bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolism-related long non-coding RNA in the stomach cancer associated with 11 AMMLs predictive nomograms for OS in STAD
Authors: Jin Wenjian , Ou Kongbo , Li Yuanyuan , Liu Wensong , Zhao Min 
Published: March 2023

Background: The metabolic processes involving amino acids are intimately linked to the onset and progression of cancer. Long non-coding RNAs (LncRNAs) perform an indispensable function in the modulation of metabolic processes as well as the advancement of tumors. Non-etheless, research into the role that amino acid metabolism-related LncRNAs (AMMLs) might play in predicting the prognosis of stomach adenocarcinoma (STAD) has not been done. Therefore, This study sought to design a model for AMMLs to predict STAD-related prognosis and elucidate their immune properties and molecular mechanisms.Methods: The STAD RNA-seq data in the TCGA-STAD dataset were randomized into the training and validation groups in a 1:1 ratio, and models were constructed and validated respectively. In the molecular signature database, This study screened for genes involved in amino acid metabolism. AMMLs were obtained by Pearson’s correlation analysis, and predictive risk characteristics were established using least absolute shrinkage and selection operator (LASSO) regression, univariate Cox analysis, and multivariate Cox analysis. Subsequently, the immune and molecular profiles of high- and low-risk patients and the benefit of the drug were examined.Results: Eleven AMMLs (LINC01697, LINC00460, LINC00592, MIR548XHG, LINC02728, RBAKDN, LINCOG, LINC00449, LINC01819, and UBE2R2-AS1) were used to develop a prognostic model. Moreover, high-risk individuals had worse overall survival (OS) than low-risk patients in the validation and comprehensive groups. A high-risk score was associated with cancer metastasis as well as angiogenic pathways and high infiltration of tumor-associated fibroblasts, Treg cells, and M2 macrophages; suppressed immune responses; and a more aggressive phenotype.Conclusion: This study identified a risk signal associated with 11 AMMLs and established predictive nomograms for OS in STAD. These findings will help us personalize treatment for gastric cancer patients.
Comparative genomics analysis of endangered wild Egyptian Moringa peregrina (Forssk.) Fiori plastome, with implications for the evolution of Brassicales order
Authors: AbdAlla Heba A. M. , Wanga Vincent Okelo , Mkala Elijah Mbandi , Amenu Sara Getachew , Amar Mohamed Hamdy , Chen Lingyun , Wang Qing-Feng 
Published: March 2023

Moringa is a mono-genus belonging to the Moringaceae family, which includes 13 species. Among them, Moringa peregrina is plant species native to the Arabian Peninsula, Southern Sinai in Egypt, and the Horn of Africa, and comprehensive studies on its nutritional, industrial, and medicinal values have been performed. Herein, we sequenced and analyzed the initial complete chloroplast genome of Moringa peregrina. Concurrently, we analyzed the new chloroplast genome along with 25 chloroplast genomes related to species representing eight families in the Brassicales order. The results indicate that the plastome sequence of M. peregrina consists of 131 genes, with an average GC content of 39.23%. There is a disparity in the IR regions of the 26 species ranging from 25,804 to 31,477 bp. Plastome structural variations generated 20 hotspot regions that could be considered prospective DNA barcode locations in the Brassicales order. Tandem repeats and SSR structures are reported as significant evidence of structural variations among the 26 tested specimens. Furthermore, selective pressure analysis was performed to estimate the substitution rate within the Moringaceae family, which revealing that the ndhA and accD genes are under positive selective pressure. The phylogenetic analysis of the Brassicales order produced an accurate monophyletic annotation cluster of the Moringaceae and Capparaceae species, offering unambiguous identification without overlapping groups between M. oleifera and M. peregrina, which are genetically strongly associated. Divergence time estimation suggests that the two Moringa species recently diversified, 0.467 Ma. Our findings highlight the first complete plastome of the Egyptian wild-type of M. peregrina, which can be used for determining plastome phylogenetic relationships and systematic evolution history within studies on the Moringaceae family.
Chronic CD27-CD70 costimulation promotes type 1-specific polarization of effector Tregs
Authors: Bowakim-Anta Natalia , Acolty Valérie , Azouz Abdulkader , Yagita Hideo , Leo Oberdan , Goriely Stanislas , Oldenhove Guillaume , Moser Muriel 
Published: March 2023

