bluuebunny/crossref_metadata_2025 huggingface dataset:
Family E-Chat Group Use Was Associated with Family Wellbeing and Personal Happiness in Hong Kong Adults amidst the COVID-19 Pandemic
Authors: Gong Wei-Jie , Wong Bonny Yee-Man , Ho Sai-Yin , Lai Agnes Yuen-Kwan , Zhao Sheng-Zhi , Wang Man-Ping , Lam Tai-Hing
Published: August 2021

Instant messaging (IM) is increasingly used for family communication amidst the COVID-19 pandemic. However, evidence remains scarce on how family e-chat groups were used and their associations with family and individual wellbeing amidst the pandemic. The numbers of family e-chat groups, functions used, and messages sent and received daily in groups were reported by 4890 adults in May 2020, and their associations with family wellbeing and personal happiness and the mediation effect of family communication quality were examined. Results showed that sending/receiving text messages was most commonly used, followed by receiving/sending photos/pictures, making voice calls, receiving/sending short videos and voice messages, and making video calls. Women and older people used more non-text functions. Higher levels of family wellbeing and personal happiness were associated with having more groups, receiving/sending photos/pictures, video calls, more IM functions used, and more IM messages received/sent daily. Forty-six point two to seventy-five point five percent of their associations with more groups and more functions used were mediated by family communication quality. People having more family e-chat groups and using more IM functions may be more resilient amidst the pandemic, while those without or with low use of family e-chat groups amidst the pandemic would need more attention and assistance in the presence of social distancing.
Rare Defects: Looking at the Dark Face of the Thrombosis
Authors: D’Andrea Giovanna , Margaglione Maurizio
Published: August 2021

Venous thromboembolism (VTE) constitutes a serious and potentially fatal disease, often complicated by pulmonary embolism and is associated with inherited or acquired factors risk. A series of risk factors are known to predispose to venous thrombosis, and these include mutations in the genes that encode anticoagulant proteins as antithrombin, protein C and protein S, and variants in genes that encode instead pro-coagulant factors as factor V (FV Leiden) and factor II (FII G20210A). However, the molecular causes responsible for thrombotic events in some individuals with evident inherited thrombosis remain unknown. An improved knowledge of risk factors, as well as a clear understanding of their role in the pathophysiology of VTE, are crucial to achieve a better identification of patients at higher risk. Moreover, the identification of genes with rare variants but a large effect size may pave the way for studies addressing new antithrombotic agents in order to improve the management of VTE patients. Over the past 20 years, qualitative or quantitative genetic risk factors such as inhibitor proteins of the hemostasis and of the fibrinolytic system, including fibrinogen, thrombomodulin, plasminogen activator inhibitor-1, and elevated concentrations of factors II, FV, VIII, IX, XI, have been associated with thrombotic events, often with conflicting results. The aim of this review is to evaluate available data in literature on these genetic variations to give a contribution to our understanding of the complex molecular mechanisms involved in physiologic and pathophysiologic clot formation and their role in clinical practice.
Medical Adhesive-Related Skin Injury Associated with Surgical Wound Dressing among Spinal Surgery Patients: A Cross-Sectional Study
Authors: Kim Jeounghee , Shin Yongsoon
Published: August 2021

The aim of this cross-sectional study was to determine the incidence, types, and factors associated with medical adhesive-related skin injuries (MARSIs) among spinal surgery patients. Adult patients who underwent planned spinal surgery under general anesthesia at a tertiary hospital in Seoul, Korea were enrolled. Data were collected from March through April 2019. Skins under surgical wound dressings were evaluated for MARSI once every morning until discharge. Skin injuries lasting for 30 min or more were considered as MARSIs. Logistic regression was performed to identify factors associated with MARSI. The incidence of MARSIs in surgical areas was 36.4% and the rate per 100 medical adhesives was 9.8%. All MARSIs occurred on postoperative day 1 or 2. A history of contact dermatitis (OR = 10.517, 95% CI = 3.540–31.241, p < 0.001) and late ambulation (OR = 1.053, 95% CI = 1.012–1.095, p = 0.010) were identified as risk factors for MARSI. Spinal surgery patients were at high risk of MARSIs associated with surgical wound dressings. Patients with a history of contact dermatitis or prolonged bed rest periods need more active skin assessment and more careful skin care to prevent MARSIs after spinal surgery.
Polybetaines in Biomedical Applications
Authors: Racovita Stefania , Trofin Marin-Aurel , Loghin Diana Felicia , Zaharia Marius-Mihai , Bucatariu Florin , Mihai Marcela , Vasiliu Silvia
Published: August 2021

Polybetaines, that have moieties bearing both cationic (quaternary ammonium group) and anionic groups (carboxylate, sulfonate, phosphate/phosphinate/phosphonate groups) situated in the same structural unit represent an important class of smart polymers with unique and specific properties, belonging to the family of zwitterionic materials. According to the anionic groups, polybetaines can be divided into three major classes: poly(carboxybetaines), poly(sulfobetaines) and poly(phosphobetaines). The structural diversity of polybetaines and their special properties such as, antifouling, antimicrobial, strong hydration properties and good biocompatibility lead to their use in nanotechnology, biological and medical fields, water remediation, hydrometallurgy and the oil industry. In this review we aimed to highlight the recent developments achieved in the field of biomedical applications of polybetaines such as: antifouling, antimicrobial and implant coatings, wound healing and drug delivery systems.
Common Genetic Aberrations Associated with Metabolic Interferences in Human Type-2 Diabetes and Acute Myeloid Leukemia: A Bioinformatics Approach
Authors: Kyriakou Theodora-Christina , Papageorgis Panagiotis , Christodoulou Maria-Ioanna
Published: August 2021

