bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptive Charging Simulation Model for Different Electric Vehicles and Mobility Patterns
Authors: Hammerschmitt Bruno Knevitz , Unsihuay-Vila Clodomiro , Sausen Jordan Passinato , Capeletti Marcelo Bruno , Aoki Alexandre Rasi , Teixeira Mateus Duarte , Barriquello Carlos Henrique , Abaide Alzenira da Rosa
Published: August 2024

Electric mobility is a sustainable alternative for mitigating carbon emissions by replacing the conventional fleet. However, the low availability of data from charging stations makes planning energy systems for the integration of electric vehicles (EVs) difficult. Given this, this work focuses on developing an adaptive computational tool for charging simulation, considering many EVs and mobility patterns. Technical specifications data from many EVs are considered for charging simulation, such as battery capacity, driving range, charging time, charging standard for each EV, and mobility patterns. Different simulations of charging many EVs and analyses of weekly charging load profiles are carried out, portraying the characteristics of the different load profiles and the challenges that system planners expect. The research results denote the importance of considering different manufacturers and models of EVs in the composition of the aggregate charging load profile and mobility patterns of the region. The developed model can be adapted to any system, expanded with new EVs, and scaled to many EVs, supporting different research areas.
Thermal Imaging-Based Abnormal Heating Detection for High-Voltage Power Equipment
Authors: Liu Jiange , Xu Chang , Ye Qian , Cao Li , Dai Xin , Li Qingwu
Published: August 2024

Thermal infrared imaging could detect hidden faults in various types of high-voltage power equipment, which is of great significance for power inspections. However, there are still certain issues with thermal-imaging-based abnormal heating detection methods due to varying appearances of abnormal regions and complex temperature interference from backgrounds. To solve these problems, a contour-based instance segmentation network is first proposed to utilize thermal (T) and visual (RGB) images, realizing high-accuracy segmentation against complex and changing environments. Specifically, modality-specific features are encoded via two-stream backbones and fused in spatial, channel, and frequency domains. In this way, modality differences are well handled, and effective complementary information is extracted for object detection and contour initialization. The transformer decoder is further utilized to explore the long-range relationships between contour points with background points, and to achieve the deformation of contour points. Then, the auto-encoder-based reconstruction network is developed to learn the distribution of power equipment using the proposed random argument strategy. Meanwhile, the UNet-like discriminative network directly explores the differences between the reconstructed and original image, capturing the deviation of poor reconstruction regions for abnormal heating detection. Many images are acquired in transformer substations with different weathers and day times to build the datasets with pixel-level annotation. Several extensive experiments are conducted for qualitative and quantitative evaluation, while the comparison results fully prove the effectiveness and robustness of the proposed instance segmentation method. The practicality and performance of the proposed abnormal heating detection method are evaluated on image patches with different kinds of insulators.
Lactoferrin Affects the Viability of Bacteria in a Biofilm and the Formation of a New Biofilm Cycle of Mannheimia haemolytica A2
Authors: Ruiz-Mazón Lucero , Ramírez-Rico Gerardo , de la Garza Mireya
Published: August 2024

Respiratory diseases in ruminants are responsible for enormous economic losses for the dairy and meat industry. The main causative bacterial agent of pneumonia in ovine is Mannheimia haemolytica A2. Due to the impact of this disease, the effect of the antimicrobial protein, bovine lactoferrin (bLf), against virulence factors of this bacterium has been studied. However, its effect on biofilm formation has not been reported. In this work, we evaluated the effect on different stages of the biofilm. Our results reveal a decrease in biofilm formation when bacteria were pre-incubated with bLf. However, when bLf was added at the start of biofilm formation and on mature biofilm, an increase was observed, which was visualized by greater bacterial aggregation and secretion of biofilm matrix components. Additionally, through SDS-PAGE, a remarkable band of ~80 kDa was observed when bLf was added to biofilms. Therefore, the presence of bLf on the biofilm was determined through the Western blot and Microscopy techniques. Finally, by using Live/Dead staining, we observed that most of the bacteria in a biofilm with bLf were not viable. In addition, bLf affects the formation of a new biofilm cycle. In conclusion, bLf binds to the biofilm of M. haemolytica A2 and affects the viability of bacteria and the formation a new biofilm cycle.
High-Protein Mulberry Leaves Improve Glucose and Lipid Metabolism via Activation of the PI3K/Akt/PPARα/CPT-1 Pathway
Authors: Shan Ziyi , Zhang Huilin , He Changhao , An Yongcheng , Huang Yan , Fu Wanxin , Wang Menglu , Du Yuhang , Xie Jiamei , Yang Yang , Zhao Baosheng
Published: August 2024

