bluuebunny/crossref_metadata_2025 huggingface dataset:
Metacyclogenesis as the Starting Point of Chagas Disease
Authors: Ferreira Alessandro Zanard Lopes , de Araújo Carla Nunes , Cardoso Isabela Cunha Costa , de Souza Mangabeira Karen Stephanie , Rocha Amanda Pereira , Charneau Sébastien , Santana Jaime Martins , Motta Flávia Nader , Bastos Izabela Marques Dourado
Published: December 2023

Chagas disease is a neglected infectious disease caused by the protozoan Trypanosoma cruzi, primarily transmitted by triatomine vectors, and it threatens approximately seventy-five million people worldwide. This parasite undergoes a complex life cycle, transitioning between hosts and shifting from extracellular to intracellular stages. To ensure its survival in these diverse environments, T. cruzi undergoes extreme morphological and molecular changes. The metacyclic trypomastigote (MT) form, which arises from the metacyclogenesis (MTG) process in the triatomine hindgut, serves as a crucial link between the insect and human hosts and can be considered the starting point of Chagas disease. This review provides an overview of the current knowledge regarding the parasite’s life cycle, molecular pathways, and mechanisms involved in metabolic and morphological adaptations during MTG, enabling the MT to evade the immune system and successfully infect human cells.
Biotic and Abiotic Stressors in Plant Metabolism
Authors: Cornara Laura , Mandrone Manuela , Smeriglio Antonella
Published: December 2023

Plants are subject to a variety of biotic and abiotic stress that affect their metabolism, physiology, morphology, and growth [...]
Genome-Wide Association Analysis of Heat Tolerance in F2 Progeny from the Hybridization between Two Congeneric Oyster Species
Authors: Du Mingyang , Jiang Zhuxiang , Wang Chaogang , Wei Chenchen , Li Qingyuan , Cong Rihao , Wang Wei , Zhang Guofan , Li Li
Published: December 2023

As the world’s largest farmed marine animal, oysters have enormous economic and ecological value. However, mass summer mortality caused by high temperature poses a significant threat to the oyster industry. To investigate the molecular mechanisms underlying heat adaptation and improve the heat tolerance ability in the oyster, we conducted genome-wide association analysis (GWAS) analysis on the F2 generation derived from the hybridization of relatively heat-tolerant Crassostrea angulata ♀ and heat-sensitive Crassostrea gigas ♂, which are the dominant cultured species in southern and northern China, respectively. Acute heat stress experiment (semi-lethal temperature 42 °C) demonstrated that the F2 population showed differentiation in heat tolerance, leading to extremely differentiated individuals (approximately 20% of individuals die within the first four days with 10% survival after 14 days). Genome resequencing and GWAS of the two divergent groups had identified 18 significant SNPs associated with heat tolerance, with 26 candidate genes located near these SNPs. Eleven candidate genes that may associate with the thermal resistance were identified, which were classified into five categories: temperature sensor (Trpm2), transcriptional factor (Gata3), protein ubiquitination (Ube2h, Usp50, Uchl3), heat shock subfamily (Dnajc17, Dnaja1), and transporters (Slc16a9, Slc16a14, Slc16a9, Slc16a2). The expressional differentiation of the above genes between C. gigas and C. angulata under sublethal temperature (37 °C) further supports their crucial role in coping with high temperature. Our results will contribute to understanding the molecular mechanisms underlying heat tolerance, and provide genetic markers for heat-resistance breeding in the oyster industry.
Expanding the Phenotype of Hereditary Congenital Facial Paresis Type 3
Authors: Murtazina Aysylu , Borovikov Artem , Kuchina Anna , Ovsova Olga , Bulakh Maria , Chukhrova Alena , Braslavskaya Svetlana , Ryzhkova Oksana , Skryabin Nikolay , Kutsev Sergey , Dadali Elena
Published: December 2023

The HOXB1 gene encodes a homeobox transcription factor pivotal in the development of rhombomere 4. Biallelic pathogenic variants in this gene are associated with congenital facial paresis type 3 (HCFP3). Only seven single nucleotide variants have been reported in the literature to date. Here, we report a 27-year-old female with a unique presentation of HCFP3 with two novel compound-heterozygous missense variants: c.763C>G, p.(Arg255Gly), which arose de novo and an inherited c.781C>T, p.(Arg261Cys) variant. The patient exhibited HCFP3 symptoms with mild upward esodeviation and lacked the documented ear malformations common in HCFP. For many years, she was misdiagnosed with facio-scapulo-humeral muscular dystrophy, due to complaints of shoulder girdle and neck muscle weakness. No alternative genetic or acquired causes of neck and shoulder girdle weakness were found, suggesting its potential inclusion in the phenotypic spectrum.
Lipids as Emerging Biomarkers in Neurodegenerative Diseases
Authors: Wei Justin , Wong Li Chin , Boland Sebastian
Published: December 2023

Biomarkers are molecules that can be used to observe changes in an individual’s biochemical or medical status and provide information to aid diagnosis or treatment decisions. Dysregulation in lipid metabolism in the brain is a major risk factor for many neurodegenerative disorders, including frontotemporal dementia, Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Thus, there is a growing interest in using lipids as biomarkers in neurodegenerative diseases, with the anionic phospholipid bis(monoacylglycerol)phosphate and (glyco-)sphingolipids being the most promising lipid classes thus far. In this review, we provide a general overview of lipid biology, provide examples of abnormal lysosomal lipid metabolism in neurodegenerative diseases, and discuss how these insights might offer novel and promising opportunities in biomarker development and therapeutic discovery. Finally, we discuss the challenges and opportunities of lipid biomarkers and biomarker panels in diagnosis, prognosis, and/or treatment response in the clinic.
Effects of Adipose Tissue-Specific Knockout of Delta-like Non-Canonical Notch Ligand 1 on Lipid Metabolism in Mice
Authors: Lu Xin , Fang Xibi , Mi Jiaqi , Liu Yue , Liu Ruimin , Li Guanghui , Li Yue , Yang Runjun
Published: December 2023