Type-2 diabetes mellitus (T2D) is a chronic metabolic disorder, associated with an increased risk of developing solid tumors and hematological malignancies, including acute myeloid leukemia (AML). However, the genetic background underlying this predisposition remains elusive. We herein aimed at the exploration of the genetic variants, related transcriptomic changes and disturbances in metabolic pathways shared by T2D and AML, utilizing bioinformatics tools and repositories, as well as publicly available clinical datasets. Our approach revealed that rs11709077 and rs1801282, on PPARG, rs11108094 on USP44, rs6685701 on RPS6KA1 and rs7929543 on AC118942.1 comprise common SNPs susceptible to the two diseases and, together with 64 other co-inherited proxy SNPs, may affect the expression patterns of metabolic genes, such as USP44, METAP2, PPARG, TIMP4 and RPS6KA1, in adipose tissue, skeletal muscle, liver, pancreas and whole blood. Most importantly, a set of 86 AML/T2D common susceptibility genes was found to be significantly associated with metabolic cellular processes, including purine, pyrimidine, and choline metabolism, as well as insulin, AMPK, mTOR and PI3K signaling. Moreover, it was revealed that the whole blood of AML patients exhibits deregulated expression of certain T2D-related genes. Our findings support the existence of common metabolic perturbations in AML and T2D that may account for the increased risk for AML in T2D patients. Future studies may focus on the elucidation of these pathogenetic mechanisms in AML/T2D patients, as well as on the assessment of certain susceptibility variants and genes as potential biomarkers for AML development in the setting of T2D. Detection of shared therapeutic molecular targets may enforce the need for repurposing metabolic drugs in the therapeutic management of AML.
Radiation-Induced Osteocyte Senescence Alters Bone Marrow Mesenchymal Stem Cell Differentiation Potential via Paracrine Signaling
Authors: Xu Linshan , Wang Yuyang , Wang Jianping , Zhai Jianglong , Ren Li , Zhu Guoying
Published: August 2021

Cellular senescence and its senescence-associated secretory phenotype (SASP) are widely regarded as promising therapeutic targets for aging-related diseases, such as osteoporosis. However, the expression pattern of cellular senescence and multiple SASP secretion remains unclear, thus leaving a large gap in the knowledge for a desirable intervention targeting cellular senescence. Therefore, there is a critical need to understand the molecular mechanism of SASP secretion in the bone microenvironment that can ameliorate aging-related degenerative pathologies including osteoporosis. In this study, osteocyte-like cells (MLO-Y4) were induced to cellular senescence by 2 Gy γ-rays; then, senescence phenotype changes and adverse effects of SASP on bone marrow mesenchymal stem cell (BMSC) differentiation potential were investigated. The results revealed that 2 Gy irradiation could hinder cell viability, shorten cell dendrites, and induce cellular senescence, as evidenced by the higher expression of senescence markers p16 and p21 and the elevated formation of senescence-associated heterochromatin foci (SAHF), which was accompanied by the enhanced secretion of SASP markers such as IL-1α, IL-6, MMP-3, IGFBP-6, resistin, and adiponectin. When 0.8 μM JAK1 inhibitors were added to block SASP secretion, the higher expression of SASP was blunted, but the inhibition in osteogenic and adipogenic differentiation potential of BMSCs co-cultured with irradiated MLO-Y4 cell conditioned medium (CM- 2 Gy) was alleviated. These results suggest that senescent osteocytes can perturb BMSCs’ differential potential via the paracrine signaling of SASP, which was also demonstrated by in vivo experiments. In conclusion, we identified the SASP factor partially responsible for the degenerative differentiation of BMSCs, which allowed us to hypothesize that senescent osteocytes and their SASPs may contribute to radiation-induced bone loss.
Genome-Wide Identification and Expression Profiling Analysis of WOX Family Protein-Encoded Genes in Triticeae Species
Authors: Shi Lei , Wang Ke , Du Lipu , Song Yuxia , Li Huihui , Ye Xingguo
Published: August 2021

The WOX family is a group of plant-specific transcription factors which regulate plant growth and development, cell division and differentiation. From the available genome sequence databases of nine Triticeae species, 199 putative WOX genes were identified. Most of the identified WOX genes were distributed on the chromosomes of homeologous groups 1 to 5 and originated via the orthologous evolution approach. Parts of WOX genes in Triticum aestivum were confirmed by the specific PCR markers using a set of Triticum. durum-T. aestivum genome D substitution lines. All of these identified WOX proteins could be grouped into three clades, similar to those in rice and Arabidopsis. WOX family members were conserved among these Triticeae plants; all of them contained the HOX DNA-binding homeodomain, and WUS clade members contained the characteristic WUS-box motif, while only WUS and WOX9 contained the EAR motif. The RNA-seq and qPCR analysis revealed that the TaWOX genes had tissue-specific expression feature. From the expression patterns of TaWOX genes during immature embryo callus production, TaWOX9 is likely closely related with the regulation of regeneration process in T. aestivum. The findings in this study could provide a basis for evolution and functional investigation and practical application of the WOX family genes in Triticeae species.
Regulation of Reactive Oxygen Species and Antioxidant Defense in Plants under Salinity
Authors: Hasanuzzaman Mirza , Raihan Md. Rakib Hossain , Masud Abdul Awal Chowdhury , Rahman Khussboo , Nowroz Farzana , Rahman Mira , Nahar Kamrun , Fujita Masayuki
Published: August 2021

