Publications by authors named "Hongyan Li"

713 Publications

Coiled-Coil Domain-Containing 68 Downregulation Promotes Colorectal Cancer Cell Growth by Inhibiting ITCH-Mediated CDK4 Degradation.

Front Oncol 2021 22;11:668743. Epub 2021 Apr 22.

Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.

Coiled-coil domain-containing 68 (CCDC68) plays different roles in cancer and is predicted as a tumor suppressor in human colorectal cancer (CRC). However, the specific role of CCDC68 in CRC and the underlying mechanisms remain unknown. Here, we showed that CCDC68 expression was lower in CRC than that in corresponding normal tissues, and CCDC68 level was positively correlated with disease-free survival. Ectopic expression of CCDC68 decreased CRC cell proliferation and suppressed the growth of CRC xenograft tumors . CCDC68 caused G0/G1 cell cycle arrest, downregulated CDK4, and upregulated ITCH, the E3 ubiquitin ligase responsible for CDK4 protein degradation. This increased CDK4 degradation, which decreased CDK4 protein levels and inhibited CRC tumor growth. Collectively, the present results identify a novel CDK4 regulatory axis consisting of CCDC68 and ITCH, which suggest that CCDC68 is a promising target for the treatment of CRC.
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http://dx.doi.org/10.3389/fonc.2021.668743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100586PMC
April 2021

Neuroprotective Effect for Cerebral Ischemia by Natural Products: A Review.

Front Pharmacol 2021 22;12:607412. Epub 2021 Apr 22.

Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Natural products have a significant role in the prevention of disease and boosting of health in humans and animals. Stroke is a disease with high prevalence and incidence, the pathogenesis is a complex cascade reaction. In recent years, it's reported that a vast number of natural products have demonstrated beneficial effects on stroke worldwide. Natural products have been discovered to modulate activities with multiple targets and signaling pathways to exert neuroprotection via direct or indirect effects on enzymes, such as kinases, regulatory receptors, and proteins. This review provides a comprehensive summary of the established pharmacological effects and multiple target mechanisms of natural products for cerebral ischemic injury and preclinical models, and their potential neuro-therapeutic applications. In addition, the biological activity of natural products is closely related to their structure, and the structure-activity relationship of most natural products in neuroprotection is lacking, which should be further explored in future. Overall, we stress on natural products for their role in neuroprotection, and this wide band of pharmacological or biological activities has made them suitable candidates for the treatment of stroke.
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http://dx.doi.org/10.3389/fphar.2021.607412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102015PMC
April 2021

Interleukin-6 participates in human pancreatic stellate cell activation and collagen I production via TGF-β1/Smad pathway.

Cytokine 2021 Apr 20:155536. Epub 2021 Apr 20.

Department of Hepatic Biliary Pancreatic Medicine, First Hospital of Jilin University, Changchun, China. Electronic address:

Pancreatic stellate cells (PSCs) play a key role in fibrogenesis during alcoholic chronic pancreatitis (ACP). Transforming growth factor-β1 (TGF-β1) is a major regulator of PSC activation and extracellular matrix production. Interleukin-6 (IL-6) has shown to participate in TGF-β1 production and rat PSC activation. This study aimed to investigate whether IL-6 promotes human PSC activation and collagen 1(Col1) production through the TGF-β1/Smad pathway. Our results showed that the expression of IL-6 and IL-6R in activated PSCs and macrophages (Mφs) were enhanced in the pancreas of ACP compared to healthy controls and that the mRNA expression of IL-6, IL-6R, TGF-β1, α-SMA or Col1a1 were significantly increased in the pancreas of ACP, showing positive correlations between elevated IL-6 levels and either TGF-β1 or α-SMA or Col1a1 levels and between elevated TGF-β1 levels and α-SMA or Col1a1 levels. In in vitro studies, we identified that IL-6R expression or IL-6 and TGF-β1 secretions were significantly increased in, respectively, Mφs and PSCs by ethanol (EtOH) or lipopolysaccharide (LPS) stimulation while EtOH- or LPS-induced α-SMA or Col1a1 mRNA and protein production in PSCs were partially blocked by IL-6 antibody. IL-6-induced TGF-β1 production in PSCs was antagonized by si-IL-6R RNA or by an inhibitor of STAT3. Additionally, IL-6-promoted α-SMA or Col1a1 protein production was blocked by TGF-β1 antibody and IL-6-induced phosphorylation of Smad2/3 and transcription of α-SMA and Col1a1 mRNA were antagonized by si-TGF-β1 RNA. Our findings indicate that IL-6 contributes to PSC activation and Col1 production through up-regulation of TGF-β1/Smad2/3 pathway.
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http://dx.doi.org/10.1016/j.cyto.2021.155536DOI Listing
April 2021

CUDC-101 enhances the chemosensitivity of gemcitabine-treated lymphoma cells.

Leuk Res 2021 Mar 31;106:106575. Epub 2021 Mar 31.

Department of Hematology, Yanbian University Hospital, Jilin, Yanji, 133000, China; Research center of Yanbian University Hospital, Jilin, Yanji, 133000, China. Electronic address:

Background: The metastasis and recurrence of Non-Hodgkin's lymphoma (NHL) is a major cause of morbidity and mortality. Recent work suggests that drugs capable of targeting epigenetic regulatory mechanisms may be well suited to the treatment of such disease progression.

Methods: This study was thus designed to evaluate the ability of the novel histone deacetylase (HDAC) inhibitor CUDC-101 to synergize with gemcitabine in order to kill human HUT78 and Pfeiffer NHL cells. To that end, we analyzed the viability of these NHL cells via CCK-8 assay, while the incidence of apoptosis among treated cells was evaluated via Annexin V-FITC/PI staining and by the Western blotting-mediated evaluation of proteins associate with apoptosis and related signaling pathways.

Results: We found that CUDC-101 and gemcitabine interacted synergistically to reduce NHL cell viability and to induce the apoptotic death of these cells via the EGFR/ PI3K/Akt and Erk pathways, which were regulated by HDAC signaling pathways.

