bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of Life and Its Associations with Religiosity and Religious Coping among Outpatients with Psychosis in Singapore
Authors: Roystonn Kumarasan , Cetty Laxman , Jeyagurunathan Anitha , Devi Fiona , Abdin Edimansyah , Tan Soo Teng , Tang Charmaine , Verma Swapna , Subramaniam Mythily
Published: July 2021

This cross-sectional study investigated the relationship of religiosity, the use of positive and negative religious coping methods, and quality of life (QOL) among 364 outpatients with psychosis in Singapore. Positive religious coping was significantly associated with better scores on physical (β = 0.51, p = 0.02) and psychological (β = 0.64, p = 0.01) QOL domains in the regression model. Negative religious coping was related to worse QOL in all four domains: physical (β = −0.44, p = 0.03), psychological (β = −0.76, p < 0.01), social (β = −0.54, p = 0.03), and environment (β = −0.65, p < 0.01). Increased participation in organizational religious activities was positively associated with higher QOL for psychological (β = 2.47, p < 0.01), social relationships (β = 2.66, p = 0.01), and environment (β = 2.09, p = 0.01) domains. Interestingly, those with no religious affiliation were found with higher scores in the QOL domain for social relationships (β = 4.59, p = 0.02). Religious coping plays an important role for the QOL of outpatients with psychosis. Greater awareness of the importance of religion in this population may improve cultural competence in treatment. Individuals with psychosis may benefit from greater community support and collaboration between clinical and religious community-based organizations to improve social integration and QOL.
Management of Amelogenesis Imperfecta in Childhood: Two Case Reports
Authors: Möhn Mirja , Bulski Julia Camilla , Krämer Norbert , Rahman Alexander , Schulz-Weidner Nelly
Published: July 2021

Amelogenesis imperfecta (AI) is defined as an interruption of enamel formation due to genetic inheritance. To prevent malfunction of the masticatory system and an unaesthetic appearance, various treatment options are described. While restoration with a compomer in the anterior region and stainless steel crowns in the posterior region is recommended for deciduous dentition, the challenges when treating such structural defects in mixed or permanent dentition are changing teeth and growing jaw, allowing only temporary restoration. The purpose of this case report is to demonstrate oral rehabilitation from mixed to permanent dentition. The dentition of a 7-year-old patient with AI type I and a 12-year-old patient with AI type II was restored under general anesthesia to improve their poor aesthetics and increase vertical dimension, which are related to problems with self-confidence and reduced oral health quality of life. These two cases show the complexity of dental care for structural anomalies of genetic origin and the challenges in rehabilitating the different phases of dentition.
Bullying and Its Associated Individual, Peer, Family and School Factors: Evidence from Malaysian National Secondary School Students
Authors: Sabramani Vikneswaran , Idris Idayu Badilla , Ismail Halim , Nadarajaw Thiyagar , Zakaria Ezarina , Kamaluddin Mohammad Rahim
Published: July 2021

Adolescents involved in bullying can be at risk of developing behavioural problems, physical health problems and suicidal ideation. In view of this, a quantitative research design using a cross-sectional study was conducted to determine the prevalence of bullying and associated individual, peer, family and school factors. The study involved 4469 Malaysian public-school students who made up the response rate of 89.4%. The students were selected using a randomized multilevel sampling method. The study found that 79.1% of student respondents were involved in bullying as perpetrators (14.4%), victims (16.3%), or bully–victims (48.4%). In a multivariate analysis, the individual domain showed a significant association between students’ bullying involvement and age (OR = 1.38; 95% CI 1.12–1.70), gender (OR = 1.73; 95% CI 1.47–0.91), ethnicity (OR = 0.66; 95% CI 0.47–0.91), duration of time spent on social media during the weekends (OR = 1.43; 95% CI 1.09–1.87) and psychological distress level (OR = 2.55; 95% CI 1.94–3.34). In the peer domain, the significantly associated factors were the number of peers (OR = 0.69; 95% CI 0.56–0.86) and frequency of quarrels or fights with peers (OR = 2.12; 95% CI 1.24–3.26). Among the items in the school domain, the significantly associated factors were students being mischievous in classrooms (OR = 1.52; 95% CI 1.06–2.06), student’s affection towards their teachers (OR = 1.53; 95% CI 1.06–2.20), frequency of appraisal from teachers (OR = 1.49; 95% CI 1.16–1.94), frequency of friends being helpful in classrooms (OR = 1.92; 95% CI 1.09–3.38) and frequency of deliberately skipping class (OR = 2.91; 95% CI 2.90–1.72). As a conclusion, the study revealed high levels and widespread bullying involvement among students in Malaysia. As such, timely bullying preventions and interventions are essential, especially in terms of enhancing their mental health capacity, which substantially influences the reduction in the prevalence rates of bullying involvement among students in Malaysia.
Pharmacological Treatment of Patients with Mild to Moderate COVID-19: A Comprehensive Review
Authors: Bestetti Reinaldo B. , Furlan-Daniel Rosemary , Silva Vinicius M. R.
Published: July 2021

