bluuebunny/crossref_metadata_2025 huggingface dataset:
Curcumin-mediated transcriptional regulation of human N-acetylgalactosamine-α2,6-sialyltransferase which synthesizes sialyl-Tn antigen in HCT116 human colon cancer cells
Authors: An So-Young , Kim Kyoung-Sook , Cho Jong-Hyun , Kim Hee-Do , Kim Cheorl-Ho , Lee Young-Choon
Published: September 2022

Human N-acetylgalactosamine-α2,6-sialyltransferase (hST6GalNAc I) is the major enzyme involved in the biosynthesis of sialyl-Tn antigen (sTn), which is known to be expressed in more than 80% of human carcinomas and correlated with poor prognosis in cancer patients. Athough high expression of hST6GalNAc I is associated with augmented proliferation, migration and invasion in various cancer cells, transcriptional mechanism regulating hST6GalNAc I gene expression remains largely unknown. In this study, we found that hST6GalNAc I gene expression was markedly augmented by curcumin in HCT116 human colon carcinoma cells. To understand the molecular mechanism for the upregulation of hST6GalNAc I gene expression by curcumin in HCT116 cells, we first determined the transcriptional start site of hST6GalNAc I gene by 5′-RACE and cloned the proximal hST6GalNAc I 5′-flanking region spanning about 2 kb by PCR. Functional analysis of the hST6GalNAc I 5′ flanking region of hST6GalNAc I by sequential 5′-deletion, transient transfection of reporter gene constructs and luciferase reporter assays showed that -378/-136 region is essential for maximal activation of transcription in response to curcumin in HCT 116 cells. This region includes putative binding sites for transcription factors c-Ets-1, NF-1, GATA-1, ER-α, YY1, and GR-α. ChIP analysis and site-directed mutagenesis demonstrated that estrogen receptor α (ER-α) binding site (nucleotides -248/-238) in this region is crucial for hST6GalNAc I gene transcription in response to curcumin stimulation in HCT116 cells. The transcription activity of hST6GalNAc I gene induced by curcumin in HCT116 cells was strongly inhibited by PKC inhibitor (Gö6983) and ERK inhibitor (U0126). These results suggest that curcumin-induced hST6GalNAc I gene expression in HCT116 cells is modulated through PKC/ERKs signal pathway.
The role of PKC/PKR in aging, Alzheimer's disease, and perioperative neurocognitive disorders
Authors: Lu Wenping , Tang Sailan , Li Ao , Huang Qiuyue , Dou Mengyun , Zhang Ye , Hu Xianwen , Chang Raymond Chuen Chung , Wong Gordon Tin Chun , Huang Chunxia
Published: September 2022

Background

The incidence of perioperative neurocognitive disorders (PNDs) is reportedly higher in older patients. Mitochondrial and synaptic dysfunctions have consistently been demonstrated in models of aging and neurodegenerative diseases; nonetheless, their role in PND is not well understood.

Methods

The Morris water maze and elevated plus maze tests were used to assess the learning and memory abilities of both C57BL/6 and 3×Tg-AD mice of different ages (8 and 18 months). PND was induced by laparotomy in C57BL/6 mice and 3×Tg-AD mice (8 months old). Markers associated with neuroinflammation, mitochondrial function, synaptic function, and autophagy were assessed postoperatively. The roles of protein kinase C (PKC) and double-stranded RNA-dependent protein kinase (PKR) were further demonstrated by using PKC-sensitive inhibitor bisindolylmaleimide X (BIMX) or PKR−/− mice.

Results

Significant cognitive impairment was accompanied by mitochondrial dysfunction and autophagy inactivation in both aged C57BL/6 and 3×Tg-AD mice. Laparotomy induced a significant neuroinflammatory response and synaptic protein loss in the hippocampus. Cognitive and neuropathological changes induced by aging or laparotomy were further exacerbated in 3×Tg-AD mice. Deficits in postoperative cognition, hippocampal mitochondria, autophagy, and synapse were significantly attenuated after pharmacological inhibition of PKC or genetic deletion of PKR.

Conclusions

Our findings suggest similar pathogenic features in aging, Alzheimer's disease, and PND, including altered mitochondrial homeostasis and autophagy dysregulation. In addition, laparotomy may exacerbate cognitive deficits associated with distinct neuronal inflammation, mitochondrial dysfunction, and neuronal loss independent of genetic background. The dysregulation of PKC/PKR activity may participate in the pathogenesis of these neurodegenerative diseases.
Predictors of prodromal Parkinson’s disease in young adult Pink1−/− rats
Authors: Lechner Sarah A. , Welsch Jacob M. , Pahapill Natalie K. , Kaldenberg Taylor A. R. , Regenbaum Amy , Kelm-Nelson Cynthia A.
Published: September 2022