Conclusion: Together, our results highlight the anti-cancer properties of CUDC-101 alone or in combination with gemcitabine as an approach to inducing the apoptotic death of lymphoma cells in vitro, while also offering insight into the underlying molecular mechanisms governing this activity.
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http://dx.doi.org/10.1016/j.leukres.2021.106575DOI Listing
March 2021

Effectiveness of Chinese herbal medicine combined with Western medicine on deferring dialysis initiation for nondialysis chronic kidney disease stage 5 patients: a multicenter prospective nonrandomized controlled study.

Ann Transl Med 2021 Mar;9(6):490

Department of Nephrology, First Affiliated Hospital of Guiyang College of Traditional Chinese Medicine, Guiyang, China.

Background: In clinical practice, Chinese herbal medicine (CHM) purportedly has beneficial therapeutic effects for chronic kidney disease (CKD), which include delaying disease progression and dialysis initiation. However, there is a lack of high-quality evidence-based results to support this. Therefore, this study aimed to evaluate the efficacy of CHM combined with Western medicine in the treatment of stage 5 CKD.

Methods: This was a prospective nonrandomized controlled study. Stage 5 CKD (nondialysis) patients were recruited form 29 AAA class hospitals across China from July 2014 to April 2019. According to doctors' advice and the patients' wishes, patients were assigned to the CHM group (Western medicine + CHM) and the non-CHM group (Western medicine). Patient demographic data, primary disease, blood pressure, Chinese and Western medical drugs, clinical test results, and time of dialysis initiation were collected during follow-up.

Results: A total of 908 patients were recruited in this study, and 814 patients were finally included for further analysis, including 747 patients in the CHM group and 67 patients in the non-CHM group. 482 patients in the CHM group and 52 patients in the non-CHM group initiated dialysis. The median time of initiating dialysis was 9 (7.90, 10.10) and 3 (0.98,5.02) months in the CHM group and non-CHM group, respectively. The multivariate Cox regression analysis showed that patients in the CHM group had a significantly lower risk of dialysis [adjusted hazard ratio (aHR): 0.38; 95% confidence interval (CI): 0.28, 0.53] compared to those in the non-CHM group. After 1:2 matching, the outcomes of 160 patients were analyzed. The multivariate Cox regression analysis showed that patients in the CHM group had a significantly lower risk of dialysis (aHR: 0.32; 95% CI: 0.21, 0.48) compared to patients in the non-CHM group. Also, the Kaplan-Meier analysis demonstrated that the cumulative incidence of dialysis in the CHM group was significantly lower than that in the non-CHM group (log-rank test, P<0.001) before and after matching.

Conclusions: This study suggest that the combination of CHM and Western medicine could effectively reduce the incidence of dialysis and delay the time of dialysis initiation in stage 5 CKD patients.
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http://dx.doi.org/10.21037/atm-21-871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039672PMC
March 2021

Value of F-FDG Hybrid PET/MR in Differentiated Thyroid Cancer Patients with Negative I Whole-Body Scan and Elevated Thyroglobulin Levels.

Cancer Manag Res 2021 29;13:2869-2876. Epub 2021 Mar 29.

Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.

Purpose: To evaluate the diagnostic performance of F-FDG PET/MR in detecting recurrent or metastatic disease in patients with differentiated thyroid cancer (DTC) who have increased thyroglobulin (Tg) levels but a negative I whole-body scan (WBS). The relationship between F-FDG PET/MR and serum Tg levels was explored. We also evaluated the therapeutic impact of PET/MR on patient clinical management.

Patients And Methods: Twenty-nine DTC patients with a negative I-WBS of the last post-therapeutic and increased Tg levels under thyroid-stimulating hormone suppression treatment who underwent F-FDG PET/MR examination were retrospectively analyzed.

Results: Of those 29 patients, F-FDG PET/MR findings were true positive, true negative, false positive, and false negative in 18, 7, 2, and 2 patients, respectively. The overall sensitivity, specificity, and accuracy were 90.0%, 77.8%, and 86.2%, respectively. We noticed significant differences in serum Tg levels between the PET/MR-positive and PET/MR-negative patient groups (=0.049). Receiver operating characteristic curve analysis showed that a Tg level of 2.4 ng/mL was the optimal cut-off value for predicting PET/MR results. The sensitivity, specificity, and accuracy of PET/MR were higher in patients with Tg levels greater than 2.4 ng/mL than in patients with lower levels. By detecting recurrent or metastatic disease, F-FDG PET/MR altered the clinical management in 7 patients (24.1%) of the overall population.

Conclusion: F-FDG PET/MR has high diagnostic accuracy for detecting recurrent or metastatic diseases in DTC patients and is useful for clinical management.
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http://dx.doi.org/10.2147/CMAR.S293005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018385PMC
March 2021

-Borneol Exerted the Neuroprotective Effect by Promoting Angiogenesis Coupled With Neurogenesis via Ang1-VEGF-BDNF Pathway.

Front Pharmacol 2021 5;12:641894. Epub 2021 Mar 5.

Department of Pathology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.

At present, Stroke is still one of the leading causes of population death worldwide and leads to disability. Traditional Chinese medicine plays an important role in the prevention or treatment of stroke. -borneol, a traditional Chinese medicine, has been used in China to treat stroke for thousands of years. However, its mechanism of action is unclear. After cerebral ischemia, promoting angiogenesis after cerebral ischemia and providing nutrition for the infarct area is an important strategy to improve the damage in the ischemic area, but it is also essential to promote neurogenesis and replenish new neurons. Here, our research shows that -borneol can significantly improve the neurological deficits of pMCAO model rats, reduce cerebral infarction, and improve the pathological damage of cerebral ischemia. and significantly increase serum level of Ang-1 and VEGF, and significantly decrease level of ACE and Tie2 to promote angiogenesis. PCR and WB showed the same results. Immunohistochemistry also showed that borneol can increase the number of CD34 positive cells, further verifying that borneol can play a neuroprotective effect by promoting angiogenesis after cerebral ischemia injury. In addition, borneol can significantly promote the expression level of VEGF, BDNF and inhibit the expression levels of TGF-β1 and MMP9 to promote neurogenesis. The above suggests that borneol can promote angiogenesis coupled neurogenesis by regulating Ang1-VEGF-BDNF to play a neuroprotective effect. Molecular docking also shows that borneol has a very high binding rate with the above target, which further confirmed the target of borneol to improve cerebral ischemic injury. These results provide strong evidence for the treatment of cerebral ischemia with borneol and provide reference for future research.
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http://dx.doi.org/10.3389/fphar.2021.641894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973462PMC
March 2021

Discovery of Selective Pituitary Adenylate Cyclase 1 Receptor (PAC1R) Antagonist Peptides Potent in a Maxadilan/PACAP38-Induced Increase in Blood Flow Pharmacodynamic Model.

