body movements. Furthermore, the microneedles would not touch the dermis, enabling a painless signal acquisition, which is beneficial to the applications of wearable human-machine interface technology.
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http://dx.doi.org/10.1109/TBME.2021.3070541DOI Listing
April 2021

[Effect of extract of Quzhou Aurantii Fructus on hepatic inflammation and NF-κB/NLRP3 inflammasome pathway in CCl_4-induced liver fibrosis mice].

Zhongguo Zhong Yao Za Zhi 2021 Mar;46(6):1474-1479

Quzhou People's Hospital Quzhou 324000,China.

To study the effect and mechanism of extract of Quzhou Aurantii Fructus(QAF) on liver inflammation in CCl_4-induced liver fibrosis mice. Totally 60 C57 BL/6 male mice were randomly divided into control group(distilled water, oral), model group(distilled water, oral), colchicines group(Col, colchicines 2 mg·kg~(-1)·d~(-1), oral), low-dose QAF group(QAF-L, QAF 100 mg·kg~(-1)·d~(-1), oral) and high-dose QAF group(QAF-H, QAF 300 mg·kg~(-1)·d~(-1), oral) by random number table method. The model group and each administration group were injected with carbon tetrachloride(CCl_4) 1 mL·kg~(-1)(CCl_4-olive oil 1∶4), twice a week, totally 6 weeks. After the last administration, the mice were sacrificed, and serum and liver tissue were collected. Serum ALT and AST levels were measured in each group to observe the liver function of mice. The pathological changes and inflammatory cell infiltration in liver were observed by HE staining and F4/80 immunohistochemical staining. The mRNA expressions of TNF-α, IL-18 and IL-1β were detected by RT-PCR. The protein expressions of IκBα, p-IKKα/β, p-p65, NLRP3, caspase-1 and cleaved caspase-1 were analyzed by Western blot. The results showed that QAF significantly reduced serum ALT and AST levels, and alleviated the degree of liver damage.The results of immunohistochemistry showed that QAF significantly reduced liver inflammatory cell infiltration in liver fibrosis mice. The results of RT-PCR and Western blot showed that QAF significantly inhibited mRNA expressions of TNF-α, IL-18 and IL-1β in liver of fibrosis mice. QAF also suppressed the degradation of IκBα protein and reduced p-IKKα/β, p-p65, NLRP3 and cleaved caspase-1 protein expressions. In conclusion, QAF improves CCl_4-induced liver fibrosis in mice. The mechanism may be related to the inhibition of NF-κB/NLRP3 inflammasome-mediated inflammation signaling pathway.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20201201.401DOI Listing
March 2021

Prophylactic transcatheter angiographic embolization reduces Forrest IIa ulcer rebleeding: A retrospective study.

Medicine (Baltimore) 2021 Mar;100(11):e23855

Department of Gastroenterology.

Abstract: The application of transcatheter angiographic embolization (TAE) is controversial in the treatment of ulcer bleeding. This study aims to determine rebleeding risk factors and evaluate the efficacy of prophylactic TAE (p-TAE) following endoscopic hemostasis in rebleeding prevention of Forrest lla ulcers.The medical records of Forrest lla ulcer patients who underwent endoscopic hemostasis (E group) and endoscopic hemostasis plus p-TAE (E + p-TAE group) in West China Hospital from May 2009 to May 2018 were retrospectively reviewed. Baseline characteristics, clinical efficacy, and rebleeding risk factors were analyzed.As a result, a total of 102 patients were included, with 75 and 27 patients in E and E + p-TAE group, respectively. Most of the baseline data in E and E + p-TAE group were similar except for the proportion of protruded non-bleeding visible vessel (NBVV) (E group vs E + p-TAE group, 50.7% vs 74.1%, P = .035). The rebleeding rate of E + p-TAE group (3.7%) was significantly lower than E group (24.0%) (P = .02). The protruded NBVV (OR: 6.896, 95% confidence interval [CI]: 1.532-30.642, P = .01) and employment of p-TAE (OR: 0.038, 95% CI: 0.003-0.448, P = .009) were identified as independent risk factors for Forrest IIa ulcer rebleeding. Additionally, log-rank test indicated the rebleeding occurrence was greatly reduced by p-TAE in patients with protruded NBVVs (P = .006).In conclusion, the protruded NBVV and employment of p-TAE were the independent risk factors tightly associated with rebleeding of Forrest IIa ulcer. P-TAE following endoscopic hemostasis could effectively prevent Forrest IIa ulcer from rebleeding.
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http://dx.doi.org/10.1097/MD.0000000000023855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982249PMC
March 2021

Swine Acute Diarrhea Syndrome Coronavirus Nucleocapsid Protein Antagonizes Interferon- Production Blocking the Interaction Between TRAF3 and TBK1.

Front Immunol 2021 22;12:573078. Epub 2021 Feb 22.

College of Animal Science, South China Agricultural University, Guangzhou, China.

