bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunomodulatory effects of extracellular vesicles in glioblastoma
Authors: Low Johannes Jun Wei , Sulaiman Siti Aishah , Johdi Nor Adzimah , Abu Nadiah
Published: November 2022

Glioblastoma (GB) is a type of brain cancer that can be considered aggressive. Glioblastoma treatment has significant challenges due to the immune privilege site of the brain and the presentation of an immunosuppressive tumor microenvironment. Extracellular vesicles (EVs) are cell-secreted nanosized vesicles that engage in intercellular communicationviadelivery of cargo that may cause downstream effects such as tumor progression and recipient cell modulation. Although the roles of extracellular vesicles in cancer progression are well documented, their immunomodulatory effects are less defined. Herein, we focus on glioblastoma and explain the immunomodulatory effects of extracellular vesicles secreted by both tumor and immune cells in detail. The tumor to immune cells, immune cells to the tumor, and intra-immune cells extracellular vesicles crosstalks are involved in various immunomodulatory effects. This includes the promotion of immunosuppressive phenotypes, apoptosis, and inactivation of immune cell subtypes, which affects the central nervous system and peripheral immune system response, aiding in its survival and progression in the brain.
Recent advances in self-assembling peptide matrices as functional coatings for implantable devices
Authors: Tian Yuan , Lu Lei
Published: November 2022

Nature has evolved numerous supramolecular machineries for modulating various cellular functions. Inspired by the assembly of these sophisticated structures in nature, the controlled assembly of synthetic peptides emerges as a promising approach to therapeutically relevant applications. The self-assembling biomimetic peptides could form well-ordered architectures through non-covalent interactions such as π-π stacking, van der Waals, electrostatic, and hydrogen bonding. In addition, the peptidic building blocks are highly biocompatible and allow facile chemical manipulation with diverse functionalities. For decades, a serious of engineered self-assembling peptides have been extensively studied as functional hydrogels for various applications. Meanwhile, the surface modification strategies based on self-assembling peptide matrices have also raised the attention of biomaterials researchers due to their programmability and 3D porous morphologies. This concise review will cover recent advances in self-assembling peptide matrices as functional coatings for implantable devices. The opportunities and challenges in this field will also be discussed.
Association of general health and lifestyle factors with the salivary microbiota – Lessons learned from the ADDITION-PRO cohort
Authors: Poulsen Casper Sahl , Nygaard Nikoline , Constancias Florentin , Stankevic Evelina , Kern Timo , Witte Daniel R. , Vistisen Dorte , Grarup Niels , Pedersen Oluf Borbye , Belstrøm Daniel , Hansen Torben
Published: November 2022

Introduction

Previous research indicates that the salivary microbiota may be a biomarker of oral as well as systemic disease. However, clarifying the potential bias from general health status and lifestyle-associated factors is a prerequisite of using the salivary microbiota for screening.

Materials & Methods

ADDDITION-PRO is a nationwide Danish cohort, nested within the Danish arm of the Anglo-Danish-Dutch Study of Intensive treatment in People with Screen-Detected Diabetes in Primary Care. Saliva samples from n=746 individuals from the ADDITION-PRO cohort were characterized using 16s rRNA sequencing. Alpha- and beta diversity as well as relative abundance of genera was examined in relation to general health and lifestyle-associated variables. Permutational multivariate analysis of variance (PERMANOVA) was performed on individual variables and all variables together. Classification models were created using sparse partial-least squares discriminant analysis (sPLSDA) for variables that showed statistically significant differences based on PERMANOVA analysis (p < 0.05).

Results

Glycemic status, hemoglobin-A1c (HbA1c) level, sex, smoking and weekly alcohol intake were found to be significantly associated with salivary microbial composition (individual variables PERMANOVA, p < 0.05). Collectively, these variables were associated with approximately 5.8% of the observed differences in the composition of the salivary microbiota. Smoking status was associated with 3.3% of observed difference, and smoking could be detected with good accuracy based on salivary microbial composition (AUC 0.95, correct classification rate 79.6%).

Conclusions

Glycemic status, HbA1c level, sex, smoking and weekly alcohol intake were significantly associated with the composition of the salivary microbiota. Despite smoking only being associated with 3.3% of the difference in overall salivary microbial composition, it was possible to create a model for detection of smoking status with a high correct classification rate. However, the lack of information on the oral health status of participants serves as a limitation in the present study. Further studies in other cohorts are needed to validate the external validity of these findings.
Cost-effectiveness of empagliflozin for the treatment of heart failure with reduced ejection fraction in China
Authors: Sang Haiqiang , Wan Yiming , Ma Zhenzhou , Zhang Shengye , Zhao Qiuping
Published: November 2022

Aim

To determine the pharmacoeconomics of empagliflozin for the treatment of heart failure (HF) with reduced ejection fraction in China and to provide evidence-based reference for clinical rational drug selection and medical decision-making.

Research design and methods

We used the Markov model to evaluate the cost-effectiveness of empagliflozin for the treatment of HF with reduced ejection fraction (HFrEF). We evaluated the cost-effectiveness of the standard treatment in addition to empagliflozin (empagliflozin group) vs. the cost-effectiveness of the standard treatment alone (standard treatment group).

Results

We found that each additional quality-adjusted life year (QALY) in the empagliflozin group costed $3,842.20 more, which was less than China’s gross domestic product (GDP) per capita in 2021 ($11,981). The steady-state mortality in the two groups was the key factor affecting the incremental cost-effectiveness ratio (ICER). Probabilistic sensitivity analysis revealed that when the willingness-to-pay (WTP) threshold was one time the GDP per capita in 2021 ($11,981) and three times the GDP per capita in 2021 ($35,943), the probability of the empagliflozin group being cost-effective was 85.8 and 91.6%, respectively.