J Med Chem 2021 Mar 15;64(6):3427-3438. Epub 2021 Mar 15.

Therapeutic Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320, United States.

Inhibition of the pituitary adenylate cyclase 1 receptor (PAC1R) is a novel mechanism that could be used for abortive treatment of acute migraine. Our research began with comparative analysis of known PAC1R ligand scaffolds, PACAP38 and Maxadilan, which resulted in the selection of des(24-42) Maxadilan, , as a starting point. C-terminal modifications of improved the peptide metabolic stability and . SAR investigations identified synergistic combinations of amino acid replacements that significantly increased the PAC1R inhibitory activity of the analogs to the pM IC range. Our modifications further enabled deletion of up to six residues without impacting potency, thus improving peptide ligand binding efficiency. Analogs and exhibited robust efficacy in the rat Maxadilan-induced increase in blood flow (MIIBF) pharmacodynamic model at 0.3 mg/kg subcutaneous dosing. The first cocrystal structure of a PAC1R antagonist peptide () with PAC1R extracellular domain is reported.
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http://dx.doi.org/10.1021/acs.jmedchem.0c01396DOI Listing
March 2021

Quality evaluation and geographical classification of immature rape and acacia honeys in China.

J Sci Food Agric 2021 Mar 7. Epub 2021 Mar 7.

State Key Laboratory of Food Science and Technology, University of Nanchang, Nanchang, China.

Background: To reflect and understand the real situation regarding immature honey, the quality parameters of 141 honey samples from different regions of China were evaluated. The possibility of classifying Chinese honey from different geographical origins was also considered.

Results: The results revealed that the values of diastase, sucrose, proline and 5-hydroxymethylfurfural (HMF) met the international honey standard, although moisture, total glucose and fructose, and invertase content in most of the honey samples failed to meet the standards. In addition, honey from different geographical locations could be well separated based on the contents of maltose, sucrose, HMF and glucose oxidase.

Conclusion: The maturity of honey has a great impact on its quality, and the geographical origin of immature honey could be classified according to the physicochemical parameters. © 2021 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.11193DOI Listing
March 2021

A Highly Expanded Polycarboxylate Gel and New Environmental Response Effects for Efficiently Adsorbing and Recovering Cu(II) from Water.

ACS Omega 2021 Mar 18;6(8):5318-5334. Epub 2021 Feb 18.

College of Chemistry and Chemical Engineering, Jiangxi Normal University, Ziyang Road 99, Nanchang 330022, China.

A new highly expanded polycarboxylate gel (EPCG) was accidentally formed in a facile cross-linking copolymerization system. When used as an adsorbent material, the EPCG could be quickly expanded 29.44 times in water to have a high permeability inside for realizing the efficient adsorption toward Cu(II) from water. The adsorption capacity of EPCG toward Cu(II) was 261.70 mg/g, which was higher than that of all the selected existing adsorbents reported in recent years. The adsorption rate of expanded EPCG was 3.61 times higher than that of the previous polyantionic gel. Similarly, due to the high expansion and high permeability of EPCG, the EPCG skeleton could be further coated with an alkaline NaOH, forming a novel NaOH-coated EPCG material, and its adsorption capacity toward Cu(II) was further improved to 333.21 mg/g compared to that of pure EPCG adsorbent. Moreover, the EPCG wastes after adsorbing Cu(II) could be fully desorbed to be regenerated for reuse. A total of 99.39% of the adsorbed Cu(II) was desorbed from EPCG wastes to be recovered. The adsorption capacity of regenerated EPCG reused for adsorbing Cu(II) was 259.05 mg/g, which was very near that of the original EPCG. In addition, a series of simulation experiments and instrumental analysis were adopted to confirm the new environmental response effects as the key factors in the purification of Cu(II)-containing wastewater, including "expansion-shrink," "alkali-coating," and "acid-desorption" responses.
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http://dx.doi.org/10.1021/acsomega.0c05431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931198PMC
March 2021

Chemotherapy-induced acute vascular injury involves intracellular generation of ROS via activation of the acid sphingomyelinase pathway.

Cell Signal 2021 Jun 26;82:109969. Epub 2021 Feb 26.

Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. Electronic address:

Several categories of chemotherapy confer substantial risk for late-term vascular morbidity and mortality. In the present study, we aimed to investigate the mechanism of acute chemotherapy-induced vascular injury in normal tissues. Specifically, we looked at activation of the acid sphingomyelinase (ASMase)/ceramide pathway, which leads to generation of reactive oxygen species (ROS) and induction of oxidative stress that may result in vascular injury. In particular, we focused on two distinct drugs, doxorubicin (DOX) and cisplatin (CIS) and their effects on normal endothelial cells. In vitro, DOX resulted in increased ASMase activity, intra-cellular ROS production and induction of apoptosis. CIS treatment generated significantly reduced effects in endothelial cells. In-vivo, murine femoral arterial blood flow was measured in real-time, during and after DOX or CIS administration, using fluorescence optical imaging system. While DOX caused constriction of small vessels and disintegration of large vessels' wall, CIS induced minor vascular changes in arterial blood flow, correlating with the in vitro findings. These results demonstrate that DOX induces acute vascular injury by increased ROS production, via activation of ASMase/ceramide pathway, while CIS increases ROS production and its immediate extracellular translocation, without causing detectable acute vascular injury. Our findings may potentially lead to the development of new strategies to prevent long-term cardiovascular morbidity in cancer survivors.
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http://dx.doi.org/10.1016/j.cellsig.2021.109969DOI Listing
June 2021

The synergistic and antagonistic antioxidant interactions of dietary phytochemical combinations.