Mild to moderate COVID-19 can be found in about 80% of patients. Although mortality is low, mild to moderate COVID-19 may progress to severe or even critical stages in about one week. This poses a substantial burden on the health care system, and ultimately culminates in death or incapacitation and hospitalization. Therefore, pharmacological treatment is paramount for patients with this condition, especially those with recognized risk factors to disease progression. We conducted a comprehensive review in the medical literature searching for randomized studies carried out in patients with mild to moderate COVID-19. A total of 14 randomized studies were identified, enrolling a total of 6848 patients. Nine studies (64%) were randomized, placebo-controlled trials, whereas five were open-label randomized trials (35%). We observed that Bamlanivimab and nitazoxanide reduced viral load, whereas ivermectin may have shortened time to viral clearance; Interferon Beta-1 reduced time to viral clearance and vitamin D reduced viral load; Favirapir, peginterferon, and levamisole improved clinical symptoms, whereas fluvoxamine halted disease progression; inhaled budesonide reduced the number of hospitalizations and visits to emergency departments; colchicine reduced the number of deaths and hospitalizations. Collectively, therefore, these findings show that treatment of early COVID-19 may be associated with reduced viral load, thus potentially decreasing disease spread in the community. Moreover, treatment of patients with mild to moderate COVID-19 may also be associated with improved clinical symptoms, hospitalization, and disease progression. We suggest that colchicine, inhaled budesonide, and nitazoxanide, along with nonpharmacological measures, based on efficacy and costs, may be used to mitigate the effects of the COVID-19 pandemic in middle-income countries.
Navigating Infodemics, Unlocking Social Capital and Maintaining Food Security during the COVID-19 First Wave in the UK: Older Adults’ Experiences
Authors: Brown Heather , Reid Kate
Published: July 2021

In March 2020, a national UK lockdown was implemented in response to rapidly rising COVID-19 infections. Those experiencing the most severe public health restrictions were ‘shielding’ groups as well as those over 70 years of age. Older age adults, many of whom were active, independent, and socially connected were immediately instructed to stay at home, to limit all external social contact and consider contingency for maintaining personal food security and social contact. The purpose of this qualitative study was to explore the experiences of older adults during the first UK lockdown (March–June 2020), specifically how our sample reacted to public health messaging, staying food secure and drawing on available social capital within their community. Semi-structured telephone interviews were conducted with eight participants. In addition, twenty-five participants completed a qualitative ‘open-ended’ survey. The data was collated and analysed, adopting a Thematic Analysis informed approach. Three themes were identified: (1) Too Much Information, (2) The Importance of Neighbours and Connections and (3) Not Wishing to be a Burden. These findings offer a rich insight into how early lockdown measures, never witnessed since World War 2, exposed existing pre-pandemic inequalities and concerns relating to loneliness, isolation and wellbeing. The findings are of relevance to researchers, older adult advocate groups and policy makers to inform post COVID-recovery within communities to ensure healthy ageing.
Get Outside! Promoting Adolescent Health through Outdoor After-School Activity
Authors: Barfield Patricia Ann , Ridder Katelyn , Hughes Justin , Rice-McNeil Kelly
Published: July 2021

Background: The Get Outside: After School Activity Program (GO-ASAP) exemplifies how a rural community can utilize its natural resources and community partnerships to promote adolescent health. Methods: A qualitative descriptive inquiry was conducted using convenience sampling. Data were collected from students (n = 13/2018; n = 13/2019) via focus group and art-based method (2018 only) and parent (n = 6/2018) focus group. Data were analyzed via qualitative content analysis using the applied theoretical frameworks of Social Cognitive Theory and Social Determination Theory. Results: (1) Increasing Health-Related Competencies. Students increased their physical activity, improved their sleep, perceived less stress, and reported changes in dietary habits and electronic use. (2) Increasing Social Relatedness. Students made new friends, felt more connected, and spent less time home alone after school. (3) Increasing Autonomy and Intrinsic Motivation. Students recognized their emerging capabilities, and their increased confidence stimulated more action-oriented behavior. Parent-perceived changes support and mirror student reports. Conclusion: Outdoor, nature-based, activity programs are a novel upstream approach to promote adolescent health, especially in rural communities where natural resources often exceed health-service resources and community partnerships are a way of life.
Association of Microbiome with Oral Squamous Cell Carcinoma: A Systematic Review of the Metagenomic Studies
Authors: Su Mun Lee , Wye Lum See , Kong Yuiin Sze Genevieve , Hock Yoong Cheong , Ching Yung Kwek , Kah Lok Liong , Gopinath Divya
Published: July 2021

The past decade has witnessed a surge in epidemiological studies that have explored the relationship between the oral microbiome and oral cancer. Owing to the diversity of the published data, a comprehensive systematic overview of the currently available evidence is critical. This review summarises the current evidence on the metagenomic studies on the oral microbiome in oral cancer. A systematic search was conducted in Medline and Embase databases to identify original studies examining the differences in the oral microbiome of oral cancer cases and controls. A total of twenty-six studies were identified that reported differences in microbial abundance between oral squamous cell carcinoma (OSCC) and controls. Although almost all the studies identified microbial dysbiosis to be associated with oral cancer, the detailed qualitative analysis did not reveal the presence/abundance of any individual bacteria or a consortium to be consistently enriched in OSCC samples across the studies. Interestingly, few studies reported a surge of periodontopathogenic taxa, especially Fusobacteria, whereas others demonstrated a depletion of commensal taxa Streptococci. Considerable heterogeneity could be identified in the parameters used for designing the studies as well as reporting the microbial data. If microbiome data needs to be translated in the future, to complement the clinical parameters for diagnosis and prognosis of oral cancer, further studies with the integration of clinical variables, adequate statistical power, reproducible methods, and models are required.
Overview of Facebook Use by Hospitals in Italy: A Nationwide Survey during the COVID-19 Emergency
Authors: Schiavone Beniamino , Vitale Andrea , Gallo Mena , Russo Gianlucasalvatore , Ponticelli Domenico , Borrelli Mario
Published: July 2021