The generation of oxygen radicals and their derivatives, known as reactive oxygen species, (ROS) is a part of the signaling process in higher plants at lower concentrations, but at higher concentrations, those ROS cause oxidative stress. Salinity-induced osmotic stress and ionic stress trigger the overproduction of ROS and, ultimately, result in oxidative damage to cell organelles and membrane components, and at severe levels, they cause cell and plant death. The antioxidant defense system protects the plant from salt-induced oxidative damage by detoxifying the ROS and also by maintaining the balance of ROS generation under salt stress. Different plant hormones and genes are also associated with the signaling and antioxidant defense system to protect plants when they are exposed to salt stress. Salt-induced ROS overgeneration is one of the major reasons for hampering the morpho-physiological and biochemical activities of plants which can be largely restored through enhancing the antioxidant defense system that detoxifies ROS. In this review, we discuss the salt-induced generation of ROS, oxidative stress and antioxidant defense of plants under salinity.
Vitamin K-Dependent Proteins in Skeletal Development and Disease
Authors: Stock Michael , Schett Georg
Published: August 2021

Vitamin K and Vitamin K-dependent proteins (VKDPs) are best known for their pivotal role in blood coagulation. Of the 14 VKPDs identified in humans to date, 6 play also important roles in skeletal biology and disease. Thus, osteocalcin, also termed bone Gla-protein, is the most abundant non-collagenous protein in bone. Matrix Gla protein and Ucma/GRP on the other hand are highly abundant in cartilage. Furthermore, periostin, protein S, and growth arrest specific 6 protein (GAS 6) are expressed in skeletal tissues. The roles for these VKDPs are diverse but include the control of calcification and turnover of bone and cartilage. Vitamin K plays an important role in osteoporosis and serum osteocalcin levels are recognized as a promising marker for osteoporosis. On the other hand, matrix Gla protein and Ucma/GRP are associated with osteoarthritis. This review focuses on the roles of these three VKDPs, osteocalcin, matrix Gla protein and Ucma/GRP, in skeletal development and disease but will also summarize the roles the other skeletal VKDPs (periostin, protein S and GAS6) in skeletal biology.
Proteome Based Approach Defines Candidates for Designing a Multitope Vaccine against the Nipah Virus
Authors: Soltan Mohamed A. , Eldeen Muhammad Alaa , Elbassiouny Nada , Mohamed Ibrahim , El-damasy Dalia A. , Fayad Eman , Abu Ali Ola A. , Raafat Nermin , Eid Refaat A. , Al-Karmalawy Ahmed A.
Published: August 2021

Nipah virus is one of the most harmful emerging viruses with deadly effects on both humans and animals. Because of the severe outbreaks, in 2018, the World Health Organization focused on the urgent need for the development of effective solutions against the virus. However, up to date, there is no effective vaccine against the Nipah virus in the market. In the current study, the complete proteome of the Nipah virus (nine proteins) was analyzed for the antigenicity score and the virulence role of each protein, where we came up with fusion glycoprotein (F), glycoprotein (G), protein (V), and protein (W) as the candidates for epitope prediction. Following that, the multitope vaccine was designed based on top-ranking CTL, HTL, and BCL epitopes from the selected proteins. We used suitable linkers, adjuvant, and PADRE peptides to finalize the constructed vaccine, which was analyzed for its physicochemical features, antigenicity, toxicity, allergenicity, and solubility. The designed vaccine passed these assessments through computational analysis and, as a final step, we ran a docking analysis between the designed vaccine and TLR-3 and validated the docked complex through molecular dynamics simulation, which estimated a strong binding and supported the nomination of the designed vaccine as a putative solution for Nipah virus. Here, we describe the computational approach for design and analysis of this vaccine.
Enhancer of Zeste Homolog 2 (EZH2) Contributes to Rod Photoreceptor Death Process in Several Forms of Retinal Degeneration and Its Activity Can Serve as a Biomarker for Therapy Efficacy
Authors: Mbefo Martial , Berger Adeline , Schouwey Karine , Gérard Xavier , Kostic Corinne , Beryozkin Avigail , Sharon Dror , Dolfuss Hélène , Munier Francis , Tran Hoai Viet , van Lohuizen Maarten , Beltran William A. , Arsenijevic Yvan
Published: August 2021

Inherited retinal dystrophies (IRD) are due to various gene mutations. Each mutated gene instigates a specific cell homeostasis disruption, leading to a modification in gene expression and retinal degeneration. We previously demonstrated that the polycomb-repressive complex-1 (PRC1) markedly contributes to the cell death process. To better understand these mechanisms, we herein study the role of PRC2, specifically EZH2, which often initiates the gene inhibition by PRC1. We observed that the epigenetic mark H3K27me3 generated by EZH2 was progressively and strongly expressed in some individual photoreceptors and that the H3K27me3-positive cell number increased before cell death. H3K27me3 accumulation occurs between early (accumulation of cGMP) and late (CDK4 expression) events of retinal degeneration. EZH2 hyperactivity was observed in four recessive and two dominant mouse models of retinal degeneration, as well as two dog models and one IRD patient. Acute pharmacological EZH2 inhibition by intravitreal injection decreased the appearance of H3K27me3 marks and the number of TUNEL-positive cells revealing that EZH2 contributes to the cell death process. Finally, we observed that the absence of the H3K27me3 mark is a biomarker of gene therapy treatment efficacy in XLRPA2 dog model. PRC2 and PRC1 are therefore important actors in the degenerative process of multiple forms of IRD.
Long-Term Efficacy of Intranasal Esketamine in Treatment-Resistant Major Depression: A Systematic Review
Authors: Capuzzi Enrico , Caldiroli Alice , Capellazzi Martina , Tagliabue Ilaria , Marcatili Matteo , Colmegna Fabrizia , Clerici Massimo , Buoli Massimiliano , Dakanalis Antonios
Published: August 2021

