bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating microRNA: Myocardium-derived prenatal biomarker of ventricular septal defects
Authors: Yang Yiru , Yang Hainan , Lian Xihua , Yang Shuping , Shen Haolin , Wu Shufen , Wang Xiali , Lyu Guorong
Published: August 2022

Background: Recently, circulating microRNAs (miRNAs) from maternal blood and amniotic fluid have been used as biomarkers for ventricular septal defect (VSD) diagnosis. However, whether circulating miRNAs are associated with fetal myocardium remains unknown.

Methods: Dimethadione (DMO) induced a VSD rat model. The miRNA expression profiles of the myocardium, amniotic fluid and maternal serum were analyzed. Differentially expressed microRNAs (DE-microRNAs) were verified by qRT–PCR. The target gene of miR-1-3p was confirmed by dual luciferase reporter assays. Expression of amniotic fluid-derived DE-microRNAs was verified in clinical samples.

Results: MiRNAs were differentially expressed in VSD fetal rats and might be involved in cardiomyocyte differentiation and apoptosis. MiR-1-3p, miR-1b and miR-293-5p were downregulated in the myocardium and upregulated in amniotic fluid/maternal serum. The expression of amniotic fluid-derived DE-microRNAs (miR-1-3p, miR-206 and miR-184) was verified in clinical samples. Dual luciferase reporter assays confirmed that miR-1-3p directly targeted SLC8A1/NCX1.

Conclusion: MiR-1-3p, miR-1b and miR-293-5p are downregulated in VSD myocardium and upregulated in circulation and may be released into circulation by cardiomyocytes. MiR-1-3p targets SLC8A1/NCX1 and participates in myocardial apoptosis. MiR-1-3p upregulation in circulation is a direct and powerful indicator of fetal VSD and is expected to serve as a prenatal VSD diagnostic marker.
RNA-Seq Comprehensive Analysis Reveals the Long Noncoding RNA Expression Profile and Coexpressed mRNA in Adult Degenerative Scoliosis
Authors: Shi Xin , Li Panpan , Wu Xiang , Wang Zhihua , Zhao Gang , Shu Jun
Published: August 2022

Objective: Owing to the intensification of the aging process worldwide, the prevalence of adult degenerative scoliosis (ADS) is increasing at an alarming rate. However, genomic research related to the etiology of ADS is rarely reported worldwide. Since long noncoding RNAs (lncRNAs) play a pivotal role in the progression of human diseases, this study aimed to investigate ADS-associated messenger RNAs (mRNAs) and lncRNAs by RNA sequencing (RNA-seq), as well as performed comprehensive bioinformatics analysis based on the lncRNA–mRNA coexpression network and protein–protein interaction (PPI) network.

Methods: Initially, six whole blood (WB) samples were obtained from three ADS and three nondegenerative lumbar trauma patients who underwent surgical operation for RNA-seq exploration to construct differential mRNA and lncRNA expression profiles. Subsequently, quantitative RT-PCR (qRT-PCR) was performed to validate three randomly selected differentially expressed mRNAs and lncRNAs derived from the nucleus pulposus (NP) tissue of 14 other subjects (seven ADS patients and seven nondegenerative lumbar trauma patients), respectively.

Results: A total of 1,651 upregulated and 1,524 downregulated mRNAs and 147 upregulated and 83 downregulated lncRNAs were screened out from the RNA-Seq data, which constructed coexpression networks to investigate their regulatory interactions further. GO gene function prediction revealed that lncRNA-targeted genes might play a vital role in ADS via participation in multiple biological processes such as the AMPK signaling pathway, lysosomes, and ubiquitin-mediated proteolysis, as well as cellular metabolic processes. Moreover, the expression levels of three selected lncRNAs and mRNAs were validated by qRT-PCR, respectively, demonstrating that the relative expression levels were consistent with the RNA-seq data. Notably, the dysregulated RNAs, AKT1, UBA52, PTPN12, and CLEC16A, were significantly differentially expressed in ADS WB samples and might serve as potentially regulated genes for research in the future.

Conclusions: This study provides the first insight into the altered transcriptome profile of long-stranded noncoding RNAs associated with ADS, which paves the way for further exploration of the clinical biomarkers and molecular regulatory mechanisms for this poorly understood degenerative disease. However, the detailed biological mechanisms underlying these candidate lncRNAs in ADS necessitate further elucidation in future studies.
CCAS: One-stop and comprehensive annotation system for individual cancer genome at multi-omics level
Authors: Zheng Xinchang , Zong Wenting , Li Zhaohua , Ma Yingke , Sun Yanling , Xiong Zhuang , Wu Song , Yang Fei , Zhao Wei , Bu Congfan , Du Zhenglin , Xiao Jingfa , Bao Yiming
Published: August 2022

