bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Acute Exercise on Cognitive Flexibility in Young Adults with Different Levels of Aerobic Fitness
Authors: Shi Beibei , Mou Hong , Tian Shudong , Meng Fanying , Qiu Fanghui
Published: July 2022

This study aimed to evaluate the effects of high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE) on cognitive flexibility in young adults with differing levels of aerobic fitness. Sixty-six young adults were grouped into high- and low-fit groups based on their final running distance on the 20 m Progressive Aerobic Cardiovascular Endurance Run (PACER) test. Individuals participated in a 10 min HIIE, a 20 min HIIE, a 20 min MICE, and a control session (reading quietly in a chair) in a counterbalanced order. The more-odd shifting task was completed before and approximately 5 min after each intervention to assess cognitive flexibility. The results showed that young adults with a high fitness level gained greater benefits in terms of switch cost from the 20 min HIIE, while low-fitness participants benefited more from the 10 min HIIE and the 20 min MICE. These findings suggest that aerobic fitness may influence the effect of acute HIIE and MICE on cognitive flexibility. Young adults should consider individual fitness level when adopting time-effective and appropriate exercise routines to improve cognitive flexibility.
Anxiety and Depression in Patients with Prostate Cancer, at Cancer Diagnosis and after a One-Year Follow-Up
Authors: Duarte Vítor , Araújo Natália , Lopes Catarina , Costa Adriana , Ferreira Augusto , Carneiro Filipa , Oliveira Jorge , Braga Isaac , Morais Samantha , Pacheco-Figueiredo Luís , Ruano Luis , Tedim Cruz Vítor , Pereira Susana , Lunet Nuno
Published: July 2022

Prostate cancer (PCa) is the most prevalent among men, and psychological symptoms may affect many patients. This study aims to describe the prevalence of probable anxiety and depression before PCa treatments and after one year and to identify sociodemographic and clinical factors associated with these outcomes. Between February 2018 and March 2020, 292 patients recently diagnosed with PCa were recruited at the Instituto Português de Oncologia—Porto. The Hospital Anxiety and Depression Scale (HADS) was used to define probable anxiety and depression (cutoff = 11). The prevalence of probable anxiety remained stable from baseline to one year (7.8% vs. 8.5%, p = 0.866) while there was an increase in probable depression (3.1% vs. 6.8%, p = 0.012). After one year, probable depression persisted in 55.6% of patients with probable depression at baseline and 47.8% of those with probable anxiety at the first assessment had normal anxiety scores. At baseline, anxiety was more frequent among dwellers in rural areas (adjusted odds ratio—aOR, 95%CI: 2.80, 0.91–8.58) and less frequent in patients with body mass index 25–29.9 kg/m2 (aOR, 95%CI: 0.33, 0.12–0.91) compared to 18.5–24.9 Kg/m2, while those living alone had higher odds of depression (aOR, 95%CI: 6.35, 1.43–28.30). The frequency of anxiety and depression fluctuated during the course of treatment. Monitoring these symptoms would identify the most affected patients, contributing for a better use of mental health services.
The Feasibility of a Training Program for Peers with Severe Mental Illness to Provide One-to-One Services in Taiwan: A Pilot Study
Authors: Cheng Kan-Yuan , Yen Chia-Feng
Published: July 2022

Background: In Taiwan, services provided by patients’ peers in the mental health care system are still lacking. Therefore, this study aimed to develop a community setting model by a training program for severe mental illness (SMI) patients’ peers that also have SMI in Taiwan. Method: This training program comprised of 13-h lectures, 15-h practice classes, and an eight-week internship. In 2018 and 2019, the trainees provided one-to-one services to service users with SMI during the internship at a halfway house. The satisfaction and outcomes among all participants were measured in this training course. Results: The total mean satisfaction score in the training course for trainees (10 items, n = 13) and internship services for service users (12 items, n = 29) were 4.7 ± 0.4 and 4.6 ± 0.5, respectively. Among the trainees, 11 demonstrated improved Brief Psychiatric Rating Scale-18 (BPRS-18), Chinese Health Questionnaire-12 (CHQ-12), and Global Assessment of Functioning (GAF) scores after the whole training course. Among the 29 service users, their scores in the BPRS-18 and CHQ-12 decreased, whereas their scores in the GAF increased significantly under the internship service. Conclusion: In this pilot study, the trainees and service users who received internship services felt satisfied. The service providers and users with SMI both showed better clinical outcomes.
Incidence of Congenital Muscular Torticollis in Babies from Southern Portugal: Types, Age of Diagnosis and Risk Factors
Authors: Minghelli Beatriz , Vitorino Noémia Guerreiro Duarte
Published: July 2022