Esketamine (ESK) has been approved as a rapid-acting intranasal treatment for treatment-resistant depression (TRD). Although existing studies have investigated the efficacy of ESK in the 4-week induction phase, our knowledge about long-term ESK efficacy remains poor. The aim of this systematic review was to summarize the available data on long-term ESK efficacy for TRD. A systematic search was performed including articles in English, up to 31 March 2021. The search found 7 relevant studies, involving 1024 adult TRD patients. Continuing treatment with ESK after the 4-week induction phase may be associated with stable efficacy in relapse prevention among TRD patients. Conversely, the long-term antidepressant effectiveness upon discontinuation of ESK might be limited, although data from three studies had a moderate to high risk of bias. Overall, the results on the effectiveness of this compound in the long term are mixed. According to our findings, ESK treatment should be continued following the induction phase to reach a stable efficacy in relapse prevention, while the long-term antidepressant and anti-suicidal effects of ESK after discontinuation are inconsistent. Currently, the level of proof of ESK efficacy in long-term TRD treatment remains low and more RCTs with larger sample sizes and active comparators are needed.
Discoidin Domain Receptor 2 Regulates AT1R Expression in Angiotensin II-Stimulated Cardiac Fibroblasts via Fibronectin-Dependent Integrin-β1 Signaling
Authors: Titus Allen Sam , Venugopal Harikrishnan , Ushakumary Mereena George , Wang Mingyi , Cowling Randy T. , Lakatta Edward G. , Kailasam Shivakumar
Published: August 2021

This study probed the largely unexplored regulation and role of fibronectin in Angiotensin II-stimulated cardiac fibroblasts. Using gene knockdown and overexpression approaches, Western blotting, and promoter pull-down assay, we show that collagen type I-activated Discoidin Domain Receptor 2 (DDR2) mediates Angiotensin II-dependent transcriptional upregulation of fibronectin by Yes-activated Protein in cardiac fibroblasts. Furthermore, siRNA-mediated fibronectin knockdown attenuated Angiotensin II-stimulated expression of collagen type I and anti-apoptotic cIAP2, and enhanced cardiac fibroblast susceptibility to apoptosis. Importantly, an obligate role for fibronectin was observed in Angiotensin II-stimulated expression of AT1R, the Angiotensin II receptor, which would link extracellular matrix (ECM) signaling and Angiotensin II signaling in cardiac fibroblasts. The role of fibronectin in Angiotensin II-stimulated cIAP2, collagen type I, and AT1R expression was mediated by Integrin-β1-integrin-linked kinase signaling. In vivo, we observed modestly reduced basal levels of AT1R in DDR2-null mouse myocardium, which were associated with the previously reported reduction in myocardial Integrin-β1 levels. The role of fibronectin, downstream of DDR2, could be a critical determinant of cardiac fibroblast-mediated wound healing following myocardial injury. In summary, our findings suggest a complex mechanism of regulation of cardiac fibroblast function involving two major ECM proteins, collagen type I and fibronectin, and their receptors, DDR2 and Integrin-β1.
Supercritical Antisolvent Fractionation of Antioxidant Compounds from Salvia officinalis
Authors: Mur Raquel , Pardo Juan I. , Pino-Otín M. Rosa , Urieta José S. , Mainar Ana M.
Published: August 2021

The increasing interest towards greener antioxidants obtained via natural sources and more sustainable processes encourages the development of new theoretical and experimental methods in the field of those compounds. Two advanced separation methods using supercritical CO2 are applied to obtain valuable antioxidants from Salvia officinalis, and a first approximation to a QSAR model relating molecular structure with antioxidant activity is explored in order to be used, in the future, as a guide for the preselection of compounds of interest in these processes. Separation experiments through antisolvent fractionation with supercritical CO2 were designed using a Response Surface Methodology to study the effect of pressure and CO2 flow rate on both mass yields and capability to obtain fractions enriched in three antioxidant compounds: chlorogenic acid, caffeic acid and rosmarinic acid which were tracked using HPLC PDA. Rosmarinic acid was completely retained in the precipitation vessel while chlorogenic and caffeic acids, though distributed between the two separated fractions, had a major presence in the precipitation vessel too. The conditions predicted for an optimal overall yield and enrichment were 148 bar and 10 g/min. Although a training dataset including much more compounds than those now considered can be recommended, descriptors calculated from the σ-profiles provided by COSMO-RS model seem to be adequate for estimating the antioxidant activity of pure compounds through QSAR.
Early Bone Healing on Hydroxyapatite-Coated and Chemically-Modified Hydrophilic Implant Surfaces in an Ovine Model
Authors: Ajami Elnaz , Fu Cong , Wen Hai Bo , Bassett Jeffrey , Park Sun Jin , Pollard Marie
Published: August 2021

