Publications by authors named "Haibo Zhang"

617 Publications

A Positive Feedback Loop of Long Noncoding RNA LINC00152 and KLF5 Facilitates Breast Cancer Growth.

Front Oncol 2021 26;11:619915. Epub 2021 Mar 26.

Department of Radiation Oncology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.

The long noncoding RNA (lncRNA) LINC00152, also known as CYTOR, displays aberrant expression in various cancers. However, its clinical value and functional mechanisms in breast cancer remain insufficiently understood. Our study found that LINC00152 is significantly upregulated in breast cancer, and that it acts as an indicator of poor survival prognosis. Further studies revealed that LINC00152 knockdown suppresses cell proliferation and tumorigenicity and . Mechanistic analyses demonstrated that LINC00152 directly binds to KLF5 protein and increases KLF5 stability. Moreover, LINC00152 is also a KLF5-responsive lncRNA, and KLF5 activates LINC00152 transcription by directly binding to its promoter. Our study suggests that LINC00152 promotes tumor progression by interacting with KLF5. LINC00152 may be a valuable prognostic predictor for breast cancer, and the positive feedback loop of LINC00152-KLF5 could be a therapeutic target in pharmacological strategies.
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http://dx.doi.org/10.3389/fonc.2021.619915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032978PMC
March 2021

Corrigendum to "TTK inhibitor promotes radiosensitivity of liver cancer cells through p21" [Biochem. Biophys. Res. Commun. 550(2021) 84-91].

Biochem Biophys Res Commun 2021 Apr 8. Epub 2021 Apr 8.

Department of Radiation Oncology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; Graduate Department, Bengbu Medical College, Bengbu, Anhui, 233000, China. Electronic address:

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http://dx.doi.org/10.1016/j.bbrc.2021.03.164DOI Listing
April 2021

Embryonic-Derived Macrophages Enhance Bacterial Clearance and Improve Survival in Rat Sepsis.

Int J Mol Sci 2021 Mar 20;22(6). Epub 2021 Mar 20.

Keenan Research Centre for Biomedical Science, Unity Health Toronto St. Michael's, University of Toronto, Toronto, ON M5B 1T8, Canada.

Peritoneal resident macrophages play a key role in combating sepsis in the peritoneal cavity. We sought to determine if peritoneal transplantation of embryonic "peritoneal-like" macrophages attenuate abdominal fecal sepsis. Directed differentiation of rodent pluripotent stem cells (PSCs) was used in factor-defined media to produce embryonic-derived large "peritoneal-like" macrophages (Ed-LPM) that expressed peritoneal macrophage markers and demonstrated phagocytic capacity. Preclinical in vivo studies determined Ed-LPM efficacy in rodent abdominal fecal sepsis with or without Meropenem. Ex vivo studies explored the mechanism and effects of Ed-LPM on host immune cell number and function, including phagocytosis, reactive oxygen species (ROS) production, efferocytosis and apoptosis. Ed-LPM reduced sepsis severity by decreasing bacterial load in the liver, spleen and lungs. Ed-LPM therapy significantly improved animal survival by ~30% and reduced systemic bacterial burden to levels comparable to Meropenem therapy. Ed-LPM therapy decreased peritoneal TNFα while increasing IL-10 concentrations. Ed-LPMs enhanced peritoneal macrophage phagocytosis of bacteria, increased macrophage production of ROS and restored homeostasis via apoptosis and efferocytosis-induced clearance of neutrophils. In conclusion, Ed-LPM reduced systemic sepsis severity, improved survival and reduced bacterial load by enhancing peritoneal macrophage bacterial phagocytosis and killing and clearance of intra-peritoneal neutrophils. Macrophage therapy may be a potential strategy to address sepsis.
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http://dx.doi.org/10.3390/ijms22063190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004006PMC
March 2021

Association between use of Qingfei Paidu Tang and mortality in hospitalized patients with COVID-19: A national retrospective registry study.

Phytomedicine 2021 Feb 28;85:153531. Epub 2021 Feb 28.

National Clinical Research Center for Cardiovascular Diseases, State Key, Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for, Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union, Medical College, Beijing, People's Republic of China; Central China Subcenter of the National Center for Cardiovascular Diseases, Zhengzhou, People's Republic of China; Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, People's Republic of China. Electronic address:

Background: Qingfei Paidu Tang (QPT), a formula of traditional Chinese medicine, which was suggested to be able to ease symptoms in patients with Coronavirus Disease 2019 (COVID-19), has been recommended by clinical guidelines and widely used to treat COVID-19 in China. However, whether it decreases mortality remains unknown.

Purpose: We aimed to explore the association between QPT use and in-hospital mortality among patients hospitalized for COVID-19.

Study Design: A retrospective study based on a real-world database was conducted.

Methods: We identified patients consecutively hospitalized with COVID-19 in 15 hospitals from a national retrospective registry in China, from January through May 2020. Data on patients' characteristics, treatments, and outcomes were extracted from the electronic medical records. The association of QPT use with COVID-19 related mortality was evaluated using Cox proportional hazards models based on propensity score analysis.

Results: Of the 8939 patients included, 28.7% received QPT. The COVID-19 related mortality was 1.2% (95% confidence interval [CI] 0.8% to 1.7%) among the patients receiving QPT and 4.8% (95% CI 4.3% to 5.3%) among those not receiving QPT. After adjustment for patient characteristics and concomitant treatments, QPT use was associated with a relative reduction of 50% in-hospital COVID-19 related mortality (hazard ratio, 0.50; 95% CI, 0.37 to 0.66 p < 0.001). This association was consistent across subgroups by sex and age. Meanwhile, the incidences of acute liver injury (8.9% [95% CI, 7.8% to 10.1%] vs. 9.9% [95% CI, 9.2% to 10.7%]; odds ratio, 0.96 [95% CI, 0.81% to 1.14%], p = 0.658) and acute kidney injury (1.6% [95% CI, 1.2% to 2.2%] vs. 3.0% [95% CI, 2.6% to 3.5%]; odds ratio, 0.85 [95% CI, 0.62 to 1.17], p = 0.318) were comparable between patients receiving QPT and those not receiving QPT. The major study limitations included that the study was an observational study based on real-world data rather than a randomized control trial, and the quality of data could be affected by the accuracy and completeness of medical records.

