bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene Therapy for Neurodegenerative Disease: Clinical Potential and Directions
Authors: Zhu Xiaolin , Zhang Yu , Yang Xin , Hao Chunyan , Duan Hubin
Published: June 2021

The pathogenesis of neurodegenerative diseases (NDDs) is complex and diverse. Over the decades, our understanding of NDD has been limited to pathological features. However, recent advances in gene sequencing have facilitated elucidation of NDD at a deeper level. Gene editing techniques have uncovered new genetic links to phenotypes, promoted the development of novel treatment strategies and equipped researchers with further means to construct effective cell and animal models. The current review describes the history of evolution of gene editing tools, with the aim of improving overall understanding of this technology, and focuses on the four most common NDD disorders to demonstrate the potential future applications and research directions of gene editing.
Vitamin B12 and Folate Levels During Pregnancy and Risk of Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis
Authors: Wang Li , Hou Yanping , Meng Dexia , Yang Li , Meng Xiang , Liu Feng
Published: June 2021

Background: The role of vitamin B12 and folate levels with risk of gestational diabetes mellitus (GDM) is unclear. The purpose of the current study was to conduct a systematic review and meta-analysis for assessing the relationship between vitamin B12 and folate concentrations during pregnancy and the risk of GDM.

Methods: PubMed, Embase, CENTRAL, and Ovid databases were searched up to 10th December, 2020 for all types of studies assessing the relationship. Qualitative and quantitative analysis of data was carried out.

Results: Twelve studies were included. Pooled serum vitamin B12 concentrations were found to be significantly lower in the GDM group as compared to the non-GDM group. No such difference was noted in serum folate levels. On pooled analysis of adjusted odds ratio's for risk of GDM with red blood cell (RBC) folate, serum folate, and vitamin B12 as continuous variables, no significant relationship was seen. On qualitative analysis, studies reported higher RBC folate levels with a significantly increased risk of GDM. Majority studies reported no relationship between serum folate and risk of GDM. Four of six studies reported a lowered risk of GDM with higher or normal vitamin B12 levels.

Conclusion: The association between vitamin B12 and folate levels during pregnancy and the risk of GDM is unclear. Limited number of studies indicate increased risk of GDM with higher RBC folate levels, but majority studies found no association between serum folate and risk of GDM. Based on available studies, the association between the risk of GDM with vitamin B12 deficiency is conflicting. There is a need for further large-scale studies from different regions worldwide to strengthen current evidence.
Malnutrition Is Associated With Impaired Functional Status in Older People Receiving Home Care Nursing Service
Authors: Leão Luana Lemos , Engedal Knut , Monteiro-Junior Renato Sobral , Tangen Gro Gujord , Krogseth Maria
Published: June 2021

Objective: This study aimed to explore the magnitude and significance of associations among nutritional status, functional status, comorbidities, age, and gender in older adults receiving assistance from the in-home nursing care service.

Method: In this cross-sectional study, 210 home-dwelling persons 65 years or older who received in-home nursing care service were evaluated. Demographic variables, nutritional status, comorbidities, and the dependency levels of activities of daily living were analyzed. To assess the correlation among the factors that influence nutritional status, a theoretical model was developed and adjusted using the path analysis model.

Results: The primary finding is that functional status is directly associated with nutritional status (β = 0.32; p < 0.001) and severity of comorbidities is indirectly associated with nutritional status (β = −0.07; p < 0.017).

Conclusion: The elicited outcomes in this study reinforce the concept that nutritional status is linked with functional status in older adults receiving in-home care nursing service.
Alteration of Cholesterol Metabolism by Metformin Is Associated With Improved Outcome in Type II Diabetic Patients With Diffuse Large B-Cell Lymphoma
Authors: Jiang Xiang-Nan , Zhang Yan , Wang Wei-Ge , Sheng Dong , Zhou Xiao-Yan , Li Xiao-Qiu
Published: June 2021

Recent studies have demonstrated the benefits of metformin on patients with lymphomas. B-cell receptor (BCR)-PI3K-AKT pathway-dependent cholesterol synthesis may represent a positive feedback mechanism responsible for the pathogenesis of BCR-dependent diffuse large B-cell lymphomas (DLBCLs). Thus, restriction of lipid synthesis would affect the integrity of lipid-forming membranes and block the BCR signaling pathway. Our in vitro findings suggested that the blocking effect of metformin on BCR signaling pathway is possibly exerted via blocking the biosynthesis of cholesterol. A retrospective case-control study was subsequently conducted on type II diabetic patients with DLBCL who were on metformin. Metformin was identified to be associated with improved response rate and PFS in diabetic patients and appeared to be an effective therapeutic drug against DLBCL.
The Novel Curcumin Derivative 1g Induces Mitochondrial and ER-Stress-Dependent Apoptosis in Colon Cancer Cells by Induction of ROS Production
Authors: Wang Hao , Xu Yingxing , Sun Jialin , Sui Zhongguo
Published: June 2021