Implant topography affects early peri-implant bone healing by changing the osteoconduction rate in the surrounding biological environment. Implant surfaces have been designed to promote faster and stronger bone formation for rapid and stable prosthesis loading. Early peri-implant bone healing has been observed with a sandblasted, acid-etched implant that was chemically modified to be hydrophilic (cmSLA). The present study investigates whether early peri-implant bone healing extends to a rough surface implant with a high crystalline hydroxyapatite surface (TSV MP-1 HA). Three implants were randomly placed in porous trabecular bone within both medial femoral condyles of 10 sheep. Early peri-implant bone stability was measured at 3- and 6-weeks healing time following implant insertion. Results indicated a similar implant stability quotient between the implants at insertion and over time. The significant increase over time of reverse torque values with respect to insertion torque (p < 0.001) did not differ between the implants. However, the bone-to-implant contact of TSV MP-1 HA was significantly higher than that of cmSLA implants at 6 weeks (p < 0.01). These data validate previous findings of a hydrophilic implant surface and extend the observation of early osseointegration to a rough surface implant in porous trabecular bone.
The Importance of Alpha-Actinin Proteins in Platelet Formation and Function, and Their Causative Role in Congenital Macrothrombocytopenia
Authors: O’Sullivan Leanne R. , Cahill Mary R. , Young Paul W.
Published: August 2021

The actin cytoskeleton plays a central role in platelet formation and function. Alpha-actinins (actinins) are actin filament crosslinking proteins that are prominently expressed in platelets and have been studied in relation to their role in platelet activation since the 1970s. However, within the past decade, several groups have described mutations in ACTN1/actinin-1 that cause congenital macrothrombocytopenia (CMTP)—accounting for approximately 5% of all cases of this condition. These findings are suggestive of potentially novel functions for actinins in platelet formation from megakaryocytes in the bone marrow and/or platelet maturation in circulation. Here, we review some recent insights into the well-known functions of actinins in platelet activation before considering possible roles for actinins in platelet formation that could explain their association with CMTP. We describe what is known about the consequences of CMTP-linked mutations on actinin-1 function at a molecular and cellular level and speculate how these changes might lead to the alterations in platelet count and morphology observed in CMTP patients. Finally, we outline some unanswered questions in this area and how they might be addressed in future studies.
Functional Characterization of a Cucumber (Cucumis sativus L.) Vacuolar Invertase, CsVI1, Involved in Hexose Accumulation and Response to Low Temperature Stress
Authors: Feng Zili , Zheng Fenghua , Wu Silin , Li Rui , Li Yue , Zhong Jiaxin , Zhao Hongbo
Published: August 2021

Cucumber (Cucumis sativus L.), an important vegetable plant species, is susceptible to low temperature stress especially during the seedling stage. Vacuolar invertase (VI) plays important roles in plant responses to abiotic stress. However, the molecular and biochemical mechanisms of VI function in cucumber, have not yet been completely understood and VI responses to low temperature stress and it functions in cold tolerance in cucumber seedlings are also in need of exploration. The present study found that hexose accumulation in the roots of cucumber seedlings under low temperature stress is closely related to the observed enhancement of invertase activity. Our genome-wide search for the vacuolar invertase (VI) genes in cucumber identified the candidate VI-encoding gene CsVI1. Expression profiling of CsVI1 showed that it was mainly expressed in the young roots of cucumber seedlings. In addition, transcriptional analysis indicated that CsVI1 expression could respond to low temperature stress. Recombinant CsVI1 proteins purified from Pichia pastoris and Nicotiana benthamiana leaves could hydrolyze sucrose into hexoses. Further, overexpression of CsVI1 in cucumber plants could increase their hexose contents and improve their low temperature tolerance. Lastly, a putative cucumber invertase inhibitor was found could form a complex with CsVI1. In summary, these results confirmed that CsVI1 functions as an acid invertase involved in hexose accumulation and responds to low temperature stress in cucumber seedlings.
Role of Heat Shock Proteins (HSP70 and HSP90) in Viral Infection
Authors: Lubkowska Anna , Pluta Waldemar , Strońska Aleksandra , Lalko Alicja
Published: August 2021

Heat shock proteins (HSPs) are a large group of chaperones found in most eukaryotes and bacteria. They are responsible for the correct protein folding, protection of the cell against stressors, presenting immune and inflammatory cytokines; furthermore, they are important factors in regulating cell differentiation, survival and death. Although the biological function of HSPs is to maintain cell homeostasis, some of them can be used by viruses both to fold their proteins and increase the chances of survival in unfavorable host conditions. Folding viral proteins as well as replicating many different viruses are carried out by, among others, proteins from the HSP70 and HSP90 families. In some cases, the HSP70 family proteins directly interact with viral polymerase to enhance viral replication or they can facilitate the formation of a viral replication complex and/or maintain the stability of complex proteins. It is known that HSP90 is important for the expression of viral genes at both the transcriptional and the translational levels. Both of these HSPs can form a complex with HSP90 and, consequently, facilitate the entry of the virus into the cell. Current studies have shown the biological significance of HSPs in the course of infection SARS-CoV-2. A comprehensive understanding of chaperone use during viral infection will provide new insight into viral replication mechanisms and therapeutic potential. The aim of this study is to describe the molecular basis of HSP70 and HSP90 participation in some viral infections and the potential use of these proteins in antiviral therapy.
Patient-Derived Xenograft Models in Cervical Cancer: A Systematic Review
Authors: Tanaka Tomohito , Nishie Ruri , Ueda Shoko , Miyamoto Shunsuke , Hashida Sousuke , Konishi Hiromi , Terada Shinichi , Kogata Yuhei , Sasaki Hiroshi , Tsunetoh Satoshi , Taniguchi Kohei , Komura Kazumasa , Ohmichi Masahide
Published: August 2021