Conclusions: QPT was associated with a substantially lower risk of in-hospital mortality, without extra risk of acute liver injury or acute kidney injury among patients hospitalized with COVID-19.
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http://dx.doi.org/10.1016/j.phymed.2021.153531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914374PMC
February 2021

Targeting AKT with costunolide suppresses the growth of colorectal cancer cells and induces apoptosis in vitro and in vivo.

J Exp Clin Cancer Res 2021 Mar 30;40(1):114. Epub 2021 Mar 30.

Department of Animal Science and Biotechnology, ITRD, Kyungpook National University, Sangju, 37224, Republic of Korea.

Background: Colorectal cancer (CRC) is a clinically challenging malignant tumor worldwide. As a natural product and sesquiterpene lactone, Costunolide (CTD) has been reported to possess anticancer activities. However, the regulation mechanism and precise target of this substance remain undiscovered in CRC. In this study, we found that CTD inhibited CRC cell proliferation in vitro and in vivo by targeting AKT.

Methods: Effects of CTD on colon cancer cell growth in vitro were evaluated in cell proliferation assays, migration and invasion, propidium iodide, and annexin V-staining analyses. Targets of CTD were identified utilizing phosphoprotein-specific antibody array; Costunolide-sepharose conjugated bead pull-down analysis and knockdown techniques. We investigated the underlying mechanisms of CTD by ubiquitination, immunofluorescence staining, and western blot assays. Cell-derived tumour xenografts (CDX) in nude mice and immunohistochemistry were used to assess anti-tumour effects of CTD in vivo.

Results: CTD suppressed the proliferation, anchorage-independent colony growth and epithelial-mesenchymal transformation (EMT) of CRC cells including HCT-15, HCT-116 and DLD1. Besides, the CTD also triggered cell apoptosis and cell cycle arrest at the G2/M phase. The CTD activates and induces p53 stability by inhibiting MDM2 ubiquitination via the suppression of AKT's phosphorylation in vitro. The CTD suppresses cell growth in a p53-independent fashion manner; p53 activation may contribute to the anticancer activity of CTD via target AKT. Finally, the CTD decreased the volume of CDX tumors without of the body weight loss and reduced the expression of AKT-MDM2-p53 signaling pathway in xenograft tumors.

Conclusions: Our project has uncovered the mechanism underlying the biological activity of CTD in colon cancer and confirmed the AKT is a directly target of CTD. All of which These results revealed that CTD might be a new AKT inhibitor in colon cancer treatment, and CTD is worthy of further exploration in preclinical and clinical trials.
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http://dx.doi.org/10.1186/s13046-021-01895-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010944PMC
March 2021

β-blocker and 1-year outcomes among patients hospitalized for heart failure with mid-range ejection fraction.

Eur Heart J Cardiovasc Pharmacother 2021 Mar 27. Epub 2021 Mar 27.

National Clinical Research Center for Cardiovascular Diseases, NHC Key Laboratory of Clinical Research for Cardiovascular Medications, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular Diseases.

Aims: The beneficial effect of β-blocker on heart failure with reduced ejection fraction (HFrEF) is well established. However, its effect on the 1-year outcome of heart failure with mid-range ejection fraction (HFmrEF) remains unclear.

Methods And Results: We analysed the data of the patients with left ventricular ejection fraction (LVEF) between 40%-49% in China Patient-centred Evaluative Assessment of Cardiac Events Prospective Heart Failure Study (China PEACE 5p-HF Study), in which patients hospitalized for heart failure (HF) from 52 Chinese hospitals were recruited from 2016 to 2018. Two primary outcomes were all-cause death and all-cause hospitalization. The associations between β-blocker use at discharge and outcomes were assessed by inverse probability of treatment weighting (IPTW)-weighted Cox regression analyses. To assess consistency, IPTW adjusting medications analyses, multivariable analyses and dose-effect analyses were performed. 1035 HFmrEF patients were included in the analysis. The mean age was 65.5 ±12.7 years and 377 (36.4%) were female. The median (interquartile range) of LVEF was 44% (42%-47%). 661 (63.8%) were treated with β-blocker. Patients using β-blocker were younger with better cardiac function, and more likely to use renin-angiotensin system inhibitor and mineralocorticoid receptor antagonist. During the 1-year follow up, death occurred in 84 (12.7%) treated and 85 (22.7%) untreated patients (P < 0.0001); all-cause hospitalization occurred in 298 (45.1%) treated and 188 (50.3%) untreated patients (P = 0.04). After IPTW-weighted adjustment, β-blocker use was significantly associated with lower risk of all-cause death [hazard ratio (HR): 0.70; confidence interval (95% CI): 0.51-0.96, P = 0.03], but not with lower all-cause hospitalization (HR, 0.92, 95% CI, 0.76-1.10, P = 0.36). Consistency analyses showed consistent favourable effect of β-blocker on all-cause death, but not on all-cause hospitalization.

Conclusions: Among patients with HFmrEF, β-blocker use was associated with lower risk of all-cause death, but not with lower risk of all-cause hospitalization.
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http://dx.doi.org/10.1093/ehjcvp/pvab029DOI Listing
March 2021

Quantification of Microplastics in Soils Using Accelerated Solvent Extraction: Comparison with a Visual Sorting Method.

Bull Environ Contam Toxicol 2021 Mar 25. Epub 2021 Mar 25.

Nanjing Institute of Soil Science, Chinese Academy of Sciences, Nanjing, 210008, China.

Visual sorting is a method that is widely used in microplastic analysis, but it has limitation in the quantification of small-size microplastics. Accelerated solvent extraction (ASE) which frequently used in the analysis of organic contaminants in soils and sediments was used here for the microplastics quantification. A recovery experiment using different spiked polymeric microplastics separately indicates that ASE was useful in the extraction of low-density and low-melting point polymeric microplastics. High recoveries and low matrix effects were observed for the polyethylene, polypropylene and polystyrene microplastics. A further comparison between ASE and visual sorting was conducted for seven soils from agricultural land used for long-term mulching with plastic films. The results confirmed that ASE was capable of microplastics quantification for farmland soils and polyethylene film in the ASE extracts could be identified by Fourier transform infrared spectroscopy. Meanwhile, ASE conducted on small samples (3.0 g) gave results that showed close agreement with the visual sorting method.
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http://dx.doi.org/10.1007/s00128-021-03200-zDOI Listing
March 2021

National Preclinical Sepsis Platform: developing a framework for accelerating innovation in Canadian sepsis research.