Background: Facebook is the most popular social network across the world and also allows users access to health information. Our study presents an overview of the official Facebook profiles of hospitals in Italy (n = 1351) and how much they are used. Methods: All hospitals were surveyed on the number of Facebook posts in May (post-lockdown) and October (second pandemic wave) 2020. The number of followers, the creation date of the official page, and the frequency of publication—that is, the average number of days between two subsequent posts—were determined. Results: In Italy, only 28% (n = 379) of the hospitals had official Facebook pages, of which 20.6% (n = 78) were public hospitals, and 79.4% (n = 301) were private hospitals. Of the hospitals with Facebook pages, 49.1% used them every week, and public hospitals published more often. Conclusions: Despite the differences between regions and types of management, the number of hospitals in Italy that use Facebook as a tool for the public dissemination of health information is still low. Hospitals should adopt an effective communication strategy using social networks to improve the quality of health care.
Advanced Glycation End Products: New Clinical and Molecular Perspectives
Authors: Salazar Juan , Navarro Carla , Ortega Ángel , Nava Manuel , Morillo Daniela , Torres Wheeler , Hernández Marlon , Cabrera Mayela , Angarita Lissé , Ortiz Rina , Chacín Maricarmen , D’Marco Luis , Bermúdez Valmore
Published: July 2021

Diabetes mellitus (DM) is considered one of the most massive epidemics of the twenty-first century due to its high mortality rates caused mainly due to its complications; therefore, the early identification of such complications becomes a race against time to establish a prompt diagnosis. The research of complications of DM over the years has allowed the development of numerous alternatives for diagnosis. Among these emerge the quantification of advanced glycation end products (AGEs) given their increased levels due to chronic hyperglycemia, while also being related to the induction of different stress-associated cellular responses and proinflammatory mechanisms involved in the progression of chronic complications of DM. Additionally, the investigation for more valuable and safe techniques has led to developing a newer, noninvasive, and effective tool, termed skin fluorescence (SAF). Hence, this study aimed to establish an update about the molecular mechanisms induced by AGEs during the evolution of chronic complications of DM and describe the newer measurement techniques available, highlighting SAF as a possible tool to measure the risk of developing DM chronic complications.
Quantitation of Silica Contents in Lung Explants of Transplanted Patients: Artificial Stone-Induced Silicosis vs. Idiopathic Pulmonary Fibrosis
Authors: Fireman Elizabeth , Mahamed Abed Elrahman , Rosengarten Dror , Ophir Noa Noach , Kramer Mordechai
Published: July 2021

Spectrophotometric techniques provide qualitative but not quantitative data on lung particles. We aimed to quantitate silica content in biopsies of lung-transplanted silicosis patients by applying X-ray fluorescence (XRF) spectrometry. Lung biopsies of 17 lung-transplanted artificial patients were quantitated for silica and other minerals particles by Niton XL3 XRF spectrometry. Occupational and clinical history data were assessed. Lung biopsies of artificial stone-induced silicosis (ASIS) patients contained significantly higher levels of silica compared to those of idiopathic pulmonary fibrosis (IPF) patients (7284.29 ± 4693.75 ppm vs. 898.88 ± 365.66 ppm, p < 0.0001). Silica content correlated negatively with age, body mass index, and pulmonary function test results. A 1128 ppm silica cut-off value yielded 100% sensitivity and 94% specificity for predicting ASIS (AUC = 0.94, p < 0.0001). In conclusion, XRF measurements in lung biopsies can differentiate between silica and mineral particles in ASIS and IPF.
Real-Time CDC Consultation during the COVID-19 Pandemic—United States, March–July, 2020
Authors: Wozniczka Daniel , Demeke Hanna B. , Thompson-Paul Angela M. , Ijeoma Ugonna , Williams Tonya R. , Taylor Allan W. , Tan Kathrine R. , Chevalier Michelle S. , Agyemang Elfriede , Dowell Deborah , Oduyebo Titilope , Shiferaw Miriam , Coleman King Sallyann M. , Minta Anna A. , Shealy Katherine , Oliver Sara E. , McLean Catherine , Glover Maleeka , Iskander John
Published: July 2021

Context: In response to the COVID-19 pandemic, the Centers for Disease Prevention and Control (CDC) clinicians provided real-time telephone consultation to healthcare providers, public health practitioners, and health department personnel. Objective: To describe the demographic and public health characteristics of inquiries, trends, and correlation of inquiries with national COVID-19 case reports. We summarize the results of real-time CDC clinician consultation service provided during 11 March to 31 July 2020 to understand the impact and utility of this service by CDC for the COVID-19 pandemic emergency response and for future outbreak responses. Design: Clinicians documented inquiries received including information about the call source, population for which guidance was sought, and a detailed description of the inquiry and resolution. Descriptive analyses were conducted, with a focus on characteristics of callers as well as public health and clinical content of inquiries. Setting: Real-time telephone consultations with CDC Clinicians in Atlanta, GA. Participants: Health care providers and public health professionals who called CDC with COVID-19 related inquiries from throughout the United States. Main Outcome Measures: Characteristics of inquiries including topic of inquiry, inquiry population, resolution, and demographic information. Results: A total of 3154 COVID-19 related telephone inquiries were answered in real-time. More than half (62.0%) of inquiries came from frontline healthcare providers and clinical sites, followed by 14.1% from state and local health departments. The majority of inquiries focused on issues involving healthcare workers (27.7%) and interpretation or application of CDC’s COVID-19 guidance (44%). Conclusion: The COVID-19 pandemic resulted in a substantial number of inquiries to CDC, with the large majority originating from the frontline clinical and public health workforce. Analysis of inquiries suggests that the ongoing focus on refining COVID-19 guidance documents is warranted, which facilitates bidirectional feedback between the public, medical professionals, and public health authorities.
Pushing the Limits of Medical Management in HCM: A Review of Current Pharmacological Therapy Options
Authors: Stătescu Cristian , Enachi Ștefana , Ureche Carina , Țăpoi Laura , Anghel Larisa , Șalaru Delia , Pleșoianu Carmen , Bostan Mădălina , Marcu Dragoș , Ovanez Balasanian Mircea , Sascău Radu Andy
Published: July 2021

