bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracellular Vesicles in Breast Cancer: From Biology and Function to Clinical Diagnosis and Therapeutic Management
Authors: Loric Sylvain , Denis Jérôme Alexandre , Desbene Cédric , Sabbah Michèle , Conti Marc
Published: April 2023

Breast cancer (BC) is the first worldwide most frequent cancer in both sexes and the most commonly diagnosed in females. Although BC mortality has been thoroughly declining over the past decades, there are still considerable differences between women diagnosed with early BC and when metastatic BC is diagnosed. BC treatment choice is widely dependent on precise histological and molecular characterization. However, recurrence or distant metastasis still occurs even with the most recent efficient therapies. Thus, a better understanding of the different factors underlying tumor escape is mainly mandatory. Among the leading candidates is the continuous interplay between tumor cells and their microenvironment, where extracellular vesicles play a significant role. Among extracellular vesicles, smaller ones, also called exosomes, can carry biomolecules, such as lipids, proteins, and nucleic acids, and generate signal transmission through an intercellular transfer of their content. This mechanism allows tumor cells to recruit and modify the adjacent and systemic microenvironment to support further invasion and dissemination. By reciprocity, stromal cells can also use exosomes to profoundly modify tumor cell behavior. This review intends to cover the most recent literature on the role of extracellular vesicle production in normal and cancerous breast tissues. Specific attention is paid to the use of extracellular vesicles for early BC diagnosis, follow-up, and prognosis because exosomes are actually under the spotlight of researchers as a high-potential source of liquid biopsies. Extracellular vesicles in BC treatment as new targets for therapy or efficient nanovectors to drive drug delivery are also summarized.
Differences in Bacterial Small RNAs in Stool Samples from Hypercholesterolemic and Normocholesterolemic Subjects
Authors: Morales Cristian , Arias-Carrasco Raul , Maracaja-Coutinho Vinicius , Seron Pamela , Lanas Fernando , Salazar Luis A. , Saavedra Nicolás
Published: April 2023

Cholesterol metabolism is important at the physiological level as well as in several diseases, with small RNA being an element to consider in terms of its epigenetic control. Thus, the aim of this study was to identify differences between bacterial small RNAs present at the gut level in hypercholesterolemic and normocholesterolemic individuals. Twenty stool samples were collected from hypercholesterolemic and normocholesterolemic subjects. RNA extraction and small RNA sequencing were performed, followed by bioinformatics analyses with BrumiR, Bowtie 2, BLASTn, DESeq2, and IntaRNA, after the filtering of the reads with fastp. In addition, the prediction of secondary structures was obtained with RNAfold WebServer. Most of the small RNAs were of bacterial origin and presented a greater number of readings in normocholesterolemic participants. The upregulation of small RNA ID 2909606 associated with Coprococcus eutactus (family Lachnospiraceae) was presented in hypercholesterolemic subjects. In addition, a positive correlation was established between small RNA ID 2149569 from the species Blautia wexlerae and hypercholesterolemic subjects. Other bacterial and archaeal small RNAs that interacted with the LDL receptor (LDLR) were identified. For these sequences, the prediction of secondary structures was also obtained. There were significant differences in bacterial small RNAs associated with cholesterol metabolism in hypercholesterolemic and normocholesterolemic participants.
A Focus on the Synergy of Radiomics and RNA Sequencing in Breast Cancer
Authors: Bellini Davide , Milan Marika , Bordin Antonella , Rizzi Roberto , Rengo Marco , Vicini Simone , Onori Alessandro , Carbone Iacopo , De Falco Elena
Published: April 2023

Radiological imaging is currently employed as the most effective technique for screening, diagnosis, and follow up of patients with breast cancer (BC), the most common type of tumor in women worldwide. However, the introduction of the omics sciences such as metabolomics, proteomics, and molecular genomics, have optimized the therapeutic path for patients and implementing novel information parallel to the mutational asset targetable by specific clinical treatments. Parallel to the “omics” clusters, radiological imaging has been gradually employed to generate a specific omics cluster termed “radiomics”. Radiomics is a novel advanced approach to imaging, extracting quantitative, and ideally, reproducible data from radiological images using sophisticated mathematical analysis, including disease-specific patterns, that could not be detected by the human eye. Along with radiomics, radiogenomics, defined as the integration of “radiology” and “genomics”, is an emerging field exploring the relationship between specific features extracted from radiological images and genetic or molecular traits of a particular disease to construct adequate predictive models. Accordingly, radiological characteristics of the tissue are supposed to mimic a defined genotype and phenotype and to better explore the heterogeneity and the dynamic evolution of the tumor over the time. Despite such improvements, we are still far from achieving approved and standardized protocols in clinical practice. Nevertheless, what can we learn by this emerging multidisciplinary clinical approach? This minireview provides a focused overview on the significance of radiomics integrated by RNA sequencing in BC. We will also discuss advances and future challenges of such radiomics-based approach.
miR-18a and miR-106a Signatures in Plasma Small EVs Are Promising Biomarkers for Early Detection of Pancreatic Ductal Adenocarcinoma
Authors: Xu Xiaohui , Bhandari Kritisha , Xu Chao , Morris Katherine , Ding Wei-Qun
Published: April 2023