Intensive Care Med Exp 2021 Mar 19;9(1):14. Epub 2021 Mar 19.

Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.

Despite decades of preclinical research, no experimentally derived therapies for sepsis have been successfully adopted into routine clinical practice. Factors that contribute to this crisis of translation include poor representation by preclinical models of the complex human condition of sepsis, bias in preclinical studies, as well as limitations of single-laboratory methodology. To overcome some of these shortcomings, multicentre preclinical studies-defined as a research experiment conducted in two or more research laboratories with a common protocol and analysis-are expected to maximize transparency, improve reproducibility, and enhance generalizability. The ultimate objective is to increase the efficiency and efficacy of bench-to-bedside translation for preclinical sepsis research and improve outcomes for patients with life-threatening infection. To this end, we organized the first meeting of the National Preclinical Sepsis Platform (NPSP). This multicentre preclinical  research collaboration of Canadian sepsis researchers and stakeholders was established to study the pathophysiology of sepsis and accelerate movement of promising therapeutics into early phase clinical trials. Integrated knowledge translation and shared decision-making were emphasized to ensure the goals of the platform align with clinical researchers and patient partners. 29 participants from 10 independent labs attended and discussed four main topics: (1) objectives of the platform; (2) animal models of sepsis; (3) multicentre methodology and (4) outcomes for evaluation. A PIRO model (predisposition, insult, response, organ dysfunction) for experimental design was proposed to strengthen linkages with interdisciplinary researchers and key stakeholders. This platform represents an important resource for maximizing translational impact of preclinical sepsis research.
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http://dx.doi.org/10.1186/s40635-020-00366-4DOI Listing
March 2021

Dassonmycins A and B, Polycyclic Thioalkaloids from a Marine Sponge-Derived SCSIO 40065.

Org Lett 2021 Mar 11. Epub 2021 Mar 11.

Key Laboratory of Tropical Marine Bioresources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.

Two polycyclic thioalkaloides dassonmycins A () and B () were isolated from SCSIO 40065 associated with marine sponge sp. Structures of and were elucidated by comprehensive spectroscopic analysis and confirmed by single-crystal X-ray diffraction experiments, to have a 6/6/6/6-fused tetracyclic ring featuring a naphthoquinone[2,3-]piperazine[1,2-]thiomorpholine scaffold. Compound formed a caged core through an additional ether bridge. Both compounds exhibited moderate antibacterial and cytotoxic activities.
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http://dx.doi.org/10.1021/acs.orglett.1c00328DOI Listing
March 2021

TTK inhibitor promotes radiosensitivity of liver cancer cells through p21.

Biochem Biophys Res Commun 2021 Apr 6;550:84-91. Epub 2021 Mar 6.

Graduate Department, Bengbu Medical College, Bengbu, Anhui, 233000, PR China; Department of Radiation Oncology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, PR China. Electronic address:

The monopolar spindle 1 ((hMps1/TTK) is a serine/threonine kinase that plays an important role in spindle assembly checkpoint signaling. To explore the possible relationship between TTK inhibition and radiosensitivity, we examined whether TTK inhibition influences cellular susceptibility of radiation. And we further revealed its mechanisms. We found that the expression of TTK was obviously higher in liver cancer tissues compared to the normal liver tissues. Kaplan-Meier Plotter demonstrated that patients with low TTK expression levels had a longer overall survival than patients with high TTK expression levels. TTK inhibitor AZ3146 could simulated liver cancer cells to accumulate in the G2/M phase, which ultimately enhances DNA damage with more γ-H2AX foci and more apoptosis and necrosis induced by radiation, which prompted that TTK inhibition sensitized liver cancer cells to radiation. In addition, TTK inhibition altered cell-cycle progression and exacerbated centrosome abnormalities, resulting in enhanced mitotic catastrophe (MC) induced by radiation in a p21-mediated manner. In this study, we present evidences that the TTK inhibitor promotes the radiosensitivity of liver cancer cells through regulating cell cycle in p21-mediated manner in vitro, indicating that TTK inhibitor may be an attractive radiosensitizer for the patients with liver cancer.
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http://dx.doi.org/10.1016/j.bbrc.2021.01.089DOI Listing
April 2021

Partial Response to Pyrotinib Plus Capecitabine in an Advanced Breast Cancer Patient with Amplification and Mutation After Anti- Treatment: A Case Report and Literature Review.

Onco Targets Ther 2021 2;14:1581-1588. Epub 2021 Mar 2.

Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China.

Human epidermal growth factor receptor2 () overexpression/amplification is associated with high malignancy, rapid disease progression and poor overall survival in breast cancer. The application of anti- drugs has greatly improved the survival of patients with -positive breast cancer, but drug resistance issues affect the long-term efficacy. The mutation is considered to be one of the reasons for resistance to anti- therapy, and there is currently no standard treatment. We report for the first time the detection of amplification with mutation by second-generation sequencing (NGS) in a 57-year-old hormone receptor-negative, -positive woman with advanced breast cancer who was resistant to multi-line anti- therapies. She subsequently received pyrotinib combined with capecitabine treatment and achieved partial response. The small-molecule pan- family irreversible inhibitor pyrotinib combined with capecitabine has shown a promising effect in the treatment of mutation-induced resistance, but the molecular mechanism and efficacy need to be further verified.
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http://dx.doi.org/10.2147/OTT.S289876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936716PMC
March 2021

Durable and chemical resistant ultra-permeable nanofiltration membrane for the separation of textile wastewater.

J Hazard Mater 2021 Feb 25;414:125489. Epub 2021 Feb 25.

Laboratory of High Performance Plastics (Jilin University), Ministry of Education, National & Local Joint Engineering Laboratory for Synthesis Technology of High Performance Polymer, College of Chemistry, Jilin University, Changchun 130012, People's Republic of China.