IntroductionMost T lymphocytes, including regulatory T cells, express the CD27 costimulatory receptor in steady state conditions. There is evidence that CD27 engagement on conventional T lymphocytes favors the development of Th1 and cytotoxic responses in mice and humans, but the impact on the regulatory lineage is unknown.MethodsIn this report, we examined the effect of constitutive CD27 engagement on both regulatory and conventional CD4+ T cells in vivo, in the absence of intentional antigenic stimulation.ResultsOur data show that both T cell subsets polarize into type 1 Tconvs or Tregs, characterized by cell activation, cytokine production, response to IFN-γ and CXCR3-dependent migration to inflammatory sites. Transfer experiments suggest that CD27 engagement triggers Treg activation in a cell autonomous fashion.ConclusionWe conclude that CD27 may regulate the development of Th1 immunity in peripheral tissues as well as the subsequent switch of the effector response into long-term memory.
Resolvin D1/N-formyl peptide receptor 2 ameliorates paclitaxel-induced neuropathic pain through the activation of IL-10/Nrf2/HO-1 pathway in mice
Authors: Su Cun-Jin , Zhang Jiang-Tao , Zhao Feng-Lun , Xu De-Lai , Pan Jie , Liu Tong 
Published: March 2023

IntroductionPaclitaxel is a chemotherapy drug that is commonly used to treat cancer, but it can cause paclitaxel-induced neuropathic pain (PINP) as a side effect. Resolvin D1 (RvD1) has been shown to be effective in promoting the resolution of inflammation and chronic pain. In this study, we evaluated the effects of RvD1 on PINP and its underlying mechanisms in mice.MethodsBehavioral analysis was used to assess the establishment of the PINP mouse model and to test the effects of RvD1 or other formulations on mouse pain behavior. Quantitative real-time polymerase chain reaction analysis was employed to detect the impact of RvD1 on 12/15 Lox, FPR2, and neuroinflammation in PTX-induced DRG neurons. Western blot analysis was used to examine the effects of RvD1 on FPR2, Nrf2, and HO-1 expression in DRG induced by PTX. TUNEL staining was used to detect the apoptosis of DRG neurons induced by BMDM conditioned medium. H2DCF-DA staining was used to detect the reactive oxygen species level of DRG neurons in the presence of PTX or RvD1+PTX treated BMDMs CM.ResultsExpression of 12/15-Lox was decreased in the sciatic nerve and DRG of mice with PINP, suggesting a potential involvement of RvD1 in the resolution of PINP. Intraperitoneal injection of RvD1 promoted pain resolution of PINP in mice. Intrathecal injection of PTX-treated BMDMs induced mechanical pain hypersensitivity in naïve mice, while pretreatment of RvD1 in BMDMs prevented it. Macrophage infiltration increased in the DRGs of PINP mice, but it was not affected by RvD1 treatment. RvD1 increased IL-10 expression in the DRGs and macrophages, while IL-10 neutralizing antibody abolished the analgesic effect of RvD1 on PINP. The effects of RvD1 in promoting IL-10 production were also inhibited by N-formyl peptide receptor 2 (FPR2) antagonist. The primary cultured DRG neurons apoptosis increased after stimulation with condition medium of PTX-treated BMDMs, but decreased after pretreatment with RvD1 in BMDMs. Finally, Nrf2-HO1 signaling was additionally activated in DRG neurons after stimulation with condition medium of RvD1+PTX-treated BMDMs, but these effects were abolished by FPR2 blocker or IL-10 neutralizing antibody.DiscussionIn conclusion, this study provides evidence that RvD1 may be a potential therapeutic strategy for the clinical treatment of PINP. RvD1/FPR2 upregulates IL-10 in macrophages under PINP condition, and then IL-10 activates the Nrf2- HO1 pathway in DRG neurons, relieve neuronal damage and PINP.
Immunogenicity, efficacy, and safety of human papillomavirus vaccine: Data from China
Authors: Li Mingzhu , Zhao Chao , Zhao Yun , Li Jingran , Wei Lihui 
Published: March 2023

