bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of miRNA-mRNA-TF regulatory networks in peripheral blood mononuclear cells of type 1 diabetes
Authors: Wang Wanqiu , Wang Huan , Liu Yuhong , Yang Liu 
Published: May 2022

Abstract
Background
Type 1 diabetes (T1D) is a T lymphocyte-mediated and B lymphocyte-assisted autoimmune disease. We aimed to identify abnormally expressed genes in peripheral blood mononuclear cells (PBMCs) of T1D and explore their possible molecular regulatory network.

Methods
Expression datasets were downloaded from the Gene Expression Omnibus (GEO) database. Then, the differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRNAs) were identified, and functional enrichment and immune cell infiltration analysis were performed. The starBase, miRTarBase, TarBase, JASPAR, ENCODE, and TRRUST databases constructed the miRNA-mRNA-TF regulatory network. The ROC curves were plotted to evaluate the sensitivity and specificity of miRNAs and mRNAs.

Result
A total of 216 DEGs directly or indirectly related to type I diabetes mellitus, natural killer cell-mediated cytotoxicity, Th1, and Th2 cell differentiation, and the IL-17 and TNF signaling pathways were obtained. The miRNA-mRNA-TF network indicates that miR-320a and SOX5 are the only miRNAs and TFs that both target ADM and RRAGD. The ROC curves showed that ADM (0.9375), RRAGD (0.8958), and hsa-mir-320a (0.9417) had high accuracy in T1D diagnosis.

Conclusion
The constructed regulatory networks, including miR-320a/ADM/SOX5 and miR-320a/RRAGD/SOX5, may provide new insight into the mechanisms of development and progression in T1D.
Jianpi Qinghua Fomula alleviates insulin resistance via restraining of MAPK pathway to suppress inflammation of the small intestine in DIO mice
Authors: Liu Yahua , Han Xu , Cai Mengjie , Jin Shenyi , Yan Zihui , Lu Hao , Chen Qingguang 
Published: May 2022

Abstract
Background
Jianpi Qinghua Fomula (JPQHF), a clinically proven prescription,has been applied to cure insulin resistance(IR) and type 2 diabetes (T2DM) for more than 20 years. Here, we will unravel the underlying molecular mechanisms relevant to the therapeutic actions of JPQHF.

Methods
High-fat(HF)diet-induced obesity(DIO)mouse were established in our research, along with insulin resistance. After the administration of JPQHF 5 or 6 weeks, the parameters of the glucose and lipid metabolism were measured. Flow cytometry and Luminex were utilized to assess the inflammation in small intestine,whilst Western blot was used to determine the relative expression levels of the MAPK pathway-related proteins. The glucose and lipid transporter of small intestine was assessed by immunofluorescence and ELISA, and the expression of insulin signaling pathway was detected by Western blot.

Results
The metabolic phenotypes of DIO mouse were ameliorated after 6-week oral administration of JPQHF; Meanwhile,JPQHF downregulated levels of IL-1β,IL-6, TNF-α and IFN-γ but upregulated the ratio of M2/M1 macrophages in the small intestine. The elevated expressions of p-P38 MAPK/P38 MAPK、p-JNK/JNK and p-ERK1/2/ERK1/2 were reversed by JPQHF. Moreover, JPQHF enhanced expression of PI3K,p-AKT/AKT, p-IRS1/ IRS1, p-IRS2/ IRS2 and apoB48 in small intestine, and facilitated the translocation of GLUT2 to the basal side of small intestine epithelial cells.

Conclusion
JPQHF alleviates insulin resistance in DIO mice, and this effect may be associated with its restraining of inflammation of small intestine via attenuating MAPK pathway, and then diminishes small intestinal glucose and lipid absorption.
Differential prognostic burden of cardiovascular disease and lower-limb amputation on the risk of all-cause death in people with long-standing type 1 diabetes
Authors: Camoin Marion , Velho Gilberto , Saulnier Pierre-Jean , Potier Louis , Abouleka Yawa , Carpentier Charlyne , Dubois Severine , Larroumet Alice , Rigalleau Vincent , Gand Elise , Bourron Olivier , Bordier Lyse , Scheen André , Hadjadj Samy , Roussel Ronan , Marre Michel , Mohammedi Kamel 
Published: May 2022

Abstract
Background
Cardiovascular disease (CVD) and nontraumatic lower-limb amputation (LLA) each results in reduced life expectancy in patients with type 1 diabetes, but the differential burden between these conditions is unknown. We compared the effects of CVD and LLA on the risk of mortality in people with type 1 diabetes.