It is highly challenging to prepare durable and chemical resistant ultra-permeable membranes that can quickly separate small organic molecules like dye or inorganic salt in the complex textile wastewater industry. Here, side-chain sulfonated poly(ether ether ketone) (SPEEK) was synthesized and prepared the poly(ether ether ketone) (PEEK) - SPEEK nanofiltration (NF) membrane by a simple dipping coating and heat treatment. Single component filtration tests of the optimized membrane showed ultrahigh pure water flux (126 Lm h bar) and relatively low NaCl rejection (6.7%). Moreover, the negatively charged membrane exhibited excellent rejection of 98.8% toward Congo red (CR). The pure water flux was about 9 folds than that of commercial NF270 with comparable solutes rejection. The separation tests of CR and NaCl mixed solution at optimized conditions exhibited ultra-high permeation flux (34 Lm h bar), satisfactory dye (98.8%)/salt (< 10%) rejection and the separation performance remained stable after 10 cycles. Finally, the contaminated membrane was washed with ethanol, the permeation flux and the CR rejection remained constant after several cycles, while the commercial NF1 membrane exhibited serious swelling only within one cycle. The prepared membrane exhibited good organic solvents resistance and antifouling properties. Thus, this work confirmed the PEEK-SPEEK NF membrane showed great potential in the sustainable treatment of textile wastewater.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125489DOI Listing
February 2021

Cylindromicin from Arctic-Derived Fungus sp. SCSIO 40433.

Molecules 2021 Feb 18;26(4). Epub 2021 Feb 18.

Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China.

The fungus strain SCSIO 40433 was isolated from an Arctic-derived glacier sediment sample and characterized as . A new compound, cylindromicin (), and seven known secondary metabolites (-) were isolated from this strain. The chemical structures of these compounds were elucidated by comprehensive spectroscopic analyses. Cylindromicin () featured a 3,4-dihydro-2-pyran skeleton. The absolute configuration of compound was assigned via interpretation of key Nuclear Overhauser Effect Spectroscopy (NOESY) correlations and Electronic Circular Dichroism (ECD) calculation. Cylindromicin () exhibited significant tyrosinase inhibition activity. This study highlights Polar fungi as a potential resource for new bioactive natural products.
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http://dx.doi.org/10.3390/molecules26041080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922244PMC
February 2021

CTA-Based Non-invasive Estimation of Pressure Gradients Across a CoA: a Validation Against Cardiac Catheterisation.

J Cardiovasc Transl Res 2021 Mar 4. Epub 2021 Mar 4.

Shanghai Aitrox Technology Co., Ltd., 1289 Yishan Road, Xuhui, Shanghai, China.

Non-invasive estimation of pressure gradients across a coarctation of the aorta (CoA) can reduce the need for diagnostic cardiac catheterisation. We aimed to validate two novel computational strategies-target-value approaching (TVA) and target-value fixing (TVF)-together with unrefined Doppler estimates, and to compare their diagnostic performance in identifying critical pressure drops for 40 patients. Compared to catheterisation, no statistically significant difference was demonstrated with TVA (P = 0.086), in contrast to TVF (P = 0.005) and unrefined Doppler echocardiography (P < 0.001). TVA manifested the strongest correlation with catheterisation (r = 0.93), compared to TVF (r = 0.83) and echocardiography (r = 0.67) (all P < 0.001). In discriminating pressure gradients greater than 20 mmHg, TVA, TVF, and echocardiography had respective sensitivities of 0.92, 0.88, and 0.80; specificities of 0.93, 0.80, and 0.73; and AUCs of 0.96, 0.89, and 0.80. The TVA strategy may serve as an effective and easily implemented approach to be used in clinical management of patients with CoA. Graphical Abstract Central illustration. Pressure gradients estimated using Doppler echocardiography and two novel computational strategies (TVA and TVF) were compared with cardiac catheterisation for 40 patients. TVA and TVF utilised the CTA images to obtain the CoA anatomy and Doppler echocardiography velocimetry to obtain velocity data for the assignment of CFD boundary conditions.
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http://dx.doi.org/10.1007/s12265-020-10092-7DOI Listing
March 2021

Anomalous left coronary artery from pulmonary artery repair: Outcomes from the European Congenital Heart Surgeons Association Database.

J Card Surg 2021 Mar 2. Epub 2021 Mar 2.

Pediatric and Congenital Cardiac Surgery Unit, Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.

Introduction: We sought to determine the surgical outcomes of patients with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) enrolled in the European Congenital Heart Surgeons Association (ECHSA) database.

Materials And Methods: From 1999 to 2019, 907 patients with ALCAPA underwent surgical repair and were included in the current study. The primary outcome was in-hospital mortality. Secondary outcomes included frequency and results of concomitant mitral valve surgery and postoperative mechanical circulatory support (MCS).

Results: The overall in-hospital mortality was 6% (54/907) and was significantly higher in neonates (p = .01), patients with lower body surface area (BSA) (p = .01), and those requiring postoperative MCS (p = .001). Associated mitral valve surgery was performed in 144 patients (15.9%) and was associated with longer cardiopulmonary bypass (CPB) and aortic cross-clamp times (AOX) (p ≤ .0001) but was not significantly related to an increase in in-hospital mortality. Postoperative MCS was required in 66 patients (7.3%). These patients were younger (p ≤ .001), had a lower BSA (p ≤ .001), and required a longer CPB (p ≤ .001) and AOX time (p ≤ .001).

Conclusions: ALCAPA repair can be achieved successfully, and with low surgical risk. Concomitant mitral valve procedures can be performed without increasing operative mortality. The use of MCS remains a valuable option, especially in younger patients.
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http://dx.doi.org/10.1111/jocs.15448DOI Listing
March 2021

Anticancer effects and potential mechanisms of ginsenoside Rh2 in various cancer types (Review).

Oncol Rep 2021 Apr 2;45(4):1-10. Epub 2021 Mar 2.

Department of Animal Science and Biotechnology, Institute for Translational Research in Dentistry, Kyungpook National University, Bukgu, Daegu 41566, Republic of Korea.

Ginsenoside Rh2 (G‑Rh2) is a natural bioactive product derived from Meyer (). G‑Rh2 exhibits anticancer activity in various human cancer cell lines both and by modulating several signaling pathways, such as those of PDZ‑binding kinase/T‑LAK cell‑originated protein kinase, phosphatidylinositol 3‑kinase, protein kinase B, mammalian target of rapamycin, epidermal growth factor receptor, p53, and reactive oxygen species. Moreover, G‑Rh2 could effectively reverse drug resistance and enhance therapeutic effects in cancer therapy. This review summarizes the chemical properties, and anticancer activity, and underlying molecular mechanisms of G‑Rh2 to facilitate cancer chemoprevention studies.
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http://dx.doi.org/10.3892/or.2021.7984DOI Listing
April 2021

Metabolic supervision by PPIP5K, an inositol pyrophosphate kinase/phosphatase, controls proliferation of the HCT116 tumor cell line.