Reactive oxygen species (ROS) play an important role in cellular metabolism. Many chemotherapeutic drugs are known to promote apoptosis through the production of ROS. In the present study, the novel curcumin derivative, 1g, was found to inhibit tumor growth in colon cancer cells both in vitro and in vivo. Bioinformatics was used to analyze the differentially expressed mRNAs. The mechanism of this effect was a change in mitochondrial membrane potential caused by 1g that increased its pro-apoptotic activity. In addition, 1g produced ROS, induced G1 checkpoint blockade, and enhanced endoplasmic reticulum (ER)-stress in colon cancer cells. Conversely, pretreatment with the ROS scavenging agent N-acetyl-l-cysteine (NAC) inhibited the mitochondrial dysfunction caused by 1g and reversed ER-stress, cell cycle stagnation, and apoptosis. Additionally, pretreatment with the p-PERK inhibitor GSK2606414 significantly reduced ER-stress and reversed the apoptosis induced by colon cancer cells. In summary, the production of ROS plays an important role in the destruction of colon cancer cells by 1g and demonstrates that targeted strategies based on ROS represent a promising approach to inhibit colon cancer proliferation. These findings reveal that the novel curcumin derivative 1g represents a potential candidate therapeutics for the treatment of colon cancer cells, via apoptosis caused by mitochondrial dysfunction and endoplasmic reticulum stress.
EGFR-Mutated Squamous Cell Lung Cancer and Its Association With Outcomes
Authors: Jin Rui , Peng Ling , Shou Jiawei , Wang Jin , Jin Yin , Liang Fei , Zhao Jing , Wu Mengmeng , Li Qin , Zhang Bin , Wu Xiaoying , Lan Fen , Xia Lixia , Yan Junrong , Shao Yang , Stebbing Justin , Shen Huahao , Li Wen , Xia Yang
Published: June 2021

Background

The therapeutic efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced EGFR-mutant lung squamous cell carcinoma (SCC) patients remains uncertain. Furthermore, the factors underlying the responsiveness have not been fully investigated. We therefore investigated the link between genomic profiles and EGFR-TKI efficacy.

Material and Methods

We consecutively enrolled stage IV, EGFR-mutant, and EGFR-TKI–treated patients with SCC. Patients with EGFR wild-type lung SCC and EGFR-mutant lung adenocarcinoma were consecutively enrolled as controls, and next-generation sequencing (NGS) was performed.

Results

In total, 28 EGFR-mutant lung SCC, 41 EGFR-mutant lung adenocarcinoma, and 40 EGFR wild-type lung SCC patients were included. Among the patients with EGFR mutations, shorter progression-free survival (PFS) was observed in SCC compared to adenocarcinoma (4.6 vs. 11.0 months, P<0.001). Comparison of the genomic profiles revealed that EGFR-mutant SCC patients had similar mutation characteristics to EGFR-mutant adenocarcinoma patients, but differed from those with EGFR wild-type SCC. Further exploration of EGFR-mutant SCC revealed that mutations in CREBBP (P = 0.005), ZNF217 (P = 0.016), and the Wnt (P = 0.027) pathway were negatively associated with PFS. Mutations in GRM8 (P = 0.025) were associated with improved PFS.

Conclusions

EGFR-mutant lung SCC has a worse prognosis than EGFR-mutant adenocarcinoma. Mutations in other genes, such as CREBBP, ZNF217, GRM8, or Wnt that had implications on PFS raise the possibility of understanding mechanisms of resistance to EGFR-TKI in lung SCC, which will aid identification of potential beneficial subgroups of patients with EGFR-mutant SCCs receiving EGFR-TKIs.
Targeting Growth Factor Signaling Pathways in Pancreatic Cancer: Towards Inhibiting Chemoresistance
Authors: Xelwa Ntombikayise , Candy Geoffrey Patrick , Devar John , Omoshoro-Jones Jones , Smith Martin , Nweke Ekene Emmanuel
Published: June 2021

Pancreatic cancer is one of the most deadly cancers, ranking amongst the top leading cause of cancer related deaths in developed countries. Features such as dense stroma microenvironment, abnormal signaling pathways, and genetic heterogeneity of the tumors contribute to its chemoresistant characteristics. Amongst these features, growth factors have been observed to play crucial roles in cancer cell survival, progression, and chemoresistance. Here we review the role of the individual growth factors in pancreatic cancer chemoresistance. Importantly, the interplay between the tumor microenvironment and chemoresistance is explored in the context of pivotal role played by growth factors. We further describe current and future potential therapeutic targeting of these factors.
An Analysis of Cardiac Disorders Associated With Chimeric Antigen Receptor T Cell Therapy in 126 Patients: A Single-Centre Retrospective Study
Authors: Qi Kunming , Yan Zhiling , Cheng Hai , Chen Wei , Wang Ying , Wang Xue , Cao Jiang , Zhang Huanxin , Sang Wei , Zhu Feng , Sun Haiying , Li Depeng , Wu Qingyun , Qiao Jianlin , Fu Chunling , Zeng Lingyu , Li Zhenyu , Zheng Junnian , Xu Kailin
Published: June 2021

Introduction

Chimeric antigen receptor T (CAR-T) cells are effective in treating hematological malignancies. However, in patients receiving CAR-T therapy, data characterizing cardiac disorders are limited.

Methods

126 patients with hematologic malignancies receiving CAR-T cell therapy were analyzed to determine the impact of CAR-T therapy on occurrence of cardiac disorders, including heart failure, arrhythmias, myocardial infarction, which were defined by the Common Terminology Criteria for Adverse Events (CTCAE). Parameters related to cardiac disorders were detected including myocardial enzyme, NT-proBNP and ejection fraction (EF). Cardiovascular (CV) events included decompensated heart failure (HF), clinically significant arrhythmias and CV death.

Results

The median age of patients was 56 years (6 to 72 years). 58% patients were male, 62% had multiple myeloma, 20% had lymphoma and 18% had ALL. 33 (26%) patients had cardiac disorders, most of which were grade 1-2. 13 patients (10%) were observed with cardiac disorders grade 3-5, which comprised 5(4%) patients with new-onset HF, 2 (2%) patients with new-onset arrhythmias, 4 (3%) patients with the acute coronary syndrome, 1(1%) patient with myocardial infarction and 1(1%) patient with left ventricular systolic dysfunction. There were 9 CV events (7%) including 6 decompensated heart failure, 1 clinically significant arrhythmias and 2 CV deaths. Among the 33 patients with cardiac disorders, the patients with cardiac disorders CTCAE grade 3-5 had higher grade CRS (grade ≥ 3) than those with cardiac disorders CTCAE grade ≤ 2 (P <0.001). More patients with cardiac disorders CTCAE grade 3-5 were observed in the cohort who did not receive corticosteroids and/or tocilizumab therapy timely comparing with those who received corticosteroids and/or tocilizumab therapy timely (P =0.0004).