Parkinson’s disease (PD) is a progressive, degenerative disease that affects nearly 10 million people worldwide. Hallmark limb motor signs and dopamine depletion have been well studied; however, few studies evaluating early stage, prodromal biology exist. Pink1−/− rats, a rodent model of PD mitochondrial dysfunction, exhibit early stage behavioral deficits, including vocal communication and anxiety, that progress during mid-to-late adulthood (6–12 months of age). Yet, the biological pathways and mechanisms that lead to prodromal dysfunction are not well understood. This study investigated the Pink1−/− rat in young adulthood (2 months of age). Mixed sex groups of Pink1−/− rats and wildtype (WT) controls were assayed for limb motor, anxiety, and vocal motor behaviors. A customized NanoString CodeSet, based on genetic work in later adulthood, was used to probe for the up regulation of genes involved in disease pathways and inflammation within the brainstem and vocal fold muscle. In summary, the data show sex- and genotype-differences in limb motor, anxiety, and vocal motor behaviors. Specifically, female Pink1−/− rats demonstrate less anxiety-like behavior compared to male Pink1−/− rats and female rats show increased locomotor activity compared to male rats. Pink1−/− rats also demonstrate prodromal ultrasonic vocalization dysfunction across all acoustic parameters and sex differences were present for intensity (loudness) and peak frequency. These data demonstrate a difference in phenotype in the Pink1−/− model. Tuba1c transcript level was identified as a key marker negatively correlated to ultrasonic vocalization at 2 months of age. Identifying genes, such as Tuba1c, may help determine early predictors of PD pathology in the Pink1−/− rat and serve as targets for future drug therapy studies.
Treatment with morning blue light increases left amygdala volume and sleep duration among individuals with posttraumatic stress disorder
Authors: Killgore William D. S. , Vanuk John R. , Dailey Natalie S.
Published: September 2022

Background

Posttraumatic stress disorder (PTSD) is associated with numerous cognitive, affective, and psychophysiological outcomes, including problems with sleep and circadian rhythms. We tested the effectiveness of a daily morning blue-light exposure treatment (BLT) versus a matched amber light treatment (ALT) to regulate sleep in individuals diagnosed with PTSD. Moreover, PTSD is also associated with reliable findings on structural neuroimaging scans, including reduced amygdala volumes and other differences in cortical gray matter volume (GMV) that may be indicative of underlying neurobehavioral dysfunctions. We examined the effect of BLT versus ALT on GMV and its association with sleep outcomes.

Methods

Seventy-six individuals (25 male; 51 female) meeting DSM-V criteria for PTSD (Age = 31.45 years, SD = 8.83) completed sleep assessments and structural neuroimaging scans, followed by random assignment one of two light groups, including BLT (469 nm; n = 39) or placebo ALT (578 nm; n = 37) light therapy daily for 30-min over 6-weeks. Participants wore a wrist actigraph for the duration of the study. After treatment, participants returned to complete sleep assessments and a structural neuroimaging scan. Neuroimaging data were analyzed using the Computational Anatomy Toolbox (CAT12) and Voxel-Based Morphometry (VBM) modules within the Statistical Parametric Mapping (SPM12) software.

Results

The BLT condition produced significant increases in total time in bed and total sleep time from actigraphy compared to the ALT condition, while ALT improved wake after sleep onset and sleep efficiency compared to BLT. Additionally, BLT led to an increase in left amygdala volume compared to ALT but did not affect hypothesized medial prefrontal regions. Finally, within group correlations showed that improvements in sleep quality and nightmare severity were correlated with increases in left amygdala volume over the course of treatment for the BLT group but not the ALT group.

Conclusion

In individuals with PTSD, daily exposure to morning blue light treatment was associated with improvements in objective sleep duration and increased volume of the left amygdala compared to amber placebo light treatment, and changes in amygdala volume correlated with subjective improvement in sleep. These findings suggest that daily morning BLT may provide an important non-pharmacologic adjunctive approach for facilitating sleep and neurobehavioral recovery from PTSD.
Oculomotor, vestibular, reaction time, and cognitive tests as objective measures of neural deficits in patients post COVID-19 infection
Authors: Kelly Kevin M. , Anghinah R. , Kullmann A. , Ashmore R. C. , Synowiec A. S. , Gibson L. C. , Manfrinati L. , Araújo A. de , Spera R. R. , Brucki S. M. D. , Tuma R. L. , Braverman A. , Kiderman A.
Published: September 2022

Objective

An alarming proportion (>30%) of patients affected by SARS-CoV-2 (COVID-19) continue to experience neurological symptoms, including headache, dizziness, smell and/or taste abnormalities, and impaired consciousness (brain fog), after recovery from the acute infection. These symptoms are self-reported and vary from patient to patient, making it difficult to accurately diagnose and initiate a proper treatment course. Objective measures to identify and quantify neural deficits underlying the symptom profiles are lacking. This study tested the hypothesis that oculomotor, vestibular, reaction time, and cognitive (OVRT-C) testing using eye-tracking can objectively identify and measure functional neural deficits post COVID-19 infection.

Methods

Subjects diagnosed with COVID-19 (n = 77) were tested post-infection with a battery of 20 OVRT-C tests delivered on a portable eye-tracking device (Neurolign Dx100). Data from 14 tests were compared to previously collected normative data from subjects with similar demographics. Post-COVID subjects were also administered the Neurobehavioral Symptom Inventory (NSI) for symptom evaluation.

Results

A significant percentage of post COVID-19 patients (up to 86%) scored outside the norms in 12 out of 14 tests, with smooth pursuit and optokinetic responses being most severely affected. A multivariate model constructed using stepwise logistic regression identified 6 metrics as significant indicators of post-COVID patients. The area under the receiver operating characteristic curve (AUC) was 0.89, the estimated specificity was 98% (with cutoff value of 0.5) and the sensitivity was 88%. There were moderate but significant correlations between NSI domain key variables and OVRT-C tests.