Background: Patient-derived xenograft (PDX) models have been a focus of attention because they closely resemble the tumor features of patients and retain the molecular and histological features of diseases. They are promising tools for translational research. In the current systematic review, we identify publications on PDX models of cervical cancer (CC-PDX) with descriptions of main methodological characteristics and outcomes to identify the most suitable method for CC-PDX. Methods: We searched on PubMed to identify articles reporting CC-PDX. Briefly, the main inclusion criterion for papers was description of PDX created with fragments obtained from human cervical cancer specimens, and the exclusion criterion was the creation of xenograft with established cell lines. Results: After the search process, 10 studies were found and included in the systematic review. Among 98 donor patients, 61 CC-PDX were established, and the overall success rate was 62.2%. The success rate in each article ranged from 0% to 75% and was higher when using severe immunodeficient mice such as severe combined immunodeficient (SCID), nonobese diabetic (NOD) SCID, and NOD SCID gamma (NSG) mice than nude mice. Subrenal capsule implantation led to a higher engraftment rate than orthotopic and subcutaneous implantation. Fragments with a size of 1–3 mm3 were suitable for CC-PDX. No relationship was found between the engraftment rate and characteristics of the tumor and donor patient, including histology, staging, and metastasis. The latency period varied from 10 days to 12 months. Most studies showed a strong similarity in pathological and immunohistochemical features between the original tumor and the PDX model. Conclusion: Severe immunodeficient mice and subrenal capsule implantation led to a higher engraftment rate; however, orthotopic and subcutaneous implantation were alternatives. When using nude mice, subrenal implantation may be better. Fragments with a size of 1–3 mm3 were suitable for CC-PDX. Few reports have been published about CC-PDX; the results were not confirmed because of the small sample size.
Auxin Metabolome Profiling in the Arabidopsis Endoplasmic Reticulum Using an Optimised Organelle Isolation Protocol
Authors: Včelařová Ludmila , Skalický Vladimír , Chamrád Ivo , Lenobel René , Kubeš Martin F. , Pěnčík Aleš , Novák Ondřej
Published: August 2021

The endoplasmic reticulum (ER) is an extensive network of intracellular membranes. Its major functions include proteosynthesis, protein folding, post-transcriptional modification and sorting of proteins within the cell, and lipid anabolism. Moreover, several studies have suggested that it may be involved in regulating intracellular auxin homeostasis in plants by modulating its metabolism. Therefore, to study auxin metabolome in the ER, it is necessary to obtain a highly enriched (ideally, pure) ER fraction. Isolation of the ER is challenging because its biochemical properties are very similar to those of other cellular endomembranes. Most published protocols for ER isolation use density gradient ultracentrifugation, despite its suboptimal resolving power. Here we present an optimised protocol for ER isolation from Arabidopsis thaliana seedlings for the subsequent mass spectrometric determination of ER-specific auxin metabolite profiles. Auxin metabolite analysis revealed highly elevated levels of active auxin form (IAA) within the ER compared to whole plants. Moreover, samples prepared using our optimised isolation ER protocol are amenable to analysis using various “omics” technologies including analyses of both macromolecular and low molecular weight compounds from the same sample.
Step-by-Step Immune Activation for Suicide Gene Therapy Reinforcement
Authors: Alekseenko Irina , Kuzmich Alexey , Kondratyeva Liya , Kondratieva Sofia , Pleshkan Victor , Sverdlov Eugene
Published: August 2021

Gene-directed enzyme prodrug gene therapy (GDEPT) theoretically represents a useful method to carry out chemotherapy for cancer with minimal side effects through the formation of a chemotherapeutic agent inside cancer cells. However, despite great efforts, promising preliminary results, and a long period of time (over 25 years) since the first mention of this method, GDEPT has not yet reached the clinic. There is a growing consensus that optimal cancer therapies should generate robust tumor-specific immune responses. The advent of checkpoint immunotherapy has yielded new highly promising avenues of study in cancer therapy. For such therapy, it seems reasonable to use combinations of different immunomodulators alongside traditional methods, such as chemotherapy and radiotherapy, as well as GDEPT. In this review, we focused on non-viral gene immunotherapy systems combining the intratumoral production of toxins diffused by GDEPT and immunomodulatory molecules. Special attention was paid to the applications and mechanisms of action of the granulocyte-macrophage colony-stimulating factor (GM–CSF), a cytokine that is widely used but shows contradictory effects. Another method to enhance the formation of stable immune responses in a tumor, the use of danger signals, is also discussed. The process of dying from GDEPT cancer cells initiates danger signaling by releasing damage-associated molecular patterns (DAMPs) that exert immature dendritic cells by increasing antigen uptake, maturation, and antigen presentation to cytotoxic T-lymphocytes. We hypothesized that the combined action of this danger signal and GM–CSF issued from the same dying cancer cell within a limited space would focus on a limited pool of immature dendritic cells, thus acting synergistically and enhancing their maturation and cytotoxic T-lymphocyte attraction potential. We also discuss the problem of enhancing the cancer specificity of the combined GDEPT–GM–CSF–danger signal system by means of artificial cancer specific promoters or a modified delivery system.
Antimicrobial Resistance and Whole-Genome Characterisation of High-Level Ciprofloxacin-Resistant Salmonella Enterica Serovar Kentucky ST 198 Strains Isolated from Human in Poland
Authors: Wołkowicz Tomasz , Zacharczuk Katarzyna , Gierczyński Rafał , Nowakowska Magdalena , Piekarska Katarzyna
Published: August 2021