Crit Rev Food Sci Nutr 2021 Feb 22:1-20. Epub 2021 Feb 22.

State Key Laboratory of Food Science and Technology, University of Nanchang, Jiangxi, China Nanchang.

The frequent intake of whole foods and dietary food variety is recommended due to their health benefits, such as prevention of multiple chronic diseases, including cancer, Alzheimer's disease, cardiovascular diseases, and type 2 diabetes mellitus. Often, consuming whole fruits or vegetables showed the enhanced effects than consuming the individual dietary supplement from natural products, which is widely explained by the interactive effects of co-existing phytochemicals in whole foods. Although research relevant to interactive effects among the bioactive compounds mounted up, the mechanism of interaction is still not clear. Especially, biological influence factors such as bioavailability are often neglected. The present review summarizes the progress on the synergistic and antagonistic effects of dietary phytochemicals, the evaluating models for antioxidant interactions, and the possible interaction mechanisms both in vitro and in vivo, and with an emphasis on biological-related molecular mechanisms of phytochemicals. The research on the interaction mechanism is of value for guiding how to take advantage of synergistic effects and avoid antagonistic effects in daily diets or phytochemical-based treatments for preventing chronic diseases.
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http://dx.doi.org/10.1080/10408398.2021.1888693DOI Listing
February 2021

Single- or dual-antiplatelet therapy after transcatheter aortic valve replacement: A protocol of systematic review and meta-analysis.

Medicine (Baltimore) 2021 Feb;100(6):e24550

Qinghai People's Hospital, Qinghai, China.

Background: The evidence related to bleeding and thromboembolic events after transcatheter aortic valve replacement (TAVR) compared single antiplatelet therapy (SAPT) with dual antiplatelet therapy (DAPT) treatment are inconsistent. Moreover, there are some limitations such as small sample size and the risk of bias in existing studies. We will conduct a comprehensive systematic review and meta-analysis to explore the safety and efficacy of SAPT or DAPT after TAVR.

Methods: A comprehensive literature search of PubMed, EMBASE, The Cochrane Library, Cochrane Central Register of Controlled Trials will be searched to retrieve studies involving SAPT versus DAPT after TAVR. Two investigators will independently select studies, extract data, and assess the quality of the included study. Any disagreement will be resolved by the third investigator. The study will use a random-effects model to pool the results of all studies and use the relative risk and 95% confidence intervals to summarize individual trial outcomes and estimate pooled effect. The study will use the Grading of Recommendations Assessment, Development, and Evaluation to assess the certainty of evidence.

Results: This study will provide high-quality evidence for treatment of TAVR in terms of effectiveness and safety.

Conclusion: This systematic review aims to provide evidence for treatment of TAVR in different antiplatelet therapies.

Registration: The systematic review and meta-analysis is registered in the OSF REGISTRIES (10.17605/OSF.IO/Q42TE) international prospective register.
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http://dx.doi.org/10.1097/MD.0000000000024550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886480PMC
February 2021

The value of predictive nursing in convalescent patients with liver cancer after operation and evaluation of nursing measures.

Panminerva Med 2021 Feb 10. Epub 2021 Feb 10.

Department of Hepatopancreatobiliary Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China -

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http://dx.doi.org/10.23736/S0031-0808.21.04295-6DOI Listing
February 2021

Quality-adjusted survival in patients with metastatic colorectal cancer treated with fruquintinib in the FRESCO trial.

Future Oncol 2021 May 10;17(15):1923-1931. Epub 2021 Feb 10.

Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis & Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, 100048, China.

To assess whether the survival benefit of fruquintinib is quality-adjusted. Data of 416 metastatic colorectal cancer patients from the Phase III FRESCO trial were used. The Quality-adjusted Time Without Symptoms or Toxicity (Q-TWiST) analysis assessed the quality-adjusted survival benefit of fruquintinib versus placebo, accounting for freedom from symptomatic disease and from severe side effects of treatment. Fruquintinib significantly improved patients' Q-TWiST (difference: 2.23 [1.41, 3.04] months) versus placebo. The Q-TWiST gain was 28.3% in the base case and ranged from 16.7 to 39.9% in the threshold analysis, favoring fruquintinib. The Q-TWiST benefit was observed in fruquintinib-treated patients regardless of prior targeted therapy. Fruquintinib provides a clinically meaningful quality-adjusted survival benefit versus placebo as a third-line treatment for metastatic colorectal cancer patients.
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http://dx.doi.org/10.2217/fon-2020-1215DOI Listing
May 2021

Predicting COVID-19 disease progression and patient outcomes based on temporal deep learning.

BMC Med Inform Decis Mak 2021 02 8;21(1):45. Epub 2021 Feb 8.

Institute of Population Research, Peking University, No.5 Yiheyuan Road, Beijing, 100871, People's Republic of China.

Background: The coronavirus disease 2019 (COVID-19) pandemic has caused health concerns worldwide since December 2019. From the beginning of infection, patients will progress through different symptom stages, such as fever, dyspnea or even death. Identifying disease progression and predicting patient outcome at an early stage helps target treatment and resource allocation. However, there is no clear COVID-19 stage definition, and few studies have addressed characterizing COVID-19 progression, making the need for this study evident.

Methods: We proposed a temporal deep learning method, based on a time-aware long short-term memory (T-LSTM) neural network and used an online open dataset, including blood samples of 485 patients from Wuhan, China, to train the model. Our method can grasp the dynamic relations in irregularly sampled time series, which is ignored by existing works. Specifically, our method predicted the outcome of COVID-19 patients by considering both the biomarkers and the irregular time intervals. Then, we used the patient representations, extracted from T-LSTM units, to subtype the patient stages and describe the disease progression of COVID-19.