Conclusion

Compared with the standard treatment alone, the addition of empagliflozin to the standard treatment was more cost-effective for the treatment of HFrEF in China.
Visualizable vs. standard, non-visualizable steerable sheath for pulmonary vein isolation procedures: Randomized, single-centre trial
Authors: Janosi Kristof , Debreceni Dorottya , Janosa Benedek , Bocz Botond , Simor Tamas , Kupo Peter
Published: November 2022

Introduction

Steerable sheaths (SSs) are frequently used to improve catheter contact during pulmonary vein isolation (PVI) procedures. A new type of visualizable (by electroanatomical mapping system) SS has become available in clinical treatment.

Purpose

We aimed to compare procedural data of visualizable vs. non-visualizable steerable sheath assisted PVI procedures in patients with atrial fibrillation (AF).

Methods

In this single-centre randomized study, we enrolled a total of 100 consecutive patients who underwent PVI due to AF.

Results

A total of 100 patients were randomized into 2 groups (visualizable SS group: 50; non-visualizable SS group: 50). Acute ablation success was 100% and the rate of the first pass isolation were similar (92% vs. 89%; p = 0.88). Using visualizable SS, left atrial (LA) procedure time (53.1 [41.3; 73.1] min vs. 59.5 [47.6; 74.1] min.; p = 0.04), LA fluoroscopy time (0 [0; 0] s vs. 17.5 [5.5; 69.25] s; p < 0.01) and LA fluoroscopy dose (0 [0; 0.27] mGy vs. 0.74 [0.16; 2.34] mGy; p < 0.01) was significantly less, however, there was no difference in the total procedural time (90 ± 35.2 min vs. 99.5 ± 31.8 min; p = 0.13), total fluoroscopy time (184 ± 89 s vs. 193 ± 44 s; p = 0.79), and total fluoroscopy dose (9.12 ± 1.98 mGy vs. 9.97 ± 2.27 mGy; p = 0.76). Compared to standard, non-visualizable SS group, the number of radiofrequency ablations was fewer (69 [58; 80] vs. 79 [73; 86); p < 0.01) as well as total ablation time was reduced (1049 sec. [853; 1175] vs. 1265 sec. [1085; 1441]; p < 0.01) in the visualizable SS cohort. No major complications occurred in either group.

Conclusion

Compared to the standard, non-visualizable SS, visualizable SS significantly reduces the left atrial procedure time, RF delivery and fluoroscopy exposure without compromising its safety or effectiveness in patients undergoing PVI procedures for AF.
Therapeutic potential of exosomes/miRNAs in polycystic ovary syndrome induced by the alteration of circadian rhythms
Authors: Chen Wei-hong , Huang Qiao-yi , Wang Zhi-yi , Zhuang Xuan-xuan , Lin Shu , Shi Qi-yang
Published: November 2022

Polycystic ovary syndrome (PCOS) is a reproductive dysfunction associated with endocrine disorders and is most common in women of reproductive age. Clinical and/or biochemical manifestations include hyperandrogenism, persistent anovulation, polycystic ovary, insulin resistance, and obesity. Presently, the aetiology and pathogenesis of PCOS remain unclear. In recent years, the role of circadian rhythm changes in PCOS has garnered considerable attention. Changes in circadian rhythm can trigger PCOS through mechanisms such as oxidative stress and inflammation; however, the specific mechanisms are unclear. Exosomes are vesicles with sizes ranging from 30–120nm that mediate intercellular communication by transporting microRNAs (miRNAs), proteins, mRNAs, DNA, or lipids to target cells and are widely involved in the regulation of various physiological and pathological processes. Circadian rhythm can alter circulating exosomes, leading to a series of related changes and physiological dysfunctions. Therefore, we speculate that circadian rhythm-induced changes in circulating exosomes may be involved in PCOS pathogenesis. In this review, we summarize the possible roles of exosomes and their derived microRNAs in the occurrence and development of PCOS and discuss their possible mechanisms, providing insights into the potential role of exosomes for PCOS treatment.
PiT2 deficiency prevents increase of bone marrow adipose tissue during skeletal maturation but not in OVX-induced osteoporosis
Authors: Frangi Giulia , Guicheteau Marie , Jacquot Frederic , Pyka Grzegorz , Kerckhofs Greet , Feyeux Magalie , Veziers Joëlle , Guihard Pierre , Halgand Boris , Sourice Sophie , Guicheux Jérôme , Prieur Xavier , Beck Laurent , Beck-Cormier Sarah
Published: November 2022

