bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary Intervention With α-Amylase Inhibitor in White Kidney Beans Added Yogurt Modulated Gut Microbiota to Adjust Blood Glucose in Mice
Authors: Wang Shenli , Guo Chongye , Xing Zhikai , Li Meng , Yang Haiying , Zhang Yunting , Ren Fazheng , Chen Lishui , Mi Shuangli
Published: October 2021

White kidney beans contain α-amylase inhibitors that can be used in diet for weight reduction. In this study, we investigated the potential of white kidney bean (phaseolus vulgaris L.) extract enriched in α-amylase inhibitor as a food additive in yogurt to regulate blood glucose in hyperglycemic animals. Five groups of C57BL/6J mice were fed for 8 weeks with standard chow diets, high-fat diets (HFD), or high-fat diets with supplement of α-amylase inhibitor in white kidney beans (P. vulgaris extract, PVE), yogurt (Y), and PVE added yogurt (YPVE), respectively. The HFD weakened glucose tolerance and caused insulin resistance in mice, and changed the characteristics of intestinal flora. The intervention of Y, PVE, and YPVE decreased blood glucose, insulin, hyperlipidemia, and inflammatory cytokine levels in mice fed with HFD. Moreover, the YPVE could regulate the components of host intestinal microbiota toward a healthy pattern, significantly increased the metabolic-related flora Corynebacterium, Granulicatella, and Streptococcus, while it decreased Paraprevotella and Allobaculum. Thus, YPVE markedly increased functions of “Amino Acid Metabolism,” “Energy Metabolism,” “Nucleotide Metabolism,” and declined functions of “Glycan Biosynthesis and Metabolism.” Consequently, YPVE could be developed as a new functional food because of its beneficial prebiotic properties in the metabolic syndrome.
Comprehensive Analysis of Prognostic Alternative Splicing Signature Reveals Recurrence Predictor for Papillary Thyroid Cancer
Authors: Liu Mian , Khushbu Rooh Afza , Chen Pei , Hu Hui-Yu , Tang Neng , Ou-yang Deng-jie , Wei Bo , Zhao Ya-xin , Huang Peng , Chang Shi
Published: October 2021

Background

Alternative splicing (AS) plays a key role in the diversity of proteins and is closely associated with tumorigenicity. The aim of this study was to systemically analyze RNA alternative splicing (AS) and identify its prognostic value for papillary thyroid cancer (PTC).

Methods

AS percent-splice-in (PSI) data of 430 patients with PTC were downloaded from the TCGA SpliceSeq database. We successfully identified recurrence-free survival (RFS)-associated AS events through univariate Cox regression, LASSO regression and multivariate regression and then constructed different types of prognostic prediction models. Gene function enrichment analysis revealed the relevant signaling pathways involved in RFS-related AS events. Simultaneously, a regulatory network diagram of AS and splicing factors (SFs) was established.

Results

We identified 1397 RFS-related AS events which could be used as the potential prognostic biomarkers for PTC. Based on these RFS-related AS events, we constructed a ten-AS event prognostic prediction signature that could distinguish high-and low-risk patients and was highly capable of predicting PTC patient prognosis. ROC curve analysis revealed the excellent predictive ability of the ten-AS events model, with an area under the curve (AUC) value of 0.889; the highest prediction intensity for one-year RFS was 0.923, indicating that the model could be used as a prognostic biomarker for PTC. In addition, the nomogram constructed by the risk score of the ten-AS model also showed high predictive efficiency for the prognosis of PTC patients. Finally, the constructed SF-AS network diagram revealed the regulatory role of SFs in PTC.

Conclusion

Through the limited analysis, AS events could be regarded as reliable prognostic biomarkers for PTC. The splicing correlation network also provided new insight into the potential molecular mechanisms of PTC.
The Roles of Exosomes as Future Therapeutic Agents and Diagnostic Tools for Glioma
Authors: Wu Xiaoben , Wang Xingbang , Wang Jing , Hao Yingying , Liu Fang , Wang Xin , Yang Lei , Lu Zhiming
Published: October 2021

Glioma is a common type of tumor originating in the brain. Glioma develops in the gluey supporting cells (glial cells) that surround and support nerve cells. Exosomes are extracellular vesicles that contain microRNAs, messenger RNA, and proteins. Exosomes are the most prominent mediators of intercellular communication, regulating, instructing, and re-educating their surrounding milieu targeting different organs. As exosomes’ diameter is in the nano range, the ability to cross the blood–brain barrier, a crucial obstacle in developing therapeutics against brain diseases, including glioma, makes the exosomes a potential candidate for delivering therapeutic agents for targeting malignant glioma. This review communicates the current knowledge of exosomes’ significant roles that make them crucial future therapeutic agents and diagnostic tools for glioma.
A New Score to Assess the Perioperative Period of the Cancer Patient Undergoing Non-Palliative Elective Surgery: A Retrospective Evaluation of a Case Report by PERIDIA Score
Authors: Andresciani Letizia , Calabrò Concetta , Laforgia Mariarita , Ronchi Maria , De Summa Simona , Cariddi Christel , Boccuzzi Rosa , De Rosa Anna , Rizzo Elisabetta , Losito Giulia , Bradascio Grazia , Napoli Gaetano , Simone Michele , Carravetta Giuseppe , Mastrandrea Giovanni
Published: October 2021