Conclusions

This study demonstrates the feasibility of OVRT-C testing to provide objective measures of neural deficits in people recovering from COVID-19 infection. Such testing may serve as an efficient tool for identifying hidden neurological deficits post COVID-19, screening patients at risk of developing long COVID, and may help guide rehabilitation and treatment strategies.
A scientometric analysis of the 100 most cited articles on magnetic resonance guided focused ultrasound
Authors: Garg Kanwaljeet , Ranjan Manish , Krishna Vibhor , Singh Manmohan , Rezai Ali
Published: September 2022

Background

Diagnostic ultrasound has long been a part of a physician’s armamentarium, but transcranial focused ultrasound (FUS) is an emerging treatment of neurological disorders. Consequently, the literature in this field is increasing at a rapid pace.

Objective

This analysis was aimed to identify the top-cited articles on FUS to discern their origin, spread, current trends highlighting future impact of this novel neurosurgical intervention.

Methods

We searched the Web of Science database on 28th May 2021 and identified the top 100 cited articles. These articles were analyzed with various scientometric parameters like the authors, corresponding authors, country of corresponding author, journal of publication, year of publication. Citation based parameters including total citations, mean citations per article and mean citations, citation count, and the citation per year, citations per year and co-authors per document were studied as well in addition to Hirsch h-index, g-index, m-index, Bradford’s Law, Lotka’s law and Collaboration index.

Results

The 100 top-cited articles were published between 1998 and 2019 in 45 different journals. The average citations per document and citations per document per year were 97.78 and 12.47, respectively. The most prolific authors were Hynynen K (Medical Biophysics—Toronto), Elias WJ (Neurosurgery—Virginia), Zadicario (InSightec). The Journal of Neurosurgery published the most top-cited articles (n = 11), and most articles originated from the United States, followed by Canada. Among individual institutions, the University of Toronto was the most productive.

Conclusion

FUS is an emerging treatment of neurological disorders. With its increasing application, the FUS literature is increasing rapidly. Eleven countries contributed to the top 100 cited articles, with the top 2 countries (the United States and Canada) contributing to more than half of these articles.
Machine learning reveals interhemispheric somatosensory coherence as indicator of anesthetic depth
Authors: Schmidt Dominik , English Gwendolyn , Gent Thomas C. , Yanik Mehmet Fatih , von der Behrens Wolfger
Published: September 2022

The goal of this study was to identify features in mouse electrocorticogram recordings that indicate the depth of anesthesia as approximated by the administered anesthetic dosage. Anesthetic depth in laboratory animals must be precisely monitored and controlled. However, for the most common lab species (mice) few indicators useful for monitoring anesthetic depth have been established. We used electrocorticogram recordings in mice, coupled with peripheral stimulation, in order to identify features of brain activity modulated by isoflurane anesthesia and explored their usefulness in monitoring anesthetic depth through machine learning techniques. Using a gradient boosting regressor framework we identified interhemispheric somatosensory coherence as the most informative and reliable electrocorticogram feature for determining anesthetic depth, yielding good generalization and performance over many subjects. Knowing that interhemispheric somatosensory coherence indicates the effectively administered isoflurane concentration is an important step for establishing better anesthetic monitoring protocols and closed-loop systems for animal surgeries.
MRF-Net: A multi-branch residual fusion network for fast and accurate whole-brain MRI segmentation
Authors: Wei Chong , Yang Yanwu , Guo Xutao , Ye Chenfei , Lv Haiyan , Xiang Yang , Ma Ting
Published: September 2022

Whole-brain segmentation from T1-weighted magnetic resonance imaging (MRI) is an essential prerequisite for brain structural analysis, e.g., locating morphometric changes for brain aging analysis. Traditional neuroimaging analysis pipelines are implemented based on registration methods, which involve time-consuming optimization steps. Recent related deep learning methods speed up the segmentation pipeline but are limited to distinguishing fuzzy boundaries, especially encountering the multi-grained whole-brain segmentation task, where there exists high variability in size and shape among various anatomical regions. In this article, we propose a deep learning-based network, termed Multi-branch Residual Fusion Network, for the whole brain segmentation, which is capable of segmenting the whole brain into 136 parcels in seconds, outperforming the existing state-of-the-art networks. To tackle the multi-grained regions, the multi-branch cross-attention module (MCAM) is proposed to relate and aggregate the dependencies among multi-grained contextual information. Moreover, we propose a residual error fusion module (REFM) to improve the network's representations fuzzy boundaries. Evaluations of two datasets demonstrate the reliability and generalization ability of our method for the whole brain segmentation, indicating that our method represents a rapid and efficient segmentation tool for neuroimage analysis.
Identification of the key immune-related genes in aneurysmal subarachnoid hemorrhage
Authors: Wang Xing , Wen Dingke , You Chao , Ma Lu
Published: September 2022

