Publications by authors named "Xun Li"

691 Publications

TANK Promotes Pressure Overload Induced Cardiac Hypertrophy Activating AKT Signaling Pathway.

Front Cardiovasc Med 2021 3;8:687540. Epub 2021 Sep 3.

Division of Cardiology, TongRen Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

TANK (TRAF family member associated NF-κB activator) acts as a member of scaffold proteins participated in the development of multiple diseases. However, its function in process of cardiac hypertrophy is still unknown. In this study, we observed an increased expression of TANK in murine hypertrophic hearts after aortic banding, suggesting that TANK may be involved in the pathogenesis of cardiac hypertrophy. We generated cardiac-specific TANK knockout mice, and subsequently subjected to aortic banding for 4-8 weeks. TANK knockout mice showed attenuated cardiac hypertrophy and dysfunction compared to the control group. In contrast, cardiac-specific TANK transgenic mice showed opposite signs. Consistently, experiments revealed that TANK knockdown decreased the cell size and expression of hypertrophic markers. Mechanistically, AKT signaling was inhibited in TANK knockout mice, but activated in TANK transgenic mice after aortic banding. Blocking AKT signaling with a pharmacological AKT inhibitor alleviated the cardiac hypertrophy and dysfunction in TANK transgenic mice. Collectively, we identified TANK accelerates the progression of pathological cardiac hypertrophy and is a potential therapeutic target.
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http://dx.doi.org/10.3389/fcvm.2021.687540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446676PMC
September 2021

Multi-step validation of a deep learning-based system for the quantification of bowel preparation: a prospective, observational study.

Lancet Digit Health 2021 Sep 16. Epub 2021 Sep 16.

Department of Gastroenterology, Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, and Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, China. Electronic address:

Background: Inadequate bowel preparation is associated with a decrease in adenoma detection rate (ADR). A deep learning-based bowel preparation assessment system based on the Boston bowel preparation scale (BBPS) has been previously established to calculate the automatic BBPS (e-BBPS) score (ranging 0-20). The aims of this study were to investigate whether there was a statistically inverse relationship between the e-BBPS score and the ADR, and to determine the threshold of e-BBPS score for adequate bowel preparation in colonoscopy screening.

Methods: In this prospective, observational study, we trained and internally validated the e-BBPS system using retrospective colonoscopy images and videos from the Endoscopy Center of Wuhan University, annotated by endoscopists. We externally validated the system using colonoscopy images and videos from the First People's Hospital of Yichang and the Third Hospital of Wuhan. To prospectively validate the system, we recruited consecutive patients at Renmin Hospital of Wuhan University aged between 18 and 75 years undergoing colonoscopy. The exclusion criteria included: contraindication to colonoscopy, family polyposis syndrome, inflammatory bowel disease, history of surgery for colorectal or colorectal cancer, known or suspected bowel obstruction or perforation, patients who were pregnant or lactating, inability to receive caecal intubation, and lumen obstruction. We did colonoscopy procedures and collected withdrawal videos, which were reviewed and the e-BBPS system was applied to all colon segments. The primary outcome of this study was ADR, defined as the proportion of patients with one or more conventional adenomas detected during colonoscopy. We calculated the ADR of each e-BBPS score and did a correlation analysis using Spearman analysis.

Findings: From May 11 to Aug 10, 2020, 616 patients underwent screening colonoscopies, which evaluated. There was a significant inverse correlation between the e-BBPS score and ADR (Spearman's rank -0·976, p<0·010). The ADR for the e-BBPS scores 1-8 was 28·57%, 28·68%, 26·79%, 19·19%, 17·57%, 17·07%, 14·81%, and 0%, respectively. According to the 25% ADR standard for screening colonoscopy, an e-BBPS score of 3 was set as a threshold to guarantee an ADR of more than 25%, and so high-quality endoscopy. Patients with scores of more than 3 had a significantly lower ADR than those with a score of 3 or less (ADR 15·93% vs 28·03%, p<0·001, 95% CI 0·28-0·66, odds ratio 0·43).

Interpretation: The e-BBPS system has potential to provide a more objective and refined threshold for the quantification of adequate bowel preparation.

Funding: Project of Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision and Hubei Province Major Science and Technology Innovation Project.
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http://dx.doi.org/10.1016/S2589-7500(21)00109-6DOI Listing
September 2021

Gly-tRF enhances LCSC-like properties and promotes HCC cells migration by targeting NDFIP2.

Cancer Cell Int 2021 Sep 18;21(1):502. Epub 2021 Sep 18.

The First Clinical Medical College of Lanzhou University, Lanzhou University, 222 Tianshui South Road, Lanzhou, 730000, China.

Background: Accumulating evidence demonstrates that tRFs (tRNA-derived small RNA fragments) and tiRNAs (tRNA-derived stress-induced RNA), an emerging category of regulatory RNA molecules derived from transfer RNAs (tRNAs), are dysregulated in in various human cancer types and play crucial roles. However, their roles and mechanisms in hepatocellular carcinoma (HCC) and liver cancer stem cells (LCSCs) are still unknown.

Methods: The expression of glycine tRNA-derived fragment (Gly-tRF) was measured by qRT-PCR. Flow cytometric analysis and sphere formation assays were used to determine the properties of LCSCs. Transwell assays and scratch wound assays were performed to detect HCC cell migration. Western blotting was conducted to evaluate the abundance change of Epithelial-mesenchymal transition (EMT)-related proteins. Dual luciferase reporter assays and signalling pathway analysis were performed to explore the underlying mechanism of Gly-tRF functions.

Results: Gly-tRF was highly expressed in HCC cell lines and tumour tissues. Gly-tRF mimic increased the LCSC subpopulation proportion and LCSC-like cell properties. Gly-tRF mimic promoted HCC cell migration and EMT. Loss of Gly-tRF inhibited HCC cell migration and EMT. Mechanistically, Gly-tRF decreased the level of NDFIP2 mRNA by binding to the NDFIP2 mRNA 3' UTR. Importantly, overexpression of NDFIP2 weakened the promotive effects of Gly-tRF on LCSC-like cell sphere formation and HCC cell migration. Signalling pathway analysis showed that Gly-tRF increased the abundance of phosphorylated AKT.