Background: Salmonella Kentucky belongs to zoonotic serotypes that demonstrate that the high antimicrobial resistance and multidrug resistance (including fluoroquinolones) is an emerging problem. To the best of our knowledge, clinical S. Kentucky strains isolated in Poland remain undescribed. Methods: Eighteen clinical S. Kentucky strains collected in the years 2018–2019 in Poland were investigated. All the strains were tested for susceptibility to 11 antimicrobials using the disc diffusion and E-test methods. Whole genome sequences were analysed for antimicrobial resistance genes, mutations, the presence and structure of SGI1-K (Salmonella Genomic Island and the genetic relationship of the isolates. Results: Sixteen of 18 isolates (88.9%) were assigned as ST198 and were found to be high-level resistant to ampicillin (>256 mg/L) and quinolones (nalidixic acid MIC ≥ 1024 mg/L, ciprofloxacin MIC range 6–16 mg/L). All the 16 strains revealed three mutations in QRDR of GyrA and ParC. The substitutions of Ser83 → Phe and Asp87 → Tyr of the GyrA subunit and Ser80→Ile of the ParC subunit were the most common. One S. Kentucky isolate had qnrS1 in addition to the QRDR mutations. Five of the ST198 strains, grouped in cluster A, had multiple resistant determinants like blaTEM1-B, aac(6′)-Iaa, sul1 or tetA, mostly in SGI1 K. Seven strains, grouped in cluster B, had shorter SGI1-K with deletions of many regions and with few resistance genes detected. Conclusion: The results of this study demonstrated that a significant part of S. Kentucky isolates from humans in Poland belonged to ST198 and were high-level resistant to ampicillin and quinolones.
Updated Information on Antimicrobial Activity of Hydrazide–Hydrazones
Authors: Popiołek Łukasz
Published: August 2021

Hydrazide–hydrazones possess a wide spectrum of bioactivity, including antibacterial, antitubercular, antifungal, anticancer, anti-inflammatory, anticonvulsant, antidepressant, antiviral, and antiprotozoal properties. This review is focused on the latest scientific reports regarding antibacterial, antimycobacterial, and antifungal activities of hydrazide–hydrazones published between 2017 and 2021. The molecules and their chemical structures presented in this article are the most active derivatives, with discussed activities having a hydrazide–hydrazone moiety as the main scaffold or as a side chain. Presented information constitute a concise summary, which may be used as a practical guide for further design of new molecules with antimicrobial activity.
Essential Oil-Based Bioherbicides: Human Health Risks Analysis
Authors: Maes Chloë , Meersmans Jeroen , Lins Laurence , Bouquillon Sandrine , Fauconnier Marie-Laure
Published: August 2021

In recent years, the development of new bio-based products for biocontrol has been gaining importance as it contributes to reducing the use of synthetic herbicides in agriculture. Conventional herbicides (i.e., the ones with synthetic molecules) can lead to adverse effects such as human diseases (cancers, neurodegenerative diseases, reproductive perturbations, etc.) but also to disturbing the environment because of their drift in the air, transport throughout aquatic systems and persistence across different environments. The use of natural molecules seems to be a very good alternative for maintaining productive agriculture but without the negative side effects of synthetic herbicides. In this context, essential oils and their components are increasingly studied in order to produce several categories of biopesticides thanks to their well-known biocidal activities. However, these molecules can also be potentially hazardous to humans and the environment. This article reviews the state of the literature and regulations with regard to the potential risks related to the use of essential oils as bioherbicides in agricultural and horticultural applications.
Myogenic Potential of Extracellular Matrix Derived from Decellularized Bovine Pericardium
Authors: Carton Flavia , Di Francesco Dalila , Fusaro Luca , Zanella Emma , Apostolo Claudio , Oltolina Francesca , Cotella Diego , Prat Maria , Boccafoschi Francesca
Published: August 2021

Skeletal muscles represent 40% of body mass and its native regenerative capacity can be permanently lost after a traumatic injury, congenital diseases, or tumor ablation. The absence of physiological regeneration can hinder muscle repair preventing normal muscle tissue functions. To date, tissue engineering (TE) represents one promising option for treating muscle injuries and wasting. In particular, hydrogels derived from the decellularized extracellular matrix (dECM) are widely investigated in tissue engineering applications thanks to their essential role in guiding muscle regeneration. In this work, the myogenic potential of dECM substrate, obtained from decellularized bovine pericardium (Tissuegraft Srl), was evaluated in vitro using C2C12 murine muscle cells. To assess myotubes formation, the width, length, and fusion indexes were measured during the differentiation time course. Additionally, the ability of dECM to support myogenesis was assessed by measuring the expression of specific myogenic markers: α-smooth muscle actin (α-sma), myogenin, and myosin heavy chain (MHC). The results obtained suggest that the dECM niche was able to support and enhance the myogenic potential of C2C12 cells in comparison of those grown on a plastic standard surface. Thus, the use of extracellular matrix proteins, as biomaterial supports, could represent a promising therapeutic strategy for skeletal muscle tissue engineering.
A Multiplex CRISPR-Screen Identifies PLA2G4A as Prognostic Marker and Druggable Target for HOXA9 and MEIS1 Dependent AML
Authors: Hassan Jacob Jalil , Lieske Anna , Dörpmund Nicole , Klatt Denise , Hoffmann Dirk , Kleppa Marc-Jens , Kustikova Olga S. , Stahlhut Maike , Schwarzer Adrian , Schambach Axel , Maetzig Tobias
Published: August 2021