Subarachnoid hemorrhage (SAH) is a major cause of death and morbidity worldwide, often due to rupture of intracranial aneurysms (IAs). Immune infiltration and inflammatory activation play key roles in the process of aneurysmal SAH (aSAH). This study aimed to elaborate the immune infiltration and identify related biomarkers both in blood and tissue samples from patients with aSAH. Expression data of aSAH and healthy control samples were obtained from gene expression omnibus (GEO) database. Overall, a blood sample dataset GSE36791 and a tissue sample dataset GSE122897 were included. Differentially expressed genes (DEGs) between aSAH and healthy samples were explored. We applied GO biological and Gene Set Enrichment Analyses (GSEA) processes to access the functional enrichment. Then feature elimination algorithms based on random forest were used to screen and verify the biomarkers of aSAH. We performed three computational algorithms including Cell type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT), Microenvironment Cell Populations-counter (MCPcounter), and xcell to evaluate the immune cell infiltration landscape to identify the unique infiltration characteristics associated with rupturing. We found 2,220 DEGs (856 upregulated and 1,364 downregulated) in the original dataset. Functional analysis revealed most of these genes are enriched in immunological process, especially related with neutrophil response. Similar signaling pathway enrichment patterns were observed in tissue sample dataset and ClueGo. Analysis of immune microenvironment infiltration suggested neutrophils were abnormally upregulated in aSAH compared with those in the control group. Key gene SRPK1 was then filtered based on feature elimination algorithms, and transcription factor (TF) ZNF281 is assumed to participate in immunomodulation by regulating expression of SRPK1. Several immunomodulators such as CXCR1 and CXCR2 also appear to be involved in the progression of aSAH. In the present study, we performed a comprehensive stratification and quantification of the immune infiltration status of aSAH. By exploring the potential mechanism for aSAH based on several computational algorithms, key genes including SRPK1 and ZNF281 were filtered. This study may be of benefit to patients who are at high risk of suffering aSAH which allows for early diagnosis and potential therapy.
A comparison of reinforcing effectiveness and drug-seeking reinstatement of 2-fluorodeschloroketamine and ketamine in self-administered rats
Authors: Du Han , Lai Miaojun , Zhuang Dingding , Fu Dan , Zhou Yiying , Chen Shanshan , Wang Fangmin , Xu Zemin , Liu Huifen , Wang Youmei , Xu Peng , Zhou Wenhua
Published: September 2022

2-Fluorodeschloroketamine (2F-DCK), a structural analog of ketamine, has been reported to cause impaired consciousness, agitation, and hallucination in abuse cases. It has similar reinforcing and discriminative effects as ketamine. However, the reinforcing efficacy and drug-seeking reinstatement of this analog have not been clarified to date. In this study, the effectiveness of 2F-DCK and ketamine was compared using a behavioral economics demand curve. The reinstatement of 2F-DCK- and ketamine-seeking behaviors induced by either conditioned cues or self-priming was also analyzed. Rats were intravenously self-administered 2F-DCK and ketamine at a dose of 0.5 mg/kg/infusion under a reinforcing schedule of fixed ratio 1 (FR1) with 4 h of daily training for at least 10 consecutive days. The elasticity coefficient parameter α and the essential value of the demand curve in the two groups were similar. Both groups of rats showed significant drug-seeking behavior induced either by conditional cues or by 2F-DCK and ketamine priming. Moreover, the α parameter was inversely related to the degree of reinstatement induced by cues or drug priming in both groups. In total, the expression levels of brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element-binding protein (p-CREB) in the nucleus accumbens in both extinguished and reinstated rats were significantly lower than those in the control. The expression of total Akt, glycogen synthase kinase (GSK)-3β, mammalian target of rapamycin (mTOR), and extracellular signal-related kinase (ERK) also decreased, but p-Akt, p-GSK-3β, p-mTOR, and p-ERK levels increased in both extinguished and reinstated rats. This is the first study to demonstrate that 2F-DCK has similar reinforcing efficacy, effectiveness, and post-withdrawal cravings as ketamine after repeated use. These data suggest that the downregulation of CREB/BDNF and the upregulation of the Akt/mTOR/GSK-3β signaling pathway in the nucleus accumbens may be involved in ketamine or 2F-DCK relapse.
Dexmedetomidine post-conditioning protects blood-brain barrier integrity by modulating microglia/macrophage polarization via inhibiting NF-κB signaling pathway in intracerebral hemorrhage
Authors: Guo Hao , Zhang Weiwei , Wang Zhi , Li Zhishan , Zhou Jing , Yang Zhaoyu
Published: September 2022

Intracerebral hemorrhage (ICH) is one of the most devastating forms of stroke. Dexmedetomidine (DEX) has shown certain neuroprotective roles in ICH. Nevertheless, the details concerning the underlying molecular mechanism of DEX’s protective effects still need further elucidation. Herein, a model of ICH was established. The rats were randomly divided into the sham group, the ICH group, and the ICH + DEX group. Neurological outcomes, neuronal injury, and apoptosis were evaluated. Brain water content, Evans blue extravasation, and the expression of tight junction-associated proteins were also detected to assess the blood-brain barrier (BBB) integrity. Subsequently, the microglia/macrophage polarization state and inflammatory cytokine levels were observed. To further explore the underlying mechanism, NF-κB signaling pathway-associated proteins were detected. The results showed that DEX exerted neuroprotective effects against ICH-induced neurological deficits. DEX significantly increased the numbers of the surviving neurons and ameliorated neuronal cell loss and apoptosis in ICH. The rats that received the DEX displayed a lower level of brain water content and EB extravasation, moreover, ZO-1, occludin, and claudin-5 were markedly increased by DEX. Additionally, DEX facilitated M2 microglia/macrophage polarization, the M1-associated markers were reduced by DEX, while the M2-associated identification significantly increased. We found that DEX dramatically diminished pro-inflammatory cytokines expression, simultaneously promoting anti-inflammatory cytokines expression. DEX inhibited nuclear translocation of NF-κB in ICH rats. Our data suggest that DEX post-conditioning protects BBB integrity by modulating microglia/macrophage polarization via inhibiting the NF-κB signaling pathway in ICH.
Effectiveness of Microecological Preparations for Improving Renal Function and Metabolic Profiles in Patients With Chronic Kidney Disease
Authors: Tan Jiaxing , Zhou Huan , Deng Jiaxin , Sun Jiantong , Zhou Xiaoyuan , Tang Yi , Qin Wei
Published: September 2022

Background

Determining whether microecological preparations, including probiotics, prebiotics, and synbiotics, are beneficial for patients with chronic kidney disease (CKD) has been debated. Moreover, determining which preparation has the best effect remains unclear. In this study, we performed a network meta-analysis of randomized clinical trials (RCTs) to address these questions.

