bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction of Riboswitches for Screening Antibacterial Agents from Forest Plants
Authors: Liu Zhanjun , Li Taotao , Zhang Xingyu , Liu Shiquan , Hu Zhiyuan , Yu Songlin , Zhou Xiaohong
Published: February 2024

Forest plants contain abundant natural products, providing a valuable resource for obtaining compounds with various functional activities, such as antimicrobial, lipid-lowering, and immunoregulatory activities. The development of efficient tools for rapidly screening functional natural products from forest plants is essential for human health. In this study, we constructed some transgenic strains (Escherichia coli) containing Ahy1-1 riboswitches that respond to cyclic di-guanylate (c-di-GMP), serving as a novel bacteriostatic target. The Ahy1-1 riboswitches contained the LacZ gene (encoding β-galactosidase) and c-di-GMP aptamer in order to monitor β-galactosidase activity due to changes in c-di-GMP. After co-incubating with extracts from fresh orange peel, fresh tea leaves, and Fuzhuan brick tea, the orange peel exhibited a significant inhibition of c-di-GMP generation. The extract of tea leaves had a minor influence on the synthesis of c-di-GMP, whereas Fuzhuan brick tea, which is fermented by various microorganisms, inhibited the production of c-di-GMP. Our constructed transgenic strains could be used to screen for antibacterial agents from forest plants. Beyond antibacterial agents, other functional compounds from forest plants could be selected by designing diverse riboswitches.
Rapid Acidification and Off-Flavor Reduction of Pea Protein by Fermentation with Lactic Acid Bacteria and Yeasts
Authors: Zipori Dor , Hollmann Jana , Rigling Marina , Zhang Yanyan , Weiss Agnes , Schmidt Herbert
Published: February 2024

Pea protein is widely used as an alternative protein source in plant-based products. In the current study, we fermented pea protein to reduce off-flavor compounds, such as hexanal, and to produce a suitable fermentate for further processing. Laboratory fermentations using 5% (w/v) pea protein suspension were carried out using four selected lactic acid bacteria (LAB) strains, investigating their growth and acidification capabilities in pea protein. Rapid acidification of pea protein was achieved with Lactococcus lactis subsp. lactis strain LTH 7123. Next, this strain was co-inoculated together with either the yeasts Kluyveromyces lactis LTH 7165, Yarrowia lipolytica LTH 6056, or Kluyveromyces marxianus LTH 6039. Fermentation products of the mixed starter cultures and of the single strains were further analyzed by gas chromatography coupled with mass spectrometry to quantify selected volatile flavor compounds. Fermentation with L. lactis LTH 7123 led to an increase in compounds associated with the “beany” off-flavors of peas, including hexanal. However, significant reduction in those compounds was achieved after fermentation with Y. lipolytica LTH 6056 with or without L. lactis LTH 7123. Thus, fermentation using co-cultures of LAB and yeasts strains could prove to be a valuable method for enhancing quality attributes of pea protein-based products.
Assessment of Technological and Sensory Properties, Digestibility, and Bioactive Compounds in Polentas from Different Maize Genotypes
Authors: Bongianino Nicolás Francisco , Steffolani María Eugenia , Rodríguez Marianela Desiree , Bustos Mariela Cecilia , Biasutti Carlos Alberto , León Alberto Edel
Published: February 2024

The sensory profile of polenta and the connections between technological attributes and varieties of maize have not been extensively studied. Thus, it is necessary to understand the possible effect of its consumption on consumers’ health in terms of postprandial glucose levels and molecules associated with healthy activities. This work aims to study polenta’s technological and sensory properties from different maize genotypes and evaluate their digestibility and the potential contribution of bioactive compounds on health. A commercial hybrid, two open-pollinated varieties, and three inbred lines were used. Grain physical determinations and physical-chemical semolina traits were determined. Polenta’s technological quality was evaluated after simulated cooking. In vitro digestion was performed for polentas, and a sensory evaluation test was conducted. A significant correlation was found between semolina polyphenols and rapidly digestible starch (r = −0.6). Panellists characterised the genotype C6006 as having a good flavour, sandier mouthfeel, and low consistency. Also, the polenta from the hybrid exhibited sensory attributes more closely resembling commercial polenta in terms of maize odour, flavour, and consistency. The higher content of polyphenols presents in semolina affected the digestion of polenta, showing a lower proportion of rapidly digestible starch and a lower amount of bioaccessible protein fraction.
Hesperitin-Copper(II) Complex Regulates the NLRP3 Pathway and Attenuates Hyperuricemia and Renal Inflammation
Authors: Peng Xi , Liu Kai , Hu Xing , Gong Deming , Zhang Guowen
Published: February 2024