The incidence rate and mortality rate of cervical cancer have steadily increased in young women in China. Therefore, it is critical to improve HPV vaccination rates, particularly for the younger population. There are currently five types of prophylactic vaccines in China: bivalent HPV vaccine (AS04-HPV-16/18), quadrivalent HPV vaccine, 9-valent HPV vaccine, homemade Escherichia coli-produced HPV bivalent vaccine, and Pichia pastoris produced HPV bivalent vaccine. All these five HPV vaccines have completed relevant clinical trials in China, and have been proven to be generally well-tolerated and immunogenic, efficacious against persistent HPV-related infections and genital precancerous lesions (data for 9-valent HPV vaccine is absent), and have demonstrated acceptable safety profiles, as previously shown in global studies. Given that the HPV vaccination rate in China is still very low, additional HPV vaccine coverage is needed to reduce the incidence and mortality rates of cervical cancer.
Modulation of low-dose ozone and LPS exposed acute mouse lung inflammation by IF1 mediated ATP hydrolysis inhibitor, BTB06584
Authors: Singh Pahul , Aulakh Gurpreet Kaur 
Published: March 2023

Ozone and bacterial lipopolysaccharide (LPS) are common air pollutants that are related to high hospital admissions due to airway hyperreactivity and increased susceptibility to infections, especially in children, older population and individuals with underlying conditions. We modeled acute lung inflammation (ALI) by exposing 6-8 week old male mice to 0.005 ppm ozone for 2 h followed by 50 μg of intranasal LPS. We compared the immunomodulatory effects of single dose pre-treatment with CD61 blocking antibody (clone 2C9.G2), ATPase inhibitor BTB06584 against propranolol as the immune-stimulant and dexamethasone as the immune-suppressant in the ALI model. Ozone and LPS exposure induced lung neutrophil and eosinophil recruitment as measured by respective peroxidase (MPO and EPX) assays, systemic leukopenia, increased levels of lung vascular neutrophil regulatory chemokines such as CXCL5, SDF-1, CXCL13 and a decrease in immune-regulatory chemokines such as BAL IL-10 and CCL27. While CD61 blocking antibody and BTB06584 produced maximum increase in BAL leukocyte counts, protein content and BAL chemokines, these treatments induced moderate increase in lung MPO and EPX content. CD61 blocking antibody induced maximal BAL cell death, a markedly punctate distribution of NK1.1, CX3CR1, CD61. BTB06584 preserved BAL cell viability with cytosolic and membrane distribution of Gr1 and CX3CR1. Propranolol attenuated BAL protein, protected against BAL cell death, induced polarized distribution of NK1.1, CX3CR1 and CD61 but presented with high lung EPX. Dexamethasone induced sparse cell membrane distribution of CX3CR1 and CD61 on BAL cells and displayed very low lung MPO and EPX levels despite highest levels of BAL chemokines. Our study unravels ATPase inhibitor IF1 as a novel drug target for lung injury.
P2RX7 signaling drives the differentiation of Th1 cells through metabolic reprogramming for aerobic glycolysis
Authors: Salles Érika Machado de , Raeder Paulo Lisboa , Angeli Claudia Blanes , Santiago Verônica Feijoli , de Souza Cristiane Naffah , Ramalho Theresa , Câmara Niels Olsen Saraiva , Palmisano Giuseppe , Álvarez José Maria , D'Império Lima Maria Regina 
Published: March 2023