Congenital torticollis (CMT) is the most common type of torticollis and is defined as a unilateral contracture of the sternocleidomastoid muscle resulting in lateral head tilt associated with contralateral rotation, and early detection and treatment may present a high probability of recovery of head posture symmetry. This study aimed to verify the incidence of torticollis in babies born in southern Portugal types, age of diagnosis and the risk factors. This study comprised 6565 infants born in the south of Portugal at Algarve University Hospital Center, Portimão unit during a 5-year period (January 2016 to December 2020). The cases diagnosed with torticollis referred to the Pediatrics and Pediatric Physiatrist consultations at this hospital were included. 118 babies—77 (65.3%) male and 41 (34.7%) female—were diagnosed with torticollis. The incidence of a 5-year period was 1.5%. Spontaneous vaginal delivery was prevalent (n = 56; 47.5%), with 106 (89.8%) deliveries with cephalic presentation. 53 (44.9%) cases of torticollis were classified as postural, 37 (31.4%) as muscular torticollis with joint limitation and 28 (23.7%) as congenital torticollis (with the presence of a nodule). Postural torticollis was diagnosed at an average age of 70.14 days, muscular torticollis with joint limitation at an average of 64.12 days and congenital torticollis at 33.25 days (p < 0.001). Plagiocephaly was present in 48 (40.7%) babies with torticollis (p = 0.005) and joint limitation in 53 (44.9%) babies (p < 0.001). The data obtained revealed a low incidence of CMT, with the majority being classified as postural. The age of diagnosis varied between 33 to 70 days from birth. The baby’s gender, mode of delivery and the fetal presentation during delivery did not show a statistically significant association with the presence of torticollis. Despite presenting a low incidence, it is important to mention the importance of professional health intervention in the implementation of prevention strategies.
The Effect of N-Acetylation on the Anti-Inflammatory Activity of Chitooligosaccharides and Its Potential for Relieving Endotoxemia
Authors: Hao Wentong , Li Kecheng , Ge Xiangyun , Yang Haoyue , Xu Chaojie , Liu Song , Yu Huahua , Li Pengcheng , Xing Ronge
Published: July 2022

Endotoxemia is mainly caused by a massive burst of inflammatory cytokines as a result of lipopolysaccharide (LPS) invasion. Chitooligosaccharides (COS) is expected to be a potential drug for relieving endotoxemia due to its anti-inflammatory properties. However, the structural parameters of COS are often ambiguous, and the effect of degree of acetylation (DA) of COS on its anti-inflammatory remains unknown. In this study, four COSs with different DAs (0%, 12%, 50% and 85%) and the same oligomers distribution were successfully obtained. Their structures were confirmed by 1H NMR and MS analysis. Then, the effect of DA on the anti-inflammatory activity and relieving endotoxemia potential of COS was researched. The results revealed that COS with a DA of 12% had better anti-inflammatory activity than COSs with other DAs, mainly in inhibiting LPS-induced inflammatory cytokines burst, down-regulating its mRNA expression and reducing phosphorylation of IκBα. Furthermore, this COS showed an obviously protective effect on endotoxemia mice, such as inhibiting the increase in inflammatory cytokines and transaminases, alleviating the injury of liver and intestinal tissue. This study explored the effect of DA on the anti-inflammatory activity of COS for the first time and lays the foundation for the development of COS as an anti-inflammatory drug against endotoxemia.
Carbamate Pesticides: Shedding Light on Their Impact on the Male Reproductive System
Authors: Moreira Sílvia , Silva Ricardo , Carrageta David F. , Alves Marco G. , Seco-Rovira Vicente , Oliveira Pedro F. , de Lourdes Pereira Maria
Published: July 2022

Carbamates are widely used and known around the world as pesticides in spite of also having medical applications. This class of chemicals is classified as acetylcholinesterase inhibitors, blocking acetylcholine hydrolyzation in a reversible manner. Their lack of species selectivity and their reported high toxicity can induce, upon exposure, adverse outcomes in male fertility that may lead to infertility. In addition, they are also considered endocrine-disrupting chemicals and can interfere with the hypothalamic–pituitary–testicular axis, essential for the normal function of the male reproductive system, thus being able to provoke male reproductive dysfunctions. Although the molecular mechanisms are not fully understood, various signaling pathways, such as those mediated by acetylcholine or kisspeptin, are affected by exposure to carbamates, thus compromising steroidogenesis and spermatogenesis. Over the last decades, several studies, both in vitro and in vivo, have reported a myriad of negative effects of carbamates on the male reproductive system. In this review, an up-to-date overview of the impact of carbamates on the male reproductive system is discussed, with an emphasis on the role of these compounds on acetylcholine regulation and the male endocrine system.
Changes in Endogenous Oxytocin Levels and the Effects of Exogenous Oxytocin Administration on Body Weight Changes and Food Intake in Polycystic Ovary Syndrome Model Rats
Authors: Yamamoto Shota , Noguchi Hiroki , Takeda Asuka , Arakaki Ryosuke , Uchishiba Maimi , Imaizumi Junki , Minato Saki , Kamada Shuhei , Kagawa Tomohiro , Yoshida Atsuko , Kawakita Takako , Yamamoto Yuri , Yoshida Kanako , Kon Masafumi , Shinohara Nobuo , Iwasa Takeshi
Published: July 2022

Polycystic ovary syndrome (PCOS) is frequently seen in females of reproductive age and is associated with metabolic disorders that are exacerbated by obesity. Although body weight reduction programs via diet and lifestyle changes are recommended for modifying reproductive and metabolic phenotypes, the drop-out rate is high. Thus, an efficacious, safe, and continuable treatment method is needed. Recent studies have shown that oxytocin (OT) reduces body weight gain and food intake, and promotes lipolysis in some mammals, including humans (especially obese individuals), without any adverse effects. In the present study, we evaluated the changes in endogenous OT levels, and the effects of acute and chronic OT administration on body weight changes, food intake, and fat mass using novel dihydrotestosterone-induced PCOS model rats. We found that the serum OT level was lower in PCOS model rats than in control rats, whereas the hypothalamic OT mRNA expression level did not differ between them. Acute intraperitoneal administration of OT during the dark phase reduced the body weight gain and food intake in PCOS model rats, but these effects were not observed in control rats. In contrast, chronic administration of OT decreased the food intake in both the PCOS model rats and control rats. These findings indicate that OT may be a candidate medicine that is efficacious, safe, and continuable for treating obese PCOS patients.
Identification of Potential Insect Growth Inhibitor against Aedes aegypti: A Bioinformatics Approach
Authors: Da Costa Glauber V. , Neto Moysés F. A. , Da Silva Alicia K. P. , De Sá Ester M. F. , Cancela Luanne C. F. , Vega Jeanina S. , Lobato Cássio M. , Zuliani Juliana P. , Espejo-Román José M. , Campos Joaquín M. , Leite Franco H. A. , Santos Cleydson B. R.
Published: July 2022