Methods

MEDLINE, EMBASE, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials were searched. Eligible RCTs with patients with CKD who received intervention measures involving probiotics, prebiotics, and/or synbiotics were included. The outcome indicators included changes in renal function, lipid profiles, inflammatory factors, and oxidative stress factors.

Results

Twenty-eight RCTs with 1,373 patients were ultimately included. Probiotics showed greater effect in lowering serum creatinine [mean difference (MD) −0.21, 95% confidence interval (CI) −0.34, −0.09] and triglycerides (MD −9.98, 95% CI −19.47, −0.49) than the placebo, with the largest surface area under the cumulative ranking curve, while prebiotics and synbiotics showed no advantages. Probiotics were also able to reduce malondialdehyde (MDA) (MD −0.54, 95% CI −0.96, −0.13) and increase glutathione (MD 72.86, 95% CI 25.44, 120.29). Prebiotics showed greater efficacy in decreasing high-sensitivity C-reactive protein (MD −2.06, 95% CI −3.79, −0.32) and tumor necrosis factor-α (MD −2.65, 95% CI −3.91, −1.39). Synbiotics showed a partially synergistic function in reducing MDA (MD −0.66, 95% CI −1.23, −0.09) and high-sensitivity C-reactive protein (MD −2.01, 95% CI −3.87, −0.16) and increasing total antioxidant capacity (MD 145.20, 95% CI 9.32, 281.08).

Conclusion

The results indicated that microbial supplements improved renal function and lipid profiles and favorably affected measures of oxidative stress and inflammation in patients with CKD. After thorough consideration, probiotics provide the most comprehensive and beneficial effects for patients with CKD and might be used as the best choice for microecological preparations.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022295497, PROSPERO 2022, identifier: CRD42022295497.
Harnessing the pillars of institutions to drive environmentally sustainable hospital foodservices
Authors: Carino Stefanie , Collins Jorja , Malekpour Shirin , Porter Judi
Published: September 2022

Background

The cultural-cognitive, normative and regulative pillars of institutions influence the ability of hospitals to change how they function at an organizational and operational level. As more hospitals and their foodservices instigate changes to address their environmental footprint and impact on food systems, they move through the “sustainability phase model” from no response through to high level action and leadership. The aim of this study was to describe and compare the pillars of institutions between hospitals in different stages of achieving environmentally sustainable foodservices (business-as-usual vs. exemplar hospitals).

Methods

For this qualitative inquiry study, interviews were conducted with 33 hospital staff from 3 business-as-usual hospitals in Melbourne, Australia and 21 hospital staff from 14 exemplar hospitals across 9 countries. Participants were asked questions about their perspectives on environmental sustainability in foodservices and the barriers, enablers and drivers they experienced. Each data set was analyzed thematically and then compared.

Findings

There was a clear and distinct difference in responses and behaviors within each pillar between the exemplar and business-as-usual hospitals. The cultural-cognitive pillar identified a similarity in personal belief in the importance of addressing environmental impacts of foodservices, but difference in how staff saw and acted on their responsibility to drive change. The normative pillar uncovered a supportive culture that encouraged change in exemplar hospitals whilst business-as-usual hospital staff felt disheartened by the difficult processes and lack of support. The regulative pillar reflected business-as-usual hospital staff feeling restricted by government policy vs. exemplar hospital participants who were motivated to internalize government policy in different ways and work with other hospitals to advocate for better policy.

Interpretation

These findings highlight strategies related to each of the three pillars of institutions that can be used to drive effective, sustainable long term change within hospitals. This includes staff education and training, revisiting hospital culture and values around environmental sustainability, embedding sustainable foodservices in internal policies, and a comprehensive government policy approach to sustainable healthcare.
Associations of serum multivitamin levels with the risk of non-alcoholic fatty liver disease: A population-based cross-sectional study in U.S. adults
Authors: Peng Hongye , Wang Miyuan , Pan Liang , Cao Zhengmin , Yao Ziang , Chen Qiuye , Li Yanbo , Wang Yuhua , Lv Wenliang
Published: September 2022

Vitamins were closely associated with non-alcoholic fatty liver disease (NAFLD) development, but no study had explored the association of serum multivitamin levels with NAFLD risk. We assessed the association between serum levels of both single-vitamin and multivitamins (VA, VB6, VB9, VB12, VC, VD, and VE) and the risk of NAFLD, using the database of National Health and Nutrition Examination Survey (NHANES) (cycles 2003–2004 and 2005–2006). We employed multivariable logistic regression and weighted quantile sum (WQS) regression models to explore the association of serum multivitamin levels with NAFLD. Among all 2,294 participants, 969 participants with NAFLD were more likely to be male, older, less educated, or have hypertension/high cholesterol/diabetes. After adjustment of covariates, serum VC/VD/VB6/VB9 levels were negatively correlated with NAFLD risk, while serum VA/VE levels were positively correlated with NAFLD risk. In the WQS model, elevated serum VA/VE levels and lowered serum VC/VD/VB6 levels were linearly associated with increased NAFLD risk. There was a non-linear relationship between serum VB9/VB12 levels and NAFLD risk. There were evident associations between serum multivitamin levels and reduced NAFLD risk, which was mainly driven by VD/VB9/VC. In conclusion, our findings suggested that serum multivitamin levels were significantly associated with the risk of NAFLD.
Fenofibrate enhances lipid deposition via modulating PPARγ, SREBP-1c, and gut microbiota in ob/ob mice fed a high-fat diet
Authors: Zhang Ying , Jia Xiu-Bin , Liu Yun-Chao , Yu Wen-Qian , Si Yan-Hong , Guo Shou-Dong
Published: September 2022