Due to the explosion of cancer genome data and the urgent needs for cancer treatment, it is becoming increasingly important and necessary to easily and timely analyze and annotate cancer genomes. However, tumor heterogeneity is recognized as a serious barrier to annotate cancer genomes at the individual patient level. In addition, the interpretation and analysis of cancer multi-omics data rely heavily on existing database resources that are often located in different data centers or research institutions, which poses a huge challenge for data parsing. Here we present CCAS (Cancer genome Consensus Annotation System, https://ngdc.cncb.ac.cn/ccas/#/home), a one-stop and comprehensive annotation system for the individual patient at multi-omics level. CCAS integrates 20 widely recognized resources in the field to support data annotation of 10 categories of cancers covering 395 subtypes. Data from each resource are manually curated and standardized by using ontology frameworks. CCAS accepts data on single nucleotide variant/insertion or deletion, expression, copy number variation, and methylation level as input files to build a consensus annotation. Outputs are arranged in the forms of tables or figures and can be searched, sorted, and downloaded. Expanded panels with additional information are used for conciseness, and most figures are interactive to show additional information. Moreover, CCAS offers multidimensional annotation information, including mutation signature pattern, gene set enrichment analysis, pathways and clinical trial related information. These are helpful for intuitively understanding the molecular mechanisms of tumors and discovering key functional genes.
The epiphany derived from T-cell–inflamed profiles: Pan-cancer characterization of CD8A as a biomarker spanning clinical relevance, cancer prognosis, immunosuppressive environment, and treatment responses
Authors: Niu Decao , Chen Yifeng , Mi Hua , Mo Zengnan , Pang Guijian
Published: August 2022

CD8A encodes the CD8 alpha chain of αβT cells, which has been proposed as a quantifiable indicator for the assessment of CD8+ cytotoxic T lymphocytes (CTLs) recruitment or activity and a robust biomarker for anti-PD-1/PD-L1 therapy responses. Nonetheless, the lack of research into the role of CD8A in tumor microenvironment predisposes to limitations in its clinical utilization. In the presented study, multiple computational tools were used to investigate the roles of CD8A in the pan-cancer study, revealing its essential associations with tumor immune infiltration, immunosuppressive environment formation, cancer progression, and therapy responses. Based on the pan-cancer cohorts of the Cancer Genome Atlas (TCGA) database, our results demonstrated the distinctive CD8A expression patterns in cancer tissues and its close associations with the prognosis and disease stage of cancer. We then found that CD8A was correlated with six major immune cell types, and immunosuppressive cells in multiple cancer types. Besides, epigenetic modifications of CD8A were related to CTL levels and T cell dysfunctional states, thereby affecting survival outcomes of specific cancer types. After that, we explored the co-occurrence patterns of CD8A mutation, thus identifying RMND5A, RNF103-CHMP3, CHMP3, CD8B, MRPL35, MAT2A, RGPD1, RGPD2, REEP1, and ANAPC1P1 genes, which co-occurred mutations with CD8A, and are concomitantly implicated in the regulation of cancer-related pathways. Finally, we tested CD8A as a therapeutic biomarker for multiple antitumor agents’ or compounds’ responsiveness on various cancer cell lines and cancer cohorts. Our findings denoted the underlying mechanics of CD8A in reflecting the T-cell-inflamed profiles, which has potential as a biomarker in cancer diagnosis, prognosis, and therapeutic responses.
Ablation of NLRP3 inflammasome rewires MDSC function and promotes tumor regression
Authors: Papafragkos Iosif , Grigoriou Maria , Boon Louis , Kloetgen Andreas , Hatzioannou Aikaterini , Verginis Panayotis
Published: August 2022

Myeloid-derived suppressor cells (MDSCs) are myeloid precursors that exert potent immunosuppressive properties in cancer. Despite the extensive knowledge on mechanisms implicated in mobilization, recruitment, and function of MDSCs, their therapeutic targeting remains an unmet need in cancer immunotherapy, suggesting that unappreciated mechanisms of MDSC-mediated suppression exist. Herein, we demonstrate an important role of NLRP3 inflammasome in the functional properties of MDSCs in tumor-bearing hosts. Specifically, Nlrp3-deficient mice exhibited reduced tumor growth compared to wild-type animals and induction of robust anti-tumor immunity, accompanied by re-wiring of the MDSC compartment. Interestingly, both monocytic (M-MDSCs) and granulocytic (G-MDSCs) subsets from Nlrp3-/- mice displayed impaired suppressive activity and demonstrated significant transcriptomic alterations supporting the loss-of-function and associated with metabolic re-programming. Finally, therapeutic targeting of NLRP3 inhibited tumor development and re-programmed the MDSC compartment. These findings propose that targeting NLRP3 in MDSCs could overcome tumor-induced tolerance and may provide new checkpoints of cancer immunotherapy.
Emerging trends and hot spots in autoimmune thyroiditis research from 2000 to 2022: A bibliometric analysis
Authors: Li Qiuxian , Yang Wanyu , Li Jiashu , Shan Zhongyan
Published: August 2022

Background

Autoimmune thyroiditis (AIT) is the most common autoimmune disease, affecting 3-5% patients worldwide. In recent years, approximately 200 articles on AIT have been published annually in various journals. However, to date, no article has systematically assessed the related literature. Therefore, we conducted a bibliometric analysis on AIT to reveal the dynamic scientific developments and help researchers gain a global perspective while exploring the hotspots and development trends.

Methods

AIT-related articles and reviews from 2000 to 2022 were retrieved from the Web of Science Core Collection (WoSCC). The following search terms were used to extract document data: TS= (“ autoimmune thyroiditi*”) OR TI= (“chronic lymphocytic thyroiditi*”) OR TI=(hashimoto*) OR TI= (“postpartum thyroiditis”). We selected articles and reviews published in English from 2000 to 2022. Three software programs (VOSviewer, CiteSpace, Pajek) were employed to analyze the contribution and co-occurrence relationships of different references, countries/regions, institutes, journals and also keywords in this field.