High-Protein Mulberry is a novel strain of mulberry. High-Protein Mulberry leaves (HPM) were the subject of this study, which aimed to investigate its efficacy and underlying mechanisms in modulating glucose and lipid metabolism. A six-week intervention using db/db mice was carried out to assess the effects of HPM on serum lipid levels, liver function, and insulin (INS) levels. qRT-PCR and Western Blotting were employed to measure key RNA and protein expressions in the PI3K/Akt and PPARα/CPT-1 pathways. UHPLC-MS and the Kjeldahl method were utilized to analyze the component content and total protein. Additionally, network pharmacology was employed to predict regulatory mechanism differences between HPM and Traditional Mulberry leaves. The results of the study revealed significant improvements in fasting blood glucose, glucose tolerance, and insulin resistance in mice treated with HPM. HPM notably reduced serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and INS, while increasing high-density lipoprotein cholesterol (HDL-C) levels. The treatment also effectively mitigated liver fatty lesions, inflammatory infiltration, and islet atrophy. HPM activation of the PI3K/Akt/PPARα/CPT-1 pathway suggested its pivotal role in the regulation of glucose and lipid metabolism. With its rich composition and pharmacodynamic material basis, HPM displayed a greater number of targets associated with glucose and lipid metabolism pathways, underscoring the need for further research into its potential therapeutic applications.
Vitronectin Levels in the Plasma of Neuroblastoma Patients and Culture Media of 3D Models: A Prognostic Circulating Biomarker?
Authors: López-Carrasco Amparo , Vieco-Martí Isaac , Granados-Aparici Sofía , Acevedo-León Delia , Estañ-Capell Nuria , Portugal Raquel , Huerta-Aragonés Jorge , Cañete Adela , Navarro Samuel , Noguera Rosa
Published: August 2024

Vitronectin is a glycoprotein present in plasma and the extracellular matrix that is implicated in cell migration. The high amount of vitronectin found in neuroblastoma biopsies has been associated with poor prognosis. Moreover, increased vitronectin levels have been described in the plasma of patients with different cancers. Our aim was to assess vitronectin as a potential circulating biomarker of neuroblastoma prognosis. Vitronectin concentration was quantified using ELISA in culture media of four neuroblastoma cell lines grown in a monolayer and in 3D models, and in the plasma of 114 neuroblastoma patients. Three of the neuroblastoma cell lines secreted vitronectin to culture media when cultured in a monolayer and 3D models. Vitronectin release was higher by neuroblastoma cells cultured in 3D models than in the monolayer and was still elevated when cells were grown in 3D scaffolds with cross-linked vitronectin. Vitronectin secretion occurred independently of cell numbers in cultures. Its concentration in the plasma of neuroblastoma patients ranged between 52.4 and 870 µg/mL (median, 218 µg/mL). A ROC curve was used to establish a cutoff of 361 µg/mL, above which patients over 18 months old had worse prognosis (p = 0.0018). Vitronectin could be considered a new plasma prognostic biomarker in neuroblastoma and warrants confirmation in collaborative studies. Drugs inhibiting vitronectin interactions with cells and/or the extracellular matrix could represent a significant improvement in survival for neuroblastoma patients.
Overexpression of the β-Subunit of Acid Ceramidase in the Epidermis of Mice Provokes Atopic Dermatitis-like Skin Symptoms
Authors: Sashikawa-Kimura Miho , Takada Mariko , Hossain Md Razib , Tsuda Hidetoshi , Xie Xiaonan , Komine Mayumi , Ohtsuki Mamitaro , Imokawa Genji
Published: August 2024

We previously reported that a pathogenic abnormality in the barrier and water-holding functions of the stratum corneum (SC) in the skin of patients with atopic dermatitis (AD) is mainly attributable to significantly decreased levels of total ceramides in the SC. That decrease is mediated by the abnormal expression of a novel ceramide-reducing enzyme, sphingomyelin/glucosylceramide deacylase (SGDase), which is the β-subunit (ASAH1b) of acid ceramidase. In this study, we determined whether mice overexpressing ASAH1b in their epidermis develop AD-like skin symptoms. We generated transgenic (TG) mice overexpressing ASAH1b, regulated by the involucrin promoter, to localize its expression in the upper epidermis. After hair removal using a depilatory cream containing glycolic acid, the TG mice without any visible skin inflammation at 8 weeks of age had increased levels of ASAH1b and decreased levels of SC ceramide, with disrupted barrier functions measured by trans-epidermal water loss compared to the wild-type (WT) mice. Interestingly, enzymatic assays revealed that SGDase activity was not detectable in the skin of the TG mice compared to WT mice. Immunological staining revealed that there was an increased expression level of IL-33 in the epidermis and an accumulation of macrophages in the dermis of TG mice compared to WT mice, which are phenotypic characteristics of AD, that were exacerbated by tape-stripping of the skin. In the skin of the TG mice, the mRNA levels of IL-5, CCL11, IL-22, CXCL10, and IFNγ were significantly upregulated compared to the WT mice, and tape-stripping significantly increased the mRNA levels of IL-4, IL-33, CXCL1, CXCL12, TLR9, and CD163 compared to WT mice. These findings strongly indicate that the skin of the depilatory cream-treated TG mice exists in an atopic dry skin condition that is highly sensitive to various environmental stimuli. The sum of our results suggests that ASAH1b itself, even in the absence of its enzymatic activity, is a major etiologic factor for atopic dry skin symptoms via an unknown mechanism.
Molecular Basis of Hydatidiform Moles—A Systematic Review
Authors: Bahutair Shadha Nasser Mohammed , Dube Rajani , Kuruba Manjunatha Goud Bellary , Salama Rasha Aziz Attia , Patni Mohamed Anas Mohamed Faruk , Kar Subhranshu Sekhar , Kar Rakhee
Published: August 2024