Aedes aegypti is the main vector that transmits viral diseases such as dengue, hemorrhagic dengue, urban yellow fever, zika, and chikungunya. Worldwide, many cases of dengue have been reported in recent years, showing significant growth. The best way to manage diseases transmitted by Aedes aegypti is to control the vector with insecticides, which have already been shown to be toxic to humans; moreover, insects have developed resistance. Thus, the development of new insecticides is considered an emergency. One way to achieve this goal is to apply computational methods based on ligands and target information. In this study, sixteen compounds with acceptable insecticidal activities, with 100% larvicidal activity at low concentrations (2.0 to 0.001 mg·L−1), were selected from the literature. These compounds were used to build up and validate pharmacophore models. Pharmacophore model 6 (AUC = 0.78; BEDROC = 0.6) was used to filter 4793 compounds from the subset of lead-like compounds from the ZINC database; 4142 compounds (dG < 0 kcal/mol) were then aligned to the active site of the juvenile hormone receptor Aedes aegypti (PDB: 5V13), 2240 compounds (LE < −0.40 kcal/mol) were prioritized for molecular docking from the construction of a chitin deacetylase model of Aedes aegypti by the homology modeling of the Bombyx mori species (PDB: 5ZNT), which aligned 1959 compounds (dG < 0 kcal/mol), and 20 compounds (LE < −0.4 kcal/mol) were predicted for pharmacokinetic and toxicological prediction in silico (Preadmet, SwissADMET, and eMolTox programs). Finally, the theoretical routes of compounds M01, M02, M03, M04, and M05 were proposed. Compounds M01–M05 were selected, showing significant differences in pharmacokinetic and toxicological parameters in relation to positive controls and interaction with catalytic residues among key protein sites reported in the literature. For this reason, the molecules investigated here are dual inhibitors of the enzymes chitin synthase and juvenile hormonal protein from insects and humans, characterizing them as potential insecticides against the Aedes aegypti mosquito.
Early Life Short-Term Exposure to Polychlorinated Biphenyl 126 in Mice Leads to Metabolic Dysfunction and Microbiota Changes in Adulthood
Authors: Tian Yuan , Rimal Bipin , Gui Wei , Koo Imhoi , Yokoyama Shigetoshi , Perdew Gary H. , Patterson Andrew D.
Published: July 2022

Early life exposure to environmental pollutants may have long-term consequences and harmful impacts on health later in life. Here, we investigated the short- and long-term impact of early life 3,3′,4,4′,5-pentacholorobiphenyl (PCB 126) exposure (24 μg/kg body weight for five days) in mice on the host and gut microbiota using 16S rRNA gene sequencing, metagenomics, and 1H NMR- and mass spectrometry-based metabolomics. Induction of Cyp1a1, an aryl hydrocarbon receptor (AHR)-responsive gene, was observed at 6 days and 13 weeks after PCB 126 exposure consistent with the long half-life of PCB 126. Early life, Short-Term PCB 126 exposure resulted in metabolic abnormalities in adulthood including changes in liver amino acid and nucleotide metabolism as well as bile acid metabolism and increased hepatic lipogenesis. Interestingly, early life PCB 126 exposure had a greater impact on bacteria in adulthood at the community structure, metabolic, and functional levels. This study provides evidence for an association between early life environmental pollutant exposure and increased risk of metabolic disorders later in life and suggests the microbiome is a key target of environmental chemical exposure.
Circ-LocNet: A Computational Framework for Circular RNA Sub-Cellular Localization Prediction
Authors: Asim Muhammad Nabeel , Ibrahim Muhammad Ali , Imran Malik Muhammad , Dengel Andreas , Ahmed Sheraz
Published: July 2022