Results

This scientometric study included 2290 English papers published in 723 journals with 39661 co-cited references from 561 institutions in 120 countries/regions. Based on the reference and keyword analysis, researchers used to focus on “apoptosis”, “insulin resistance”, “encephalopathy”, “IFN-γ” related to AIT during the past 20 years. However, with the development of other novel directions such as “papillary thyroid cancer” (2018-2022), “Vitamin D” (2016-2022), “oxidative stress” (2018-2022), “polymorphism” (2019-2022) and “association” (2020-2022), researchers are more interested in the relationship between papillary thyroid carcinoma and AIT, the effect of vitamin D supplementation on AIT, the oxidative stress in thyroid disease as well as the influence of polymorphism.

Conclusion

Bibliometric analysis of the outputs of AIT shows an overview of the current status of the research on AIT. The associations between papillary thyroid carcinoma, vitamin D, oxidative stress, polymorphism and AIT are major research frontiers. However, further research and collaboration are still required worldwide. Our findings can help researchers grasp the research status of AIT and quickly determine new directions for future research.
Influence of Indo-Pacific ocean currents on the distribution and demographic patterns of the brown seaweed Sargassum polycystum in tropical east Asia
Authors: Liang Yanshuo , Zhang Shuangshuang , Yan Changxiang , Draisma Stefano G. A. , Kantachumpoo Attachai , Li Zhao , Lin Yude , Zhu Jiang , Zhang Jie , Duan Delin
Published: August 2022

Long-distance drifting of seaweeds driven by ocean currents is an ideal model for exploring population-level genetic connectivity and phylogeographic structure. In the Indo-Pacific convergence region, we integrated phylogeographic and ocean current data and Lagrangian particle simulations to explore how the ocean currents contributed to the biogeographical patterns and population genetic connectivity of Sargassum polycystum. The oceanographic transport and direction of gene flow was in line with contemporary ocean currents. The S. polycystum geographical dispersal from glacial refugia homogenized the footprint of genetic divergence. The multidisciplinary intersection provides insights into the evolutionary history and biogeographic conservation of tropical seaweeds in the Indo-Pacific convergence region.
Transgenerational effects and temperature variation alter life history traits of the moon jellyfish
Authors: Chi Xupeng , Zhang Fang , Sun Song
Published: August 2022

Understanding the life history strategy of organisms is key to predicting their population dynamics. The population of scyphozoan jellyfish has displayed an increasing trend in recent decades, yet its life history strategy is not fully understood. To interpret the reproduction strategy of scyphozoan jellyfish from an evolutionary ecology perspective, we dissected 10 asexual generations of Aurelia coerulea polyps to investigate the relationships between transgenerational effects on their budding reproduction and strobilation. Our results reveal that a polyp’s average budding reproduction rate declined 32.82% through asexual generations within the experimental time. Furthermore, a longer culture duration counteracted the transgenerational effects on budding rates and strobilation afterward. Thus, this effort provides insight into the necessity of sexual reproduction in organisms involving a metagenic life cycle, i.e., to renew the asexual reproduction ability of a population. Besides this, we suggest taking note that it is necessary to know the “asexual age” of polyps when performing experimental studies and mathematical modeling to explore their population dynamics. Our results also present a valuable data set to interpret the evolution of the scyphozoan jellyfish’s life history strategy under multifactorial environments.
Differential effects of warming and acidification on chemosensory transmission and detection may strengthen non-consumptive effects of blue crab predators (Callinectes sapidus) on mud crab prey (Panopeus herbstii)
Authors: Draper Alex M. , Weissburg Marc J.
Published: August 2022

Predators control prey abundance and behavior, both of which strongly influence community dynamics. However, the relative importance of these predator effects may shift with climate change stressors, suggesting understanding the potential effects on these different processes is critical to predicting effects of climate change on community function. We investigated the effects of global warming and ocean acidification on the transmission and detection of chemical cues from blue crab predators (Callinectes sapidus) by mud crab prey (Panopeus herbstii). We measured mud crab feeding rates in the presence of blue crab predator cues, using either predator cues stressed in acidified conditions or mud crabs stressed in warmed and acidified conditions. Mud crabs consumed less food in the presence of predator cues, but acidifying the cues or subjecting mud crabs receiving the cues to acidified environment did not affect this antipredator response. Mud crabs in warmed conditions consumed significantly less food regardless of predator cue, but this effect was reversed in ambient conditions. Therefore, climate change may produce shifts in community regulation as warming potentially compromises consumptive effects of predators by reducing motor function, whereas non-consumptive effects mediated by sensory transmission and detection remain unaffected by acidification. Overall, warming may have stronger effects than acidification on community dynamics in oyster reefs as global temperatures continue to rise.
Plastic additive di(2-ethylhexyl)phthalate (DEHP) causes cell death and micronucleus induction on a bottlenose dolphin’s (Tursiops truncatus) in vitro-exposed skin cell line
Authors: Giovani Giada , Filippi Silvia , Molino Chiara , Peruffo Antonella , Centelleghe Cinzia , Meschini Roberta , Angeletti Dario
Published: August 2022