Pancreatic cancer is the third leading cause of cancer-related death in the United States. Pancreatic ductal adenocarcinoma (PDAC) is the major form of pancreatic cancer with the worst outcomes. Early detection is key to improving the overall survival rate of PDAC patients. Recent studies have demonstrated that microRNA (miRNA) signatures in plasma small extracellular vesicles (EVs) are potential biomarkers for the early detection of PDAC. However, published results are inconsistent due to the heterogeneity of plasma small EVs and the methods used for small EV isolation. We have recently refined the process of plasma small EV isolation using double filtration and ultracentrifugation. In the present study, we applied this protocol and analyzed plasma small EV miRNA signatures by small RNA sequencing and quantitative RT-PCR in a pilot cohort, consisting of patients with early-stage PDAC, and age- and gender-matched healthy subjects (n = 20). We found, via small RNA sequencing, that there are several miRNAs enriched in plasma small EVs of PDAC patients, and the levels of miR-18a and miR-106a were confirmed by quantitative RT-PCR to be significantly elevated in patients with early-stage PDAC compared with age- and gender-matched healthy subjects. Furthermore, using an immunoaffinity-based plasma small EV isolation approach, we confirmed that the levels of miR-18a and miR-106a in plasma small EVs were significantly higher in PDAC patients versus the healthy subjects. We thus conclude that the levels of miR-18a and miR-106a in plasma small EVs are promising biomarkers for the early detection of PDAC.
Essential Oils from Mediterranean Plants Inhibit In Vitro Monocyte Adhesion to Endothelial Cells from Umbilical Cords of Females with Gestational Diabetes Mellitus
Authors: Schiavone Valeria , Romasco Tea , Di Pietrantonio Nadia , Garzoli Stefania , Palmerini Carola , Di Tomo Pamela , Pipino Caterina , Mandatori Domitilla , Fioravanti Rossella , Butturini Elena , Sabatino Manuela , Baldassarre Maria Pompea Antonia , Ragno Rino , Pandolfi Assunta , Di Pietro Natalia
Published: April 2023

Essential oils (EOs) are mixtures of volatile compounds belonging to several chemical classes derived from aromatic plants using different distillation techniques. Recent studies suggest that the consumption of Mediterranean plants, such as anise and laurel, contributes to improving the lipid and glycemic profile of patients with diabetes mellitus (DM). Hence, the aim of the present study was to investigate the potential anti-inflammatory effect of anise and laurel EOs (AEO and LEO) on endothelial cells isolated from the umbilical cord vein of females with gestational diabetes mellitus (GDM-HUVEC), which is a suitable in vitro model to reproduce the pro-inflammatory phenotype of a diabetic endothelium. For this purpose, the Gas Chromatographic/Mass Spectrometric (GC-MS) chemical profiles of AEO and LEO were first analyzed. Thus, GDM-HUVEC and related controls (C-HUVEC) were pre-treated for 24 h with AEO and LEO at 0.025% v/v, a concentration chosen among others (cell viability by MTT assay), and then stimulated with TNF-α (1 ng/mL). From the GC-MS analysis, trans-anethole (88.5%) and 1,8-cineole (53.9%) resulted as the major components of AEO and LEO, respectively. The results in C- and GDM-HUVEC showed that the treatment with both EOs significantly reduced: (i) the adhesion of the U937 monocyte to HUVEC; (ii) vascular adhesion molecule-1 (VCAM-1) protein and gene expression; (iii) Nuclear Factor-kappa B (NF-κB) p65 nuclear translocation. Taken together, these data suggest the anti-inflammatory efficacy of AEO and LEO in our in vitro model and lay the groundwork for further preclinical and clinical studies to study their potential use as supplements to mitigate vascular endothelial dysfunction associated with DM.
Aluminium in the Human Brain: Routes of Penetration, Toxicity, and Resulting Complications
Authors: Bryliński Łukasz , Kostelecka Katarzyna , Woliński Filip , Duda Piotr , Góra Joanna , Granat Michał , Flieger Jolanta , Teresiński Grzegorz , Buszewicz Grzegorz , Sitarz Ryszard , Baj Jacek
Published: April 2023

Aluminium (Al) is the most ubiquitous metal in the Earth’s crust. Even though its toxicity is well-documented, the role of Al in the pathogenesis of several neurological diseases remains debatable. To establish the basic framework for future studies, we review literature reports on Al toxicokinetics and its role in Alzheimer’s disease (AD), autism spectrum disorder (ASD), alcohol use disorder (AUD), multiple sclerosis (MS), Parkinson’s disease (PD), and dialysis encephalopathy (DE) from 1976 to 2022. Despite poor absorption via mucosa, the biggest amount of Al comes with food, drinking water, and inhalation. Vaccines introduce negligible amounts of Al, while the data on skin absorption (which might be linked with carcinogenesis) is limited and requires further investigation. In the above-mentioned diseases, the literature shows excessive Al accumulation in the central nervous system (AD, AUD, MS, PD, DE) and epidemiological links between greater Al exposition and their increased prevalence (AD, PD, DE). Moreover, the literature suggests that Al has the potential as a marker of disease (AD, PD) and beneficial results of Al chelator use (such as cognitive improvement in AD, AUD, MS, and DE cases).
A Novel Gemcitabine-Resistant Gallbladder Cancer Model Provides Insights into Molecular Changes Occurring during Acquired Resistance
Authors: Vergara-Gómez Luis , Bizama Carolina , Zhong Jun , Buchegger Kurt , Suárez Felipe , Rosa Lorena , Ili Carmen , Weber Helga , Obreque Javiera , Espinoza Karena , Repetto Gabriela , Roa Juan C. , Leal Pamela , García Patricia
Published: April 2023

