bluuebunny/crossref_metadata_2025 huggingface dataset:
Putting Policy into Practice: How Three Cancer Services Perform against Indigenous Health and Cancer Frameworks
Authors: Taylor Emma V. , Lyford Marilyn , Parsons Lorraine , Holloway Michele , Gough Karla , Sabesan Sabe , Thompson Sandra C.
Published: January 2022

Improving cancer outcomes for Indigenous people by providing culturally safe, patient-centred care is a critical challenge for health services worldwide. This article explores how three Australian cancer services perform when compared to two national best practice guidelines: the National Aboriginal and Torres Strait Islander Cancer Framework (Cancer Framework) and the National Safety and Quality Health Service (NSQHS) User Guide for Aboriginal and Torres Strait Islander Health (User Guide). The services were identified through a nationwide project undertaken to identify cancer services providing treatment to Indigenous cancer patients. A small number of services which were identified as particularly focused on providing culturally safe cancer care participated in case studies. Interviews were conducted with 35 hospital staff (Indigenous and non-Indigenous) and 8 Indigenous people affected by cancer from the three services. The interviews were analysed and scored using a traffic light system according to the seven priorities of the Cancer Framework and the six actions of the NSQHS User Guide. While two services performed well against the User Guide, all three struggled with the upstream elements of the Cancer Framework, suggesting that the treatment-focused Optimal Care Pathway for Aboriginal and Torres Strait Islander People with Cancer (Cancer Pathway) may be a more appropriate framework for tertiary services. This article highlights the importance of a whole-of-organisation approach when addressing and embedding the six actions of the User Guide. Health services which have successfully implemented the User Guide are in a stronger position to implement the Cancer Framework and Cancer Pathway.
An Overview of the Obese-Asthma Phenotype in Children
Authors: Fainardi Valentina , Passadore Lucrezia , Labate Marialuisa , Pisi Giovanna , Esposito Susanna
Published: January 2022

Asthma is the most common chronic disease in childhood. Overweight and obesity are included among the comorbidities considered in patients with difficult-to-treat asthma, suggesting a specific phenotype of the disease. Therefore, the constant increase in obesity prevalence in children and adolescents raises concerns about the parallel increase of obesity-associated asthma. The possible correlation between obesity and asthma has been investigated over the last decade by different authors, who suggest a complex multifactorial relationship. Although the particular non-eosinophilic endotype of obesity-related asthma supports the concept that high body weight precedes asthma development, there is ongoing debate about the direct causality of these two entities. A number of mechanisms may be involved in asthma in combination with obesity disease in children, including reduced physical activity, abnormal ventilation, chronic systemic inflammation, hormonal influences, genetics and additional comorbidities, such as gastroesophageal reflux and dysfunctional breathing. The identification of the obesity-related asthma phenotype is crucial to initiate specific therapeutic management. Besides the cornerstones of asthma treatment, lifestyle should be optimized, with interventions aiming to promote physical exercise, healthy diet, and comorbidities. Future studies should clarify the exact association between asthma and obesity and the mechanisms underlying the pathogenesis of these two related conditions with the aim to define personalized therapeutic strategies for asthma management in this population.
N-Acetylcysteine Alleviated the Deltamethrin-Induced Oxidative Cascade and Apoptosis in Liver and Kidney Tissues
Authors: Allam Ali , Abdeen Ahmed , Devkota Hari Prasad , Ibrahim Samar S. , Youssef Gehan , Soliman Ahmed , Abdel-Daim Mohamed M. , Alzahrani Khalid J. , Shoghy Khaled , Ibrahim Samah F. , Aboubakr Mohamed
Published: January 2022

Deltamethrin (DLM) is a synthetic pyrethroid with anti-acaricide and insecticidal properties. It is commonly used in agriculture and veterinary medicine. Humans and animals are exposed to DLM through the ingestion of polluted food and water, resulting in severe health issues. N-acetylcysteine (NAC) is a prodrug of L-cysteine, the precursor to glutathione. It can restore the oxidant-antioxidant balance. Therefore, this research aimed to examine whether NAC may protect broiler chickens against oxidative stress, at the level of biochemical and molecular alterations caused by DLM intoxication. The indicators of liver and kidney injury in the serum of DLM-intoxicated and NAC-treated groups were examined. Furthermore, lipid peroxidation, antioxidant markers, superoxide dismutase activity, and apoptotic gene expressions (caspase-3 and Bcl-2) were investigated. All parameters were significantly altered in the DLM-intoxicated group, suggesting that DLM could induce oxidative damage and apoptosis in hepato-renal tissue. The majority of the changes in the studied parameters were reversed when NAC therapy was used. In conclusion, by virtue of its antioxidant and antiapoptotic properties, NAC enabled the provision of significant protection effects against DLM-induced hepato-renal injury.
Envy and Environmental Decision Making: The Mediating Role of Self-Control
Authors: Wei Xinni , Yu Feng
Published: January 2022