Proc Natl Acad Sci U S A 2021 Mar;118(10)

Signal Transduction Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709.

Identification of common patterns of cancer metabolic reprogramming could assist the development of new therapeutic strategies. Recent attention in this field has focused on identifying and targeting signal transduction pathways that interface directly with major metabolic control processes. In the current study we demonstrate the importance of signaling by the diphosphoinositol pentakisphosphate kinases (PPIP5Ks) to the metabolism and proliferation of the HCT116 colonic tumor cell line. We observed reciprocal cross talk between PPIP5K catalytic activity and glucose metabolism, and we show that CRISPR-mediated PPIP5K deletion suppresses HCT116 cell proliferation in glucose-limited culture conditions that mimic the tumor cell microenvironment. We conducted detailed, global metabolomic analyses of wild-type and PPIP5K knockout (KO) cells by measuring both steady-state metabolite levels and by performing isotope tracing experiments. We attribute the growth-impaired phenotype to a specific reduction in the supply of precursor material for de novo nucleotide biosynthesis from the one carbon serine/glycine pathway and the pentose phosphate pathway. We identify two enzymatic control points that are inhibited in the PPIP5K KO cells: serine hydroxymethyltransferase and phosphoribosyl pyrophosphate synthetase, a known downstream target of AMP-regulated protein kinase, which we show is noncanonically activated independently of adenine nucleotide status. Finally, we show the proliferative defect in PPIP5K KO cells can be significantly rescued either by addition of inosine monophosphate or a nucleoside mixture or by stable expression of PPIP5K activity. Overall, our data describe multiple, far-reaching metabolic consequences for metabolic supervision by PPIP5Ks in a tumor cell line.
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http://dx.doi.org/10.1073/pnas.2020187118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958180PMC
March 2021

Effect of substrate load on anaerobic fermentation of rice straw with rumen liquid as inoculum: Hydrolysis and acidogenesis efficiency, enzymatic activities and rumen bacterial community structure.

Waste Manag 2021 Apr 23;124:235-243. Epub 2021 Feb 23.

College of Environmental Science & Engineering, Beijing Forestry University, Beijing 100083, China.

Rumen liquid is excellent to effectively degrade lignocellulose. In this study, the suitable rice straw load during anaerobic fermentation of rice straw with rumen liquid as inoculum was explored to improve volatile fatty acid (VFA) production. At 10.0% rice straw load, the highest VFA concentration reached 10821.4 mg/L, and acetic acid and propionic acid were the main components. In 10.0% rice straw load system, high concentration of soluble chemical oxygen demand (SCOD) was also observed, and the enzymatic activities at 48 h were higher than those at other rice straw loads. At 10.0% rice straw load, lower diversity and richness of rumen bacteria were found than those at other rice straw loads. Bacteroides, Prevotella, and Ruminococcus were the main rumen bacteria during rice straw degradation, and the rumen bacteria might secret effective lignocellulolytic enzymes to enhance the hydrolysis and acidogenesis of rice straw. The determination of suitable rice straw load will be beneficial to the application of rumen liquid as inoculum in actual production.
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http://dx.doi.org/10.1016/j.wasman.2021.02.017DOI Listing
April 2021

Tai Chi for the elderly patients with COVID-19 in recovery period: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Jan;100(3):e24111

School of Acupuncture, Moxibustion and Tuina.

Background: The coronavirus disease 2019 (COVID-19) outbreak has caused a great impact in many countries. Older people are more susceptible to the virus than other people. As a good health exercise suitable for the elderly, Tai Chi has a positive impact on heart function, blood pressure, lung function, immunity, etc. It can enhance cardiopulmonary function, increase the elasticity of blood vessels, and improve the body's self-regulation function. For the elder patients with COVID-19, Tai Chi has outstanding merits.

Methods: We will search PubMed, EMBASE, MEDLINE, the Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Science and Technology Periodical Database, Wanfang Database, Clinical Trials and Chinese Clinical Trial Registry. The complete process will include study selection, data extraction, risk of bias assessment and meta-analyses. Endnote X9.3 will be used to manage data screening. The statistical analysis will be completed by Stata/SE 15.1 software.

Results: This proposed study will evaluate the effectiveness and safety of Tai Chi for the improvement of psychological pressure, cardiopulmonary function, and immunity in elderly COVID-19 patients during the recovery period.

Conclusion: The conclusion of this study will provide evidence to prove the safety and effectiveness of Tai Chi on elderly COVID-19 patients during the recovery period.

Ethics And Dissemination: This protocol will not evaluate individual patient information or infringe patient rights and therefore does not require ethical approval.

Registration: PEROSPERO CRD42020220128.
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http://dx.doi.org/10.1097/MD.0000000000024111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837887PMC
January 2021

Gastric Cancer Harboring an Mutation Treated with a Pyrotinib-Irinotecan Combo: A Case Study.

Onco Targets Ther 2021 18;14:545-550. Epub 2021 Jan 18.

Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China.

Gastric cancer is common, especially in East Asian countries, and is associated with high recurrence and mortality rates. Currently, there is no standard third-line treatment for metastatic gastric cancer. In this report, we present the case of a 69-year-old man with advanced gastric cancer, whose tumor was negative for human epidermal growth factor receptor 2 (HER2) according to immunohistochemical analysis. Next-generation sequencing performed on paraffin sections of the postoperative tumor samples indicated the presence of the V104L mutation. The patient received irinotecan plus pyrotinib as a third-line therapy and achieved a progression-free survival of 7.6 months with a high quality of life. Therefore, the combined administration of irinotecan and pyrotinib may improve the clinical condition of patients with gastric cancer harboring an mutation. Moreover, could be a potential therapeutic target for gastric cancer.
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http://dx.doi.org/10.2147/OTT.S286024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823137PMC
January 2021

Risk factors for postoperative recurrent tricuspid regurgitation after concomitant tricuspid annuloplasty during left heart surgery and the association between tricuspid annular circumference and secondary tricuspid regurgitation.

BMC Cardiovasc Disord 2021 Jan 26;21(1):50. Epub 2021 Jan 26.

Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, China.