Conclusions: Gly-tRF enhances LCSC-like cell properties and promotes EMT by targeting NDFIP2 and activating the AKT signalling pathway. Gly-tRF plays tumor-promoting role in HCC and may lead to a potential therapeutic target for HCC.
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http://dx.doi.org/10.1186/s12935-021-02102-8DOI Listing
September 2021

High serum uric acid may associate with the increased risk of colorectal cancer in females: A prospective cohort study.

Int J Cancer 2021 Sep 14. Epub 2021 Sep 14.

The First Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China.

Elevated serum uric acid (SUA) levels have been previously reported to play a role in multiple types of cancers. However, epidemiological studies evaluating SUA levels and colorectal cancer risk remain sparse. This cohort study included 444,462 participants between the ages of 40 and 69 years from the UK Biobank, followed-up from 2006 to 2010. Multivariable adjusted Cox regression models were used to estimate hazard ratios (HRs). During a mean follow-up of 6.6 years, 2,033 and 855 cases of colon and rectal cancers, respectively, were diagnosed. The multivariable-adjusted HRs for risks of colon cancer in the lowest uric acid categories (≤3.5 mg/dL) compared with the reference groups were 1.31 (95% confidence interval [CI]: 0.75-2.29) in males and 1.26 (95% CI: 1.03-1.55) in females. The HRs in the highest uric acid groups (>8.4 mg/dL) were 1.16 (95% CI: 0.83-1.63) in males and 2.00 (95% CI: 1.02-3.92) in females. The corresponding HRs of rectal cancer in the lowest uric acid groups compared with the reference group were 2.21 (95% CI: 1.15-4.23) in males and 0.98 (95% CI: 0.66-1.45) in females. The HRs in the highest uric acid groups were 1.35 (95% CI: 0.82-2.23) in males and 3.81 (95% CI: 1.38-10.56) in females. In conclusion, SUA showed a U-shaped association with colon cancer risk in both male and female populations. The same pattern was observed in male patients with rectal cancer. However, SUA levels were positively associated with occurrence of rectal cancer in female subjects. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/ijc.33807DOI Listing
September 2021

Broadband acoustic invisibility and illusions.

Sci Adv 2021 Sep 10;7(37):eabi9627. Epub 2021 Sep 10.

Institute of Geophysics, ETH Zürich, 8092 Zürich, Switzerland.

[Figure: see text].
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http://dx.doi.org/10.1126/sciadv.abi9627DOI Listing
September 2021

The US COVID Atlas: A dynamic cyberinfrastructure surveillance system for interactive exploration of the pandemic.

Trans GIS 2021 Aug 30;25(4):1741-1765. Epub 2021 Jun 30.

Division of Social Sciences Center for Spatial Data Science University of Chicago Chicago IL USA.

Distributed spatial infrastructures leveraging cloud computing technologies can tackle issues of disparate data sources and address the need for data-driven knowledge discovery and more sophisticated spatial analysis central to the COVID-19 pandemic. We implement a new, open source spatial middleware component (libgeoda) and system design to scale development quickly to effectively meet the need for surveilling county-level metrics in a rapidly changing pandemic landscape. We incorporate, wrangle, and analyze multiple data streams from volunteered and crowdsourced environments to leverage multiple data perspectives. We integrate explorative spatial data analysis (ESDA) and statistical hotspot standards to detect infectious disease clusters in real time, building on decades of research in GIScience and spatial statistics. We scale the computational infrastructure to provide equitable access to data and insights across the entire USA, demanding a basic but high-quality standard of ESDA techniques. Finally, we engage a research coalition and incorporate principles of user-centered design to ground the direction and design of Atlas application development.
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http://dx.doi.org/10.1111/tgis.12786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420397PMC
August 2021

De novo biosynthesis of tyrosol acetate and hydroxytyrosol acetate from glucose in engineered Escherichia coli.

Enzyme Microb Technol 2021 Oct 19;150:109886. Epub 2021 Aug 19.

Key Laboratory of Organo-Pharmaceutical Chemistry, Jiangxi Province, Gannan Normal University, Ganzhou, 341000, China. Electronic address:

Tyrosol and hydroxytyrosol derived from virgin olive oil and olives extract, have wide applications both as functional food components and as nutraceuticals. However, they have low bioavailability due to their low absorption and high metabolism in human liver and small intestine. Acetylation of tyrosol and hydroxytyrosol can effectively improve their bioavailability and thus increase their potential use in the food and cosmeceutical industries. There is no report on the bioproductin of tyrosol acetate and hydroxytyrosol acetate so far. Thus, it is of great significance to develop microbial cell factories for achieving tyrosol acetate or hydroxytyrosol acetate biosynthesis. In this study, a de novo biosynthetic pathway for the production of tyrosol acetate and hydroxytyrosol acetate was constructed in Escherichia coli. First, an engineered E. coli that allows production of tyrosol from simple carbon sources was established. Four aldehyde reductases were compared, and it was found that yeaE is the best aldehyde reductase for tyrosol accumulation. Subsequently, the pathway was extended for tyrosol acetate production by further overexpression of alcohol acetyltransferase ATF1 for the conversion of tyrosol to tyrosol acetate. Finally, the pathway was further extended for hydroxytyrosol acetate production by overexpression of 4-hydroxyphenylacetate 3-hydroxylase HpaBC.
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http://dx.doi.org/10.1016/j.enzmictec.2021.109886DOI Listing
October 2021

Biosynthesis of actarit using engineered Escherichia coli.

Enzyme Microb Technol 2021 Oct 3;150:109858. Epub 2021 Jul 3.

Key Laboratory of Organo-Pharmaceutical Chemistry, Gannan Normal University, Ganzhou, Jiangxi Province, 341000, China. Electronic address:

Actarit is widely regarded as a safe and effective drug for the treatment of rheumatoid arthritis. There is no report on the bioproductin of actarit so far. In this study, we demonstrated for the first time the development of an artificial actarit biosynthetic pathway in Escherichia coli. First, 4-aminophenylacetic acid is selected as precursor substrates for the production of actarit. Second, an N-acetyltransferase that can efficiently catalyse the esterification of acetyl-CoA and 4-aminophenylacetic acid to form actarit was discovered. Subsequently, an engineered E. coli that allows production of actarit from simple carbon sources was established. Finally, we further increased the production of actarit to 206 ± 16.9 mg/L by overexpression of shikimate dehydrogenase ydiB and shikimate kinase aroK.
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http://dx.doi.org/10.1016/j.enzmictec.2021.109858DOI Listing
October 2021

Transient Hydrodynamic Lattice Cooling by Picosecond Laser Irradiation of Graphite.