Hypertrophic cardiomyopathy (HCM) is the most common monogenic cardiac disease with a highly variable phenotypic expression, ranging from asymptomatic to drug refractory heart failure (HF) presentation. Pharmacological therapy is the first line of treatment, but options are currently limited to nonspecific medication like betablockers or calcium channel inhibitors, with frequent suboptimal results. While being the gold standard practice for the management of drug refractory HCM patients, septal reduction therapy (SRT) remains an invasive procedure with associated surgical risks and it requires the expertise of the operating centre, thus limiting its accessibility. It is therefore with high interest that researchers look for pharmacological alternatives that could provide higher rates of success. With new data gathering these past years as well as the development of a new drug class showing promising results, this review provides an up-to-date focused synthesis of existing medical treatment options and future directions for HCM pharmacological treatment.
Hypoxia and Hypoxia-Inducible Factor Signaling in Muscular Dystrophies: Cause and Consequences
Authors: Nguyen Thuy-Hang , Conotte Stephanie , Belayew Alexandra , Declèves Anne-Emilie , Legrand Alexandre , Tassin Alexandra
Published: July 2021

Muscular dystrophies (MDs) are a group of inherited degenerative muscle disorders characterized by a progressive skeletal muscle wasting. Respiratory impairments and subsequent hypoxemia are encountered in a significant subgroup of patients in almost all MD forms. In response to hypoxic stress, compensatory mechanisms are activated especially through Hypoxia-Inducible Factor 1 α (HIF-1α). In healthy muscle, hypoxia and HIF-1α activation are known to affect oxidative stress balance and metabolism. Recent evidence has also highlighted HIF-1α as a regulator of myogenesis and satellite cell function. However, the impact of HIF-1α pathway modifications in MDs remains to be investigated. Multifactorial pathological mechanisms could lead to HIF-1α activation in patient skeletal muscles. In addition to the genetic defect per se, respiratory failure or blood vessel alterations could modify hypoxia response pathways. Here, we will discuss the current knowledge about the hypoxia response pathway alterations in MDs and address whether such changes could influence MD pathophysiology.
C-Terminal Fragment of Vitellogenin II, a Potential Yolkin Polypeptide Complex Precursor Protein—Heterologous Expression, Purification, and Immunoregulatory Activity
Authors: Szmyt Agnieszka , Zabłocka Agnieszka , Macała Józefa , Chrzanowska Józefa , Dąbrowska Anna
Published: July 2021

The aim of this research was to analyze the heterologous expression, purification, and immunoregulatory activity of recombinant YGP40 (rYGP40), the potential precursor of the yolkin peptide complex. The ygp40 coding sequence was codon optimized, successfully expressed in the E. coli system, and purified from inclusion bodies with a yield of about 1.1 mg/L of culture. This study showed that the protein exhibits immunomodulatory activity, expressed by the stimulation of TNF-α and IL-10 production and nitric oxide induction at a level comparable to that of the natural yolkin peptide complex obtained by other authors from hen egg yolk. At the highest dose of 100 µg/mL, rYGP40 also caused the up-regulation of iNOS expression in murine bone marrow-derived macrophages (BMDM). Moreover, no cytotoxic effects of rYGP40 on the BMDM cell line were observed.
The Implications of Pruritogens in the Pathogenesis of Atopic Dermatitis
Authors: Wong Lai-San , Yen Yu-Ta , Lee Chih-Hung
Published: July 2021

Atopic dermatitis (AD) is a prototypic inflammatory disease that presents with intense itching. The pathophysiology of AD is multifactorial, involving environmental factors, genetic susceptibility, skin barrier function, and immune responses. A recent understanding of pruritus transmission provides more information about the role of pruritogens in the pathogenesis of AD. There is evidence that pruritogens are not only responsible for eliciting pruritus, but also interact with immune cells and act as inflammatory mediators, which exacerbate the severity of AD. In this review, we discuss the interaction between pruritogens and inflammatory molecules and summarize the targeted therapies for AD.
Ineffective Erythropoiesis in β-Thalassaemia: Key Steps and Therapeutic Options by Drugs
Authors: Longo Filomena , Piolatto Andrea , Ferrero Giovanni Battista , Piga Antonio
Published: July 2021