Circular ribonucleic acids (circRNAs) are novel non-coding RNAs that emanate from alternative splicing of precursor mRNA in reversed order across exons. Despite the abundant presence of circRNAs in human genes and their involvement in diverse physiological processes, the functionality of most circRNAs remains a mystery. Like other non-coding RNAs, sub-cellular localization knowledge of circRNAs has the aptitude to demystify the influence of circRNAs on protein synthesis, degradation, destination, their association with different diseases, and potential for drug development. To date, wet experimental approaches are being used to detect sub-cellular locations of circular RNAs. These approaches help to elucidate the role of circRNAs as protein scaffolds, RNA-binding protein (RBP) sponges, micro-RNA (miRNA) sponges, parental gene expression modifiers, alternative splicing regulators, and transcription regulators. To complement wet-lab experiments, considering the progress made by machine learning approaches for the determination of sub-cellular localization of other non-coding RNAs, the paper in hand develops a computational framework, Circ-LocNet, to precisely detect circRNA sub-cellular localization. Circ-LocNet performs comprehensive extrinsic evaluation of 7 residue frequency-based, residue order and frequency-based, and physio-chemical property-based sequence descriptors using the five most widely used machine learning classifiers. Further, it explores the performance impact of K-order sequence descriptor fusion where it ensembles similar as well dissimilar genres of statistical representation learning approaches to reap the combined benefits. Considering the diversity of statistical representation learning schemes, it assesses the performance of second-order, third-order, and going all the way up to seventh-order sequence descriptor fusion. A comprehensive empirical evaluation of Circ-LocNet over a newly developed benchmark dataset using different settings reveals that standalone residue frequency-based sequence descriptors and tree-based classifiers are more suitable to predict sub-cellular localization of circular RNAs. Further, K-order heterogeneous sequence descriptors fusion in combination with tree-based classifiers most accurately predict sub-cellular localization of circular RNAs. We anticipate this study will act as a rich baseline and push the development of robust computational methodologies for the accurate sub-cellular localization determination of novel circRNAs.
A Novel In Vivo Model for Multiplexed Analysis of Callosal Connections upon Cortical Damage
Authors: González-Manteiga Ana , Navarro-González Carmen , Sebestyén Valentina Evita , Saborit-Torres Jose Manuel , Talhada Daniela , Vayá María de la Iglesia , Ruscher Karsten , Fazzari Pietro
Published: July 2022

Brain damage is the major cause of permanent disability and it is particularly relevant in the elderly. While most studies focused on the immediate phase of neuronal loss upon injury, much less is known about the process of axonal regeneration after damage. The development of new refined preclinical models to investigate neuronal regeneration and the recovery of brain tissue upon injury is a major unmet challenge. Here, we present a novel experimental paradigm in mice that entails the (i) tracing of cortico-callosal connections, (ii) a mechanical lesion of the motor cortex, (iii) the stereological and histological analysis of the damaged tissue, and (iv) the functional characterization of motor deficits. By combining conventional microscopy with semi-automated 3D reconstruction, this approach allows the analysis of fine subcellular structures, such as axonal terminals, with the tridimensional overview of the connectivity and tissue integrity around the lesioned area. Since this 3D reconstruction is performed in serial sections, multiple labeling can be performed by combining diverse histological markers. We provide an example of how this methodology can be used to study cellular interactions. Namely, we show the correlation between active microglial cells and the perineuronal nets that envelop parvalbumin interneurons. In conclusion, this novel experimental paradigm will contribute to a better understanding of the molecular and cellular interactions underpinning the process of cortical regeneration upon brain damage.
Sweet Taste Signaling: The Core Pathways and Regulatory Mechanisms
Authors: Sukumaran Sunil Kumar , Palayyan Salin Raj
Published: July 2022

Sweet taste, a proxy for sugar-derived calories, is an important driver of food intake, and animals have evolved robust molecular and cellular machinery for sweet taste signaling. The overconsumption of sugar-derived calories is a major driver of obesity and other metabolic diseases. A fine-grained appreciation of the dynamic regulation of sweet taste signaling mechanisms will be required for designing novel noncaloric sweeteners with better hedonic and metabolic profiles and improved consumer acceptance. Sweet taste receptor cells express at least two signaling pathways, one mediated by a heterodimeric G-protein coupled receptor encoded by taste 1 receptor members 2 and 3 (TAS1R2 + TAS1R3) genes and another by glucose transporters and the ATP-gated potassium (KATP) channel. Despite these important discoveries, we do not fully understand the mechanisms regulating sweet taste signaling. We will introduce the core components of the above sweet taste signaling pathways and the rationale for having multiple pathways for detecting sweet tastants. We will then highlight the roles of key regulators of the sweet taste signaling pathways, including downstream signal transduction pathway components expressed in sweet taste receptor cells and hormones and other signaling molecules such as leptin and endocannabinoids.
Social Fear Affects Limbic System Neuronal Activity and Gene Expression
Authors: Hamann Catharina S. , Bankmann Julian , Mora Maza Hanna , Kornhuber Johannes , Zoicas Iulia , Schmitt-Böhrer Angelika
Published: July 2022

Social anxiety disorder (SAD) is a highly prevalent and comorbid anxiety disorder with rather unclear underlying mechanisms. Here, we aimed to characterize neurobiological changes occurring in mice expressing symptoms of social fear and to identify possible therapeutic targets for SAD. Social fear was induced via social fear conditioning (SFC), a validated animal model of SAD. We assessed the expression levels of the immediate early genes (IEGs) cFos, Fosl2 and Arc as markers of neuronal activity and the expression levels of several genes of the GABAergic, serotoninergic, oxytocinergic, vasopressinergic and neuropeptide Y (NPY)-ergic systems in brain regions involved in social behavior or fear-related behavior in SFC+ and SFC− mice 2 h after exposure to a conspecific. SFC+ mice showed a decreased number and density of cFos-positive cells and decreased expression levels of IEGs in the dorsal hippocampus. SFC+ mice also showed alterations in the expression of NPY and serotonin system-related genes in the paraventricular nucleus of the hypothalamus, basolateral amygdala, septum and dorsal raphe nucleus, but not in the dorsal hippocampus. Our results describe neuronal alterations occurring during the expression of social fear and identify the NPY and serotonergic systems as possible targets in the treatment of SAD.
Unraveling the Transcriptional Dynamics of NASH Pathogenesis Affecting Atherosclerosis
Authors: van den Hoek Anita M. , Özsezen Serdar , Caspers Martien P. M. , van Koppen Arianne , Hanemaaijer Roeland , Verschuren Lars
Published: July 2022