Marine plastic pollution is one of the most concerning worldwide environmental issues, and research is day by day demonstrating its adverse effects on marine ecosystems. Nevertheless, little is still known about the toxic potential on marine fauna of chemical additives released by plastic debris. Here we investigated the cyto- and genotoxicity of the most used plasticizer in plastic production, di(2-ethylhexyl)phthalate (DEHP), on a skin cell line (TT) derived from the bottlenose dolphin (Tursiops truncatus), a species particularly exposed to the accumulation of this lipophilic pollutant, being a coastal top predator rich in fatty subcutaneous tissues. Dolphin cell cultures were exposed to increasing DEHP doses (0.01–5 mM) to evaluate effects on cell viability, cell death, and induction of DNA damage. On the hypothesis that bottlenose dolphin cells show greater resistance to DEHP toxicity than terrestrial mammals, as already shown for other pollutants, the same parameters were analyzed on exposed Chinese hamster ovary (CHO) cell lines. Both MTT and Trypan Blue assays showed no significant decrease in dolphin’s cell viability after 24-h DEHP exposure. No induction of primary DNA damage was detected by the comet assay, whereas the cytokinesis-block micronucleus assay revealed significant micronuclei induction and inhibition of cell proliferation starting from the lowest DEHP doses. DEHP had similar but sharper and significant effects on cell viability in CHO cells, also causing a much greater induction of necrosis than that recorded on dolphin cells. For both cell lines, the lack of induction of primary DNA damage (i.e., strand breaks) together with the increase of micronuclei yield after DEHP treatment suggests an aneugenic effect of the phthalate, that is, the loss of entire chromosomes during cell division. Overall, the potential chromosome loss detected could constitute a threat for species of marine mammals constantly exposed to plastic marine litter.
Climate-driven changes to taste and aroma determining metabolites in an economically valuable portunid (Portunus armatus) have implications for future harvesting
Authors: Champion Curtis , Frank Damian , Taylor Matthew C. , Kaczmarska Kornelia , Piyasiri Udayasika , Broadhurst Matt K. , Shalders Tanika C. , Coleman Melinda A.
Published: August 2022

The effects of climate change on the distribution and biology of fisheries species have received substantial attention, but quantitative assessments of changes to taste and aroma determining compounds remain limited—despite sensory quality being a key driver of demand for most harvested species. Utilising the economically important blue swimmer crab (Portunus armatus), we tested the effects of temperature and salinity treatments aligned with near-future climate change projections on volatile and non-volatile sensory compounds that determine seafood flavour. Volatile compounds were analysed using solid phase microextraction and gas chromatography-mass spectrometry and non-volatiles were identified using liquid chromatography (mass spectrometry analysis). Multivariate analyses revealed that temperature, but not salinity, significantly affected the compositions of both volatile and non-volatile compounds in crab meat following a 30-day exposure period. Univariate analyses highlighted significant reductions in amino acids and amines associated with bitter and sweet organoleptic properties following exposure to elevated temperature. These results imply the potential for climate change to alter taste and aroma determining compounds in seafood, which could affect future harvesting priorities. Assessments of seafood sensory quality under climate change can produce valuable information to help predict shifts in fishing effort for harvested species that form the basis of important global fisheries.
Structural design and optimization of double-cross shape broadband absorption metamaterial based on CB-ABS
Authors: Chen Mengzhou , Wang Liuying , Liu Gu , Ge Chaoqun , Wang Long , Xu Kejun , Wang Weichao
Published: August 2022

This work presents a novel broadband double-cross shape metamaterial structure based on the Carbon Black-Acrylonitrile-Butadiene-Styrene (CB-ABS) composite material. The optimal metamaterial structure with the thickness of 7 mm shows a broadband absorption characteristic in the frequency range of 5.1–40 GHz. Additionally, the low volume filling fraction of the proposed metamaterial structure will be helpful to achieve lightweight broadband absorption performance. Meanwhile, the metamaterial structure can also display a wide-angle absorption performance from 0° to 55° for TE mode and 0°–75° for TM mode. Moreover, this research provides an effective and promising way for the practical application of the lightweight broadband and wide-angle microwave strong absorption metamaterial in the future.
Clarifying the chemical reactions of the weakening of adhesion between epoxy resin and aluminum by molecular dynamic simulation and experiment
Authors: Wang Jian , Wang Zhe , Yan Ningning , Han Zhiyun , Chang Yanan , Wang Jingrui , Li Qingmin
Published: August 2022

In molecular dynamics simulation, the cross-linked epoxy resin model can well simulate the performance of epoxy resin in actual use. We have established a cross-linked epoxy resin model and a composite model of epoxy resin and aluminum at the molecular level. Based on ReaxFF, the reaction molecular dynamics simulation of pyrolysis aging was carried out by Lammps. The aged epoxy resin is decomposed into H2, CO, H2O, CO2, CH4 and CH2O. Tensile simulation of aged epoxy resin and aluminum system was carried out, and the stress-strain curve was obtained. Compared with non-aging, the maximum stress is reduced by 25.77%. In order to verify the correctness of the simulation results, an epoxy resin with Diglycidyl ether of Bisphenol A (DGEBA) as the resin substrate and 4,4′- Diaminodiphenyl sulfone (44DDS) as the curing agent was prepared, which is coated on the surface of aluminum for curing. In order to explore the change of adhesion during aging, we put the samples in high-temperature vacuum drying oven at 160°C for thermal oxygen aging experiment. The state of epoxy resin at different aging time was studied by SEM, XPS and FTIR. The results showed that the adhesion decreased by 27.16% after aging. The chemical bond in epoxy resin was seriously damaged, the content of the O/C element increased from 15.95% to 22.76%, and the surface cracks of epoxy resin coating increased significantly. Through molecular dynamics simulation and thermal aging experiments, this paper reveals the reasons for the reduction of adhesion between epoxy resin and aluminum caused by thermal aging, which provided theoretical guidance for the aging and falling off of epoxy resin coating in gas-insulated transmission line.
Guts Imbalance Imbalances the Brain: A Review of Gut Microbiota Association With Neurological and Psychiatric Disorders
Authors: Mitrea Laura , Nemeş Silvia-Amalia , Szabo Katalin , Teleky Bernadette-Emőke , Vodnar Dan-Cristian
Published: August 2022