Conclusions

Cardiac disorders CAR-T cell therapy were common and associated with occurrence of CRS. However, most cases were mild. For patients with CRS grade 3-5, timely administration of corticosteroids and/or tocilizumab can effectively prevent the occurrence and progression of cardiac disorders.
Comparing Robot-Assisted Laparoscopic Pyeloplasty vs. Laparoscopic Pyeloplasty in Infants Aged 12 Months or Less
Authors: Wong Yuenshan Sammi , Pang Kristine Kit Yi , Tam Yuk Him
Published: June 2021

Objective: To investigate the outcomes of minimally invasive approach to infants with ureteropelvic junction (UPJ) obstruction by comparing the two surgical modalities of robot-assisted laparoscopic pyeloplasty (RALP) and laparoscopic pyeloplasty (LP).

Methods: We conducted a retrospective review of all consecutive infants aged ≤12 months who underwent either LP or RALP in a single institution over the period of 2008–Jul 2020. We included primary pyeloplasty cases that were performed by or under the supervision of the same surgeon.

Results: Forty-six infants (LP = 22; RALP = 24) were included with medians of age and body weight at 6 months (2–12months) and 8.0 kg (5.4–10 kg), respectively. There was no difference between the two groups in the patients' demographics and pre-operative characteristics. All infants underwent LP or RALP successfully without conversion to open surgery. None had intraoperative complications. Operative time (OT) was 242 min (SD = 59) in LP, compared with 225 min (SD = 39) of RALP (p = 0.25). Linear regression analysis showed a significant trend of decrease in OT with increasing case experience of RALP(p = 0.005). No difference was noted in the post-operative analgesic requirement. RALP was associated with a shorter hospital length of stay than LP (3 vs. 3.8 days; p = 0.009). 4/22(18%) LP and 3/24(13%) RALP developed post-operative complications (p = 0.59), mostly minor and stent-related. The success rates were 20/22 (91%) in LP and 23/24 (96%) in RALP (p = 0.49).

Conclusions: Pyeloplasty by minimally invasive approach is safe and effective in the infant population. RALP may have superiority over LP in infants with its faster recovery and a more manageable learning curve to acquire the skills.
sVEGFR1 Is Enriched in Hepatic Vein Blood—Evidence for a Provisional Hepatic Factor Candidate?
Authors: Spearman Andrew D. , Gupta Ankan , Pan Amy Y. , Gudausky Todd M. , Foerster Susan R. , Konduri G. Ganesh , Ramchandran Ramani
Published: June 2021

Background: Pulmonary arteriovenous malformations (PAVMs) are common sequelae of palliated univentricular congenital heart disease, yet their pathogenesis remain poorly defined. In this preliminary study, we used paired patient blood samples to identify potential hepatic factor candidates enriched in hepatic vein blood.

Methods: Paired venous blood samples were collected from the hepatic vein (HV) and superior vena cava (SVC) from children 0 to 10 years with univentricular and biventricular congenital heart disease (n = 40). We used three independent protein analyses to identify proteomic differences between HV and SVC blood. Subsequently, we investigated the relevance of our quantified protein differences with human lung microvascular endothelial assays.

Results: Two independent protein arrays (semi-quantitative immunoblot and quantitative array) identified that soluble vascular endothelial growth factor receptor 1 (sVEGFR1) is significantly elevated in HV serum compared to SVC serum. Using ELISA, we confirmed the previous findings that sVEGFR1 is enriched in HV serum (n = 24, p < 0.0001). Finally, we studied the quantified HV and SVC serum levels of sVEGFR1 in vitro. HV levels of sVEGFR1 decreased tip cell selection (p = 0.0482) and tube formation (fewer tubes [p = 0.0246], shorter tube length [p = 0.0300]) in vitro compared to SVC levels of sVEGFR1.

Conclusions: Based on a small heterogenous cohort, sVEGFR1 is elevated in HV serum compared to paired SVC samples, and the mean sVEGFR1 concentrations in these two systemic veins cause pulmonary endothelial phenotypic differences in vitro. Further research is needed to determine whether sVEGFR1 has a direct role in pulmonary microvascular remodeling and PAVMs in patients with palliated univentricular congenital heart disease.
Predictive Indicators for Necrotizing Enterocolitis With the Presence of Portal Venous Gas and Outcomes of Surgical Interventions
Authors: Lin Xin , Zeng Hui-Ping , Fang Yi-Fan , Lin Ying-Ying , Yang Chang-Yi
Published: June 2021

Objectives: Portal venous gas (PVG) was an important clinical sign in stage II or III necrotizing enterocolitis (NEC) in preterm neonates. Not a proper predictive indicator was found to predict the diseases (NEC with the presence of PVG) up to now. There is a need to put forward predictive indicators and compare the predictive effects among them.

Methods: We conducted a retrospective study of preterm neonates with NEC-PVG (n = 61) or NEC-non PVG (n = 62) from 2014 to 2021. Predictive indicators were put forward and determined by receiver operating characteristic curve analysis. An analysis of the surgical interventions and their outcomes was performed.

Results: The incidence rate of NEC among preterm neonates was 4.99%; surgical and conservative interventions accounted for 20.47 and 75.07%, and the mortality rate was 0.03%. The composition ratio of shock in the NEC-PVG group increased 13.2% (P = 0.029). C-reactive protein, fibrinogen degradation product, and blood glucose had better predictive effects in the predictive indicators (P < 0.05). Intestinal necrosis and subependymal hemorrhage in the outcomes of surgical interventions had a strong relationship with the presence of PVG in NEC II/III (P < 0.05).