The common cellular origin between bone marrow adipocytes (BMAds) and osteoblasts contributes to the intimate link between bone marrow adipose tissue (BMAT) and skeletal health. An imbalance between the differentiation ability of BMSCs towards one of the two lineages occurs in conditions like aging or osteoporosis, where bone mass is decreased. Recently, we showed that the sodium-phosphate co-transporter PiT2/SLC20A2 is an important determinant for bone mineralization, strength and quality. Since bone mass is reduced in homozygous mutant mice, we investigated in this study whether the BMAT was also affected in PiT2-/- mice by assessing the effect of the absence of PiT2 on BMAT volume between 3 and 16 weeks, as well as in an ovariectomy-induced bone loss model. Here we show that the absence of PiT2 in juveniles leads to an increase in the BMAT that does not originate from an increased adipogenic differentiation of bone marrow stromal cells. We show that although PiT2-/- mice have higher BMAT volume than control PiT2+/+ mice at 3 weeks of age, BMAT volume do not increase from 3 to 16 weeks of age, leading to a lower BMAT volume in 16-week-old PiT2-/- compared to PiT2+/+ mice. In contrast, the absence of PiT2 does not prevent the increase in BMAT volume in a model of ovariectomy-induced bone loss. Our data identify SLC20a2/PiT2 as a novel gene essential for the maintenance of the BMAd pool in adult mice, involving mechanisms of action that remain to be elucidated, but which appear to be independent of the balance between osteoblastic and adipogenic differentiation of BMSCs.
Diabetic retinopathy risk prediction in patients with type 2 diabetes mellitus using a nomogram model
Authors: Wang Qian , Zeng Ni , Tang Hongbo , Yang Xiaoxia , Yao Qu , Zhang Lin , Zhang Han , Zhang Ying , Nie Xiaomei , Liao Xin , Jiang Feng
Published: November 2022

Background

This study aims to develop a diabetic retinopathy (DR) hazard nomogram for a Chinese population of patients with type 2 diabetes mellitus (T2DM).

Methods

We constructed a nomogram model by including data from 213 patients with T2DM between January 2019 and May 2021 in the Affiliated Hospital of Zunyi Medical University. We used basic statistics and biochemical indicator tests to assess the risk of DR in patients with T2DM. The patient data were used to evaluate the DR risk using R software and a least absolute shrinkage and selection operator (LASSO) predictive model. Using multivariable Cox regression, we examined the risk factors of DR to reduce the LASSO penalty. The validation model, decision curve analysis, and C-index were tested on the calibration plot. The bootstrapping methodology was used to internally validate the accuracy of the nomogram.

Results

The LASSO algorithm identified the following eight predictive variables from the 16 independent variables: disease duration, body mass index (BMI), fasting blood glucose (FPG), glycated hemoglobin (HbA1c), homeostatic model assessment-insulin resistance (HOMA-IR), triglyceride (TG), total cholesterol (TC), and vitamin D (VitD)-T3. The C-index was 0.848 (95% CI: 0.798–0.898), indicating the accuracy of the model. In the interval validation, high scores (0.816) are possible from an analysis of a DR nomogram’s decision curve to predict DR.

Conclusion

We developed a non-parametric technique to predict the risk of DR based on disease duration, BMI, FPG, HbA1c, HOMA-IR, TG, TC, and VitD.
The effect of public–private partnership investment, financial development, and renewable energy consumption on the ecological footprint in South Asia and the Pacific region
Authors: Wen Ya , Qu Chenchen , Gao Chen , Song Pingting , Yang Deyong
Published: November 2022

The improvement of environmental quality has become a major challenge for all countries. Against the strategic background of environmental protection, this study investigated the role of public–private partnership investment (PPPI) in energy and transport, financial development, and renewable energy on ecological footprint (EF) in South Asia and the Pacific region, utilizing the autoregressive distributive lag (ARDL) model spanning the time 1990–2017. The outcomes of the ARDL show that PPPI in energy and transport has a significantly positive effect on the EF in the full sample and Pacific region in the long run. Financial development has a positive impact on the EF in South Asia and the Pacific region in the long term. Renewable energy causes a significant and negative impact on the EF in the full sample in both time periods, and only in the short run in South Asia. As for the panel granger causalities test, PPPI in energy and transport and renewable energy has a negative causal relationship with the EF. The results also reveal that there is a unidirectional negative and positive causality from financial development to the EF in the long term in South Asia and the Pacific region, respectively. On the basis of the analysis, corresponding recommendations are proposed.
Floristic composition, biological spectrum, and phytogeographic distribution of the Bin Dara Dir, in the western boundary of Pakistan
Authors: Manan Fazal , Khan Shujaul Mulk , Muhammad Zahir , Ahmad Zeeshan , Abdullah Abdullah , Rahman Amjad ur , Han Heesup , Ariza-Montes Antonio , Contreras-Barraza Nicolás , Raposo António
Published: November 2022

This study assessed the floristic composition, biological spectrum, and phytogeographical elements of the Bin Dara western boundary of Pakistan. The flora consisted of 140 plant species belonging to 47 families. The most dominant family was Poaceae (with 14 species), followed by Asteraceae (11 species). The biological spectrum showed the therophytes (71 species, 50.71%) as the dominant life form class, followed by mega-phanerophytes (27 species, 19.28%), nano-phanerophytes (15 species, 10.71%), geophytes (10 species, 7.14%), chamaephytes (9 species, 6.42%), and hemi-cryptophytes (8 species, 5.71%). Leaf size classes comprised of nanophylls (48 species, 34.28%), microphylls (32 species, 22.85%), mesophylls (22 species, 15.71%), macrophylls (17 species, 12.14%), leptophylls (12 species, 8.57), megaphylls (8 species, 5.75%), and aphyllous (1 species, 0.71%). Cosmopolitan was the most prominent form of phytogeographic elements (with 17 species, 12.14%), followed by pantropical and Euro-Siberian Mediterranean Irano-Turanian (14 species, 10%) each. The pluriregional represented (13 species, 9.28%), Holarctic and Mediterranean Irano-Turanian (10 species, 7.14%), Irano-Turanian and Western Himalayan (9 species, 6.42%) each. It is recommended that further study is needed to map the vegetation, its indicators, and rare species that face a huge threat of endangerment.
Causal association between inflammatory bowel disease and IgA nephropathy: A bidirectional two-sample Mendelian randomization study
Authors: Xiao Mofan , Ran Yan , Shao Jiayuan , Lei Zhangni , Chen Yuling , Li Yingchao
Published: November 2022

Background: An association between inflammatory bowel disease (IBD) [which includes ulcerative colitis (UC) and Crohn’s disease (CD)] and IgA nephropathy (IgAN) has been discovered in observational studies, but the causal relationship is still unknown. The aim of this study was to clarify the causal link between IBD (which includes UC and CD) and IgAN via a two-sample Mendelian randomization (MR) analysis.