Swine acute diarrhea syndrome coronavirus (SADS-CoV), first discovered in 2017, is a porcine enteric coronavirus that can cause acute diarrhea syndrome (SADS) in piglets. Here, we studied the role of SADS-CoV nucleocapsid (N) protein in innate immunity. Our results showed that SADS-CoV N protein could inhibit type I interferon (IFN) production mediated by Sendai virus (Sev) and could block the phosphorylation and nuclear translocation of interferon regulatory factor 3 (IRF3). Simultaneously, the IFN- promoter activity mediated by TANK binding kinase 1 (TBK1) or its upstream molecules in the RLRs signal pathway was inhibited by SADS-CoV N protein. Further investigations revealed that SADS-CoV N protein could counteract interaction between TNF receptor-associated factor 3 (TRAF3) and TBK1, which led to reduced TBK1 activation and IFN- production. Our study is the first report of the interaction between SADS-CoV N protein and the host antiviral innate immune responses, and the mechanism utilized by SADS-CoV N protein provides a new insight of coronaviruses evading host antiviral innate immunity.
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http://dx.doi.org/10.3389/fimmu.2021.573078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937869PMC
April 2021

Magnetic resonance imaging and contrast-enhanced ultrasound findings of a recurrent primary breast angiosarcoma: A case report.

Medicine (Baltimore) 2021 Feb;100(5):e24625

Department of Breast Surgery.

Rationale: Primary breast angiosarcoma (PBA) is a rare and overly aggressive entity and account for less than 1% of all breast cancer cases. PBA had a high rate of delayed preoperative diagnosis due to absent distinctive radiographic characteristics.

Patient Concerns: We report a case of a 47-year-old female patient who had a previous history of luminal cancer in the right breast with mastectomy; the patient complained of asymmetrically diffuse enlarged, accompanying with a painless mass in the left breast 12 years after the mastectomy of her right breast.

Diagnoses: The tumor mimicked idiopathic granulomatous mastitis on magnetic resonance imaging (MRI) at the first presentation. Contrast-enhanced ultrasound (CEUS) was performed for further lesion characterization and showed heterogeneous rapid hyper enhanced. An ultrasound-guided core needle biopsy was performed, and the pathology report indicated a breast angiosarcoma.

Interventions: The patient underwent a nipple-sparing simple mastectomy with immediate reconstruction of the left breast.

Outcomes: After 8 months later, the tumor recurred, CEUS and MRI examination suggested PBA recurrence, then re-excision with implant removal was performed, the patient had a lung metastasis 4 months later eventually died 22 months after diagnosis.

Lessons: It is not easy to diagnose PBA with the radiographic examination. This case's importance is by combining CEUS and MRI to reflect enhanced morphology and hemodynamic characteristics of PBA and help diagnose breast angiosarcomas.
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http://dx.doi.org/10.1097/MD.0000000000024625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870214PMC
February 2021

Co-treatment with disulfiram and glycyrrhizic acid suppresses the inflammatory response of chondrocytes.

J Orthop Surg Res 2021 Feb 12;16(1):132. Epub 2021 Feb 12.

The Orthopedics Department of The First Hospital of Kunming, Kunming, 650000, Yunnan, China.

Background: Osteoarthritis (OA) is a kind of systemic musculoskeletal disorder and a most important factor for causing disability and physical painfulness. Nevertheless, due to the fact that OA can be triggered by multiple etiological factors, this disease is hard to be cured. Therefore, it is of great necessity for us to find novel targets or drugs for OA treatment.

Materials And Methods: The chondrocytes were treated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP) to induce pyroptosis in OA. The cell proliferation was detected by Cell Counting Kit-8 assay (CCK-8 assay). Enzyme-linked immunosorbent assay (ELISA) was used for the detection of pyroptosis-related inflammatory factors. Then, the antagonists for gasdermin D (GSDMD) (disulfiram) and high mobility group box 1 (HMGB1) (glycyrrhizic acid) were used to treat the cell model to observe the effects of disulfiram and glycyrrhizic acid on the proliferation of chondrocytes in OA. The protein levels of pyroptosis-related inflammatory factors were measured by western blot, and the levels of aldehyde dehydrogenase (ALDH) and reactive oxygen species (ROS) were measured by corresponding commercial kits.

Results: After chondrocytes were induced by LPS and ATP, the cell proliferation was decreased and the expressions of pyroptosis-related inflammatory factors were increased. Disulfiram and glycyrrhizic acid treatment led to enhanced cell proliferation and increased expressions of pyroptosis-related inflammatory factors, while disulfiram showed better alleviative effects on the inflammation in chondrocytes in OA. However, co-treatment with disulfiram at a high concentration and glycyrrhizic acid did not result in higher proliferation of chondrocytes and alleviated inflammation, but led to oxidative stress.

Conclusion: In conclusion, co-treatment with disulfiram and glycyrrhizic acid at a standard concentration suppresses the inflammatory response of chondrocytes, which may provide guidance for the use of the drugs in the treatment of OA.
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http://dx.doi.org/10.1186/s13018-021-02262-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879531PMC
February 2021

Cordycepin Ameliorates Nonalcoholic Steatohepatitis via Activation of AMP-Activated Protein Kinase Signaling Pathway.

Hepatology 2021 Feb 12. Epub 2021 Feb 12.

Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China.

Background & Aims: Nonalcoholic fatty liver disease (NAFLD), especially the nonalcoholic steatohepatitis (NASH), have become a major cause of liver transplantation and liver-associated death. NASH is the hepatic manifestation of metabolic syndrome and is characterized by hepatic steatosis, inflammation, hepatocellular injury and different degrees of fibrosis. However, there is no FDA-approved medication to treat this devastating disease. Therapeutic activators of the AMP-Activated Protein Kinase (AMPK) have been proposed as a potential treatment for metabolic diseases such as NASH. Cordycepin, a natural product isolated from the traditional Chinese medicine Cordyceps militaris, has recently emerged as a promising drug candidate for metabolic diseases.