The complexity of cancer patients and the use of advanced and demolitive surgical techniques frequently need post-operatory ICU hospitalization. To increase safety and to select the best medical strategies for the patient, a multidisciplinary team has performed a new peri-operatory assessment, arising from evidence-based literature data. Verifying that most of the cancer patients, admitted to the intensive care unit, undergo major surgery with localizations in the supramesocolic thoraco-abdominal area, the team focused the attention on supramesocolic peridiaphragmatic cancer surgery. Some scores already in use in clinical practice were selected for the peri-operatory evaluation process. None of them evaluate parameters relating to the entire peri-operative period. In detail, only a few study models were found that concern the assessment of the intra-operative period. Therefore, we wanted to see if using a mix of validated scores, it was possible to build a single evaluation score (named PERIDIAphragmatic surgery score or PERIDIA-score) for the entire peri-operative period that could be obtained at the end of the patient’s hospitalization period in post-operative ICU. The main property sought with the creation of the PERIDIA-score is the proportionality between the score and the incidence of injuries, deaths, and the length of stay in the ward. This property could organize a tailor-made therapeutic path for the patient based on pre-rehabilitation, physiotherapy, activation of social assistance services, targeted counseling, collaborations with the continuity of care network. Furthermore, if the pre-operative score is particularly high, it could suggest different or less invasive therapeutic options, and if the intra-operative score is particularly high, it could suggest a prolongation of hospitalization in ICU. The retrospective prospective study conducted on 83 patients is still ongoing. The first data would seem to prove an increase of clinical complications in patients who were assigned a one-third score with respect to the maximum (16/48) of PERIDIA-score. Moreover, patients with a 10/16 score within each phase of the evaluation (pre, peri, and post) more frequently develop injuries. In the light of these evidence, the 29-point score assigned to our patient can be considered as predictive for the subsequent critical and fatal complications the patient faced up.
Radiomics Based on Contrast-Enhanced MRI in Differentiation Between Fat-Poor Angiomyolipoma and Hepatocellular Carcinoma in Noncirrhotic Liver: A Multicenter Analysis
Authors: Zhao Xiangtian , Zhou Yukun , Zhang Yuan , Han Lujun , Mao Li , Yu Yizhou , Li Xiuli , Zeng Mengsu , Wang Mingliang , Liu Zaiyi
Published: October 2021

Objective

This study aims to develop and externally validate a contrast-enhanced magnetic resonance imaging (CE-MRI) radiomics-based model for preoperative differentiation between fat-poor angiomyolipoma (fp-AML) and hepatocellular carcinoma (HCC) in patients with noncirrhotic livers and to compare the diagnostic performance with that of two radiologists.

Methods

This retrospective study was performed with 165 patients with noncirrhotic livers from three medical centers. The dataset was divided into a training cohort (n = 99), a time-independent internal validation cohort (n = 24) from one center, and an external validation cohort (n = 42) from the remaining two centers. The volumes of interest were contoured on the arterial phase (AP) images and then registered to the venous phase (VP) and delayed phase (DP), and a total of 3,396 radiomics features were extracted from the three phases. After the joint mutual information maximization feature selection procedure, four radiomics logistic regression classifiers, including the AP model, VP model, DP model, and combined model, were built. The area under the receiver operating characteristic curve (AUC), diagnostic accuracy, sensitivity, and specificity of each radiomics model and those of two radiologists were evaluated and compared.

Results

The AUCs of the combined model reached 0.789 (95%CI, 0.579–0.999) in the internal validation cohort and 0.730 (95%CI, 0.563–0.896) in the external validation cohort, higher than the AP model (AUCs, 0.711 and 0.638) and significantly higher than the VP model (AUCs, 0.594 and 0.610) and the DP model (AUCs, 0.547 and 0.538). The diagnostic accuracy, sensitivity, and specificity of the combined model were 0.708, 0.625, and 0.750 in the internal validation cohort and 0.619, 0.786, and 0.536 in the external validation cohort, respectively. The AUCs for the two radiologists were 0.656 and 0.594 in the internal validation cohort and 0.643 and 0.500 in the external validation cohort. The AUCs of the combined model surpassed those of the two radiologists and were significantly higher than that of the junior one in both validation cohorts.

Conclusions

The proposed radiomics model based on triple-phase CE-MRI images was proven to be useful for differentiating between fp-AML and HCC and yielded comparable or better performance than two radiologists in different centers, with different scanners and different scanning parameters.
Diagnosis and Treatment of Myeloproliferative Neoplasms With PCM1-JAK2 Rearrangement: Case Report and Literature Review
Authors: Sun Yingxin , Cai Yifeng , Chen Jia , Cen Jiannong , Zhu Mingqing , Pan Jinlan , Wu Depei , Sun Aining , Chen Suning
Published: October 2021

Myeloproliferative neoplasm (MPN) with PCM1-JAK2 rearrangement is a rare disease with poor prognosis and lacks uniform treatment guidelines. Several studies confirmed the efficacy of ruxolitinib in hematological malignancies with PCM1-JAK2 fusion, but the efficacy is variable. Here, we report two patients diagnosed with MPN with PCM1-JAK2 fusion who were treated with ruxolitinib-based regimen, including the first case of ruxolitinib combined with pegylated interferon (Peg-IFN), and we conduct a literature review. We found that ruxolitinib combined with Peg-IFN is an effective treatment option in the case of poor efficacy of ruxolitinib monotherapy.
MiR-27a-3p Promotes Non-Small Cell Lung Cancer Through SLC7A11-Mediated-Ferroptosis
Authors: Lu Xuan , Kang Ningning , Ling Xinxin , Pan Ming , Du Wenjing , Gao Shan
Published: October 2021

Background

Ferroptosis is a newly generated regulatory cell death promoted by the accumulated lipid-based reactive oxygen species (ROS). Solute carrier family 7 member 11 (SLC7A11), the cystine/glutamate antiporter, is known as a ferroptosis executor that exhibits a positive correlation with carcinoma progression because of antioxidant function. Nonetheless, it is yet unclear on the understanding of ferroptosis regulation in lung cancer.

