bluuebunny/crossref_metadata_2025 huggingface dataset:
Ionic Regulation of T-Cell Function and Anti-Tumour Immunity
Authors: Ginefra Pierpaolo , Carrasco Hope Helen , Spagna Mattia , Zecchillo Alessandra , Vannini Nicola
Published: December 2021

The capacity of T cells to identify and kill cancer cells has become a central pillar of immune-based cancer therapies. However, T cells are characterized by a dysfunctional state in most tumours. A major obstacle for proper T-cell function is the metabolic constraints posed by the tumour microenvironment (TME). In the TME, T cells compete with cancer cells for macronutrients (sugar, proteins, and lipid) and micronutrients (vitamins and minerals/ions). While the role of macronutrients in T-cell activation and function is well characterized, the contribution of micronutrients and especially ions in anti-tumour T-cell activities is still under investigation. Notably, ions are important for most of the signalling pathways regulating T-cell anti-tumour function. In this review, we discuss the role of six biologically relevant ions in T-cell function and in anti-tumour immunity, elucidating potential strategies to adopt to improve immunotherapy via modulation of ion metabolism.
Therapeutic Potential of Mesenchymal Stem Cells (MSCs) and MSC-Derived Extracellular Vesicles for the Treatment of Spinal Cord Injury
Authors: Kim Gang-Un , Sung Soo-Eun , Kang Kyung-Ku , Choi Joo-Hee , Lee Sijoon , Sung Minkyoung , Yang Seung Yun , Kim Seul-Ki , Kim Young In , Lim Ju-Hyeon , Seo Min-Soo , Lee Gun Woo
Published: December 2021

Spinal cord injury (SCI) is a life-threatening condition that leads to permanent disability with partial or complete loss of motor, sensory, and autonomic functions. SCI is usually caused by initial mechanical insult, followed by a cascade of several neuroinflammation and structural changes. For ameliorating the neuroinflammatory cascades, MSC has been regarded as a therapeutic agent. The animal SCI research has demonstrated that MSC can be a valuable therapeutic agent with several growth factors and cytokines that may induce anti-inflammatory and regenerative effects. However, the therapeutic efficacy of MSCs in animal SCI models is inconsistent, and the optimal method of MSCs remains debatable. Moreover, there are several limitations to developing these therapeutic agents for humans. Therefore, identifying novel agents for regenerative medicine is necessary. Extracellular vesicles are a novel source for regenerative medicine; they possess nucleic acids, functional proteins, and bioactive lipids and perform various functions, including damaged tissue repair, immune response regulation, and reduction of inflammation. MSC-derived exosomes have advantages over MSCs, including small dimensions, low immunogenicity, and no need for additional procedures for culture expansion or delivery. Certain studies have demonstrated that MSC-derived extracellular vesicles (EVs), including exosomes, exhibit outstanding chondroprotective and anti-inflammatory effects. Therefore, we reviewed the principles and patho-mechanisms and summarized the research outcomes of MSCs and MSC-derived EVs for SCI, reported to date.
nc886, a Non-Coding RNA, Is a New Biomarker and Epigenetic Mediator of Cellular Senescence in Fibroblasts
Authors: Kim Yuna , Ji Hyanggi , Cho Eunae , Park Nok-Hyun , Hwang Kyeonghwan , Park Wonseok , Lee Kwang-Soo , Park Deokhoon , Jung Eunsun
Published: December 2021

Functional studies of organisms and human models have revealed that epigenetic changes can significantly impact the process of aging. Non-coding RNA (ncRNA), one of epigenetic regulators, plays an important role in modifying the expression of mRNAs and their proteins. It can mediate the phenotype of cells. It has been reported that nc886 (=vtRNA2-1 or pre-miR-886), a long ncRNA, can suppress tumor formation and photo-damages of keratinocytes caused by UVB. The aim of this study was to determine the role of nc886 in replicative senescence of fibroblasts and determine whether substances capable of controlling nc886 expression could regulate cellular senescence. In replicative senescence fibroblasts, nc886 expression was decreased while methylated nc886 was increased. There were changes of senescence biomarkers including SA-β-gal activity and expression of p16INK4A and p21Waf1/Cip1 in senescent cells. These findings indicate that the decrease of nc886 associated with aging is related to cellular senescence of fibroblasts and that increasing nc886 expression has potential to suppress cellular senescence. AbsoluTea Concentrate 2.0 (ATC) increased nc886 expression and ameliorated cellular senescence of fibroblasts by inhibiting age-related biomarkers. These results indicate that nc886 has potential as a new target for anti-aging and that ATC can be a potent epigenetic anti-aging ingredient.
Induced Pluripotent Stem Cells (iPSCs) and Gene Therapy: A New Era for the Treatment of Neurological Diseases
Authors: Paolini Sguazzi Giulia , Muto Valentina , Tartaglia Marco , Bertini Enrico , Compagnucci Claudia
Published: December 2021

To date, gene therapy has employed viral vectors to deliver therapeutic genes. However, recent progress in molecular and cell biology has revolutionized the field of stem cells and gene therapy. A few years ago, clinical trials started using stem cell replacement therapy, and the induced pluripotent stem cells (iPSCs) technology combined with CRISPR-Cas9 gene editing has launched a new era in gene therapy for the treatment of neurological disorders. Here, we summarize the latest findings in this research field and discuss their clinical applications, emphasizing the relevance of recent studies in the development of innovative stem cell and gene editing therapeutic approaches. Even though tumorigenicity and immunogenicity are existing hurdles, we report how recent progress has tackled them, making engineered stem cell transplantation therapy a realistic option.
Hormonomic Changes Driving the Negative Impact of Broomrape on Plant Host Interactions with Arbuscular Mycorrhizal Fungi
Authors: Mishev Kiril , Dobrev Petre I. , Lacek Jozef , Filepová Roberta , Yuperlieva-Mateeva Bistra , Kostadinova Anelia , Hristeva Tsveta
Published: December 2021