Approach & Results: We evaluated the effects of cordycepin on lipid storage in hepatocytes, inflammation, and fibrosis development in mice with NASH. Cordycepin attenuated lipid accumulation, inflammation and lipotoxicity in hepatocytes subjected to metabolic stress. In addition, cordycepin treatment significantly and dose-dependently decreased the elevated levels of serum aminotransferases in mice with diet-induced NASH. Furthermore, cordycepin treatment significantly reduced hepatic triglyceride accumulation, inflammatory cell infiltration and hepatic fibrosis in mice. In vitro and in vivo mechanistic studies revealed that a key mechanism linking the protective effects of cordycepin were AMPK phosphorylation-dependent, as indicated by the finding that treatment with the AMPK inhibitor Compound C abrogated cordycepin-induced hepatoprotection in hepatocytes and mice with NASH.

Conclusion: Cordycepin exerts significant protective effects against hepatic steatosis, inflammation, liver injury, and fibrosis in mice under metabolic stress through activation of the AMPK signaling pathway. Cordycepin might be a novel AMPK activator that can be used for the treatment of NASH.
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http://dx.doi.org/10.1002/hep.31749DOI Listing
February 2021

Circular RNA circDLC1 inhibits MMP1-mediated liver cancer progression via interaction with HuR.

Theranostics 2021 1;11(3):1396-1411. Epub 2021 Jan 1.

Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China.

circular RNAs (circRNAs) have been demonstrated to play a crucial role in cancer progression. KIAA1429, a key component of the m6A methyltransferase complex, has recently been reported to promote hepatocellular carcinoma (HCC) progression by regulating the m6A methylation. The aim of present study is to investigate the role of circular RNAs in KIAA1429-mediated HCC progression. RNA sequencing (RNA-seq) and methylated RNA immunoprecipitation sequencing (m6A-seq) were utilized to identify KIAA1429-regulated circRNAs. The effects of circDLC1 on proliferation and metastasis of hepatoma cells were examined and . RT-qPCR was used to measure the expression of circDLC1 in HCC tissues and hepatoma cells. RNA FISH, RIP assays and biotin-labeled RNA pull-down were used to investigate the downstream effector of circDLC1. The downstream targets of circDLC1 were identified using RNA-seq. Our data demonstrated that circDLC1 was downregulated in HCC tissues and closely relevant to favorable prognosis. Overexpression of circDLC1 inhibited the proliferation and motility of hepatoma cells and while silencing of circDLC1 played the opposite role. Mechanistic investigations revealed that circDLC1 could bind to RNA-binding protein HuR, which subsequently reduced the interaction between HuR and MMP1 mRNAs, and thus inhibited the expression of MMP1, ultimately contributing to inhibition of HCC progression. Our work suggests that circDLC1, a downstream target of KIAA1429, is a promising prognostic marker for HCC patients, and the circDLC1-HuR-MMP1 axis may serve as a potential therapeutic target for HCC treatment.
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http://dx.doi.org/10.7150/thno.53227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738888PMC
January 2021

The role of chemotherapy in patients with T1bN0M0 triple-negative breast cancer: a real-world competing risk analysis.

J Cancer 2021 1;12(1):10-17. Epub 2021 Jan 1.

Department of Breast Surgery, Guangxing Hospital Affiliated to Zhejiang Traditional Chinese Medicine University, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang, People's Republic of China.

The objective of the present study was to implement Kaplan-Meier analysis, competing risk analysis, and propensity score matching to evaluate whether the patients with T1bN0M0 triple-negative breast (TNBC) could benefit from adjuvant chemotherapy. A total of 1849 patients were identified in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. All eligible patients were divided into two cohorts, the chemotherapy (1155 patients) and the no-chemotherapy (694 patients) cohorts. Similar 5-year breast cancer-specific survival (BCSS) was observed in the chemotherapy and no-chemotherapy cohorts (96.1% vs. 96.0%, p=0.820). The results of the competing risk analysis showed a comparable 5-year breast cancer-specific death (BCSD) in both groups (chemotherapy 3.6% vs. no-chemotherapy 3.4%, p=0.778). Also, a higher 5-year other causes death (OCD) was observed in the no-chemotherapy cohort (0.7% vs. 5.4%, p<0.001). Multivariable competing risks regression models showed no association between chemotherapy and BCSS (HR, 1.21; 95%CI, 0.64-2.31; p=0.560). After 1:1 PSM, no significant difference was also observed for BCSD and OCD between two cohorts. The value of adjuvant chemotherapy in patients with T1bN0M0 TNBC is less than the present guidelines recommend, suggesting that de-escalated treatment could be a potentially beneficial strategy in appropriately selected patients.
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http://dx.doi.org/10.7150/jca.52540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738821PMC
January 2021

Detection and genetic characterization of porcine circovirus 4 (PCV4) in Guangxi, China.

Gene 2021 Mar 29;773:145384. Epub 2020 Dec 29.