Delta-like non-canonical Notch ligand 1 (DLK1), which inhibits the differentiation of precursor adipocytes, is a recognized marker gene for precursor adipocytes. Lipids play a crucial role in energy storage and metabolism as a vital determinant of beef quality. In this study, we investigated the mechanism of the DLK1 gene in lipid metabolism by constructing adipose tissue-specific knockout mice. We examined some phenotypic traits, including body weight, liver coefficient, fat index, the content of triglyceride (TG) and cholesterol (CHOL) in abdominal white adipose tissue (WAT) and blood. Subsequently, the fatty acid content and genes related to lipid metabolism expression were detected in DLK1−/− and wild-type mice via GC-MS/MS analysis and quantitative real-time PCR (qRT-PCR), respectively. The results illustrated that DLK1−/− mice exhibited significant abdominal fat deposition compared to wild-type mice. HE staining and immunohistochemistry (IHC) results showed that the white adipocytes of DLK1−/− mice were larger, and the protein expression level of DLK1−/− was significantly lower. Regarding the blood biochemical parameters of female mice, DLK1−/− mice had a strikingly higher triglyceride content (p < 0.001). The fatty acid content in DLK1−/− mice was generally reduced. There was a significant reduction in the expression levels of the majority of genes that play a crucial role in lipid metabolism. This study reveals the molecular regulatory mechanism of fat metabolism in mice and provides a molecular basis and reference for the future application of the DLK1 gene in the breeding of beef cattle with an excellent meat quality traits. It also provides a molecular basis for unravelling the complex and subtle relationship between adipose tissue and health.
Comprehensive Evaluation of Polyaniline-Doped Lignosulfonate in Adsorbing Dye and Heavy Metal Ions
Authors: Wu Wenjuan , Li Penghui , Wang Mingkang , Liu Huijun , Zhao Xiufu , Wu Caiwen , Ren Jianpeng
Published: December 2023

Lignosulfonate/polyaniline (LS/PANI) nanocomposite adsorbent materials were prepared by the chemical polymerization of lignosulfonate with an aniline monomer as a dopant and structure-directing agent, and the adsorption behavior of dyes as well as heavy metal ions was investigated. LS/PANI composites were used as dye adsorbents for the removal of different cationic dyes (malachite green, methylene blue, and crystal violet). The adsorption behavior of LS/PANI composites as dye adsorbents for malachite green was investigated by examining the effects of the adsorbent dosage, solution pH, initial concentration of dye, adsorption time, and temperature on the adsorption properties of this dye. The following conclusions were obtained. The optimum adsorption conditions for the removal of malachite green dye when LS/PANI composites were used as malachite green dye adsorbents were as follows: an adsorbent dosage of 20 mg, an initial concentration of the dye of 250 mg/L, an adsorption time of 300 min, and a temperature of 358 K. The LS/PANI composite adsorbed malachite green dye in accordance with the Langmuir adsorption model and pseudo-second-order kinetic model, which belongs to chemisorption-based monomolecular adsorption, and the equilibrium adsorption amount was 245.75 mg/g. In particular, the adsorption of heavy metal ion Pb2+ was investigated, and the removal performance was also favorable for Pb2+.
A Novel Role for DOC2B in Ameliorating Palmitate-Induced Glucose Uptake Dysfunction in Skeletal Muscle Cells via a Mechanism Involving β-AR Agonism and Cofilin
Authors: Hwang Jinhee , Balakrishnan Rekha , Oh Eunjin , Veluthakal Rajakrishnan , Thurmond Debbie C.
Published: December 2023

Diet-related lipotoxic stress is a significant driver of skeletal muscle insulin resistance (IR) and type 2 diabetes (T2D) onset. β2-adrenergic receptor (β-AR) agonism promotes insulin sensitivity in vivo under lipotoxic stress conditions. Here, we established an in vitro paradigm of lipotoxic stress using palmitate (Palm) in rat skeletal muscle cells to determine if β-AR agonism could cooperate with double C-2-like domain beta (DOC2B) enrichment to promote skeletal muscle insulin sensitivity under Palm-stress conditions. Previously, human T2D skeletal muscles were shown to be deficient for DOC2B, and DOC2B enrichment resisted IR in vivo. Our Palm-stress paradigm induced IR and β-AR resistance, reduced DOC2B protein levels, triggered cytoskeletal cofilin phosphorylation, and reduced GLUT4 translocation to the plasma membrane (PM). By enhancing DOC2B levels in rat skeletal muscle, we showed that the deleterious effects of palmitate exposure upon cofilin, insulin, and β-AR-stimulated GLUT4 trafficking to the PM and glucose uptake were preventable. In conclusion, we revealed a useful in vitro paradigm of Palm-induced stress to test for factors that can prevent/reverse skeletal muscle dysfunctions related to obesity/pre-T2D. Discerning strategies to enrich DOC2B and promote β-AR agonism can resist skeletal muscle IR and halt progression to T2D.
Development of A Radiomic Model for MGMT Promoter Methylation Detection in Glioblastoma Using Conventional MRI
Authors: Doniselli Fabio M. , Pascuzzo Riccardo , Agrò Massimiliano , Aquino Domenico , Anghileri Elena , Farinotti Mariangela , Pollo Bianca , Paterra Rosina , Cuccarini Valeria , Moscatelli Marco , DiMeco Francesco , Sconfienza Luca Maria
Published: December 2023