Treatment options for advanced gallbladder cancer (GBC) are scarce and usually rely on cytotoxic chemotherapy, but the effectiveness of any regimen is limited and recurrence rates are high. Here, we investigated the molecular mechanisms of acquired resistance in GBC through the development and characterization of two gemcitabine-resistant GBC cell sublines (NOZ GemR and TGBC1 GemR). Morphological changes, cross-resistance, and migratory/invasive capabilities were evaluated. Then, microarray-based transcriptome profiling and quantitative SILAC-based phosphotyrosine proteomic analyses were performed to identify biological processes and signaling pathways dysregulated in gemcitabine-resistant GBC cells. The transcriptome profiling of parental and gemcitabine-resistant cells revealed the dysregulation of protein-coding genes that promote the enrichment of biological processes such as epithelial-to-mesenchymal transition and drug metabolism. On the other hand, the phosphoproteomics analysis of NOZ GemR identified aberrantly dysregulated signaling pathways in resistant cells as well as active kinases, such as ABL1, PDGFRA, and LYN, which could be novel therapeutic targets in GBC. Accordingly, NOZ GemR showed increased sensitivity toward the multikinase inhibitor dasatinib compared to parental cells. Our study describes transcriptome changes and altered signaling pathways occurring in gemcitabine-resistant GBC cells, which greatly expands our understanding of the underlying mechanisms of acquired drug resistance in GBC.
Genome-Wide Identification and Characterization of the Soybean Snf2 Gene Family and Expression Response to Rhizobia
Authors: Wang Jianhao , Sun Zhihui , Liu Huan , Yue Lin , Wang Fan , Liu Shuangrong , Su Bohong , Liu Baohui , Kong Fanjiang , Fang Chao
Published: April 2023

Sucrose nonfermenting 2 (Snf2) family proteins are the core component of chromatin remodeling complexes that can alter chromatin structure and nucleosome position by utilizing the energy of ATP, playing a vital role in transcription regulation, DNA replication, and DNA damage repair. Snf2 family proteins have been characterized in various species including plants, and they have been found to regulate development and stress responses in Arabidopsis. Soybean (Glycine max) is an important food and economic crop worldwide, unlike other non-leguminous crops, soybeans can form a symbiotic relationship with rhizobia for biological nitrogen fixation. However, little is known about Snf2 family proteins in soybean. In this study, we identified 66 Snf2 family genes in soybean that could be classified into six groups like Arabidopsis, unevenly distributed on 20 soybean chromosomes. Phylogenetic analysis with Arabidopsis revealed that these 66 Snf2 family genes could be divided into 18 subfamilies. Collinear analysis showed that segmental duplication was the main mechanism for expansion of Snf2 genes rather than tandem repeats. Further evolutionary analysis indicated that the duplicated gene pairs had undergone purifying selection. All Snf2 proteins contained seven domains, and each Snf2 protein had at least one SNF2_N domain and one Helicase_C domain. Promoter analysis revealed that most Snf2 genes had cis-elements associated with jasmonic acid, abscisic acid, and nodule specificity in their promoter regions. Microarray data and real-time quantitative PCR (qPCR) analysis revealed that the expression profiles of most Snf2 family genes were detected in both root and nodule tissues, and some of them were found to be significantly downregulated after rhizobial infection. In this study, we conducted a comprehensive analysis of the soybean Snf2 family genes and demonstrated their responsiveness to Rhizobia infection. This provides insight into the potential roles of Snf2 family genes in soybean symbiotic nodulation.
Editorial to the IJMS Special Issue “Aptamer-Mediated Cancer Theranostics”
Authors: Danquah Michael K.
Published: April 2023

Aptamers have emerged as a new generation of bioaffinity probes with enhanced target binding specificity and selectivity [...]
Disturbances of Hormonal Circadian Rhythms by Light Pollution
Authors: Zeman Michal , Okuliarova Monika , Rumanova Valentina Sophia
Published: April 2023

The circadian rhythms evolved to anticipate and cope with cyclic changes in environmental conditions. This adaptive function is currently compromised by increasing levels of artificial light at night (ALAN), which can represent a risk for the development of diseases of civilisation. The causal links are not completely understood, and this featured review focuses on the chronodisruption of the neuroendocrine control of physiology and behaviour by dim ALAN. The published data indicate that low levels of ALAN (2–5 lux) can attenuate the molecular mechanisms generating circadian rhythms in the central oscillator, eliminate the rhythmic changes in dominant hormonal signals, such as melatonin, testosterone and vasopressin, and interfere with the circadian rhythm of the dominant glucocorticoid corticosterone in rodents. These changes are associated with a disturbed daily pattern of metabolic changes and behavioural rhythms in activity and food and water intake. The increasing levels of ALAN require the identification of the pathways mediating possible negative consequences on health to design effective mitigation strategies to eliminate or minimise the effects of light pollution.
Reorganization and Suppression of Store-Operated Calcium Entry in Podocytes of Type 2 Diabetic Rats
Authors: Gusev Konstantin , Shalygin Alexey , Kolesnikov Dmitrii , Shuyskiy Leonid , Makeenok Sofia , Glushankova Lyubov , Sivak Konstantin , Yakovlev Kirill , Orshanskaya Yana , Wang Guanghui , Bakhtyukov Andrey , Derkach Kira , Shpakov Alexander , Kaznacheyeva Elena
Published: April 2023

Type 2 diabetes mellitus (DM2) is a widespread metabolic disorder that results in podocyte damage and diabetic nephropathy. Previous studies demonstrated that TRPC6 channels play a pivotal role in podocyte function and their dysregulation is associated with development of different kidney diseases including nephropathy. Here, using single channel patch clamp technique, we demonstrated that non-selective cationic TRPC6 channels are sensitive to the Ca2+ store depletion in human podocyte cell line Ab8/13 and in freshly isolated rat glomerular podocytes. Ca2+ imaging indicated the involvement of ORAI and sodium–calcium exchanger in Ca2+ entry induced upon store depletion. In male rats fed a high-fat diet combined with a low-dose streptozotocin injection, which leads to DM2 development, we observed the reduction of a store-operated Ca2+ entry (SOCE) in rat glomerular podocytes. This was accompanied by a reorganization of store-operated Ca2+ influx such that TRPC6 channels lost their sensitivity to Ca2+ store depletion and ORAI-mediated Ca2+ entry was suppressed in TRPC6-independent manner. Altogether our data provide new insights into the mechanism of SOCE organization in podocytes in the norm and in pathology, which should be taken into account when developing pharmacological treatment of the early stages of diabetic nephropathy.
Exploring the Involvement of Gut Microbiota in Cancer Therapy-Induced Cardiotoxicity
Authors: Kunika  , Frey Norbert , Rangrez Ashraf Y.
Published: April 2023