Guangxi Center for Animal Disease Control and Prevention, Nanning 530001, China. Electronic address:

Porcine circovirus type 4 (PCV4), a novel circovirus, was identified in pigs with serious symptoms, including porcine dermatitis and nephropathy syndrome (PDNS)-like signs, in China in 2019. This study investigated the prevalence and genome diversity of PCV4 in pigs from Guangxi Province, China, between 2015 and 2019. Thirteen of 257 (5.1%) samples were positive for PCV4, 9 of these (69.2%) PCV4-positive samples were coinfected with PCV2 or PCV3, and one PCV4-positive sample was coinfected with both PCV2 and PCV3. Three complete PCV4 genomes shared 36.9-73.8% nucleotide similarity with other representative circovirus genomes. Phylogenetic analysis indicated that PCV4 was most closely related to bat-associated circovirus and mink circovirus. In summary, this is the first epidemiological investigation and evolutionary analysis of PCV4 in Guangxi Province, China, and the results provide insight into the molecular epidemiology of PCV4.
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http://dx.doi.org/10.1016/j.gene.2020.145384DOI Listing
March 2021

Four Immune-Related Long Non-coding RNAs for Prognosis Prediction in Patients With Hepatocellular Carcinoma.

Front Mol Biosci 2020 8;7:566491. Epub 2020 Dec 8.

Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Background: Long non-coding RNA (LncRNA) plays an important role in the occurrence and development of hepatocellular carcinoma (HCC). This study aims to establish an immune-related LncRNA model for risk assessment and prognosis prediction in HCC patients.

Methods: Hepatocellular carcinoma patient samples with complete clinical data and corresponding whole transcriptome expression were obtained from the Cancer Genome Atlas (TCGA). Immune-related genes were acquired from the Gene Set Enrichment Analysis (GSEA) website and matched with LncRNA in the TCGA to get immune-related LncRNA. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for screening the candidate LncRNAs and calculating the risk coefficient to establish the prognosis model. Patients were divided into a high-risk group and a low-risk group depending on the median risk score. The reliability of the prediction was evaluated in the validation cohort and the whole cohort. GSEA and principal component analysis were used for function evaluation.

Results: A total of 319 samples met the screening criteria and were randomly distributed across the training cohort and the validation cohort. After comparison with the IMMUNE_RESPONSE gene set and the IMMUNE_SYSTEM_PROCESS gene set, a total of 3094 immune-related LncRNAs were screened. Ultimately, four immune-related LncRNAs were used to construct a formula using LASSO regression. According to the formula, the low-risk group showed a higher survival rate than the high-risk group in the validation cohort and the whole cohort. The receiver operating characteristic curves data demonstrated that the risk score was more specific than other traditional clinical characteristics in predicting the 5-year survival rate for HCC.

Conclusion: The four-immune-related-LncRNA model can be used for survival prediction in HCC and guide clinical therapy.
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http://dx.doi.org/10.3389/fmolb.2020.566491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752774PMC
December 2020

Calculating the Wasserstein Metric-Based Boltzmann Entropy of a Landscape Mosaic.

Entropy (Basel) 2020 Mar 26;22(4). Epub 2020 Mar 26.

State Key Laboratory of Earth Surface Processes and Resource Ecology, Beijing Normal University, Beijing 100875, China.

Shannon entropy is currently the most popular method for quantifying the disorder or information of a spatial data set such as a landscape pattern and a cartographic map. However, its drawback when applied to spatial data is also well documented; it is incapable of capturing configurational disorder. In addition, it has been recently criticized to be thermodynamically irrelevant. Therefore, Boltzmann entropy was revisited, and methods have been developed for its calculation with landscape patterns. The latest method was developed based on the Wasserstein metric. This method incorporates spatial repetitiveness, leading to a Wasserstein metric-based Boltzmann entropy that is capable of capturing the configurational disorder of a landscape mosaic. However, the numerical work required to calculate this entropy is beyond what can be practically achieved through hand calculation. This study developed a new software tool for conveniently calculating the Wasserstein metric-based Boltzmann entropy. The tool provides a user-friendly human-computer interface and many functions. These functions include multi-format data file import function, calculation function, and data clear or copy function. This study outlines several essential technical implementations of the tool and reports the evaluation of the software tool and a case study. Experimental results demonstrate that the software tool is both efficient and convenient.
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http://dx.doi.org/10.3390/e22040381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516855PMC
March 2020

The Dynamic Changes of Gut Microbiota during the Perinatal Period in Sows.

Animals (Basel) 2020 Nov 30;10(12). Epub 2020 Nov 30.

College of Animal Science, National Engineering Research Center for Breeding swine Industry, South China Agricultural University, Guangzhou 510642, China.

The gut microbiota in sows is important for the health of the host, and potential benefits may also be transferred to piglets during pregnancy. Therefore, systematic studies investigating the changes in the gut microbiota of sows are needed to elucidate the microbial compositions and functions. This study was conducted at 12 time points to investigate the temporal variations in gut microbiota on Days 27, 46, 64, 81, 100, and 113 during gestation (G) and Days 3, 5, 7, 10, 14, and 21 during lactation (L). Results suggested that the gut microbiota changed across the perinatal period with microbial function and abundance varying between the prenatal and postnatal periods. The alpha diversity was higher in the postnatal period than in the prenatal period. Thirty-eight genera were distributed between the two periods with , , , and r being enriched in the prenatal period while , , , , , , , were enriched in the postnatal period. Analysis done at the different time points of the prenatal period suggested that Days 27 and 113 had more microbial biomarkers than other days. , , and were enriched on the 27th day, while bacteria belonging to the and were enriched on the 113th day. On the other hand, , , , and unclassified were enriched three days after delivery. Predicted microbial KO functions were also more enriched on Day 27 of the gestation period and Day 3 of the lactation period. Random forest, a machine learning method, was used to identify the top five important genera of , , , , and , while the most important function was arginine and proline metabolism. These systematic results provide important information for the gut microbiota of sows.
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http://dx.doi.org/10.3390/ani10122254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761118PMC
November 2020

N-Acetylcysteine Rescues Hippocampal Oxidative Stress-Induced Neuronal Injury Suppression of p38/JNK Signaling in Depressed Rats.