Background: Hyperuricaemia (HUA) is a disorder of purine metabolism in the body. We previously synthesized a hesperitin (Hsp)-Cu(II) complex and found that the complex possessed strong uric acid (UA)-reducing activity in vitro. In this study we further explored the complex’s UA-lowering and nephroprotective effects in vivo. Methods: A mouse with HUA was used to investigate the complex’s hypouricemic and nephroprotective effects via biochemical analysis, RT-PCR, and Western blot. Results: Hsp-Cu(II) complex markedly decreased the serum UA level and restored kidney tissue damage to normal in HUA mice. Meanwhile, the complex inhibited liver adenosine deaminase (ADA) and xanthine oxidase (XO) activities to reduce UA synthesis and modulated the protein expression of urate transporters to promote UA excretion. Hsp-Cu(II) treatment significantly suppressed oxidative stress and inflammatory in the kidney, reduced the contents of cytokines and inhibited the activation of the nucleotide-binding oligomerization domain (NOD)-like receptor thermal protein domain associated protein 3 (NLRP3) inflammatory pathway. Conclusions: Hsp-Cu(II) complex reduced serum UA and protected kidneys from renal inflammatory damage and oxidative stress by modulating the NLRP3 pathway. Hsp-Cu(II) complex may be a promising dietary supplement or nutraceutical for the therapy of hyperuricemia.
Escape Criteria Using Hybrid Picard S-Iteration Leading to a Comparative Analysis of Fractal Mandelbrot Sets Generated with S-Iteration
Authors: Srivastava Rekha , Tassaddiq Asifa , Kasmani Ruhaila Md
Published: February 2024

Fractals are a common characteristic of many artificial and natural networks having topological patterns of a self-similar nature. For example, the Mandelbrot set has been investigated and extended in several ways since it was first introduced, whereas some authors characterized it using various complex functions or polynomials, others generalized it using iterations from fixed-point theory. In this paper, we generate Mandelbrot sets using the hybrid Picard S-iterations. Therefore, an escape criterion involving complex functions is proved and used to provide numerical and graphical examples. We produce a wide range of intriguing fractal patterns with the suggested method, and we compare our findings with the classical S-iteration. It became evident that the newly proposed iteration method produces novel images that are more spontaneous and fascinating than those produced by the S-iteration. Therefore, the generated sets behave differently based on the parameters involved in different iteration schemes.
miR-665-Mediated Regulation of AHCYL2 and BVES Genes in Recurrent Implantation Failure
Authors: Cho Sung Hwan , Kim Young Myeong , An Hui Jeong , Kim Ji Hyang , Kim Nam Keun
Published: February 2024

The primary goal of this investigation was to identify mRNA targets affected by dysregulated miRNAs in RIF. This was accomplished by comprehensively analyzing mRNA and miRNA expression profiles in two groups: female subjects with normal reproductive function (control, n = 5) and female subjects experiencing recurrent implantation failure (RIF, n = 5). We conducted transcriptome sequencing and small RNA sequencing on endometrial tissue samples from these cohorts. Subsequently, we validated a selection of intriguing findings using real-time PCR with samples from the same cohort. In total, our analysis revealed that 929 mRNAs exhibited differential expression patterns between the control and RIF patient groups. Notably, our investigation confirmed the significant involvement of dysregulated genes in the context of RIF. Furthermore, we uncovered promising correlation patterns within these mRNA/miRNA pairs. Functional categorization of these miRNA/mRNA pairs highlighted that the differentially expressed genes were predominantly associated with processes such as angiogenesis and cell adhesion. We identified new target genes that are regulated by miR-665, including Blood Vessel Epicardial Substance (BVES) and Adenosylhomocysteinase like 2 (AHCYL2). Our findings suggest that abnormal regulation of genes involved in angiogenesis and cell adhesion, including BVES and AHCYL2, contributes to the endometrial dysfunction observed in women with recurrent implantation failure (RIF) compared to healthy women.
Hmo1 Promotes Efficient Transcription Elongation by RNA Polymerase I in Saccharomyces cerevisiae
Authors: Huffines Abigail K. , Schneider David A.
Published: February 2024