β-thalassaemia is a rare genetic condition caused by mutations in the β-globin gene that result in severe iron-loading anaemia, maintained by a detrimental state of ineffective erythropoiesis (IE). The role of multiple mechanisms involved in the pathophysiology of the disease has been recently unravelled. The unbalanced production of α-globin is a major source of oxidative stress and membrane damage in red blood cells (RBC). In addition, IE is tightly linked to iron metabolism dysregulation, and the relevance of new players of this pathway, i.e., hepcidin, erythroferrone, matriptase-2, among others, has emerged. Advances have been made in understanding the balance between proliferation and maturation of erythroid precursors and the role of specific factors in this process, such as members of the TGF-β superfamily, and their downstream effectors, or the transcription factor GATA1. The increasing understanding of IE allowed for the development of a broad set of potential therapeutic options beyond the current standard of care. Many candidates of disease-modifying drugs are currently under clinical investigation, targeting the regulation of iron metabolism, the production of foetal haemoglobin, the maturation process, or the energetic balance and membrane stability of RBC. Overall, they provide tools and evidence for multiple and synergistic approaches that are effectively moving clinical research in β-thalassaemia from bench to bedside.
Protective Effects of Ethanolic Extract from Rhizome of Polygoni avicularis against Renal Fibrosis and Inflammation in a Diabetic Nephropathy Model
Authors: Yoon Jung-Joo , Park Ji-Hun , Lee Yun-Jung , Kim Hye-Yoom , Han Byung-Hyuk , Jin Hong-Guang , Kang Dae-Gill , Lee Ho-Sub
Published: July 2021

Progressive diabetic nephropathy (DN) in diabetes leads to major morbidity and mortality. The major pathological alterations of DN include mesangial expansion, extracellular matrix alterations, tubulointerstitial fibrosis, and glomerular sclerosis. Polygoni avicularis is widely used in traditional oriental medicine and has long been used as a diuretic, astringent, insecticide and antihypertensive. However, to the best of the authors’ knowledge, the effects of the ethanolic extract from rhizome of Polygoni avicularis (ER-PA) on DN have not yet been assessed. The present study aimed to identify the effect of ER-PA on renal dysfunction, which has been implicated in DN in human renal mesangial cells and db/db mice and investigate its mechanism of action. The in vivo experiment was performed using Polygoni avicularis-ethanol soluble fraction (ER-PA) and was administrated to db/db mice at 10 and 50 mg/kg dose. For the in vitro experiments, the human renal mesangial cells were induced by high glucose (HG, 25 mM). The ER-PA group showed significant amelioration in oral glucose tolerance, and insulin resistance index. ER-PA significantly improved the albumin excretion and markedly reduced plasma creatinine, kidney injury molecule-1 and C-reactive protein. In addition, ER-PA significantly suppressed inflammatory cytokines. Histopathologically, ER-PA attenuated glomerular expansion and tubular fibrosis in db/db mice. Furthermore, ER-PA suppressed the expression of renal fibrosis biomarkers (TGF and Collagen IV). ER-PA also reduced the NLR family pyrin domain containing 3 inflammatory factor level. These results suggest that ER-PA has a protective effect against renal dysfunction through improved insulin resistance as well as the inhibition of nephritis and fibrosis in DN.
Norepinephrine Protects against Methamphetamine Toxicity through β2-Adrenergic Receptors Promoting LC3 Compartmentalization
Authors: Lazzeri Gloria , Busceti Carla L. , Biagioni Francesca , Fabrizi Cinzia , Morucci Gabriele , Giorgi Filippo S. , Ferrucci Michela , Lenzi Paola , Puglisi-Allegra Stefano , Fornai Francesco
Published: July 2021

Norepinephrine (NE) neurons and extracellular NE exert some protective effects against a variety of insults, including methamphetamine (Meth)-induced cell damage. The intimate mechanism of protection remains difficult to be analyzed in vivo. In fact, this may occur directly on target neurons or as the indirect consequence of NE-induced alterations in the activity of trans-synaptic loops. Therefore, to elude neuronal networks, which may contribute to these effects in vivo, the present study investigates whether NE still protects when directly applied to Meth-treated PC12 cells. Meth was selected based on its detrimental effects along various specific brain areas. The study shows that NE directly protects in vitro against Meth-induced cell damage. The present study indicates that such an effect fully depends on the activation of plasma membrane β2-adrenergic receptors (ARs). Evidence indicates that β2-ARs activation restores autophagy, which is impaired by Meth administration. This occurs via restoration of the autophagy flux and, as assessed by ultrastructural morphometry, by preventing the dissipation of microtubule-associated protein 1 light chain 3 (LC3) from autophagy vacuoles to the cytosol, which is produced instead during Meth toxicity. These findings may have an impact in a variety of degenerative conditions characterized by NE deficiency along with autophagy impairment.
Comparative Mitogenomic Analysis Reveals Gene and Intron Dynamics in Rubiaceae and Intra-Specific Diversification in Damnacanthus indicus
Authors: Han Eun-Kyeong , Cho Won-Bum , Tamaki Ichiro , Choi In-Su , Lee Jung-Hyun
Published: July 2021