Phys Rev Lett 2021 Aug;127(8):085901

Walker Department of Mechanical Engineering, The University of Texas at Austin, Austin, Texas 78712, USA.

Recent theories and experiments have suggested hydrodynamic phonon transport features in graphite at unusually high temperatures. Here, we report a picosecond pump-probe thermal reflectance measurement of heat-pulse propagation in graphite. The measurement results reveal transient lattice cooling near the adiabatic center of a 15-μm-diameter ring-shape pump beam at temperatures between 80 and 120 K. While such lattice cooling has not been reported in recent diffraction measurements of second sound in graphite, the observation here is consistent with both hydrodynamic phonon transport theory and prior heat-pulse measurements of second sound in bulk sodium fluoride.
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http://dx.doi.org/10.1103/PhysRevLett.127.085901DOI Listing
August 2021

Genome-wide analyses of ATP-Binding Cassette (ABC) transporter gene family and its expression profile related to deltamethrin tolerance in non-biting midge Propsilocerus akamusi.

Aquat Toxicol 2021 Aug 19;239:105940. Epub 2021 Aug 19.

Tianjin Key Laboratory of Conservation and Utilization of Animal Diversity, Tianjin Normal University, Tianjin, China; Tianjin Key Laboratory of Animal and Plant Resistance, Tianjin Normal University, Tianjin, China. Electronic address:

Non-biting midges are dominant species in aquatic systems and often used for studying the toxicological researches of insecticides. ATP-binding cassette (ABC) transporters represent the largest known members in detoxification genes but is little known about their function in non-biting midges. Here, we selected Propsilocerus akamusi, widespread in urban streams, to first uncover the gene structure, location, characteristics, and phylogenetics of chironomid ABC transporters at genome-scale. Fifty-seven ABC transporter genes are located on four chromosomes, including eight subfamilies (ABCA-H). The ABCC, ABCG, and ABCH subfamilies experienced the duplication events to different degrees. The study showed that expression of the PaABCG17 gene is uniquely significantly elevated, with deltamethrin concentration increasing (1, 4, and 20 ug/L) both in RNA-seq and qPCR results. Additionally, the ABC transporter members of other six chironomids with assembled genomes are first described and used to investigate the characteristic of those living in the different adverse habitats. The ABC transporter frame for Propsilocerus akamusi and its transcriptomic results lay an important foundation for providing valuable resources for understanding the ABC transporter function in insecticide toxification of this species as well as those of other non-biting midges. The PaABCG17 gene is shown to play an important role in deltamethrin detoxification, and it functions need to be further investigated and might be used in the management of insecticide-resistance in chironomid adults.
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http://dx.doi.org/10.1016/j.aquatox.2021.105940DOI Listing
August 2021

Triage Modeling for Differential Diagnosis Between COVID-19 and Human Influenza A Pneumonia: Classification and Regression Tree Analysis.

Front Med (Lausanne) 2021 10;8:673253. Epub 2021 Aug 10.

Huashan Hospital, Fudan University, Shanghai, China.

The coronavirus disease 2019 (COVID-19) pandemic has lasted much longer than an influenza season, but the main signs, symptoms, and some imaging findings are similar in COVID-19 and influenza patients. The aim of the current study was to construct an accurate and robust model for initial screening and differential diagnosis of COVID-19 and influenza A. All patients in the study were diagnosed at Fuyang No. 2 People's Hospital, and they included 151 with COVID-19 and 155 with influenza A. The patients were randomly assigned to training set or a testing set at a 4:1 ratio. Predictor variables were selected based on importance, assessed by random forest algorithms, and analyzed to develop classification and regression tree models. In the optimal model A, the best single predictor of COVID-19 patients was a normal or high level of low-density lipoprotein cholesterol, followed by low level of creatine kinase, then the presence of <3 respiratory symptoms, then a highest temperature on the first day of admission <38°C. In the suboptimal model B, the best single predictor of COVID-19 was a low eosinophil count, then a normal monocyte ratio, then a normal hematocrit value, then a highest temperature on the first day of admission of <37°C, then a complete lack of respiratory symptoms. The two models provide clinicians with a rapid triage tool. The optimal model can be used to developed countries/regions and major hospitals, and the suboptimal model can be used in underdeveloped regions and small hospitals.
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http://dx.doi.org/10.3389/fmed.2021.673253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382719PMC
August 2021

Development of an artificial biosynthetic pathway for biosynthesis of (S)-reticuline based on HpaBC in engineered Escherichia coli.

Biotechnol Bioeng 2021 Aug 24. Epub 2021 Aug 24.

Key Laboratory of Organo-Pharmaceutical Chemistry, Gannan Normal University, Ganzhou, Jiangxi, China.

Benzylisoquinoline alkaloids (BIAs) are an important class of plant secondary metabolites with a variety of pharmacological activities. Although they are widely used, traditionally these compounds are extracted from natural sources because their structure is too complicated to achieve economically feasible chemical synthesis. Thus, microbial biosynthesis of BIAs is expected to reduce dependence on natural extracts. (S)-Reticuline is an important precursor for BIAs biosynthesis. Therefore, it is an attractive engineering target. In this study, we reported the development of a novel (S)-reticuline biosynthetic pathway based on 4-hydroxyphenylacetate 3-hydroxylase (HpaBC) in Escherichia coli. Then, we further improved the (S)-reticuline production to 307 ± 26.8 mg/L by increasing the availability of the precursor 3, 4-dihydroxyphenylacetaldehyde. The E. coli cell factory developed in this study can be used as a potential platform for further efficient biosynthesis of BIAs derivatives.
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http://dx.doi.org/10.1002/bit.27924DOI Listing
August 2021

Development and clinical evaluation of a rapid antibody lateral flow assay for the diagnosis of SARS-CoV-2 infection.