Results: Using our method, the accuracy of the outcome of prediction results was more than 90% at 12 days and 98, 95 and 93% at 3, 6, and 9 days, respectively. Most importantly, we found 4 stages of COVID-19 progression with different patient statuses and mortality risks. We ranked 40 biomarkers related to disease and gave the reference values of them for each stage. Top 5 is Lymph, LDH, hs-CRP, Indirect Bilirubin, Creatinine. Besides, we have found 3 complications - myocardial injury, liver function injury and renal function injury. Predicting which of the 4 stages the patient is currently in can help doctors better assess and cure the patient.

Conclusions: To combat the COVID-19 epidemic, this paper aims to help clinicians better assess and treat infected patients, provide relevant researchers with potential disease progression patterns, and enable more effective use of medical resources. Our method predicted patient outcomes with high accuracy and identified a four-stage disease progression. We hope that the obtained results and patterns will aid in fighting the disease.
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http://dx.doi.org/10.1186/s12911-020-01359-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869774PMC
February 2021

Reviewing immunopathology characteristics of SARS-CoV-2 for cancer entwisted with SARS-CoV-2.

SAGE Open Med 2021 27;9:2050312121989504. Epub 2021 Jan 27.

General Surgery Department, Xuanwu Hospital, Beijing, China.

In December 2019, the outbreak of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infection that started in Wuhan, Hubei Province, China, has spread to all world. Based on the accumulated data and knowledge on the coronavirus infection and immunology characteristics, this review would hope to give some hints on human immune response to SARS-CoV-2 infection in cancer patients. This insight may help in designing the appropriate immune intervention for treatment and the prophylactic/therapeutic methods against cancer under current coronavirus from immunopathology characteristics of SARS-CoV-2 and cancer entwisted with it. We should achieve accurate diagnosis and treatment for cancer patients through advantages of multidisciplinary diagnosis and treatment team. It is believed that we will eventually overcome the epidemic and win in the future.
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http://dx.doi.org/10.1177/2050312121989504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844443PMC
January 2021

Structural comparisons of pyrodextrins during thermal degradation process: The role of hydrochloric acid.

Food Chem 2021 Jul 27;349:129174. Epub 2021 Jan 27.

China-Canada Joint Lab of Food Nutrition and Health (Beijing), School of Food and Health, Beijing Technology and Business University (BTBU), 11 Fucheng Road, Beijing 100048, China.

Hydrochloric acid (HCl) is widely used to prepare pyrodextrins, especially the water-soluble pyrodextrin. In this study, the structural difference between pyrodextrins as affected by HCl is compared by characterizing the molecular size, chain-length distributions (CLDs), crystallinity, and solubility. It is found that: 1) dry heating of starch granules without HCl mainly degrades long-amylose chains while slightly affects amylopectin branches; 2) the presence of HCl during dry heating decreases the degree of polymerization (DP) range of amylose chains upon degradation from DP ~ 833-1267 to DP ~ 206-432, suggesting that the presence of HCl accelerates the breakdown of long-amylose chains; 3) both pyroconversion processes have slight effects on A-(DP ~ 6-12) and B- chains (DP ~ 12-24), which might explain the retained granular and crystalline structure during the process. This study could improve the understanding of the role of HCl in affecting the structure and property during pyroconversion of native starch.
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http://dx.doi.org/10.1016/j.foodchem.2021.129174DOI Listing
July 2021

Spontaneous unscarred uterine rupture in a twin pregnancy complicated by adenomyosis: A case report.

Medicine (Baltimore) 2021 Jan;100(3):e24048

Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University.

Introduction: Uterine rupture during pregnancy is a serious obstetric complication accompanied by a high incidence of maternal morbidity and mortality, and the presence of uterine scars is the main risk factor. In the present case, uterine rupture occurred in an unscarred uterus in a nonlaboring primigravida woman with adenomyosis and twin pregnancy in the third trimester.

Patient Concerns: In this case, the patient suspected to have a history of endometriosis have got twin pregnancies following intracytoplasmic sperm injection, and complained of recurrent lower abdominal pain from 16 weeks to 29 weeks of gestation.

Diagnosis: After exploratory laparotomy, the patient was diagnosed with uterine rupture and adenomyosis.

Interventions: The patient was first administered expectant treatment such as antibiotics, tocolytics, and fluid replacement therapy. Symptoms then appeared repeatedly and worsened, followed by eventual peritoneal irritation, and exploratory laparotomy was performed.

Outcomes: Two live female fetuses were extracted by cesarean section, and the uterine laceration was repaired. The mother recovered without any postoperative complications, and the babies were discharged after receiving one month of prematurity care without any postnatal complications.

Conclusion: Adenomyosis and the conception of twins may lead to uterine rupture. For pregnant women with a history of adenomyosis with multiple gestations, close monitoring for signs of uterine rupture is necessary. Single-embryo transfer and multifetal pregnancy reduction should be recommended for infertile patients with adenomyosis.
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http://dx.doi.org/10.1097/MD.0000000000024048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837926PMC
January 2021

Do short chain fatty acids and phenolic metabolites of the gut have synergistic anti-inflammatory effects? - New insights from a TNF-α-induced Caco-2 cell model.

Food Res Int 2021 Jan 27;139:109833. Epub 2020 Oct 27.

Guelph Research & Development Centre, Agriculture and Agri-Food Canada, Guelph, ON, Canada. Electronic address:

Fermentation of dietary fiber and metabolism of polyphenols by the gut microbiota produce short chain fatty acids (SCFAs) and some simple phenolic acids, both of which have been independently shown to have anti-inflammatory effects and to improve gut health. While synergistic interactions between the two colonic metabolite groups have been speculated, direct evidence on whether and how these compounds work together towards collective anti-inflammatory effect and gut health remain unclear. In this study, the most important SCFA butyric acid (BtA) and three phenolic metabolites benzoic acid (BzA), phenylacetic acid (PAA) and phenylpropionic acid (PPA) were selected and assessed for the anti-inflammatory effects and the underlying mechanisms in a TNF-α-induced Caco-2 cell model. Significantly stronger inhibition of TNF-α-induced IL-8 production was found in cells pre-treated with different concentrations of mixtures of BtA and the phenolic metabolites than individual compounds. Further study showed that the synergistic effect was via significant down-regulation of the gene expressions of IL-8, TNF-α and VCAM-1, and of phosphorylation of JNK, p38 and IĸBα, cellular signaling mediators of the MAPK and NF-κB pathways. Although these are results of a cell model, they do provide significant insights into the synergistic anti-inflammatory effects between SCFAs and phenolic metabolites. As both metabolite groups are simultaneously present in the gut, our findings therefore also suggest a potential synergistic effect between the two colonic metabolite groups in maintaining gut health.
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http://dx.doi.org/10.1016/j.foodres.2020.109833DOI Listing
January 2021

Functional Characteristics of and Yeast Single Starter Cultures in the Ripening Process of Dry Fermented Sausage.