IntroductionThis study provides evidence of how Th1 cell metabolism is modulated by the purinergic receptor P2X7 (P2RX7), a cation cannel activated by high extracellular concentrations of adenosine triphosphate (ATP).MethodsIn vivo analysis was performed in the Plasmodium chabaudi model of malaria in view of the great relevance of this infectious disease for human health, as well as the availability of data concerning Th1/Tfh differentiation.ResultsWe show that P2RX7 induces T-bet expression and aerobic glycolysis in splenic CD4+ T cells that respond to malaria, at a time prior to Th1/Tfh polarization. Cell-intrinsic P2RX7 signaling sustains the glycolytic pathway and causes bioenergetic mitochondrial stress in activated CD4+ T cells. We also show in vitro the phenotypic similarities of Th1-conditioned CD4+ T cells that do not express P2RX7 and those in which the glycolytic pathway is pharmacologically inhibited. In addition, in vitro ATP synthase blockade and the consequent inhibition of oxidative phosphorylation, which drives cellular metabolism for aerobic glycolysis, is sufficient to promote rapid CD4+ T cell proliferation and polarization to the Th1 profile in the absence of P2RX7.ConclusionThese data demonstrate that P2RX7-mediated metabolic reprograming for aerobic glycolysis is a key event for Th1 differentiation and suggest that ATP synthase inhibition is a downstream effect of P2RX7 signaling that potentiates the Th1 response.
Integrated pan-cancer analysis and experimental verification of the roles of tropomyosin 4 in gastric cancer
Authors: Guo Qijing , Zhao Linglin , Yan Nan , Li Yan , Guo Cuiping , Dang Shengyan , Shen Xianliang , Han Jianfang , Luo Yushuang 
Published: March 2023

ObjectiveTo investigate the function of tropomyosin 4 (TPM4) using pan-cancer data, especially in gastric cancer (GC), using comprehensive bioinformatics analysis and molecular experiments.MethodsWe used UCSC Xena, The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), TIMER2.0, GEPIA, cBioPortal, Xiantao tool, and UALCAN websites and databases for the extraction of pan-cancer data on TPM4. TPM4 expression was investigated with respect to prognosis, genetic alterations, epigenetic alterations, and immune infiltration. RNA22, miRWalk, miRDB, Starbase 2.0, and Cytoscape were used for identifying and constructing the regulatory networks of lncRNAs, miRNAs, and TPM4 in GC. Data from GSCALite, drug bank databases, and Connectivity Map (CMap) were used to analyze the sensitivity of drugs dependent on TPM4 expression. Gene Ontology (GO), enrichment analyses of the Kyoto Encyclopedia of Genes and Genomes (KEGG), wound healing assays, and (Matrigel) transwell experiments were used to investigate the biological functions of TPM4 in GC.ResultThe findings of the comprehensive pan-cancer analysis revealed that TPM4 has a certain diagnostic and prognosis value in most cancers. Alterations in the expression of TPM4, including duplications and deep mutations, and epigenetic alterations revealed that TPM4 expression is related to the expression of DNA methylation inhibitors and RNA methylation regulators at high concentrations. Besides, TPM4 expression was found to correlate with immune cell infiltration, immune checkpoint (ICP) gene expression, the tumor mutational burden (TMB), and microsatellite instability (MSI). Neoantigens (NEO) were also found to influence its response to immunotherapy. A lncRNA-miRNA -TPM4 network was found to regulate GC development and progression. TPM4 expression was related to docetaxel,5-fluorouracil, and eight small molecular targeted drugs sensitivity. Gene function enrichment analyses revealed that genes that were co-expressed with TPM4 were enriched within the extracellular matrix (ECM)-related pathways. Wound-healing and (Matrigel) transwell assays revealed that TPM4 promotes cell migration and invasion. TPM4, as an oncogene, plays a biological role, perhaps via ECM remodeling in GC.ConclusionsTPM4 is a prospective marker for the diagnosis, treatment outcome, immunology, chemotherapy, and small molecular drugs targeted for pan-cancer treatment, including GC treatment. The lncRNA-miRNA-TPM4network regulates the mechanism underlying GC progression. TPM4 may facilitate the invasion and migration of GC cells, possibly through ECM remodeling.
Long-term outcome of Bartter syndrome in 54 patients: A multicenter study in Korea
Authors: Choi Naye , Kim Seong Heon , Bae Eun Hui , Yang Eun Mi , Lee Keum Hwa , Lee Sang-Ho , Lee Joo Hoon , Ahn Yo Han , Cheong Hae Il , Kang Hee Gyung , Hyun Hye Sun , Kim Ji Hyun 
Published: March 2023