Trillions of microbes in the human intestinal tract, including bacteria, viruses, fungi, and protozoa, are collectively referred to as the gut microbiome. Recent technological developments have led to a significant increase in our understanding of the human microbiome. It has been discovered that the microbiome affects both health and the progression of diseases, including cancer and heart disease. Several studies have indicated that the gut microbiota may serve as a potential target in cancer therapy modulation, by enhancing the effectiveness of chemotherapy and/or immunotherapy. Moreover, altered microbiome composition has been linked to the long-term effects of cancer therapy; for example, the deleterious effects of chemotherapy on microbial diversity can, in turn, lead to acute dysbiosis and serious gastrointestinal toxicity. Specifically, the relationship between the microbiome and cardiac diseases in cancer patients following therapy is poorly understood. In this article, we provide a summary of the role of the microbiome in cancer treatment, while also speculating on a potential connection between treatment-related microbial changes and cardiotoxicity. Through a brief review of the literature, we further explore which bacterial families or genera were differentially affected in cancer treatment and cardiac disease. A deeper understanding of the link between the gut microbiome and cardiotoxicity caused by cancer treatment may help lower the risk of this critical and potentially fatal side effect.
HIV-Differentiated Metabolite N-Acetyl-L-Alanine Dysregulates Human Natural Killer Cell Responses to Mycobacterium tuberculosis Infection
Authors: Yang Baojun , Mukherjee Tanmoy , Radhakrishnan Rajesh , Paidipally Padmaja , Ansari Danish , John Sahana , Vankayalapati Ramakrishna , Tripathi Deepak , Yi Guohua
Published: April 2023

Mycobacterium tuberculosis (Mtb) has latently infected over two billion people worldwide (LTBI) and caused ~1.6 million deaths in 2021. Human immunodeficiency virus (HIV) co-infection with Mtb will affect the Mtb progression and increase the risk of developing active tuberculosis by 10–20 times compared with HIV- LTBI+ patients. It is crucial to understand how HIV can dysregulate immune responses in LTBI+ individuals. Plasma samples collected from healthy and HIV-infected individuals were investigated using liquid chromatography–mass spectrometry (LC-MS), and the metabolic data were analyzed using the online platform Metabo-Analyst. ELISA, surface and intracellular staining, flow cytometry, and quantitative reverse-transcription PCR (qRT-PCR) were performed using standard procedures to determine the surface markers, cytokines, and other signaling molecule expressions. Seahorse extra-cellular flux assays were used to measure mitochondrial oxidative phosphorylation and glycolysis. Six metabolites were significantly less abundant, and two were significantly higher in abundance in HIV+ individuals compared with healthy donors. One of the HIV-upregulated metabolites, N-acetyl-L-alanine (ALA), inhibits pro-inflammatory cytokine IFN-γ production by the NK cells of LTBI+ individuals. ALA inhibits the glycolysis of LTBI+ individuals’ NK cells in response to Mtb. Our findings demonstrate that HIV infection enhances plasma ALA levels to inhibit NK-cell-mediated immune responses to Mtb infection, offering a new understanding of the HIV–Mtb interaction and providing insights into the implication of nutrition intervention and therapy for HIV–Mtb co-infected patients.
Morphological and Physiological Mechanisms of Melatonin on Delaying Drought-Induced Leaf Senescence in Cotton
Authors: Yang Kai , Sun Hongchun , Liu Mengxing , Zhu Lingxiao , Zhang Ke , Zhang Yongjiang , Li Anchang , Zhang Haina , Zhu Jijie , Liu Xiaoqing , Bai Zhiying , Liu Liantao , Li Cundong
Published: April 2023

Leaf senescence reduces the photosynthetic capacity of leaves, thus significantly affecting the growth, development, and yield formation of cotton. Melatonin (MT) is a multipotent substance proven to delay leaf senescence. However, its potential mechanism in delaying leaf senescence induced by abiotic stress remains unclear. This study aimed to explore the effect of MT on delaying drought-induced leaf senescence in cotton seedlings and to clarify its morphological and physiological mechanisms. Drought stress upregulated the leaf senescence marker genes, destroyed the photosystem, and led to excessive accumulation of reactive oxygen species (ROS, e.g., H2O2 and O2−), thus accelerating leaf senescence. However, leaf senescence was significantly delayed when 100 μM MT was sprayed on the leaves of the cotton seedlings. The delay was embodied by the increased chlorophyll content, photosynthetic capacity, and antioxidant enzyme activities, as well as decreased H2O2, O2−, and abscisic acid (ABA) contents by 34.44%, 37.68%, and 29.32%, respectively. MT significantly down-regulated chlorophyll degradation-related genes and senescence marker genes (GhNAC12 and GhWRKY27/71). In addition, MT reduced the chloroplast damage caused by drought-induced leaf senescence and maintained the integrity of the chloroplast lamellae structure under drought stress. The findings of this study collectively suggest that MT can effectively enhance the antioxidant enzyme system, improve photosynthetic efficiency, reduce chlorophyll degradation and ROS accumulation, and inhibit ABA synthesis, thereby delaying drought-induced leaf senescence in cotton.
Mild Chronic Kidney Disease Associated with Low Bone Formation and Decrease in Phosphate Transporters and Signaling Pathways Gene Expression
Authors: Bogdanova Evdokia , Sadykov Airat , Ivanova Galina , Zubina Irina , Beresneva Olga , Semenova Natalia , Galkina Olga , Parastaeva Marina , Sharoyko Vladimir , Dobronravov Vladimir
Published: April 2023