Front Microbiol 2020 8;11:611260. Epub 2021 Jan 8.

China-Canada Joint Lab of Food Nutrition and Health (Beijing), Beijing Advanced Innovation Center for Food Nutrition and Human Health (BTBU), Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology & Business University (BTBU), Beijing, China.

Dry fermented sausage is popular among the world because of its rich nutrition and unique flavor. Starter cultures play an important role in the quality of dry fermented sausage. In this study, probiotics lactic acid bacteria N102, H1-5, Y4-1, and Y12-3 were isolated from food-borne materials. The physicochemical properties, microbial populations, TBARS, lipolysis, proteolysis, and volatile flavor compounds of dry fermented sausages with different starter cultures were evaluated comparatively during the ripening process. The results showed that both N102 and H1-5 grow well and could rapidly reduce the pH value of the products. At the same time, they could significantly reduce the number of , so as to ensure the safety of the products. In addition, the strains N102 promoted the formation of flavor compounds 2,3-butanedione, 3-hydroxy-2-butanone, and carnosine, whereas taurine content of batch H1-5 was significantly increased, while yeast y4-1 and y12-3 could also grow faster in sausage and promoted the esters and alcohols formation such as ethyl acetate and linalool, with the formation of γ-aminobutyric acid by y4-1. Compared with lactic acid bacteria, yeasts showed to contribute more in flavor formation and effective inhibition of lipid oxidation. The starter cultures played different roles in flavor contribution and had obvious differentiation in the ripening process of dry fermented sausage.
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http://dx.doi.org/10.3389/fmicb.2020.611260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819883PMC
January 2021

Effect of alkylresorcinols on the formation of Nε-(carboxymethyl)lysine and sensory profile of wheat bread.

Food Sci Nutr 2021 Jan 18;9(1):489-498. Epub 2020 Nov 18.

China-Canada Joint Lab of Food Nutrition and Health (Beijing) Beijing Technology & Business University (BTBU) Beijing China.

Alkylresorcinols (ARs) are important bioactive components in wheat bran which have been used as biomarkers for whole grain wheat consumption. In this study, the impact of ARs on the formation of Nε-(carboxymethyl)lysine (CML), the main component of dietary advanced glycation end products which could induce chronic disease was analyzed. Moreover, the influence of the addition of ARs on the sensory profiles of wheat bread was evaluated. ARs supplementation (0.03%, 0.1%, and 0.3% w/w) could significantly decrease the formation of CML by 21.70%, 35.11%, and 42.18%, respectively, compared with the control. Moreover, ARs-supplemented bread achieved a higher score in overall acceptability and buttery-like aroma through sensory evaluation. The volatile compounds in bread supplemented with ARs were characterized by headspace solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS), among which acetoin, 2,3-butanedione, 3-methyl-1-butanol, 2-phenylethanol, and 2-methylbutanal were confirmed as the main volatile compounds through determination of odor activity value. In addition, ARs supplementation had no negative impact on the chewiness, hardness, and springiness of bread. These findings demonstrated that ARs could be applied as potential food additives to improve the quality and sensory profile of bread.
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http://dx.doi.org/10.1002/fsn3.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802564PMC
January 2021

CCDC68 Upregulation by IL-6 Promotes Endometrial Carcinoma Progression.

J Interferon Cytokine Res 2021 01;41(1):12-19

The First Affiliated Hospital of Anhui Medical University, Hefei, China.

The elevation of circulating interleukin 6 (IL-6) is one of the major molecular characteristics of endometrial carcinoma. In this study, we investigated the role of coiled-coil domain-containing 68 (CCDC68) in IL-6-associated endometrial carcinoma progression. CCDC68 expression levels and the activation of IL-6 pathway were detected by qPCR and Western blot. Stable CCDC68 knockdown Ishikawa and RL-95 cells were created to investigate cancer cell proliferation, migration, and invasion with or without IL-6 administration. Kaplan-Meier's analysis was used to determine the correlation between CCDC68 expression and overall survival or recurrence-free survival in endometrial carcinoma patients. CCDC68 expression level is significantly uregulated by IL-6 stimulation. Increased CCDC68 expression predicts poor prognosis in endometrial carcinoma patients. CCDC68 knockdown dramatically inhibit IL-6-associated cancer cell proliferation, migration, invasion, and downregulate the expression of proto-oncogenes in endometrial carcinoma cells. CCDC68 acts as a cancer-promoting factor in IL-6-stimulated endometrial carcinoma cells, and blocking the expression of CCDC68 might be a novel therapeutic strategy for the endometrial carcinoma treatment.
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http://dx.doi.org/10.1089/jir.2020.0193DOI Listing
January 2021

Crosstalk of the Caspase Family and Mammalian Target of Rapamycin Signaling.

Int J Mol Sci 2021 Jan 15;22(2). Epub 2021 Jan 15.

Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Road, Lanzhou 730000, China.

Cell can integrate the caspase family and mammalian target of rapamycin (mTOR) signaling in response to cellular stress triggered by environment. It is necessary here to elucidate the direct response and interaction mechanism between the two signaling pathways in regulating cell survival and determining cell fate under cellular stress. Members of the caspase family are crucial regulators of inflammation, endoplasmic reticulum stress response and apoptosis. mTOR signaling is known to mediate cell growth, nutrition and metabolism. For instance, over-nutrition can cause the hyperactivation of mTOR signaling, which is associated with diabetes. Nutrition deprivation can inhibit mTOR signaling via SH3 domain-binding protein 4. It is striking that Ras GTPase-activating protein 1 is found to mediate cell survival in a caspase-dependent manner against increasing cellular stress, which describes a new model of apoptosis. The components of mTOR signaling-raptor can be cleaved by caspases to control cell growth. In addition, mTOR is identified to coordinate the defense process of the immune system by suppressing the vitality of caspase-1 or regulating other interferon regulatory factors. The present review discusses the roles of the caspase family or mTOR pathway against cellular stress and generalizes their interplay mechanism in cell fate determination.
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http://dx.doi.org/10.3390/ijms22020817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830632PMC
January 2021

Whole genome sequencing of 10K patients with acute ischaemic stroke or transient ischaemic attack: design, methods and baseline patient characteristics.