RNA polymerase I (Pol I) is responsible for synthesizing the three largest eukaryotic ribosomal RNAs (rRNAs), which form the backbone of the ribosome. Transcription by Pol I is required for cell growth and, therefore, is subject to complex and intricate regulatory mechanisms. To accomplish this robust regulation, the cell engages a series of trans-acting transcription factors. One such factor, high mobility group protein 1 (Hmo1), has long been established as a trans-acting factor for Pol I in Saccharomyces cerevisiae; however, the mechanism by which Hmo1 promotes rRNA synthesis has not been defined. Here, we investigated the effect of the deletion of HMO1 on transcription elongation by Pol I in vivo. We determined that Hmo1 is an important activator of transcription elongation, and without this protein, Pol I accumulates across rDNA in a sequence-specific manner. Our results demonstrate that Hmo1 promotes efficient transcription elongation by rendering Pol I less sensitive to pausing in the G-rich regions of rDNA.
Nutrition, Physical Activity and Smoking Habit in the Italian General Adult Population: CUORE Project Health Examination Survey 2018–2019
Authors: Donfrancesco Chiara , Buttari Brigitta , Marcozzi Benedetta , Sieri Sabina , Di Lonardo Anna , Lo Noce Cinzia , Profumo Elisabetta , Vespasiano Francesca , Agnoli Claudia , Vannucchi Serena , Silano Marco , Galeone Daniela , Bellisario Paolo , Vaia Francesco , Palmieri Luigi
Published: February 2024

Background: Tobacco consumption, incorrect nutrition and insufficient physical activity/sedentariness represent modifiable NCDs risk factors in Western countries. To evaluate recent lifestyle indicators in Italy, data from the national Health Examination Survey (HES), implemented in 2018–2019 within the CUORE Project, were assessed. Methods: Age–sex standardized results from random samples of Italian general population (35–74 years) were reported by sex, age-class, educational level and geographical area. From 2106 participants, 2090 were considered for smoking habit, 2016 for physical activity and 1578 for nutrition. Standardized questionnaires were used for smoking habit and physical activity, and the EPIC questionnaire for nutrition. Results: Total cigarette current smokers were 23% in men and 19% in women; sedentariness during leisure time was 34% in men and 45% in women and at work 45% and 47% in men and women, respectively. Prevalence of balanced eating behaviours for vegetables was 28% in men and 39% in women; and for fruits 50% and 52%, respectively; prevalence of correct lifestyle (not smoker, regular physical activity and following at least five correct eating behaviours) was 7% and 12% for men and women, respectively. Conclusions: In 2018–2019, levels of unhealthy lifestyles were found to be still epidemic and basically stable compared to 10 years earlier (slight smoking habit decrease, slight sedentariness increase and slight nutrition improvements); intersectoral strategies and monitoring need to be continued.
Exploring the Viability and Acceptance of Nudge in Public Policies for Health Promotion
Authors: Forte Teresa , Santinha Gonçalo , Patrão Marta
Published: February 2024

Background: Behaviorally informed interventions, such as nudging, encourage actions intended to promote longer and healthier lives. Holding significant potential for influencing health policies and healthcare practices, these interventions are partaking of a shift in governance and public health policymaking. However, a substantial knowledge gap remains regarding the feasibility and appropriateness of implementing policies that draw on nudge. Methods: Ae survey on nudge’s acceptability) was adapted to the Portuguese context to access attitudes towards 16 nudge measures. The research focused on evaluating attitudes among political science and public administration BSc and MSc students from nine Portuguese universities, and analyzing the relationship between these attitudes, sociodemographic characteristics, and sociopolitical attitudes. The data analysis involved the application of descriptive and inferential statistics. Results: The participants exhibited a moderate-to-high level of approval for various nudge measures, particularly those related to nutrition and public education/awareness raising. The study identified a nuanced relationship between the level of intrusiveness of nudges and their public approval, indicating that interventions preserving the architecture of choice gathered higher acceptance compared to more intrusive approaches. Notably, approval was associated with a high level of trust in social groups and a low propensity for risk-taking and alcohol consumption. Conclusions: This study not only sheds light on the types of nudge measures that are likely to be more acceptable for promoting healthy behaviors, but also establishes a crucial link between behavioral interventions and healthcare policies. Understanding the nuanced factors influencing the public acceptance of nudges contributes to the discourse on the implementation of behaviorally informed health policies and emphasizes the importance of tailoring interventions to align with public values and preferences.
Sibling Violence and Bullying Behaviors in Peers: The Mediational Role of Self-Esteem
Authors: Mota Catarina Pinheiro , Sousa Joana Rita , Relva Inês Carvalho
Published: February 2024