BMC Infect Dis 2021 Aug 23;21(1):860. Epub 2021 Aug 23.

Institute of Infectious Disease, The 1st Hospital, Lanzhou University, Lanzhou, China.

Background: The novel coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has quickly spread worldwide since its outbreak in December 2019. One of the primary measures for controlling the spread of SARS-CoV-2 infection is an accurate assay for its diagnosis. SARS-CoV-2 real-time PCR kits suffer from some limitations, including false-negative results in the clinic. Therefore, there is an urgent need for the development of a rapid antibody test kit for COVID-19 diagnosis.

Methods: The nuclear capsid protein (N) and spike protein 1 (S1) fragments of SARS-CoV-2 were expressed in Escherichia coli, and rapid antibody-based tests for the diagnosis of SARS-CoV-2 infection were developed. To evaluate their clinical applications, the serum from COVID-19 patients, suspected COVID-19 patients, recovering COVID-19 patients, patients with general fever or pulmonary infection, doctors and nurses who worked at the fever clinic, and health professionals was analyzed by the rapid antibody test kits. The serum from patients infected with Mycoplasma pneumoniae and patients with respiratory tract infection was further analyzed to test its cross-reactivity with other respiratory pathogens.

Results: A 47 kDa N protein and 67 kDa S1 fragment of SARS-CoV-2 were successfully expressed, purified, and renatured. The rapid antibody test with recombinant N protein showed higher positive rate than the rapid IgM antibody test with recombinant S1 protein. Clinical evaluation showed that the rapid antibody test kit with recombinant N protein had 88.56 % analytical sensitivity and 97.42 % specificity for COVID-19 patients, 53.48 % positive rate for suspected COVID-19 patients, 57.14 % positive rate for recovering COVID-19 patients, and 0.5-0.8 % cross-reactivity with other respiratory pathogens. The analytical sensitivity of the kit did not significantly differ in COVID-19 patients with different disease courses (p < 0.01).

Conclusions: The rapid antibody test kit with recombinant N protein has high specificity and analytical sensitivity, and can be used for the diagnosis of SARS-CoV-2 infection combined with RT-PCR.
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http://dx.doi.org/10.1186/s12879-021-06568-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381135PMC
August 2021

Circular RNA circ_Cabin1 promotes DNA damage in multiple mouse organs via inhibition of non-homologous end-joining repair upon PM exposure.

Arch Toxicol 2021 Oct 17;95(10):3235-3251. Epub 2021 Aug 17.

State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.

Fine particulate matter (PM) has been shown to induce DNA damage. Circular RNAs (circRNAs) have been implicated in various disease processes related to environmental chemical exposure. However, the role of circRNAs in the regulation of DNA damage response (DDR) after PM exposure remains unclear. In this study, male ICR mice were exposed to PM at a daily mean concentration of 382.18 μg/m for 3 months in an enriched-ambient PM exposure system in Shijiazhuang, China, and PM collected form Shijiazhuang was applied to RAW264.7 cells at 100 µg/mL for 48 h. The results indicated that exposure to PM induced histopathological changes and DNA damage in the lung, kidney and spleen of male ICR mice, and led to decreased cell viability, increased LDH activity and DNA damage in RAW264.7 cells. Furthermore, circ_Cabin1 expression was significantly upregulated in multiple mouse organs as well as in RAW264.7 cells upon exposure to PM. PM exposure also resulted in impairment of non-homologous end joining (NHEJ) repair via the downregulation of Lig4 or Dclre1c expression in vivo and in vitro. Importantly, circ_Cabin1 promoted PM-induced DNA damage via inhibiting of NHEJ repair. Moreover, the expression of circ_Cabin1 and Lig4 or Dclre1c was strongly correlated in multiple mouse organs, as well as in the blood. In summary, our study provides a new perspective on circRNAs in the regulation of DDR after environmental chemical exposure.
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http://dx.doi.org/10.1007/s00204-021-03138-5DOI Listing
October 2021

Chinese expert recommendations on management of hepatocellular carcinoma during COVID-19 pandemic: a nationwide multicenter survey.

HPB (Oxford) 2021 Jul 26. Epub 2021 Jul 26.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Background: This study aimed to investigate the work status of clinicians in China and their management strategy alteration for patients with hepatocellular carcinoma (HCC) during the COVID-19 pandemic.

Methods: A nationwide online questionnaire survey was conducted in 42 class-A tertiary hospitals across China. Experienced clinicians of HCC-related specialties responded with their work status and management suggestions for HCC patients during the pandemic.

Results: 716 doctors responded effectively with a response rate of 60.1%, and 664 were included in the final analysis. Overall, 51.4% (341/664) of clinicians reported more than a 60% reduction of the regular workload and surgeons declared the highest proportion of workload reduction. 92.5% (614/664) of the respondents have been using online medical consultation to substitute for the "face-to-face" visits. Adaptive adjustment for the treatment strategy for HCC was made, including the recommendations of noninvasive and minimally invasive treatments such as transcatheter arterial chemoembolization for early and intermediate stage. Targeted therapy has been the mainstay for advanced stage and also as a bridge therapy for resectable HCC.

Discussion: During the COVID-19 pandemic, online medical consultation is recommended to avoid social contact. Targeted therapy as a bridge therapy is recommended for resectable HCC considering the possibility of delayed surgery.
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http://dx.doi.org/10.1016/j.hpb.2021.07.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312214PMC
July 2021

ERK-Peptide-Inhibitor-Modified Ferritin Enhanced the Therapeutic Effects of Paclitaxel in Cancer Cells and Spheroids.

Mol Pharm 2021 Sep 9;18(9):3365-3377. Epub 2021 Aug 9.

College of Chemical Engineering, Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Jiangsu Provincial Key Laboratory for the Chemistry and Utilization of Agro-Forest Biomass, Jiangsu Key Laboratory of Biomass-Based Green Fuels and Chemicals, Nanjing Forestry University, Nanjing 210037, P. R. China.