The methylation of the O6-methylguanine-DNA methyltransferase (MGMT) promoter is a molecular marker associated with a better response to chemotherapy in patients with glioblastoma (GB). Standard pre-operative magnetic resonance imaging (MRI) analysis is not adequate to detect MGMT promoter methylation. This study aims to evaluate whether the radiomic features extracted from multiple tumor subregions using multiparametric MRI can predict MGMT promoter methylation status in GB patients. This retrospective single-institution study included a cohort of 277 GB patients whose 3D post-contrast T1-weighted images and 3D fluid-attenuated inversion recovery (FLAIR) images were acquired using two MRI scanners. Three separate regions of interest (ROIs) showing tumor enhancement, necrosis, and FLAIR hyperintensities were manually segmented for each patient. Two machine learning algorithms (support vector machine (SVM) and random forest) were built for MGMT promoter methylation prediction from a training cohort (196 patients) and tested on a separate validation cohort (81 patients), based on a set of automatically selected radiomic features, with and without demographic variables (i.e., patients’ age and sex). In the training set, SVM based on the selected radiomic features of the three separate ROIs achieved the best performances, with an average of 83.0% (standard deviation: 5.7%) for accuracy and 0.894 (0.056) for the area under the curve (AUC) computed through cross-validation. In the test set, all classification performances dropped: the best was obtained by SVM based on the selected features extracted from the whole tumor lesion constructed by merging the three ROIs, with 64.2% (95% confidence interval: 52.8–74.6%) accuracy and 0.572 (0.439–0.705) for AUC. The performances did not change when the patients’ age and sex were included with the radiomic features into the models. Our study confirms the presence of a subtle association between imaging characteristics and MGMT promoter methylation status. However, further verification of the strength of this association is needed, as the low diagnostic performance obtained in this validation cohort is not sufficiently robust to allow clinically meaningful predictions.
Longitudinal Transcription Profiling of Bladder Cancers Dictate the Response to BCG Treatment and Disease Progression
Authors: Lee Seo-Young , Lee Yun-Hee , Kim Tae-Min , Ha U-Syn
Published: December 2023

Although the intravesical instillation of Bacillus Calmette-Guerin (BCG) is widely used as adjuvant treatment for nonmuscle-invasive bladder cancers, the clinical benefit is variable across patients, and the molecular mechanisms underlying the sensitivity to BCG administration and disease progression are poorly understood. To establish the molecular signatures that predict the responsiveness and disease progression of bladder cancers treated with BCG, we performed transcriptome sequencing (RNA-seq) for 13 treatment-naïve and 22 post-treatment specimens obtained from 14 bladder cancer patients. To overcome disease heterogeneity, we used non-negative matrix factorization to identify the latent molecular features associated with drug responsiveness and disease progression. At least 12 molecular features were present, among which the immune-related feature was associated with drug responsiveness, indicating that pre-treatment anti-cancer immunity might dictate BCG responsiveness. We also identified disease progression-associated molecular features indicative of elevated cellular proliferation in post-treatment specimens. The progression-associated molecular features were validated in an extended cohort of BCG-treated bladder cancers. Our study advances understanding of the molecular mechanisms of BCG activity in bladder cancers and provides clinically relevant gene markers for evaluating and monitoring patients.
Phosphorylated Adapter RNA Export Protein Is Methylated at Lys 381 by an Methyltransferase-like 21C (METTL21C)
Authors: Ke Meiling , Yu Xiaoke , Sun Yuanyuan , Han Shuai , Wang Ling , Zhang Tao , Zeng Wenxian , Lu Hongzhao
Published: December 2023

Methyltransferase-like 21C (METTL21C) is a member of the non-histone methyltransferase superfamily, which mainly mediates the methylation of lysine (Lys) residues. The main types of modification are Lys dimethylation and trimethylation. However, at present, most of the studies on METTL21C are focused on humans and mice, and there are few reports on poultry. Therefore, chicken embryo fibroblasts (DF-1) were selected as the object of study. To explore the function of chicken METTL21C (chMETTL21C) in the proliferation of DF-1 cells, flow cytometry and qPCR were used to detect the function of chicken METTL21C in the proliferation of DF-1 cells. The results showed that overexpression of METTL21C blocked the cell cycle in the G1max S phase, thus inhibiting cell proliferation. In addition, based on proteomic analysis, stable overexpression of METTL21C may inhibit the proliferation of DF-1 cells by mediating lysine trimethylation of proliferation-related proteins phosphorylated adapter RNA export protein (PHAX), nucleoside diphosphate kinases (NDPKs), eukaryotic transcription extension factor (eukaryotic translation elongation factor 1A,e EF1A), and inversin (Invs). Through immunoprecipitation (co-IP) and liquid chromatography-mass spectrometry (LC-MS/MS) analysis, METTL21C-mediated PHAX Lys-381 methylation was confirmed to be involved in the regulation of DF-1 cell proliferation. The results of this study provide a reference for analyzing the methylation function of METTL21C and the mechanism of regulating the growth and development of chicken cells.
Activation and Functions of Col6a1+ Fibroblasts in Colitis-Associated Cancer
Authors: Chalkidi Niki , Melissari Maria-Theodora , Henriques Ana , Stavropoulou Athanasia , Kollias George , Koliaraki Vasiliki
Published: December 2023