Front Cell Neurosci 2020 11;14:554613. Epub 2020 Nov 11.

Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.

Progression of neuronal deterioration within specific brain regions is considered as one of the principal bases for the development of major depressive disorders. Therefore, protects and promotes the maintaining of normal structure and function of neurons might be a potential therapeutic strategy in the treatment of depression. Here, we report that the antioxidant, N-acetylcysteine (NAC), inhibited neuronal injury through its capacity to reduce oxidative stress and exerted antidepressant effects. Specifically, we show that antioxidant enzyme activity was significantly decreased in the hippocampal CA1 region of depressive rats, while treatment with NAC (300 mg/kg, i.p.) produced neuroprotective effects against mitochondrial oxidative stress injuries and oxidative DNA damage in CA1 neurons of these rats. Moreover, NAC treatment alleviated neuronal injury resulting from neuroinflammation and apoptosis in depressed rats, effects that were associated with reductions in dendritic spine atrophy, and synapse deficits. These effects appear to involve a down-regulation of p38 mitogen-activated protein kinase (MAPK)-JNK signaling along with an up-regulation of ERK signaling within the hippocampal CA1 region. Moreover, this NAC treatment significantly ameliorated depression-like behaviors as indicated by performance in the sucrose preference and forced swim tests (FST). Taken together, these results reveal the potential involvement of oxidative stress in the generation of depression. And, the antidepressant-like effects exerted by NAC may involve reductions in this oxidative stress that can result in neuronal deterioration. Such neuroprotective effects of NAC may indicate a potential therapeutic strategy for the treatment of stress-related depression.
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http://dx.doi.org/10.3389/fncel.2020.554613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686549PMC
November 2020

Oncostatin M expression and mutation status regulate tumor-infiltration of immune cells and survival outcomes in cholangiocarcinoma.

Aging (Albany NY) 2020 11 7;12(21):21518-21543. Epub 2020 Nov 7.

Department of Pancreatico-Biliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China.

In this study, we used bioinformatics tools to analyze transcriptome data from cholangiocarcinoma (CCA) patients in multiple datasets (Sun Yat-sen University, TCGA and GSE32225 cohorts) to identify mechanisms that regulate tumor infiltration by immune cells and survival outcomes. We identified 96 differentially expressed genes (DEGs), including 13 upregulated and 83 downregulated genes, in CCA tissues as regulatory T cells were significantly higher and the proportions of activated natural killer cells and monocytes were significantly lower in CCA tissues than the precancerous tissues. The survival outcomes of CCA patients were associated with the gene mutation status, levels of Oncostatin M (OSM) expression, and the proportions of tumor-infiltrating immune cell types, including dendritic cells, monocytes, and T follicular helper cells. Functional enrichment analysis of the DEGs in the high OSM-expressing CCA tissues showed that pathways related to tumor progression and immune response were significantly upregulated. Our study demonstrates that OSM expression and mutation status regulate the tumor infiltration by immune cells and survival outcomes in CCA. OSM is thus a potential prognostic biomarker and therapeutic target in cholangiocarcinoma.
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http://dx.doi.org/10.18632/aging.103936DOI Listing
November 2020

ARHGEF11 promotes proliferation and epithelial-mesenchymal transition of hepatocellular carcinoma through activation of β-catenin pathway.

Aging (Albany NY) 2020 10 29;12(20):20235-20253. Epub 2020 Oct 29.

Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu 610041, China.

Rho guanine nucleotide exchange factor 11 (ARHGEF11) has been proved to promote tumor metastasis in glioblastoma and ovarian carcinoma. However, the role of ARHGEF11 in hepatocellular carcinoma (HCC) progression is largely unknown. Here, we found that ARHGEF11 was upregulated in HCC samples and highly metastatic hepatoma cell lines. Knockdown of ARHGEFF11 inhibited the cell proliferation and invasion in both HCCLM3 and SKHEP1 cell lines. Subsequent mechanistic investigation showed that downregulation of ARHGEF11 significantly attenuated β-catenin nuclear translocation, thereafter repressed the expression of ZEB1 and cyclinD1, finally contributing to inhibition of epithelial-mesenchymal transition (EMT) and cell cycle arrest. Moreover, high levels of ARHGEF11 were found to be associated with shorter disease free and overall survival. A prognostic nomogram model that integrated ARHGEF11, tumor size and BCLC classification showed good performance in predicting clinical outcomes of HCC patients. Overall, this study demonstrated that ARHGEF11 could promote proliferation and metastasis of HCC via activating β-catenin pathway, suggesting that ARHGEF11 might serve as a potential prognostic biomarker for HCC.
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http://dx.doi.org/10.18632/aging.103772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655160PMC
October 2020

Underwater Ambiguity Elimination Method Based on Co-Prime Sensor Array.

Sensors (Basel) 2020 Oct 24;20(21). Epub 2020 Oct 24.

Acoustic Science and Technology Laboratory, Harbin Engineering University, Harbin 150001, China.