Over the last 10 years, there has been a growing interest in the relationship between gut microbiota, the brain, and neurologic-associated affections. As multiple preclinical and clinical research studies highlight gut microbiota’s potential to modulate the general state of health state, it goes without saying that gut microbiota plays a significant role in neurogenesis, mental and cognitive development, emotions, and behaviors, and in the progression of neuropsychiatric illnesses. Gut microbiota produces important biologic products that, through the gut-brain axis, are directly connected with the appearance and evolution of neurological and psychiatric disorders such as depression, anxiety, bipolar disorder, autism, schizophrenia, Parkinson’s disease, Alzheimer’s disease, dementia, multiple sclerosis, and epilepsy. This study reviews recent research on the link between gut microbiota and the brain, and microbiome’s role in shaping the development of the most common neurological and psychiatric illnesses. Moreover, special attention is paid to the use of probiotic formulations as a potential non-invasive therapeutic opportunity for prevention and management of neuropsychiatric-associated affections.
The radiographic assessment of lung edema score of lung edema severity correlates with inflammatory parameters in patients with coronavirus disease 2019—Potential new admission biomarkers to predict coronavirus disease 2019 worsening
Authors: Marques Patrice , Fernandez-Presa Lucia , Carretero Aitor , Gómez-Cabrera Maria-Carmen , Viña José , Signes-Costa Jaime , Sanz Maria-Jesus
Published: August 2022

Background

Coronavirus disease 2019 (COVID-19) has placed enormous pressure on intensive care units (ICUs) and on healthcare systems in general. A deeper understanding of the pathophysiology of the most severe forms of COVID-19 would help guide the development of more effective interventions. Herein, we characterized the inflammatory state of patients with COVID-19 of varying degrees of severity to identify admission biomarkers for predicting COVID-19 worsening.

Design

Admission blood samples were obtained from 78 patients with COVID-19. Radiographic assessment of lung edema (RALE) scoring was calculated by imaging. Platelet and leukocyte counts were measured by flow cytometry, and plasma levels of C-reactive protein were assessed by immunoturbidimetry, and interleukin (IL)-8/CXCL8, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and monocyte chemoattractant protein-1 (MCP-1/CCL2) levels by enzyme-linked immunosorbent assay (ELISA).

Results

The RALE score correlated with several admission hemogram (platelets, neutrophils, and lymphocytes) and inflammatory (IL-8/CXCL8, MCP-1/CCL2, IL-10, and C-reactive protein) parameters. COVID-19 worsening, based on the need for oxygen (Δoxygen supply) during hospitalization, correlated negatively with admission lymphocyte counts but positively with neutrophil-to-lymphocyte ratio and with plasma levels of the inflammatory parameters correlating with RALE score.

Conclusion

Our data indicate a correlation between the RALE score and Δoxygen supply and admission inflammatory status. The identification of a panel of biomarkers that reflect COVID severity might be useful to predict disease worsening during hospitalization and to guide clinical management of COVID-19-related complications. Finally, therapies targeting IL-8/CXCL8- or IL-10 activity may offer therapeutic approaches in COVID-19 treatment.
Multi-gene panel testing increases germline predisposing mutations’ detection in a cohort of breast/ovarian cancer patients from Southern Italy
Authors: Nunziato Marcella , Di Maggio Federica , Pensabene Matilde , Esposito Maria Valeria , Starnone Flavio , De Angelis Carmine , Calabrese Alessandra , D’Aiuto Massimiliano , Botti Gerardo , De Placido Sabino , D’Argenio Valeria , Salvatore Francesco
Published: August 2022

Breast cancer is the most common neoplasia in females worldwide, about 10% being hereditary/familial and due to DNA variants in cancer-predisposing genes, such as the highly penetrant BRCA1/BRCA2 genes. However, their variants explain up to 25% of the suspected hereditary/familial cases. The availability of NGS methodologies has prompted research in this field. With the aim to improve the diagnostic sensitivity of molecular testing, a custom designed panel of 44 genes, including also non-coding regions and 5’ and 3’ UTR regions, was set up. Here, are reported the results obtained in a cohort of 64 patients, including also few males, from Southern Italy. All patients had a positive personal and/or familial history for breast and other cancers, but tested negative to routine BRCA analysis. After obtaining their written informed consent, a genomic DNA sample/patient was used to obtain an enriched DNA library, then analyzed by NGS. Sequencing data analysis allowed the identification of pathogenic variants in 12 of tested patients (19%). Interestingly, MUTYH was the most frequently altered gene, followed by RNASEL, ATM, MSH6, MRE11A, and PALB2 genes. The reported resultsreinforce the need for enlarged molecular testing beyond BRCA genes, at least in patients with a personal and familial history, strongly suggestive for a hereditary/familial form. This gives also a hint to pursue more specific precision oncology therapy.
Current evidence on the role of lipid lowering drugs in the treatment of psoriasis
Authors: Wang Jiao , Zhang Shuo , Xing Meng , Hong Seokgyeong , Liu Liu , Ding Xiao-Jie , Sun Xiao-ying , Luo Ying , Wang Chun-xiao , Zhang Miao , Li Bin , Li Xin
Published: August 2022

Background

Abnormal lipid distribution is observed in patients with psoriasis, which increases their risk for atherosclerosis. Lipid-lowering drugs have a certain curative effect in the treatment of psoriasis, but there is no relevant evidence-based medical evaluation.