Cancer-associated fibroblasts (CAFs) comprise a group of heterogeneous subpopulations with distinct identities indicative of their diverse origins, activation patterns, and pro-tumorigenic functions. CAFs originate mainly from resident fibroblasts, which are activated upon different stimuli, including growth factors and inflammatory mediators, but the extent to which they also maintain some of their homeostatic properties, at least at the earlier stages of carcinogenesis, is not clear. In response to cytokines, such as interleukin 1 (IL-1) and tumor necrosis factor (TNF), as well as microbial products, CAFs acquire an immunoregulatory phenotype, but its specificity and pathophysiological significance in individual CAF subsets is yet to be determined. In this study, we analyzed the properties of Col6a1-positive fibroblasts in colitis-associated cancer. We found that Col6a1+ cells partly maintain their homeostatic features during adenoma development, while their activation is characterized by the acquisition of a distinct proangiogenic signature associated with their initial perivascular location. In vitro and in vivo experiments showed that Col6a1+ cells respond to innate immune stimuli and exert pro-tumorigenic functions. However, Col6a1+-specific inhibition of TNF receptor 1 (TNFR1) or IL-1 receptor (IL-1R) signaling does not significantly affect tumorigenesis, suggesting that activation of other subsets acts in a compensatory way or that multiple immune stimuli are necessary to drive the proinflammatory activation of this subset. In conclusion, our results show that adenoma-associated CAF subsets can partly maintain the properties of homeostatic fibroblasts while they become activated to support tumor growth through distinct and compensatory mechanisms.
Ethyl Acetate Fraction from a Catalpa ovata G. Don Extract Inhibits ɑ-MSH-Induced Melanogenesis through the cAMP/CREB Pathway
Authors: Kim Yon-Suk , Lee Eun-Bin , Yu Ye-Ji , Kim Ga-Won , Kim Woo-Jung , Choi Dong-Kug
Published: December 2023

The whitening effect of reducing skin pigmentation is one of the most important goals of cosmetics. The purpose of this study was to determine whether Catalpa ovata extract and its fractions have potential as natural skin-lightening agents. Initially, we screened various fractions of Catalpa ovata extract using an in vitro antioxidant assay. Then, the inhibitory effects of C. ovata extract and its fraction on melanogenesis and the related mechanisms were investigated in B16F1 melanoma cells. The results showed that the ethyl acetate fraction (EF) from C. ovata extract markedly inhibited melanin synthesis in a dose-dependent manner at non-toxic concentrations. Furthermore, EF downregulated both the protein and mRNA levels of tyrosinase, which is a specific enzyme that catalyzes the conversion of tyrosine into melanin. We also found that EF decreased the microphthalmia-associated transcription factor (MITF) at the protein and mRNA levels. EF increased the phosphorylation of ERK and suppressed the phosphorylation of JNK and p38 in ɑ-MSH-induced B16F1 cells. These results indicate that EF can regulate the MAPK pathway. In addition, EF has an anti-melanogenic effect via the downregulation of intracellular cyclic-AMP (cAMP). Nineteen major compounds of EF were identified using LC-MS/MS. Taken together, these results suggest that EF may be a potential anti-melanogenic agent for use in skin-whitening cosmetics and in topical treatments for hyperpigmentation disorders.
Unlocking Prognostic Genes and Multi-Targeted Therapeutic Bioactives from Herbal Medicines to Combat Cancer-Associated Cachexia: A Transcriptomics and Network Pharmacology Approach
Authors: Muthamil Subramanian , Muthuramalingam Pandiyan , Kim Hyun-Yong , Jang Hyun-Jun , Lyu Ji-Hyo , Shin Ung Cheol , Go Younghoon , Park Seong-Hoon , Lee Hee Gu , Shin Hyunsuk , Park Jun Hong
Published: December 2023

Cachexia is a devastating fat tissue and muscle wasting syndrome associated with every major chronic illness, including cancer, chronic obstructive pulmonary disease, kidney disease, AIDS, and heart failure. Despite two decades of intense research, cachexia remains under-recognized by oncologists. While numerous drug candidates have been proposed for cachexia treatment, none have achieved clinical success. Only a few drugs are approved by the FDA for cachexia therapy, but a very low success rate is observed among patients. Currently, the identification of drugs from herbal medicines is a frontier research area for many diseases. In this milieu, network pharmacology, transcriptomics, cheminformatics, and molecular docking approaches were used to identify potential bioactive compounds from herbal medicines for the treatment of cancer-related cachexia. The network pharmacology approach is used to select the 32 unique genes from 238 genes involved in cachexia-related pathways, which are targeted by 34 phytocompounds identified from 12 different herbal medicines used for the treatment of muscle wasting in many countries. Gene expression profiling and functional enrichment analysis are applied to decipher the role of unique genes in cancer-associated cachexia pathways. In addition, the pharmacological properties and molecular interactions of the phytocompounds were analyzed to find the target compounds for cachexia therapy. Altogether, combined omics and network pharmacology approaches were used in the current study to untangle the complex prognostic genes involved in cachexia and phytocompounds with anti-cachectic efficacy. However, further functional and experimental validations are required to confirm the efficacy of these phytocompounds as commercial drug candidates for cancer-associated cachexia.
A Cancer-Specific Monoclonal Antibody against Podocalyxin Exerted Antitumor Activities in Pancreatic Cancer Xenografts
Authors: Suzuki Hiroyuki , Ohishi Tomokazu , Tanaka Tomohiro , Kaneko Mika K. , Kato Yukinari
Published: December 2023