Recently, the direction of arrival estimation with co-prime arrays has gradually been applied in underwater scenarios because of its significant advantages over traditional uniform linear arrays. Despite the advantages of co-prime arrays, the spatial spectra obtained directly from conventional beamforming can be degraded by grating lobes due to the sparse spatial sampling in passive sensing applications, which will seriously deteriorate the estimation performance. In this paper, capon beamforming is applied to a co-prime sensor array as a pretreatment before high-resolution direction of arrival (DOA) estimation methods. The amplitudes extracted from the beam-domain outputs of two subarrays and the phases extracted from the cross-spectrum of the spatial spectrum are exploited to suppress the spurious peaks in beam patterns and eliminate ambiguities. Consequently, interference can be further mitigated, and the performance of high-resolution DOA methods will be guaranteed. Simulations show that the method proposed can improve the reliability and accuracy of DOA estimation with great value in practice.
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http://dx.doi.org/10.3390/s20216058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662939PMC
October 2020

Comparative pharmacokinetics of intravenous and intramuscular cefquinome sulfate administration in ducklings and goslings.

Am J Vet Res 2020 Nov;81(11):837-877

Objective: To compare the pharmacokinetics of cefquinome sulfate in ducklings and goslings after IV or IM administration of a single dose.

Animals: 216 healthy Muscovy ducklings () and 216 healthy Sichuan white goslings ().

Procedures: Ducklings and goslings were each randomly assigned to 3 groups (n = 72/group) that received a single dose (2 mg/kg) of injectable cefquinome sulfate administered IV or IM or of injectable cefquinome sulfate suspension administered IM. Blood samples were collected at various points after drug administration (n = 6 birds/time point). Plasma cefquinome concentrations were measured by high-performance liquid chromatography with UV detection, and pharmacokinetic parameters were calculated with a 2-compartment model method.

Results: After IV injection, mean distribution half-life of cefquinome was longer in goslings (0.446 hours) than in ducklings (0.019 hours), whereas volume of distribution at steady state was greater (0.432 vs 0.042 L/kg) and elimination half-life was slower (1.737 vs 0.972 hours). After IM administration of injectable cefquinome sulfate, bioavailability of the drug was higher in goslings (113.9%) than in ducklings (67.5%). After IM administration of injectable cefquinome sulfate suspension, bioavailability was also higher in goslings (123.1%) than in ducklings (96.8%), whereas elimination half-life was slower (6.917 vs 1.895 hours, respectively).

Conclusions And Clinical Relevance: In goslings, IV administration of cefquinome resulted in slower distribution and metabolism of the drug than in ducklings and IM administration resulted in higher bioavailability. The delayed-release effect of the injectable cefquinome sulfate suspension when administered IM was observed only in goslings.
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http://dx.doi.org/10.2460/ajvr.81.11.873DOI Listing
November 2020

Ultrasound-Combined Sterilization Technology: An Effective Sterilization Technique Ensuring the Microbial Safety of Grape Juice and Significantly Improving Its Quality.

Foods 2020 Oct 21;9(10). Epub 2020 Oct 21.

College of Food Science and Engineering, College of Enology, Northwest A&F University, Yangling 712100, China.

The effects of ultrasound (US), thermosonication (TS), ultrasound combined with nisin (USN), TS combined with nisin (TSN), and conventional thermal sterilization (CTS) treatments on the inactivation of microorganisms in grape juice were evaluated. TS, TSN, and CTS treatments provided the desirable bactericidal and enzyme inactivation, and nisin had a synergistic lethal effect on aerobic bacteria in grape juice while not having any obvious effect on the mold and yeast. Compared with CTS, the sensory characteristics of grape juice treated with TS and TSN are closer to that of fresh juice, its microbial safety is ensured, and the physicochemical properties are basically unchanged. More importantly, the total phenolic content and antioxidant capacity of juice treated with TS and TSN were significantly increased, and the total anthocyanin and flavonoid contents were largely retained. Taken together, these findings suggest that TS and TSN has great potential application value and that it can ensure microbial safety and improve the quality of grape juice.
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http://dx.doi.org/10.3390/foods9101512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590025PMC
October 2020

Sequencing dropout-and-batch effect normalization for single-cell mRNA profiles: a survey and comparative analysis.

Brief Bioinform 2020 Oct 19. Epub 2020 Oct 19.

Faculty of Engineering and IT in the University of Technology Sydney.

Single-cell mRNA sequencing has been adopted as a powerful technique for understanding gene expression profiles at the single-cell level. However, challenges remain due to factors such as the inefficiency of mRNA molecular capture, technical noises and separate sequencing of cells in different batches. Normalization methods have been developed to ensure a relatively accurate analysis. This work presents a survey on 10 tools specifically designed for single-cell mRNA sequencing data preprocessing steps, among which 6 tools are used for dropout normalization and 4 tools are for batch effect correction. In this survey, we outline the main methodology for each of these tools, and we also compare these tools to evaluate their normalization performance on datasets which are simulated under the constraints of dropout inefficiency, batch effect or their combined effects. We found that Saver and Baynorm performed better than other methods in dropout normalization, in most cases. Beer and Batchelor performed better in the batch effect normalization, and the Saver-Beer tool combination and the Baynorm-Beer combination performed better in the mixed dropout-and-batch effect normalization. Over-normalization is a common issue occurred to these dropout normalization tools that is worth of future investigation. For the batch normalization tools, the capability of retaining heterogeneity between different groups of cells after normalization can be another direction for future improvement.
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http://dx.doi.org/10.1093/bib/bbaa248DOI Listing
October 2020

Calcium-mediated parathyroid hormone suppression test in uraemic secondary hyperparathyroidism.