Objective

The purpose of this systematic evaluation was to assess the efficacy, safety, and potential mechanisms of action of lipid-lowering drugs for the treatment of psoriasis.

Methods

The PubMed, Embase, Cochrane Central Register of Controlled Trials, Clinical Trial, Chinese National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database, and Wanfang Database were searched for relevant articles from inception to 31 December 2021. The RevMan 5.3 and Cochrane risk-of-bias tool were used for data analysis and risk assessment, respectively. The psoriasis area and severity index (PASI) score is the primary outcome indicator in clinical studies. Based on preclinical studies, we elucidated and mapped the action mechanisms of lipid-lowering drugs in the treatment of psoriasis.

Results

The study included eight randomized controlled studies, four single-arm studies, and four in vitro studies. The results showed that lipid-lowering drugs, particularly statins, administered both orally and topically, can significantly improve psoriatic skin lesions and reduce the PASI scores [standardized mean difference, (SMD): −0.94; 95% CI: [−1.58, −0.31]; p = 0.004]. Oral statins performed best at week eight (SMD: −0.92; 95% CI: [−1.39, −0.44]; p = 0.0001). The mechanism of lipid-lowering drugs in the treatment of psoriasis may be related to the inhibition of keratinocyte proliferation, inhibition of CCL20–CCR6 interaction, and reduction in the levels of inflammatory factors.

Limitations

There are few studies on lipid-lowering drugs and psoriasis, and their small sample sizes may render the evidence unconvincing.

Conclusion

The present findings suggest that lipid-lowering drugs are relieving symptoms in psoriasis. Lipid-lowering drugs, particularly statins, can be used to treat psoriasis with good efficacy and few side effects.
What is the appropriate treatment strategy for cryptogenic multifocal ulcerative stenosing enteritis? A single-center experience from China
Authors: Yan Pengguang , Li Kemin , Cao Yang , Wu Dong , Li Ji , Qian Jiaming , Zhou Weixun , Li Jingnan
Published: August 2022

Background

There are few reports on standard treatment and long-term prognosis in patients with cryptogenic multifocal ulcerative stenosing enteritis (CMUSE), particularly in patients in whom remission could not be induced by steroids. The aim of this study was to evaluate the treatment response and progression-free periods of patients with CMUSE and to identify the factors predictive of steroid resistance.

Methods

This was a retrospective cohort study that included 25 patients with clinically confirmed CMUSE between 1984 and 2021 from the enteropathy clinic of a tertiary care center. For statistical analyses, chi-square test or Fisher’s exact test were used for categorical variables. Survival curves were plotted using the Kaplan–Meier method.

Results

The overall median progression-free period was 48 months (range, 1–108 months) after comprehensive therapy, and initial manifestation with severe bleeding rather than ileus was associated with the long-term efficacy. Patients with steroid resistance (N = 10, 55.6%) had poor prognosis, and non-responders had more favorable baseline clinical characteristics, with a higher percentage of female patients (60% vs. 12.5%), earlier disease onset (26.5 years vs. 39 years), rapid progression (42 vs. 108 months), severe anemia (80% vs. 50%), and hypoalbuminemia (50% vs. 0%), in accord with lymphangiectasia or angioectasia identified in pathology.

Conclusion

There is no guaranteed treatment strategy in the maintenance of long-term clinical remission for CMUSE patients, particularly in whom with steroid resistance. Female patients with early symptoms onset, severe gastrointestinal hemorrhage and hypoalbuminemia seem to have poor long-term prognosis.
GSA Central—A web platform to perform, learn, and discuss gene set analysis
Authors: Huang Xiaowei , Lu Xuanyi , Xie Chengshu , Jauhari Shaurya , Xie Zihong , Mei Songqing , Mora Antonio
Published: August 2022

Gene Set Analysis (GSA) is one of the most commonly used strategies to analyze omics data. Hundreds of GSA-related papers have been published, giving birth to a GSA field in Bioinformatics studies. However, as the field grows, it is becoming more difficult to obtain a clear view of all available methods, resources, and their quality. In this paper, we introduce a web platform called “GSA Central” which, as its name indicates, acts as a focal point to centralize GSA information and tools useful to beginners, average users, and experts in the GSA field. “GSA Central” contains five different resources: A Galaxy instance containing GSA tools (“Galaxy-GSA”), a portal to educational material (“GSA Classroom”), a comprehensive database of articles (“GSARefDB”), a set of benchmarking tools (“GSA BenchmarKING”), and a blog (“GSA Blog”). We expect that “GSA Central” will become a useful resource for users looking for introductory learning, state-of-the-art updates, method/tool selection guidelines and insights, tool usage, tool integration under a Galaxy environment, tool design, and tool validation/benchmarking. Moreover, we expect this kind of platform to become an example of a “thematic platform” containing all the resources that people in the field might need, an approach that could be extended to other bioinformatics topics or scientific fields.
Effect of arbuscular mycorrhizal fungi and phosphorus on drought-induced oxidative stress and 14-3-3 proteins gene expression of Populus cathayana
Authors: Han Yanyan , Zhang Wenrui , Xu Tingying , Tang Ming
Published: August 2022