In the context of the existing research on families, sibling violence is a less explored area. However, it has seemingly received more attention recently, and it can assume a relevant role in understanding the maladaptive behavior of youngsters and bullying. Additionally, adolescents involved in bullying and self-esteem are associated with disruptive violence inside the family context. This study’s sample consisted of 286 students, aged between 12 and 17 years, from both sexes. This study intends to explore the association between sibling violence and bullying behavior in peers and the mediator effect of self-esteem. The measures for data collection were a demographic questionnaire, the Social Exclusion and School Violence Questionnaire, The Revised Conflict Tactics Scales (Portuguese version for siblings), and the Rosenberg Self-Esteem Scale. The results show a negative effect between negotiation in the sibling relationship (victimization) and social exclusion and verbal aggression related to bullying behavior. Self-esteem represents a total and negative mediator in this connection. Our results also show a variety of indirect outcomes amongst the negotiation dimension, psychological aggression and injury between siblings, and the social exclusion and verbal aggression dimensions (on the aggression and victimization scales). The results will be discussed according to the attachment theory but considering the importance of affective bonds with siblings as a predisposing factor to an adaptive development course.
Evaluation of the Performance of Rapid Diagnostic Tests for Malaria Diagnosis and Mapping of Different Plasmodium Species in Mali
Authors: Dembélé Pascal , Cissoko Mady , Diarra Adama Zan , Doumbia Lassana , Koné Aïssata , Magassa Mahamadou H. , Mehadji Maissane , Thera Mahamadou A. , Ranque Stéphane
Published: February 2024

Background: The first-line diagnosis of malaria in Mali is based on the use of rapid diagnostic tests (RDT) that detect the Histidin Rich Protein 2 (HRP2) antigen specific to Plasmodium falciparum. Our study, based on a real-time polymerase chain reaction (qPCR) gold standard, aimed to describe the distribution of the Plasmodium species in each administrative region of Mali and to assess the performance of RDTs. Methods: We randomly selected 150 malaria-negative and up to 30 malaria-positive RDTs in 41 sites distributed in 9 regions of Mali. DNA extracted from the RDT nitrocellulose strip was assayed with a pan-Plasmodium qPCR. Positive samples were then analyzed with P. falciparum-, P. malariae-, P. vivax-, or P. ovale-specific qPCRs. Results: Of the 1496 RDTs, 258 (18.6%) were positive for Plasmodium spp., of which 96.9% were P. falciparum. The P. vivax prevalence reached 21.1% in the north. RDT displayed acceptable diagnostic indices; the lower CI95% bounds of Youden indices were all ≥0.50, except in the north (Youden index 0.66 (95% CI [0.44–0.82]) and 0.63 (95% CI [0.33–0.83]. Conclusions: Overall, RDT diagnostic indices are adequate for the biological diagnosis of malaria in Mali. We recommend the use of RDTs detecting P. vivax-specific antigens in the north.
Ubuntu Is a Critical Component in the Fight against Human Immunodeficiency Virus and Tuberculosis Stigma: Nursing Students’ Perceptions
Authors: Rasweswe Melitah Molatelo , Kgatla Nancy Mamoeng , Ramavhoya Irene Thifhelimbilu , Mulaudzi Fhumulani Mavis
Published: February 2024

Stigma is one of the documented barriers to achieving universal access to human immunodeficiency virus (HIV) and tuberculosis (TB) prevention, treatment, care, and support programs. The lack of African social theories to emphasize these issues may be the cause of the continent’s failure to reduce stigma. We can use Ubuntu, an African philosophy that emphasizes sociability and ethics, to deepen our understanding of how to reduce HIV- and TB-related stigma in South Africa. In many African regions, Ubuntu values and principles were found to assist in reducing problems related to HIV. Ubuntu is a comprehensive phrase used by Africans to signify the characteristics that incorporate the core human virtues of compassion and humanity. We explored the perceptions of nursing students regarding the use of Ubuntu in the fight against HIV and TB stigma. Qualitative participatory research was used to engage all first- and second-level nursing students enrolled for the 2023 academic year at the selected university in South Africa. Purposive sampling was used to recruit the participants. An interactive workshop was used to gather data. The data from the recordings and flip charts were analysed together. Throughout the study, trustworthiness and ethical principles were upheld. Two primary themes emerged as expressions of Ubuntu in relation to a reduction in HIV and TB stigma and recognition of Ubuntu as a tool to combat stigma associated with HIV and TB. This confirms that within Ubuntu, there are elements that might be applied to reduce stigma attached to HIV and TB.
Association of Blood Metabolomics Biomarkers with Brain Metabolites and Patient-Reported Outcomes as a New Approach in Individualized Diagnosis of Schizophrenia
Authors: Krzyściak Wirginia , Bystrowska Beata , Karcz Paulina , Chrzan Robert , Bryll Amira , Turek Aleksander , Mazur Paulina , Śmierciak Natalia , Szwajca Marta , Donicz Paulina , Furman Katarzyna , Pilato Fabio , Kozicz Tamas , Popiela Tadeusz , Pilecki Maciej
Published: February 2024