IntroductionBartter syndrome (BS) is a rare salt-wasting tubulopathy caused by mutations in genes encoding sodium, potassium, or chloride transporters of the thick ascending limb of the loop of Henle and/or the distal convoluted tubule of the kidney. BS is characterized by polyuria, failure to thrive, hypokalemia, metabolic alkalosis, hyperreninemia, and hyperaldosteronism. Potassium and/or sodium supplements, potassium-sparing diuretics, and nonsteroidal anti-inflammatory drugs can be used to treat BS. While its symptoms and initial management are relatively well known, long-term outcomes and treatments are scarce.MethodsWe retrospectively reviewed 54 Korean patients who were clinically or genetically diagnosed with BS from seven centers in Korea.ResultsAll patients included in this study were clinically or genetically diagnosed with BS at a median age of 5 (range, 0–271) months, and their median follow-up was 8 (range, 0.5–27) years. Genetic diagnosis of BS was confirmed in 39 patients: 4 had SLC12A1 gene mutations, 1 had KCNJ1 gene mutations, 33 had CLCNKB gene mutations, and 1 had BSND mutation. Potassium chloride supplements and potassium-sparing diuretics were administered in 94% and 68% of patients, respectively. The mean dosage of potassium chloride supplements was 5.0 and 2.1 mEq/day/kg for patients younger and older than 18 years, respectively. Nephrocalcinosis was a common finding of BS, and it also improved with age in some patients. At the last follow-up of 8 years after the initial diagnosis, 41% had short stature (height less than 3rd percentile) and impaired kidney function was observed in six patients [chronic kidney disease (CKD) G3, n = 4; CKD G5, n = 2].ConclusionBS patients require a large amount of potassium supplementation along with potassium-sparing agents throughout their lives, but tend to improve with age. Despite management, a significant portion of this population exhibited growth impairment, while 11% developed CKD G3–G5.
Super-infection by multiple microorganisms in COVID-19 patients
Authors: Gomez Andrea C. , Ortiz Tamin , Valenzuela Angélica , Egoávil-Espejo Rocío , Huerto-Huanuco Rosario , Pinto Joseph A. , Lagos Jose , Ruiz Joaquim 
Published: March 2023