The prevalence of non-alcoholic steatohepatitis (NASH) is rapidly increasing and associated with cardiovascular disease (CVD), the major cause of mortality in NASH patients. Although sharing common risk factors, the mechanisms by which NASH may directly contribute to the development to CVD remain poorly understood. The aim of this study is to gain insight into key molecular processes of NASH that drive atherosclerosis development. Thereto, a time-course study was performed in Ldlr−/−.Leiden mice fed a high-fat diet to induce NASH and atherosclerosis. The effects on NASH and atherosclerosis were assessed and transcriptome analysis was performed. Ldlr−/−.Leiden mice developed obesity, hyperlipidemia and insulin resistance, with steatosis and hepatic inflammation preceding atherosclerosis development. Transcriptome analysis revealed a time-dependent increase in pathways related to NASH and fibrosis followed by an increase in pro-atherogenic processes in the aorta. Gene regulatory network analysis identified specific liver regulators related to lipid metabolism (SC5D, LCAT and HMGCR), inflammation (IL1A) and fibrosis (PDGF, COL3A1), linked to a set of aorta target genes related to vascular inflammation (TNFA) and atherosclerosis signaling (CCL2 and FDFT1). The present study reveals pathogenic liver processes that precede atherosclerosis development and identifies hepatic key regulators driving the atherogenic pathways and regulators in the aorta.
Prognostic Role of sST2 in Acute Heart Failure and COVID-19 Infection—A Narrative Review on Pathophysiology and Clinical Prospective
Authors: Marino Luca , Concistrè Antonio , Suppa Marianna , Galardo Gioacchino , Rosa Antonello , Bertazzoni Giuliano , Pugliese Francesco , Letizia Claudio , Petramala Luigi
Published: July 2022

The importance of cardiovascular biomarkers in clinical practice increased dramatically in the last years, and the interest extends from the diagnosis purpose to prognostic applications and response to specific treatment. Acute heart failure, ischemic heart failure, and COVID-19 infection represent different clinical settings that are challenging in terms of the proper prognostic establishment. The aim of the present review is to establish the useful role of sST2, the soluble form of the interleukin-1 receptor superfamily (ST2), physiologically involved in the signaling of interleukin-33 (IL-33)-ST2 axis, in the clinical setting of acute heart failure (HF), ischemic heart disease, and SARS-CoV-2 acute infection. Molecular mechanisms associated with the IL33/ST2 signaling pathways are discussed in view of the clinical usefulness of biomarkers to early diagnosis, evaluation therapy to response, and prediction of adverse outcomes in cardiovascular diseases.
Cardiotoxicity of Chimeric Antigen Receptor T-Cell (CAR-T) Therapy: Pathophysiology, Clinical Implications, and Echocardiographic Assessment
Authors: Nenna Antonio , Carpenito Myriam , Chello Camilla , Nappi Pierluigi , Annibali Ombretta , Vincenzi Bruno , Grigioni Francesco , Chello Massimo , Nappi Francesco
Published: July 2022

Contemporary anticancer immunotherapy with chimeric antigen receptor T-cell (CAR-T) therapy has dramatically changed the treatment of many hematologic malignancies previously associated with poor prognosis. The clinical improvement and the survival benefit unveiled the risk of cardiotoxicity, ranging from minimal effects to severe cardiac adverse events, including death. Immunotherapy should also be proposed even in patients with pre-existing cardiovascular risk factors, thereby increasing the potential harm of cardiotoxicity. CAR-T therapy frequently results in cytokine release syndrome (CRS), and inflammatory activation is sustained by circulating cytokines that foster a positive feedback mechanism. Prompt diagnosis and treatment of CAR-T cardiotoxicity might significantly improve outcomes and reduce the burden associated with cardiovascular complications. Clinical and echocardiographic examinations are crucial to perform a tailored evaluation and follow-up during CAR-T treatment. This review aims to summarize the pathophysiology, clinical implications, and echocardiographic assessment of CAR-T-related cardiotoxicity to enlighten new avenues for future research.
Myeloperoxidase as a Marker to Differentiate Mouse Monocyte/Macrophage Subsets
Authors: Gurski Cody J. , Dittel Bonnie N.
Published: July 2022

Macrophages are present in every tissue in the body and play essential roles in homeostasis and host defense against microorganisms. Some tissue macrophages derive from the yolk sac/fetal liver that populate tissues for life. Other tissue macrophages derive from monocytes that differentiate in the bone marrow and circulate through tissues via the blood and lymphatics. Circulating monocytes are very plastic and differentiate into macrophages with specialized functions upon entering tissues. Specialized monocyte/macrophage subsets have been difficult to differentiate based on cell surface markers. Here, using a combination of “pan” monocyte/macrophage markers and flow cytometry, we asked whether myeloperoxidase (MPO) could be used as a marker of pro-inflammatory monocyte/macrophage subsets. MPO is of interest because of its potent microbicidal activity. In wild-type SPF housed mice, we found that MPO+ monocytes/macrophages were present in peripheral blood, spleen, small and large intestines, and mesenteric lymph nodes, but not the central nervous system. Only monocytes/macrophages that expressed cell surface F4/80 and/or Ly6C co-expressed MPO with the highest expression in F4/80HiLy6CHi subsets regardless of tissue. These cumulative data indicate that MPO expression can be used as an additional marker to differentiate between monocyte/macrophage subsets with pro-inflammatory and microbicidal activity in a variety of tissues.
Curcumin Induces Apoptosis of Chemoresistant Lung Cancer Cells via ROS-Regulated p38 MAPK Phosphorylation
Authors: Wu Ming-Fang , Huang Yen-Hsiang , Chiu Ling-Yen , Cherng Shur-Hueih , Sheu Gwo-Tarng , Yang Tsung-Ying
Published: July 2022