Belowground interactions of plants with other organisms in the rhizosphere rely on extensive small-molecule communication. Chemical signals released from host plant roots ensure the development of beneficial arbuscular mycorrhizal (AM) fungi which in turn modulate host plant growth and stress tolerance. However, parasitic plants have adopted the capacity to sense the same signaling molecules and to trigger their own seed germination in the immediate vicinity of host roots. The contribution of AM fungi and parasitic plants to the regulation of phytohormone levels in host plant roots and root exudates remains largely obscure. Here, we studied the hormonome in the model system comprising tobacco as a host plant, Phelipanche spp. as a holoparasitic plant, and the AM fungus Rhizophagus irregularis. Co-cultivation of tobacco with broomrape and AM fungi alone or in combination led to characteristic changes in the levels of endogenous and exuded abscisic acid, indole-3-acetic acid, cytokinins, salicylic acid, and orobanchol-type strigolactones. The hormonal content in exudates of broomrape-infested mycorrhizal roots resembled that in exudates of infested non-mycorrhizal roots and differed from that observed in exudates of non-infested mycorrhizal roots. Moreover, we observed a significant reduction in AM colonization of infested tobacco plants, pointing to a dominant role of the holoparasite within the tripartite system.
Angiotensin Type 2 and Mas Receptor Activation Prevents Myocardial Fibrosis and Hypertrophy through the Reduction of Inflammatory Cell Infiltration and Local Sympathetic Activity in Angiotensin II-Dependent Hypertension
Authors: Castoldi Giovanna , Carletti Raffaella , Ippolito Silvia , Stella Andrea , Zerbini Gianpaolo , Pelucchi Sara , Zatti Giovanni , di Gioia Cira R. T.
Published: December 2021

Compound 21 (C21), an AT2 receptor agonist, and Angiotensin 1-7 (Ang 1-7), through Mas receptor, play an important role in the modulation of the protective arm of the renin-angiotensin system. The aim of this study was to investigate in an experimental model of angiotensin II-dependent hypertension whether the activation of the potentially protective arm of the renin-angiotensin system, through AT2 or Mas receptor stimulation, counteracts the onset of myocardial fibrosis and hypertrophy, and whether these effects are mediated by inflammatory mechanism and/or sympathetic activation. Sprague Dawley rats (n = 67) were treated for 1 (n = 25) and 4 (n = 42) weeks and divided in the following groups: (a) Angiotensin II (Ang II, 200 ng/kg/min, osmotic minipumps, sub cutis); (b) Ang II+Compound 21 (C21, 0.3 mg/kg/day, intraperitoneal); (c) Ang II+Ang 1-7 (576 µg/kg/day, intraperitoneal); (d) Ang II+Losartan (50 mg/kg/day, per os); (e) control group (physiological saline, sub cutis). Systolic blood pressure was measured by tail cuff method and, at the end of the experimental period, the rats were euthanized and the heart was excised to evaluate myocardial fibrosis, hypertrophy, inflammatory cell infiltration and tyrosine hydroxylase expression, used as marker of sympathetic activity. Ang II caused a significant increase of blood pressure, myocardial interstitial and perivascular fibrosis and myocardial hypertrophy, as compared to control groups. C21 or Ang 1-7 administration did not modify the increase in blood pressure in Ang II treated rats, but both prevented the development of myocardial fibrosis and hypertrophy. Treatment with losartan blocked the onset of hypertension and myocardial fibrosis and hypertrophy in Ang II treated rats. Activation of AT2 receptors or Mas receptors prevents the onset of myocardial fibrosis and hypertrophy in Ang II-dependent hypertension through the reduction of myocardial inflammatory cell infiltration and tyrosine hydroxylase expression. Unlike what happens in case of treatment with losartan, the antifibrotic and antihypertrophic effects that follow the activation of the AT2 or Mas receptors are independent on the modulation of blood pressure.
Paternal Exercise Improves the Metabolic Health of Offspring via Epigenetic Modulation of the Germline
Authors: Costa-Júnior José Maria , Ferreira Sandra Mara , Kurauti Mirian Ayumi , Bernstein Diana L. , Ruano Elena G. , Kameswaran Vasumathi , Schug Jonathan , Freitas-Dias Ricardo , Zoppi Claudio C. , Boschero Antonio C. , Oliveira Camila A. M. de , Santos Gustavo J. , Carneiro Everardo M. , Kaestner Klaus H.
Published: December 2021