Methods: Eligible single-nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) for analyses and were obtained from the publicly available genome-wide association study (GWAS) summary statistics. Inverse-variance weighting (IVW), Mendelian randomization–Egger (MR-Egger) regression, the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test, and the weighted median were utilized to obtain the results. The MR-PRESSO test and MR-Egger regression were also performed to detect and correct horizontal pleiotropy. The Cochran’s Q test and “leave-one-out” analysis were also conducted to assess the stability and reliability of the MR results.

Results: This study found that IBD, UC, and CD all had significant positive causal effects on IgAN risk (IBD: OR = 1.58, 95% CI 1.15–2.16, p = 4.53 × 10–3; UC: OR = 1.55, 95% CI 1.14–2.11, p = 4.88 × 10–3; CD: OR = 1.57, 95% CI 1.21–2.03, p = 5.97 × 10–4). No significant horizontal pleiotropic effect was found for the causal association between IBD, UC, CD, and the risk of IgAN. Cochran’s Q test identified no evidence of heterogeneity for the IV estimates. The “leave-one-out” sensitivity analysis also revealed that the MR results were robust.

Conclusion: The results of this two-sample MR analysis supported that IBD, UC, and CD were causally associated with the risk of IgAN, while there was no sufficient evidence for the causal effect of IgAN on IBD, UC, or CD. Our findings provide theoretical support and a new perspective for the diagnosis and treatment of these two diseases.
Potential value of the homologous recombination deficiency signature we developed in the prognosis and drug sensitivity of gastric cancer
Authors: Wu Xin , Wang Qiong , Liu Peifa , Sun Linde , Wang Yu
Published: November 2022

Background: Homologous recombination is an important DNA repair mechanism, which deficiency is a common feature of many cancers. Defining homologous recombination deficiency (HRD) status can provide information for treatment decisions of cancer patients. HRD score is a widely accepted method to evaluate HRD status. This study aimed to explored HRD in gastric cancer (GC) patients’ clinical outcomes with genes related to HRD score and HRD components score [HRD-loss of heterozygosity (LOH), large-scale state transitions (LST), and telomeric allelic imbalance (NtAI)].

Methods: Based on LOH, NtAI scores, LST, and integrated HRD scores-related genes, a risk model for stratifying 346 TCGA GC cases were developed by Cox regression analysis and LASSO Cox regression. The risk scores of 33 cancers in TCGA were calculated to analyze the relationship between risk scores of each cancer and HRD scores and 3 HRD component scores. Relationship between the risk model and patient survival, BRCA1, BRCA2 mutation, response to Cisplatin and Talazoparib treatment was analyzed by generating Kaplan-Meier curve, mutations waterfall map and conducting Pearson correlation analysis.

Results: An gene signature was constructed based on 11 HRD scores-related gene (BEX2, C1QL2, DKK1, DRC1, GLUD2, HCAR1, IGFBP1, NXPH1, PROC, SERPINA5, and SLCA1A2). Risk groups were stratified by risk score. Prognosis of the high-risk score group was worse than the low-risk ones. Risk score was associated with BRCA2 mutation, and patients grouped according to BRCA2 mutation status had distinguishable risk score, NtAI score, HRD-LOH, LST, and HRD scores. The low-score group showed higher sensitivity to Cisplatin and Talazoparib. The risk score of adrenocortical carcinoma (ACC), stomach adenocarcinoma (STAD), uterine corpus endometrial carcinoma (UCEC), kidney renal clear cell carcinoma (KIRC), sarcoma (SARC), prostate adenocarcinoma (PRAD), breast invasive carcinoma (BRCA) was significantly positively correlated with HRD score.

Conclusion: We developed an 11 HRD scores-related genes risk model and revealed the potential association between HRD status and GC prognosis, gene mutations, patients’ sensitivity to therapeutic drugs.
Systematic pan-cancer analysis showed that RAD51AP1 was associated with immune microenvironment, tumor stemness, and prognosis
Authors: Liu Renwang , Zhu Guangsheng , Li Mingbiao , Cao Peijun , Li Xuanguang , Zhang Xiuwen , Huang Hua , Song Zuoqing , Chen Jun
Published: November 2022

Although RAD51 associated protein 1 (RAD51AP1) is crucial in genome stability maintenance, it also promotes cancer development with an unclear mechanism. In this study, we collected intact expression data of RAD51AP1 from the public database, and verified it was significantly over-expressed in 33 cancer types and correlated with poor prognosis in 13 cancer types, including glioma, adrenocortical carcinoma, lung adenocarcinoma. We further authenticated that RAD51AP1 is up-regulated in several typical cancer cell lines and promotes cancer cell proliferation in vitro. Moreover, we also demonstrated that RAD51AP1 was significantly positively related to cancer stemness score mRNAsi in 27 cancer types and broadly correlated to tumor-infiltrating immune cells in various cancers in a diverse manner. It was also negatively associated with immunophenoscore (IPS) and Estimation of STromal and Immune cells in MAlignant Tumours using Expression data (ESTIMATE) scores and positively correlated with mutant-allele tumor heterogeneity (MATH), tumor mutational burden (TMB), microsatellite instability (MSI), and PD-L1 expression in multiple cancers. The tumor stemness enhancing and tumor immune microenvironment affecting functions of RAD51AP1 might compose its carcinogenesis mechanism. Further investigations beyond the bioinformatics level should confirm these findings in each specific cancer.
Microglia autophagy in ischemic stroke: A double-edged sword
Authors: Peng Li , Hu Guangqiang , Yao Qianfang , Wu Jianming , He Ziyang , Law Betty Yuen-Kwan , Hu Guishan , Zhou Xiaogang , Du Junrong , Wu Anguo , Yu Lu
Published: November 2022