Background: To identify the association between tricuspid annular circumference and secondary tricuspid regurgitation and analyze the risk factors of recurrent tricuspid regurgitation after concomitant tricuspid annuloplasty during left heart surgery.

Methods: From October 2018 to June 2019, a total of 117 patients receiving concomitant tricuspid annuloplasty within left heart surgery were enrolled. Severity of tricuspid regurgitation was classified as 4 subtypes: normal, mild, moderate and severe. Perioperative data and mid-term outcome were collected. Tricuspid annular circumference (TAC) was measured under cardiac arrest during surgery procedure by cardioplegia. Optimal TAC and TAC index (TAC/body surface area, BSA) cutoffs of significant tricuspid annulus dilatation (moderate and severe) were obtained. Univariable and multivariable logistic regression analyses were performed to identify the risk factors of postoperative recurrent tricuspid regurgitation. The follow up period is 13-19 months (mean 15.5 ± 3.2 months).

Results: There was 1 patient was excluded who died after surgery. A total of 116 patients receiving tricuspid annuloplasty were included. Optimal cutoffs of significant tricuspid annulus dilatation were recommended (TAC 11.45 cm, Sensitivity 82.89%, Specificity 73.68%, AUC 0.915; TAC index 7.09 cm/m, Sensitivity 73.68%, Specificity 85%, AUC 0.825, respectively). Based on findings of multivariable logistic regression, it has been showed that TAC index and postoperative atrial fibrillation were the independent risk factors of recurrent regurgitation after surgery. Optimal TAC index cutoff to predict recurrent tricuspid regurgitation was 7.86 cm/m CONCLUSIONS: The severity of secondary tricuspid regurgitation is associated with the tricuspid annular circumference. The cut-offs of significant tricuspid regurgitation (more than moderate) were TAC 11.45 cm and TAC index 7.09 cm/m, respectively. Clinically, concomitant tricuspid annuloplasty is relative safe and effective. TAC index ≥ 7.86 cm/m and postoperative atrial fibrillation are the risk factors of recurrent significant tricuspid regurgitation after concomitant tricuspid annuloplasty during left heart surgery.
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http://dx.doi.org/10.1186/s12872-021-01870-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836580PMC
January 2021

Intrinsic dialogues between the two hemispheres in middle-aged male alcoholics: a resting-state functional MRI study.

Neuroreport 2021 02;32(3):206-213

Departments of Radiology.

Background: The purpose of this study was to investigate the interhemispheric intrinsic connectivity measured by resting-state functional MRI (R-fMRI) in middle-aged male alcoholics.

Methods: Thirty male alcoholics (47.33 ± 8.30 years) and 30 healthy males (47.20 ± 6.17 years) were recruited and obtained R-fMRI data. Inter- and intrahemispheric coordination was performed by using voxel-mirrored homotopic connectivity (VMHC) and seed-based functional connectivity analysis.

Results: We found significantly decreased VMHC in a set of regions in male alcoholics patients, including lateral temporal, inferior frontal gyrus, insular/insulae operculum, precuneus/posterior cingulate gyrus, and pars triangularis (P < 0.05, corrected). Subsequent seed-based functional connectivity analysis demonstrated disrupted functional connectivity between the regions of local homotopic connectivity deficits and other areas of the brain, particularly the areas subserving the default, salience, primary somatomotor, and language systems.

Conclusions: Middle-aged male alcoholic subjects demonstrated prominent reductions in inter- and intrahemispheric functional coherence. These abnormal changes may reflect degeneration of system/network integration, particularly the domains subserving default, linguistic processing, and salience integration.
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http://dx.doi.org/10.1097/WNR.0000000000001579DOI Listing
February 2021

Three-Dimensional Coating of SF/PLGA Coaxial Nanofiber Membranes on Surfaces of Calcium Phosphate Cement for Enhanced Bone Regeneration.

ACS Biomater Sci Eng 2020 05 10;6(5):2970-2984. Epub 2020 Apr 10.

Norman Bethune First Hospital, Jilin University, Changchun 130021, P. R. China.

Calcium phosphate cements (CPCs) have been widely used for the study of bone regeneration because of their excellent physical and chemical properties, but poor biocompatibility and lack of osteoinductivity limit potential clinical applications. To overcome these limitations, and based on our previous research, CPC scaffolds were prepared with CPC as the principal material and polyethylene glycol (PEG) as a porogen to introduce interconnected macropores. Using a bespoke electrospinning auxiliary receiver, silk fibroin (SF)/poly(lactide--glycolide) (PLGA) coaxial nanofibers containing dexamethasone (DXM) and recombinant human bone morphogenetic protein-2 (rhBMP2) were fabricated which were coated on the surface of the CPC. By comparing the surface morphology by SEM, hydrophilicity, results of FTIR spectroscopy, and mechanical properties of the composite materials fabricated using different electrospinning times (20, 40, 60 min), the CPC surface constructed by electrospinning for 40 min was found to exhibit the most appropriate physical and chemical properties. Therefore, composite materials were built for further study by electrospinning for 40 min. The osteogenic capacity of the SF/PLGA/CPC, SF-DXM/PLGA/CPC, and SF-DXM/PLGA-rhBMP2/CPC scaffolds was evaluated by in vitro cell culture with rat bone marrow mesenchymal stem cells (BMSCs) and using a rat cranial defect repair model. ALP activity, calcium deposition levels, upregulation of osteogenic genes, and bone regeneration in skull defects in rats with SF-DXM/PLGA-rhBMP2/CPC implants were significantly higher than in rats implanted with the other scaffolds. These results suggest that drug-loaded coaxial nanofiber coatings prepared on a CPC surface can continuously and effectively release bioactive drugs and further stimulate osteogenesis. Therefore, the SF-DXM/PLGA-rhBMP2/CPC scaffolds prepared in this study demonstrated the most significant potential for the treatment of bone defects.
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http://dx.doi.org/10.1021/acsbiomaterials.9b01729DOI Listing
May 2020

20(S)-Ginsenoside Rh2 Suppresses Oral Cancer Cell Growth by Inhibiting the Src-Raf-ERK Signaling Pathway.

Anticancer Res 2021 Jan;41(1):227-235

Department of Animal Science and Biotechnology, Kyungpook National University, Sangju, Republic of Korea;

Background: 20(S)-Ginsenoside Rh2 (G-Rh2) has demonstrated therapeutic effects in many types of cancers. We aimed to investigate the potential anticancer activity and underlying mechanisms of G-Rh2 in oral cancer cells.