Rational design of a drug delivery system with enhanced therapeutic potency is critical for efficient tumor chemotherapy. Many protein-based drug delivery platforms have been designed to deliver drugs to target sites and improve the therapeutic efficacy. In this study, paclitaxel (PTX) molecules were encapsulated within an apoferritin nanocage-based drug delivery system with the modification of an extracellular-signal-regulated kinase (ERK) peptide inhibitor at the C-terminus of ferritin (HERK). Apoferritin is an endogenous nano-sized spherical protein which has the ability to specially bind to a majority of tumor cells via interacting with transferrin receptor 1. The ERK peptide inhibitor is a peptide which can disrupt the interaction of MEK with ERK in the mitogen-activated protein kinase/ERK pathway. By combining the targeted delivery effect of ferritin and the inhibitory effect of the ERK peptide inhibitor, the newly fabricated ferritin carrier nanoparticle HERK could still be taken up by tumor cells, and it displayed higher cell cytotoxicity than the parent ferritin. After loading with PTX, HERK-PTX displayed a favorable anticancer effect in human breast cancer cells MDA-MB-231 and lung carcinoma cells A549. The remarkable inhibitory effect on MDA-MB-231 tumor spheroids was also identified. These results indicated that the constructed HERK nanocarrier is a promising multi-functional drug delivery vehicle to enhance the therapeutic effect of drugs in cancer therapy.
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http://dx.doi.org/10.1021/acs.molpharmaceut.1c00303DOI Listing
September 2021

Tetrahydroxy stilbene glycoside ameliorates Alzheimer's disease in APP/PS1 mice via glutathione peroxidase related ferroptosis.

Int Immunopharmacol 2021 Oct 29;99:108002. Epub 2021 Jul 29.

Department of Pharmacy, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing Engineering Research Center for Nervous System Drugs, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China. Electronic address:

Amyloid beta peptide (Aβ) has been confirmed to be an essential reason of Alzheimer's disease (AD) for a long time. Ferroptosis is a newly recognized oxidative cell death mechanism, which is highly related to AD. Recently, tetrahydroxy stilbene glycoside (TSG) has been beneficial in alleviating learning and memory of AD and aged mouse model. Unfortunately, the underlying mechanisms between TSG and ferroptosis in AD are poorly understood. Herein, we investigated whether neural cells in cerebral cortex and hippocampus that were seriously afflicted in APP/PS1 mice might be vulnerable to ferroptosis. Treatment with non-toxic TSG dose-dependently resisted Aβ-caused cytotoxic death in neuronal cells by regulating ferroptosis related proteins and enzymes in APP/PS1 mice. TSG also alleviated cellular oxidative stress and inflammatory damage in response to Aβ by attenuating the levels of oxidation products. Importantly, TSG administration abrogated Aβ-caused brain damage, indicating that TSG rescued brain cells. Subsequently, TSG promoted the activation of GSH/GPX4/ROS and Keap1/Nrf2/ARE signaling pathways. Notably, markers related to ferroptosis including increased lipid peroxidation, enhanced neuroinflammation such as NLRP3, and also the expression of DMT1, ACSL4 and NCOA4, were reduced by TSG administration. In addition, TSG enhanced antioxidative stress via the upregulation of SOD, and the expression of FTH1, CD98 and xCT. Taken together, our data indicated a novel mechanism of TSG in reversing Aβ-caused injury through restoring mitochondrial function via several signaling pathways, implying a promising candidate against neurodegenerative diseases especially AD. Hence, TSG should be taken into consideration during treatment of AD in the future.
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http://dx.doi.org/10.1016/j.intimp.2021.108002DOI Listing
October 2021

Steering non-Hermitian skin modes by synthetic gauge fields in optical ring resonators.

Opt Lett 2021 Aug;46(15):3512-3515

We show that the synthetic gauge fields for photons provide a versatile approach to generate and control the non-Hermitian skin effect. By utilizing indirectly coupled optical ring resonator arrays with long-range couplings and on-site gain and loss, we find that the skin effect appears once the gauge field is not an integer multiple of π. In addition to tunable localization direction, the skin modes display anisotropic behaviors with frequency-dependent decay length, which can be explained by the split subregion of the generalized Brillouin zone (GBZ) and an effective model under adiabatic elimination. Through numerical simulation, we can also demonstrate exotic features in propagation effects enabled by the skin effect, including asymmetric transmission and reconfigurable accumulation interface. Our study paves the way to dynamically steer skin modes, which may find applications in laser, optical switch, and signal processing.
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http://dx.doi.org/10.1364/OL.431904DOI Listing
August 2021

Detachable string magnetically controlled capsule endoscopy for detecting high-risk varices in compensated advanced chronic liver disease (CHESS1801): A prospective multicenter study.

Lancet Reg Health West Pac 2021 Jan 11;6:100072. Epub 2020 Dec 11.

Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

Background: Gastroesophageal varices is a serious complication of compensated advanced chronic liver disease (cACLD). Primary prophylaxis to reduce the risk of variceal hemorrhage is recommended if high-risk varices (HRV) are detected. We performed this study to compare the accuracy, patients' satisfaction and safety of detection of HRV by detachable string magnetically controlled capsule endoscopy (DS-MCCE) with esophagogastroduodenoscopy (EGD) as the reference.

Methods: We prospectively recruited participants with cACLD from 12 university hospitals (11 in China and one in the United Kingdom) between November 2018 and December 2019 (ClinicalTrials.gov, NCT03749954). All participants underwent DS-MCCE, followed by EGD within a week in a blinded fashion. Following endoscopy, and on the same day, participants were asked to fill in a satisfaction questionnaire regarding their experience.

Findings: A total of 105 eligible participants were enrolled. With EGD as the reference standard, the concordance index, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of DS-MCCE in diagnosis of HRV were 0•90 (95% confidence interval [CI]: 0•83-0•95), 92% (95% CI: 78-98%), 88% (95% CI: 78-95%), 80% (95% CI: 70-92%), 95% (95% CI: 90-100%), 7•91 (95% CI: 4•10-15•30), and 0•09 (95% CI: 0•03-0•30), respectively. The kappa score of 0•78 (95% CI: 0•65-0•90) suggested substantial agreement between DS-MCCE and EGD. Moreover, in participants undergoing EGD without sedation, the satisfaction of DS-MCCE was significantly better than that of EGD ( < 0•0001,  = 1•15 [95%CI: 0•88-1•42]). All participants confirmed the excretion of the capsule, and no adverse events occurred.