Ischemic stroke (IS) is one of the major types of cerebrovascular diseases causing neurological morbidity and mortality worldwide. In the pathophysiological process of IS, microglia play a beneficial role in tissue repair. However, it could also cause cellular damage, consequently leading to cell death. Inflammation is characterized by the activation of microglia, and increasing evidence showed that autophagy interacts with inflammation through regulating correlative mediators and signaling pathways. In this paper, we summarized the beneficial and harmful effects of microglia in IS. In addition, we discussed the interplay between microglia autophagy and ischemic inflammation, as along with its application in the treatment of IS. We believe this could help to provide the theoretical references for further study into IS and treatments in the future.
Emerging insights and challenges for understanding T cell function through the proteome
Authors: Solt Laura A.
Published: November 2022

T cells rapidly transition from a quiescent state into active proliferation and effector function upon exposure to cognate antigen. These processes are tightly controlled by signal transduction pathways that influence changes in chromatin remodeling, gene transcription, and metabolism, all of which collectively drive specific T cell memory or effector cell development. Dysregulation of any of these events can mediate disease and the past several years has shown unprecedented novel approaches to understand these events, down to the single-cell level. The massive explosion of sequencing approaches to assess the genome and transcriptome at the single cell level has transformed our understanding of T cell activation, developmental potential, and effector function under normal and various disease states. Despite these advances, there remains a significant dearth of information regarding how these events are translated to the protein level. For example, resolution of protein isoforms and/or specific post-translational modifications mediating T cell function remains obscure. The application of proteomics can change that, enabling significant insights into molecular mechanisms that regulate T cell function. However, unlike genomic approaches that have enabled exquisite visualization of T cell dynamics at the mRNA and chromatin level, proteomic approaches, including those at the single-cell level, has significantly lagged. In this review, we describe recent studies that have enabled a better understanding of how protein synthesis and degradation change during T cell activation and acquisition of effector function. We also highlight technical advances and how these could be applied to T cell biology. Finally, we discuss future needs to expand upon our current knowledge of T cell proteomes and disease.
Recent progress and perspectives on the relationship between hyperuricemia and periodontitis
Authors: Hou Wenxue , Xia Xiaomin , Li Ying , Lv Hanlin , Liu Jie , Li Xue
Published: November 2022

Periodontitis is one of the most prevalent diseases in oral cavity, which could not merely lead to the destruction of supporting or surrounding tooth structures but also affect the whole-body health such as the digestive and nervous systems. Epidemiological investigations suggested that in some developed countries, more than 45% or even 50% population were suffering from periodontitis. However, the prevalence increases with age remarkably and it is investigated that a high prevalence (>50%) is affecting the elderly who is over 65 years old. There is an increasing interest in the direct and indirect relationships between periodontitis and hyperuricemia. Currently, hyperuricemia has become the second major metabolic disease in modern society and the prevalence of hyperuricemia among adult males and females was 21.7% and 14.4% respectively. As an inflammatory disease associated with various systemic diseases, periodontitis may have certain connections with hyperuricemia. Partial existing research announced that hyperuricemia could act as an inhibitory factor for periodontitis, while other scholars presented that a high uric acid (UA) level was more likely to aggravate inflammatory immune response and lead to more serious tissue destruction. This article provides a detailed and comprehensive overview of the relationship underlying hyperuricemia and periodontitis in the molecular mechanisms. Given the impact of hyperuricemia, this review could provide insight into its comorbidities.
Association of concomitant autoimmunity with the disease features and long-term treatment and health outcomes in Celiac disease
Authors: Tauschi Riku , Eurén Anna , Vuorela Nina , Koskimaa Sara , Huhtala Heini , Kaukinen Katri , Kivelä Laura , Kurppa Kalle
Published: November 2022

Background

Celiac disease (CeD) is often accompanied by other autoimmune diseases (AID). However, the association of co-existing autoimmunity with the presentation and treatment success in CeD is unclear. We investigated these issues with a large and well-defined cohort of Finnish patients.

Methods

Adult CeD patients (n = 806) were collected from multiple heath care sites via nationwide recruitment. They were interviewed, underwent measurement of CeD autoantibodies, and filled out questionnaires to ascertain quality of life (PGWB) and gastrointestinal symptoms (GSRS) after a median of 9.7 years on a gluten-free diet. Data were supplemented retrospectively from patient records. The results were compared between CeD patients with and without a coexisting AID.