Background/Aims: Epigenetic regulation is considered the main molecular mechanism underlying the developmental origin of health and disease’s (DOHAD) hypothesis. Previous studies that have investigated the role of paternal exercise on the metabolic health of the offspring did not control for the amount and intensity of the training or possible effects of adaptation to exercise and produced conflicting results regarding the benefits of parental exercise to the next generation. We employed a precisely regulated exercise regimen to study the transgenerational inheritance of improved metabolic health. Methods: We subjected male mice to a well-controlled exercise -training program to investigate the effects of paternal exercise on glucose tolerance and insulin sensitivity in their adult progeny. To investigate the molecular mechanisms of epigenetic inheritance, we determined chromatin markers in the skeletal muscle of the offspring and the paternal sperm. Results: Offspring of trained male mice exhibited improved glucose homeostasis and insulin sensitivity. Paternal exercise modulated the DNA methylation profile of PI3Kca and the imprinted H19/Igf2 locus at specific differentially methylated regions (DMRs) in the skeletal muscle of the offspring, which affected their gene expression. Remarkably, a similar DNA methylation profile at the PI3Kca, H19, and Igf2 genes was present in the progenitor sperm indicating that exercise-induced epigenetic changes that occurred during germ cell development contributed to transgenerational transmission. Conclusion: Paternal exercise might be considered as a strategy that could promote metabolic health in the offspring as the benefits can be inherited transgenerationally.
Historical Roles of Selenium and Selenoproteins in Health and Development: The Good, the Bad and the Ugly
Authors: Tsuji Petra A. , Santesmasses Didac , Lee Byeong J. , Gladyshev Vadim N. , Hatfield Dolph L.
Published: December 2021

Selenium is a fascinating element that has a long history, most of which documents it as a deleterious element to health. In more recent years, selenium has been found to be an essential element in the diet of humans, all other mammals, and many other life forms. It has many health benefits that include, for example, roles in preventing heart disease and certain forms of cancer, slowing AIDS progression in HIV patients, supporting male reproduction, inhibiting viral expression, and boosting the immune system, and it also plays essential roles in mammalian development. Elucidating the molecular biology of selenium over the past 40 years generated an entirely new field of science which encompassed the many novel features of selenium. These features were (1) how this element makes its way into protein as the 21st amino acid in the genetic code, selenocysteine (Sec); (2) the vast amount of machinery dedicated to synthesizing Sec uniquely on its tRNA; (3) the incorporation of Sec into protein; and (4) the roles of the resulting Sec-containing proteins (selenoproteins) in health and development. One of the research areas receiving the most attention regarding selenium in health has been its role in cancer prevention, but further research has also exposed the role of this element as a facilitator of various maladies, including cancer.
Cytosolic Quality Control of Mitochondrial Protein Precursors—The Early Stages of the Organelle Biogenesis
Authors: Lenkiewicz Anna M. , Krakowczyk Magda , Bragoszewski Piotr
Published: December 2021

With few exceptions, proteins that constitute the proteome of mitochondria originate outside of this organelle in precursor forms. Such protein precursors follow dedicated transportation paths to reach specific parts of mitochondria, where they complete their maturation and perform their functions. Mitochondrial precursor targeting and import pathways are essential to maintain proper mitochondrial function and cell survival, thus are tightly controlled at each stage. Mechanisms that sustain protein homeostasis of the cytosol play a vital role in the quality control of proteins targeted to the organelle. Starting from their synthesis, precursors are constantly chaperoned and guided to reduce the risk of premature folding, erroneous interactions, or protein damage. The ubiquitin-proteasome system provides proteolytic control that is not restricted to defective proteins but also regulates the supply of precursors to the organelle. Recent discoveries provide evidence that stress caused by the mislocalization of mitochondrial proteins may contribute to disease development. Precursors are not only subject to regulation but also modulate cytosolic machinery. Here we provide an overview of the cellular pathways that are involved in precursor maintenance and guidance at the early cytosolic stages of mitochondrial biogenesis. Moreover, we follow the circumstances in which mitochondrial protein import deregulation disturbs the cellular balance, carefully looking for rescue paths that can restore proteostasis.
Epigenetic Biomarkers as Diagnostic Tools for Neurodegenerative Disorders
Authors: Martínez-Iglesias Olaia , Naidoo Vinogran , Cacabelos Natalia , Cacabelos Ramón
Published: December 2021

Epigenetics is the study of heritable changes in gene expression that occur without alterations to the DNA sequence, linking the genome to its surroundings. The accumulation of epigenetic alterations over the lifespan may contribute to neurodegeneration. The aim of the present study was to identify epigenetic biomarkers for improving diagnostic efficacy in patients with neurodegenerative diseases. We analyzed global DNA methylation, chromatin remodeling/histone modifications, sirtuin (SIRT) expression and activity, and the expression of several important neurodegeneration-related genes. DNA methylation, SIRT expression and activity and neuregulin 1 (NRG1), microtubule-associated protein tau (MAPT) and brain-derived neurotrophic factor (BDNF) expression were reduced in buffy coat samples from patients with neurodegenerative disorders. Our data suggest that these epigenetic biomarkers may be useful in clinical practical for the diagnosis, surveillance, and prognosis of disease activity in patients with neurodegenerative diseases.
Neuroinflammation in Cerebral Ischemia and Ischemia/Reperfusion Injuries: From Pathophysiology to Therapeutic Strategies
Authors: Jurcau Anamaria , Simion Aurel
Published: December 2021

Its increasing incidence has led stroke to be the second leading cause of death worldwide. Despite significant advances in recanalization strategies, patients are still at risk for ischemia/reperfusion injuries in this pathophysiology, in which neuroinflammation is significantly involved. Research has shown that in the acute phase, neuroinflammatory cascades lead to apoptosis, disruption of the blood–brain barrier, cerebral edema, and hemorrhagic transformation, while in later stages, these pathways support tissue repair and functional recovery. The present review discusses the various cell types and the mechanisms through which neuroinflammation contributes to parenchymal injury and tissue repair, as well as therapeutic attempts made in vitro, in animal experiments, and in clinical trials which target neuroinflammation, highlighting future therapeutic perspectives.
Human Cytomegalovirus miR-UL70-3p Downregulates the H2O2-Induced Apoptosis by Targeting the Modulator of Apoptosis-1 (MOAP1)
Authors: Pandeya Abhishek , Khalko Raj Kumar , Mishra Anup , Singh Nishant , Singh Sukhveer , Saha Sudipta , Yadav Sanjay , Saxena Sangeeta , Gosipatala Sunil Babu
Published: December 2021