The initial phases of molecular and cellular maladaptive bone responses in early chronic kidney disease (CKD) remain mostly unknown. We induced mild CKD in spontaneously hypertensive rats (SHR) by either causing arterial hypertension lasting six months (sham-operated rats, SO6) or in its’ combination with 3/4 nephrectomy lasting two and six months (Nx2 and Nx6, respectively). Sham-operated SHRs (SO2) and Wistar Kyoto rats (WKY2) with a two-month follow-up served as controls. Animals were fed standard chow containing 0.6% phosphate. Upon follow-up completion in each animal, we measured creatinine clearance, urine albumin-to-creatinine ratio, renal interstitial fibrosis, inorganic phosphate (Pi) exchange, intact parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), Klotho, Dickkopf-1, sclerostin, and assessed bone response by static histomorphometry and gene expression profiles. The mild CKD groups had no increase in renal Pi excretion, FGF23, or PTH levels. Serum Pi, Dickkopf-1, and sclerostin were higher in Nx6. A decrease in trabecular bone area and osteocyte number was obvious in SO6. Nx2 and Nx6 had additionally lower osteoblast numbers. The decline in eroded perimeter, a resorption index, was only apparent in Nx6. Significant downregulation of genes related to Pi transport, MAPK, WNT, and BMP signaling accompanied histological alterations in Nx2 and Nx6. We found an association between mild CKD and histological and molecular features suggesting lower bone turnover, which occurred at normal levels of systemic Pi-regulating factors.
Transcriptional Activation of a Pro-Inflammatory Response (NF-κB, AP-1, IL-1β) by the Vibrio cholerae Cytotoxin (VCC) Monomer through the MAPK Signaling Pathway in the THP-1 Human Macrophage Cell Line
Authors: Escartín-Gutiérrez Julio Rodrigo , Ponce-Figueroa Mariana , Torres-Vega Miguel Ángel , Aguilar-Faisal Leopoldo , Figueroa-Arredondo Paula
Published: April 2023

This study describes, to some extent, the VCC contribution as an early stimulation of the macrophage lineage. Regarding the onset of the innate immune response caused by infection, the β form of IL-1 is the most important interleukin involved in the onset of the inflammatory innate response. Activated macrophages treated in vitro with VCC induced the activation of the MAPK signaling pathway in a one-hour period, with the activation of transcriptional regulators for a surviving and pro-inflammatory response, suggesting an explanation inspired and supported by the inflammasome physiology. The mechanism of IL-1β production induced by VCC has been gracefully outlined in murine models, using bacterial knockdown mutants and purified molecules; nevertheless, the knowledge of this mechanism in the human immune system is still under study. This work shows the soluble form of 65 kDa of the Vibrio cholerae cytotoxin (also known as hemolysin), as it is secreted by the bacteria, inducing the production of IL-1β in the human macrophage cell line THP-1. The mechanism involves triggering the early activation of the signaling pathway MAPKs pERK and p38, with the subsequent activation of (p50) NF-κB and AP-1 (cJun and cFos), determined by real-time quantitation. The evidence shown here supports that the monomeric soluble form of the VCC in the macrophage acts as a modulator of the innate immune response, which is consistent with the assembly of the NLRP3 inflammasome actively releasing IL-1β.
Placental Remote Control of Fetal Metabolism: Trophoblast mTOR Signaling Regulates Liver IGFBP-1 Phosphorylation and IGF-1 Bioavailability
Authors: Rosario Fredrick J. , Chopra Anand , Biggar Kyle , Powell Theresa L. , Gupta Madhulika B. , Jansson Thomas
Published: April 2023

The mechanisms mediating the restricted growth in intrauterine growth restriction (IUGR) remain to be fully established. Mechanistic target of rapamycin (mTOR) signaling functions as a placental nutrient sensor, indirectly influencing fetal growth by regulating placental function. Increased secretion and the phosphorylation of fetal liver IGFBP-1 are known to markedly decrease the bioavailability of IGF-1, a major fetal growth factor. We hypothesized that an inhibition of trophoblast mTOR increases liver IGFBP-1 secretion and phosphorylation. We collected conditioned media (CM) from cultured primary human trophoblast (PHT) cells with a silenced RAPTOR (specific inhibition of mTOR Complex 1), RICTOR (inhibition of mTOR Complex 2), or DEPTOR (activates both mTOR Complexes). Subsequently, HepG2 cells, a well-established model for human fetal hepatocytes, were cultured in CM from PHT cells, and IGFBP-1 secretion and phosphorylation were determined. CM from PHT cells with either mTORC1 or mTORC2 inhibition caused the marked hyperphosphorylation of IGFBP-1 in HepG2 cells as determined by 2D-immunoblotting while Parallel Reaction Monitoring-Mass Spectrometry (PRM-MS) identified increased dually phosphorylated Ser169 + Ser174. Furthermore, using the same samples, PRM-MS identified multiple CK2 peptides coimmunoprecipitated with IGFBP-1 and greater CK2 autophosphorylation, indicating the activation of CK2, a key enzyme mediating IGFBP-1 phosphorylation. Increased IGFBP-1 phosphorylation inhibited IGF-1 function, as determined by the reduced IGF-1R autophosphorylation. Conversely, CM from PHT cells with mTOR activation decreased IGFBP-1 phosphorylation. CM from non-trophoblast cells with mTORC1 or mTORC2 inhibition had no effect on HepG2 IGFBP-1 phosphorylation. Placental mTOR signaling may regulate fetal growth by the remote control of fetal liver IGFBP-1 phosphorylation.
Calcification of Various Bioprosthetic Materials in Rats: Is It Really Different?
Authors: Zhuravleva Irina Y. , Karpova Elena V. , Dokuchaeva Anna A. , Titov Anatoly T. , Timchenko Tatiana P. , Vasilieva Maria B.
Published: April 2023