Conclusion: Early and reasonable use of antibiotics, improvement of coagulation function, rectification of acidosis, and decreased blood glucose could cut down the occurrence of the disease (NEC with the presence of PVG). Except for subependymal hemorrhage and intestinal necrosis, NEC with the presence of PVG did not increase the occurrence of other outcomes after surgery.
Continuous Renal Replacement Therapy in Critically Ill Children in the Pediatric Intensive Care Unit: A Retrospective Analysis of Real-Life Prescriptions, Complications, and Outcomes
Authors: Buccione Emanuele , Guzzi Francesco , Colosimo Denise , Tedesco Brigida , Romagnoli Stefano , Ricci Zaccaria , L'Erario Manuela , Villa Gianluca
Published: June 2021

Introduction: Severe acute kidney injury is a common finding in the Pediatric Intensive Care Unit (PICU), however, Continuous Renal Replacement Therapy (CRRT) is rarely applied in this setting. This study aims to describe our experience in the rate of application of CRRT, patients' clinical characteristics at admission and CRRT initiation, CRRT prescription, predictors of circuit clotting, short- and long-term outcomes.

Methods: A 6-year single center retrospective study in a tertiary PICU.

Results: Twenty-eight critically ill patients aged 0 to 18 years received CRRT between January 2012 and December 2017 (1.4% of all patients admitted to PICU). Complete clinical and CRRT technical information were available for 23/28 patients for a total of 101 CRRT sessions. CRRT was started, on average, 40 h (20–160) after PICU admission, mostly because of fluid overload. Continuous veno-venous hemodiafiltration and systemic heparinization were applied in 83.2 and 71.3% of sessions, respectively. Fifty-nine sessions (58.4%) were complicated by circuit clotting. At multivariate Cox-regression analysis, vascular access caliber larger than 8 Fr [HR 0.37 (0.19–0.72), p = 0.004] and regional citrate anticoagulation strategy [HR 0.14 (0.03–0.60), p = 0.008] were independent protective factors for clotting. PICU mortality rate was 42.8%, and six survivors developed chronic kidney disease (CKD), within an average follow up of 3.5 years.

Conclusions: CRRT is uncommonly applied in our PICU, mostly within 2 days after admission and because of fluid overload. Larger vascular access and citrate anticoagulation are independent protective factors for circuit clotting. Patients' PICU mortality rate is high and survival often complicated by CKD development.
Pioglitazone Inhibits Diabetes-Induced Atrial Mitochondrial Oxidative Stress and Improves Mitochondrial Biogenesis, Dynamics, and Function Through the PPAR-γ/PGC-1α Signaling Pathway
Authors: Zhang Zhiwei , Zhang Xiaowei , Meng Lei , Gong Mengqi , Li Jian , Shi Wen , Qiu Jiuchun , Yang Yajuan , Zhao Jianping , Suo Ya , Liang Xue , Wang Xinghua , Tse Gary , Jiang Ning , Li Guangping , Zhao Yungang , Liu Tong
Published: June 2021

Background: Oxidative stress contributes to adverse atrial remodeling in diabetes mellitus. This remodeling can be prevented by the PPAR-γ agonist pioglitazone via its antioxidant and anti-inflammatory effects. In this study, we examined the molecular mechanisms underlying the protective effects of pioglitazone on atrial remodeling in a rabbit model of diabetes.

Methods: Rabbits were randomly divided into control, diabetic, and pioglitazone-treated diabetic groups. Echocardiographic, hemodynamic, and electrophysiological parameters were measured. Serum PPAR-γ levels, serum and tissue oxidative stress and inflammatory markers, mitochondrial morphology, reactive oxygen species (ROS) production rate, respiratory function, and mitochondrial membrane potential (MMP) levels were measured. Protein expression of the pro-fibrotic marker TGF-β1, the PPAR-γ coactivator-1α (PGC-1α), and the mitochondrial proteins (biogenesis-, fusion-, and fission-related proteins) was measured. HL-1 cells were transfected with PGC-1α small interfering RNA (siRNA) to determine the underlying mechanisms of pioglitazone improvement of mitochondrial function under oxidative stress.

Results: The diabetic group demonstrated a larger left atrial diameter and fibrosis area than the controls, which were associated with a higher incidence of inducible atrial fibrillation (AF). The lower serum PPAR-γ level was associated with lower PGC-1α and higher NF-κB and TGF-β1 expression. Lower mitochondrial biogenesis (PGC-1α, NRF1, and TFAM)-, fusion (Opa1 and Mfn1)-, and fission (Drp1)-related proteins were detected. Mitochondrial swelling, higher mitochondrial ROS, lower respiratory control rate, and lower MMP were observed. The pioglitazone group showed a reversal of structural remodeling and a lower incidence of inducible AF, which were associated with higher PPAR-γ and PGC-1α. The pioglitazone group had lower NF-κB and TGF-β1 expression levels, whereas biogenesis-, fusion-, and fission-related protein expression was higher. Further, mitochondrial structure and function were improved. In HL-1 cells, PGC-1α siRNA transfection blunted the effect of pioglitazone on Mn-SOD protein expression and MMP collapse in H2O2-treated cells.