Human Cytomegalovirus (HCMV) is a prototypic beta herpesvirus, causing persistent infections in humans. There are medications that are used to treat the symptoms; however, there is no cure yet. Thus, understanding the molecular mechanisms of HCMV replication and its persistence may reveal new prevention strategies. HCMV evasive strategies on the antiviral responses of the human host largely rely on its significant portion of genome. Numerous studies have highlighted the importance of miRNA-mediated regulation of apoptosis, which is an innate immune mechanism that eradicates virus-infected cells. In this study, we explore the antiapoptotic role of hcmv-miR-UL70-3p in HEK293T cells. We establish that hcmv-miR-UL70-3p targets the proapoptotic gene Modulator of Apoptosis-1 (MOAP1) through interaction with its 3’UTR region of mRNA. The ectopic expression of hcmv-miR-UL70-3p mimic significantly downregulates the H2O2-induced apoptosis through the translational repression of MOAP1. Silencing of MOAP1 through siRNA also inhibits the H2O2-induced apoptosis, which further supports the hcmv-miR-UL70-3p mediated antiapoptotic effect by regulating MOAP1 expression. These results uncover a role for hcmv-miR-UL70-3p and its target MOAP1 in regulating apoptosis.
Ly6c as a New Marker of Mouse Blood Vessels: Qualitative and Quantitative Analyses on Intact and Ischemic Retinas
Authors: Martínez-Carmona Marina , Lucas-Ruiz Fernando , Gallego-Ortega Alejandro , Galindo-Romero Caridad , Norte-Muñoz María , González-Riquelme María José , Valiente-Soriano Francisco J. , Vidal-Sanz Manuel , Agudo-Barriuso Marta
Published: December 2021

Ly6c is an antigen commonly used to differentiate between classical and non-classical monocytes/macrophages. Here we show its potential as a marker of the mouse vasculature, particularly of the retinal vascular plexuses. Ly6c was immunodetected in several tissues of C57BL/6 mice using isolectin IB4 as the control of vasculature staining. In the retina, Ly6c expression was analyzed qualitatively and quantitatively in intact, ischemic, and contralateral retinas from 0 to 30 days after the insult. Ly6c expression was observed in all organs and tissues tested, with a brighter signal and more homogeneous staining than the IB4. In the retinas, Ly6c was well expressed, allowing a detailed study of their anatomy. The three retinal plexuses were morphologically different, and from the superficial to the deep one occupied 15 ± 2, 24 ± 7, and 38 ± 1.4 percent of the retinal surface, respectively. In the injured retinas, there was extravasation of the classically activated monocyte/macrophages (Ly6chigh) and the formation of new vessels in the superficial plexus, increasing the area occupied by it to 25 ± 1%. In the contralateral retinas, the superficial plexus area decreased gradually, reaching significance at 30 days, and Ly6c expression progressively disappeared in the intermediate and deep plexuses. Although the role of Ly6c in vascular endothelial cell function is still not completely understood, we demonstrate here that Ly6c can be used as a new specific marker of the mouse vasculature and to assess, qualitatively and quantitatively, vascular changes in health and disease.
Meta-Analysis and Bioinformatics Detection of Susceptibility Genes in Diabetic Nephropathy
Authors: Tziastoudi Maria , Cholevas Christos , Theoharides Theoharis C. , Stefanidis Ioannis
Published: December 2021

The latest meta-analysis of genome-wide linkage studies (GWLS) identified nine cytogenetic locations suggestive of a linkage with diabetic nephropathy (DN) due to type 1 diabetes mellitus (T1DM) and seven locations due to type 2 diabetes mellitus (T2DM). In order to gain biological insight about the functional role of the genes located in these regions and to prioritize the most significant genetic loci for further research, we conducted a gene ontology analysis with an over representation test for the functional annotation of the protein coding genes. Protein analysis through evolutionary relationships (PANTHER) version 16.0 software and Cytoscape with the relevant plugins were used for the gene ontology analysis, and the overrepresentation test and STRING database were used for the construction of the protein network. The findings of the over-representation test highlight the contribution of immune related molecules like immunoglobulins, cytokines, and chemokines with regard to the most overrepresented protein classes, whereas the most enriched signaling pathways include the VEGF signaling pathway, the Cadherin pathway, the Wnt pathway, the angiogenesis pathway, the p38 MAPK pathway, and the EGF receptor signaling pathway. The common section of T1DM and T2DM results include the significant over representation of immune related molecules, and the Cadherin and Wnt signaling pathways that could constitute potential therapeutic targets for the treatment of DN, irrespective of the type of diabetes.
Carbon-Based Materials in Photodynamic and Photothermal Therapies Applied to Tumor Destruction
Authors: Lagos Karina J. , Buzzá Hilde H. , Bagnato Vanderlei S. , Romero María Paulina
Published: December 2021

Within phototherapy, a grand challenge in clinical cancer treatments is to develop a simple, cost-effective, and biocompatible approach to treat this disease using ultra-low doses of light. Carbon-based materials (CBM), such as graphene oxide (GO), reduced GO (r-GO), graphene quantum dots (GQDs), and carbon dots (C-DOTs), are rapidly emerging as a new class of therapeutic materials against cancer. This review summarizes the progress made in recent years regarding the applications of CBM in photodynamic (PDT) and photothermal (PTT) therapies for tumor destruction. The current understanding of the performance of modified CBM, hybrids and composites, is also addressed. This approach seeks to achieve an enhanced antitumor action by improving and modulating the properties of CBM to treat various types of cancer. Metal oxides, organic molecules, biopolymers, therapeutic drugs, among others, have been combined with CBM to treat cancer by PDT, PTT, or synergistic therapies.
Molecular Mechanisms of Cardiac Amyloidosis
Authors: Saito Yukihiro , Nakamura Kazufumi , Ito Hiroshi
Published: December 2021