Obesity is characterized by lipid accumulation in distinct organs. Presently, fenofibrate is a commonly used triglyceride-lowering drug. This study is designed to investigate whether long-term fenofibrate intervention can attenuate lipid accumulation in ob/ob mouse, a typical model of obesity. Our data demonstrated that fenofibrate intervention significantly decreased plasma triglyceride level by 21.0%, increased liver index and hepatic triglyceride content by 31.7 and 52.1%, respectively, and elevated adipose index by 44.6% compared to the vehicle group. As a PPARα agonist, fenofibrate intervention significantly increased the expression of PPARα protein in the liver by 46.3% and enhanced the expression of LDLR protein by 3.7-fold. However, fenofibrate dramatically increased the expression of PPARγ and SREBP-1c proteins by ~2.1- and 0.9-fold in the liver, respectively. Fenofibrate showed no effects on the expression of genes-related to fatty acid β-oxidation. Of note, it significantly increased the gene expression of FAS and SCD-1. Furthermore, fenofibrate modulated the gut microbiota. Collectively, long-term fenofibrate induces lipid accumulation in liver and adipose tissues in ob/ob mice by enhancing the expression of adipogenesis-related proteins and gut microbiota. These data suggest that fenofibrate may have limited effects on attenuating lipid deposition in obese patients.
Associations between dietary fiber intake and cardiovascular risk factors: An umbrella review of meta-analyses of randomized controlled trials
Authors: Fu Lingmeng , Zhang Guobing , Qian Shasha , Zhang Qin , Tan Mingming
Published: September 2022

Although several meta-analyses have revealed the beneficial effects of dietary fiber intake on human health, some have reported inconsistent findings. The purpose of this work was to perform an umbrella meta-analysis to evaluate the relevant evidence and elucidate the effect of dietary fiber intake on glycemic control, lipid profiles, systematic inflammation, and blood pressure. Eligible studies were searched in several electronic databases, including Web of Science, PubMed, Scopus, and the Cochrane Library, up to March 2022. A total of 52 meta-analyses involving 47,197 subjects were identified to assess the pooled effect size. Overall, higher dietary fiber intake was significantly associated with reductions in parameters involving glycemic control, including fasting plasma glucose (ES = −0.55, 95% CI: −0.73, −0.38, P < 0.001), fasting plasma insulin (ES = −1.22, 95% CI: −1.63, −0.82, P < 0.001), homeostasis model assessment of insulin resistance (HOMA-IR) (ES = −0.43, 95% CI: −0.60, −0.27, P < 0.001), and glycosylated hemoglobin (HbA1c) (ES = −0.38, 95% CI: −0.50, −0.26, P < 0.001). In terms of lipid profiles, higher dietary fiber intake was associated with significant reductions in the serum level of total cholesterol (ES = −0.28, 95% CI: −0.39, −0.16, P < 0.001) and low-density lipoprotein cholesterol (ES = −0.25, 95% CI: −0.34, −0.16, P < 0.001), but not triglycerides (ES = −0.001, 95% CI: −0.006, 0.004, P = 0.759) and high-density lipoprotein cholesterol (ES = −0.002, 95% CI: −0.004, 0.000, P = 0.087). Higher dietary fiber intake was also significantly associated with improved tumor necrosis factor-alpha serum levels (ES = −0.78, 95% CI: −1.39, −0.16, P = 0.013), while no significant effect was observed for C-reactive protein (ES = −0.14, 95% CI: −0.33, 0.05, P = 0.156). Finally, blood pressure was also significantly improved following higher dietary fiber intake (systolic blood pressure: ES = −1.72, 95% CI: −2.13, −1.30, P < 0.001; diastolic blood pressure: ES = −0.67, 95% CI: −0.96, −0.37, P < 0.001). Subgroup analysis revealed that the study population and type of dietary fiber could be partial sources of heterogeneity. In conclusion, the present umbrella meta-analysis provides evidence for the role of dietary fiber supplementation in the improvement of established cardiovascular risk factors.
Insights into flavor and key influencing factors of Maillard reaction products: A recent update
Authors: Liu Shuyun , Sun Hanju , Ma Gang , Zhang Tao , Wang Lei , Pei Hui , Li Xiao , Gao Lingyan
Published: September 2022

During food processing, especially heating, the flavor and color of food change to a great extent due to Maillard reaction (MR). MR is a natural process for improving the flavor in various model systems and food products. Maillard reaction Products (MRPs) serve as ideal materials for the production of diverse flavors, which ultimately improve the flavor or reduce the odor of raw materials. Due to the complexity of the reaction, MR is affected by various factors, such as protein source, hydrolysis conditions, polypeptide molecular weight, temperature, and pH. In the recent years, much emphasis is given on conditional MR that could be used in producing of flavor-enhancing peptides and other compounds to increase the consumer preference and acceptability of processed foods. Recent reviews have highlighted the effects of MR on the functional and biological properties, without elaborating the flavor compounds obtained by the MR. In this review, we have mainly introduced the Maillard reaction-derived flavors (MF), the main substances producing MF, and detection methods. Subsequently, the main factors influencing MF, from the selection of materials (sugar sources, protein sources, enzymatic hydrolysis methods, molecular weights of peptides) to the reaction conditions (temperature, pH), are also described. In addition, the existing adverse effects of MR on the biological properties of protein are also pointed out.
Exploring wild Aspleniaceae ferns as safety sources of polyphenols: The case of Asplenium trichomanes L. and Ceterach officinarum Willd.
Authors: Farràs Adrià , Mitjans Montserrat , Maggi Filippo , Caprioli Giovanni , Vinardell María Pilar , López Víctor
Published: September 2022