HOXA9 and MEIS1 are frequently upregulated in acute myeloid leukemia (AML), including those with MLL-rearrangement. Because of their pivotal role in hemostasis, HOXA9 and MEIS1 appear non-druggable. We, thus, interrogated gene expression data of pre-leukemic (overexpressing Hoxa9) and leukemogenic (overexpressing Hoxa9 and Meis1; H9M) murine cell lines to identify cancer vulnerabilities. Through gene expression analysis and gene set enrichment analyses, we compiled a list of 15 candidates for functional validation. Using a novel lentiviral multiplexing approach, we selected and tested highly active sgRNAs to knockout candidate genes by CRISPR/Cas9, and subsequently identified a H9M cell growth dependency on the cytosolic phospholipase A2 (PLA2G4A). Similar results were obtained by shRNA-mediated suppression of Pla2g4a. Remarkably, pharmacologic inhibition of PLA2G4A with arachidonyl trifluoromethyl ketone (AACOCF3) accelerated the loss of H9M cells in bulk cultures. Additionally, AACOCF3 treatment of H9M cells reduced colony numbers and colony sizes in methylcellulose. Moreover, AACOCF3 was highly active in human AML with MLL rearrangement, in which PLA2G4A was significantly higher expressed than in AML patients without MLL rearrangement, and is sufficient as an independent prognostic marker. Our work, thus, identifies PLA2G4A as a prognostic marker and potential therapeutic target for H9M-dependent AML with MLL-rearrangement.
The Differential Roles for Neurodevelopmental and Neuroendocrine Genes in Shaping GnRH Neuron Physiology and Deficiency
Authors: Oleari Roberto , Massa Valentina , Cariboni Anna , Lettieri Antonella
Published: August 2021

Gonadotropin releasing hormone (GnRH) neurons are hypothalamic neuroendocrine cells that control sexual reproduction. During embryonic development, GnRH neurons migrate from the nose to the hypothalamus, where they receive inputs from several afferent neurons, following the axonal scaffold patterned by nasal nerves. Each step of GnRH neuron development depends on the orchestrated action of several molecules exerting specific biological functions. Mutations in genes encoding for these essential molecules may cause Congenital Hypogonadotropic Hypogonadism (CHH), a rare disorder characterized by GnRH deficiency, delayed puberty and infertility. Depending on their action in the GnRH neuronal system, CHH causative genes can be divided into neurodevelopmental and neuroendocrine genes. The CHH genetic complexity, combined with multiple inheritance patterns, results in an extreme phenotypic variability of CHH patients. In this review, we aim at providing a comprehensive and updated description of the genes thus far associated with CHH, by dissecting their biological relevance in the GnRH system and their functional relevance underlying CHH pathogenesis.
The Relationship between Perceived Health Message Motivation and Social Cognitive Beliefs in Persuasive Health Communication
Authors: Oyibo Kiemute
Published: August 2021

People respond to different types of health messages in persuasive health communication aimed at motivating behavior change. Hence, in human factors design, there is a need to tailor health applications to different user groups rather than change the human characteristics and conditions. However, in the domain of fitness app design, there is limited research on the relationship between users’ perceived motivation of health messages and their social–cognitive beliefs about exercise, and how this relationship is moderated by gender. Knowledge of the gender difference will help in tailoring fitness apps to the two main gender types. Hence, I conducted an empirical study to investigate the types of health messages that are most likely to motivate users and how these messages are related to outcome expectation, self-efficacy, and self-regulation beliefs in the context of exercise modeling. The results of the data analysis show that users are more motivated by illness- and death-related messages compared with obesity-, social stigma-, and financial cost-related messages. Moreover, illness- and death-related messages have a significant relationship with users’ social–cognitive beliefs about bodyweight exercise. These findings indicate that, in the fitness domain, illness- and death-related messages may be employed as a persuasive technique to motivate regular exercise.
2-Aminopyrimidinium Decavanadate: Experimental and Theoretical Characterization, Molecular Docking, and Potential Antineoplastic Activity
Authors: García-García Amalia , Noriega Lisset , Meléndez-Bustamante Francisco J. , Castro María Eugenia , Sánchez-Gaytán Brenda L. , Choquesillo-Lazarte Duane , González-Vergara Enrique , Rodríguez-Diéguez Antonio
Published: August 2021

The interest in decavanadate anions has increased in recent decades, since these clusters show interesting applications as varied as sensors, batteries, catalysts, or new drugs in medicine. Due to the capacity of the interaction of decavanadate with a variety of biological molecules because of its high negative charge and oxygen-rich surface, this cluster is being widely studied both in vitro and in vivo as a treatment for several global health problems such as diabetes mellitus, cancer, and Alzheimer’s disease. Here, we report a new decavanadate compound with organic molecules synthesized in an aqueous solution and structurally characterized by elemental analysis, infrared spectroscopy, thermogravimetric analysis, and single-crystal X-ray diffraction. The decavanadate anion was combined with 2-aminopyrimidine to form the compound [2-ampymH]6[V10O28]·5H2O (1). In the crystal lattice, organic molecules are stacked by π–π interactions, with a centroid-to-centroid distance similar to that shown in DNA or RNA molecules. Furthermore, computational DFT calculations of Compound 1 corroborate the hydrogen bond interaction between pyrimidine molecules and decavanadate anions, as well as the π–π stacking interactions between the central pyrimidine molecules. Finally, docking studies with test RNA molecules indicate that they could serve as other potential targets for the anticancer activity of decavanadate anion.