Cardiac involvement has a profound effect on the prognosis of patients with systemic amyloidosis. Therapeutic methods for suppressing the production of causative proteins have been developed for ATTR amyloidosis and AL amyloidosis, which show cardiac involvement, and the prognosis has been improved. However, a method for removing deposited amyloid has not been established. Methods for reducing cytotoxicity caused by amyloid deposition and amyloid precursor protein to protect cardiovascular cells are also needed. In this review, we outline the molecular mechanisms and treatments of cardiac amyloidosis.
Antibacterial Therapy by Ag+ Ions Complexed with Titan Yellow/Congo Red and Albumin during Anticancer Therapy of Urinary Bladder Cancer
Authors: Jagusiak Anna , Gosiewski Tomasz , Romaniszyn Dorota , Lasota Małgorzata , Wiśniewska Anna , Chłopaś Katarzyna , Ostrowska Barbara , Kościk Izabela , Bulanda Małgorzata
Published: December 2021

According to the World Health Organization report, the increasing antibiotic resistance of microorganisms is one of the biggest global health problems. The percentage of bacterial strains showing multidrug resistance (MDR) to commonly used antibiotics is growing rapidly. Therefore, the search for alternative solutions to antibiotic therapy has become critical to combat this phenomenon. It is especially important as frequent and recurring infections can cause cancer. One example of this phenomenon is urinary tract infections that can contribute to the development of human urinary bladder carcinoma. This tumor is one of the most common malignant neoplasms in humans. It occurs almost three times more often in men than in women, and in terms of the number of cases, it is the fifth malignant neoplasm after prostate, lung, colon, and stomach cancer. The risk of developing the disease increases with age. Despite the improvement of its treatment methods, the current outcome in the advanced stages of this tumor is not satisfactory. Hence, there is an urgent need to introduce innovative solutions that will prove effective even in the advanced stage of the disease. In our study, a nanosystem based on ionic silver (Ag+) bound to a carrier—Titan yellow (TY) was analyzed. The possibility of binding the thus formed TY-Ag system to Congo red (CR) and albumin (BSA) was determined. TY-Ag binding to CR provides for better nanosystem solubility and enables its targeted intracellular transport and binding to immune complexes. The binding of TY-Ag or CR-TY-Ag to albumin also protects the system against the uncontrolled release of silver ions. It will also allow the delivery of silver in a targeted manner directly to the desired site in the case of intravenous administration of such a system. In this study, the MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values of the TY-Ag or BSA-TY-Ag systems were determined in two reference strains (Escherichia coli and Staphylococcus aureus). The paper presents nanosystems with a size of about 40–50 nm, with an intense antibacterial effect obtained at concentrations of 0.019 mM. We have also discovered that TY-Ag free or complexed with BSA (with a minimal Ag+ dose of 15–20 μM) inhibited cancer cells proliferation. TY-Ag complex diminished migration and effectively inhibited the T24 cell viability and induced apoptosis. On the basis of the obtained results, it has been shown that the presented systems may have anti-inflammatory and antitumor properties at the same time. TY-Ag or BSA-TY-Ag are new potential drugs and may become in future important therapeutic compounds in human urinary bladder carcinoma treatment and/or potent antimicrobial factors as an alternative to antibiotics.
Molecular Weight Analysis of Blue Shark (Prionace glauca) Collagen Hydrolysates by GPC-LS; Effect of High Molecular Weight Hydrolysates on Fibroblast Cultures: mRNA Collagen Type I Expression and Synthesis
Authors: Blanco María , Sanz Noelia , Sánzhez Ana C. , Correa Begoña , Pérez-Martín Ricardo I. , Sotelo Carmen G.
Published: December 2021

High molecular weight (Mw) collagen hydrolysates have been demonstrated to produce a higher synthesis of collagen type I mRNA. Mw determination is a key factor maximizing the effect of collagen hydrolysates on collagen type I synthesis by fibroblasts. This work aimed to achieve a high average Mw in Blue Shark Collagen Hydrolysate, studying different hydrolysis parameters by GPC-LS analysis and testing its effect on mRNA Type I collagen expression. Analysis revealed differences in blue shark collagen hydrolysates Mw depending on hydrolysis conditions. Papain leads to obtaining a significantly higher Mw hydrolysate than Alcalase at different times of hydrolysis and at different enzyme/substrate ratios. Besides, the time of the hydrolysis factor is more determinant than the enzyme/substrate ratio factor for obtaining a higher or lower hydrolysate Mw when using Papain as the enzyme. Contrary, Alcalase hydrolysates resulted in similar Mw with no significant differences between different conditions of hydrolysis assayed. Blue shark collagen hydrolysate showing the highest Mw showed neither cytotoxic nor proliferation effect on fibroblast cell culture. Besides, it exhibited an increasing effect on both mRNA expression and pro-collagen I production.
Hyperthermia Enhances Doxorubicin Therapeutic Efficacy against A375 and MNT-1 Melanoma Cells
Authors: Salvador Diana , Bastos Verónica , Oliveira Helena
Published: December 2021