Methods

Database, qRT-PCR, Western-blot (WB), and immunohistochemistry were utilized to determine SLC7A11 expression and function, as well as gene iron related to necrosis in clinical tissue specimens and cells; a ferroptosis inducer, inhibitors, and SLC7A11 lentivirus were used to confirm SLC7A11’s biological activity in cell viability, oxidative stress, lipid peroxidation, and iron ion enrichment in non-small cell lung cancer (NSCLC) in different cells; lentivirus was used to infect lung adenocarcinoma cell lines to acquire miR-27a-3p overexpression and knockdown cell lines, and to detect SLC7A11 level through qRT-PCR and WB. The influence of upregulated/downregulated miR-27a-3p on ferroptosis and other related biological characteristics of lung adenocarcinoma cell lines was detected.

Results

Upregulated SLC7A11 was shown in NSCLC patients and cells, and increased SLC7A11 had a relation to the poorly prognostic status of NSCLC patients. Besides, a novel miRNA, miR-27a-3p, was an essential modulator of ferroptosis via directly targeting SLC7A11 in NSCLC cells. Overexpressing miR-27a-3p led to SLC7A11 suppression via directly binding to its 3’-UTR, followed by the reduction of erastin-caused ferroptosis. In contrast, inhibited miR-27a-3p resulted in an increase in NSCLC cells’ sensitivity to erastin. Of importance, the accumulated lipid ROS and cell death of iron peptide mediated by anti-miR-27a-3p can be eliminated by impeding the glutamylation process. Our literature collectively uncovered that miR-27a-3p modulated ferroptosis by targeting SLC7A11 in NSCLC cells, illustrating the important role of miRNA in ferroptosis.

Conclusion

MiR-27a-3p modulates ferroptosis via targeting SLC7A11 in NSCLC cells, implying the significant role of miR-27a-3p/SLC7A11 in ferroptosis.
[18F](2S,4R)-4-Fluoroglutamine as a New Positron Emission Tomography Tracer in Myeloma
Authors: Valtorta Silvia , Toscani Denise , Chiu Martina , Sartori Andrea , Coliva Angela , Brevi Arianna , Taurino Giuseppe , Grioni Matteo , Ruffini Livia , Vacondio Federica , Zanardi Franca , Bellone Matteo , Moresco Rosa Maria , Bussolati Ovidio , Giuliani Nicola
Published: October 2021

The high glycolytic activity of multiple myeloma (MM) cells is the rationale for use of Positron Emission Tomography (PET) with18F-fluorodeoxyglucose ([18F]FDG) to detect both bone marrow (BM) and extramedullary disease. However, new tracers are actively searched because [18F]FDG-PET has some limitations and there is a portion of MM patients who are negative. Glutamine (Gln) addiction has been recently described as a typical metabolic feature of MM cells. Yet, the possible exploitation of Gln as a PET tracer in MM has never been assessed so far and is investigated in this study in preclinical models. Firstly, we have synthesized enantiopure (2S,4R)-4-fluoroglutamine (4-FGln) and validated it as a Gln transport analogue in human MM cell lines, comparing its uptake with that of3H-labelled Gln. We then radiosynthesized [18F]4-FGln, tested its uptake in two differentin vivomurine MM models, and checked the effect of Bortezomib, a proteasome inhibitor currently used in the treatment of MM. Both [18F]4-FGln and [18F]FDG clearly identified the spleen as site of MM cell colonization in C57BL/6 mice, challenged with syngeneic Vk12598 cells and assessed by PET. NOD.SCID mice, subcutaneously injected with human MM JJN3 cells, showed high values of both [18F]4-FGln and [18F]FDG uptake. Bortezomib significantly reduced the uptake of both radiopharmaceuticals in comparison with vehicle at post treatment PET. However, a reduction of glutaminolytic, but not of glycolytic, tumor volume was evident in mice showing the highest response to Bortezomib. Our data indicate that [18F](2S,4R)-4-FGln is a new PET tracer in preclinical MM models, yielding a rationale to design studies in MM patients.
Cancer CRC: A Comprehensive Cancer Core Transcriptional Regulatory Circuit Resource and Analysis Platform
Authors: Wei Ling , Chen Jiaxin , Song Chao , Zhang Yuexin , Zhang Yimeng , Xu Mingcong , Feng Chenchen , Gao Yu , Qian Fengcui , Wang Qiuyu , Shang Desi , Zhou Xinyuan , Zhu Jiang , Wang Xiaopeng , Jia Yijie , Liu Jiaqi , Zhu Yanbing , Li Chunquan
Published: October 2021

A core transcriptional regulatory circuit (CRC) is a group of interconnected auto-regulating transcription factors (TFs) that form loops and can be identified by super-enhancers (SEs). Studies have indicated that CRCs play an important role in defining cellular identity and determining cellular fate. Additionally, core TFs in CRCs are regulators of cell-type-specific transcriptional regulation. However, a global view of CRC properties across various cancer types has not been generated. Thus, we integrated paired cancer ATAC-seq and H3K27ac ChIP-seq data for specific cell lines to develop the Cancer CRC (http://bio.liclab.net/Cancer_crc/index.html). This platform documented 94,108 cancer CRCs, including 325 core TFs. The cancer CRC also provided the “SE active core TFs analysis” and “TF enrichment analysis” tools to identify potentially key TFs in cancer. In addition, we performed a comprehensive analysis of core TFs in various cancer types to reveal conserved and cancer-specific TFs.
Necrotizing Enterocolitis: LPS/TLR4-Induced Crosstalk Between Canonical TGF-β/Wnt/β-Catenin Pathways and PPARγ
Authors: Gomart Alexia , Vallée Alexandre , Lecarpentier Yves
Published: October 2021