Gestational trophoblastic diseases (GTDs) encompass a spectrum of conditions characterized by abnormal trophoblastic cell growth, ranging from benign molar pregnancies to malignant trophoblastic neoplasms. This systematic review explores the molecular underpinnings of GTDs, focusing on genetic and epigenetic factors that influence disease progression and clinical outcomes. Based on 71 studies identified through systematic search and selection criteria, key findings include dysregulations in tumor suppressor genes such as p53, aberrant apoptotic pathways involving BCL-2 (B-cell lymphoma), and altered expression of growth factor receptors and microRNAs (micro-ribose nucleic acid). These molecular alterations not only differentiate molar pregnancies from normal placental development but also contribute to their clinical behavior, from benign moles to potentially malignant forms. The review synthesizes insights from immunohistochemical studies and molecular analyses to provide a comprehensive understanding of GTD pathogenesis and implications for personalized care strategies.
Long-Term Stability and Efficacy of NCT Solutions
Authors: Staudinger Gabriel J. , Thomas Zach M. , Hooper Sarah E. , Williams Jeffrey F. , Robins Lori I.
Published: August 2024

To realize the potential for the use of N-chlorotaurine (NCT) in healthcare, a better understanding of the long-term stability of the compound in water is needed. An array of analytical procedures is required that can measure changes in NCT concentration over time and allow for the detection and identification of contaminants and likely degradation end products. We used UV-Vis and NMR spectroscopy, HPLC, and LCMS to establish the stability of NCT in solutions subjected to prolonged ambient and elevated temperatures. Stability proved to be dependent on concentration with half-lives of ~120 days and ~236 days for 1% and 0.5% solutions of NCT at ~20 °C. Regardless of initial pH, all solutions shifted toward and maintained a pH of ~8.3 at 20 °C and 40 °C. NCT at 500 µg/mL and 250 µg /mL inhibited biofilm formation by Pseudomonas aeruginosa and Staphylococcus aureus but did not disperse established biofilms. NCT exposure to the biofilms had profound effects on the viability of both bacteria, reducing live organisms by >90%. Exposure of Interleukin-6 (IL-6) to 11 µM NCT reduced the binding of IL-6 to an immobilized specific antibody by ~48%, which is 5× the amount required for HOCl to bring about the same effect in this test system. Our data demonstrate the potency of the compound as an antimicrobial agent with potential benefits in the management of infected chronic wounds and suggest that NCT may contribute to anti-inflammatory processes in vivo by direct modification of cytokine mediators.
Integrative Analysis of Transcriptomic Profiles and Physiological Responses Provide New Insights into Drought Stress Tolerance in Oil Palm (Elaeis guineensis Jacq.)
Authors: Mejía-Alvarado Fernan Santiago , Caicedo-Zambrano Arley Fernando , Botero-Rozo David , Araque Leonardo , Bayona-Rodríguez Cristihian Jarri , Jazayeri Seyed Mehdi , Montoya Carmenza , Ayala-Díaz Iván , Ruiz-Romero Rodrigo , Romero Hernán Mauricio
Published: August 2024

Oil palm (Elaeis guineensis Jacq.) is a highly productive crop economically significant for food, cosmetics, and biofuels. Abiotic stresses such as low water availability, salt accumulation, and high temperatures severely impact oil palm growth, physiology, and yield by restricting water flux among soil, plants, and the environment. While drought stress’s physiological and biochemical effects on oil palm have been extensively studied, the molecular mechanisms underlying drought stress tolerance remain unclear. Under water deficit conditions, this study investigates two commercial E. guineensis cultivars, IRHO 7001 and IRHO 2501. Water deficit adversely affected the physiology of both cultivars, with IRHO 2501 being more severely impacted. After several days of water deficit, there was a 40% reduction in photosynthetic rate (A) for IRHO 7001 and a 58% decrease in IRHO 2501. Further into the drought conditions, there was a 75% reduction in A for IRHO 7001 and a 91% drop in IRHO 2501. Both cultivars reacted to the drought stress conditions by closing stomata and reducing the transpiration rate. Despite these differences, no significant variations were observed between the cultivars in stomatal conductance, transpiration, or instantaneous leaf-level water use efficiency. This indicates that IRHO 7001 is more tolerant to drought stress than IRHO 2501. A differential gene expression and network analysis was conducted to elucidate the differential responses of the cultivars. The DESeq2 algorithm identified 502 differentially expressed genes (DEGs). The gene coexpression network for IRHO 7001 comprised 274 DEGs and 46 predicted HUB genes, whereas IRHO 2501’s network included 249 DEGs and 3 HUB genes. RT-qPCR validation of 15 DEGs confirmed the RNA-Seq data. The transcriptomic profiles and gene coexpression network analysis revealed a set of DEGs and HUB genes associated with regulatory and transcriptional functions. Notably, the zinc finger protein ZAT11 and linoleate 13S-lipoxygenase 2-1 (LOX2.1) were overexpressed in IRHO 2501 but under-expressed in IRHO 7001. Additionally, phytohormone crosstalk was identified as a central component in the response and adaptation of oil palm to drought stress.
Caveolin and NOS in the Development of Muscular Dystrophy
Authors: Nakashima Moeka , Suga Naoko , Yoshikawa Sayuri , Matsuda Satoru
Published: August 2024