This study aimed to challenge chemoresistance by curcumin (CUR) with drug-selected human lung cancer A549 sublines that continuously proliferate in the present of docetaxel (DOC) and vincristine (VCR). Their sensitivities to CUR were measured by MTT assay and the particular intracellular reactive oxygen species (ROS) was detected by fluorescence activated cell sorting (FACS) analysis. Apoptosis was analyzed by Annexin V assay of the flow cytometry. Inhibitors and RNA interference were used to examine the signaling pathway regulated by the kinases. The obtained data demonstrated that CUR induces chemoresistant cell apoptosis by generating ROS and application of N-acetylcysteine (NAC) blocks ROS production, resulting in apoptosis suppression. Phosphorylation of extracellular regulated kinase (ERK), p38 MAPK, and eIF-2α were increased but c-Jun N-terminal kinase (JNK) did not increase when chemoresistant cells were treated with CUR. Downregulation of ERK and p38 MAPK phosphorylation by their inhibitors had no effect on CUR-induced apoptosis. Interestingly, the knockdown of p38 MAPK with shRNA significantly reduced CUR-induced apoptosis on the chemoresistant sublines. Phosphorylation of the eIF-2α protein was inhibited when p38 MAPK was knocked down in DOC-resistant A549 cells, but a high level of phosphorylated eIF-2α protein remained on the VCR-resistant A549 cells when p38 MAPK was knocked down. These data confirmed that CUR-augmented ROS potently induced apoptosis via upregulated p38 MAPK phosphorylation. Therefore, activated p38 MAPK is considered a pro-apoptotic signal for CUR-induced apoptosis of chemoresistant human lung cancer cells.
Boron Nitride Nanoparticles Loaded with a Boron-Based Hybrid as a Promising Drug Carrier System for Alzheimer’s Disease Treatment
Authors: Yıldırım Özge Çağlar , Arslan Mehmet Enes , Öner Sena , Cacciatore Ivana , Di Stefano Antonio , Mardinoglu Adil , Turkez Hasan
Published: July 2022

The search for an innovative and effective drug delivery system that can carry and release targeted drugs with enhanced activity to treat Alzheimer’s disease has received much attention in the last decade. In this study, we first designed a boron-based drug delivery system for effective treatment of AD by integrating the folic acid (FA) functional group into hexagonal boron nitride (hBN) nanoparticles (NPs) through an esterification reaction. The hBN-FA drug carrier system was assembled with a new drug candidate and a novel boron-based hybrid containing an antioxidant as BLA, to constitute a self-assembled AD nano transport system. We performed molecular characterization analyses by using UV-vis spectroscopy, Fourier transform infrared spectrophotometer (FTIR), scanning electron microscope (SEM), Energy-dispersive X-ray spectroscopy (EDS) and Zeta potential investigations. Second, we tested the anti-Alzheimer properties of the carrier system on a differentiated neuroblastoma (SHSY5-Y) cell line, which was exposed to beta-amyloid (1–42) peptides to stimulate an experimental in vitro AD model. Next, we performed cytotoxicity analyses of synthesized molecules on the human dermal fibroblast cell line (HDFa) and the experimental AD model. Cytotoxicity analyses showed that even higher concentrations of the carrier system did not enhance the toxicological outcome in HDFa cells. Drug loading analyses reported that uncoated hBN nano conjugate could not load the BLA, whereas the memantine loading capacity of hBN was 84.3%. On the other hand, memantine and the BLA loading capacity of the hBN-FA construct was found to be 95% and 97.5%, respectively. Finally, we investigated the neuroprotective properties of the nano carrier systems in the experimental AD model. According to the results, 25 µg/mL concentrations of hBN-FA+memantine (94% cell viability) and hBN-FA+BLA (99% cell viability) showed ameliorative properties against beta-amyloid (1–42) peptide toxicity (50% cell viability). These results were generated through the use of flow cytometry, acetylcholinesterase (AChE) and antioxidant assays. In conclusion, the developed drug carrier system for AD treatment showed promising potential for further investigations and enlightened neuroprotective capabilities of boron molecules to treat AD and other neurodegenerative diseases. On the other hand, enzyme activity, systematic toxicity analyses, and animal studies should be performed to understand neuroprotective properties of the designed carrier system comprehensively.
Sexual Dimorphism in Brown Adipose Tissue Activation and White Adipose Tissue Browning
Authors: Gómez-García Iker , Trepiana Jenifer , Fernández-Quintela Alfredo , Giralt Marta , Portillo María P.
Published: July 2022