Results

Altogether 185 patients had CeD+AID and 621 had CeD only. At CeD diagnosis, patients with CeD+AID were older (median 42 vs. 36 years, p = 0.010) and had more joint symptoms (9.1 vs. 4.2%, p = 0.011), whereas the groups were comparable in sex, family history of CeD, other presenting symptoms, proportion of screen-detected subjects, and severity of duodenal lesion. During follow-up on gluten-free diet, CeD+AID patients experienced poorer general health (median score 12 vs. 14, p < 0.001) in PGWB, more overall gastrointestinal symptoms (2.1 vs. 1.9, p = 0.001), and constipation (2.0 vs. 1.7, p < 0.001) in GSRS, whereas there was no difference in histological and serological recovery, dietary adherence, use of gluten-free oats, smoking, and presence of regular follow-up.

Conclusions

Co-existing AID was not significantly associated with the baseline features or with most long-term outcomes in CeD. However, the increased prevalence of gastrointestinal symptoms and reduced poorer self-perceived health during treatment indicates these patients' need for special support.
BLNK mutation associated with T-cell LGL leukemia and autoimmune diseases: Case report in hematology
Authors: Fouquet Guillemette , Rossignol Julien , Ricard Laure , Guillem Flavia , Couronné Lucile , Asnafi Vahid , Vavasseur Manon , Parisot Mélanie , Garcelon Nicolas , Rieux-Laucat Frédéric , Mekinian Arsène , Hermine Olivier
Published: November 2022

We present the case of a female patient with a heterozygous somatic BLNK mutation, a T-cell LGL (large granular lymphocyte) leukemia, and multiple autoimmune diseases. Although this mutation seems uncommon especially in this kind of clinical observation, it could represent a new mechanism for autoimmune diseases associated with LGL leukemia. The patient developed several autoimmune diseases: pure red blood cell apalsia, thyroiditis, oophoritis, and alopecia areata. She also presented a T-cell LGL leukemia which required treatment with corticosteroids and cyclophosphamide, with good efficacy. Interestingly, she had no notable infectious history. The erythroblastopenia also resolved, the alopecia evolves by flare-ups, and the patient is still under hormonal supplementation for thyroiditis and oophoritis. We wanted to try to understand the unusual clinical picture presented by this patient. We therefore performed whole-genome sequencing, identifying a heterozygous somatic BLNK mutation. Her total gamma globulin level was slightly decreased. Regarding the lymphocyte subpopulations, she presented a B-cell deficiency with increased autoreactive B-cells and a CD4+ and Treg deficiency. This B-cell deficiency persisted after complete remission of erythroblastopenia and LGL leukemia. We propose that the persistent B-cell deficiency linked to the BLNK mutation can explain her clinical phenotype.
Pan-genomic analysis of Corynebacterium amycolatum gives insights into molecular mechanisms underpinning the transition to a pathogenic phenotype
Authors: Jesus Hendor N. R. , Rocha Danilo J. P. G. , Ramos Rommel T. J. , Silva Artur , Brenig Bertram , Góes-Neto Aristóteles , Costa Mateus M. , Soares Siomar C. , Azevedo Vasco , Aguiar Eric R. G. R. , Martínez-Martínez Luiz , Ocampo Alain , Alibi Sana , Dorta Alexis , Pacheco Luis G. C. , Navas Jesus
Published: November 2022

Corynebacterium amycolatum is a nonlipophilic coryneform which is increasingly being recognized as a relevant human and animal pathogen showing multidrug resistance to commonly used antibiotics. However, little is known about the molecular mechanisms involved in transition from colonization to the MDR invasive phenotype in clinical isolates. In this study, we performed a comprehensive pan-genomic analysis of C. amycolatum, including 26 isolates from different countries. We obtained the novel genome sequences of 8 of them, which are multidrug resistant clinical isolates from Spain and Tunisia. They were analyzed together with other 18 complete or draft C. amycolatum genomes retrieved from GenBank. The species C. amycolatum presented an open pan-genome (α = 0.854905), with 3,280 gene families, being 1,690 (51.52%) in the core genome, 1,121 related to accessory genes (34.17%), and 469 related to unique genes (14.29%). Although some classic corynebacterial virulence factors are absent in the species C. amycolatum, we did identify genes associated with immune evasion, toxin, and antiphagocytosis among the predicted putative virulence factors. Additionally, we found genomic evidence for extensive acquisition of antimicrobial resistance genes through genomic islands.
Tryptophan was metabolized into beneficial metabolites against coronary heart disease or prevented from producing harmful metabolites by the in vitro drug screening model based on Clostridium sporogenes
Authors: Tian XiaoXue , Wu Yuanyuan , Duan Cheng , Zhou Xiaohong , Li Yong , Zheng Jiabin , Lai Weihua , Zhang Shuyao , Cao Lixiang , Zhong Shilong
Published: November 2022

In our previous study of 2,130 Chinese patients with coronary heart disease (CHD), we found that tryptophan (TRP) metabolites contributed to elevated risks of death. Many TRP-derived metabolites require the participation of intestinal bacteria to produce, and they play an important role in the pathogenesis of metabolic diseases such as CHD. So it is necessary to metabolize TRP into beneficial metabolites against CHD or prevent the production of harmful metabolites through external intervention. Indole-3-butyric acid (IBA) may be a key point of gut microbiota that causes TRP metabolism disorder and affects major adverse cardiovascular events in CHD. Therefore, this study aimed to develop a method based on in vitro culture bacteria to evaluate the effects of IBA on specific microbial metabolites quickly. We detected the concentrations of TRP and its metabolites in 11 bacterial strains isolated from feces using liquid chromatography–mass spectrometry, and selected Clostridium sporogenes as the model strain. Then, IBA was used in our model to explore its effect on TRP metabolism. Results demonstrated that the optimal culture conditions of C. sporogenes were as follows: initial pH, 6.8; culture temperature, 37°C; and inoculum amount, 2%. Furthermore, we found that IBA increases the production of TRP and 5-HIAA by intervening TRP metabolism, and inhibits the production of KYNA. This new bacteria-specific in vitro model provides a flexible, reproducible, and cost-effective tool for identifying harmful agents that can decrease the levels of beneficial TRP metabolites. It will be helpful for researchers when developing innovative strategies for studying gut microbiota.
Maize-soybean intercropping facilitates chemical and microbial transformations of phosphorus fractions in a calcareous soil
Authors: Liu Jin , Li Yang , Han Chaoqun , Yang Dongling , Yang Jianjun , Cade-Menun Barbara J. , Chen Yuanquan , Sui Peng
Published: November 2022