Emotions have strong impacts on decision making, yet research on the association between social interpersonal emotion and environmental decisions is limited. The present study uses experimental manipulation and cross-sectional investigation to examine how envy state and personality trait envy influence environmental actions. In Study 1, participants were manipulated to elicit benign and malicious envy, and it was found that benign envy acts as an antecedent of pro-environmental behavior, while malicious envy could contribute to behavior harmful to the environment. Study 2 replicated the results of Study 1 and examined the mediator of self-control through a correlational study. Consequently, people who are high in malicious envy tend to engage in more environmentally harmful activities rather than living a sustainable life, while dispositional benign envy could significantly predict pro-environmental behavior. Moreover, the link between dispositional malicious envy and environmental behavior can be explained by trait self-control, while the mediating effect was silent in dispositional benign envy. The findings shed new light on the impact of social interpersonal emotion on making environmental decisions and its related psychological mechanisms.
Coronary Heart Disease in Type 2 Diabetes Mellitus: Genetic Factors and Their Mechanisms, Gene-Gene, and Gene-Environment Interactions in the Asian Populations
Authors: Zarkasi Khairul Anwar , Abdul Murad Nor Azian , Ahmad Norfazilah , Jamal Rahman , Abdullah Noraidatulakma
Published: January 2022

Asians are more susceptible to type 2 diabetes mellitus (T2D) and its coronary heart disease (CHD) complications than the Western populations, possibly due to genetic factors, higher degrees of obesity, insulin resistance, and endothelial dysfunction that could occur even in healthy individuals. The genetic factors and their mechanisms, along with gene-gene and gene-environment interactions associated with CHD in T2D Asians, are yet to be explored. Therefore, the objectives of this paper were to review the current evidence of genetic factors for CHD, summarize the proposed mechanisms of these genes and how they may associate with CHD risk, and review the gene-gene and gene-environment interactions in T2D Asians with CHD. The genetic factors can be grouped according to their involvement in the energy and lipoprotein metabolism, vascular and endothelial pathology, antioxidation, cell cycle regulation, DNA damage repair, hormonal regulation of glucose metabolism, as well as cytoskeletal function and intracellular transport. Meanwhile, interactions between single nucleotide polymorphisms (SNPs) from different genes, SNPs within a single gene, and genetic interaction with environmental factors including obesity, smoking habit, and hyperlipidemia could modify the gene’s effect on the disease risk. Collectively, these factors illustrate the complexities of CHD in T2D, specifically among Asians.
A Predictive Model of Pandemic Disaster Fear Caused by Coronavirus (COVID-19): Implications for Decision-Makers
Authors: Cvetković Vladimir M. , Nikolić Neda , Ocal Adem , Martinović Jovana , Dragašević Aleksandar
Published: January 2022

This paper presents quantitative research results regarding a predictive model of pandemic disaster fear caused by the coronavirus disease (COVİD-19). The aim of this paper was to establish the level and impact of certain demographic and socioeconomic characteristics on pandemic disaster fear caused by the coronavirus (COVID-19). The research was conducted using a questionnaire that was provided and then collected online for 1226 respondents during May 2021. A closed, five-point Likert scale was used to create the structured questionnaire. The first section of the questionnaire included research questions about the participants’ socioeconomic and demographic characteristics, while the second section included issue questions about fear caused by COVID-19. The results of multivariate regression analyses showed the most important predictor for fear of COVID-19 to be gender, followed by age and education level. Furthermore, the results of t-tests showed statistically significant differences between men and women in terms of different aspects of pandemic disaster fear caused by the coronavirus disease. Our results have several significant public health implications. Women who were more educated and knowledgeable, married, and older, reported a greater fear of the outbreak at various levels. Decision-makers can use these findings to identify better strategic opportunities for pandemic disaster risk management.
Physical Exercise in People with Chronic Kidney Disease—Practices and Perception of the Knowledge of Health Professionals and Physical Activity and Sport Science Professionals about Their Prescription
Authors: Martínez-Majolero Víctor , Urosa Belén , Hernández-Sánchez Sonsoles
Published: January 2022

There is evidence on the need to include physical exercise as a treatment for diseases. A large number of professionals are involved in this, but it is not known how physical exercise is prescribed and which professionals are involved. This research has two objectives: (a) to find out the current practices in Spain regarding the prescription of physical exercise in patients with Chronic Kidney Disease (CKD) and (b) to analyse the perception that different health and physical activity professionals have of their knowledge to prescribe of physical exercise in the treatment of CKD. This is an empirical research with an ex post facto retrospective analysis of the information in a descriptive and correlational way. A total of 692 health and sports professionals participated. A questionnaire validated by a committee of experts was administered. Descriptive analyses were carried out and the differences in the study variables were analysed using Chi-square tests and one-factor Analysis of Variance. From the results obtained, we conclude there is a need to develop specific training programmes in the field of physical exercise for health professionals, as well as the establishment of multiprofessional teams for the prescription of physical exercise in CKD treatment, including physical exercise professionals (Cafyde).
Understanding Determinants of Pregnant Women’s Knowledge of Lifestyle-Related Risk Factors: A Cross-Sectional Study
Authors: Nawabi Farah , Krebs Franziska , Lorenz Laura , Shukri Arim , Alayli Adrienne , Stock Stephanie
Published: January 2022