Stroke Vasc Neurol 2020 Dec 18. Epub 2020 Dec 18.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

Background And Purpose: Stroke is the second leading cause of death worldwide and the leading cause of mortality and long-term disability in China, but its underlying risk genes and pathways are far from being comprehensively understood. We here describe the design and methods of whole genome sequencing (WGS) for 10 914 patients with acute ischaemic stroke or transient ischaemic attack from the Third China National Stroke Registry (CNSR-III).

Methods: Baseline clinical characteristics of the included patients in this study were reported. DNA was extracted from white blood cells of participants. Libraries are constructed using qualified DNA, and WGS is conducted on BGISEQ-500 platform. The average depth is intended to be greater than 30× for each subject. Afterwards, Sentieon software is applied to process the sequencing data under the Genome Analysis Toolkit best practice guidance to call genotypes of single nucleotide variants (SNVs) and insertion-deletions. For each included subject, 21 fingerprint SNVs are genotyped by MassARRAY assays to verify that DNA sample and sequencing data originate from the same individual. The copy number variations and structural variations are also called for each patient. All of the genetic variants are annotated and predicted by bioinformatics software or by reviewing public databases.

Results: The average age of the included 10 914 patients was 62.2±11.3 years, and 31.4% patients were women. Most of the baseline clinical characteristics of the 10 914 and the excluded patients were balanced.

Conclusions: The WGS data together with abundant clinical and imaging data of CNSR-III could provide opportunity to elucidate the molecular mechanisms and discover novel therapeutic targets for stroke.
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http://dx.doi.org/10.1136/svn-2020-000664DOI Listing
December 2020

Template-less Synthesis of Coded Au Nanowires.

Nano Lett 2021 Jan 14;21(2):1156-1160. Epub 2021 Jan 14.

Institute of Advanced Synthesis, and School of Chemistry and Molecular Engineering, Jiangsu National Synergetic Innovation Center for Advanced Materials, Nanjing Tech University, Nanjing 211816, People's Republic of China.

Morphological coding of nanostructures represents a capability in rapid modulation of structural features and most importantly, the transcription of information into nanoscale. Exploiting the regioselectivity in the template-less electrochemical synthesis of ultrathin Au nanowires, we show that rapid alternation of applied potential would cause corresponding change in the width of the emerging nanowire segments. By understanding the growth kinetics, a strong correlation between the nanowire morphologies and the deposition potential is established and applied in emulating the Morse code.
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http://dx.doi.org/10.1021/acs.nanolett.0c04678DOI Listing
January 2021

Influence of indications on perinatal outcomes after radio frequency ablation in complicated monochorionic pregnancies: a retrospective cohort study.

BMC Pregnancy Childbirth 2021 Jan 9;21(1):41. Epub 2021 Jan 9.

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

Background: Radiofrequency ablation (RFA) is recommended to prevent potential neurological injury or intrauterine foetal death (IUFD) of the co-twin(s) in complicated monochorionic (MC) pregnancies. However, the impacts of various indications on the pregnancy outcome following RFA remain unclear. This study aimed to determine how the indications influence the perinatal outcomes in complicated MC pregnancies undergoing radiofrequency ablation.

Methods: This was a retrospective cohort study performed in a single centre. All consecutive MC pregnancies treated with RFA between July 2011 and July 2019 were included. The adverse perinatal outcomes and the survival rate were analysed based on various indications. The continuous variables with and without normal distribution were compared between the groups using Student's t-test and Mann-Whitney U test, respectively, and for categorical variables, Chi-square and Fisher's exact tests were used. P < 0.05 indicated a significant difference.

Results: We performed 272 RFA procedures in 268 complicated MC pregnancies, including 60 selective intrauterine growth restriction (sIUGR), 64 twin-twin transfusion syndrome (TTTS), 12 twin reversed arterial perfusion sequence (TRAPs), 66 foetal anomaly and 66 elective foetal reduction (EFR) cases. The overall survival rate of the co-twin was 201/272 (73.9%). The overall technical successful rate was determined at 201/263 (76.7%). The IUFD rate in the co-twin was 20/272 (7.4%). The TTTS group had recorded the lowest survival rate (37/64, 57. 8%), and the survival rate was significantly correlated with Quintero stages (P = 0.029). Moreover, the sIUGR III subgroup had a lower survival rate compared with sIUGR II (55.6%, versus 84.3%). The subgroup of foetal anomaly of gastroschisis or exomphalos had the highest IUFD rate (4/10, 40%), followed by sIUGR III (2/9, 22.2%) and dichorionic triamniotic (DCTA) subgroup (8/46, 17.9%). In EFR group, eight IUFD cases were all coming from the DCTA subgroup and received RFA before 17 weeks.

Conclusions: The perinatal outcome of RFA was correlated with the indications, with the lowest survival rate in TTTS IV and the highest IUFD incidence in abdominal wall defect followed by sIUGR III. Elective RFA after 17 weeks may prevent IUFD in DCTA pregnancies.
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http://dx.doi.org/10.1186/s12884-020-03530-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797138PMC
January 2021

Nomograms based on SUVmax of F-FDG PET/CT and clinical parameters for predicting progression-free and overall survival in patients with newly diagnosed extranodal natural killer/T-cell lymphoma.

Cancer Imaging 2021 Jan 8;21(1). Epub 2021 Jan 8.

Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan, 430022, China.