The present narrative review gathers the studies reported so far, addressing sex differences in the effects of cold exposure, feeding pattern and age on brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning. In rodents, when exposed to decreasing temperatures, females activate thermogenesis earlier. Results obtained in humans go in the same line, although they do not provide results as solid as those obtained in rodents. Regarding the effects of overfeeding, interesting sex differences on BAT thermogenic capacity have been reported, and the greater or lower sensitivity of each sex to this dietary situation seems to be dependent on the type of feeding. In the case of energy restriction, females are more sensitive than males. In addition, sex differences have also been observed in thermogenesis changes induced by phenolic compound administration. During sexual development, an increase in BAT mass and BAT activity takes place. This phenomenon is greater in boys than in girls, probably due to its relation to muscle-mass growth. The opposite situation takes place during ageing, a lifespan period where thermogenic capacity declines, this being more acute in men than in women. Finally, the vast majority of the studies have reported a higher susceptibility to developing WAT browning amongst females. The scarcity of results highlights the need for further studies devoted to analysing this issue, in order to provide valuable information for a more personalised approach.
An Integrated Proteomic and Glycoproteomic Investigation Reveals Alterations in the N-Glycoproteomic Network Induced by 2-Deoxy-D-Glucose in Colorectal Cancer Cells
Authors: Ma Cheng , Tsai Hong-Yuan , Zhang Qi , Senavirathna Lakmini , Li Lian , Chin Lih-Shen , Chen Ru , Pan Sheng
Published: July 2022

As a well-known glycolysis inhibitor for anticancer treatment, 2-Deoxy-D-glucose (2DG) inhibits the growth and survival of cancer cells by interfering with the ATP produced by the metabolism of D-glucose. In addition, 2DG inhibits protein glycosylation in vivo by competing with D-mannose, leading to endoplasmic reticulum (ER) stress and unfolded protein responses in cancer cells. However, the molecular details underlying the impact of 2DG on protein glycosylation remain largely elusive. With an integrated approach to glycoproteomics and proteomics, we characterized the 2DG-induced alterations in N-glycosylation, as well as the cascading impacts on the whole proteome using the HT29 colorectal cancer cell line as a model system. More than 1700 site-specific glycoforms, represented by unique intact glycopeptides (IGPs), were identified. The treatment of 2DG had a broad effect on the N-glycoproteome, especially the high-mannose types. The glycosite occupancy of the high-mannose N-glycans decreased the most compared with the sialic acid and fucose-containing N-glycans. Many of the proteins with down-regulated high-mannose were implicated in functional networks related to response to topologically incorrect protein, integrin-mediated signaling, lysosomal transport, protein hydroxylation, vacuole, and protein N-glycosylation. The treatment of 2DG also functionally disrupted the global cellular proteome, evidenced by significant up-regulation of the proteins implicated in protein folding, endoplasmic reticulum, mitochondrial function, cellular respiration, oxidative phosphorylation, and translational termination. Taken together, these findings reveal the complex changes in protein glycosylation and expression underlying the various effects of 2DG on cancer cells, and may provide insightful clues to inform therapeutic development targeting protein glycosylation.
Effects of Probiotic Supplementation during Pregnancy on the Future Maternal Risk of Metabolic Syndrome
Authors: Obuchowska Aleksandra , Gorczyca Kamila , Standyło Arkadiusz , Obuchowska Karolina , Kimber-Trojnar Żaneta , Wierzchowska-Opoka Magdalena , Leszczyńska-Gorzelak Bożena
Published: July 2022

Probiotics are live microorganisms that induce health benefits in the host. Taking probiotics is generally safe and well tolerated by pregnant women and their children. Consumption of probiotics can result in both prophylactic and therapeutic effects. In healthy adult humans, the gut microbiome is stable at the level of the dominant taxa: Bacteroidetes, Firmicutes and Actinobacteria, and has a higher presence of Verrucomicrobia. During pregnancy, an increase in the number of Proteobacteria and Actinobacteria phyla and a decrease in the beneficial species Roseburia intestinalis and Faecalibacterium prausnitzii are observed. Pregnancy is a “window” to the mother’s future health. The aim of this paper is to review studies assessing the potentially beneficial effects of probiotics in preventing the development of diseases that appear during pregnancy, which are currently considered as risk factors for the development of metabolic syndrome, and consequently, reducing the risk of developing maternal metabolic syndrome in the future. The use of probiotics in gestational diabetes mellitus, preeclampsia and excessive gestational weight gain is reviewed. Probiotics are a relatively new intervention that can prevent the development of these disorders during pregnancy, and thus, would reduce the risk of metabolic syndrome resulting from these disorders in the mother’s future.
Orientation Polarization Spectroscopy—Toward an Atomistic Understanding of Dielectric Relaxation Processes
Authors: Kremer Friedrich , Kipnusu Wycliffe Kiprop , Fränzl Martin
Published: July 2022

The theory of orientation polarization and dielectric relaxation was developed by P. Debye more than 100 years ago. It is based on approximating a molecule by a sphere having one or more dipole moments. By that the detailed intra- and intermolecular interactions are explicitly not taken into consideration. In this article, the principal limitations of the Debye approximation are discussed. Taking advantage of the molecular specificity of the infrared (IR) spectral range, measurements of the specific IR absorption of the stretching vibration υ(OH) (at 3370 cm−1) and the asymmetric υas(CH2) (at 2862.9 cm−1) are performed in dependence on the frequency and the strength of external electric fields and at varying temperature. The observed effects are interpreted as caused by orientation polarization of the OH and the adjacent CH2 moieties.
HDL Cholesterol Efflux and Serum Cholesterol Loading Capacity Alterations Associate to Macrophage Cholesterol Accumulation in FH Patients with Achilles Tendon Xanthoma
Authors: Adorni Maria Pia , Biolo Marta , Zimetti Francesca , Palumbo Marcella , Ronda Nicoletta , Scarinzi Paolo , Simioni Paolo , Lupo Maria Giovanna , Ferri Nicola , Previato Lorenzo , Bernini Franco , Zambon Alberto
Published: July 2022