Research indicates that a woman’s lifestyle during pregnancy influences her child’s health and development. Therefore, women need to possess sufficient knowledge regarding the elements of a healthy lifestyle during pregnancy. To date, there has been little research on the assessment of lifestyle knowledge of pregnant women in the perinatal healthcare setting. This study describes the development and application of a knowledge-based questionnaire for pregnancy to be used in a lifestyle intervention trial conducted in Germany. Within the trial, pregnant women receive counselling on lifestyle topics. These topics are based on the German initiative ‘Healthy Start—Young Family Network’ (GiL), which provides evidence-based recommendations regarding diet and lifestyle before and during pregnancy. These serve as a basis for health professionals who provide counselling on healthy lifestyle choices during the antenatal period. The questionnaire consists of eight items, each of which can be answered using ‘Yes’, ‘No’ or ‘Don’t know’. The pregnant women who completed the questionnaire at baseline around the twelfth week of gestation were recruited within the host trial from gynaecological practices in Germany. Demographic variables and the respondents’ answers to the questionnaire were analysed using descriptive statistics and regression analyses. Descriptive statistics show that more than 85% of participants answered the majority of questions (n = 5) correctly. Questions on whether tap water is safe and the normal range for gestational weight gain (GWG) were answered correctly by about 62% and 74% of the women, respectively, and the question on whether it is beneficial to obtain information on breastfeeding at an early stage was answered correctly by about 29%. The results of the regression analyses indicate that age, gestational week, education and income are positive predictors for answering the questionnaire correctly. Nullipara and migration background are predictors for answering the questions incorrectly. This study indicates that there are gaps in women’s knowledge regarding lifestyle during pregnancy. Particular focus on certain topics, such as breastfeeding and normal GWG ranges, is still required during counselling. Our analysis shows that migration background is a predictor of insufficient knowledge and incorrect answers to the questions. Women with such backgrounds require special attention during antenatal counselling in order to cater to their needs and the gaps in their knowledge.
Improving the Thermostability of a Fungal GH11 Xylanase via Fusion of a Submodule (C2) from Hyperthermophilic CBM9_1-2
Authors: Miao Huabiao , Ma Yu , Zhe Yuanyuan , Tang Xianghua , Wu Qian , Huang Zunxi , Han Nanyu
Published: January 2022

Xylanases have been applied in many industrial fields. To improve the activity and thermostability of the xylanase CDBFV from Neocallimastix patriciarum (GenBank accession no. KP691331), submodule C2 from hyperthermophilic CBM9_1-2 was inserted into the N- and/or C-terminal regions of the CDBFV protein (producing C2-CDBFV, CDBFV-C2, and C2-CDBFV-C2) by genetic engineering. CDBFV and the hybrid proteins were successfully expressed in Escherichia coli BL21 (DE3). Enzymatic property analysis indicates that the C2 submodule had a significant effect on enhancing the thermostability of the CDBFV. At the optimal temperature (60.0 °C), the half-lives of the three chimeras C2-CDBFV, CDBFV-C2, and C2-CDBFV-C2 are 1.5 times (37.5 min), 4.9 times (122.2 min), and 3.8 times (93.1 min) longer than that of wild-type CDBFV (24.8 min), respectively. More importantly, structural analysis and molecular dynamics (MD) simulation revealed that the improved thermal stability of the chimera CDBFV-C2 was on account of the formation of four relatively stable additional hydrogen bonds (S42-S462, T59-E277, S41-K463, and S44-G371), which increased the protein structure’s stability. The thermostability characteristics of CDBFV-C2 make it a viable enzyme for industrial applications.
Deficiency in the Treatment Description of mTOR Inhibitor Resistance in Medulloblastoma, a Systematic Review
Authors: Alammar Hajar , Nassani Rayan , Alshehri Mana M. , Aljohani Alaa A. , Alrfaei Bahauddeen M.
Published: January 2022

Medulloblastoma is a common fatal pediatric brain tumor. More treatment options are required to prolong survival and decrease disability. mTOR proteins play an essential role in the disease pathogenesis, and are an essential target for therapy. Three generations of mTOR inhibitors have been developed and are clinically used for immunosuppression and chemotherapy for multiple cancers. Only a few mTOR inhibitors have been investigated for the treatment of medulloblastoma and other pediatric tumors. The first-generation mTOR, sirolimus, temsirolimus, and everolimus, went through phase I clinical trials. The second-generation mTOR, AZD8055 and sapanisertib, suppressed medulloblastoma cell growth; however, limited studies have investigated possible resistance pathways. No clinical trials have been found to treat medulloblastoma using third-generation mTOR inhibitors. This systematic review highlights the mechanisms of resistance of mTOR inhibitors in medulloblastoma and includes IDO1, T cells, Mnk2, and eIF4E, as they prolong malignant cell survival. The findings promote the importance of combination therapy in medulloblastoma due to its highly resistant nature.
Generation of Lasso Peptide-Based ClpP Binders
Authors: Malik Imran T. , Hegemann Julian D. , Brötz-Oesterhelt Heike
Published: January 2022