Materials And Methods: The antigrowth effect of G-Rh2 in oral cancer cells was stimulated by cell proliferation, soft agar colony formation, and migration and invasion assay. The cell cycle and apoptosis were detected by flow cytometry. The underlying mechanism of G-Rh2 in oral cancer cells was explored by immunoblotting.

Results: G-Rh2 significantly inhibited oral cancer cell growth by inducing apoptosis and cell cycle G/G-phase arrest. G-Rh2 inhibited oral cancer cell migration and invasion through regulation of epithelial-mesenchymal transition (EMT)-related proteins. G-Rh2 inhibited the Src/Raf/ERK signaling pathway in YD10B and Ca9-22 cells.

Conclusion: G-Rh2 exerted anticancer activity in vitro by inhibiting the Src/Raf/ERK signaling pathway in oral cancer. G-Rh2 is a potential therapeutic drug for oral cancer treatment.
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http://dx.doi.org/10.21873/anticanres.14769DOI Listing
January 2021

Imatinib and GNF-5 Exhibit an Inhibitory Effect on Growth of Hepatocellar Carcinoma Cells by Downregulating S-phase Kinase-associated Protein 2.

J Cancer Prev 2020 Dec;25(4):252-257

Department of Animal Science and Biotechnology, Kyungpook National University, Sangju, Korea.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is one of the leading causes of cancer-related deaths worldwide. Imatinib and GNF-5 are breakpoint cluster region-Abelson murine leukemia tyrosine kinase inhibitors which have been approved for the treatment of chronic myeloid leukemia and various solid tumors. However, the effect and underlying mechanisms of imatinib and GNF-5 in HCC remain poorly defined. In this study, we investigated the anticancer activity and underlying mechanisms of imatinib and GNF-5 in HepG2 human hepatocarcinoma cells. Cell proliferation and anchorage-independent colony formation assays were done to evaluate the effects of imatinib and GNF-5 on the growth of HepG2 cells. The cell cycle was assessed by flow cytometry and verified by immunoblot analysis. Gene overexpression and knockdown assays were conducted to evaluate the function of S-phase kinase-associated protein 2 (Skp2). Imatinib and GNF-5 significantly inhibited the growth of HepG2 cells. Imatinib and GNF-5 induced G0/G1 phase cell cycle arrest by downregulating Skp2 and upregulating p27 and p21. Overexpression of Skp2 reduced the effect of imatinib and GNF-5 on HepG2 cells. Knockdown of Skp2 suppressed the proliferation and induced G0/G1 phase arrest. Furthermore, knockdown of Skp2 enhanced the effect of imatinib and GNF-5 on growth of HepG2 cells. In conclusion, imatinib and GNF-5 effectively suppress HepG2 cell growth by inhibiting Skp2 expression. Skp2 promotes the cell proliferation and reverse G0/G1 phase cell cycle arrest and it represents a potential therapeutic target for HCC treatment.
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http://dx.doi.org/10.15430/JCP.2020.25.4.252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783238PMC
December 2020

Modified FOLFOXIRI With or Without Cetuximab as Conversion Therapy in Patients with RAS/BRAF Wild-Type Unresectable Liver Metastases Colorectal Cancer: The FOCULM Multicenter Phase II Trial.

Oncologist 2021 Jan 3;26(1):e90-e98. Epub 2020 Sep 3.

Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.

Purpose: This trial evaluated the addition of cetuximab to a modified FOLFOXIRI (mFOLFOXIRI: 5-fluorouracil/folinic acid, oxaliplatin, irinotecan) as conversion therapy in a two-group, nonrandomized, multicenter, phase II trial in patients with initially technically unresectable colorectal liver-limited metastases (CLM) and BRAF/RAS wild-type.

Patients And Methods: Patients were enrolled to receive cetuximab (500 mg/m ) plus mFOLFOXIRI (oxaliplatin 85 mg/m , irinotecan 165 mg/m , folinic acid 400 mg/m , 5-fluorouracil 2,800 mg/m 46-hour infusion, every 2 weeks) (the cetuximab group) or the same regimen of mFOLFOXIRI alone (the control group), in a 2:1 ratio allocation. The primary endpoint was the rate of no evidence of disease (NED) achieved. Secondary endpoints included resection rate, objective response rate (ORR), survival, and safety.

Results: Between February 2014 and July 2019, 117 patients were registered for screening at six centers in China, and 101 of these were enrolled (67 cetuximab group, 34 control group). The rate of NED achieved was 70.1% in the cetuximab group and 41.2% in the control group (difference 29.0%; 95% confidence interval [CI], 9.1%-48.8%; p = .005). Patients in the cetuximab group had improved ORR (95.5% vs. 76.5%; difference 19.1%; 95% CI, 17.4%-36.4%; p = .010) compared with those in control group. Progression-free survival and overall survival showed the trend to favor the cetuximab group. The incidence of grade 3 and 4 adverse events was similar in the two groups.

Conclusion: Addition of cetuximab to mFOLFOXIRI improved the rate of NED achieved. This combination could be an option of conversion regimen for molecularly selected patients with initially technically unresectable CLM.

Implications For Practice: This trial evaluated the addition of cetuximab to a modified FOLFOXIRI as conversion therapy in a phase II trial in patients with initially technically unresectable colorectal liver-limited metastases and BRAF/RAS wild-type. The rate of no evidence of disease achieved was 70.1% in the cetuximab plus modified FOLFOXIRI group and 41.2% in the modified FOLFOXIRI group. Objective response rates, overall survival, and progression-free survival were improved in the cetuximab group when compared with the modified FOLFOXIRI group. Addition of cetuximab to modified FOLFOXIRI increased the rate of no evidence of disease achieved, and this combination could be an option of conversion regimen for molecularly selected patients with initially technically unresectable colorectal liver-limited metastasis.
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http://dx.doi.org/10.1634/theoncologist.2020-0563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794191PMC
January 2021

Acute Respiratory Distress Syndrome Prediction Score: Derivation and Validation.

Am J Crit Care 2021 01;30(1):64-71

Guangfa Zhu is a professor, Department of Pulmonary and Critical Care Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.

Background: Despite advances in treatment strategies, acute respiratory distress syndrome (ARDS) after cardiac surgery remains associated with high morbidity and mortality. A method of screening patients for risk of ARDS after cardiac surgery is needed.