Caveolin is a structural protein within caveolae that may be involved in transmembrane molecular transport and/or various intercellular interactions within cells. Specific mutations of caveolin-3 in muscle fibers are well known to cause limb–girdle muscular dystrophy. Altered expression of caveolin-3 has also been detected in Duchenne muscular dystrophy, which may be a part of the pathological process leading to muscle weakness. Interestingly, it has been shown that the renovation of nitric oxide synthase (NOS) in sarcolemma with muscular dystrophy could improve muscle health, suggesting that NOS may be involved in the pathology of muscular dystrophy. Here, we summarize the notable function of caveolin and/or NOS in skeletal muscle fibers and discuss their involvement in the pathology as well as possible tactics for the innovative treatment of muscular dystrophies.
Uncovering the Expression Pattern of the Costimulatory Receptors ICOS, 4-1BB, and OX-40 in Exhausted Peripheral and Tumor-Infiltrating Natural Killer Cells from Patients with Cervical Cancer
Authors: Rojas-Diaz Jose Manuel , Solorzano-Ibarra Fabiola , Garcia-Barrientos Nadia Tatiana , Klimov-Kravtchenko Ksenia , Guitron-Aviña Marcela Sofia , Cruz-Ramos Jose Alfonso , Ortiz-Lazareno Pablo Cesar , Urciaga-Gutierrez Pedro Ivan , Bueno-Topete Miriam Ruth , Garcia-Chagollan Mariel , Haramati Jesse , del Toro-Arreola Susana
Published: August 2024

Cervical cancer (CC) poses a significant health burden, particularly in low- and middle-income countries. NK cells play a crucial role against CC; however, they can become exhausted and lose their cytotoxic capacity. This work explores the expression of costimulatory receptors (ICOS, 4-1BB, OX-40) in exhausted NK cells from CC patients. Peripheral blood and tumor biopsies were collected, and flow cytometry was used to evaluate the expression of costimulatory receptors in exhausted NK cells. There is an increase of peripheral exhausted NK cells (PD-1+TIGIT+) in CC patients; this subpopulation has a selectively increased expression of the costimulatory receptors ICOS and 4-1BB. An exhausted population is also highly increased in tumor-infiltrating NK cells, and it shows a dramatically increased expression of the costimulatory receptors ICOS (>15×) and 4-1BB (>10×) compared to peripheral NK cells. The exhausted cells, both in the periphery and in the tumor infiltrating lymphocytes (TILs), are also more likely than non-exhausted NK cell populations (PD-1−TIGIT−) to express these costimulatory receptors; increases ranging from 2.0× ICOS, 2.4× 4-1BB, and 2.6× OX-40 in CD56dim PBMCs to 1.5× ICOS, 5× 4-1BB, and 10× OX-40 in TILs were found. Our study demonstrates for the first time the increased expression of the costimulatory receptors ICOS, 4-1BB, and OX-40 in peripheral CD56dim, CD56bright, and tumor-infiltrating NK cells in CC. Targeting these receptors for stimulation could reverse exhaustion and be a promising immunotherapy strategy.
Chromosome-Level Assembly Reveals a Fifteen-Chromosome Aneuploid Genome and Environmental Adaptation Strategy of Chinese Traditional Medical Fungus Wolfiporia hoelen
Authors: Li Shoujian , Li Bing , Guo Shunxing
Published: August 2024

The sclerotia of Wolfiporia hoelen are one of the most important traditional Chinese medicines and foods commonly used in China, Japan, Korea, and other Asian countries. To provide a high-quality reference genome and deepen our understanding of the genome of W. hoelen to elucidate various biological phenomena. In this study, we assembled three genomes of W. hoelen using a combination of Nanopore and Illumina sequencing strategies. The fifteen-chromosome genome L7 of W. hoelen was assembled with two-sided telomere and rDNA sequences for the first time. The chromosome count was subsequently confirmed through collinearity analysis, correcting the previous belief that W. hoelen had only fourteen chromosomes. Moreover, the aneuploid genome was discovered in W. hoelen for the first time through sequencing depth analysis of different chromosomes, and only some strains of W. hoelen exhibit aneuploid genomes. According to the genome analysis of homokaryotic offspring and protoplast-isolated strains, a potential variation in chromosome allocation patterns was revealed. Moreover, the gene function enrichment analysis of genes on reduplicated chromosomes demonstrated that aneuploidy in the genome may be the result of environmental adaptation for W. hoelen. The discovery of an aneuploid genome also provides new ideas for genetic improvement of W. hoelen.
Activation of the 5-HT1A Receptor by Eltoprazine Restores Mitochondrial and Motor Deficits in a Drosophila Model of Fragile X Syndrome
Authors: Vannelli Anna , Mariano Vittoria , Bagni Claudia , Kanellopoulos Alexandros K.
Published: August 2024

Neurons rely on mitochondrial energy metabolism for essential functions like neurogenesis, neurotransmission, and synaptic plasticity. Mitochondrial dysfunctions are associated with neurodevelopmental disorders including Fragile X syndrome (FXS), the most common cause of inherited intellectual disability, which also presents with motor skill deficits. However, the precise role of mitochondria in the pathophysiology of FXS remains largely unknown. Notably, previous studies have linked the serotonergic system and mitochondrial activity to FXS. Our study investigates the potential therapeutic role of serotonin receptor 1A (5-HT1A) in FXS. Using the Drosophila model of FXS, we demonstrated that treatment with eltoprazine, a 5-HT1A agonist, can ameliorate synaptic transmission, correct mitochondrial deficits, and ultimately improve motor behavior. While these findings suggest that the 5-HT1A-mitochondrial axis may be a promising therapeutic target, further investigation is needed in the context of FXS.
MODY Only Monogenic? A Narrative Review of the Novel Rare and Low-Penetrant Variants
Authors: Hasballa Iderina , Maggi Davide
Published: August 2024