The Clp protease system fulfills a plethora of important functions in bacteria. It consists of a tetradecameric ClpP barrel holding the proteolytic centers and two hexameric Clp-ATPase rings, which recognize, unfold, and then feed substrate proteins into the ClpP barrel for proteolytic degradation. Flexible loops carrying conserved tripeptide motifs protrude from the Clp-ATPases and bind into hydrophobic pockets (H-pockets) on ClpP. Here, we set out to engineer microcin J25 (MccJ25), a ribosomally synthesized and post-translationally modified peptide (RiPP) of the lasso peptide subfamily, by introducing the conserved tripeptide motifs into the lasso peptide loop region to mimic the Clp-ATPase loops. We studied the capacity of the resulting lasso peptide variants to bind to ClpP and affect its activity. From the nine variants generated, one in particular (12IGF) was able to activate ClpP from Staphylococcus aureus and Bacillus subtilis. While 12IGF conferred stability to ClpP tetradecamers and stimulated peptide degradation, it did not trigger unregulated protein degradation, in contrast to the H-pocket-binding acyldepsipeptide antibiotics (ADEPs). Interestingly, synergistic interactions between 12IGF and ADEP were observed.
Effects of Various Muscle Disuse States and Countermeasures on Muscle Molecular Signaling
Authors: Sharlo Kristina , Tyganov Sergey A. , Tomilovskaya Elena , Popov Daniil V. , Saveko Alina A. , Shenkman Boris S.
Published: January 2022

Skeletal muscle is capable of changing its structural parameters, metabolic rate and functional characteristics within a wide range when adapting to various loading regimens and states of the organism. Prolonged muscle inactivation leads to serious negative consequences that affect the quality of life and work capacity of people. This review examines various conditions that lead to decreased levels of muscle loading and activity and describes the key molecular mechanisms of muscle responses to these conditions. It also details the theoretical foundations of various methods preventing adverse muscle changes caused by decreased motor activity and describes these methods. A number of recent studies presented in this review make it possible to determine the molecular basis of the countermeasure methods used in rehabilitation and space medicine for many years, as well as to identify promising new approaches to rehabilitation and to form a holistic understanding of the mechanisms of gravity force control over the muscular system.
The Role of Molecular Imaging as a Marker of Remyelination and Repair in Multiple Sclerosis
Authors: Ben-Shalom Ido , Karni Arnon , Kolb Hadar
Published: January 2022

The appearance of new disease-modifying therapies in multiple sclerosis (MS) has revolutionized our ability to fight inflammatory relapses and has immensely improved patients’ quality of life. Although remarkable, this achievement has not carried over into reducing long-term disability. In MS, clinical disability progression can continue relentlessly irrespective of acute inflammation. This “silent” disease progression is the main contributor to long-term clinical disability in MS and results from chronic inflammation, neurodegeneration, and repair failure. Investigating silent disease progression and its underlying mechanisms is a challenge. Standard MRI excels in depicting acute inflammation but lacks the pathophysiological lens required for a more targeted exploration of molecular-based processes. Novel modalities that utilize nuclear magnetic resonance’s ability to display in vivo information on imaging look to bridge this gap. Displaying the CNS through a molecular prism is becoming an undeniable reality. This review will focus on “molecular imaging biomarkers” of disease progression, modalities that can harmoniously depict anatomy and pathophysiology, making them attractive candidates to become the first valid biomarkers of neuroprotection and remyelination.
Niclosamide Suppresses Migration and Invasion of Human Osteosarcoma Cells by Repressing TGFBI Expression via the ERK Signaling Pathway
Authors: Yeh Liang-Tsai , Lin Chiao-Wen , Lu Ko-Hsiu , Hsieh Yi-Hsien , Yeh Chao-Bin , Yang Shun-Fa , Yang Jia-Sin
Published: January 2022

Osteosarcoma is a highly common malignant bone tumor. Its highly metastatic properties are the leading cause of mortality for cancer. Niclosamide, a salicylanilide derivative, is an oral antihelminthic drug of known anticancer potential. However, the effect of niclosamide on osteosarcoma cell migration, invasion and the mechanisms underlying have not been fully clarified. Therefore, this study investigated niclosamide’s underlying pathways and antimetastatic effects on osteosarcoma. In this study, U2OS and HOS osteosarcoma cell lines were treated with niclosamide and then subjected to assays for determining cell migration ability. The results indicated that niclosamide, at concentrations of up to 200 nM, inhibited the migration and invasion of human osteosarcoma U2OS and HOS cells and repressed the transforming growth factor beta-induced protein (TGFBI) expression of U2OS cells, without cytotoxicity. After TGFBI knockdown occurred, cellular migration and invasion behaviors of U2OS cells were significantly reduced. Moreover, niclosamide significantly decreased the phosphorylation of ERK1/2 in U2OS cells and the combination treatment of the MEK inhibitor (U0126) and niclosamide resulted in the intensive inhibition of the TGFBI expression and the migratory ability in U2OS cells. Therefore, TGFBI derived from osteosarcoma cells via the ERK pathway contributed to cellular migration and invasion and niclosamide inhibited these processes. These findings indicate that niclosamide may be a powerful preventive agent against the development and metastasis of osteosarcoma.
How Cold Shock Affects Ploidy Level and Early Ontogenetic Development of the Sterlet, A. ruthenus L.
Authors: Fopp-Bayat Dorota , Chandra Gyan , Nitkiewicz Anna
Published: January 2022