Necrotizing enterocolitis (NEC) represents one of the major causes of morbidity and mortality in premature infants. Several recent studies, however, have contributed to a better understanding of the pathophysiology of this dreadful disease. Numerous intracellular pathways play a key role in NEC, namely: bacterial lipopolysaccharide (LPS), LPS toll-like receptor 4 (TLR4), canonical Wnt/β-catenin signaling and PPARγ. In a large number of pathologies, canonical Wnt/β-catenin signaling and PPARγ operate in opposition to one another, so that when one of the two pathways is overexpressed the other is downregulated andvice-versa. In NEC, activation of TLR4 by LPS leads to downregulation of the canonical Wnt/β-catenin signaling and upregulation of PPARγ. This review aims to shed light on the complex intracellular mechanisms involved in this pathophysiological profile by examining additional pathways such as the GSK-3β, NF-κB, TGF-β/Smads, and PI3K-Akt pathways.
Altered Cytokine Endotoxin Responses in Neonatal Encephalopathy Predict MRI Outcomes
Authors: O'Dea Mary Isabel , Kelly Lynne A. , McKenna Ellen , Strickland Tammy , Hurley Tim P. , Butler John , Vavasseur Claudine , EL-Khuffash Afif F. , Miletin Jan , Fallah Lida , White Arthur , Wyse Jason , Molloy Eleanor J.
Published: October 2021

Background: Neonatal encephalopathy (NE) is associated with adverse neurodevelopmental outcome and is linked with systemic inflammation. Pro-inflammatory and anti-inflammatory cytokines are known to play a role in the pathology of NE by activating innate immune cells.

Methods: Eighty-seven infants were enrolled including 53 infants with NE of whom 52 received therapeutic hypothermia (TH) and 34 term infant healthy controls (TC). Whole blood sampling was performed in the first 4 days of life, and a 14-spot ELISA Multiplex Cytokine Array was carried out on baseline samples or after stimulation with lipopolysaccharide (LPS) as an additional inflammatory stimulus. The cytokine medians were examined for differences between infants with NE and healthy TC; and then short-term outcomes of Sarnat stage, seizures, and MRI brain were examined within the NE group. The potential of LPS stimulation to predict abnormal MRI was explored using receiver operating characteristic (ROC) curves.

Results: At baseline, infants with NE had significantly higher levels of erythropoietin (Epo), interleukin (IL)-6, and IL-1ra and significantly lower vascular endothelial growth factor (VEGF) than had controls. All cytokines were increased after LPS stimulation in infants with NE with an excessive Epo and IL-1ra response than in controls. Infants with NE had lower IL-8, IL-2, IL-6, tumor necrosis factor (TNF)-α, granulocyte-macrophage colony-stimulating factor (GM-CSF), VEGF, and interferon (IFN)-γ than controls had following LPS. GM-CSF and IFN-γ, IL-1β, IL-1ra, and VEGF were higher on days 1–2 in NE infants with abnormal neuroimaging. GM-CSF, IFN-γ, and TNF-α levels with LPS stimulation were different upon stimulation between normal and abnormal neuroimaging. TNF-α is the only strong cytokine predictor both pre- and post-LPS stimulation of abnormal brain imaging.

Conclusions: Altered cytokine responses are found in infants with NE vs. controls, and more significant differences are unmasked by the additional stimulus of LPS, which potentially improves the predictive power of these cytokines for the detection of abnormal MRIs. Infants with NE undergoing TH demonstrate both trained immunity and tolerance, and understanding these responses will facilitate adjunctive immunomodulatory treatments.
Longitudinal Trajectories of Hair Cortisol: Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Early Childhood
Authors: Rovnaghi Cynthia R. , Rigdon Joseph , Roué Jean-Michel , Ruiz Monica O. , Carrion Victor G. , Anand Kanwaljeet J. S.
Published: October 2021

The objective of this study was to examine if longitudinal trajectories of hair cortisol concentrations (HCC) measured at two or three yearly time points can identify 1-3 year old children at risk for altered hypothalamic-pituitary-adrenal (HPA)-axis function due to early life stress (ELS). HCC was measured (N = 575) in 265 children using a validated enzyme-linked immunosorbent assay. Hair was sampled in Clinic Visits (CV) centered at years 1, 2, and 3 (n = 45); 1 and 2 (n = 98); 1 and 3 (n = 27); 2 and 3 (n = 95). Log-transformed HCC values were partitioned using latent class mixed models (LCMM) to minimize the Bayesian Information Criterion. Multivariable linear mixed effects models for ln-HCC as a function of fixed effects for age in months and random effects for participants (to account for repeated measures) were generated to identify the factors associated with class membership. Children in Class 1 (n = 69; 9% Black) evidenced declining ln-HCC across early childhood, whereas Class 2 members (n = 196; 43% Black) showed mixed trajectories. LCMM with only Class 2 members revealed Class 2A (n = 17, 82% Black) with sustained high ln-HCC and Class 2B (n = 179, 40% Blacks) with mixed ln-HCC profiles. Another LCMM limited to only Class 2B members revealed Class 2B1 (n = 65, 57% Black) with declining ln-HCC values (at higher ranges than Class 1), and Class 2B2 (n = 113, 30% Black) with sustained high ln-HCC values. Class 1 may represent hair cortisol trajectories associated with adaptive HPA-axis profiles, whereas 2A, 2B1, and 2B2 may represent allostatic load with dysregulated profiles of HPA-axis function in response to varying exposures to ELS. Sequential longitudinal hair cortisol measurements revealed the allostatic load associated with ELS and the potential for developing maladaptive or dysregulated HPA-axis function in early childhood.
Hepatic Ischemia-Reperfusion Impairs Blood-Brain Barrier Partly Due to Release of Arginase From Injured Liver
Authors: Zhu Liang , Zhou Han , Xu Feng , Yang Hanyu , Li Ping , Sheng Yun , Liu Peihua , Kong Weimin , Liu Xiaonan , Yang Lu , Liu Li , Liu Xiaodong
Published: October 2021