Nephrology (Carlton) 2021 Feb 18;26(2):164-169. Epub 2020 Nov 18.

Division of Nephrology, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu, China.

Aim: The present study aimed to investigate the value of calcium-mediated parathyroid hormone (PTH) suppression test in evaluating the autonomic secretory function of parathyroid, and the management of uraemic secondary hyperparathyroidism (SHPT).

Methods: Calcium-mediated PTH suppression test was performed in dialysis with SHPT, who were candidates for parathyroidectomy from June 2017 to December 2019 in our hospital. The PTH inhibition rate (PTH-IR) was calculated, and the correlation between PTH-IR and clinical indicators was explored.

Results: Fifty-one subjects were included. PTH-IR was negatively correlated with baseline PTH (r = -0.35, P = .012), it was also correlated with dialysis years, coronary artery calcification score (CACS) and parathyroid mass (r = -0.397, P = .004; r = -0.327, P = .028; r = -0.363, P = .015), which were not found for baseline PTH. Forty-four patients underwent surgical treatment. According to the histological results, 26 patients presented with parathyroid non-nodular hyperplasia, and 18 patients presented with parathyroid nodular hyperplasia. The mass of parathyroid of patients with nodular hyperplasia was higher than that of patients with non-nodular hyperplasia (ρ = 0.01). The difference of the PTH-IR was not found between the two groups (ρ = 0.296). During the test, the highest serum calcium was 2.9 ± 0.4 mmol/L, which dropped to normal at the end of the test.

Conclusion: Parathyroid hormone inhibition rate might be a useful indicator in evaluating the autonomic secretory function of parathyroid and the progression of SHPT on top of intact PTH. Calcium-mediated PTH suppression test was safe in uraemic SHPT patients, but need to monitor for transient hypercalcaemia.
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http://dx.doi.org/10.1111/nep.13807DOI Listing
February 2021

Carmustine as a Supplementary Therapeutic Option for Glioblastoma: A Systematic Review and Meta-Analysis.

Front Neurol 2020 17;11:1036. Epub 2020 Sep 17.

Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China.

Glioblastoma (GBM) is the most aggressive type of primary malignant brain tumor. Carmustine is used by intravenous injection or local implantation in the resection cavity for gliomas, including GBMs. However, the therapeutic potential of carmustine is not well-recognized. This analysis aimed to evaluate the survival benefits of carmustine in glioma patients, especially those with GBM. Randomized controlled trials (RCTs) and cohort studies regarding carmustine for glioma treatment were searched in PubMed, the Cochrane Library, and Embase from January 1979 to March 2020. Quality assessment was conducted with Jadad and Newcastle-Ottawa scales (NOS). Statistical analysis was conducted by the Revman 5.3 software. eligible RCTs and cohort studies involving 5,821 glioma patients were included. Overall, glioma patients receiving carmustine as an adjuvant therapy had better progression-free survival [PFS; hazard ratio (HR) = 0.85, 95% CI = 0.77-0.94, = 0.002] and overall survival (OS; HR = 0.85, 95% CI = 0.79-0.92, < 0.0001) than those without carmustine treatment. Subgroup analysis showed that the OS benefit was observed in GBM (HR = 0.84, 95% CI = 0.78-0.91, < 0.00001) but not in anaplastic glioma patients (HR = 1.20, 95% CI = 0.70-2.07, = 0.50). Additionally, both newly diagnosed and recurrent GBM patients who received carmustine treatment showed better OS (HR = 0.86, 95% CI = 0.79-0.95, = 0.002; HR = 0.77, 95% CI = 0.67-0.89, = 0.0002, respectively). Both carmustine implantation in resection cavity and intravenous administration significantly prolonged OS (HR = 0.84, 95% CI = 0.78-0.92, < 0.0001; HR = 0.86, 95% CI = 0.75-0.99, = 0.04, respectively). Moreover, GBM patients receiving a combined carmustine and temozolomide (TMZ) therapy had longer OS than those receiving TMZ alone (HR = 0.78, 95% CI = 0.63-0.97, = 0.03). Carmustine implantation in resection cavity provides survival benefit for GBM patients, and it may be a promising supplement to standard therapeutic protocol by offering a bridge between surgical resection and onset of TMZ therapy.
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http://dx.doi.org/10.3389/fneur.2020.01036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527463PMC
September 2020

Explore of the beneficial effects of Huang-Lian-Jie-Du Decoction on diabetic encephalopathy in db/db mice by UPLC-Q-Orbitrap HRMS/MS based untargeted metabolomics analysis.

J Pharm Biomed Anal 2021 Jan 28;192:113652. Epub 2020 Sep 28.

Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administration of TCM and Engineering & Technology Research Center for Chinese Materia Medica Quality of Guangdong Province, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China; School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China. Electronic address:

Diabetic encephalopathy (DE) is a severe diabetic complication with cognitive dysfunction. Huang-Lian-Jie-Du Decoction (HLJDD), a famous traditional Chinese formula, is effective for the treatment of diabetes mellitus and Alzheimer's disease in clinical practices, however, the therapeutic effects and the underlying mechanisms of HLJDD on DE is unclear yet. With this purpose, behavior test, brain histological and biochemical analysis were estimated to assess the beneficial effects of HLJDD on DE. Plasma samples were collected for metabolomics analysis based on UPLC-Q-Orbitrap HRMS/MS and chemometric analysis. As a result, morris water maze test revealed that HLJDD could effectively improve the learning and memory abilities in db/db mice. Brain histological and biochemical analysis indicated that HLJDD could protect against neurodegeneration and oxidative stress in db/db mice. Meanwhile, a total of 21 potential biomarkers with significant differences were identified between Model group and Control group using untargeted metabolomics strategy. Among them, 11 metabolites showed a trend towards the normal levels after HLJDD intervention. These metabolites principally involved in glycerophospholipid metabolism, fatty acid β-oxidation, linoleic acid metabolism, glucose metabolism and glutathione metabolism based on the metabolic pathway analysis, which were regulated in DE model mice after HLJDD intervention. Generally, the results demonstrated that HLJDD had beneficial effects on DE, which could be mediated via ameliorating the metabolic disorders.
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http://dx.doi.org/10.1016/j.jpba.2020.113652DOI Listing
January 2021

Efficacy and safety of Kanglaite injection combined with chemotherapy for colorectal cancer: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2020 Sep;99(39):e22357

People's Hospital of QuZhou, Quzhou, Zhejiang province.

Background: The incidence and mortality of colorectal cancer are high. Chemotherapy is currently the commonly used therapeutic scheme, but there are drug resistance and toxic and side effects. Kanglaite (KLT) injection is a broad-spectrum anticancer drug extracted from Semen Coicis (Yi Yi Ren), which has been widely used in the treatment of colorectal cancer. Clinical practice shows that KLT injection combined with chemotherapy has certain therapeutic advantages, but there is a lacking of evidence of evidence-based medicine. The purpose of this study is to systematically investigate the efficacy and safety of KLT injection combined with chemotherapy in the treatment of colorectal cancer.

Methods: Randomized controlled trials of KLT injection combined with chemotherapy in the treatment of colorectal cancer were retrieved from English databases (PubMed, Embase, Web of Science, the Cochrane Library) and Chinese databases (China National Knowledge Infrastructure, Wanfang, Chongqing VIP Chinese Science and Technology Periodical Database, Chinese Biological and Medical database), as well as searching Baidu academic and Google academic manually, and the retrieval time was from their establishment to August 2020. Two researchers independently conducted data extraction and literature quality evaluation on the quality of the included literatures, and meta-analysis was conducted on the included literatures using RevMan 5.3 (developed by the UK's International Cochrane Collaboration).

Results: This study assessed the efficacy and safety of KLT injection combined with chemotherapy in the treatment of colorectal cancer by effective rate, Karnofsky Performance Status, Carcinoemybryonic Angtigen remission rate, pain remission rate, and incidence of adverse reactions etc. CONCLUSIONS:: This study will provide reliable evidence-based evidence for the clinical application of KLT injection combined with chemotherapy in the treatment of colorectal cancer.

Ethics And Dissemination: The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences.

Osf Registration Number: DOI 10.17605/OSF.IO/EKVAF.
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http://dx.doi.org/10.1097/MD.0000000000022357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523838PMC
September 2020

MicroRNA miR-155-5p knockdown attenuates Angiostrongylus cantonensis-induced eosinophilic meningitis by downregulating MMP9 and TSLP proteins.

Int J Parasitol 2021 Jan 20;51(1):13-22. Epub 2020 Sep 20.

Department of Pathogen Biology and Experimental Teaching Center of Preventive Medicine, Guangdong Provincial Key Laboratory of Tropical Disease, School of Public Health, Southern Medical University, Guangzhou 510515, PR China. Electronic address:

Angiostrongylus cantonensis infection is a major cause of eosinophilic meningitis (EM). Severe cases or cases that involve infants and children present poor prognoses. MicroRNAs (miRNAs), which are important regulators of gene expression in many biological processes, were recently found to be regulators of the host response to infection by parasites; however, their roles in brain inflammation caused by A. cantonensis are still unclear. The current study confirmed that miR-155-5p peaked at 21 days after A. cantonensis infection, and its expression was positively correlated with the concentration of excretory and secretory products (ESPs). We found that miR-155-5p knockdown lentivirus successfully ameliorated brain injury and downregulated the expression of major basic protein (MBP) in vivo, and the number of eosinophils in CSF (and the percentage of eosinophils in peripheral blood were also decreased in the miR-155-5p knockdown group. Moreover, the expression of several eosinophilic inflammation cytokines such as CCL6/C10, ICAM-1, and MMP9, declined after the miR-155-5p knockdown. SOCS1 protein, which is an important negative regulator of inflammation activation, was identified as a direct miR-155-5p target. We further detected the effect of miR-155-5p knockdown on phosphorylated-STAT3 and phosphorylated-p65 proteins, which were found to be negatively regulated by SOCS1 and play an important role in regulating the inflammatory response. We found that miR-155-5p knockdown decreased the activity of p-STAT3 and p-p65, thereby leading to lower expression of MMP9 and TSLP proteins, which were closely related to the chemotaxis and infiltration of eosinophils. Interestingly, the inhibition of p-STAT3 or p-p65 was found to induce the downregulation of miR-155-5p in an opposite manner. These observations suggest that a positive feedback loop was formed between miR-155-5p, STAT3, and NF-κB in A. cantonensis infection and that miR-155-5p inhibition might provide a novel strategy to attenuate eosinophilic meningitis.
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http://dx.doi.org/10.1016/j.ijpara.2020.07.013DOI Listing
January 2021