Interpretation: DS-MCCE is an accurate alternative to EGD for detecting HRV in cACLD, which is safe and associated with better satisfaction.

Funding: A full list of funding can be found in the Funding Support section.
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http://dx.doi.org/10.1016/j.lanwpc.2020.100072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315440PMC
January 2021

A pancreas tumor derived organoid study: from drug screen to precision medicine.

Cancer Cell Int 2021 Jul 27;21(1):398. Epub 2021 Jul 27.

Department of General Surgery, The First Hospital of Lanzhou University, The First Clinical Medical School of Lanzhou University, Lanzhou, 730000, Gansu, China.

Pancreatic ductal adenocarcinoma (PDAC) one of the deadliest malignant tumor. Despite considerable progress in pancreatic cancer treatment in the past 10 years, PDAC mortality has shown no appreciable change, and systemic therapies for PDAC generally lack efficacy. Thus, developing biomarkers for treatment guidance is urgently required. This review focuses on pancreatic tumor organoids (PTOs), which can mimic the characteristics of the original tumor in vitro. As a powerful tool with several applications, PTOs represent a new strategy for targeted therapy in pancreatic cancer and contribute to the advancement of the field of personalized medicine.
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http://dx.doi.org/10.1186/s12935-021-02044-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314636PMC
July 2021

Fabrication of an Anti-Reflective Microstructure on ZnS by Femtosecond Laser Bessel Beams.

Molecules 2021 Jul 14;26(14). Epub 2021 Jul 14.

State Key Laboratory of Transient Optics and Photonics, Xi'an Institute of Optics and Precision Mechanics of CAS, Xi'an 710119, China.

As an important mid-infrared to far-infrared optical window, ZnS is extremely important to improve spectral transmission performance, especially in the military field. However, on account of the Fresnel reflection at the interface between the air and the high-strength substrate, surface optical loss occurs in the ZnS optical window. In this study, the concave antireflective sub-wavelength structures (ASS) on ZnS have been experimentally investigated to obtain high transmittance in the far-infrared spectral range from 6 μm to 10 μm. We proposed a simple method to fabricate microhole array ASS by femtosecond Bessel beam, which further increased the depth of the microholes and suppressed the thermal effects effectively, including the crack and recast layer of the microhole. The influence of different Gaussian and Bessel beam parameters on the microhole morphology were explored, and three ASS structures with different periods were prepared by the optimized Bessel parameters. Ultimately, the average transmittance of the sample with the ASS microhole array period of 2.6 μm increased by 4.1% in the 6 μm to 10 μm waveband, and the transmittance was increased by 5.7% at wavelength of 7.2 μm.
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http://dx.doi.org/10.3390/molecules26144278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307567PMC
July 2021

Embryonic Stem Cell-Derived Exosomes Attenuate Transverse Aortic Constriction Induced Heart Failure by Increasing Angiogenesis.

Front Cardiovasc Med 2021 28;8:638771. Epub 2021 Jun 28.

Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, China.

Although there are concerns regarding their clinical use, embryonic stem cells (ESCs) hold a great promise for cardiac repair. Exosomes deriving from ESCs constitute a promising alternative for heart restoration. However, their effects in hypertension-induced heart failure are still unknown. To investigate the effects of ESCs-derived exosomes on hypertension-induced heart failure and the underlying mechanisms, sustained transverse aortic constriction (TAC) was performed on 8-week-old C57BL/6 male mice. After 1 months, ESCs-derived exosomes were isolated and injected intravenously once a week for 6 weeks. Echocardiography, wheat germ agglutinin (WGA), Masson staining, immunohistochemistry, and tube formation assays were all involved in our study. Proteomics analyses revealed that ESC-derived exosomes contain FGF2 protein. Tube formation induced by these exosomes could be inhibited by FGF2R siRNA interference. ESCs-derived exosomes evidently attenuated TAC-induced heart failure, improving cardiac function and promoting myocardial angiogenesis which can be attenuated by selective FGF2 inhibitor AZD4547. ESC-derived exosomes attenuate TAC-induced heart failure mostly by promoting myocardial angiogenesis. FGF2 signaling plays a vital role in the myocardial angiogenesis induced by ESC-derived exosomes.
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http://dx.doi.org/10.3389/fcvm.2021.638771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273241PMC
June 2021

Traditional Chinese Medicine in Cancer Care: An Overview of 5834 Randomized Controlled Trials Published in Chinese.

Integr Cancer Ther 2021 Jan-Dec;20:15347354211031650

Beijing University of Chinese Medicine, Beijing, China.

Background: Traditional Chinese medicine (TCM) is widely integrated into cancer care in China. An overview in 2011 identified 2384 randomized and non-randomized controlled trials (RCTs, non-RCTs) on TCM for cancer published in the Chinese literature. This article summarizes updated evidence of RCTs on TCM for cancer care.

Methods: We searched 4 main Chinese databases: China National Knowledge Infrastructure, Chinese Scientific Journal Database, SinoMed, and Wanfang. RCTs on TCM used in cancer care were analyzed in this bibliometric study.

Results: Of 5834 RCTs (477 157 cancer patients), only 62 RCTs were indexed in MEDLINE. The top 3 cancers treated were lung, stomach, and breast cancer. About 4752 RCTs (81.45%) tested TCM combined with conventional treatment, and 1082 RCTs (18.55%) used TCM alone for treating symptoms and side-effects. Herbal medicine was the most frequently used TCM modality (5087 RCTs; 87.20%). The most frequently reported outcome was symptom improvement (3712 RCTs; 63.63%) followed by quality of life (2725 RCTs; 46.71%), and biomarkers (2384 RCTs; 40.86%). The majority of RCTs (4051; 69.44%) concluded there were beneficial effects using either TCM alone or TCM plus conventional treatment compared with conventional treatment.