Aim: Hepatic ischemia-reperfusion (HIR) induces remote organs injury, including the brain. The homeostasis of the brain is maintained by the blood-brain barrier (BBB); thus, we aimed to investigate whether HIR impaired BBB and attempted to elucidate its underlying mechanism.

Methods: Cell viability of human cerebral microvascular endothelial cells (hCMEC/D3) was measured following 24 h incubation with a serum of HIR rat undergoing 1 h ischemia and 4 h reperfusion, liver homogenate, or lysate of primary hepatocytes of the rat. The liver homogenate was precipitated using (NH4)2SO4 followed by separation on three columns and electrophoresis to identify the toxic molecule. Cell activity, apoptosis, proliferation, cell cycle, and expressions of proteins related to cell cycle were measured in hCMEC/D3 cells incubated with identified toxic molecules. HIR rats undergoing 1 h ischemia and 24 h reperfusion were developed to determine the release of an identified toxic molecule. BBB function was indexed as permeability to fluorescein and brain water. Endothelial cell proliferation and expressions of proteins related to the cell cycle in cerebral microvessels were measured by immunofluorescence and western blot.

Results: Toxic molecule to BBB in the liver was identified to be arginase. Arginase inhibitor nor-NOHA efficiently attenuated hCMEC/D3 damage caused by liver homogenate and serum of HIR rats. Both arginase and serum of HIR rats significantly lowered arginine (Arg) in the culture medium. Arg addition efficiently attenuated the impairment of hCMEC/D3 caused by arginase or Arg deficiency, demonstrating that arginase impaired hCMEC/D3 via depriving Arg. Both arginase and Arg deficiency damaged hCMEC/D3 cells by inhibiting cell proliferation, retarding the cell cycle to G1 phase, and downregulating expressions of cyclin A, cyclin D, CDK2, and CDK4. HIR notably increased plasma arginase activity and lowered Arg level, increased the BBB permeability accompanied with enhanced brain water, and decreased the proliferative cells (marked by Ki67) in cerebral microvessels (marked by CD31) and protein expressions of cyclin A, cyclin D, CDK2 and CDK4 in isolated brain microvessels. Oral supplement of Arg remarkably attenuated these HIR-induced alterations.

Conclusion: HIR leads to substantial release of arginase from the injured liver and then deprives systemic Arg. The Arg deficiency further impairs BBB via inhibiting the proliferation of brain microvascular endothelial cells by cell cycle arrest.
Micronized Palmitoylethanolamide Ameliorates Methionine- and Choline-Deficient Diet–Induced Nonalcoholic Steatohepatitis via Inhibiting Inflammation and Restoring Autophagy
Authors: Hu Jiaji , Ying Hanglu , Yao Jie , Yang Longhe , Jin Wenhui , Ma Huabin , Li Long , Zhao Yufen
Published: October 2021

Nonalcoholic steatohepatitis (NASH) has become one of the serious causes of chronic liver diseases, characterized by hepatic steatosis, hepatocellular injury, inflammation and fibrosis, and lack of efficient therapeutic agents. Palmitoylethanolamide (PEA) is an endogenous bioactive lipid with various pharmacological activities, including anti-inflammatory, analgesic, and neuroprotective effects. However, the effect of PEA on nonalcoholic steatohepatitis is still unknown. Our study aims to explore the potential protective role of PEA on NASH and to reveal the underlying mechanism. In this study, the C57BL/6 mice were used to establish the NASH model through methionine- and choline-deficient (MCD) diet feeding. Here, we found that PEA treatment significantly improved liver function, alleviated hepatic pathological changes, and attenuated the lipid accumulation and hepatic fibrosis in NASH mice induced by MCD diet feeding. Mechanistically, the anti-steatosis effect of PEA may be due to the suppressed expression of ACC1 and CD36, elevated expression of PPAR-α, and the phosphorylation levels of AMPK. In addition, hepatic oxidative stress was greatly inhibited in MCD-fed mice treated with PEA via enhancing the expression and activities of antioxidant enzymes, including GSH-px and SOD. Moreover, PEA exerted a clear anti-inflammatory effect though ameliorating the expression of inflammatory mediators and suppressing the NLRP3 inflammasome pathway activation. Furthermore, the impaired autophagy in MCD-induced mice was reactivated with PEA treatment. Taken together, our research suggested that PEA protects against NASH through the inhibition of inflammation and restoration of autophagy. Thus, PEA may represent an efficient therapeutic agent to treat NASH.
The Role of Traditional Plant Knowledge in the Fight Against Infectious Diseases: A Meta-Analytic Study in the Catalan Linguistic Area
Authors: Gras Airy , Parada Montse , Vallès Joan , Garnatje Teresa
Published: October 2021