The application of arbuscular mycorrhizal fungi (AM fungi) and phosphorus (P) can improve plant growth under drought stress by upregulating the antioxidant system and osmotic accumulation. The 14-3-3 protein can respond to different abiotic stresses such as low P and drought. The purpose of this experiment was to study the effects of AM fungi (Rhizophagus intraradices) inoculation on reactive oxygen species (ROS) homeostasis, P metabolism, and 14-3-3 gene expression of Populus cathayana at different P levels and drought stress (WW: well-watered and WD: water deficit). Under WD conditions, AM fungi inoculation significantly increased the P content in leaves and roots, but the benefit in roots is limited by the level of P addition, and the roots may have more alkaline phosphatase and phytase under P stress, and these activities in the rhizosphere soil inoculated with AM fungi were stronger. Under WD conditions, the activities of catalase (leaf and root) and peroxidase (root) inoculated with AM fungi were significantly higher than those without inoculation and decreased with P addition. 14-3-3 genes, PcGRF10 and PcGRF11, have a positive correlation with the antioxidant system, osmotic regulation, and P metabolism, which may be more significant after inoculation with AM fungi. Our results provide new insights into the mechanism of ROS homeostasis and P metabolism in mycorrhizal plants under drought stress.
Mammalian Resilience Revealed by a Comparison of Human Diseases and Mouse Models Associated With DNA Helicase Deficiencies
Authors: Kohzaki Masaoki
Published: August 2022

Maintaining genomic integrity is critical for sustaining individual animals and passing on the genome to subsequent generations. Several enzymes, such as DNA helicases and DNA polymerases, are involved in maintaining genomic integrity by unwinding and synthesizing the genome, respectively. Indeed, several human diseases that arise caused by deficiencies in these enzymes have long been known. In this review, the author presents the DNA helicases associated with human diseases discovered to date using recent analyses, including exome sequences. Since several mouse models that reflect these human diseases have been developed and reported, this study also summarizes the current knowledge regarding the outcomes of DNA helicase deficiencies in humans and mice and discusses possible mechanisms by which DNA helicases maintain genomic integrity in mammals. It also highlights specific diseases that demonstrate mammalian resilience, in which, despite the presence of genomic instability, patients and mouse models have lifespans comparable to those of the general population if they do not develop cancers; finally, this study discusses future directions for therapeutic applications in humans that can be explored using these mouse models.
Host cell stress response as a predictor of COVID-19 infectivity and disease progression
Authors: Caillet Celine , Stofberg Melissa Louise , Muleya Victor , Shonhai Addmore , Zininga Tawanda
Published: August 2022

The coronavirus disease (COVID-19) caused by a coronavirus identified in December 2019 has caused a global pandemic. COVID-19 was declared a pandemic in March 2020 and has led to more than 6.3 million deaths. The pandemic has disrupted world travel, economies, and lifestyles worldwide. Although vaccination has been an effective tool to reduce the severity and spread of the disease there is a need for more concerted approaches to fighting the disease. COVID-19 is characterised as a severe acute respiratory syndrome . The severity of the disease is associated with a battery of comorbidities such as cardiovascular diseases, cancer, chronic lung disease, and renal disease. These underlying diseases are associated with general cellular stress. Thus, COVID-19 exacerbates outcomes of the underlying conditions. Consequently, coronavirus infection and the various underlying conditions converge to present a combined strain on the cellular response. While the host response to the stress is primarily intended to be of benefit, the outcomes are occasionally unpredictable because the cellular stress response is a function of complex factors. This review discusses the role of the host stress response as a convergent point for COVID-19 and several non-communicable diseases. We further discuss the merits of targeting the host stress response to manage the clinical outcomes of COVID-19.
Ferroptosis-related gene signature predicts the clinical outcome in pediatric acute myeloid leukemia patients and refines the 2017 ELN classification system
Authors: Tao Yu , Wei Li , You Hua
Published: August 2022

Background: The prognostic roles of ferroptosis-related mRNAs (FG) and lncRNAs (FL) in pediatric acute myeloid leukemia (P-AML) patients remain unclear.

Methods: RNA-seq and clinical data of P-AML patients were downloaded from the TARGET project. Cox and LASSO regression analyses were performed to identify FG, FL, and FGL (combination of FG and FL) prognostic models, and their performances were compared. Tumor microenvironment, functional enrichment, mutation landscape, and anticancer drug sensitivity were analyzed.

Results: An FGL model of 22 ferroptosis-related signatures was identified as an independent parameter, and it showed performance better than FG, FL, and four additional public prognostic models. The FGL model divided patients in the discovery cohort (N = 145), validation cohort (N = 111), combination cohort (N = 256), and intermediate-risk group (N = 103) defined by the 2017 European LeukemiaNet (ELN) classification system into two groups with distinct survival. The high-risk group was enriched in apoptosis, hypoxia, TNFA signaling via NFKB, reactive oxygen species pathway, oxidative phosphorylation, and p53 pathway and associated with low immunity, while patients in the low-risk group may benefit from anti-TIM3 antibodies. In addition, patients within the FGL high-risk group might benefit from treatment using SB505124_1194 and JAK_8517_1739.