Podocalyxin (PODXL) overexpression is associated with poor clinical outcomes in various tumors. PODXL is involved in tumor malignant progression through the promotion of invasiveness and metastasis. Therefore, PODXL is considered a promising target of monoclonal antibody (mAb)-based therapy. However, PODXL also plays an essential role in normal cells, such as vascular and lymphatic endothelial cells. Therefore, cancer specificity or selectivity is required to reduce adverse effects on normal cells. Here, we developed an anti-PODXL cancer-specific mAb (CasMab), PcMab-6 (IgG1, kappa), by immunizing mice with a soluble PODXL ectodomain derived from a glioblastoma LN229 cell. PcMab-6 reacted with the PODXL-positive LN229 cells but not with PODXL-knockout LN229 cells in flow cytometry. Importantly, PcMab-6 recognized pancreatic ductal adenocarcinoma (PDAC) cell lines (MIA PaCa-2, Capan-2, and PK-45H) but did not react with normal lymphatic endothelial cells (LECs). In contrast, one of the non-CasMabs, PcMab-47, showed high reactivity to both the PDAC cell lines and LECs. Next, we engineered PcMab-6 into a mouse IgG2a-type (PcMab-6-mG2a) and a humanized IgG1-type (humPcMab-6) mAb and further produced the core fucose-deficient types (PcMab-6-mG2a-f and humPcMab-6-f, respectively) to potentiate the antibody-dependent cellular cytotoxicity (ADCC). Both PcMab-6-mG2a-f and humPcMab-6-f exerted ADCC and complement-dependent cellular cytotoxicity in the presence of effector cells and complements, respectively. In the PDAC xenograft model, both PcMab-6-mG2a-f and humPcMab-6-f exhibited potent antitumor effects. These results indicated that humPcMab-6-f could apply to antibody-based therapy against PODXL-expressing pancreatic cancers.
Loliolide in Sargassum horneri Alleviates Ultrafine Urban Particulate Matter (PM 0.1)-Induced Inflammation in Human RPE Cells
Authors: Lee Eun Jeoung , Lee Sol , Jang Hyun-Jae , Yoo Wonbeak
Published: December 2023

Owing to increasing air pollution due to industrial development, fine dust has been associated with threatening public health. In particular, ultrafine urban particulate matter (uf-UP, PM 0.1) can easily enter our bodies, causing inflammation-related diseases. Therefore, in the present study, we evaluated the effects of hydrothermal extracts of Sargassum horneri and its bioactive compound, loliolide, on uf-UP-induced inflammation as a potential treatment strategy for retinal disorders. Human retinal pigment epithelial cells (ARPE-19) stimulated with TNF-α or uf-UPs were treated with S. horneri extract and loliolide. S. horneri extracts exhibited anti-inflammatory effects on uf-UP-induced inflammation without cell toxicity through downregulating the mRNA expression of MCP-1, IL-8, IL-6, and TNF-α. UPLC-QTOF/MS analysis confirmed that the hydrothermal extract of S. horneri contained loliolide, which has anti-inflammatory effects. Loliolide effectively reduced the mRNA expression and production of proinflammatory chemokines (IL-8) and cytokines (IL-1β and IL-6) by downregulating the MAPK/NF-ĸB signaling pathway on TNF-α-stimulated inflammatory ARPE-19 cells. These effects were further confirmed in inflammatory ARPE-19 cells after stimulation with uf-UPs. Collectively, these results suggested the application of S. horneri as a functional ingredient for treating ocular disorders caused by particular matters.
The Tumor Necrosis Factor-α Level in Platelet-Rich Plasma Might Be Associated with Treatment Outcome in Patients with Interstitial Cystitis/Bladder Pain Syndrome or Recurrent Urinary Tract Infection
Authors: Jhang Jia-Fong , Jiang Yuan-Hong , Lin Teng-Yi , Kuo Hann-Chorng
Published: December 2023

Using platelet-rich plasma (PRP) injections to treat urological diseases has attracted great attention. This study investigated the impact of cytokine concentrations in PRP on the treatment outcome of patients with recurrent urinary tract infection (rUTI) and interstitial cystitis/bladder pain syndrome (IC/BPS). Forty patients with IC/BPS and twenty-one patients with rUTI were enrolled for four-monthly repeated PRP injections. PRP was collected at the first injection and analyzed with multiplex immunoassays for 12 target cytokines. In patients with IC/BPS, a Global Response Assessment (GRA) score ≥ 2 was defined as a successful outcome. In rUTI patients, ≤2 episodes of UTI recurrence during one year of follow-up was considered a successful outcome. Nineteen (47.5%) patients with IC/BPS and eleven (52.4%) patients with rUTI had successful outcomes. The IC/BPS patients with successful outcomes had significantly lower levels of tumor necrosis factor-α (TNF-α) in their PRP than those with unsuccessful outcomes (p = 0.041). The rUTI patients with successful outcomes also had a lower level of TNF-α (p = 0.025) and a higher level of epidermal growth factor (p = 0.035) and transforming growth factor-β2 (p = 0.024) in PRP than those with unsuccessful outcomes. A lower level of TNF-α in PRP might be a potentially predictive factor of treatment outcome.
Patent Foramen Ovale Percutaneous Closure: Evolution and Ongoing Challenges
Authors: Devos Perrine , Guedeney Paul , Montalescot Gilles
Published: December 2023