Intercropping often substantially increases phosphorus (P) availability to plants compared with monocropping, which could be an effective strategy for soil legacy P recovery and agricultural production. However, the biogeochemical interactions among plants, microbes, and soil that mobilize P remain largely unknown in intercropping systems. Pot experiments with maize-soybean intercropping in a calcareous soil were conducted to investigate the potential chemical and biological transformation mechanisms of inorganic P (Pi) and organic P (Po) using sequential extraction and Illumina MiSeq sequencing. Compared to monocropping of each crop, maize-soybean intercropping significantly enhanced total P uptake of the two crops by mobilizing Ca2-Pi[extracted by bicarbonate (NaHCO3)], Al-Pi/Po[extracted by ammonium fluoride (NH4F)] and Fe-Pi[extracted by sodium hydroxide and sodium carbonate (NaOH-Na2CO3)] fractions. Furthermore, there were significant increases in the organic carbon content and alkaline phosphomonoesterase (ALP) and phosphodiesterase (PDE) activities as well as the abundances ofMicrovirga,Lysobacter,MicrolunatusandSphingomonasunder maize-soybean intercropping relative to monocropping. In contrast, compared to monocroppping, no significant change in the soil pH was observed under maize-soybean intercropping. Therefore, the enhanced P uptake of the maize-soybean intercropping probably resulted from a synergistic effect of rhizosphere organic carbon deposit, increased activities of ALP and PDE, together with the bacteria (Microvirga,Lysobacter,MicrolunatusandSphingomonas) which showed correlation with soil P forms, while the generally recognized rhizosphere acidification was excluded in this investigated calcareous soil. Moreover, the selected bacterial genera exhibited a closer network in the rhizosphere of soybean compared to maize, suggesting enhanced interactions among bacteria in the soybean rhizosphere. These results provide theoretical bases for the recovery of soil legacy P by maize-soybean intercropping.
No safe renal warm ischemia time—The molecular network characteristics and pathological features of mild to severe ischemia reperfusion kidney injury
Authors: Chen Ya-Lei , Li Huai-Kang , Wang Lei , Chen Jian-Wen , Ma Xin
Published: November 2022

Ischemic acute kidney injury (AKI) has always been a hot and difficult research topic in the field of renal diseases. This study aims to illustrate the safe warm ischemia time of kidney and the molecular network characteristics and pathological features of mild to severe ischemia reperfusion kidney injury. We established varying degrees of renal injury due to different ischemia time (0 min, 16 min, 18 min, 20 min, 22 min, 24 min, 26 min, 28 min, and 30 min) on unilateral (left kidney) ischemia-reperfusion injury and contralateral (right kidney) resection (uIRIx) mouse model. Mice were sacrificed 24 h after uIRIx, blood samples were harvested to detect serum creatinine (Scr), and kidney tissue samples were harvested to perform Periodic Acid-Schiff (PAS) staining and RNA-Seq. Differentially expressed genes (DEGs) were identificated, time-dependent gene expression patterns and functional enrichment analysis were further performed. Finally, qPCR was performed to validated RNA-Seq results. Our results indicated that there was no absolute safe renal warm ischemia time, and every minute of ischemia increases kidney damage. Warm ischemia 26min or above in mice makes severe kidney injury, renal pathology and SCr were both significantly changed. Warm ischemia between 18 and 26 min makes mild kidney injury, with changes in pathology and renal molecular expression, while SCr did not change. No obvious pathological changes but significant differences in molecular expression were found less than 16min warm ischemia. There are two key time intervals in the process of renal ischemia injury, 0 min–16 min (short-term) and 26 min–28 min (long-term). Gene expression of immune-related pathways were most significantly down-regulated in short-term ischemia, while metabolism-related pathways were the mainly enriched pathway in long-term ischemia. Taken together, this study provides novel insights into safe renal artery occlusion time in partial nephrectomy, and is of great value for elucidating molecular network characteristics and pathological features of mild to severe ischemia reperfusion kidney injury, and key genes related to metabolism and immune found in this study also provide potential diagnostic and therapeutic biomarkers for AKI.
Morphological and biomolecular targets in retina and vitreous from Reelin-deficient mice (Reeler): Potential implications for age-related macular degeneration in Alzheimer’s dementia
Authors: Balzamino Bijorn Omar , Esposito Graziana , Marino Ramona , Calissano Pietro , Latina Valentina , Amadoro Giuseppina , Keller Flavio , Cacciamani Andrea , Micera Alessandra
Published: November 2022