Melanoma is the deadliest form of skin cancer, and its incidence has alarmingly increased in the last few decades, creating a need for novel treatment approaches. Thus, we evaluated the combinatorial effect of doxorubicin (DOX) and hyperthermia on A375 and MNT-1 human melanoma cell lines. Cells were treated with DOX for 24, 48, and 72 h and their viabilities were assessed. The effect of DOX IC10 and IC20 (combined at 43 °C for 30, 60, and 120 min) on cell viability was further analyzed. Interference on cell cycle dynamics, reactive oxygen species (ROS) production, and apoptosis upon treatment (with 30 min at 43 °C and DOX at the IC20 for 48 h) were analyzed by flow cytometry. Combined treatment significantly decreased cell viability, but not in all tested conditions, suggesting that the effect depends on the drug concentration and heat treatment duration. Combined treatment also mediated a G2/M phase arrest in both cell lines, as well as increasing ROS levels. Additionally, it induced early apoptosis in MNT-1 cells, while in A375 cells this effect was similar to the one caused by hyperthermia alone. These findings demonstrate that hyperthermia enhances DOX effect through cell cycle arrest, oxidative stress, and apoptotic cell death.
The Energy Sensor AMPKα1 Is Critical in Rapamycin-Inhibition of mTORC1-S6K-Induced T-cell Memory
Authors: Ara Anjuman , Xu Aizhang , Ahmed Khawaja Ashfaque , Leary Scot C. , Islam Md. Fahmid , Wu Zhaojia , Chibbar Rajni , Xiang Jim
Published: December 2021

Energy sensors mTORC1 and AMPKα1 regulate T-cell metabolism and differentiation, while rapamycin (Rapa)-inhibition of mTORC1 (RIM) promotes T-cell memory. However, the underlying pathway and the role of AMPKα1 in Rapa-induced T-cell memory remain elusive. Using genetic and pharmaceutical tools, we demonstrate that Rapa promotes T-cell memory in mice in vivo post Listeria monocytogenesis rLmOVA infection and in vitro transition of effector T (TE) to memory T (TM) cells. IL-2- and IL-2+Rapa-stimulated T [IL-2/T and IL-2(Rapa+)/T] cells, when transferred into mice, differentiate into short-term IL-7R−CD62L−KLRG1+ TE and long-lived IL-7R+CD62L+KLRG1− TM cells, respectively. To assess the underlying pathways, we performed Western blotting, confocal microscopy and Seahorse-assay analyses using IL-2/T and IL-2(Rapa+)/T-cells. We determined that IL-2(Rapa+)/T-cells activate transcription FOXO1, TCF1 and Eomes and metabolic pAMPKα1(T172), pULK1(S555) and ATG7 molecules and promote mitochondrial biogenesis and fatty-acid oxidation (FAO). We found that rapamycin-treated AMPKα-deficient AMPKα1-KO IL-2(Rapa+)/TM cells up-regulate transcription factor HIF-1α and induce a metabolic switch from FAO to glycolysis. Interestingly, despite the rapamycin treatment, AMPKα-deficient TM cells lost their cell survival capacity. Taken together, our data indicate that rapamycin promotes T-cell memory via transcriptional FOXO1-TCF1-Eomes programs and AMPKα1-ULK1-ATG7 metabolic axis, and that AMPKα1 plays a critical role in RIM-induced T-cell memory.
Whole-Tissue Three-Dimensional Imaging of Rice at Single-Cell Resolution
Authors: Sato Moeko , Akashi Hiroko , Sakamoto Yuki , Matsunaga Sachihiro , Tsuji Hiroyuki
Published: December 2021

The three-dimensional (3D) arrangement of cells in tissues provides an anatomical basis for analyzing physiological and biochemical aspects of plant and animal cellular development and function. In this study, we established a protocol for tissue clearing and 3D imaging in rice. Our protocol is based on three improvements: clearing with iTOMEI (clearing solution suitable for plants), developing microscopic conditions in which the Z step is optimized for 3D reconstruction, and optimizing cell-wall staining. Our protocol successfully 3D imaged rice shoot apical meristems, florets, and root apical meristems at cellular resolution throughout whole tissues. Using fluorescent reporters of auxin signaling in rice root tips, we also revealed the 3D distribution of auxin signaling events that are activated in the columella, quiescent center, and multiple rows of cells in the stele of the root apical meristem. Examination of cells with higher levels of auxin signaling revealed that only the central row of cells was connected to the quiescent center. Our method provides opportunities to observe the 3D arrangement of cells in rice tissues.
The Choice of a Set of Operations for Forest Landscape Restoration Technology
Authors: Novikova Tatyana P.
Published: December 2021

The study is intended for forest farmers who need to make a mathematically sound and objective decision on the choice of technological operations and technical means for forest restoration. Currently, in studies implementing the forest landscapes restoration approach from the point of view of technology and the use of technical devices (FLR technology), there is some discreteness and fragmentation of the issues. There is a need for a comprehensive study of FLR technology using frontier techniques and devices, and the construction of a single technological FLR algorithm. Preliminary analysis indicates a sharp increase in the number of operational sets from nine for the implementation of the classical technological FLR algorithm to 268 in the first approximation when implementing the proposed algorithm. The FLR algorithm construction is based on the algorithm’s theory, and the verification of the similarity degree of operational sets is based on the cluster analysis by Ward and intra-group connections methods. The algorithm decomposition into six conditionally similar clusters will help plan new forest experiments taking into account interdisciplinary interaction, in addition to the modernization of plant propagation protocols for sustainable reforestation quality management. However, some questions remain for the future: which criterion should be used as a universal basis for choosing operational sets? How can the effectiveness of the FLR technology procedure be evaluated and predicted before its practical implementation?
The Influence of Cardiovascular Risk Factors and Hypogonadism on Cardiac Outcomes in an Aging Population of Beta-Thalassemia Patients
Authors: Barbero Umberto , Ajassa Matteo , Gaglioti Carmen Maria , Piga Antonio , Ferrero Giovanni Battista , Longo Filomena
Published: December 2021