The dynamic evolution of mitochondrial gene and intron content has been reported across the angiosperms. However, a reference mitochondrial genome (mitogenome) is not available in Rubiaceae. The phylogenetic utility of mitogenome data at a species level is rarely assessed. Here, we assembled mitogenomes of six Damnacanthus indicus (Rubiaceae, Rubioideae) representing two varieties (var. indicus and var. microphyllus). The gene and intron content of D. indicus was compared with mitogenomes from representative angiosperm species and mitochondrial contigs from the other Rubiaceae species. Mitogenome structural rearrangement and sequence divergence in D. indicus were analyzed in six individuals. The size of the mitogenome in D. indicus varied from 417,661 to 419,435 bp. Comparing the number of intact mitochondrial protein-coding genes in other Gentianales taxa (38), D. indicus included 32 genes representing several losses. The intron analysis revealed a shift from cis to trans splicing of a nad1 intron (nad1i728) in D. indicus and it is a shared character with the other four Rubioideae taxa. Two distinct mitogenome structures (type A and B) were identified. Two-step direct repeat-mediated recombination was proposed to explain structural changes between type A and B mitogenomes. The five individuals from two varieties in D. indicus diverged well in the whole mitogenome-level comparison with one exception. Collectively, our study elucidated the mitogenome evolution in Rubiaceae along with D. indicus and showed the reliable phylogenetic utility of the whole mitogenome data at a species-level evolution.
Tumor-Associated Macrophages: Combination of Therapies, the Approach to Improve Cancer Treatment
Authors: Moeini Pedram , Niedźwiedzka-Rystwej Paulina
Published: July 2021

Macrophages are one of the most important cells of the innate immune system and are known for their ability to engulf and digest foreign substances, including cellular debris and tumor cells. They can convert into tumor-associated macrophages (TAMs) when mature macrophages are recruited into the tumor microenvironment. Their role in cancer progression, metastasis, and therapy failure is of special note. The aim of this review is to understand how the presence of TAMs are both advantageous and disadvantageous in the immune system.
The Hexosamine Biosynthetic Pathway as a Therapeutic Target after Cartilage Trauma: Modification of Chondrocyte Survival and Metabolism by Glucosamine Derivatives and PUGNAc in an Ex Vivo Model
Authors: Riegger Jana , Baumert Julia , Zaucke Frank , Brenner Rolf E.
Published: July 2021

The hexosamine biosynthetic pathway (HBP) is essential for the production of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), the building block of glycosaminoglycans, thus playing a crucial role in cartilage anabolism. Although O-GlcNAcylation represents a protective regulatory mechanism in cellular processes, it has been associated with degenerative diseases, including osteoarthritis (OA). The present study focuses on HBP-related processes as potential therapeutic targets after cartilage trauma. Human cartilage explants were traumatized and treated with GlcNAc or glucosamine sulfate (GS); PUGNAc, an inhibitor of O-GlcNAcase; or azaserine (AZA), an inhibitor of GFAT-1. After 7 days, cell viability and gene expression analysis of anabolic and catabolic markers, as well as HBP-related enzymes, were performed. Moreover, expression of catabolic enzymes and type II collagen (COL2) biosynthesis were determined. Proteoglycan content was assessed after 14 days. Cartilage trauma led to a dysbalanced expression of different HBP-related enzymes, comparable to the situation in highly degenerated tissue. While GlcNAc and PUGNAc resulted in significant cell protection after trauma, only PUGNAc increased COL2 biosynthesis. Moreover, PUGNAc and both glucosamine derivatives had anti-catabolic effects. In contrast, AZA increased catabolic processes. Overall, “fueling” the HBP by means of glucosamine derivatives or inhibition of deglycosylation turned out as cells and chondroprotectives after cartilage trauma.
Tumor Escape Phenotype in Bladder Cancer Is Associated with Loss of HLA Class I Expression, T-Cell Exclusion and Stromal Changes
Authors: Gil-Julio Hernani , Perea Francisco , Rodriguez-Nicolas Antonio , Cozar Jose Manuel , González-Ramirez Amanda Rocío , Concha Angel , Garrido Federico , Aptsiauri Natalia , Ruiz-Cabello Francisco
Published: July 2021

Cancer eradication and clinical outcome of immunotherapy depend on tumor cell immunogenicity, including HLA class I (HLA-I) and PD-L1 expression on malignant cells, and on the characteristics of the tumor microenvironment, such as tumor immune infiltration and stromal reaction. Loss of tumor HLA-I is a common mechanism of immune escape from cytotoxic T lymphocytes and is linked to cancer progression and resistance to immunotherapy with the inhibitors of PD-L1/PD-1 signaling. Here we observed that HLA-I loss in bladder tumors is associated with T cell exclusion and tumor encapsulation with stromal elements rich in FAP-positive cells. In addition, PD-L1 upregulation in HLA-I negative tumors demonstrated a correlation with high tumor grade and worse overall- and cancer-specific survival of the patients. These changes define common immuno-morphological signatures compatible with cancer immune escape and acquired resistance to therapeutic interventions across different types of malignancy. They also may contribute to the search of new targets for cancer treatment, such as FAP-expressing cancer-associated fibroblasts, in refractory bladder tumors.
Liver Injury and the Macrophage Issue: Molecular and Mechanistic Facts and Their Clinical Relevance
Authors: Roohani Siyer , Tacke Frank
Published: July 2021

The liver is an essential immunological organ due to its gatekeeper position to bypassing antigens from the intestinal blood flow and microbial products from the intestinal commensals. The tissue-resident liver macrophages, termed Kupffer cells, represent key phagocytes that closely interact with local parenchymal, interstitial and other immunological cells in the liver to maintain homeostasis and tolerance against harmless antigens. Upon liver injury, the pool of hepatic macrophages expands dramatically by infiltrating bone marrow-/monocyte-derived macrophages. The interplay of the injured microenvironment and altered macrophage pool skews the subsequent course of liver injuries. It may range from complete recovery to chronic inflammation, fibrosis, cirrhosis and eventually hepatocellular cancer. This review summarizes current knowledge on the classification and role of hepatic macrophages in the healthy and injured liver.
Knockdown of a β-Adrenergic-Like Octopamine Receptor Affects Locomotion and Reproduction of Tribolium castaneum
Authors: Zheng Li-Sha , Liu Xiao-Qiang , Liu Ge-Ge , Huang Qian-Qiao , Wang Jin-Jun , Jiang Hong-Bo
Published: July 2021