Achilles tendon xanthoma (ATX) formation involves macrophage cholesterol accumulation within the tendon, similar to that occurring in atheroma. Macrophage cholesterol homeostasis depends on serum lipoprotein functions, namely the high-density lipoprotein (HDL) capacity to promote cell cholesterol efflux (cholesterol efflux capacity, CEC) and the serum cholesterol loading capacity (CLC). We explored the HDL-CEC and serum CLC, comparing 16 FH patients with ATX to 29 FH patients without ATX. HDL-CEC through the main efflux mechanisms mediated by the transporters ATP binding cassette G1 (ABCG1) and A1 (ABCA1) and the aqueous diffusion (AD) process was determined by a cell-based radioisotopic technique and serum CLC fluorimetrically. Between the two groups, no significant differences were found in terms of plasma lipid profile. A trend toward reduction of cholesterol efflux via AD and a significant increase in ABCA1-mediated HDL-CEC (+18.6%) was observed in ATX compared to no ATX patients. In ATX-presenting patients, ABCG1-mediated HDL-CEC was lower (−11%) and serum CLC was higher (+14%) compared to patients without ATX. Considering all the patients together, ABCG1 HDL-CEC and serum CLC correlated with ATX thickness inversely (p = 0.013) and directly (p < 0.0001), respectively. In conclusion, lipoprotein dysfunctions seem to be involved in ATX physiopathology and progression in FH patients.
Linguistic Profiling of Text Genres: An Exploration of Fictional vs. Non-Fictional Texts
Authors: Mendhakar Akshay
Published: July 2022

Texts are composed for multiple audiences and for numerous purposes. Each form of text follows a set of guidelines and structure to serve the purpose of writing. A common way of grouping texts is into text types. Describing these text types in terms of their linguistic characteristics is called ‘linguistic profiling of texts’. In this paper, we highlight the linguistic features that characterize a text type. The findings of the present study highlight the importance of parts of speech distribution and tenses as the most important microscopic linguistic characteristics of the text. Additionally, we demonstrate the importance of other linguistic characteristics of texts and their relative importance (top 25th, 50th and 75th percentile) in linguistic profiling. The results are discussed with the use case of genre and subgenre classifications with classification accuracies of 89 and 73 percentile, respectively.
Mechanical Acaricides Active against the Blacklegged Tick, Ixodes scapularis
Authors: Richardson Elise A. , Ponnusamy Loganathan , Roe R. Michael
Published: July 2022

Cases of Lyme disease in humans are on the rise in the United States and Canada. The vector of the bacteria that causes this disease is the blacklegged tick, Ixodes scapularis. Current control methods for I. scapularis mainly involve chemical acaricides. Unfortunately, ticks are developing resistance to these chemicals, and more and more, the public prefers non-toxic alternatives to chemical pesticides. We discovered that volcanic glass, ImergardTM WP, and other industrial minerals such as Celite 610 were efficacious mechanical insecticides against mosquitoes, filth flies, and agricultural pests. In this report, when 6–10- and 50–70-day old unfed I. scapularis nymphs were dipped for 1–2 s into Celite, the time to 50% mortality (LT50) was 66.8 and 81.7 min, respectively, at 30 °C and 50% relative humidity (RH). The LT50 was actually shorter at a higher 70% RH, 43.8 min. Scanning electron microscopy showed that the ticks were coated over most of their body surface, including partial to almost total coverage of the opening to their respiratory system. The other mechanical insecticide, Imergard, had similar efficacy against blacklegged unfed nymphs with an LT50 at 30 °C and 50% RH of 70.4 min. Although more research is needed, this study suggests that industrial minerals could be used as an alternative to chemical pesticides to control ticks and Lyme disease.
The Interdisciplinary Management of Lung Cancer in the European Community
Authors: Bertolaccini Luca , Mohamed Shehab , Bardoni Claudia , Lo Iacono Giorgio , Mazzella Antonio , Guarize Juliana , Spaggiari Lorenzo
Published: July 2022

Lung cancer continues to be the largest cause of cancer-related mortality among men and women globally, accounting for around 27% of all cancer-related deaths. Recent advances in lung cancer medicines, particularly for non-small-cell lung cancer (NSCLC), have increased the need for multidisciplinary disease care, thereby enhancing patient outcomes and quality of life. Different studies in the European community have evaluated the impact of multidisciplinary care on outcomes for lung cancer patients, including its impact on survival, adherence to guideline treatment, utilization of all treatment modalities, timeliness of treatment, patient satisfaction, quality of life, and referral to palliative care. This publication will examine the roles and duties of all multidisciplinary members and the influence of multidisciplinary care on lung cancer outcomes in Europe. Multidisciplinary treatment is the foundation of lung cancer treatment. The optimal setting for interdisciplinary collaboration between specialists with complementary functions is multidisciplinary meetings. Multidisciplinary care in lung cancer facilitates the delivery of a high-quality service, which may improve lung cancer patients’ survival, utilization of all treatment modalities, adherence to guideline management, and quality of life, despite the fact that only limited observational data have demonstrated these results. To confirm the relationship between multidisciplinary treatment and improved lung cancer patient outcomes, however, further research is required.