Conclusion: Diabetes mellitus induces adverse atrial structural, electrophysiological remodeling, and mitochondrial damage and dysfunction. Pioglitazone prevented these abnormalities through the PPAR-γ/PGC-1α pathway.
Dendrobium Officinale Polysaccharide Attenuates Insulin Resistance and Abnormal Lipid Metabolism in Obese Mice
Authors: Qu Jian , Tan Shengyu , Xie Xinyan , Wu Wenqiang , Zhu Haihong , Li Hang , Liao Xiaobo , Wang Jiaojiao , Zhou Zhi-Ang , Huang Song , Lu Qiong
Published: June 2021

Objectives: Dendrobium officinale polysaccharide (DOP) is the main active ingredient in a valuable traditional Chinese medicine, which exerts several pharmacological activities including hepatoprotection and hypoglycemic effects. However, the effects of DOP on obesity-associated insulin resistance (IR) and lipid metabolism remain unknown. This study aimed to investigate the role of DOP in IR and abnormal lipid metabolism in obese mice.

Methods: IR models were established using 3T3-L1 adipocytes, C2C12 myocytes, and primary cultured hepatocytes exposed to palmitate acid. After treatment with DOP, insulin-stimulated glucose uptake, glucose release, and AKT phosphorylation was detected. Fasting blood glucose, fasting serum insulin, the glucose tolerance test (GTT), and the insulin tolerance test (ITT) were measured to evaluate IR of obese mice. Lipid analysis was conducted to evaluate the effects of DOP on lipid metabolism in obese mice.

Results:In vitro, DOP treatment ameliorated palmitic acid-induced IR in adipocytes, myocytes, and hepatocytes. DOP regulated cellular insulin sensitivity via the peroxisome proliferator-activated receptor-γ (PPAR-γ). Furthermore, administration of DOP significantly reduced the IR and visceral adipose tissue (VAT) inflammation of diet-induced obese (DIO) and the genetically-induced obesity mice (ob/ob) mouse models. In addition, DOP treatment attenuated the high-fat diet (HFD)-induced liver lipid accumulation by reducing liver triglycerides (TG), plasma free fatty acid (FFA), serum cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels, while increasing HDL-C levels.

Conclusion: DOP could improve obesity-associated IR and abnormal lipid metabolism through its activities on PPAR-γ, and may serve as a potential therapeutic agent for obesity-associated insulin resistance and lipid metabolism disorder.
Serum Metabolomic Analysis of Coronary Heart Disease Patients with Stable Angina Pectoris Subtyped by Traditional Chinese Medicine Diagnostics Reveals Biomarkers Relevant to Personalized Treatments
Authors: Guo Na , Wang Peili , Yang Jiaying , Yang Xiaofang , van der Voet Monique , Wildwater Marjolein , Wei Junying , Tang Xuan , Wang Mei , Yang Hongjun
Published: June 2021

To improve the treatment of patients with coronary heart disease (CHD), personalized treatments based on potential biomarkers could make a difference. To investigate if such potential biomarkers could be found for CHD inhomogeneous, we combined traditional Chinese medicine based diagnosis with untargeted and targeted metabolomics analyses. Shi and Xu patient subtype groups of CHD with angina pectoris were identified. Different metabolites including lipids, fatty acids and amino acids were further analyzed with targeted metabolomics and mapped to disease-related pathways. The long-chain unsaturated lipids ceramides metabolism, bile acid metabolism were differentially affected in the Xu subtype groups. While, Shi-subtype patients seemed to show inflammation, anomalous levels of bioactive phospholipids and antioxidant molecules. Furthermore, variations in the endothelial damage response and energy metabolism found based on ELISA analysis are the key divergence points between different CHD subtypes. The results showed Xu subtype patients might benefit from long-chain unsaturated lipids ceramides as therapeutic targets. Shi subtype patients might benefit more from levels of polyunsaturated fatty acid consumption and treatments that help in restoring energy balance. Metabolic differences can be essential for treatment protocols. Thus, patient group specific differences can serve as important information to refine current treatment approaches in a personalized manner.
Sesamolin Protects Mice From Ovariectomized Bone Loss by Inhibiting Osteoclastogenesis and RANKL-Mediated NF-κB and MAPK Signaling Pathways
Authors: Yang Xue , Liang Jiamin , Wang Ziyi , Su Yuangang , Zhan Yunfei , Wu Zuoxing , Li Jing , Li Xuedong , Chen Runfeng , Zhao Jinmin , Xu Jiake , Liu Qian , Zhou Bo
Published: June 2021

This article was submitted to Experimental Pharmacology and Drug Discovery, a section of the journal Frontiers in Pharmacology. Postmenopausal osteoporosis (PMOP), which increases the risk of fracture, is the most common bone disease in women. PMOP not only increases the risk of death but also imposes a financial burden on countless families. At present, most of the drugs used to treat osteoporosis have significant side effects, so it is important to find effective anti-osteoporosis medications without major side effects. Sesamolin (Ses) is a kind of natural lignan extracted from sesame oil. Many researches have shown that Ses has anti-inflammatory, antioxidative, and anticancer effects, however it is still unknown whether it has any effect on osteoporosis. In this research, we explored the therapeutic effect of Ses in the process of osteoclast formation and bone resorption and found that Ses effectively inhibited osteoclast formation in vitro through TRAcP staining and hydroxyapatite resorption assays. Through Western blot analysis of the NF-κB pathway, MAPK pathway, c-Fos and NFATc1, it was found that Ses not only effectively inhibited the activation of NF-κB and MAPK signaling pathways induced by RANKL but also significantly reduced the protein expression of c-Fos and NFATc1. Several genes specifically expressed in osteoclasts were determined by qPCR, and Ses was also found to play a significant inhibitory role on the expression of these genes. Besides, an osteoporosis model induced in ovariectomized (OVX) mice was employed to verify that Ses could effectively reduce bone loss caused by estrogen deficiency in vivo. In conclusion, Ses showed promise as a new treatment for postmenopausal osteoporosis.
ROS-Eliminating Carboxymethyl Chitosan Hydrogel to Enhance Burn Wound-Healing Efficacy
Authors: Yang Cheng , Chen Yuhui , Huang Hai , Fan Shicai , Yang Chengliang , Wang Liping , Li Wenqiang , Niu Wenxin , Liao Jianwen
Published: June 2021