The forest ecosystem is a source of material resources used since ancient times by mankind. Ferns are part of different oriental systems of traditional medicine due to the phytochemical variety of their fronds, which have allowed their traditional use to be validated through ethnopharmacological studies. In Europe, different cultures have used the same fern with a wide variety of applications due to its presence in most European forests. In recent years, studies on the phytocharacterization and biological activity of the fronds of the main European ferns have been published. In this study, the presence of polyphenolic phytochemicals has been evaluated by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) in the fronds of two wild ferns together with in vitro activities in non-tumoral and human tumoral cell lines. The polyphenols were extracted from Asplenium trichomanes L. and Ceterach officinarum Willd. by cold maceration using methanol. The main phytochemicals of polyphenolic origin in the extracts of A. trichomanes and C. officinarum determined by HPLC-MS/MS were the flavonol hyperoside and the phenolic acid chlorogenic acid, respectively. This different polyphenolic nature of both extracts contributes to the divergence of the behavior experienced in the biological activities tested, but none of the extracts showed a cytotoxic or phototoxic profile in the different tested cell lines. However, the cytoprotective values in front of the H2O2 oxidative stress induced in the 3T3 and HaCaT cell lines position these extracts as possible candidates for future health applications.
Amide proton transfer weighted imaging combined with dynamic contrast-enhanced MRI in predicting lymphovascular space invasion and deep stromal invasion of IB1-IIA1 cervical cancer
Authors: Song Qingling , Tian Shifeng , Ma Changjun , Meng Xing , Chen Lihua , Wang Nan , Lin Liangjie , Wang Jiazheng , Song Qingwei , Liu Ailian
Published: September 2022

Objectives

To investigate the value of amide proton transfer weighted (APTw) imaging combined with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting intermediate-risk factors of deep stromal invasion (DSI) and lymphovascular vascular space invasion (LVSI) in cervical cancer.

Methods

Seventy patients with cervical cancer who underwent MRI before operation from July 2019 to February 2022 were retrospectively included in this study. Clinical information including age, histologic subtype etc. were recorded for patients. ATPw imaging parameter APTmean and DCE-MRI parameters Ktrans, Kep and Ve were measured and analyzed. The independent-sample t-test, Mann-Whitney U test, or Chi-square test was used to compare the differences of parameters between DSI/LVSI positive and negative groups. Logistic analysis was used to develop a combined predictive model. The receiver operating characteristic curve was for predictive performance. ANOVA and Kruskal-Wallis test were used to compare the differences of consecutive parameters among multiple groups.

Results

Ktrans and SCC-Ag were independent factors in predicting DSI; Ktrans+SCC-Ag had the highest AUC 0.819 with sensitivity and specificity of 71.74% and 91.67%, respectively. APTmean and Ktrans were independent factors in predicting LVSI; APTmean+Ktrans had the highest AUC 0.874 with sensitivity and specificity of 92.86% and 75.00%, respectively. Ktrans and Ve could discriminate coexistence of DSI and LVSI from presence of single one, APTmean could discriminate the presence of DSI or LVSI from no risk factor presence.

Conclusion

The combination of APTw and DCE-MRI is valuable in predicting intermediate-risk factors of DSI and LVSI in cervical cancer.
A novel nomogram for decision-making assistance on exemption of axillary lymph node dissection in T1–2 breast cancer with only one sentinel lymph node metastasis
Authors: Liu Lei , Lin Yaoxin , Li Guozheng , Zhang Lei , Zhang Xin , Wu Jiale , Wang Xinheng , Yang Yumei , Xu Shouping
Published: September 2022

Background

T1–2 breast cancer patients with only one sentinel lymph node (SLN) metastasis have an extremely low non-SLN (NSLN) metastatic rate and are favorable for axillary lymph node dissection (ALND) exemption. This study aimed to construct a nomogram-based preoperative prediction model of NSLN metastasis for such patients, thereby assisting in preoperatively selecting proper surgical procedures.

Methods

A total of 729 T1–2 breast cancer patients with only one SLN metastasis undergoing sentinel lymph node biopsy and ALND were retrospectively selected from Harbin Medical University Cancer Hospital between January 2013 and December 2020, followed by random assignment into training (n=467) and validation cohorts (n=262). A nomogram-based prediction model for NSLN metastasis risk was constructed by incorporating the independent predictors of NSLN metastasis identified from multivariate logistic regression analysis in the training cohort. The performance of the nomogram was evaluated by the calibration curve and the receiver operating characteristic (ROC) curve. Finally, decision curve analysis (DCA) was used to determine the clinical utility of the nomogram.

Results

Overall, 160 (21.9%) patients had NSLN metastases. Multivariate analysis in the training cohort revealed that the number of negative SLNs (OR: 0.98), location of primary tumor (OR: 2.34), tumor size (OR: 3.15), and lymph-vascular invasion (OR: 1.61) were independent predictors of NSLN metastasis. The incorporation of four independent predictors into a nomogram-based preoperative estimation of NSLN metastasis demonstrated a satisfactory discriminative capacity, with a C-index and area under the ROC curve of 0.740 and 0.689 in the training and validation cohorts, respectively. The calibration curve showed good agreement between actual and predicted NSLN metastasis risks. Finally, DCA revealed the clinical utility of the nomogram.