Infectious diseases represent, as a group, the main cause of mortality in the world. The most important reasons are multidrug-resistant pathogens, the rapid spread of emerging diseases aggravated by globalization, and the extended reach of tropical and vector-borne diseases resulting from continued climate change. Given the increase in these diseases and the limited effectiveness of antibiotics, traditional knowledge can constitute a useful tool to address these new health challenges. The aim of this work is to analyze extensively the available ethnobotanical data linked to infections and infestations in the Catalan linguistic area, with the intention of depicting the panorama of the folk use of herbal products to address the quoted ailments, preserving the popular plant knowledge and management data. The meta-analytic work performed in the present study covers 29 research studies belonging to different regions throughout the Catalan linguistic area. The medicinal ethnoflora to treat infections and infestations in the Catalan linguistic area includes 326 taxa belonging to 78 botanical families of vascular plants. The informant consensus factor (FIC) was 0.92, and the ethnobotanicity index (EI) was 7.26%. Artemisia absinthium (10.98%; 0.37) and Thymus vulgaris (8.06%; 0.27) are the most quoted taxa and have the highest values of the cultural importance index. The most reported use was antihelminthic (30.15%), followed by internal antiseptic (19.43%) and antipyretic (13.69%). The medicinal importance index shows the relevance of the antihelminthic use (14.23) and also the use against measles (10.19). The information is coincidental with at least one of the comprehensive pharmacological literature sources checked for 47.42% of ethnobotanical uses. These results, centered on the plants used to treat infection and infestation diseases, are the first step toward selecting some of the most interesting species to develop phytochemical and pharmacological studies and suggesting an alternative regarding how to face the health emergency involving the expansion of infectious diseases, based on local and traditional knowledge.
Modulating Sirtuin Biology and Nicotinamide Adenine Diphosphate Metabolism in Cardiovascular Disease—From Bench to Bedside
Authors: Wang Yu-Jen , Paneni Francesco , Stein Sokrates , Matter Christian M.
Published: October 2021

Sirtuins (SIRT1–7) comprise a family of highly conserved deacetylases with distribution in different subcellular compartments. Sirtuins deacetylate target proteins depending on one common substrate, nicotinamide adenine diphosphate (NAD+), thus linking their activities to the status of cellular energy metabolism. Sirtuins had been linked to extending life span and confer beneficial effects in a wide array of immune-metabolic and cardiovascular diseases. SIRT1, SIRT3, and SIRT6 have been shown to provide protective effects in various cardiovascular disease models, by decreasing inflammation, improving metabolic profiles or scavenging oxidative stress. Sirtuins may be activated collectively by increasing their co-substrate NAD+. By supplementing NAD+ precursors, NAD+ boosters confer pan-sirtuin activation with protective cardiometabolic effects in the experimental setting: they improve endothelial dysfunction, protect from experimental heart failure, hypertension and decrease progression of liver steatosis. Different precursor molecules were applied ranging from nicotinamide (NAM), nicotinamide mononucleotide (NMN) to nicotinamide riboside (NR). Notably, not all experimental results showed protective effects. Moreover, the results are not as striking in clinical studies as in the controlled experimental setting. Species differences, (lack of) genetic heterogeneity, different metabolic pathways, dosing, administration routes and disease contexts may account for these challenges in clinical translation. At the clinical scale, caloric restriction can reduce the risks of cardiovascular disease and raise NAD+ concentration and sirtuin expression. In addition, antidiabetic drugs such as metformin or SGLT2 inhibitors may confer cardiovascular protection, indirectly via sirtuin activation. Overall, additional mechanistic insight and clinical studies are needed to better understand the beneficial effects of sirtuin activation and NAD+ boosters from bench to bedside.
Characterization of Frond and Flower Development and Identification of FT and FD Genes From Duckweed Lemna aequinoctialis Nd
Authors: Yoshida Akiko , Taoka Ken-ichiro , Hosaka Aoi , Tanaka Keisuke , Kobayashi Hisato , Muranaka Tomoaki , Toyooka Kiminori , Oyama Tokitaka , Tsuji Hiroyuki
Published: October 2021

Duckweeds (Araceae: Lemnoideae) are aquatic monocotyledonous plants that are characterized by their small size, rapid growth, and wide distribution. Developmental processes regulating the formation of their small leaf-like structures, called fronds, and tiny flowers are not well characterized. In many plant species, flowering is promoted by the florigen activation complex, whose major components are florigen FLOWERING LOCUS T (FT) protein and transcription factor FD protein. How this complex is regulated at the molecular level during duckweed flowering is also not well understood. In this study, we characterized the course of developmental changes during frond development and flower formation in Lemna aequinoctialis Nd, a short-day plant. Detailed observations of frond and flower development revealed that cell proliferation in the early stages of frond development is active as can be seen in the separate regions corresponding to two budding pouches in the proximal region of the mother frond. L. aequinoctialis produces two stamens of different lengths with the longer stamen growing more rapidly. Using high-throughput RNA sequencing (RNA-seq) and de novo assembly of transcripts from plants induced to flower, we identified the L. aequinoctialis FT and FD genes, whose products in other angiosperms form a transcriptional complex to promote flowering. We characterized the protein-protein interaction of duckweed FT and FD in yeast and examined the functions of the two gene products by overexpression in Arabidopsis. We found that L. aequinoctialis FTL1 promotes flowering, whereas FTL2 suppresses flowering.
Stoichiometry of C:N:P in the Roots of Alhagi sparsifolia Is More Sensitive to Soil Nutrients Than Aboveground Organs
Authors: Yin Hui , Zheng Hongwei , Zhang Bo , Tariq Akash , Lv Guanghui , Zeng Fanjiang , Graciano Corina
Published: October 2021