Methods
We used pooled data from the SURGENE, GENEDIAB, and GENESIS prospective cohorts. Data were divided into: 1/absence of CVD (myocardial infarction and/or stroke) nor LLA, 2/history of CVD alone without LLA, 3/LLA alone without CVD or 4/both conditions at baseline. Participants with baseline history of peripheral artery disease were excluded from groups 1 and 2. The study endpoint was any death occurring during follow-up, regardless of the causes.

Results
Among 1169 participants (male 55%, age 40 ± 13 years, diabetes duration 23 ± 11 years), CVD, LLA or both were present at baseline in 49 (4.2%), 62 (5.3%) and 20 (1.7%) subjects, respectively. All-cause death occurred in 304 (26%) participants during 17-year follow-up, corresponding to 18,426 person-years and an incidence rate of 16 (95%CI, 15–18) per 1000 person-years. The risk of death increased in individuals with baseline history of CVD (adjusted HR 2.00 [95% CI 1.34–3.01], p = 0.0008) or LLA (2.26 [1.56–3.28], p < 0.0001), versus no condition, with an additive effect in people with both conditions (5.32 [3.14–9.00], p < 0.0001). No incremental risk of death was observed in people with CVD versus LLA (0.87 [0.54–1.41]). Compared with no condition, CVD and LLA were similarly associated with reduced life expectancy during follow-up: 2.79 (95% CI 1.26–4.32) and 3.38 (1.87–4.88) years, respectively. Combined conditions expose to 7.04 (4.76–9.31) less years of life expectancy (all p < 0.0001).

Conclusions
CVD and LLA conferred a similar burden regarding mortality in type 1 diabetes population. Our findings encourage a careful consideration of people with type 1 diabetes and LLA as usually recommended for those with CVD, in terms of management of risk factors, treatments and prevention.
Exploring the impact of the recombinant Escherichia coli strain on defensins antimicrobial activity: BL21 versus Origami strain
Authors: López-Cano Adrià , Martínez-Miguel Marc , Guasch Judith , Ratera Imma , Arís Anna , Garcia-Fruitós Elena 
Published: May 2022

AbstractThe growing emergence of microorganisms resistant to antibiotics has prompted the development of alternative antimicrobial therapies. Among them, the antimicrobial peptides produced by innate immunity, which are also known as host defense peptides (HDPs), hold great potential. They have been shown to exert activity against both Gram-positive and Gram-negative bacteria, including those resistant to antibiotics. These HDPs are classified into three categories: defensins, cathelicidins, and histatins. Traditionally, HDPs have been chemically synthesized, but this strategy often limits their application due to the high associated production costs. Alternatively, some HDPs have been recombinantly produced, but little is known about the impact of the bacterial strain in the recombinant product. This work aimed to assess the influence of the Escherichia coli strain used as cell factory to determine the activity and stability of recombinant defensins, which have 3 disulfide bonds. For that, an α-defensin [human α-defensin 5 (HD5)] and a β-defensin [bovine lingual antimicrobial peptide (LAP)] were produced in two recombinant backgrounds. The first one was an E. coli BL21 strain, which has a reducing cytoplasm, whereas the second was an E. coli Origami B, that is a strain with a more oxidizing cytoplasm. The results showed that both HD5 and LAP, fused to Green Fluorescent Protein (GFP), were successfully produced in both BL21 and Origami B strains. However, differences were observed in the HDP production yield and bactericidal activity, especially for the HD5-based protein. The HD5 protein fused to GFP was not only produced at higher yields in the E. coli BL21 strain, but it also showed a higher quality and stability than that produced in the Origami B strain. Hence, this data showed that the strain had a clear impact on both HDPs quantity and quality.
Profile of dorsal root ganglion neurons: study of oxytocin expression
Authors: Noguri Taisei , Hatakeyama Dai , Kitahashi Takashi , Oka Kotaro , Ito Etsuro 
Published: May 2022