The neurohormone octopamine regulates many crucial physiological processes in insects and exerts its activity via typical G-protein coupled receptors. The roles of octopamine receptors in regulating behavior and physiology in Coleoptera (beetles) need better understanding. We used the red flour beetle, Tribolium castaneum, as a model species to study the contribution of the octopamine receptor to behavior and physiology. We cloned the cDNA of a β-adrenergic-like octopamine receptor (TcOctβ2R). This was heterologously expressed in human embryonic kidney (HEK) 293 cells and was demonstrated to be functional using an in vitro cyclic AMP assay. In an RNAi assay, injection of dsRNA demonstrated that TcOctβ2R modulates beetle locomotion, mating duration, and fertility. These data present some roles of the octopaminergic signaling system in T. castaneum. Our findings will also help to elucidate the potential functions of individual octopamine receptors in other insects.
The Cellular Choreography of Osteoblast Angiotropism in Bone Development and Homeostasis
Authors: Neag Georgiana , Finlay Melissa , Naylor Amy J.
Published: July 2021

Interaction between endothelial cells and osteoblasts is essential for bone development and homeostasis. This process is mediated in large part by osteoblast angiotropism, the migration of osteoblasts alongside blood vessels, which is crucial for the homing of osteoblasts to sites of bone formation during embryogenesis and in mature bones during remodeling and repair. Specialized bone endothelial cells that form “type H” capillaries have emerged as key interaction partners of osteoblasts, regulating osteoblast differentiation and maturation and ensuring their migration towards newly forming trabecular bone areas. Recent revolutions in high-resolution imaging methodologies for bone as well as single cell and RNA sequencing technologies have enabled the identification of some of the signaling pathways and molecular interactions that underpin this regulatory relationship. Similarly, the intercellular cross talk between endothelial cells and entombed osteocytes that is essential for bone formation, repair, and maintenance are beginning to be uncovered. This is a relatively new area of research that has, until recently, been hampered by a lack of appropriate analysis tools. Now that these tools are available, greater understanding of the molecular relationships between these key cell types is expected to facilitate identification of new drug targets for diseases of bone formation and remodeling.
Role of Long Non-Coding RNAs and the Molecular Mechanisms Involved in Insulin Resistance
Authors: Tello-Flores Vianet Argelia , Beltrán-Anaya Fredy Omar , Ramírez-Vargas Marco Antonio , Esteban-Casales Brenda Ely , Navarro-Tito Napoleón , Alarcón-Romero Luz del Carmen , Luciano-Villa Carlos Aldair , Ramírez Mónica , del Moral-Hernández Óscar , Flores-Alfaro Eugenia
Published: July 2021

Long non-coding RNAs (lncRNAs) are single-stranded RNA biomolecules with a length of >200 nt, and they are currently considered to be master regulators of many pathological processes. Recent publications have shown that lncRNAs play important roles in the pathogenesis and progression of insulin resistance (IR) and glucose homeostasis by regulating inflammatory and lipogenic processes. lncRNAs regulate gene expression by binding to other non-coding RNAs, mRNAs, proteins, and DNA. In recent years, several mechanisms have been reported to explain the key roles of lncRNAs in the development of IR, including metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), imprinted maternal-ly expressed transcript (H19), maternally expressed gene 3 (MEG3), myocardial infarction-associated transcript (MIAT), and steroid receptor RNA activator (SRA), HOX transcript antisense RNA (HOTAIR), and downregulated Expression-Related Hexose/Glucose Transport Enhancer (DREH). LncRNAs participate in the regulation of lipid and carbohydrate metabolism, the inflammatory process, and oxidative stress through different pathways, such as cyclic adenosine monophosphate/protein kinase A (cAMP/PKA), phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), polypyrimidine tract-binding protein 1/element-binding transcription factor 1c (PTBP1/SREBP-1c), AKT/nitric oxide synthase (eNOS), AKT/forkhead box O1 (FoxO1), and tumor necrosis factor-alpha (TNF-α)/c-Jun-N-terminal kinases (JNK). On the other hand, the mechanisms linked to the molecular, cellular, and biochemical actions of lncRNAs vary according to the tissue, biological species, and the severity of IR. Therefore, it is essential to elucidate the role of lncRNAs in the insulin signaling pathway and glucose and lipid metabolism. This review analyzes the function and molecular mechanisms of lncRNAs involved in the development of IR.
NMDARs, Coincidence Detectors of Astrocytic and Neuronal Activities
Authors: Sherwood Mark W. , Oliet Stéphane H. R. , Panatier Aude
Published: July 2021