Maturity-onset diabetes of the young (MODY) represents the most frequent form of monogenic diabetes mellitus (DM), currently classified in 14 distinct subtypes according to single gene mutations involved in the differentiation and function of pancreatic β-cells. A significant proportion of MODY has unknown etiology, suggesting that the genetic landscape is still to be explored. Recently, novel potentially MODY-causal genes, involved in the differentiation and function of β-cells, have been identified, such as RFX6, NKX2.2, NKX6.1, WFS1, PCBD1, MTOR, TBC1D4, CACNA1E, MNX1, AKT2, NEUROG3, EIF2AK3, GLIS3, HADH, and PTF1A. Genetic and clinical features of MODY variants remain highly heterogeneous, with no direct genotype–phenotype correlation, especially in the low-penetrant subtypes. This is a narrative review of the literature aimed at describing the current state-of-the-art of the novel likely MODY-associated variants. For a deeper understanding of MODY complexity, we also report some related controversies concerning the etiological role of some of the well-known pathological genes and MODY inheritance pattern, as well as the rare association of MODY with autoimmune diabetes. Due to the limited data available, the assessment of MODY-related genes pathogenicity remains challenging, especially in the setting of rare and low-penetrant subtypes. In consideration of the crucial importance of an accurate diagnosis, prognosis and management of MODY, more studies are warranted to further investigate its genetic landscape and the genotype–phenotype correlation, as well as the pathogenetic contribution of the nongenetic modifiers in this cohort of patients.
Unbiased Proteomic Exploration Suggests Overexpression of Complement Cascade Proteins in Plasma from Patients with Psoriasis Compared with Healthy Individuals
Authors: Kromann Bjørn , Niu Lili , Møller Line B. P. , Sølberg Julie , Sulek Karolina , Gyldenløve Mette , Dyring-Andersen Beatrice , Skov Lone , Løvendorf Marianne B.
Published: August 2024

Knowledge about the molecular mechanisms underlying the systemic inflammation observed in psoriasis remains incomplete. In this study, we applied mass spectrometry-based proteomics to compare the plasma protein levels between patients with psoriasis and healthy individuals, aiming to unveil potential systemically dysregulated proteins and pathways associated with the disease. Plasma samples from adult patients with moderate-to-severe psoriasis vulgaris (N = 59) and healthy age- and sex-matched individuals (N = 21) were analyzed using liquid chromatography–tandem mass spectrometry. Patients did not receive systemic anti-psoriatic treatment for four weeks before inclusion. A total of 776 protein groups were quantified. Of these, 691 were present in at least 60% of the samples, providing the basis for the downstream analysis. We identified 20 upregulated and 22 downregulated proteins in patients with psoriasis compared to controls (p < 0.05). Multiple proteins from the complement system were upregulated, including C2, C4b, C5, and C9, and pathway analysis revealed enrichment of proteins involved in complement activation and formation of the terminal complement complex. On the other end of the spectrum, periostin was the most downregulated protein in sera from patients with psoriasis. This comprehensive proteomic investigation revealed significantly elevated levels of complement cascade proteins in psoriatic plasma, which might contribute to increased systemic inflammation in patients with psoriasis.
Altered Host microRNAomics in HIV Infections: Therapeutic Potentials and Limitations
Authors: Santiago Maria J. , Chinnapaiyan Srinivasan , Panda Kingshuk , Rahman Md. Sohanur , Ghorai Suvankar , Rahman Irfan , Black Stephen M. , Liu Yuan , Unwalla Hoshang J.
Published: August 2024

microRNAs have emerged as essential regulators of health and disease, attracting significant attention from researchers across diverse disciplines. Following their identification as noncoding oligonucleotides intricately involved in post-transcriptional regulation of protein expression, extensive efforts were devoted to elucidating and validating their roles in fundamental metabolic pathways and multiple pathologies. Viral infections are significant modifiers of the host microRNAome. Specifically, the Human Immunodeficiency Virus (HIV), which affects approximately 39 million people worldwide and has no definitive cure, was reported to induce significant changes in host cell miRNA profiles. Identifying and understanding the effects of the aberrant microRNAome holds potential for early detection and therapeutic designs. This review presents a comprehensive overview of the impact of HIV on host microRNAome. We aim to review the cause-and-effect relationship between the HIV-induced aberrant microRNAome that underscores miRNA’s therapeutic potential and acknowledge its limitations.
Activation of the TRPML1 Ion Channel Induces Proton Secretion in the Human Gastric Parietal Cell Line HGT-1
Authors: Mueller Alina Ulrike , Andersen Gaby , Richter Phil , Somoza Veronika
Published: August 2024

The lysosomal Ca2+ channel TRPML1 was found to be responsible for gastric acid secretion in murine gastric parietal cells by inducing the trafficking of H+/K+-ATPase containing tubulovesicles to the apical membrane. Therefore, we hypothesized a similar role of TRPML1 in regulating proton secretion in the immortalized human parietal cell line HGT-1. The primary focus was to investigate the involvement of TRPML1 in proton secretion using the known synthetic agonists ML-SA1 and ML-SA5 and the antagonist ML-SI3 and, furthermore, to identify food-derived compounds that target the channel. Proton secretion stimulated by ML-SA1 was reduced by 122.2 ± 22.7% by the antagonist ML-SI3. The steroid hormone 17β-estradiol, present in animal-derived foods, diminished the proton secretory effect of ML-SA1 by 63.4 ± 14.5%. We also demonstrated a reduction in the proton secretory effects of ML-SA1 and ML-SA5 on TRPML1 knock-down cells. The food-derived compounds sulforaphane and trehalose promoted proton secretion in HGT-1 cells but may act independently of TRPML1. Also, histamine- and caffeine-induced proton secretion were affected by neither the TRPML1 antagonist ML-SI3 nor the TRPML1 knock-down. In summary, the results obtained suggest that the activation of TRPML1 promotes proton secretion in HGT-1 cells, but the channel may not participate in canonical signaling pathways.
High Resolution HLA-A, HLA-B, and HLA-C Allele Frequencies in Romanian Hematopoietic Stem Cell Donors
Authors: Caragea Andreea Mirela , Ursu Radu-Ioan , Maruntelu Ion , Tizu Maria , Constantinescu Alexandra-Elena , Tălăngescu Adriana , Constantinescu Ileana
Published: August 2024