Conclusion: Substantial randomized trials demonstrated different types/stages of cancer were treated by various TCM modalities, alone or in combination with conventional medicine. Further evaluation on the effects and safety of TCM modalities focusing on outcomes such as quality of life is required.
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http://dx.doi.org/10.1177/15347354211031650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287414PMC
July 2021

Diagnostic Time Lag of Pediatric Haemophagocytic Lymphohistiocytosis and Patient Characteristics: A Retrospective Cohort Study.

Front Pediatr 2021 17;9:692849. Epub 2021 Jun 17.

Department of Pediatric Intensive Care Unit, Hunan Children's Hospital, Changsha, China.

The difficulties and challenges of applying the HLH-2004 diagnostic criteria to early identification and diagnosis of haemophagocytic lymphohistiocytosis have been fully addressed in previous studies. However, the distribution of the diagnostic time lag of haemophagocytic lymphohistiocytosis and related patient characteristics remain unclear. This study investigated the time lags between symptom onset and diagnosis and between hospital admission and diagnosis among pediatric patients with haemophagocytic lymphohistiocytosis, and identified factors that associated with a shorter or longer diagnostic time lag. The cohort of patients with haemophagocytic lymphohistiocytosis was drawn from a tertiary children's hospital and consisted of 122 pediatric patients. The distributions of symptom-to-diagnosis and admission-to-diagnosis time lags were assessed. Clinical characteristics within 48 h of admission and the fulfillment of HLH-2004 diagnostic criteria were compared among admission-to-diagnosis time lag categories. Logistic regression analyses were conducted to identify factors associated with an admission-to-diagnosis time lag >3 days. The median interval from first symptom onset to HLH diagnosis was 12 days (range 4-71 days) and the median interval from hospital admission to HLH diagnosis was 2 days (range 0-23 days). The following factors were negatively associated with admission-to-diagnosis > 3 days: Epstein-Barr virus infection; admission through pediatric intensive care unit; diagnosis established without NK-cell activity and soluble CD25 tests; the performance of all readily available diagnostic tests for HLH (within 48 and 72 h); concurrent fever, splenomegaly, and cytopenias within 48 h; hemophagocytosis, hypertriglyceridemia and/or hypofibrinogenemia within 48 h; and elevated ferritin, total bilirubin, alanine aminotransferase, and prothrombin time within 48 h. Our findings suggest that performance of adequate diagnostic tests for HLH is essential for early diagnosis of HLH. Once suspected, immediate and adequate diagnostic tests for HLH should be arranged for PICU patients. Improvements in diagnostic procedures and monitoring plans are needed to promote early diagnosis of HLH.
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http://dx.doi.org/10.3389/fped.2021.692849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247774PMC
June 2021

3D printing of functional nerve guide conduits.

Burns Trauma 2021 7;9:tkab011. Epub 2021 May 7.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China.

Nerve guide conduits (NGCs), as alternatives to nerve autografts and allografts, have been widely explored as an advanced tool for the treatment of peripheral nerve injury. However, the repairing efficiency of NGCs still needs significant improvements. Functional NGCs that provide a more favorable microenvironment for promoting axonal elongation and myelination are of great importance. In recent years, 3D printing technologies have been widely applied in the fabrication of customized and complex constructs, exhibiting great potential for tissue engineering applications, especially for the construction of functional NGCs. In this review, we introduce the 3D printing technologies for manufacturing functional NGCs, including inkjet printing, extrusion printing, stereolithography-based printing and indirect printing. Further, we summarize the current methods and strategies for constructing functional NGCs, such as designing special conduit architectures, using appropriate materials and co-printing with different biological cues. Finally, the challenges and prospects for construction of functional NGCs are also presented.
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http://dx.doi.org/10.1093/burnst/tkab011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240533PMC
May 2021

Satellite-based survey of extreme methane emissions in the Permian basin.

Sci Adv 2021 Jun 30;7(27). Epub 2021 Jun 30.

School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.

Industrial emissions play a major role in the global methane budget. The Permian basin is thought to be responsible for almost half of the methane emissions from all U.S. oil- and gas-producing regions, but little is known about individual contributors, a prerequisite for mitigation. We use a new class of satellite measurements acquired during several days in 2019 and 2020 to perform the first regional-scale and high-resolution survey of methane sources in the Permian. We find an unexpectedly large number of extreme point sources (37 plumes with emission rates >500 kg hour), which account for a range between 31 and 53% of the estimated emissions in the sampled area. Our analysis reveals that new facilities are major emitters in the area, often due to inefficient flaring operations (20% of detections). These results put current practices into question and are relevant to guide emission reduction efforts.
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http://dx.doi.org/10.1126/sciadv.abf4507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245034PMC
June 2021

Cardiac mechanical efficiency is preserved in primary cardiac hypertrophy despite impaired mechanical function.

J Gen Physiol 2021 Aug 28;153(8). Epub 2021 Jun 28.

Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand.

Increased heart size is a major risk factor for heart failure and premature mortality. Although abnormal heart growth subsequent to hypertension often accompanies disturbances in mechano-energetics and cardiac efficiency, it remains uncertain whether hypertrophy is their primary driver. In this study, we aimed to investigate the direct association between cardiac hypertrophy and cardiac mechano-energetics using isolated left-ventricular trabeculae from a rat model of primary cardiac hypertrophy and its control. We evaluated energy expenditure (heat output) and mechanical performance (force length work production) simultaneously at a range of preloads and afterloads in a microcalorimeter, we determined energy expenditure related to cross-bridge cycling and Ca2+ cycling (activation heat), and we quantified energy efficiency. Rats with cardiac hypertrophy exhibited increased cardiomyocyte length and width. Their trabeculae showed mechanical impairment, evidenced by lower force production, extent and kinetics of shortening, and work output. Lower force was associated with lower energy expenditure related to Ca2+ cycling and to cross-bridge cycling. However, despite these changes, both mechanical and cross-bridge energy efficiency were unchanged. Our results show that cardiac hypertrophy is associated with impaired contractile performance and with preservation of energy efficiency. These findings provide direction for future investigations targeting metabolic and Ca2+ disturbances underlying cardiac mechanical and energetic impairment in primary cardiac hypertrophy.
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http://dx.doi.org/10.1085/jgp.202012841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241536PMC
August 2021

Hair growth predicts a depression-like phenotype in rats as a mirror of stress traceability.