Patent foramen ovale (PFO) concerns nearly a quarter of the general population and incidence may reach up to 50% in patients with cryptogenic stroke. Recent randomized clinical trials confirmed that percutaneous closure of PFO-related stroke reduces the risk of embolic event recurrence. PFO also comes into play in other pathogenic conditions, such as migraine, decompression sickness or platypnea–orthodeoxia syndrome, where the heterogeneity of patients is high and evidence for closure is less well-documented. In this review, we describe the current indications for PFO percutaneous closure and the remaining challenges, and try to provide future directions regarding the technique and its indications.
Tailoring Rheumatoid Arthritis Treatment through a Sex and Gender Lens
Authors: Carmona Loreto , Aurrecoechea Elena , García de Yébenes María Jesús
Published: December 2023

Rheumatoid arthritis (RA) occurs more frequently in women than in men, and the studies that have addressed clinical and prognostic differences between the sexes are scarce and have contradictory results and methodological problems. The present work aims to evaluate sex- and gender-related differences in the clinical expression and prognosis of RA as well as on the impact on psychosocial variables, coping behavior, and healthcare use and access. By identifying between sex differences and gender-related outcomes in RA, it may be possible to design tailored therapeutic strategies that consider the differences and unmet needs. Being that sex, together with age, is the most relevant biomarker and health determinant, a so-called personalized medicine approach to RA must include clear guidance on what to do in case of differences.
Treatment of Refractory Cardiac Arrest by Controlled Reperfusion of the Whole Body: A Multicenter, Prospective Observational Study
Authors: Trummer Georg , Benk Christoph , Pooth Jan-Steffen , Wengenmayer Tobias , Supady Alexander , Staudacher Dawid L. , Damjanovic Domagoj , Lunz Dirk , Wiest Clemens , Aubin Hug , Lichtenberg Artur , Dünser Martin W. , Szasz Johannes , Dos Reis Miranda Dinis , van Thiel Robert J. , Gummert Jan , Kirschning Thomas , Tigges Eike , Willems Stephan , Beyersdorf Friedhelm ,   on behalf of the Extracorporeal Multi-Organ Repair Study Group
Published: December 2023

Background: Survival following cardiac arrest (CA) remains poor after conventional cardiopulmonary resuscitation (CCPR) (6–26%), and the outcomes after extracorporeal cardiopulmonary resuscitation (ECPR) are often inconsistent. Poor survival is a consequence of CA, low-flow states during CCPR, multi-organ injury, insufficient monitoring, and delayed treatment of the causative condition. We developed a new strategy to address these issues. Methods: This all-comers, multicenter, prospective observational study (69 patients with in- and out-of-hospital CA (IHCA and OHCA) after prolonged refractory CCPR) focused on extracorporeal cardiopulmonary support, comprehensive monitoring, multi-organ repair, and the potential for out-of-hospital cannulation and treatment. Result: The overall survival rate at hospital discharge was 42.0%, and a favorable neurological outcome (CPC 1+2) at 90 days was achieved for 79.3% of survivors (CPC 1+2 survival 33%). IHCA survival was very favorable (51.7%), as was CPC 1+2 survival at 90 days (41%). Survival of OHCA patients was 35% and CPC 1+2 survival at 90 days was 28%. The subgroup of OHCA patients with pre-hospital cannulation showed a superior survival rate of 57.1%. Conclusions: This new strategy focusing on repairing damage to multiple organs appears to improve outcomes after CA, and these findings should provide a sound basis for further research in this area.
Impact of Physical Activity Interventions on High-Risk Pregnancies: A Systematic Review and Meta-Analysis
Authors: Silva-Jose Cristina , Mottola Michelle F. , Palacio Montse , Sánchez-Polán Miguel , Zhang Dingfeng , Refoyo Ignacio , Barakat Rubén
Published: December 2023

Pregnant women with absolute contraindications may be advised against physical activity throughout pregnancy. In this context, bed rest elevates the short-term risk of neonatal complications, thereby exacerbating negative long-term effects on childhood development. The aim of the current study was to investigate the impact of various physical activity interventions during bed rest or activity restriction in pregnancy on factors such as birth weight, preterm birth, maternal hypertension, gestational age at delivery, and the incidence of cesarean sections. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was designed. The protocol was registered in the International Prospective Registry of Systematic Reviews (PROSPERO) (CRD42022370875). Nine studies, with a total sample of 3173 women, from six countries on four continents were included. There were significant differences in the relationship between bed rest status and birth weight (Z = 2.64; p = 0.008) (MD = 142.57, 95% CI = 36.56, 248.58, I2 = 0%, Pheterogeneity = 0.45) favourable to active groups. No significant differences were found in other analyzed outcomes. Pregnant women who experience this problem must maintain a minimum of daily activity to alleviate these physiological complications and the medical field must understand the consequences of physical inactivity during pregnancy.
Comparative Analysis of Intellectual Quotient in Developmental Population with Severe Hearing Loss: Hearing Aids vs. Cochlear Implant Users
Authors: Di Stadio Arianna , De Luca Pietro , Ippolito Valentina , Vedova Paola , Garofalo Sabina , Turchetta Rosaria , Ferlito Salvatore , della Volpe Antonio
Published: December 2023