The objective of the present research was to study the effect of cold shock (3 °C and 6 °C) on fertilized eggs of the sterlet, Acipenser ruthenus L. Cold shock was applied for various durations (30, 60 and 90 min) and the ploidy levels, survival, and genotypes of the treated embryos/larvae were recorded. Analysis of ploidy levels confirmed the presence of diploid, triploid, and mosaic (1n/2n, 2n/3n, and 1n/2n/3n) genotypes in experimental groups, while it was strictly diploid in control groups. Microsatellite genotyping confirmed both the incidence of polyspermy and retention of the 2nd polar body in experimental groups. However, patterns of inheritance in all diploid offspring in experimental and control groups revealed classical Mendelian disomic inheritance. Interestingly, the observed mosaic sterlets had normal morphology and were alive. However, some larvae had abnormal morphology which may be due to haploid syndrome. In all treatment groups (treatments: 3 °C–30 min; 3 °C–60 min; 3 °C–90 min; 6 °C–60 min), where the percentage of polyploid/mosaic larvae were high, the mortality was also high. Whereas, in the control groups (where there were only diploid (2n) larvae), the mortality was relatively low.
The Two β-Arrestins Regulate Distinct Metabolic Processes: Studies with Novel Mutant Mouse Models
Authors: Wess Jürgen
Published: January 2022

The two β-arrestins (β-arrestin-1 and -2; alternative names: arrestin-2 and -3, respectively) are well known for their ability to inhibit signaling via G protein-coupled receptors. However, β-arrestins can also act as signaling molecules in their own right. Although the two proteins share a high degree of sequence and structural homology, early studies with cultured cells indicated that β-arrestin-1 and -2 are not functionally redundant. Recently, the in vivo metabolic roles of the two β-arrestins have been studied using mutant mice selectively lacking either β-arrestin-1 or -2 in cell types that are of particular relevance for regulating glucose and energy homeostasis. These studies demonstrated that the β-arrestin-1 and -2 mutant mice displayed distinct metabolic phenotypes in vivo, providing further evidence for the functional heterogeneity of these two highly versatile signaling proteins.
Graphene for Antimicrobial and Coating Application
Authors: Srimaneepong Viritpon , Skallevold Hans Erling , Khurshid Zohaib , Zafar Muhammad Sohail , Rokaya Dinesh , Sapkota Janak
Published: January 2022

Graphene is a versatile compound with several outstanding properties, providing a combination of impressive surface area, high strength, thermal and electrical properties, with a wide array of functionalization possibilities. This review aims to present an introduction of graphene and presents a comprehensive up-to-date review of graphene as an antimicrobial and coating application in medicine and dentistry. Available articles on graphene for biomedical applications were reviewed from January 1957 to August 2020) using MEDLINE/PubMed, Web of Science, and ScienceDirect. The selected articles were included in this study. Extensive research on graphene in several fields exists. However, the available literature on graphene-based coatings in dentistry and medical implant technology is limited. Graphene exhibits high biocompatibility, corrosion prevention, antimicrobial properties to prevent the colonization of bacteria. Graphene coatings enhance adhesion of cells, osteogenic differentiation, and promote antibacterial activity to parts of titanium unaffected by the thermal treatment. Furthermore, the graphene layer can improve the surface properties of implants which can be used for biomedical applications. Hence, graphene and its derivatives may hold the key for the next revolution in dental and medical technology.
Hepatocellular Carcinoma in Chronic Viral Hepatitis: Where Do We Stand?
Authors: Russo Francesco Paolo , Zanetto Alberto , Pinto Elisa , Battistella Sara , Penzo Barbara , Burra Patrizia , Farinati Fabio
Published: January 2022

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death. Although the burden of alcohol- and NASH-related HCC is growing, chronic viral hepatitis (HBV and HCV) remains a major cause of HCC development worldwide. The pathophysiology of viral-related HCC includes liver inflammation, oxidative stress, and deregulation of cell signaling pathways. HBV is particularly oncogenic because, contrary to HCV, integrates in the cell DNA and persists despite virological suppression by nucleotide analogues. Surveillance by six-month ultrasound is recommended in patients with cirrhosis and in “high-risk” patients with chronic HBV infection. Antiviral therapy reduces the risks of development and recurrence of HCC; however, patients with advanced chronic liver disease remain at risk of HCC despite virological suppression/cure and should therefore continue surveillance. Multiple scores have been developed in patients with chronic hepatitis B to predict the risk of HCC development and may be used to stratify individual patient’s risk. In patients with HCV-related liver disease who achieve sustained virological response by direct acting antivirals, there is a strong need for markers/scores to predict long-term risk of HCC. In this review, we discuss the most recent advances regarding viral-related HCC.
Protective Effect of Gamma Aminobutyric Acid against Aggravation of Renal Injury Caused by High Salt Intake in Cisplatin-Induced Nephrotoxicity
Authors: Lee Hyesook , Ji Seon Yeong , Hwangbo Hyun , Kim Min Yeong , Kim Da Hye , Park Beom Su , Park Joung-Hyun , Lee Bae-Jin , Kim Gi-Young , Jeon You-Jin , Choi Yung Hyun
Published: January 2022