Overexpression of reactive oxygen species (ROS) can lead to chronic inflammation, which limits skin wound healing. Therefore, it is of great significance to develop materials that can locally control the adverse reactions caused by excessive ROS. In this research, an ROS-sensitive hydrogel with strong free radical scavenging ability was prepared by introducing the thione (Tk) group into carboxymethyl chitosan (CMCTS) hydrogel. CMCTS hydrogel was cross-linked by NH2-Tk-NH2 agent and loaded curcumin (Cur), which possessed favorable nontoxicity, water absorption, mechanical property, biodegradability, drug release behavior, the M2 phenotype, and inflammatory factor regulating the capacity of macrophages. It is worth noting that Cur@CMCTS-Tk hydrogel can significantly inhibit oxidative damage of human fibroblasts in the H2O2-induced microenvironment and protect their viability by reducing the production of intracellular ROS. In vivo, ROS-removing hydrogel effectively accelerated the process of wound healing and possessed good regenerative properties, including hair follicle formation, promotion of new blood vessel formation, and highly orderly arrangement of collagen fibers in the full-thickness skin burn defect rat model. Hence, we expect that the Cur@CMCTS-Tk hydrogel could be used for wound treatment and tissue regeneration due to the ability to scavenge excess ROS.
Melatonin Attenuates Intervertebral Disk Degeneration via Maintaining Cartilaginous Endplate Integrity in Rats
Authors: Wu Xiexing , Liu Yijie , Du Jiacheng , Li Xiaoping , Lin Jiayi , Ni Li , Zhu Pengfei , Zhou Hong , Kong Fanchen , Yang Huilin , Geng Dechun , Mao Haiqing
Published: June 2021

Objective

The aim of this study is to verify whether melatonin (Mel) could mitigate intervertebral disk degeneration (IVDD) in rats and to investigate the potential mechanism of it.

Method

A rat acupuncture model of IVDD was established with intraperitoneal injection of Mel. The effect of Mel on IVDD was analyzed via radiologic and histological evaluations. The specific Mel receptors were investigated in both the nucleus pulposus (NP) and cartilaginous endplates (EPs). In vitro, EP cartilaginous cells (EPCs) were treated by different concentrations of Mel under lipopolysaccharide (LPS) and Luzindole conditions. In addition, LPS-induced inflammatory response and matrix degradation following nuclear factor kappa-B (NF-κB) pathway activation were investigated to confirm the potential mechanism of Mel on EPCs.

Results

The percent disk height index (%DHI) and MRI signal decreased after initial puncture in the degeneration group compared with the control group, while Mel treatment protected disk height from decline and prevented the loss of water during the degeneration process. In the meantime, the histological staining of the Mel groups showed more integrity and well-ordered construction of the NP and EPs in both low and high concentration than that of the degeneration group. In addition, more deep-brown staining of type II collagen (Coll-II) was shown in the Mel groups compared with the degeneration group. Furthermore, in rat samples, immunohistochemical staining showed more positive cells of Mel receptors 1a and 1b in the EPs, instead of in the NP. Moreover, evident osteochondral lacuna formation was observed in rat EPs in the degeneration group; after Mel treatment, the osteochondral destruction alleviated accompanying fewer receptor activator for nuclear factor-κB ligand (RANKL) and tartrate-resistant acid phosphatase (TRAP)-stained positive cells expressed in the EPs. In vitro, Mel could promote the proliferation of EPCs, which protected EPCs from degeneration under LPS treatment. What is more, Mel downregulated the inflammatory response and matrix degradation of EPCs activated by NF-κB pathway through binding to its specific receptors.

Conclusion

These results indicate that Mel protects the integrity of the EPs and attenuates IVDD by binding to the Mel receptors in the EPs. It may alleviate the inflammatory response and matrix degradation of EPCs activated by NF-κB pathway.
Heterotic Patterns of Temperate and Tropical Maize by Ear Photometry
Authors: Tolley Seth A. , Singh Amritpal , Tuinstra Mitchell R.
Published: June 2021

As the plant variety protection (PVP) of commercial inbred lines expire, public breeding programs gain a wealth of genetic materials that have undergone many years of intense selection; however, the value of these inbred lines is only fully realized when they have been well characterized and are used in hybrid combinations. Additionally, while yield is the primary trait by which hybrids are evaluated, new phenotyping technologies, such as ear photometry (EP), may provide an assessment of yield components that can be scaled to breeding programs. The objective of this experiment was to use EP to describe the testcross performance of inbred lines from temperate and tropical origins. We evaluated the performance of 298 public and ex-PVP inbred lines and 274 Drought Tolerant Maize for Africa (DTMA) inbred lines when crossed to Iodent (PHP02) and/or Stiff Stalk (2FACC) testers for 25 yield-related traits. Kernel weight, kernels per ear, and grain yield predicted by EP were correlated with their reference traits withr= 0.49,r= 0.88, andr= 0.75, respectively. The testcross performance of each maize inbred line was tester dependent. When lines were crossed to a tester within the heterotic group, many yield components related to ear size and kernels per ear were significantly reduced, but kernel size was rarely impacted. Thus, the effect of heterosis was more noticeable on traits that increased kernels per ear rather than kernel size. Hybrids of DTMA inbred lines crossed to PHP02 exhibited phenotypes similar to testcrosses of Stiff Stalk and Non-Stiff Stalk heterotic groups for yield due to significant increases in kernel size to compensate for a reduction in kernels per ear. Kernels per ear and ear length were correlated (r= 0.89 andr= 0.84, respectively) with and more heritable than yield, suggesting these traits could be useful for inbred selection.
Pars Pro Toto: Every Single Cell Matters
Authors: Christiaens Fien , Canher Balkan , Lanssens Fien , Bisht Anchal , Stael Simon , De Veylder Lieven , Heyman Jefri
Published: June 2021