The development of language, memory and intellectual functions is linked to normal hearing and correct sounds interpretation. Hearing loss (HL), especially in its severe form, negatively affects the development of these functions. This prospective study aimed at comparing the Intelligent Quotients (IQ) of children with cochlear implants (CI) with the ones of people wearing hearing aids (HA) after one year of hearing rehabilitation. 21 subjects with severe/profound bilateral hearing loss (deafness) were included in this study. Eleven children with congenital profound HL underwent CI and ten children with moderate to severe HL (congenital and acquired) were rehabilitated by HA. Children’s IQs were assessed at enrolment (T0) and 12 months after hearing aids/CI use plus speech therapy. Statistical analyses were performed to analyze the data within and between groups. Comparison of IQs showed no statistically significant differences between CI and HA none at T0 and T1. The subtests showed lower scores in verbal comprehension and process speed index in patients treated with HA when compared to CI. This study showed that auditory rehabilitation can support the normal development of cognitive function in children between six and eight years of age. The use of the correct hearing aids based on the patient’s hearing thresholds is important to maximize the rehabilitation outcomes. Due to the small sample size, although stratified for age, our results must be considered preliminary and further analyses on larger samples are needed to confirm our data.
Serum Angiopoietin-like Protein 3 Levels Are Associated with Endothelial Function in Patients with Maintenance Hemodialysis
Authors: Wu Tzu-Chiang , Hsu Bang-Gee , Kuo Chiu-Huang , Wang Chih-Hsien , Tsai Jen-Pi
Published: December 2023

Angiopoietin-like protein 3 (ANGPTL3) plays an important role in lipid and lipoprotein trafficking and metabolism and is positively correlated with cardiovascular disease. Our objective was to evaluate the association between serum ANGPTL3 levels and endothelial function in patients on maintenance hemodialysis (MHD). We enrolled 116 patients on MHD and obtained their blood test results from their medical records. Using a noninvasive digital thermal monitor, we determined the vascular reactivity index (VRI) as a measure of endothelial function. Serum ANGPTL3 concentration was measured by a commercial-enzyme-linked immunosorbent assay. Vascular reactivity was classified as poor in 17 (14.7%) patients, intermediate (1.0 ≤ VRI < 2.0) in 50 (43.1%) patients, and high (VRI ≥ 2.0) in 49 (42.2%) patients. Serum levels of ANGPTL3 (p < 0.001) and alkaline phosphatase (ALP, p = 0.025) increased significantly as the VRI decreased. The log-transformed serum ALP (log-ALP, r = −0.187, p = 0.045) and log-ANGPTL3 (r = −0.319, p < 0.001) showed a negative correlation with the VRI on univariate linear regression analysis. A significant negative correlation was found between log-ANGPTL3 and VRI (p < 0.001) on multivariate stepwise linear regression analysis. The findings of our investigation showed that, in patients with MHD, the ANGPTL3 concentration had a negative correlation with the VRI.
The Non-Linear Elasticity of Unidirectional Continuous Carbon Fibre-Reinforced Composites and of Carbon Fibres
Authors: Keryvin Vincent , Marchandise Adrien
Published: December 2023

A database of non-linear elastic parameters in axial tension and compression is provided for continuous carbon fibre polymer composites and carbon fibres of different stiffnesses. Composite laminates manufactured by conventional or automated processes are tested in bending, and parameters are extracted for strains of less than 0.5%. While fibre composites with fibres of standard and intermediate moduli exhibit a stiffening of ∼15 GPa/% (of strain) and a softening of ∼20 GPa/%, those with high-modulus carbon fibres exhibit much higher values of ∼50 GPa/% for both. This database is useful for designing composite structures in a stiffness-based design and for correlating the processing of carbon fibres with their nanostructure and induced properties. The latter is discussed in terms of reorientation of crystallites of graphene sheets vis-à-vis the carbon fibre axis during loading.
In Vitro Comparison of Differences in Setting Time of Premixed Calcium Silicate-Based Mineral Trioxide Aggregate According to Moisture Content of Gypsum
Authors: Kim Hyun-Jin , Lee Jun-Seok , Gwak Dong-Hoon , Ko Yong-Seok , Lim Chun-Il , Lee Seung-Youl
Published: December 2023

Recently, a paste-type premixed calcium silicate-based mineral trioxide aggregate (MTA) product that quickly solidifies through a pozzolanic reaction was introduced to replace existing MTA, which has the disadvantage of a long setting time. In this study, we evaluated the effect of moisture content in the root canal on the setting time of premixed calcium silicate-based MTA in a simulated root canal environment using Endoseal MTA and Well-Root ST, among commercially available products. The setting time was measured according to ISO 6876/2012. A mold made using grades 2, 3, and 4 dental gypsum according to the classification of ISO 6873/2013 was used to reproduce the difference in moisture environment. Differences in moisture content were measured using micro-computed X-ray tomography (micro-CT). The micro-CT results showed that the moisture content was the highest and lowest in the grade 2 and 4 gypsum molds, respectively. Moreover, the setting time indicated by the manufacturer was the shortest for the grade 2 gypsum mold. Hence, the differences in moisture content significantly affect the setting time of MTA. This result can help set future experimental conditions and develop premixed calcium silicate-based MTA products.
Effects of Anionic Emulsifiers and Emulsified Asphalt on Hydration and Microstructure of Cement
Authors: Zhang Panpan , Hou Yitong , Niu Kaimin , Tian Bo , Wang Hao
Published: December 2023