AbstractAlthough dorsal root ganglion (DRG) neurons have been so far classified according to the difference in their fibers (Aβ, Aδ, and C), this classification should be further subdivided according to gene expression patterns. We focused on oxytocin (OXT) and its related receptors, because OXT plays a local role in DRG neurons. We measured the mRNA levels of OXT, OXT receptor (OXTR), vasopressin V1a receptor (V1aR), transient receptor potential cation channel subfamily V member 1 (TRPV1), and piezo-type mechanosensitive ion channel component 2 (Piezo2) in single DRG neurons by using real-time PCR, and then performed a cluster analysis. According to the gene expression patterns, DRG neurons were classified into 4 clusters: Cluster 1 was characterized mainly by Piezo2, Cluster 2 by TRPV1, Cluster 4 by OXTR, and neurons in Cluster 3 did not express any of the target genes. The cell body diameter of OXT-expressing neurons was significantly larger in Cluster 1 than in Cluster 2. These results suggest that OXT-expressing DRG neurons with small cell bodies (Cluster 2) and large cell bodies (Cluster 1) probably correspond to C-fiber neurons and Aβ-fiber neurons, respectively. Furthermore, the OXT-expressing neurons contained not only TRPV1 but also Piezo2, suggesting that OXT may be released by mechanical stimulation regardless of nociception. Thus, mechanoreception and nociception themselves may induce the autocrine/paracrine function of OXT in the DRG, contributing to alleviation of pain.
Exogenous expression of an allatotropin-related peptide receptor increased the membrane excitability in Aplysia neurons
Authors: Zhang Guo , Guo Shi-Qi , Yin Si-Yuan , Yuan Wang-Ding , Chen Ping , Kim Ji-il , Wang Hui-Ying , Zhou Hai-Bo , Susswein Abraham J. , Kaang Bong-Kiun , Jing Jian 
Published: May 2022

AbstractNeuropeptides act mostly on a class of G-protein coupled receptors, and play a fundamental role in the functions of neural circuits underlying behaviors. However, physiological functions of some neuropeptide receptors are poorly understood. Here, we used the molluscan model system Aplysia and microinjected the exogenous neuropeptide receptor apATRPR (Aplysia allatotropin-related peptide receptor) with an expression vector (pNEX3) into Aplysia neurons that did not express the receptor endogenously. Physiological experiments demonstrated that apATRPR could mediate the excitability increase induced by its ligand, apATRP (Aplysia allatotropin-related peptide), in the Aplysia neurons that now express the receptor. This study provides a definitive evidence for a physiological function of a neuropeptide receptor in molluscan animals.
CaVβ-subunit dependence of forward and reverse trafficking of CaV1.2 calcium channels
Authors: Ferron Laurent , Guderyan Sydney D. , Smith Ethan J. , Zamponi Gerald W. 
Published: May 2022

AbstractAuxiliary CaVβ subunits interact with the pore forming CaVα1 subunit to promote the plasma membrane expression of high voltage-activated calcium channels and to modulate the biophysical properties of Ca2+ currents. However, the effect of CaVβ subunits on channel trafficking to and from the plasma membrane is still controversial. Here, we have investigated the impact of CaVβ1b and CaVβ2a subunits on plasma membrane trafficking of CaV1.2 using a live-labeling strategy. We show that the CaVβ1b subunit is more potent in increasing CaV1.2 expression at the plasma membrane than the CaVβ2a subunit and that this effect is not related to modification of intracellular trafficking of the channel (i.e. neither forward trafficking, nor recycling, nor endocytosis). We conclude that the differential effect of CaVβ subunit subtypes on CaV1.2 surface expression is likely due to their differential ability to protect CaV1.2 from degradation.
Single-cell profiling of human dura and meningioma reveals cellular meningeal landscape and insights into meningioma immune response
Authors: Wang Anthony Z. , Bowman-Kirigin Jay A. , Desai Rupen , Kang Liang-I , Patel Pujan R. , Patel Bhuvic , Khan Saad M. , Bender Diane , Marlin M. Caleb , Liu Jingxian , Osbun Joshua W. , Leuthardt Eric C. , Chicoine Michael R. , Dacey Ralph G. , Zipfel Gregory J. , Kim Albert H. , DeNardo David G. , Petti Allegra A. , Dunn Gavin P. 
Published: May 2022

Abstract
Background
Recent investigations of the meninges have highlighted the importance of the dura layer in central nervous system immune surveillance beyond a purely structural role. However, our understanding of the meninges largely stems from the use of pre-clinical models rather than human samples.

Methods
Single-cell RNA sequencing of seven non-tumor-associated human dura samples and six primary meningioma tumor samples (4 matched and 2 non-matched) was performed. Cell type identities, gene expression profiles, and T cell receptor expression were analyzed. Copy number variant (CNV) analysis was performed to identify putative tumor cells and analyze intratumoral CNV heterogeneity. Immunohistochemistry and imaging mass cytometry was performed on selected samples to validate protein expression and reveal spatial localization of select protein markers.