The causes of heart valve bioprosthetic calcification are still not clear. In this paper, we compared the calcification in the porcine aorta (Ao) and the bovine jugular vein (Ve) walls, as well as the bovine pericardium (Pe). Biomaterials were crosslinked with glutaraldehyde (GA) and diepoxide (DE), after which they were implanted subcutaneously in young rats for 10, 20, and 30 days. Collagen, elastin, and fibrillin were visualized in non-implanted samples. Atomic absorption spectroscopy, histological methods, scanning electron microscopy, and Fourier-transform infrared spectroscopy were used to study the dynamics of calcification. By the 30th day, calcium accumulated most intensively in the collagen fibers of the GA-Pe. In elastin-rich materials, calcium deposits were associated with elastin fibers and localized differences in the walls of Ao and Ve. The DE-Pe did not calcify at all for 30 days. Alkaline phosphatase does not affect calcification since it was not found in the implant tissue. Fibrillin surrounds elastin fibers in the Ao and Ve, but its involvement in calcification is questionable. In the subcutaneous space of young rats, which are used to model the implants’ calcification, the content of phosphorus was five times higher than in aging animals. We hypothesize that the centers of calcium phosphate nucleation are the positively charged nitrogen of the pyridinium rings, which is the main one in fresh elastin and appears in collagen as a result of GA preservation. Nucleation can be significantly accelerated at high concentrations of phosphorus in biological fluids. The hypothesis needs further experimental confirmation.
Effects of Electrode Materials on Electron Transport for Single-Molecule Junctions
Authors: Gu Mong-Wen , Chen Chun-hsien
Published: April 2023

The contact at the molecule–electrode interface is a key component for a range of molecule-based devices involving electron transport. An electrode–molecule–electrode configuration is a prototypical testbed for quantitatively studying the underlying physical chemistry. Rather than the molecular side of the interface, this review focuses on examples of electrode materials in the literature. The basic concepts and relevant experimental techniques are introduced.
Functional and Anatomical Outcomes of Anti-Vascular Endothelial Growth Factor Treatment for Exudative Age-Related Macular Degeneration with or without Obstructive Sleep Apnea
Authors: Chen Nan-Ni , Chen Chau-Yin , Wang Jin-Jhe , Huang Heng-Chiao , Chen Wei-Dar , Chen Ching-Lung , Yang Yao-Hsu , Lin Meng-Hung , Kuo Ting-Yu , Lai Chien-Hsiung
Published: April 2023

(1) To investigate the functional and anatomical outcomes of anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with exudative age-related macular degeneration (AMD) with or without obstructive sleep apnea (OSA); (2) In total, 65 patients with AMD with or without OSA who received three consecutive doses of intravitreal anti-VEGF injections were enrolled. The primary outcomes—best-corrected visual acuity (BCVA) and central macular thickness (CMT)—were assessed at 1 and 3 months. Moreover, morphological changes observed through optical coherence tomography were analyzed; (3) In total, 15 of the 65 patients had OSA and were included in the OSA group; the remaining 50 patients were included in the non-OSA (control) group. At 1 and 3 months after treatment, BCVA and CMT had improved but did not differ significantly between the groups. More patients in the OSA group demonstrated subretinal fluid (SRF) resorption at 3 months after treatment than in the non-OSA group (p = 0.009). Changes in other imaging biomarkers, such as intraretinal cysts, retinal pigment epithelium detachment, hyperreflective dots, and ellipsoid zone disruptions, did not differ significantly between the groups; (4) Our results suggest that the BCVA and CMT outcomes 3 months after anti-VEGF treatment are similar between patients with and without OSA. Moreover, patients with OSA may exhibit superior SRF resorption. A large-scale prospective study is mandatory to evaluate the association between SRF resorption and visual outcomes in AMD patients with OSA.
Hyaluronic Acid-Based Nanosystems for CD44 Mediated Anti-Inflammatory and Antinociceptive Activity
Authors: Salathia Saniya , Gigliobianco Maria Rosa , Casadidio Cristina , Di Martino Piera , Censi Roberta
Published: April 2023

The nervous and immune systems go hand in hand in causing inflammation and pain. However, the two are not mutually exclusive. While some diseases cause inflammation, others are caused by it. Macrophages play an important role in modulating inflammation to trigger neuropathic pain. Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan that has a well-known ability to bind with the cluster of differentiation 44 (CD44) receptor on classically activated M1 macrophages. Resolving inflammation by varying the molecular weight of HA is a debated concept. HA-based drug delivery nanosystems such as nanohydrogels and nanoemulsions, targeting macrophages can be used to relieve pain and inflammation by loading antinociceptive drugs and enhancing the effect of anti-inflammatory drugs. This review will discuss the ongoing research on HA-based drug delivery nanosystems regarding their antinociceptive and anti-inflammatory effects.
Metal-Based Complexes in Cancer
Authors: Riccardi Claudia , Piccolo Marialuisa
Published: April 2023