Cement-emulsified asphalt (CEA) has been widely used in slab ballastless track and asphalt pavement cold recycling projects because of its high stiffness and toughness. In CEA material, emulsifiers and asphalt affect the cement’s hydration process and microstructure. Thus, to further investigate the effects of anionic emulsifiers (AEs) and anionic emulsified asphalt (AEA) with different demulsification rates on the hydration process and microstructure of cement, two types of AE (rapid-setting and slow-setting) and their corresponding AEA were used to prepare modified cement pastes. First, it was confirmed that the AEs and AEA delayed cement hydration by measuring the setting time, X-ray diffraction (XRD) patterns, and electrical resistivity of the cement paste. Then, the microstructure of the cement paste was determined with mercury intrusion porosimetry (MIP) and a scanning electron microscope (SEM), and it was found that AEs and AEA have varying degrees of inhibitory effects on the formation of the cement paste microstructure. Finally, based on the energy dispersive spectrometer (EDS) element content of the cement paste and Fourier transform infrared spectroscopy (FTIR) on the two AEs, the inhibition mechanism of AE and AEA with different demulsifier rates on the cement hydration process was analyzed. The experimental results showed that both AEs and AEA delayed the hydration process of cement to varying degrees and altered the microstructure of cement, and slow setting anionic emulsified asphalt (SAEA) had the greatest impact on the hydration process and microstructure of cement. Compared to pure cement paste, the initial setting time of cement paste mixed with SAEA was delayed by 73.9%, and the final setting time was delayed by 66.7%. After adding SAEA, the most probable aperture of the cement paste increased from 62.50 nm to 71.19 nm after one day of hydration. Due to the fact that there were more carboxyl groups with negative charges, more -COO− was adsorbed onto the surface of cement particles in the slow-cracking anionic emulsifier (SAE); compared with the rapid-setting anionic emulsifier (RAE) and the rapid-setting anionic emulsified asphalt (RAEA), the SAE and the SAEA had a stronger delaying effect on the hydration reaction of cement.
Highly Reinforced Acrylic Resins for Hard Tissue Engineering and Their Suitability to Be Additively Manufactured through Nozzle-Based Photo-Printing
Authors: Gallicchio Vito , Spinelli Vincenzo , Russo Teresa , Marino Ciro , Spagnuolo Gianrico , Rengo Carlo , De Santis Roberto
Published: December 2023

Mineralized connective tissues represent the hardest materials of human tissues, and polymer based composite materials are widely used to restore damaged tissues. In particular, light activated resins and composites are generally considered as the most popular choice in the restorative dental practice. The first purpose of this study is to investigate novel highly reinforced light activated particulate dental composites. An innovative additive manufacturing technique, based on the extrusion of particle reinforced photo-polymers, has been recently developed for processing composites with a filler fraction (w/w) only up to 10%. The second purpose of this study is to explore the feasibility of 3D printing highly reinforced composites. A variety of composites based on 2,2-bis(acryloyloxymethyl)butyl acrylate and trimethylolpropane triacrylate reinforced with silica, titanium dioxide, and zirconia nanoparticles were designed and investigated through compression tests. The composite showing the highest mechanical properties was processed through the 3D bioplotter AK12 equipped with the Enfis Uno Air LED Engine. The composite showing the highest stiffness and strength was successfully processed through 3D printing, and a four-layer composite scaffold was realized. Mechanical properties of particulate composites can be tailored by modifying the type and amount of the filler fraction. It is possible to process highly reinforced photopolymerizable composite materials using additive manufacturing technologies consisting of 3D fiber deposition through extrusion in conjunction with photo-polymerization.
Characterization and Simulation of Shear-Induced Damage in Selective-Laser-Sintered Polyamide 12
Authors: Schob Daniela , Richter Lukas , Kotecki Krzysztof , Kurpisz Dariusz , Roszak Robert , Maasch Philipp , Ziegenhorn Matthias
Published: December 2023

This paper presents the characterisation of selective-laser-sintered (SLS) samples of polyamide 12 (PA12) under shear loading. PA12 is a semi-crystalline thermoplastic and is used in various industries. Its behaviour under shear stress, which is particularly important for product reliability, has not yet been sufficiently investigated. This research focuses on understanding the material and damage behaviour of PA12 under shear-induced stress conditions. The study included quasi-static experiments and numerical simulations. Samples were prepared via SLS and tested according to ASTM standards. Digital image correlation (DIC) was used for precise deformation measurements. The Chaboche material model was used for the viscoplastic behaviour in the numerical simulations. Due to existing material discontinuities in the form of voids, the material model was coupled with the Gurson–Tvergaard–Needleman (GTN) damage model. A modified approach of the GTN model was used to account for low stress triaxiality under shear loading. These models were implemented in MATLAB and integrated into Abaqus via a User Material (UMAT) subroutine. The results of the experiments and simulations showed a high degree of accuracy. An important finding was the significant influence of the shear factor kw on the damage behaviour, especially during failure. This factor proved to be essential for the accurate prediction of material behaviour under shear-induced stress conditions. The integration of the modified GTN model with the Chaboche material model in UMAT enables an accurate prediction of the material and damage behaviour and thus makes an important contribution to the understanding of the mechanical material behaviour of SLS PA12 specimens.
The Influence of the Burnishing Process on the Change in Surface Hardness, Selected Surface Roughness Parameters and the Material Ratio of the Welded Joint of Aluminum Tubes
Authors: Labuda Wojciech , Wieczorska Agata , Charchalis Adam
Published: December 2023

This paper presents the effect of burnishing on the surface hardness, selected surface roughness parameters and material ratio of tubes made of an EN AW-6060 aluminum alloy after welding. The prepared specimens were subjected to a 141-TIG welding process, after which the surfaces to be burnished were given a finishing turning treatment with DURACARB’s CCGT09T302-DL cutting insert to remove the weld face. After the turning process, the surface finish treatment was carried out by rolling burnishing, for which Yamato’s SRMD burnishing tool was used. The surface hardness, selected surface roughness parameters and material ratio were then measured. An analysis of the results showed an increase in hardness in the surface layer, as well as an improvement in the analyzed surface roughness parameters and the material ratio of the native material and the weld.