The stoichiometry of carbon, nitrogen, and phosphorus (C:N:P) among leaves, stems, and roots reflects trade-offs in plants for acquiring resources and their growth strategy. The widely distributed plant Alhagi sparsifolia is an ideal species to study the ecological stoichiometry in different organs in response to the availability of nutrients and water in the desert ecosystem. However, which response of organs is most sensitive to environmental conditions is still unclear. To answer this question, we collected samples of plants and soils including not only aboveground leaves and stems, but also underground roots and soils from a wide range of arid areas during the growing season. The C, N, P, C:N, C:P, and N:P ratios in leaves, thorns, stems, and roots were derived to explore their relationship as well as their response mechanisms to nutrients and water spanning 1 m deep in the soil. The results showed that the order of N concentration was leaves > thorns > stems > roots, that the concentration of P in the leaves, thorns, and stems was similar, and that their values were higher than those in the roots. First, the C:N ratios in the leaves and stems were significantly positively correlated with the ratio in roots. The C:N ratios in each organ showed a significant relationship with the soil alkali hydrolyzable nitrogen (SAN) above a depth of 60 cm. In addition to SAN, soil available phosphorus (SAP) and soil organic carbon (SOC) affect the C:N ratio in the roots. Second, the C:P and N:P ratios in aboveground organs showed no correlations with the ratios in roots. The C:P and N:P ratios in the leaves and thorns have no relationship with soil nutrients, while the C:P ratio in roots was influenced by SAN and SOC in all soil layers. Finally, the N:P ratios in roots were also affected by nutrients in different soil depths at 0–20 and 60–80 cm. These results illustrate that the roots were more sensitive to soil nutrients than the aboveground parts. Our study of ecological stoichiometry also suggests a novel systematic approach for analyzing the sensitivity of responses of an organ to environmental conditions.
Exogenous Spermidine Priming Mitigates the Osmotic Damage in Germinating Seeds of Leymus chinensis Under Salt-Alkali Stress
Authors: Hongna Chen , Junmei Shi , Leyuan Tao , Xiaori Han , Guolin Lin , Xianguo Cheng
Published: October 2021

Spermidine (Spd) is known to protect macromolecules involved in physiological and biochemical processes in plants. However, it is possible that Spd also plays an osmotic regulatory role in promoting the seed germination of Leymus chinensis (L. chinensis) under salt-alkali stress. To investigate this further, seeds of L. chinensis were soaked in Spd solution or distilled water, and a culture experiment was performed by sowing the soaked seeds in saline-alkaline soils. The data showed that the Spd priming resulted in an increase of more than 50% in soluble sugar content and an increase of more than 30% in proline content in the germinating seeds. In addition, the Spd priming resulted in an increase of more than 30% in catalase activity and an increase of more than 25% in peroxidase activity in the germinating seeds and effectively mitigated the oxidative damage to the plasma membrane in the germinating seeds under salt-alkali stress. Moreover, the Spd priming of seeds affected the accumulation of polyamine (PA) and maintained the activities of macromolecules involved in physiological metabolism in germinating seeds exposed to salt-alkali stress. Furthermore, the Spd priming treatment increased the hydrogen peroxide (H2O2) level to more than 30% and the Ca2+ concentration to more than 20% in the germinating seeds, thus breaking the dormancy induction pathways in L. chinensis seeds through beneficial hormone enrichment. This study provides an insight into the Spd-mediated regulation pathway during exogenous Spd priming of L. chinensis seeds, which mitigates osmotic and oxidative damage and maintains the integrality of the cell lipid membrane. Thus, exogenous Spd priming increases PA oxidase activity and maintains the accumulation of H2O2. We found that the H2O2 beneficially affected the balance of Ca2+ and hormones, promoting the vigor and germination of L. chinensis in response to salt-alkali stress.
Comparative Genomic Analysis of Quantitative Trait Loci Associated With Micronutrient Contents, Grain Quality, and Agronomic Traits in Wheat (Triticum aestivum L.)
Authors: Shariatipour Nikwan , Heidari Bahram , Tahmasebi Ahmad , Richards Christopher
Published: October 2021

Comparative genomics and meta-quantitative trait loci (MQTLs) analysis are important tools for the identification of reliable and stable QTLs and functional genes controlling quantitative traits. We conducted a meta-analysis to identify the most stable QTLs for grain yield (GY), grain quality traits, and micronutrient contents in wheat. A total of 735 QTLs retrieved from 27 independent mapping populations reported in the last 13 years were used for the meta-analysis. The results showed that 449 QTLs were successfully projected onto the genetic consensus map which condensed to 100 MQTLs distributed on wheat chromosomes. This consolidation of MQTLs resulted in a three-fold reduction in the confidence interval (CI) compared with the CI for the initial QTLs. Projection of QTLs revealed that the majority of QTLs and MQTLs were in the non-telomeric regions of chromosomes. The majority of micronutrient MQTLs were located on the A and D genomes. The QTLs of thousand kernel weight (TKW) were frequently associated with QTLs for GY and grain protein content (GPC) with co-localization occurring at 55 and 63%, respectively. The co- localization of QTLs for GY and grain Fe was found to be 52% and for QTLs of grain Fe and Zn, it was found to be 66%. The genomic collinearity within Poaceae allowed us to identify 16 orthologous MQTLs (OrMQTLs) in wheat, rice, and maize. Annotation of promising candidate genes (CGs) located in the genomic intervals of the stable MQTLs indicated that several CGs (e.g., TraesCS2A02G141400, TraesCS3B02G040900, TraesCS4D02G323700, TraesCS3B02G077100, and TraesCS4D02G290900) had effects on micronutrients contents, yield, and yield-related traits. The mapping refinements leading to the identification of these CGs provide an opportunity to understand the genetic mechanisms driving quantitative variation for these traits and apply this information for crop improvement programs.
Missing Links in Predicting Berry Sunburn in Future Vineyards
Authors: Bahr Christopher , Schmidt Dominik , Kahlen Katrin
Published: October 2021