The HLA genes are associated with various autoimmune pathologies, with the control of the immune response also being significant in organs and cells transplantation. The aim of the study is to identify the HLA-A, HLA-B, and HLA-C alleles frequencies in the analyzed Romanian cohort. We performed HLA typing using next-generation sequencing (NGS) in a Romanian cohort to estimate class I HLA allele frequencies up to a six-digit resolution. A total of 420 voluntary donors from the National Registry of Voluntary Hematopoietic Stem Cell Donors (RNDVCSH) were included in the study for HLA genotyping. Peripheral blood samples were taken and brought to the Fundeni Clinical Institute during 2020–2021. HLA genotyping was performed using the Immucor Mia Fora NGS MFlex kit. A total of 109 different alleles were detected in 420 analyzed samples, out of which 31 were for HLA-A, 49 for HLA-B, and 29 for HLA-C. The most frequent HLA-A alleles were HLA-A*02:01:01 (26.11%), HLA-A*01:01:01 (12.5%), HLA-A*24:02:01 (11.67%), HLA-A*03:01:01 (9.72%), HLA-A*11:01:01, and HLA-A*32:01:01 (each with 8.6%). For the HLA-B locus, the most frequent allele was HLA-B*18:01:01 (11.25%), followed by HLA-B*51:01:01 (10.83%) and HLA-B*08:01:01 (7.78%). The most common HLA-C alleles were HLA-C*07:01:01 (17.36%), HLA-C*04:01:01 (13.47%), and HLA-C*12:03:01 (10.69%). Follow-up studies are ongoing for confirming the detected results.
Preclinical Evaluation of Soluble Epoxide Hydrolase Inhibitor AMHDU against Neuropathic Pain
Authors: Babkov Denis , Eliseeva Natalya , Adzhienko Kristina , Bagmetova Viktoria , Danilov Dmitry , McReynolds Cynthia B. , Morisseau Christophe , Hammock Bruce D. , Burmistrov Vladimir
Published: August 2024

Inhibition of soluble epoxide hydrolase (sEH) is a promising therapeutic strategy for treating neuropathic pain. These inhibitors effectively reduce diabetic neuropathic pain and inflammation induced by Freund’s adjuvant which makes them a suitable alternative to traditional opioids. This study showcased the notable analgesic effects of compound AMHDU (1,1′-(hexane-1,6-diyl)bis(3-((adamantan-1-yl)methyl)urea)) in both inflammatory and diabetic neuropathy models. While lacking anti-inflammatory properties in a paw edema model, AMHDU is comparable to celecoxib as an analgesic in 30 mg/kg dose administrated by intraperitoneal injection. In a diabetic tactile allodynia model, AMHDU showed a prominent analgesic activity in 10 mg/kg intraperitoneal dose (p < 0.05). The effect is comparable to that of gabapentin, but without the risk of dependence due to a different mechanism of action. Low acute oral toxicity (>2000 mg/kg) and a high therapeutic index makes AMHDU a promising candidate for further structure optimization and preclinical evaluation.
Role of PRMT1 and PRMT5 in Breast Cancer
Authors: Martinez Sébastien , Sentis Stéphanie , Poulard Coralie , Trédan Olivier , Le Romancer Muriel
Published: August 2024

Breast cancer is the most common cancer diagnosed in women worldwide. Early-stage breast cancer is curable in ~70–80% of patients, while advanced metastatic breast cancer is considered incurable with current therapies. Breast cancer is a highly heterogeneous disease categorized into three main subtypes based on key markers orientating specific treatment strategies for each subtype. The complexity of breast carcinogenesis is often associated with epigenetic modification regulating different signaling pathways, involved in breast tumor initiation and progression, particularly by the methylation of arginine residues. Protein arginine methyltransferases (PRMT1-9) have emerged, through their ability to methylate histones and non-histone substrates, as essential regulators of cancers. Here, we present an updated overview of the mechanisms by which PRMT1 and PRMT5, two major members of the PRMT family, control important signaling pathways impacting breast tumorigenesis, highlighting them as putative therapeutic targets.
Evaluation of the Antifibrotic Effects of Drugs Commonly Used in Inflammatory Intestinal Diseases on In Vitro Intestinal Cellular Models
Authors: Artone Serena , Ciafarone Alessia , Augello Francesca Rosaria , Lombardi Francesca , Cifone Maria Grazia , Palumbo Paola , Cinque Benedetta , Latella Giovanni
Published: August 2024