The neurosensory retina is an outgrowth of the Central Nervous System (CNS), and the eye is considered “a window to the brain.” Reelin glycoprotein is directly involved in neurodevelopment, in synaptic plasticity, learning and memory. Consequently, abnormal Reelin signaling has been associated with brain neurodegeneration but its contributing role in ocular degeneration is still poorly explored. To this aim, experimental procedures were assayed on vitreous or retinas obtained from Reeler mice (knockout for Reelin protein) at different postnatal days (p) p14, p21 and p28. At p28, a significant increase in the expression of Amyloid Precursor Protein (APP) and its amyloidogenic peptide (Aβ1-42 along with truncated tau fragment (i.e., NH2htau)- three pathological hallmarks of Alzheimer’s disease (AD)-were found in Reeler mice when compared to their age-matched wild-type controls. Likewise, several inflammatory mediators, such as Interleukins, or crucial biomarkers of oxidative stress were also found to be upregulated in Reeler mice by using different techniques such as ELLA assay, microchip array or real-time PCR. Taken together, these findings suggest that a dysfunctional Reelin signaling enables the expression of key pathological features which are classically associated with AD neurodegenerative processes. Thus, this work suggests that Reeler mouse might be a suitable animal model to study not only the pathophysiology of developmental processes but also several neurodegenerative diseases, such as AD and Age-related Macular Degeneration (AMD), characterized by accumulation of APP and/or Aβ1-42, NH2htau and inflammatory markers.
Structural network efficiency mediates the association between glymphatic function and cognition in mild VCI: a DTI-ALPS study
Authors: Song Hao , Ruan Zhao , Gao Lei , Lv Dongwei , Sun Dong , Li Zeng , Zhang Ran , Zhou Xiaoli , Xu Haibo , Zhang Junjian
Published: November 2022

Background and objective: Vascular cognitive impairment (VCI) can be caused by multiple types of cerebrovascular pathology and is considered a network disconnection disorder. The heterogeneity hinders research progress in VCI. Glymphatic failure has been considered as a key common pathway to dementia recently. The emergence of a new method, Diffusion Tensor Image Analysis Along the Perivascular Space (DTI-ALPS), makes it possible to investigate the changes of the glymphatic function in humans non-invasively. We aimed to investigate alterations of glymphatic function in VCI and its potential impact on network connectivity.

Methods: We recruited 79 patients with mild VCI, including 40 with cerebral small vessel disease cognitive impairment (SVCI) and 39 with post-stroke cognitive impairment (PSCI); and, 77 normal cognitive (NC) subjects were recruited. All subjects received neuropsychological assessments and multimodal magnetic resonance imaging scans. ALPS-index was calculated and structural networks were constructed by deterministic tractography, and then, the topological metrics of these structural connectivity were evaluated.

Results: The ALPS-index of VCI patients was significantly lower than that of NC subjects (P < 0.001). Multiple linear regression analysis showed that ALPS-index affects cognitive function independently (β = 0.411, P < 0.001). The results of correlation analysis showed that the ALPS-index was correlated with overall vascular risk factor burden (r = −0.263, P = 0.001) and multiple cerebrovascular pathologies (P < 0.05). In addition, global efficiency (Eg) of network was correlated with ALPS-index in both SVCI (r = 0.348, P = 0.028) and PSCI (r = 0.732, P < 0.001) patients. Finally, the results of mediation analysis showed that Eg partially mediated in the impact of glymphatic dysfunction on cognitive impairment (indirect effect = 7.46, 95% CI 4.08–11.48).

Conclusion: In both major subtypes of VCI, the ALPS-index was decreased, indicating impaired glymphatic function in VCI. Glymphatic dysfunction may affect cognitive function in VCI by disrupting network connectivity, and, may be a potential common pathological mechanism of VCI. ALPS-index is expected to become an emerging imaging marker for VCI.
Neural cue reactivity is not stronger in male than in female patients with alcohol use disorder
Authors: Gerhardt Sarah , Hoffmann Sabine , Tan Haoye , Gerchen Martin Fungisai , Kirsch Peter , Vollstädt-Klein Sabine , Kiefer Falk , Bach Patrick , Lenz Bernd
Published: November 2022

Background

Males consume more alcohol than females, and alcohol use disorder (AUD) is more prevalent in males than females. However, females progress faster to AUD. Sex differences in neural alcohol cue reactivity were previously observed in young social drinkers, indicating a role of hypersensitivity to alcohol-related cues in very early stages of addiction. To our knowledge, this is the first study on patients diagnosed with AUD to test sex differences in neural reactivity to alcohol cues in order to widen previous findings.

Methods

We analyzed data from previous studies, using a well-established functional magnetic resonance imaging (fMRI) paradigm to compare neural reactivity to alcohol cues between 42 female and 124 male patients with AUD (mean age 45 and 46 years) in predefined regions of interest that were implicated by previous studies (ventral and dorsal striatum as well as caudate, putamen, amygdala, hippocampus, insula, anterior cingulate cortex, and medial prefrontal cortex) using independent samples t-tests. Post-hoc, effect size calculations were performed.

Results

Throughout all nine regions of interest, we found no statistically significant sex differences in neural reactivity toward alcoholic pictures alone or in comparison to neutral pictures (p > 0.05, FDR-corrected). Post-hoc effect size estimates indicated a magnitude between 0.137 and 0.418 (Hedge’s g) on alcohol reactivity to alcohol cues compared to neutral cues and indicate very small to less than medium effect sizes in the direction of higher cue reactivity in female patients.

Conclusion

Previous studies showed sex differences in neural alcohol cue reactivity in younger social and problematic alcohol drinkers, i.e., stronger striatal cue-reactivity in males. After correction for multiple comparisons, we did not observe significant sex differences in a cohort of middle-aged females and males with AUD. Sex differences that are present during early phases of addiction development might disappear at later stages of AUD and might thus be considered as clinically less relevant in patients with more severe AUD.