Results
In this study, we use single-cell RNA sequencing to perform the first characterization of both non-tumor-associated human dura and primary meningioma samples. First, we reveal a complex immune microenvironment in human dura that is transcriptionally distinct from that of meningioma. In addition, we characterize a functionally diverse and heterogenous landscape of non-immune cells including endothelial cells and fibroblasts. Through imaging mass cytometry, we highlight the spatial relationship among immune cell types and vasculature in non-tumor-associated dura. Utilizing T cell receptor sequencing, we show significant TCR overlap between matched dura and meningioma samples. Finally, we report copy number variant heterogeneity within our meningioma samples.

Conclusions
Our comprehensive investigation of both the immune and non-immune cellular landscapes of human dura and meningioma at single-cell resolution builds upon previously published data in murine models and provides new insight into previously uncharacterized roles of human dura.
Melatonin ameliorates tau-related pathology via the miR-504-3p and CDK5 axis in Alzheimer’s disease
Authors: Chen Dongmei , Lan Guihua , Li Ruomeng , Mei Yingxue , Shui Xindong , Gu Xi , Wang Long , Zhang Tao , Gan Chen-Ling , Xia Yongfang , Hu Li , Tian Yuan , Zhang Mi , Lee Tae Ho 
Published: May 2022

AbstractBackgroundIntracellular accumulation of the microtubule-associated protein tau and its hyperphosphorylated forms is a key neuropathological feature of Alzheimer’s disease (AD). Melatonin has been shown to prevent tau hyperphosphorylation in cellular and animal models. However, the molecular mechanisms by which melatonin attenuates tau hyperphosphorylation and tau-related pathologies are not fully understood.MethodsImmunofluorescence, immunoblotting analysis and thioflavin-S staining were employed to examine the effects of early and late treatment of melatonin on tau-related pathology in hTau mice, in which nonmutated human tau is overexpressed on a mouse tau knockout background. High-throughput microRNA (miRNA) sequencing, quantitative RT-PCR, luciferase reporter assay and immunoblotting analysis were performed to determine the molecular mechanism.ResultsWe found that both early and late treatment of melatonin efficiently decreased the phosphorylation of soluble and insoluble tau at sites related to AD. Moreover, melatonin significantly reduced the number of neurofibrillary tangles (NFTs) and attenuated neuronal loss in the cortex and hippocampus. Furthermore, using miRNA microarray analysis, we found that miR-504-3p expression was upregulated by melatonin in the hTau mice. The administration of miR-504-3p mimics dramatically decreased tau phosphorylation by targeting p39, an activator of the well-known tau kinase cyclin-dependent kinase 5 (CDK5). Compared with miR-504-3p mimics alone, co-treatment with miR-504-3p mimics and p39 failed to reduce tau hyperphosphorylation.ConclusionsOur results suggest for the first time that melatonin alleviates tau-related pathologies through upregulation of miR-504-3p expression by targeting the p39/CDK5 axis and provide novel insights into AD treatment strategies.
Bilateral oncoplastic breast-conserving surgery with volume replacement technique using the omental flap: a case report
Authors: Zaha Hisamitsu , Abe Norie , Matsumoto Hirofumi , Koki Ayako , Unesoko Mikiko 
Published: May 2022

Abstract
Background
Many oncoplastic volume replacement techniques have been reported, however, it is generally difficult to utilize a single distant flap for bilateral breast carcinomas.

Case presentation
We report a case of bilateral multiple breast carcinomas successfully treated with immediate volume replacement technique with an omental flap. Bilateral partial mastectomies were performed for bilateral breast carcinomas (one in the left breast and two in the right breast). The pedicled omental flap was laparoscopically harvested, and divided at the mid-portion of the flap. The proximal half of the flap was used to fill the right defect, and the distal half of the flap filled two defects in the left breast. Cosmetic outcome was excellent with minimal donor-site scars.

Conclusions
The omental flap can be considered for highly selected patients with bilateral breast carcinomas.
Key process features of personalized diet counselling in metabolic syndrome: secondary analysis of feasibility study in primary care
Authors: Brauer Paula , Royall Dawna , Li Airu , Rodrigues Ariellia , Green Jennifer , Macklin Sharon , Craig Alison , Chan Miranda , Pasanen Jennifer , Brunelle Lucie , Dhaliwal Rupinder , Klein Doug , Tremblay Angelo , Rheaume Caroline , Mutch David M. , Jeejeebhoy Khursheed 
Published: May 2022

Abstract
Background
Personalized diet counselling, as part of lifestyle change programs for cardiometabolic risk conditions (combinations of prediabetes or type 2 diabetes, hypertension, dyslipidemia and high waist circumference) has been shown to reduce progression to type 2 diabetes overall. To identify key process of care measures that could be linked to changes in diet, we undertook a secondary analysis of a Canadian pre-post study of lifestyle treatment of metabolic syndrome (MetS). Diet counselling process measures were documented and association with diet quality changes after 3 months were assessed. Results of the primary study showed 19% reversal of MetS after 1 year.