Synaptic plasticity is an extensively studied cellular correlate of learning and memory in which NMDARs play a starring role. One of the most interesting features of NMDARs is their ability to act as a co-incident detector. It is unique amongst neurotransmitter receptors in this respect. Co-incident detection is possible because the opening of NMDARs requires membrane depolarisation and the binding of glutamate. Opening of NMDARs also requires a co-agonist. Although the dynamic regulation of glutamate and membrane depolarization have been well studied in coincident detection, the role of the co-agonist site is unexplored. It turns out that non-neuronal glial cells, astrocytes, regulate co-agonist availability, giving them the ability to influence synaptic plasticity. The unique morphology and spatial arrangement of astrocytes at the synaptic level affords them the capacity to sample and integrate information originating from unrelated synapses, regardless of any pre-synaptic and post-synaptic commonality. As astrocytes are classically considered slow responders, their influence at the synapse is widely recognized as modulatory. The aim herein is to reconsider the potential of astrocytes to participate directly in ongoing synaptic NMDAR activity and co-incident detection.
FTY720 Inhibits Expansion of Breast Cancer Stem Cells via PP2A Activation
Authors: Hirata Naoya , Yamada Shigeru , Yanagida Shota , Ono Atsushi , Kanda Yasunari
Published: July 2021

Growing evidence suggests that breast cancer originates from a minor population of cancer cells termed cancer stem cells (CSCs), which can be identified by aldehyde dehydrogenase (ALDH) activity-based flow cytometry analysis. However, novel therapeutic drugs for the eradication of CSCs have not been discovered yet. Recently, drug repositioning, which finds new medical uses from existing drugs, has been expected to facilitate drug discovery. We have previously reported that sphingosine kinase 1 (SphK1) induced proliferation of breast CSCs. In the present study, we focused on the immunosuppressive agent FTY720 (also known as fingolimod or Gilenya), since FTY720 is known to be an inhibitor of SphK1. We found that FTY720 blocked both proliferation of ALDH-positive cells and formation of mammospheres. In addition, we showed that FTY720 reduced the expression of stem cell markers such as Oct3/4, Sox2 and Nanog via upregulation of protein phosphatase 2A (PP2A). These results suggest that FTY720 is an effective drug for breast CSCs in vitro.
Increased Endocytosis of Cadmium-Metallothionein through the 24p3 Receptor in an In Vivo Model with Reduced Proximal Tubular Activity
Authors: Zavala-Guevara Itzel Pamela , Ortega-Romero Manolo Sibael , Narváez-Morales Juana , Jacobo-Estrada Tania Libertad , Lee Wing-Kee , Arreola-Mendoza Laura , Thévenod Frank , Barbier Olivier Christophe
Published: July 2021

Background: The proximal tubule (PT) is the major target of cadmium (Cd2+) nephrotoxicity. Current dogma postulates that Cd2+ complexed to metallothionein (MT) (CdMT) is taken up through receptor-mediated endocytosis (RME) via the PT receptor megalin:cubilin, which is the predominant pathway for reuptake of filtered proteins in the kidney. Nevertheless, there is evidence that the distal parts of the nephron are also sensitive to damage induced by Cd2+. In rodent kidneys, another receptor for protein endocytosis, the 24p3 receptor (24p3R), is exclusively expressed in the apical membranes of distal tubules (DT) and collecting ducts (CD). Cell culture studies have demonstrated that RME and toxicity of CdMT and other (metal ion)–protein complexes in DT and CD cells is mediated by 24p3R. In this study, we evaluated the uptake of labeled CdMT complex through 24p3R after acute kidney injury (AKI) induced by gentamicin (GM) administration that disrupts PT function. Subcutaneous administration of GM at 10 mg/kg/day for seven days did not alter the structural and functional integrity of the kidney’s filtration barrier. However, because of PT injury, the concentration of the renal biomarker Kim-1 increased. When CdMT complex coupled to FITC was administered intravenously, both uptake of the CdMT complex and 24p3R expression in DT increased and also colocalized after PT injury induced by GM. Although megalin decreased in PT after GM administration, urinary protein excretion was not changed, which suggests that the increased levels of 24p3R in the distal nephron could be acting as a compensatory mechanism for protein uptake. Altogether, these results suggest that PT damage increases the uptake of the CdMT complex through 24p3R in DT (and possibly CD) and compensate for protein losses associated with AKI.
Platelet Microparticles Decrease Daunorubicin-Induced DNA Damage and Modulate Intrinsic Apoptosis in THP-1 Cells
Authors: Cacic Daniel , Nordgård Oddmund , Meyer Peter , Hervig Tor
Published: July 2021

Platelets can modulate cancer through budding of platelet microparticles (PMPs) that can transfer a plethora of bioactive molecules to cancer cells upon internalization. In acute myelogenous leukemia (AML) this can induce chemoresistance, partially through a decrease in cell activity. Here we investigated if the internalization of PMPs protected the monocytic AML cell line, THP-1, from apoptosis by decreasing the initial cellular damage inflicted by treatment with daunorubicin, or via direct modulation of the apoptotic response. We examined whether PMPs could protect against apoptosis after treatment with a selection of inducers, primarily associated with either the intrinsic or the extrinsic apoptotic pathway, and protection was restricted to the agents targeting intrinsic apoptosis. Furthermore, levels of daunorubicin-induced DNA damage, assessed by measuring gH2AX, were reduced in both 2N and 4N cells after PMP co-incubation. Measuring different BCL2-family proteins before and after treatment with daunorubicin revealed that PMPs downregulated the pro-apoptotic PUMA protein. Thus, our findings indicated that PMPs may protect AML cells against apoptosis by reducing DNA damage both dependent and independent of cell cycle phase, and via direct modulation of the intrinsic apoptotic pathway by downregulating PUMA. These findings further support the clinical relevance of platelets and PMPs in AML.