Metal-based drugs have attracted growing interest in biomedicine [...]
Impacts of Salt Stress on the Rhizosphere and Endophytic Bacterial Role in Plant Salt Alleviation
Authors: Slama Houda Ben , Chenari Bouket Ali , Alenezi Faizah N. , Luptakova Lenka , Baranov Oleg , Ahadi Reza , Belbahri Lassaad
Published: April 2023

Salinity stress is among the key challenges for sustainable food production. It is continuously increasing against the backdrop of constant climate change and anthropogenic practices leading to a huge drop in soil, water, and cultivated crop quality and productivity. Halotolerant plants represent hot spots for endophytic bacteria which may have mechanisms to overcome salt stress. This research initiative aims to highlight the possible exploitation of bacterial endophytes as a microbial biotechnology tool in the productive success of plants exposed to saline stress. We started by solely studying the mechanisms of stress tolerance by plants and halotolerant bacteria. After that, we focused on the beneficial mechanisms of endophytic bacteria in salt stress mitigation. On one side, potent bacterium works by promoting plant performances by facilitating the plant’s nutrient uptake (P, K, Zn, N, and Fe) and by promoting the production of growth hormones (IAA and CKs). On the other side, they balance stress phytohormones (ABA, JA, GA, and ACC) produced by plants in case of soil salt augmentation. The selected potent endophytic bacteria could be exploited and applied to ameliorate the production and salt tolerance of food crops. Lastly, we elucidated deeper advanced technologies including (i) genomics unveiling the plant’s culture-dependent and culture-independent microbiomes, (ii) metabolomics focusing on genes’ metabolic pathways to discover novel secondary metabolites, (iii) transcriptomics studying gene expression, and (iv) proteomics delimiting proteins expressed in stress alleviation. These technologies have been used to understand the plant–bacterial mechanisms of interaction to combat salt stress.
Anti-Inflammatory and Anti-Adipogenesis Effects of Alchemilla vulgaris L., Salvia officinalis L., and Vitis vinifera L. in THP-1-Derived Macrophages and 3T3-L1 Cell Line
Authors: Mansour Bayan , Shaheen Nora , Kmail Abdalsalam , Haggag Nawal , Saad Salah , Sadiq Omar , Zaid Ramez , Saad Bashar
Published: April 2023

The production of pro-inflammatory and anti-inflammatory cytokines, as well as adipocyte differentiation and fat accumulation in the 3T3-L1 mouse embryo fibroblast cell line and the human monocytic cell line THP-1 were measured to determine the anti-inflammatory and antiadipogenic effects of ethanolic extracts of verjuice (unripe grape juice (Vitis vinifera L.)), Salvia officinalis L., and Alchemilla vulgaris L. On both cell lines, the three extracts had much greater cytostatic effects than cytotoxic effects. With an IC50 of 505 μg/mL, S. officinalis had the highest cytostatic effect on THP-1-derived macrophages. After treatment with 125 μg/mL, the three extracts dramatically reduced the LPS-induced NO generation in THP-1-derived macrophages from 80 μM to control values after treatment with 125 µg/mL. Furthermore, the extracts reduced the levels of TNF-α and IL-6 production in a dose-dependent manner with the highest effects reached at 250 µg/mL. The production of TNF-α decreased at higher levels compared to IL-6 production. V. vinifera, S. officinalis, and A. vulgaris extracts improved the production levels of IL-10 from 32 pg/mL to 86 pg/mL, 98 pg/mL, and 80 pg/mL at an extract concentration of 125 µg/mL, respectively. The adipocyte differentiation and fat accumulation in 3T3-L1 were decreased to 20% of control values after treatment with plant extracts. Taken together, these results suggest that V. vinifera, S. officinalis, and A. vulgaris likely exert their anti-obesity effects through cytostatic actions and modulation of pro-inflammatory and anti-inflammatory cytokine production, as well as by reducing adipocyte differentiation and fat accumulation.
Evaluation of a Resilience-Driven Operational Concept to Manage Drone Intrusions in Airports
Authors: Pascarella Domenico , Gigante Gabriella , Vozella Angela , Sodano Maurizio , Ippolito Marco , Bieber Pierre , Dubot Thomas , Martinavarro Edgar
Published: April 2023

The drone market’s growth poses a serious threat to the negligent, illicit, or non-cooperative use of drones, especially in airports and their surroundings. Effective protection of an airport against drone intrusions should guarantee mandatory safety levels but should also rely on a resilience-driven operational concept aimed at managing the intrusions without necessarily implying the closure of the airport. The concept faces both safety-related and security-related threats and is based on the definitions of: (i) new roles and responsibilities; (ii) a set of operational phases, accomplished by means of specific technological building blocks; (iii) a new operational procedure blending smoothly with existing aerodrome procedures in place. The paper investigates the evaluation of such a resilience-driven operational concept tailored to drone-intrusion features, airport features, and current operations. The proposed concept was evaluated by applying it to a concrete case study related to Milan Malpensa Airport. The evaluation was carried out by real-time simulations and event tree analysis, exploiting the implementation of specific simulation tools and the assessment of resilience-oriented metrics. The achieved results show the effectiveness of the proposed operational concept and elicit further requirements for future counter-drone systems in airports.
Comparison of Preference for Chemicals Associated with Fruit Fermentation between Drosophila melanogaster and Drosophila suzukii and between Virgin and Mated D. melanogaster
Authors: Kim Hyemin , Kim YeongHo , Roh Gwang Hyun , Kim Young Ho
Published: April 2023