Methods
Registered dietitians (RDs) reported on contact time, specific food behaviour goals (FBG), behaviour change techniques (BCT; adapted from the Michie CALO-RE taxonomy) and teaching resources at each contact. Diet quality was measured by 2005 Canadian Healthy Eating Index (HEI-C) and assessed for possible associations with individual BCT and FBG.

Results
Food behaviour goals associated with improved HEI-C at 3 months were: poultry more than red meat, increased plant protein, increased fish, increased olive oil, increased fruits and vegetables, eating breakfast, increased milk and alternatives, healthier fats, healthier snacks and increased nuts, with an adverse association noted for more use (> 2 times/ 3 months) of the balanced meal concept (F test; p < 0.001). Of 16 BCT, goal setting accounted for 15% of all BCT recorded, yet more goal setting (> 3 times/3 months) was associated with poorer HEI-C at 3 months (F test; p = 0.007). Only self-monitoring, feedback on performance and focus on past success were associated with improved HEI-C.

Conclusions
These results identify key aspects of process that impact diet quality. Documentation of both FBG and BCT is highly relevant in diet counselling and a summary diet quality score is a promising target for assessing short-term counselling success.
Is vegetarianism related to anxiety and depression? A cross-sectional survey in a French sample
Authors: Bègue Laurent , Shankland Rebecca 
Published: May 2022

Abstract
Objective
The relationship between vegetarianism and mental health is controversial. The aim of the present study is to examine the cross-sectional association between anxiety, depression, and vegetarianism in a French sample while controlling for potential confounders.

Design
Self-reported questionnaire data were obtained from a large cross-sectional sample.

Participants and setting
We included an online sample of 6578 participants aged 18–90, 70.8% females.

Results
Analyses of variance with age, gender, body mass index (BMI), educational level, monthly income, and city size as covariates showed that vegetarians and non-vegetarians did not appear to have significantly different levels of anxiety or depression.

Conclusion
Our findings do not suggest a link between plant-based diet and anxiety or depression, either before or after adjustment for relevant factors.
Anxiety and depression among epilepsy patients in low-risk areas for COVID-19 in the northern part of Guizhou Province, China, during the COVID-19 pandemic
Authors: Wang Shen , Yang Juan , Wei Nian , Lv Wenbo , Jiang Zhigang , Huang Hao , Zhang Jun , Xu Ping , Yu Chang Yin , Xu Zucai 
Published: May 2022

Abstract
Background
This study was aimed to investigate whether patients with epilepsy (PWE) have higher depression and anxiety levels than the normal population in low-risk areas for coronavirus disease 2019 (COVID-19) in the northern part of Guizhou Province, China, during the COVID-19 epidemic, to evaluate their knowledge on COVID-19, and to analyze related factors for the psychological distress of PWE at this special time.

Methods
The survey was conducted online from February 28, 2020 to March 7, 2020 via a questionnaire. PWE from the outpatient clinic of epilepsy of the Affiliated Hospital of Zunyi Medical University, and healthy people matched for age and sex, participated in this study. Mental health was assessed via a generalized anxiety self-rating scale (GAD-7) and the self-rating depression scale (PHQ-9). The knowledge of COVID-19 in both groups was investigated.

Results
There were no significant differences in the general demographics between the PWE and healthy control groups. The scores of PHQ-9 (P < 0.01) and GAD-7 (P < 0.001) were higher in the PWE group than in the healthy group. There was a significant difference in the proportions of respondents with different severities of depression and anxiety, between the two groups, which revealed significantly higher degree of depression and anxiety in PWE than in healthy people (P = 0, P = 0). Overwhelming awareness and stressful concerns for the pandemic and female patients with epilepsy were key factors that affect the level of anxiety and depression in PWE. Further, the PWE had less accurate knowledge of COVID-19 than healthy people (P < 0.001). There was no statistically significant difference between the two groups in the knowledge of virus transmission route, incubation period, susceptible population, transmission speed, clinical characteristics, and isolation measures on COVID-19 (P > 0.05). PWE knew less about some of the prevention and control measures of COVID-19 than healthy people.

Conclusions
During the COVID-19 epidemic, excessive attention to the epidemic and the female sex are factors associated with anxiety and depression in PWE, even in low-risk areas.