Compared to other species, plants stand out by their unparalleled self-repair capacities. Being the loss of a single cell or an entire tissue, most plant species are able to efficiently repair the inflicted damage. Although this self-repair process is commonly referred to as “regeneration,” depending on the type of damage and organ being affected, subtle to dramatic differences in the modus operandi can be observed. Recent publications have focused on these different types of tissue damage and their associated response in initiating the regeneration process. Here, we review the regeneration response following loss of a single cell to a complete organ, emphasizing key molecular players and hormonal cues involved in the model species Arabidopsis thaliana. In addition, we highlight the agricultural applications and techniques that make use of these regenerative responses in different crop and tree species.
Effect of the Boron Concentration in Irrigation Water on the Elemental Composition of Edible Parts of Tomato, Green Bean, Potato, and Cabbage Grown on Soils With Different Textures
Authors: Rékási Márk , Ragályi Péter , Füzy Anna , Uzinger Nikolett , Dobosy Péter , Záray Gyula , Szűcs-Vásárhelyi Nóra , Makó András , Takács Tünde
Published: June 2021

The most important environmental source of boron (B) contamination is irrigation water. The data on the effect of B on the elemental composition in the edible parts of vegetables are scarce. A greenhouse pot experiment investigated the effect of irrigation water containing 0.1 and 0.5 mg/L B on the biomass, elemental (e.g., B, Mg, K, Fe, Cu, and Zn) composition, and photosynthetic parameters of tomato (Solanum lycopersicum), green bean (Phaseolus vulgaris), potato (Solanum tuberosum), and cabbage (Brassica oleracea) plants grown on 10 kg of sand, silty sand, or silty soil. The biomass of the edible part was unaffected by B treatment. The soil type determined the effect of B irrigation on the elemental composition of vegetables. The B content increased by 19% in tomatoes grown on silty soil. The 0.1 mg/L B treatment facilitated tomato fruit ripening on all soils, and the 0.5 mg/L B treatment doubled its chlorophyll content index (CCI) on silty soil. The 0.5 mg/L B treatment negatively affected the nutritional value of green beans on all soils, decreasing the Fe and K contents by an average of 83 and 34%, respectively. The elemental composition of potato was unaffected by the treatments, but the CCI of potato leaves increased in the 0.5 mg/L B treatment by 26%. The B content was increased by 39% in cabbages grown on light-textured soils. In conclusion, B concentration of up to 0.5 mg/L in irrigation water had no significant beneficial or adverse effect on the investigated vegetables, but 0.1 mg/L B treatment could shorten tomato fruit maturation time on B-poor soils. The B levels in vegetables remained suitable for human consumption.
Genomic Selection in an Outcrossing Autotetraploid Fruit Crop: Lessons From Blueberry Breeding
Authors: Ferrão Luís Felipe V. , Amadeu Rodrigo R. , Benevenuto Juliana , de Bem Oliveira Ivone , Munoz Patricio R.
Published: June 2021

Blueberry (Vaccinium corymbosumand hybrids) is a specialty crop with expanding production and consumption worldwide. The blueberry breeding program at the University of Florida (UF) has greatly contributed to expanding production areas by developing low-chilling cultivars better adapted to subtropical and Mediterranean climates of the globe. The breeding program has historically focused on recurrent phenotypic selection. As an autopolyploid, outcrossing, perennial, long juvenile phase crop, blueberry breeding cycles are costly and time consuming, which results in low genetic gains per unit of time. Motivated by applying molecular markers for a more accurate selection in the early stages of breeding, we performed pioneering genomic selection studies and optimization for its implementation in the blueberry breeding program. We have also addressed some complexities of sequence-based genotyping and model parametrization for an autopolyploid crop, providing empirical contributions that can be extended to other polyploid species. We herein revisited some of our previous genomic selection studies and showed for the first time its application in an independent validation set. In this paper, our contribution is three-fold: (i) summarize previous results on the relevance of model parametrizations, such as diploid or polyploid methods, and inclusion of dominance effects; (ii) assess the importance of sequence depth of coverage and genotype dosage calling steps; (iii) demonstrate the real impact of genomic selection on leveraging breeding decisions by using an independent validation set. Altogether, we propose a strategy for using genomic selection in blueberry, with the potential to be applied to other polyploid species of a similar background.
Circadian Control of Metabolism by the Clock Component TOC1
Authors: Cervela-Cardona Luis , Yoshida Takuya , Zhang Youjun , Okada Masaaki , Fernie Alisdair , Mas Paloma
Published: June 2021

Photosynthesis in chloroplasts during the day and mitochondrial respiration during the night execute nearly opposing reactions that are coordinated with the internal cellular status and the external conditions. Here, we describe a mechanism by which the Arabidopsis clock component TIMING OF CAB EXPRESSION1 (TOC1) contributes to the diurnal regulation of metabolism. Proper expression of TOC1 is important for sustaining cellular energy and for the diel and circadian oscillations of sugars, amino acids and tricarboxylic acid (TCA) cycle intermediates. TOC1 binds to the promoter of the TCA-related gene FUMARASE 2 to repress its expression at night, which results in decreased fumarate accumulation in TOC1 over-expressing plants and increased in toc1-2 mutant. Genetic interaction studies confirmed that over-expression of FUMARASE 2 in TOC1 over-expressing plants alleviates the molecular and physiological energy-deprivation phenotypes of TOC1 over-expressing plants. Thus, we propose that the tandem TOC1-FUMARASE 2 is one of the mechanisms that contribute to the regulation of plant metabolism during the day and night.
Comparative Transcriptome Analysis of Two Contrasting Chinese Cabbage (Brassica rapa L.) Genotypes Reveals That Ion Homeostasis Is a Crucial Biological Pathway Involved in the Rapid Adaptive Response to Salt Stress
Authors: Li Na , Zhang Zhihuan , Chen Zijing , Cao Bili , Xu Kun
Published: June 2021