The mechanism underlying intestinal fibrosis, the main complication of inflammatory bowel disease (IBD), is not yet fully understood, and there is no therapy to prevent or reverse fibrosis. We evaluated, in in vitro cellular models, the ability of different classes of drugs currently used in IBD to counteract two pivotal processes of intestinal fibrosis, the differentiation of intestinal fibroblasts to activated myofibroblasts using CCD-18Co cells, and the epithelial-to-mesenchymal transition (EMT) of intestinal epithelial cells using Caco-2 cells (IEC), both being processes induced by transforming growth factor-β1 (TGF-β1). The drugs tested included mesalamine, azathioprine, methotrexate, prednisone, methylprednisolone, budesonide, infliximab, and adalimumab. The expression of fibrosis and EMT markers (collagen-I, α-SMA, pSmad2/3, occludin) was assessed by Western blot analysis and by immunofluorescence. Of the drugs used, only prednisone, methylprednisolone, budesonide, and adalimumab were able to antagonize the pro-fibrotic effects induced by TGF-β1 on CCD-18Co cells, reducing the fibrosis marker expression. Methylprednisolone, budesonide, and adalimumab were also able to significantly counteract the TGF-β1-induced EMT process on Caco-2 IEC by increasing occludin and decreasing α-SMA expression. This is the first study that evaluates, using in vitro cellular models, the direct antifibrotic effects of drugs currently used in IBD, highlighting which drugs have potential antifibrotic effects.
Heart Rate Variability as a Potential Predictor of Response to Intranasal Esketamine in Patients with Treatment-Resistant Depression: A Preliminary Report
Authors: Moccia Lorenzo , Bartolucci Giovanni , Pepe Maria , Marcelli Ilaria , Grisoni Flavia , Brugnami Andrea , Caso Romina , Bardi Francesca , Calderoni Claudia , Giannico Alessandro Michele , Benini Elisabetta , Di Nicola Marco , Sani Gabriele
Published: August 2024

Background: Esketamine has received approval as a nasal spray (ESK-NS) for treatment-resistant depression (TRD) and evidence from real-world investigations has confirmed the effectiveness of ESK-NS, albeit with interindividual differences in response. Heart rate variability (HRV), defined as the fluctuation in time interval between consecutive heartbeats, can be used to measure autonomic dysfunction in psychiatric disorders and its role has been investigated in diagnosis and prognosis of depression. Methods: This preliminary report aims to evaluate HRV parameters and their association with treatment outcome in 18 patients (55.6% males, 55.6 ± 9.39 years old) with TRD treated with a target dose of ESK-NS for one month (mean dose: 80.9 ± 9.05 mg). The Beck Depression Inventory (BDI) and a 3 min resting electrocardiogram were used to assess changes in depressive symptoms and HRV measurements before and after treatment. Results: Responders (n = 8, 44.5%; based on ≥30% BDI scores reduction) displayed lower HRV values than non-responders at baseline (p = 0.019), which increased at one month (p = 0.038). Receiver–Operating Characteristic (ROC) curves obtained from a logistic regression displayed a discriminative potential for baseline HRV in our sample (AUC = 0.844). Conclusions: These preliminary observations suggest a mutual interaction between esketamine and HRV, especially in relation to treatment response. Further studies are required to investigate electrophysiological profiles among predictors of response to ESK-NS and allow for personalized intervention strategies in TRD that still represent a public health concern.
Contemporary Multimodality Imaging for Diagnosis and Management of Fabry Cardiomyopathy
Authors: Kaur Simrat , Bhalla Jaideep Singh , Erwin Angelika L. , Jaber Wael , Wang Tom Kai Ming
Published: August 2024

Fabry disease (FD) is an X-linked lysosomal storage disorder which leads to the accumulation of globotriaosylceramide (Gb3) in various organs, including the heart. FD can be subdivided into classic disease resulting from negligible residual enzyme activity and a milder, atypical phenotype with later onset and less severe clinical presentation. The use of multimodality cardiac imaging including echocardiography, cardiac magnetic resonance and nuclear imaging is important for the diagnostic and prognostic evaluation in these patients. There are gaps in the literature regarding the comprehensive description of cardiac findings of FD and its evaluation by multimodality imaging. In this review, we describe the contemporary practices and roles of multimodality cardiac imaging in individuals affected with Fabry disease.
Use and Benefit of Sacubitril/Valsartan in Elderly Patients with Heart Failure with Reduced Ejection Fraction
Authors: Roca Luis Nieto , García Marcelino Cortés , Germán Jorge Balaguer , Becerra Antonio José Bollas , Otero José María Romero , Chapel José Antonio Esteban , López Carlos Rodríguez , Lázaro Ana María Pello , Urquía Mikel Taibo , Tuñón José
Published: August 2024

Background: Heart failure (HF) is a highly prevalent syndrome in elderly subjects. Currently, multiple drugs have shown clinical benefits in patients with HF and reduced ejection fraction (HFrEF). However, evidence is scarce in elderly patients (beyond 75 years old), even more so for the latest drugs, such as angiotensin receptor-neprilysin inhibitors (ARNIs). This study aims to evaluate the use and benefits of ARNIs in elderly patients with HFrEF. Methods: A prospective observational cohort study was designed. Patients with left ventricular systolic dysfunction (defined by left ventricular ejection fraction [LVEF] < 40%) and age ≥ 75 years from January 2016 to December 2020 were prospectively included. Patients with an indication for ARNIs at inclusion or throughout follow-up were selected. Clinical, electrocardiographic and echocardiographic variables were collected. Results: A total of 616 patients were included, 34.4% of them female, with a mean age of 83.3 years, mean LVEF of 28.5% and ischemic etiology in 53.9% of patients. Only 14.3% of patients were taking ARNIs. After a mean follow-up of 34 months, 50.2% of patients died, and 62.2% had a cardiac event (total mortality or hospital admission due to HF). Multivariate Cox regression analysis showed that the use of ARNIs was independently and significantly associated with lower rates of mortality [HR 0.36 (95% CI 0.21–0.61)], with similar results in relation to all-cause mortality in a propensity-score-matched analysis [HR 0.33 (95% CI 0.19–0.57)]. Conclusions: We observed an important underuse of ARNIs in a cohort of elderly HFrEF patients, in which treatment with ARNIs was associated with a significant reduction in mortality. Greater implementation of clinical practice guidelines in this group of patients could improve their prognosis.
Cranioplasty after Decompressive Craniectomy (DC) in a Patient with Intracerebral Hemorrhage after SARS-CoV-2 Vaccination-Related Vaccine-Induced Thrombotic Thrombocytopenia (VITT)—Proposal of a Management Protocol for This Rare Pathological Condition
Authors: Spanehl Lennard , Walter Uwe , Thiele Thomas , Dubinski Daniel , Behmanesh Bedjan , Freiman Thomas M. , Wittstock Matthias , Schuss Patrick , Vatter Hartmut , Schneider Matthias , Gessler Florian , Won Sae-Yeon
Published: August 2024