Beta-thalassemia major (β-TM) is a hereditary genetic disease worsened by many comorbidities due to transfusion-related iron despite chelation therapy. Since there has recently been an increase in life expectancy of patients to up to 50 years old, which influences the prevalence of these diseases and the time span for traditional cardiovascular risk factors to play their role, this study aims to evaluate their distribution and prevalence in a population of thalassemia major patients and their relationship with observed cardiovascular events and potential modifying factors. One hundred and fifty-nine β-TM patients with at least 15 years of follow-up were included in this study. The mean age was 40.9 ± 8.4 years; 28% had diabetes mellitus and 62% had hypogonadism. The cardiovascular risk assessed using algorithms (CUORE and Pooled Cohort Risk Equation—PCRE) was low, but 3.8% of patients had at least one episode of heart failure, 35.9% showed early signs of heart failure, 22% received a diagnosis of diastolic dysfunction, and 21.4% showed supraventricular arrhythmias. Hypogonadism was shown to be related to the occurrence of cardiovascular events. The chronic accumulation of iron in the heart and the specific metabolic profile, mainly observed in patients with hypogonadism, allows us to define β-TM as a condition with a high level of cardiovascular risk from many points of view (iron-related myopathy, atherosclerosis and arrhythmias), which requires better stratification tools and a specific follow-up program.
The Vitamin D Role in Preventing Primary Headache in Adult and Pediatric Population
Authors: Dell’Isola Giovanni Battista , Tulli Eleonora , Sica Rossella , Vinti Valerio , Mencaroni Elisabetta , Di Cara Giuseppe , Striano Pasquale , Verrotti Alberto
Published: December 2021

Headache is among the main neurological disorders with a great impact on both adults and children. The diagnosis of primary headache and proper management is often delayed with a great impact on work productivity and overall quality of life. Chronic headache often requires prophylactic therapy to reduce the frequency and severity of the attacks and the use of abortive medications. Besides the use of several classes of drugs, another treatment modality is the use of Nutraceuticals. Some studies have suggested a possible role of vitamin D in headache prophylaxis. Indeed, vitamin D is involved in several pathways of brain development, neuroprotection and neurotransmission. Moreover, there is data suggesting a close relationship between primary headache and vitamin D deficiency, both in children and in adults. To date, a few studies have evaluated the effect of vitamin D on headaches. The aim of this review is to summarize the data collected on headache prophylaxis with vitamin D comparing the effects of vitamin D in pediatric and adult populations.
Prognostic Value of the Acute-to-Chronic Glycemic Ratio at Admission in Heart Failure: A Prospective Study
Authors: Carrera Mª José , Moliner Pedro , Llauradó Gemma , Enjuanes Cristina , Conangla Laura , Chillarón Juan-José , Ballesta Silvia , Climent Elisenda , Comín-Colet Josep , Flores-Le Roux Juana-Antonia
Published: December 2021

Acute hyperglycemia has been associated with worse prognosis in patients hospitalized for heart failure (HF). Nevertheless, studies evaluating the impact of glycemic control on long-term prognosis have shown conflicting results. Our aim was to assess the relationship between acute-to-chronic (A/C) glycemic ratio and 4-year mortality in a cohort of subjects hospitalized for acute HF. A total of 1062 subjects were consecutively included. We measured glycaemia at admission and estimated average chronic glucose levels and the A/C glycemic ratio were calculated. Subjects were stratified into groups according to the A/C glycemic ratio tertiles. The primary endpoint was 4-year mortality. Subjects with diabetes had higher risk for mortality compared to those without (HR 1.35 [95% CI: 1.10–1.65]; p = 0.004). A U-shape curve association was found between glucose at admission and mortality, with a HR of 1.60 [95% CI: 1.22–2.11]; p = 0.001, and a HR of 1.29 [95% CI: 0.97–1.70]; p = 0.078 for the first and the third tertile, respectively, in subjects with diabetes. Additionally, the A/C glycemic ratio was negatively associated with mortality (HR 0.76 [95% CI: 0.58–0.99]; p = 0.046 and HR 0.68 [95% CI: 0.52–0.89]; p = 0.005 for the second and third tertile, respectively). In multivariable analysis, the A/C glycemic ratio remained an independent predictor. In conclusion, in subjects hospitalized for acute HF, the A/C glycemic ratio is significantly associated with mortality, improving the ability to predict mortality compared with glucose levels at admission or average chronic glucose concentrations, especially in subjects with diabetes.
Ampicillin Plus Ceftriaxone Combined Therapy for Enterococcus faecalis Infective Endocarditis in OPAT
Authors: Herrera-Hidalgo Laura , Lomas-Cabezas Jose Manuel , López-Cortés Luis Eduardo , Luque-Márquez Rafael , López-Cortés Luis Fernando , Martínez-Marcos Francisco J. , de la Torre-Lima Javier , Plata-Ciézar Antonio , Hidalgo-Tenorio Carmen , García-López Maria Victoria , Vinuesa David , Gutiérrez-Valencia Alicia , Gil-Navarro Maria Victoria , De Alarcón Arístides
Published: December 2021