Neurochem Int 2021 09 21;148:105110. Epub 2021 Jun 21.

Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, Hunan University of Chinese Medicine, Changsha Hunan, 410208, China; State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. Electronic address:

As a subjective mood-related disorder with an unclear mechanism, depression has many problems in its diagnosis, which offers great space and value for research. At present, the methods commonly used to judge whether an animal model of depression has been established are mainly by biochemical index detection and behavioral tests, both of which inevitably cause stress in animals. Stress-induced hair growth inhibition has been widely reported in humans and animals. The simplicity of collecting hair samples and the observable state of hair growth has significant advantages; we tried to explore whether the parameters related to hair growth could be used as auxiliary indicators to evaluate a depression model in animals. The length and weight of the hair were calculated. Correlation analysis was conducted between the depressive behavioral results and the glucocorticoid levels in hair and serum. Learned helplessness combined with chronic restraint stress, and chronic unpredictable stress in the animal were detectable by superficial observation, weight ratio, and length of hair, and follicular development scores were significantly reduced compared to the control. The hair growth parameters of rats with depression, the rise in corticosterone, and the corresponding changes in behavioral parameters were significantly correlated. The neurotrophic factors, glucocorticoid-receptor (GR), brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2), and fibroblast growth factor 5 (FGF5), are associated with depression and hair growth. Significant differences were detected between the stress and control groups, suggesting that the mechanism underlying the stress-phenomenon inhibition of hair growth may be related to growth factor mediation.
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http://dx.doi.org/10.1016/j.neuint.2021.105110DOI Listing
September 2021

Long non-coding RNA NORAD inhibition upregulates microRNA-323a-3p to suppress tumorigenesis and development of breast cancer through the PUM1/eIF2 axis.

Cell Cycle 2021 Jul 14;20(13):1295-1307. Epub 2021 Jun 14.

Department of Thyroid and Breast Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Long non-coding RNAs (lncRNAs) are known to competitively bind with microRNAs (miRNAs) to participate in human cancers. We aim to explore the role of non-coding RNA activated by DNA damage (NORAD) binding to miR-323a-3p in breast cancer (BC) with the involvement of pumilio RNA-binding family member 1 (PUM1)/eukaryotic initiation factor 2 (eIF2) axis. Expression of NORAD, miR-323a-3p and PUM1 in tissues and cell lines was detected, and the correlation between NORAD expression and clinicopathological features of BC patients was analyzed. The screened cell line was respectively transfected with altered NORAD or miR-323a-3p to reveal their roles in viability, migration, invasion and apoptosis of BC cells . The tumor growth was observed in nude mice. The binding relationships among NORAD, miR-323a-3p and PUM1 were analyzed, and the regulatory role of NORAD and miR-323a-3p in the eIF2 signaling pathway was assessed. NORAD and PUM1 were upregulated and miR-323a-3p was downregulated in BC. High NORAD expression indicated a poor prognosis of BC patients. NORAD inhibition or miR-323a-3p elevation inhibited malignant behaviors of BC cells. The assay revealed that NORAD inhibition or miR-323a-3p elevation inhibited tumor growth as well. MiR-323a-3p inhibition reversed the role of NORAD knockdown in the biological functions of BC cells while silencing PUM1 reversed the influence of NORAD overexpression on BC cells. NORAD bound with miR-323a-3p and miR-323a-3p targeted PUM1. NORAD and miR-323a-3p functioned through the PUM1/eIF2 axis. NORAD inhibition or miR-323a-3p elevation suppresses the development of BC through the PUM1/eIF2 axis.
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http://dx.doi.org/10.1080/15384101.2021.1934627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8331030PMC
July 2021

The Anti-Neuroinflammatory Effect of Fuzi and Ganjiang Extraction on LPS-Induced BV2 Microglia and Its Intervention Function on Depression-Like Behavior of Cancer-Related Fatigue Model Mice.

Front Pharmacol 2021 28;12:670586. Epub 2021 May 28.

Hunan University of Chinese Medicine and Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, Changsha, China.

The Chinese herb couple Fuzi and Ganjiang (FG) has been a classic combination of traditional Chinese medicine that is commonly used clinically in China for nearly 2000 years. Traditional Chinese medicine suggests that FG can treat various ailments, including heart failure, fatigue, gastrointestinal upset, and depression. Neuroinflammation is one of the main pathogenesis of many neurodegenerative diseases in which microglia cells play a critical role in the occurrence and development of neuroinflammation. FG has been clinically proven to have an efficient therapeutic effect on depression and other neurological disorders, but its mechanism remains unknown. Cancer-related fatigue (CRF) is a serious threat to the quality of life of cancer patients and is characterized by both physical and psychological fatigue. Recent studies have found that neuroinflammation is a key inducement leading to the occurrence and development of CRF. Traditional Chinese medicine theory believes that extreme fatigue and depressive symptoms of CRF are related to deficiency, and the application of Yang tonic drugs such as Fuzi and Ganjiang can relieve CRF symptoms, but the underlying mechanisms remain unknown. In order to define whether FG can inhibit CRF depression-like behavior by suppressing neuroinflammation, we conducted a series of experimental studies and . According to the UPLC-Q-TOF/MS results, we speculated that there were 49 compounds in the FG extraction, among which 30 compounds were derived from Fuzi and 19 compounds were derived from Ganjiang. Our research data showed that FG can effectively reduce the production of pro-inflammatory mediators IL-6, TNF-α, ROS, NO, and PGE and suppress the expression of iNOS and COX2, which were related to the inhibition of NF-κB/activation of Nrf2/HO-1 signaling pathways. In addition, our research results revealed that FG can improve the depression-like behavior performance of CRF model mice in the tail suspension test, open field test, elevated plus maze test, and forced swimming test, which were associated with the inhibition of the expression of inflammatory mediators iNOS and COX2 in the prefrontal cortex and hippocampus of CRF model mice. Those research results suggested that FG has a satisfactory effect on depression-like behavior of CRF, which was related to the inhibition of neuroinflammation.
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http://dx.doi.org/10.3389/fphar.2021.670586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193093PMC
May 2021
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