Gamma-aminobutyric acid (GABA) is one of the inhibitory neurotransmitters. Several studies have suggested that GABA supplements can reduce blood pressure and modulate the renal immune system in vitro and in vivo. In the present study, we investigated the effect of GABA-enriched salt as an alternative to traditional salt on aggravated renal injury by high salt intake in cisplatin-induced nephrotoxicity mice. High salt intake accelerated the increase of biomarkers, such as blood urea nitrogen and serum creatinine levels for renal injury in cisplatin-induced nephrotoxicity mice. However, oral administration of GABA-contained salt notably suppressed serum BUN and creatinine levels. The efficacy of GABA salt was superior to lacto GABA salt and postbiotics GABA salt. Furthermore, GABA-enriched salt markedly restored histological symptoms of nephrotoxicity including renal hypertrophy, tubular dilation, hemorrhage, and collagen deposition aggravated by salt over-loading in cisplatin-exposed mice. Among them, GABA salt showed a higher protective effect against cisplatin-induced renal histological changes than lacto GABA salt and postbiotics GABA salt. In addition, administration of high salt significantly enhanced expression levels of apoptosis and inflammatory mediators in cisplatin-induced nephrotoxicity mice, while GABA-enriched salt greatly down-regulated the expression of these mediators. Taken together, these results demonstrate the protective effect of GABA against damage caused by high salt intake in cisplatin-induced renal toxicity. Its mechanism may be due to the suppression of hematological and biochemical toxicity, apoptosis, and inflammation. In conclusion, although the protective efficacy of GABA salt on renal injury is different depending on the sterilization and filtration process after fermentation with L. brevis BJ20 and L. plantarum BJ21, our findings suggest that GABA-enriched salt has a beneficial effect against immoderate high salt intake-mediated kidney injury in patients with cisplatin-induced nephrotoxicity.
Pseudomonas syringae pv. actinidiae Effector HopAU1 Interacts with Calcium-Sensing Receptor to Activate Plant Immunity
Authors: Zhang Jinlong , Zhou Mingxia , Liu Wei , Nie Jiajun , Huang Lili
Published: January 2022

Kiwifruit canker, caused by Pseudomonas syringae pv. actinidiae (Psa), is a destructive pathogen that globally threatens the kiwifruit industry. Understanding the molecular mechanism of plant-pathogen interaction can accelerate applying resistance breeding and controlling plant diseases. All known effectors secreted by pathogens play an important role in plant-pathogen interaction. However, the effectors in Psa and their function mechanism remain largely unclear. Here, we successfully identified a T3SS effector HopAU1 which had no virulence contribution to Psa, but could, however, induce cell death and activate a series of immune responses by agroinfiltration in Nicotiana benthamiana, including elevated transcripts of immune-related genes, accumulation of reactive oxygen species (ROS), and callose deposition. We found that HopAU1 interacted with a calcium sensing receptor in N. benthamiana (NbCaS) as well as its close homologue in kiwifruit (AcCaS). More importantly, silencing CaS by RNAi in N. benthamiana greatly attenuated HopAU1-triggered cell death, suggesting CaS is a crucial component for HopAU1 detection. Further researches showed that overexpression of NbCaS in N. benthamiana significantly enhanced plant resistance against Sclerotinia sclerotiorum and Phytophthora capsici, indicating that CaS serves as a promising resistance-related gene for disease resistance breeding. We concluded that HopAU1 is an immune elicitor that targets CaS to trigger plant immunity.
Genome-Wide Characterization and Expression Analysis of KH Family Genes Response to ABA and SA in Arabidopsis thaliana
Authors: Zhang Yanjie , Ma Yu , Liu Ruiqi , Li Guanglin
Published: January 2022

K-homologous (KH) family is a type of nucleic acid-binding protein containing the KH domain and has been found to affect splicing and transcriptional regulation. However, KH family genes haven’t been investigated in plant species systematically. In this study, we identified 30 genes that belonged to the KH family based on HMM of the KH domain in Arabidopsis thaliana. Phylogenetic tree analysis showed that the KH family is grouped into three subgroups. Synteny analysis showed that AtKH9 and AtKH29 have the conserved synteny relationship between A. thaliana and the other five species. The AtKH9 and AtKH29 were located in the cytoplasm and nucleus. The seed germination rates of the mutants atkh9 and atkh29 were higher than wild-type after abscisic acid (ABA) and salicylic acid (SA) treatments. In addition, the expression of ABA-related genes, such as ABRE-binding factor 2 (ABF2), ABRE-binding factor 4 (ABF4), and delta 1-pyrroline-5-carboxylate synthase (P5CS), and an SA-related gene pathogenesis-related proteins b (PR1b) were downregulated after ABA and SA treatments, respectively. These results suggested that atkh9 and atkh29 mutants inhibit the effect of ABA and SA on seed germination. In conclusion, our results provide valuable information for further exploration of the function of KH family genes and propose directions and ideas for the identification and characterization of KH family genes in other plants.
Exposure of Toluene Diisocyanate Induces DUSP6 and p53 through Activation of TRPA1 Receptor
Authors: Kim Soee , Kim Min , Sung Jung-Suk
Published: January 2022