Background: The prognostic value of F-FDG PET/CT in extranodal natural killer/T-cell lymphoma (ENKTL) is not well established. We aimed to develop nomograms for individualized estimates of progression-free survival (PFS) and overall survival (OS) in patients with ENKTL using F-FDG PET/CT parameters and clinical parameters.

Methods: A total of 171 patients with newly diagnosed ENKTL undergoing F-FDG PET/CT scanning were retrospectively analyzed. Nomograms were constructed according to multivariate Cox proportional hazards regression. The predictive and discriminatory capacities of the nomograms were then measured using the concordance index (C-index), calibration plots, and Kaplan-Meier curves. The C-index, the area under receiver operating characteristic (ROC) curve (AUC), and decision curve analysis (DCA) were used to contrast the predictive and discriminatory capacities of the nomograms against with the International Prognostic Index (IPI) and Korean Prognostic Index (KPI).

Results: Multivariate analysis demonstrated that pretreatment SUVmax≥9.5, disease stage II and III-IV, elevated lactate dehydrogenase (LDH), and elevated β2-microglobulin (β2-MG) had the strongest association with unfavorable PFS and OS. In addition, hemoglobin (Hb) < 120 g/L had a tendency to be associated with PFS. Both nomogram models incorporated SUVmax, Ann Arbor stage, LDH, and β2-MG. The PFS nomogram also included Hb. The nomograms showed good prediction accuracies, with the C-indexes for PFS and OS were 0.729 and 0.736, respectively. The calibration plots for 3-year and 5-year PFS/OS reported good consistency between predicted and observed probabilities for survival time. The PFS and OS were significantly different according to tertiles of nomogram scores (p < 0.001). The C-index and AUCs of the nomograms were higher than that of IPI and KPI. Moreover, DCA showed that the predictive accuracy of the nomograms for PFS and OS were both higher than that of IPI and KPI.

Conclusions: This study established nomograms that incorporate pretreatment SUVmax and clinical parameters, which could be effective tools for individualized prognostication of both PFS and OS in patients with newly diagnosed ENKTL.
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http://dx.doi.org/10.1186/s40644-020-00379-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796613PMC
January 2021

Association of apoE gene polymorphisms with lipid metabolism in renal diseases.

Afr Health Sci 2020 Sep;20(3):1368-1381

Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, 515041, Shantou, China.

Background And Objectives: Apolipoprotein E (apoE) plays a central role in the metabolism and homeostasis of lipids. ApoE gene encodes three major isoforms: ε2, ε3 a nd ε4 forming six phenotypes: E2E2, E2E3, E2E4, E3E3, E3E3 and E4E4. Disorders of the lipid metabolism and the homeostasis are frequently coexist in renal diseases. The association between gene polymorphisms of apoE and lipid metabolism were not consistent. This meta-analysis was performed to assess the association between gene polymorphisms of apoE and lipid metabolism in renal diseases.

Methods: A pre-defined literatures search and selection of eligible relevant investigations were performed to extract and collect data from electronic databases.

Results: Sixteen articles were enrolled for the analysis of association between apoE gene polymorphisms and lipid metabolism. Subjects with E3E4 had a higher total cholesterol (TC) than those with E3E3, and subjects with E2E3 had a lower TC than those with E3E3. Subjects with ε2, had a lower TC than those with ε3 or ε4, and subjects with ε4 had a higher TC than those with, ε3. Subjects with E2E2, E2E3 or E4E4 had a higher triglyceride (TG) than those with E3E3. Subjects with ε4 had a higher TG than those with ε3. Subjects with ε2, had a higher level of TG than those with non-ε2. Subjects with E3E4 had a slightly lower high-density lipoprotein (HDL) than those with E3E3. E3E4 appeared to be associated with lower levels of HDL. Subjects with E2E2, E2E3 had a notably lower low-density lipoprotein (LDL) than those with E3E3. Subjects with ε2, had a lower LDL than those with ε3 or ε4 ApoE gene polymorphisms were not associated with very low-density lipoprotein, and lipoprotein (a) [Lp(a)]. Subjects with E2E3 or E2E4 had higher apoE levels than those with E3E3, and subjects with E4E4 had lower apoE levels than those with E3E3.

Conclusion: ApoE gene polymorphisms are associated with the expression of TC, TG HDL, LDL, Lp(a) or apoE.
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http://dx.doi.org/10.4314/ahs.v20i3.43DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751546PMC
September 2020

Loss of PIGK function causes severe infantile encephalopathy and extensive neuronal apoptosis.

Hum Genet 2021 May 4;140(5):791-803. Epub 2021 Jan 4.

Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, 110 Xiangya Road, Changsha, 410078, Hunan, China.

PIGK gene, encoding a key component of glycosylphosphatidylinositol (GPI) transamidase, was recently reported to be associated with inherited GPI deficiency disorders (IGDs). However, little is known about the specific downstream effects of PIGK on neurodevelopment due to the rarity of the disease and the lack of in vivo study. Here, we described 2 patients in a Chinese family presented with profound global developmental delay, severe hypotonia, seizures, and postnatal progressive global brain atrophy including hemisphere, cerebellar and corpus callosum atrophy. Two novel compound heterozygous variants in PIGK were identified via genetic analysis, which was proved to cause significant decrease of PIGK protein and reduced cell surface presence of GPI-APs in the patients. To explore the role of Pigk on embryonic and neuronal development, we constructed Pigk knock-down zebrafish and knock-in mouse models. Zebrafish injected with a small dose of morpholino oligonucleotides displayed severe developmental defects including small eyes, deformed head, curly spinal cord, and unconsumed yolk sac. Primary motor neuronal dysplasia and extensive neural cell apoptosis were further observed. Meanwhile, the mouse models, carrying the two variants respectively homologous with the patients, both resulted in complete embryonic lethality of the homozygotes, which suggested the intolerable effect caused by amino acid substitution of Asp204 as well as the truncated mutation. Our findings provide the in vivo evidence for the essential role of PIGK during the embryonic and neuronal development. Based on these data, we propose a basis for further study of pathological and molecular mechanisms of PIGK-related neurodevelopmental defects.
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http://dx.doi.org/10.1007/s00439-020-02243-2DOI Listing
May 2021