Ampicillin plus ceftriaxone (AC) is a well-recognized inpatient regimen for Enterococcus faecalis infective endocarditis (IE). In this regimen, ceftriaxone is usually administered 2 g every 2 h (AC12). The administration of AC in outpatient parenteral antibiotic treatment (OPAT) programs is challenging because multiple daily doses are required. AC regimens useful for OPAT programs include once-daily high-dose administration of ceftriaxone (AC24) or AC co-diluted and jointly administered in bolus every 4 h (ACjoined). In this retrospective analysis of prospectively collected cases, we aimed to assess the clinical effectivity and safety of three AC regimens for the treatment of E. faecalis IE. Fifty-nine patients were treated with AC combinations (AC12 n = 32, AC24 n = 17, and ACjoined n = 10). Six relapses occurred in the whole cohort: five (29.4%) treated with AC24 regimen and one (10.0%) with ACjoined. Patients were cured in 30 (93.3%), 16 (94.1%), and eight (80.0%) cases in the AC12, AC24 and ACjoined groups, respectively. Unplanned readmission occurred in eight (25.0%), six (35.3%), and two (20.0%) patients in the AC12, AC24 and ACjoined groups, respectively. The outcome of patients with E. faecalis IE treated with AC in OPAT programs relies on an optimization of the delivery of the combination. AC24 exhibit an unexpected rate of failures, however, ACjoined might be an effective alternative which clinical results should corroborate in further studies.
Effect of a New Tele-Rehabilitation Program versus Standard Rehabilitation in Patients with Chronic Obstructive Pulmonary Disease
Authors: Cerdán-de-las-Heras Jose , Balbino Fernanda , Løkke Anders , Catalán-Matamoros Daniel , Hilberg Ole , Bendstrup Elisabeth
Published: December 2021

In chronic obstructive pulmonary disease (COPD), rehabilitation is recommended, but attendance rates are low. Tele-rehabilitation may be key. We evaluate the effect of a tele-rehabilitation program vs. standard rehabilitation on COPD. A randomized, non-inferiority study comparing eight weeks of tele-rehabilitation (physiotherapist video/chat-consultations and workout sessions with a virtual-autonomous-physiotherapist-agent (VAPA)) and standard rehabilitation in stable patients with COPD. At baseline, after 8 weeks and 3 and 6 months of follow-up, 6 min walk test distance (6MWTD), 7-day pedometry, quality of life, exercise tolerance, adherence, patient satisfaction and safety were assessed. Fifty-four patients (70 ± 9 years, male 57%, FEV1% 34.53 ± 11.67, FVC% 68.8 ± 18.81, 6MWT 376.23 ± 92.02) were included. Twenty-seven patients were randomized to tele-rehabilitation. Non-inferiority in Δ6MWTD at 8 weeks (47.4 ± 31.4), and at 3 (56.0 ± 38.0) and 6 (95.2 ± 47.1) months follow-up, was observed. No significant difference was observed in 7-day pedometry or quality of life. In the intervention group, 6MWTD increased by 25% and 66% at 3 and 6 months, respectively; adherence was 81%; and patient satisfaction was 4.27 ± 0.77 (Likert scale 0–5). Non-inferiority between groups and high adherence, patient satisfaction and safety in the intervention group were found after rehabilitation and at 3 and 6 months of follow-up. Tele-rehabilitation with VAPA seems to be a promising alternative.
Properties and Applications of PDMS for Biomedical Engineering: A Review
Authors: Miranda Inês , Souza Andrews , Sousa Paulo , Ribeiro João , Castanheira Elisabete M. S. , Lima Rui , Minas Graça
Published: December 2021

Polydimethylsiloxane (PDMS) is an elastomer with excellent optical, electrical and mechanical properties, which makes it well-suited for several engineering applications. Due to its biocompatibility, PDMS is widely used for biomedical purposes. This widespread use has also led to the massification of the soft-lithography technique, introduced for facilitating the rapid prototyping of micro and nanostructures using elastomeric materials, most notably PDMS. This technique has allowed advances in microfluidic, electronic and biomedical fields. In this review, an overview of the properties of PDMS and some of its commonly used treatments, aiming at the suitability to those fields’ needs, are presented. Applications such as microchips in the biomedical field, replication of cardiovascular flow and medical implants are also reviewed.
Examining the Differential Role of General and Specific Processing Speed in Predicting Mathematical Achievement in Junior High School
Authors: Cheng Dazhi , Shi Kaihui , Wang Naiyi , Miao Xinyang , Zhou Xinlin
Published: December 2021

Processing speed is divided into general (including perceptual speed and decision speed) and specific processing speed (including reading fluency and arithmetic fluency). Despite several study findings reporting the association between processing speed and children’s mathematical achievement, it is still unclear whether general or specific processing speed differentially predicts mathematical achievement. The current study aimed to examine the role of general and specific processing speed in predicting mathematical achievements of junior high school students. Cognitive testing was performed in 212 junior school students at the beginning of the 7th grade year, along with assessment of general and specific processing speed. Relevant academic achievement scores were also recorded at the end of the 7th and 9th grade years. Hierarchical regression analyses showed that specific processing speed made a significant unique contribution in mathematical achievement by the end of the 7th grade and could significantly predict mathematical achievements in the high school entrance examinations by end of the 9th grade after controlling for age, gender, and general cognitive abilities. However, general processing speed could not predict mathematical achievements. Moreover, specific processing speed could significantly predict all academic achievements for both the 7th and 9th grade. These results demonstrated that specific processing speed, rather than general processing speed, was able to predict mathematical achievement and made a generalised contribution to all academic achievements in junior school. These findings suggest that specific processing speed could be a reflection of academic fluency and is therefore critical for long-term academic development.