Introduction: This study aimed to describe the clinical characteristics of patients with COVID-19 co-infected with multiple multidrug-resistant bacteria.Methods: Patients hospitalized in the AUNA network between January and May 2021, diagnosed with COVID-19 and at least two other infecting microorganisms, were retrospectively included in the analysis. Clinical and epidemiological data were extracted from clinical records. The susceptibility levels of the microorganisms were determined using automated methods. Antibiotic resistance was established among infecting bacteria accounting for ≥5 isolates.Results: A total of 27 patients (21 male and 6 female patients) met the inclusion criteria, with a maximum of eight co-infecting bacteria or fungi during admission time. Seven patients (25.9%) died, with a higher but not significant lethality among women (50% vs. 19.0%). A total of 15 patients presented at least one established comorbidity, with hypertension being the most frequent. The time elapsed between COVID-19 diagnosis and hospital attendance was 7.0 days, with that of patients with a fatal outcome being longer than that of living patients (10.6 vs. 5.4). Up to 20 different microorganisms were isolated, with Pseudomonas aeruginosa being the most common (34 isolates). In general, antibiotic resistance levels were high, especially in Acinetobacter baumannii isolates, with resistance levels of 88.9% to all antimicrobial agents tested, except colistin (0%).Conclusion: In conclusion, the present results show the presence of multiple microorganisms that co-infect COVID-19 patients. When fatal outcome rates are in the range of other reports, the presence of a series of multidrug-resistant microorganisms is of concern, showing the need to reinforce control measures to limit the expansion of almost untreatable microorganisms.
A non-pharmacological multidomain intervention of dual-task exercise and social activity affects the cognitive function in community-dwelling older adults with mild to moderate cognitive decline: A randomized controlled trial
Authors: Lee Sangyoon , Harada Kenji , Bae Seongryu , Harada Kazuhiro , Makino Keitaro , Anan Yuya , Suzuki Takao , Shimada Hiroyuki 
Published: March 2023

The present study aimed to determine the impact of a 10-month multidomain program using dual-task exercise and social activity conducted at a community-based facility on improved cognitive function in older adults with mild to moderate cognitive decline. The participants included 280 community-dwelling older adults (age 71–91 years) with mild to moderate cognitive decline. The intervention group exercised for 90 min/day, once a week. Their routine included aerobic exercise and dual-task training which cognitive tasks were performed in combination with exercise. The control group attended health education classes thrice. Before and after the intervention, we measured their cognitive function, physical function, daily conversation, and physical activity. The mean adherence rate of the intervention class was 83.0%. According to a repeated-measures multivariate analysis of covariance in an intent-to-treat analysis, logical memory and 6-min walking distance demonstrated a significant time and group interaction effect. Regarding daily physical activities, we observed significant differences in the daily step count and moderate-to-vigorous physical activity in the intervention group. Our non-pharmacological multidomain intervention resulted in a modest improvement in the cognitive or physical function and building health behavior. It may be a helpful program with a potential role in preventing dementia.Clinical Trial Registration: http://clinicaltrials.gov Identifier ID: UMIN000013097.
Association of thyroid disease with risks of dementia and cognitive impairment: A meta-analysis and systematic review
Authors: Ma Li-Yun , Zhao Bing , Ou Ya-Nan , Zhang Dan-Dan , Li Qiong-Yao , Tan Lan 
Published: March 2023

IntroductionIt is still uncertain whether the risk of dementia and cognitive impairment is related to thyroid disease. we carried out a meta-analysis and systematic review (PROSPERO: CRD42021290105) on the associations between thyroid disease and the risks of dementia and cognitive impairment.MethodsWe searched PubMed, Embase, and Cochrane Library for studies published up to August 2022. The overall relative risk (RRs) and its 95% confidence interval (CIs) were calculated in the random-effects models. Subgroup analyses and meta-regression were conducted to explore the potential source of heterogeneity among studies. We tested and corrected for publication bias by funnel plot-based methods. The Newcastle-Ottawa Scale (NOS) or Agency for Healthcare Research and Quality (AHRQ) scale were used to evaluate the study quality of longitudinal studies and cross-sectional studies, respectively.ResultsA total of 15 studies were included in our meta-analysis. Our meta-analysis showed that hyperthyroidism (RR = 1.14, 95% CI = 1.09–1.19) and subclinical hyperthyroidism (RR = 1.56, 95% CI = 1.26–1.93) might be associated with an elevated risk for dementia, while hypothyroidism (RR = 0.93, 95% CI = 0.80–1.08) and subclinical hypothyroidism (RR = 0.84, 95% CI = 0.70–1.01) did not affect the risk.DiscussionHyperthyroidism and subclinical hyperthyroidism are predictors of dementia.Systematic review registrationPROSPERO, Identifier: CRD42021290105.