Two taxonomically similar Drosophila species, Drosophila melanogaster and Drosophila suzukii, are known to have distinct habitats: D. melanogaster is mostly found near overripe and fermented fruits, whereas D. suzukii is attracted to fresh fruits. Since chemical concentrations are typically higher in overripe and fermented fruits than in fresh fruits, D. melanogaster is hypothesized to be attracted to higher concentrations of volatiles than D. suzukii. Therefore, the chemical preferences of the two flies were compared via Y-tube olfactometer assays and electroantennogram (EAG) experiments using various concentrations of 2-phenylethanol, ethanol, and acetic acid. D. melanogaster exhibited a higher preference for high concentrations of all the chemicals than that of D. suzukii. In particular, since acetic acid is mostly produced at the late stage of fruit fermentation, the EAG signal distance to acetic acid between the two flies was higher than those to 2-phenylethanol and ethanol. This supports the hypothesis that D. melanogaster prefers fermented fruits compared to D. suzukii. When comparing virgin and mated female D. melanogaster, mated females showed a higher preference for high concentrations of chemicals than that of virgin females. In conclusion, high concentrations of volatiles are important attraction factors for mated females seeking appropriate sites for oviposition.
Role of Lung Ultrasonography (LUS) as a Tool for Evaluating Children with Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS)
Authors: Tomczonek-Moruś Jolanta , Krysiak Natalia , Blomberg Agnieszka , Depczyk-Bukała Marta , Tkaczyk Marcin , Zeman Krzysztof
Published: April 2023

Background: Pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is a novel entity. The inflammatory process involves the circulatory, digestive, respiratory, and central nervous systems, as well as the skin. Making a diagnosis requires extensive differential diagnoses, including lung imaging. The aim of our study was to retrospectively assess the pathologies found in lung ultrasound (LUS) in children diagnosed with PIMS-TS and to evaluate the usefulness of the examination in diagnostics and monitoring. Methods: The study group consisted of 43 children diagnosed with PIMS-TS, in whom LUS was performed at least three times, including on admission to hospital, on discharge, and 3 months after disease onset. Results: Pneumonia (mild to severe) was diagnosed in 91% of the patients based on the ultrasound image; the same number had at least one pathology, including consolidations, atelectasis, pleural effusion, and interstitial or interstitial-alveolar syndrome. By the time of discharge, the inflammatory changes had completely regressed in 19% of the children and partially in 81%. After 3 months, no pathologies were detected in the entire study group. Conclusion: LUS is a useful tool for diagnosing and monitoring children with PIMS-TS. Inflammatory lesions of the lungs resolve completely when the generalized inflammatory process subsides.
Systematic Innominate Artery Cannulation Strategy in Acute Type A Aortic Dissection: Better Perfusion, Better Results
Authors: Feier Horea , Grigorescu Andrei , Braescu Laurentiu , Falnita Lucian , Sintean Marius , Luca Constantin Tudor , Mocan Mihaela
Published: April 2023

(1) Background: Arterial cannulation in type A acute aortic dissection (TAAAD) is still subject to debate. We describe a systematic approach of using the innominate artery for arterial perfusion (2) Methods: The hospital records of 110 consecutive patients with acute TAAAD operated on between January 2014 and December 2022 were retrospectively analyzed. The effect of the cannulation site on early and late mortality, as well as on cardio-pulmonary perfusion indices (lactate and base excess levels, and cooling and rewarming speed) were investigated. (3) Results: There was a significant difference in early mortality (8.82% vs. 40.79%, p < 0.01) but no difference in long-term survival beyond the first 30 days. Using the innominate artery enabled the use of approximately 20% higher CPB flows (2.73 ± 0.1 vs. 2.42 ± 0.06 L/min/m2 BSA, p < 0.01), which resulted in more rapid cooling (1.89 ± 0.77 vs. 3.13 ± 1.62 min/°C/m2 BSA, p < 0.01), rewarming (2.84 ± 1.36 vs. 4.22 ± 2.23, p < 0.01), lower mean base excess levels during CPB (−5.01 ± 2.99 mEq/L vs. −6.66 ± 3.37 mEq/L, p = 0.01) and lower lactate levels at the end of the procedure (4.02 ± 2.48 mmol/L vs. 6.63 ± 4.17 mmol/L, p < 0.01). Postoperative permanent neurologic insult (3.12% vs. 20%, p = 0.02) and acute kidney injury (3.12% vs. 32.81%, p < 0.01) were significantly reduced. (4) Conclusions: systematic use of the innominate artery enables better perfusion and superior results in TAAAD repair.
Influence of Hemorrhagic Complications of Pancreatoduodenectomy in Patients with Cancer on Short- and Long-Term Mortality
Authors: Thobie Alexandre , Robin Fabien , Menahem Benjamin , Lubrano Jean , Boudjema Karim , Alves Arnaud , Dejardin Olivier , Sulpice Laurent
Published: April 2023

Background: With a mortality rate of up to 30%, post-pancreatectomy hemorrhage (PPH) remains a serious complication after pancreatoduodenectomy (PD) for cancer. Little is known about the long-term survival of patients after PPH. This retrospective study aimed to evaluate the impact of PPH on long-term survival after PD. Methods: The study included 830 patients (PPH, n = 101; non-PPH, n = 729) from two centers, who underwent PD for oncological indications. PPH was defined as any bleeding event occurring within 90 days after surgery. A flexible parametric survival model was used to determine the evolution of the risk of death over time. Results: At postoperative day 90, PPH significantly increased the mortality rate (PPH vs. non-PPH: 19.8% vs. 3.7%, p < 0.0001) and severe postoperative complication rate (85.1% vs. 14.1%, p < 0.0001), and decreased median survival (18.6 months vs. 30.1 months, p = 0.0001). PPH was associated with an increased mortality risk until the sixth postoperative month. After this 6-month period, PPH had no more influence on mortality. Conclusions: PPH had a negative impact on the short-term overall survival beyond postoperative day 90 and up to six months after PD. However, compared to non-PPH patients, this adverse event had no impact on mortality after a 6-month period.