Sunburn in grapevine berries is known as a recurring disorder causing severe yield losses and a decline in berry quality. The transition from healthy to sunburnt along a temporal trajectory is not fully understood. It is driven by light-boosted local heat impact and modulated by, e.g., past environments of the berry and its developmental state. Events of berry sunburn are often associated with heatwaves, indicating a link to climate change. In addition, the sensitivity of grapevine architecture to changing environmental condition indicates an urgent need to investigate and adapt mitigation strategies of berry sunburn in future vineyards. In this perspective, we want to identify missing links in predicting berry sunburn in vineyards and propose a modeling framework that may help us to investigate berry sunburn in future vineyards. For this, we propose to address open issues in both developing a model of berry sunburn and considering dynamic canopy growth, and canopy interaction with the environment and plant management such as shoot positioning or leaf removal. Because local environmental conditions drive sunburn, we aim at showing that identifying sunburn-reducing strategies in a vineyard under future environmental conditions can be supported by a modeling approach that integrates effects of management practices over time and takes grapevine architecture explicitly into account. We argue that functional-structural plant models may address such complex tasks. Once open issues are solved, they might be a promising tool to advance our knowledge on reducing risks of berry sunburnin silico.
Kernel Water Relations and Kernel Filling Traits in Maize (Zea mays L.) Are Influenced by Water-Deficit Condition in a Tropical Environment
Authors: Alam Md. Robiul , Nakasathien Sutkhet , Molla Md. Samim Hossain , Islam Md. Ariful , Maniruzzaman Md. , Ali Md. Akkas , Sarobol Ed , Vichukit Vichan , Hassan Mohamed M. , Dessoky Eldessoky S. , Abd El-Ghany Enas M. , Brestic Marian , Skalicky Milan , Jagadish S. V. Krishna , Hossain Akbar
Published: October 2021

Water deficit is a major limiting condition for adaptation of maize in tropical environments. The aims of the current observations were to evaluate the kernel water relations for determining kernel developmental progress, rate, and duration of kernel filling, stem reserve mobilization in maize. In addition, canopy temperature, cell membrane stability, and anatomical adaptation under prolonged periods of pre- and post-anthesis water deficit in different hybrids was quantified to support observations related to kernel filling dynamics. In this context, two field experiments in two consecutive years were conducted with five levels of water regimes: control (D1), and four water deficit treatments [V10 to V13 (D2); V13 to V17 (D3); V17 to blister stage (D4); blisters to physiological maturity (D5)], on three maize hybrids (Pioneer 30B80, NK 40, and Suwan 4452) in Expt. 1. Expt. 2 had four water regimes: control (D1), three water deficit treatments [V10 to anthesis (D2); anthesis to milk stage (D3); milk to physiological maturity (D4)], and two maize hybrids (NK 40 and Suwan 4452). Water deficit imposed at different stages significantly reduced maximum kernel water content (MKWC), kernel filling duration (KFD), final kernel weight (FKW), and kernel weight ear–1 while it increased kernel water loss rate (KWLR), kernel filling rate (KFR), and stem weight depletion (SWD) across maize hybrids in both experiments. The lowest MKWC under water deficit was at D3 in both experiments, indicating that lower KFR results in lowest FKW in maize. Findings indicate that the MKWC (R2 = 0.85 and 0.41) and KFR (R2 = 0.62 and 0.37) were positively related to FKW in Expt. 1 and 2, respectively. The KFD was reduced by 5, 7, 7, and 11 days under water deficit at D3, D4 in Expt. 2 and D4, D5 in Expt. 1 as compared to control, respectively. Water deficit at D5 in Expt. 1 and D4 in Expt. 2 increased KWLR, KFR, and SWD. In Expt. 2, lower canopy temperature and electrical conductivity indicated cell membrane stability across water regimes in NK 40. Hybrid NK 40 under water deficit had significantly higher cellular adaptation by increasing the number of xylem vessel while reducing vessel diameter in leaf mid-rib and attached leaf blade. These physiological adjustments improved efficient transport of water from root to the shoot, which in addition to higher kernel water content, MKWC, KFD, KFR, and stem reserve mobilization capacity, rendered NK 40 to be better adapted to water-deficit conditions under tropical environments.
Allometry Between Vegetative and Reproductive Traits in Orchids
Authors: Feng Jing-Qiu , Zhang Feng-Ping , Huang Jia-Lin , Hu Hong , Zhang Shi-Bao
Published: October 2021

In flowering plants, inflorescence characteristics influence both seed set and pollen contribution, while inflorescence and peduncle size can be correlated with biomass allocation to reproductive organs. Peduncles also play a role in water and nutrient supply of flowers, and mechanical support. However, it is currently unclear whether inflorescence size is correlated with peduncle size. Here, we tested whether orchids with large diameter peduncles bear more and larger flowers than those with smaller peduncles by analyzing 10 traits of inflorescence, flower, and leaf in 26 species. Peduncle diameters were positively correlated with inflorescence length and total floral area, indicating that species with larger peduncles tended to have larger inflorescences and larger flowers. We also found strongly positive correlation between inflorescence length and leaf area, and between total floral area and total leaf area, which suggested that reproductive organs may be allometrically coordinated with vegetative organs. However, neither flower number nor floral dry mass per unit area were correlated with leaf number or leaf dry mass per unit area, implying that the function between leaf and flower was uncoupled. Our findings provided a new insight for understanding the evolution of orchids, and for horticulturalists interested in improving floral and inflorescence traits in orchids.