Toluene diisocyanate (TDI), a major intermediate agent used in the manufacturing industry, causes respiratory symptoms when exposed to the human body. In this study, we aimed to determine the molecular mechanism of TDI toxicity. To investigate the impact of TDI exposure on global gene expression, we performed transcriptomic analysis of human bronchial epithelial cells (BEAS-2B) after TDI treatment. Differentially expressed genes (DEGs) were sorted and used for clustering and network analysis. Among DEGs, dual-specificity phosphatase 6 (DUSP6) was one of the genes significantly changed by TDI exposure. To verify the expression level of DUSP6 and its effect on lung cells, the mRNA and protein levels of DUSP6 were analyzed. Our results showed that DUSP6 was dose-dependently upregulated by TDI treatment. Thereby, the phosphorylation of ERK1/2, one of the direct inhibitory targets of DUSP6, was decreased. TDI exposure also increased the mRNA level of p53 along with its protein and activity which trans-activates DUSP6. Since TRPA1 is known as a signal integrator activated by TDI, we analyzed the relevance of TRPA1 receptor in DUSP6 regulation. Our data revealed that up-regulation of DUSP6 mediated by TDI was blocked by a specific antagonist against TRPA1. TDI exposure attenuated the apoptotic response, which suggests that it promotes the survival of cancerous cells. In conclusion, our results suggest that TDI induces DUSP6 and p53, but attenuates ERK1/2 activity through TRPA1 receptor activation, leading to cytotoxicity.
Flubendazole Plays an Important Anti-Tumor Role in Different Types of Cancers
Authors: Chen Chaoran , Ding Yueming , Liu Huiyang , Sun Mengyao , Wang Honggang , Wu Dongdong
Published: January 2022

Flubendazole, belonging to benzimidazole, is a broad-spectrum insect repellent and has been repurposed as a promising anticancer drug. In recent years, many studies have shown that flubendazole plays an anti-tumor role in different types of cancers, including breast cancer, melanoma, prostate cancer, colorectal cancer, and lung cancer. Although the anti-tumor mechanism of flubendazole has been studied, it has not been fully understood. In this review, we summarized the recent studies regarding the anti-tumor effects of flubendazole in different types of cancers and analyzed the related mechanisms, in order to provide the theoretical reference for further studies in the future.
Is Protein Folding a Thermodynamically Unfavorable, Active, Energy-Dependent Process?
Authors: Sorokina Irina , Mushegian Arcady R. , Koonin Eugene V.
Published: January 2022

The prevailing current view of protein folding is the thermodynamic hypothesis, under which the native folded conformation of a protein corresponds to the global minimum of Gibbs free energy G. We question this concept and show that the empirical evidence behind the thermodynamic hypothesis of folding is far from strong. Furthermore, physical theory-based approaches to the prediction of protein folds and their folding pathways so far have invariably failed except for some very small proteins, despite decades of intensive theory development and the enormous increase of computer power. The recent spectacular successes in protein structure prediction owe to evolutionary modeling of amino acid sequence substitutions enhanced by deep learning methods, but even these breakthroughs provide no information on the protein folding mechanisms and pathways. We discuss an alternative view of protein folding, under which the native state of most proteins does not occupy the global free energy minimum, but rather, a local minimum on a fluctuating free energy landscape. We further argue that ΔG of folding is likely to be positive for the majority of proteins, which therefore fold into their native conformations only through interactions with the energy-dependent molecular machinery of living cells, in particular, the translation system and chaperones. Accordingly, protein folding should be modeled as it occurs in vivo, that is, as a non-equilibrium, active, energy-dependent process.
Nuclear Envelope Alterations in Myotonic Dystrophy Type 1 Patient-Derived Fibroblasts
Authors: Viegas Diana , Pereira Cátia D. , Martins Filipa , Mateus Tiago , da Cruz e Silva Odete A. B. , Herdeiro Maria Teresa , Rebelo Sandra
Published: January 2022

Myotonic dystrophy type 1 (DM1) is a hereditary and multisystemic disease characterized by myotonia, progressive distal muscle weakness and atrophy. The molecular mechanisms underlying this disease are still poorly characterized, although there are some hypotheses that envisage to explain the multisystemic features observed in DM1. An emergent hypothesis is that nuclear envelope (NE) dysfunction may contribute to muscular dystrophies, particularly to DM1. Therefore, the main objective of the present study was to evaluate the nuclear profile of DM1 patient-derived and control fibroblasts and to determine the protein levels and subcellular distribution of relevant NE proteins in these cell lines. Our results demonstrated that DM1 patient-derived fibroblasts exhibited altered intracellular protein levels of lamin A/C, LAP1, SUN1, nesprin-1 and nesprin-2 when compared with the control fibroblasts. In addition, the results showed an altered location of these NE proteins accompanied by the presence of nuclear deformations (blebs, lobes and/or invaginations) and an increased number of nuclear inclusions. Regarding the nuclear profile, DM1 patient-derived fibroblasts had a larger nuclear area and a higher number of deformed nuclei and micronuclei than control-derived fibroblasts. These results reinforce the evidence that NE dysfunction is a highly relevant pathological characteristic observed in DM1.
Missense Mutations in Desmoplakin Plakin Repeat Domains Have Dramatic Effects on Domain Structure and Function
Authors: Mohammed Fiyaz , Odintsova Elena , Chidgey Martyn
Published: January 2022