Conclusion: Our established FGL model may refine and provide a reference for clinical prognosis judgment and immunotherapies for P-AML patients.
Pyroptosis in sepsis: Comprehensive analysis of research hotspots and core genes in 2022
Authors: Xia Demeng , Wang Sheng , Yao Renqi , Han Yuexue , Zheng Liyu , He Pengyi , Liu Ying , Yang Lu
Published: August 2022

Sepsis, a life-threatening disease caused by dysregulated host response to infection, is a major public health problem with a high mortality and morbidity rate. Pyroptosis is a new type of programmed cell death discovered in recent years, which has been proved to play an important role in sepsis. Nevertheless, there is no comprehensive report, which can help researchers get a quick overview and find research hotspots. Thus, we aimed to identify the study status and knowledge structures of pyroptosis in sepsis and summarize the key mechanism of pyroptosis in sepsis. The data were retrieved and downloaded from the WOS database. Software such as VOSviewer was used to analyze these publications. Key genes were picked out by using (https://www.genecards.org) and (http://www.bioinformatics.com). Then, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to performed these key genes. From 2011 to 2021, a total of 299 papers met the search criteria, and the global interest in pyroptosis in sepsis measured by the value of (RRI) has started to increase since 2016. China ranked first in the number of publications, followed by the USA. The journal Frontiers in Immunology published the most relevant articles. Through keyword co-occurrence analysis, the high-frequency subject terms were divided into three clusters like “animal research”, “cell research,” and “molecular research” clusters. “mir,” “aki,” “monocyte,” and “neutrophil” were the newest keywords that may be the hotspot. In addition, a total of 15 genes were identified as hub genes. TNF, IL-1β, AKT1, CASP1, and STAT3 were highly expressed in lung tissues, thymus tissues, and lymphocytes. KEGG analysis indicated that pyroptosis may play a vital role in sepsis via the NOD, PI3K/AKT, and MAPK/JNK pathways. Through the quantitative analysis of the literature on pyroptosis in sepsis, we revealed the current status and hotspots of research in this field and provided some guidance for further studies.
Structure based design of effective HtpG-derived vaccine antigens against M. tuberculosis
Authors: Ruggiero Alessia , Choi Han-Gyu , Barra Giovanni , Squeglia Flavia , Back Young Woo , Kim Hwa-Jung , Berisio Rita
Published: August 2022

Vaccine development against Tuberculosis is a strong need, given the low efficacy of the sole vaccine hitherto used, the Bacillus Calmette–Guérin (BCG) vaccine. The chaperone-like protein HtpGMtb of M. tuberculosis is a large dimeric and multi-domain protein with promising antigenic properties. We here used biophysical and biochemical studies to improve our understanding of the structural basis of HtpGMtb functional role and immunogenicity, a precious information to engineer improved antigens. We showed that HtpGMtb is a dimeric nucleotide-binding protein and identified the dimerisation interface on the C-terminal domain of the protein. We also showed that the most immunoreactive regions of the molecule are located on the C-terminal and middle domains of the protein, whereas no role is played by the catalytic N-terminal domain in the elicitation of the immune response. Based on these observations, we experimentally validated our predictions in mice, using a plethora of immunological assays. As an outcome, we designed vaccine antigens with enhanced biophysical properties and ease of production, albeit conserved or enhanced antigenic properties. Our results prove the efficacy of structural vaccinology approaches in improving our understanding of the structural basis of immunogenicity, a precious information to engineer more stable, homogeneous, efficiently produced, and effective vaccine antigens.
Effectiveness of home-based, non-exercise interventions for dementia: A systematic review
Authors: Tan Davynn Gim Hoon , Boo Belinda Melody Bernadette , Chong Cheyenne Shuen , Tan Megan Michelle Ling-Li , Wong Boon-Seng
Published: August 2022

Introduction

Dementia is a neurodegenerative condition characterized by cognitive decline and increased functional dependency. With most persons living with dementia (PLWDs) residing at home, home-based interventions provide a convenient and individualized alternative for person-centered care. Most of the evidence focused on specific interventions or exercise-based activities; there remains a gap in understanding the impacts of a broader range of non-exercise interventions on PLWDs and their caregivers. This review aimed to understand the impacts of home-based, non-exercise interventions on the behavioral, functional, cognitive, and mood outcomes of PLWDs, and their caregiver's quality of life (QoL), burden and mood.

Methods

Search for studies published up to June 2020 was conducted on CINAHL, PsycArticles, PubMed, SAGE Journals, Science Direct, and Web of Science. A search was also done manually based on the bibliographies of selected articles. The inclusion criteria for the systematic review were: (i) participants with a medical diagnosis of dementia, (ii) participants who resided at own home, (iii) intervention in the home setting, (iv) investigate interventions other than physical exercise, (v) randomized controlled trials (RCTs) or quasi-experimental studies, and (vi) full-text study published in English and in a peer-reviewed journal.

Results and discussion

Eighteen studies consisting of 14 RCTs and 4 quasi-experimental studies were included. Interventions included were occupational therapy, cognitive rehabilitation, tailored activity program, cognitive stimulation therapy, personalized reminiscence, music therapy, reality orientation, biobehavioral and multicomponent interventions. Results were mixed, but important intervention features were highlighted. Personalized activities for PLWDs that are aligned to their interest and ability appeared to contribute to intervention effectiveness especially in reducing behavioral symptoms and improving functional status. Involvement of caregivers in interventions is another feature of effective interventions for both the PLWDs and the caregivers' QoL, provided it is not deemed demanding or challenging to the caregivers. The inclusion of caregiver's education was effective in reducing caregivers' burden, particularly when the interventions improved the PLWD's functional status.