Salt is the most important limiting factor in plant yield and quality. Different Chinese cabbage cultivars appeared different salt tolerances, but there are few studies attempting to elucidate the mechanism underlying this phenomenon. In this study, 100 mmol L–1 NaCl was found to be the most suitable treatment concentration according to a sprouting bag test of 39 Chinese cabbage cultivars, and through comprehensive comparison and analysis, the relative values of fresh weight and electrolyte leakage in leaves proved to be convenient indicators for the identification of salt tolerance in Chinese cabbage. We analyzed the physiological responses of Qinghua45 (salt-tolerant) and Biyuchunhua (salt-sensitive) in terms of the growth indexes, ion homeostasis and Photosynthesis, the results indicated that Qinghua45 could ensure osmotic regulation, ion homeostasis and photosynthesis under salt stress. Next, we compared the transcriptome dynamics of the two cultivars. Overall, 2,859 differentially expressed genes (DEGs) were identified, and the number of DEGs in Qinghua45 was significantly less than that in Biyuchunhua. VDAC promoted the release of Ca2+, which indirectly promoted the transport of Na+ to vacuoles through the SOS2 pathway. Cation/H (+) antiporter 17 and V-H + -ATPase improve the exchange of Na+ and H+ and maintain Na+ in the vacuoles, thereby reducing the injury affected by salt stress. Increases in galactinol synthase and soluble protein synthesis helped relieve osmotic stress caused by salt, together, they regulated the Na+ content and chlorophyll biosynthesis of the plant and enabled the plant to adapt to salt stress over time.
New Sources of Eastern Filbert Blight Resistance and Simple Sequence Repeat Markers on Linkage Group 6 in Hazelnut (Corylus avellana L.)
Authors: Komaei Koma Golnaz , Şekerli Merve , Snelling Jacob W. , Mehlenbacher Shawn A.
Published: June 2021

Commercial production of hazelnut (Corylus avellana) in Oregon’s Willamette Valley is threatened by eastern filbert blight (EFB), a serious canker disease caused by the pyrenomycete Anisogramma anomala (Peck) E. Müller. The fungus also prevents the establishment of hazelnut orchards in eastern North America. Genetic resistance is considered the most effective way to control the disease. A high level of EFB resistance was first discovered in ’Gasaway’. This resistance is conferred by a dominant allele at a single locus on linkage group 6 (LG6). Resistance from several additional sources has been assigned to the same chromosomal region. In this study, new simple sequence repeat (SSR) markers were developed for the resistance region on LG6 and new sources of resistance were investigated. Forty-two new SSR markers were developed from four contigs in the genome sequence of ‘Jefferson’ hazelnut, characterized, and nine of them were placed on LG6 of the genetic map. Accessions representing 12 new sources of EFB resistance were crossed with susceptible selections resulting in 18 seedling populations. Segregation ratios in the seedling populations fit the expected 1:1 ratio for 10 sources, while one source showed an excess of resistant seedlings and another showed an excess of susceptible seedlings. Based on correlation of disease response and scores of SSR markers in the ‘Gasaway’ resistance region in the seedlings, eight resistance sources were assigned to LG6. Linkage maps were constructed for each progeny using SSR markers. The LG6 resistance sources include two selections (#23 and #26) from the Russian Research Institute of Forestry and Mechanization near Moscow, four selections from southern Russia, one selection (OSU 1185.126) from Crimea, one selection (OSU 533.129) from Michigan, Corylus heterophylla ‘Ogyoo’ from the South Korea, and the interspecific hybrid ’Estrella #1’. These new LG6 resistance sources and SSR markers should be useful in breeding new cultivars, including the pyramiding of resistance genes. For the other four resistance sources (Moscow #37, hybrid selection OSU 401.014, C. americana ‘Winkler’ and C. americana OSU 366.060), SSR marker scores on linkage groups 6, 7 and 2 were not correlated with disease response and merit further investigation.
Two Arabidopsis Homologs of Human Lysine-Specific Demethylase Function in Epigenetic Regulation of Plant Defense Responses
Authors: Noh Seong Woo , Seo Ri-Ra , Park Hee Jin , Jung Ho Won
Published: June 2021

Epigenetic marks such as covalent histone modification and DNA methylation are crucial for mitotically and meiotically inherited cellular memory-based plant immunity. However, the roles of individual players in the epigenetic regulation of plant immunity are not fully understood. Here we reveal the functions of two Arabidopsis thaliana homologs of human lysine-specific demethylase1-like1, LDL1 and LDL2, in the maintenance of methyl groups at lysine 4 of histone H3 and in plant immunity to Pseudomonas syringae infection. The growth of virulent P. syringae strains was reduced in ldl1 and ldl2 single mutants compared to wild-type plants. Local and systemic disease resistance responses, which coincided with the rapid, robust transcription of defense-related genes, were more stably expressed in ldl1 ldl2 double mutants than in the single mutants. At the nucleosome level, mono-methylated histone H3K4 accumulated in ldl1 ldl2 plants genome-wide and in the mainly promoter regions of the defense-related genes examined in this study. Furthermore, in silico comparative analysis of RNA-sequencing and chromatin immunoprecipitation data suggested that several WRKY transcription factors, e.g., WRKY22/40/70, might be partly responsible for the enhanced immunity of ldl1 ldl2. These findings suggest that LDL1 and LDL2 control the transcriptional sensitivity of a group of defense-related genes to establish a primed defense response in Arabidopsis.