The COVID-19 (coronavirus disease) pandemic had a severe impact on public health worldwide. A rare but serious complication after administration of adenoviral vaccines against SARS-CoV-2 (AstraZeneca–Oxford and Johnson & Johnson) is vaccine-induced immune thrombotic thrombocytopenia and thrombosis (VITT), which can lead to serious complications such as cerebral venous sinus thrombosis (CVST). CVST itself can cause subarachnoid hemorrhage (SAH) and/or intracerebral hemorrhage (ICH), leading to high mortality due to herniation of brain parenchyma. In those patients, an emergent decompressive hemicraniectomy (DC) is regularly performed. Herein, the authors want to focus on the patients who survive DC following VITT-associated CVST and shed light on the neurosurgical considerations in those patients. We herein propose a treatment algorithm regarding the timing and the perioperative management of cranioplasty. We describe an exemplary case highlighting that special circumstances may result in a more urgent need for autologous cranioplasty than usual, based on individual risk assessment.
Global Insights on Prehospital Stroke Care: A Comprehensive Review of Challenges and Solutions in Low- and Middle-Income Countries
Authors: Wiyarta Elvan , Fisher Marc , Kurniawan Mohammad , Hidayat Rakhmad , Geraldi Iskandar Purba , Khan Qaisar Ali , Widyadharma I Putu Eka , Badshah Aliena , Pandian Jeyaraj Durai
Published: August 2024

Stroke is a leading cause of disability and mortality worldwide, and it disproportionately affects low- and middle-income countries (LMICs), which account for 88% of stroke fatalities. Prehospital stroke care delays are a crucial obstacle to successful treatment in these settings, especially given the limited therapeutic window for thrombolytic treatments, which may greatly improve recovery chances when initiated early after stroke onset. These delays are caused by a lack of public understanding of stroke symptoms, sociodemographic and cultural variables, and insufficient healthcare infrastructure. This review discusses these issues in detail, emphasizing the disparities in stroke awareness and reaction times between locations and socioeconomic classes. Innovative options for reducing these delays include the deployment of mobile stroke units and community-based educational campaigns. This review also discusses how technology improvements and personalized educational initiatives might improve stroke awareness and response in LMICs. The primary goal is to give a thorough assessment of the challenges and potential remedies that might serve as the foundation for policy reforms and healthcare improvements in LMICs, eventually improving stroke care and lowering disease-related mortality and disability.
Optimizing Diabetic Macular Edema Treatment: A Meta-Analysis of Subthreshold Micropulse Laser and Anti-Vascular Endothelial Growth Factor Combination Therapy
Authors: Ma Ching-Chih , Chen Po-Huang , Hsieh Yun-Hsiu
Published: August 2024

Background: Diabetic macular edema (DME) is the primary cause of visual impairment in individuals with diabetes. Anti-vascular endothelial growth factor (VEGF) is the current first-line treatment for DME owing to its effectiveness. However, frequent anti-VEGF injections may be inconvenient for patients. Therefore, this study aimed to investigate whether the addition of subthreshold micropulse laser (SML) to anti-VEGF therapy could reduce the requirement for anti-VEGF injections while maintaining the treatment efficacy for DME. Methods: Clinical trials retrieved from the databases of PubMed, EMBASE, and the Cochrane Library were evaluated to determine the effectiveness of combination treatment with SML and anti-VEGF medication compared with that of anti-VEGF treatment alone. The primary outcome measures were the changes in CMT, best-corrected visual acuity (BCVA), and the total number of intravitreal injections (IVIs). Results: The IVI + SML group revealed a substantial increase in the logarithm of the minimum angle of the resolution BCVA and a reduction in CMT at the 12-month follow-up (BCVA: random-effects; mean difference [MD], −0.05; 95% confidence interval [CI]: −0.10 to −0.01; p-value = 0.28, and CMT: random-effects; MD, −18.27; 95% confidence interval, −27.36 to −9.18; p-value = 0.20). The number of required IVIs in the IVI + SML group was lower than that in the IVI only group (random-effects; MD, −2.22; 95% CI: −3.13 to −1.31; p-value < 0.01). Conclusions: Combining SML therapy with anti-VEGF injections may reduce the total number of injections required, improve VA, and reduce CMT at the 12-month follow-up. Although the included studies used different SML regimens and anti-VEGF agents, this review indicates that the application of additional SML therapy results in positive clinical outcomes.