Objectives: To develop and validate an ARDS prediction score designed to identify patients at high risk of ARDS after cardiac or aortic surgery.

Methods: An ARDS prediction score was derived from a retrospective derivation cohort and validated in a prospective cohort. Discrimination and calibration of the score were assessed with area under the receiver operating characteristic curve and the Hosmer-Lemeshow goodness-of-fit test, respectively. A sensitivity analysis was conducted to assess model performance at different cutoff points.

Results: The retrospective derivation cohort consisted of 201 patients with and 602 patients without ARDS who had undergone cardiac or aortic surgery. Nine routinely available clinical variables were included in the ARDS prediction score. In the derivation cohort, the score distinguished patients with versus without ARDS with area under the curve of 0.84 (95% CI, 0.81-0.88; Hosmer-Lemeshow P = .55). In the validation cohort, 46 of 1834 patients (2.5%) had ARDS develop within 7 days after cardiac or aortic surgery. Area under the curve was 0.78 (95% CI, 0.71-0.85), and the score was well calibrated (Hosmer-Lemeshow P = .53).

Conclusions: The ARDS prediction score can be used to identify high-risk patients from the first day after cardiac or aortic surgery. Patients with a score of 3 or greater should be closely monitored. The score requires external validation before clinical use.
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http://dx.doi.org/10.4037/ajcc2021753DOI Listing
January 2021

A new xanthostatin analogue from the marine sponge-associated actinomycete sp. SCSIO 40064.

Nat Prod Res 2020 Dec 30:1-9. Epub 2020 Dec 30.

Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Innovation Academy of South China Sea Ecology and Environmental Engineering, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China.

A new cyclo-heptadepsipeptide xanthostatin B (), together with isobutyryl hexapeptide (), xanthostatin (), TXS-1 () and TXS-2 (), were isolated from the marine sponge derived sp. SCSIO 40064. The structures were elucidated by comprehensive spectroscopic data analyses and comparison with the literatures. The D-Val unit in was assigned by Marfey's method. The absolute configuration of was determined by X-ray crystallographic analysis. Compounds ‒ were evaluated for the inhibitory activities against four pharmaceutical targets and six antibacterial indicator strains. Compound displayed -glucosidase inhibitory activity with IC value of 18.67 ± 1.27 µM.
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http://dx.doi.org/10.1080/14786419.2020.1867131DOI Listing
December 2020

Efficient Removal of Cu(II), Zn(II), and Cd(II) from Aqueous Solutions by a Mineral-Rich Biochar Derived from a Spent Mushroom () Substrate.

Materials (Basel) 2020 Dec 23;14(1). Epub 2020 Dec 23.

College of Resources and Environment, Shanxi Agricultural University, Taigu 030801, China.

This study evaluated the novel application of a mineral-rich biochar derived from a spent substrate (SAS). Biochars with various pyrolysis temperatures (350-750 °C) were used to remove Cu(II), Zn(II), and Cd(II) from aqueous solutions. The adsorption characteristics and removal mechanisms of the biochars were investigated. The adsorption kinetics and isotherm data were fitted well by pseudo-second-order and Freundlich models. The Langmuir maximum removal capacity () values of Cu(II), Zn(II), and Cd(II) were ordered as SAS750 > SAS350 > SAS550, and the values of SAS750 were 68.1, 55.2, and 64.8 mg·g, respectively. Overall, the removal mechanisms of biochar at a low production temperature (350 °C) to Cu(II), Zn(II), and Cd(II) were mainly via ion exchange (54.0, 56.0, and 43.0%), and at a moderate production temperature (550 °C), removal mechanisms were mainly via coordination with π electrons (38.3, 45.9, and 55.0%), while mineral precipitation (65.2, 44.4, and 76.3%, respectively) was the dominant mechanism at a high produced temperature (750 °C). The variation of the mutual effect of minerals and heavy metals was the predominant factor in the sorption mechanism of mineral precipitation and ion exchange. The results demonstrated that spent substrate biochar is a potential candidate for the efficient removal of heavy metals, which provides a utilization route for spent mushroom substrates.
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http://dx.doi.org/10.3390/ma14010035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794708PMC
December 2020

Surrogate Humane Endpoints in Small Animal Models of Acute Lung Injury: A Modified Delphi Consensus Study of Researchers and Laboratory Animal Veterinarians.

Crit Care Med 2021 Feb;49(2):311-323

Department of Anesthesiology and Pain Medicine, The Ottawa Hospital, Faculty of Medicine, University of Ottawa, ON, Canada.

Objectives: In many jurisdictions, ethical concerns require surrogate humane endpoints to replace death in small animal models of acute lung injury. Heterogenous selection and reporting of surrogate endpoints render interpretation and generalizability of findings between studies difficult. We aimed to establish expert-guided consensus among preclinical scientists and laboratory animal veterinarians on selection and reporting of surrogate endpoints, monitoring of these models, and the use of analgesia.

Design: A three-round consensus process, using modified Delphi methodology, with researchers who use small animal models of acute lung injury and laboratory animal veterinarians who provide care for these animals. Statements on the selection and reporting of surrogate endpoints, monitoring, and analgesia were generated through a systematic search of MEDLINE and Embase. Participants were asked to suggest any additional potential statements for evaluation.

Setting: A web-based survey of participants representing the two stakeholder groups (researchers, laboratory animal veterinarians). Statements were rated on level of evidence and strength of support by participants. A final face-to-face meeting was then held to discuss results.

Subjects: None.

Interventions: None.

Measurements And Main Results: Forty-two statements were evaluated, and 29 were rated as important, with varying strength of evidence. The majority of evidence was based on rodent models of acute lung injury. Endpoints with strong support and evidence included temperature changes and body weight loss. Behavioral signs and respiratory distress also received support but were associated with lower levels of evidence. Participants strongly agreed that analgesia affects outcomes in these models and that none may be necessary following nonsurgical induction of acute lung injury. Finally, participants strongly supported transparent reporting of surrogate endpoints. A prototype composite score was also developed based on participant feedback.

Conclusions: We provide a preliminary framework that researchers and animal welfare committees may adapt for their needs. We have identified knowledge gaps that future research should address.
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http://dx.doi.org/10.1097/CCM.0000000000004734DOI Listing
February 2021