Conclusion

The nomogram showed a satisfactory discriminative capacity of NSLN metastasis risk in T1–2 breast cancer patients with only one SLN metastasis, and it could be used to preoperatively estimate NSLN metastasis risk, thereby facilitating in precise clinical decision-making on the selective exemption of ALND in such patients.
Fibroblasts mediate the angiogenesis of pheochromocytoma by increasing COX4I2 expression
Authors: Mao Yongxin , Zhuo Ran , Ma Wenming , Dai Jun , Alimu Parehe , Fang Chen , Xu Danfeng , Ye Lei , Wang Weiqing , Sun Fukang
Published: September 2022

Objective

Our previous work found COX4I2 was associated with angiogenesis in pheochromocytoma. The purpose of this study was to explore the role of COX4I2 in regulating angiogenesis in pheochromocytoma.

Methods

Distribution of COX4I2 was evaluated by scRNA-seq in one case of pheochromocytoma and the findings were verified by immunostaining. COX4I2 was further knocked down in target cells. Changes of angiogenesis-related genes were evaluated by qPCR in target cells.

Results

The scRNA-seq revealed high mRNA expression of COX4I2 in fibroblasts rather than tumor cells. Immunostaining of COX4I2 confirmed its distribution in fibroblasts. Knocking down COX4I2 in NIH3T3 cell line led to significant reduction of angiogenesis-related genes, especially ANG1 and HGF.

Conclusions

Fibroblasts mediate the angiogenesis of pheochromocytoma by increasing COX4I2 expression, possibly by affecting ANG1 and HGF.
ADAMDEC1 accelerates GBM progression via activation of the MMP2-related pathway
Authors: Qi Huimin , Wang Ping , Sun Hongliang , Li Xiaohan , Hao Xinwei , Tian Wenxiu , Yu Liting , Tang Jiajian , Dong Junhong , Wang Hongmei
Published: September 2022

The ADAM (a disintegrin and metalloprotease) gene-related family including ADAM, ADAMTS, and ADAM-like decysin-1 has been reported to play an important role in the pathogenesis of multiple diseases, including cancers (lung cancer, gliomas, colorectal cancer, and gastrointestinal cancer). However, its biological role in gliomas remains largely unknown. Here, we aimed to investigate the biological functions and potential mechanism of ADAMDEC1 in gliomas. The mRNA and protein expression levels of ADAMDEC1 were upregulated in glioma tissues and cell lines. ADAMDEC1 showed a phenomenon of “abundance and disappear” expression in gliomas and normal tissues in that the higher the expression of ADAMDEC1 presented, the higher the malignancy of gliomas and the worse the prognosis. High expression of ADAMDEC1 was associated with immune response. Knockdown of ADAMDEC1 could decrease the proliferation and colony-forming ability of LN229 cells, whereas ADAMDEC1 overexpression has opposite effects in LN229 cells in vitro. Furthermore, we identified that ADAMDEC1 accelerates GBM progression via the activation of the MMP2 pathway. In the present study, we found that the expression levels of ADAMDEC1 were significantly elevated compared with other ADAMs by analyzing the expression levels of ADAM family proteins in gliomas. This suggests that ADAMDEC1 has potential as a glioma clinical marker and immunotherapy target.
Safety and efficacy of lenvatinib combined with camrelizumab plus transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: A two-center retrospective study
Authors: Sun Bo , Zhang Lijie , Sun Tao , Ren Yanqiao , Cao Yanyan , Zhang Weihua , Zhu Licheng , Guo Yusheng , Gui Yuxi , Liu Fengyong , Chen Lei , Xiong Fu , Zheng Chuansheng
Published: September 2022

Objectives

To compare the safety and efficacy of lenvatinib (LEN) combined with camrelizumab plus transcatheter arterial chemoembolization (TACE-LEN-C) and TACE combined with LEN (TACE-LEN) in patients with unresectable hepatocellular carcinoma (uHCC).

Methods

Eighty-three patients with uHCC treated with TACE-LEN-C or TACE-LEN from September 2018 to May 2021 were enrolled in this retrospective study. Overall survival (OS), progression-free survival (PFS), local tumor response, and adverse events (AEs) were evaluated. Univariate and multivariate analyses were used to determine the factors affecting survival.

Results

There were 31 patients in the TACE-LEN-C group and 52 patients in the TACE-LEN group. The median follow-up period was 14.2 months (range 7.2–25.2 months) in the whole study. The combination of triple therapy was found to significantly prolong the PFS (12.5 months vs. 6.6 months, P<0.001) and OS (18.9 months vs. 13.9 months, P<0.001. In terms of tumor response, the combination demonstrated a higher objective response rate (71% vs. 42.3% by the modified Response Evaluation Criteria in Solid Tumors, P=0.023) without a statistically significant difference in the disease control rate (93.5% in TACE-LEN-C, 80.8% in TACE-LEN, P=0.195). In the multivariate analysis, two independent factors affecting PFS were identified: number of tumors and treatment. Three independent factors affected OS: number of tumors, Barcelona Clinic Liver Cancer (BCLC) stage, and treatment. All the AEs were tolerable.

Conclusion

TACE-LEN-C is a safe and effective treatment for patients with uHCC, and could be a potential treatment option.