Plakin repeat domains (PRDs) are globular modules that mediate the interaction of plakin proteins with the intermediate filament (IF) cytoskeleton. These associations are vital for maintaining tissue integrity in cardiac muscle and epithelial tissues. PRDs are subject to mutations that give rise to cardiomyopathies such as arrhythmogenic right ventricular cardiomyopathy, characterised by ventricular arrhythmias and associated with an increased risk of sudden heart failure, and skin blistering diseases. Herein, we have examined the functional and structural effects of 12 disease-linked missense mutations, identified from the human gene mutation database, on the PRDs of the desmosomal protein desmoplakin. Five mutations (G2056R and E2193K in PRD-A, G2338R and G2375R in PRD-B and G2647D in PRD-C) rendered their respective PRD proteins either fully or partially insoluble following expression in bacterial cells. Each of the residues affected are conserved across plakin family members, inferring a crucial role in maintaining the structural integrity of the PRD. In transfected HeLa cells, the mutation G2375R adversely affected the targeting of a desmoplakin C-terminal construct containing all three PRDs to vimentin IFs. The deletion of PRD-B and PRD-C from the construct compromised its targeting to vimentin. Bioinformatic and structural modelling approaches provided multiple mechanisms by which the disease-causing mutations could potentially destabilise PRD structure and compromise cytoskeletal linkages. Overall, our data highlight potential molecular mechanisms underlying pathogenic missense mutations and could pave the way for informing novel curative interventions targeting cardiomyopathies and skin blistering disorders.
Psoriasis-Associated Inflammatory Conditions Induce IL-23 mRNA Expression in Normal Human Epidermal Keratinocytes
Authors: Kelemen Evelyn , Ádám Éva , Sági Stella Márta , Göblös Anikó , Kemény Lajos , Bata-Csörgő Zsuzsanna , Széll Márta , Danis Judit
Published: January 2022

Psoriasis is a multifactorial, chronic inflammatory skin disease, the development of which is affected by both genetic and environmental factors. Cytosolic nucleic acid fragments, recognized as pathogen- and danger-associated molecular patterns, are highly abundant in psoriatic skin. It is known that psoriatic skin exhibits increased levels of IL-23 compared to healthy skin. However, the relationship between free nucleic acid levels and IL-23 expression has not been clarified yet. To examine a molecular mechanism by which nucleic acids potentially modulate IL-23 levels, an in vitro system was developed to investigate the IL-23 mRNA expression of normal human epidermal keratinocytes under psoriasis-like circumstances. This system was established using synthetic nucleic acid analogues (poly(dA:dT) and poly(I:C)). Signaling pathways, receptor involvement and the effect of PRINS, a long non-coding RNA previously identified and characterized by our research group, were analyzed to better understand the regulation of IL-23 in keratinocytes. Our results indicate that free nucleic acids regulate epithelial IL-23 mRNA expression through the TLR3 receptor and specific signaling pathways, thereby, contributing to the development of an inflammatory milieu favorable for the appearance of psoriatic symptoms. A moderate negative correlation was confirmed between the nucleic-acid-induced IL-23 mRNA level and the rate of its decrease upon PRINS overexpression.
Hydroxy Pentacyclic Triterpene Acid, Kaempferol, Inhibits the Human 5-Hydroxytryptamine Type 3A Receptor Activity
Authors: Lee Shinhui , Seol Hee-Soo , Eom Sanung , Lee Jaeeun , Kim Chaelin , Park Jong-Hwan , Kim Tae-Hwan , Lee Junho H.
Published: January 2022

Monoamine serotonin is a major neurotransmitter that acts on a wide range of central nervous system and peripheral nervous system functions and is known to have a role in various processes. Recently, it has been found that 5-HT is involved in cognitive and memory functions through interaction with cholinergic pathways. The natural flavonoid kaempferol (KAE) extracted from Cudrania tricuspidata is a secondary metabolite of the plant. Recently studies have confirmed that KAE possesses a neuroprotective effect because of its strong antioxidant activity. It has been confirmed that KAE is involved in the serotonergic pathway through an in vivo test. However, these results need to be confirmed at the molecular level, because the exact mechanism that is involved in such effects of KAE has not yet been elucidated. Therefore, the objective of this study is to confirm the interaction of KAE with 5-HT3A through electrophysiological studies at the molecular level using KAE extracted from Cudrania tricuspidata. This study confirmed the interaction between 5-HT3A and KAE at the molecular level. KAE inhibited 5-HT3A receptors in a concentration-dependent and voltage-independent manner. Site-directed mutagenesis and molecular-docking studies confirmed that the binding sites D177 and F199 are the major binding sites of human 5-HT3A receptors of KAE.
Epigenetic Mechanisms in Parenchymal Lung Diseases: Bystanders or Therapeutic Targets?
Authors: Avci Edibe , Sarvari Pouya , Savai Rajkumar , Seeger Werner , Pullamsetti Soni S.
Published: January 2022

Epigenetic responses due to environmental changes alter chromatin structure, which in turn modifies the phenotype, gene expression profile, and activity of each cell type that has a role in the pathophysiology of a disease. Pulmonary diseases are one of the major causes of death in the world, including lung cancer, idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH), lung tuberculosis, pulmonary embolism, and asthma. Several lines of evidence indicate that epigenetic modifications may be one of the main factors to explain the increasing incidence and prevalence of lung diseases including IPF and COPD. Interestingly, isolated fibroblasts and smooth muscle cells from patients with pulmonary diseases such as IPF and PH that were cultured ex vivo maintained the disease phenotype. The cells often show a hyper-proliferative, apoptosis-resistant phenotype with increased expression of extracellular matrix (ECM) and activated focal adhesions suggesting the presence of an epigenetically imprinted phenotype. Moreover, many abnormalities observed in molecular processes in IPF patients are shown to be epigenetically regulated, such as innate immunity, cellular senescence, and apoptotic cell death. DNA methylation, histone modification, and microRNA regulation constitute the most common epigenetic modification mechanisms.