Given its polygenic nature, there is a need for a personalized approach to schizophrenia. The aim of the study was to select laboratory biomarkers from blood, brain imaging, and clinical assessment, with an emphasis on patients’ self-report questionnaires. Metabolomics studies of serum samples from 51 patients and 45 healthy volunteers, based on the liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS/MS), led to the identification of 3 biochemical indicators (cortisol, glutamate, lactate) of schizophrenia. These metabolites were sequentially correlated with laboratory tests results, imaging results, and clinical assessment outcomes, including patient self-report outcomes. The hierarchical cluster analysis on the principal components (HCPC) was performed to identify the most homogeneous clinical groups. Significant correlations were noted between blood lactates and 11 clinical and 10 neuroimaging parameters. The increase in lactate and cortisol were significantly associated with a decrease in immunological parameters, especially with the level of reactive lymphocytes. The strongest correlations with the level of blood lactate and cortisol were demonstrated by brain glutamate, N-acetylaspartate and the concentrations of glutamate and glutamine, creatine and phosphocreatine in the prefrontal cortex. Metabolomics studies and the search for associations with brain parameters and self-reported outcomes may provide new diagnostic evidence to specific schizophrenia phenotypes.
Autoimmune Autonomic Neuropathy: From Pathogenesis to Diagnosis
Authors: Nakane Shunya , Koike Haruki , Hayashi Tomohiro , Nakatsuji Yuji
Published: February 2024

Autoimmune autonomic ganglionopathy (AAG) is a disease of autonomic failure caused by ganglionic acetylcholine receptor (gAChR) autoantibodies. Although the detection of autoantibodies is important for distinguishing the disease from other neuropathies that present with autonomic dysfunction, other factors are important for accurate diagnosis. Here, we provide a comprehensive review of the clinical features of AAG, highlighting differences in clinical course, clinical presentation, and laboratory findings from other neuropathies presenting with autonomic symptoms. The first step in diagnosing AAG is careful history taking, which should reveal whether the mode of onset is acute or chronic, followed by an examination of the time course of disease progression, including the presentation of autonomic and extra-autonomic symptoms. AAG is a neuropathy that should be differentiated from other neuropathies when the patient presents with autonomic dysfunction. Immune-mediated neuropathies, such as acute autonomic sensory neuropathy, are sometimes difficult to differentiate, and therefore, differences in clinical and laboratory findings should be well understood. Other non-neuropathic conditions, such as postural orthostatic tachycardia syndrome, chronic fatigue syndrome, and long COVID, also present with symptoms similar to those of AAG. Although often challenging, efforts should be made to differentiate among the disease candidates.
Generation of Endotoxin-Specific Monoclonal Antibodies by Phage and Yeast Display for Capturing Endotoxin
Authors: Fux Alexandra C. , Casonato Melo Cristiane , Schlahsa Laura , Burzan Nico B. , Felsberger André , Gessner Isabel , Fauerbach Jonathan A. , Horejs-Hoeck Jutta , Droste Miriam , Siewert Christiane
Published: February 2024

Endotoxin, a synonym for lipopolysaccharide (LPS), is anchored in the outer membranes of Gram-negative bacteria. Even minute amounts of LPS entering the circulatory system can have a lethal immunoactivating effect. Since LPS is omnipresent in the environment, it poses a great risk of contaminating any surface or solution, including research products and pharmaceuticals. Therefore, monitoring LPS contamination and taking preventive or decontamination measures to ensure human safety is of the utmost importance. Nevertheless, molecules used for endotoxin detection or inhibition often suffer from interferences, low specificity, and low affinity. For this reason, the selection of new binders that are biocompatible, easy to produce, and that can be used for biopharmaceutical applications, such as endotoxin removal, is of high interest. Powerful techniques for selecting LPS-binding molecules in vitro are display technologies. In this study, we established and compared the selection and production of LPS-specific, monoclonal, human single-chain variable fragments (scFvs) through two display methods: yeast and phage display. After selection, scFvs were fused to a human constant fragment crystallizable (Fc). To evaluate the applicability of the constructs, they were conjugated to polystyrene microbeads. Here, we focused on comparing the functionalized beads and their LPS removal capacity to a polyclonal anti-lipid A bead. Summarized, five different scFvs were selected through phage and yeast display, with binding properties comparable to a commercial polyclonal antibody. Two of the conjugated scFv-Fcs outperformed the polyclonal antibody in terms of the removal of LPS in aqueous solution, resulting in 265 times less residual LPS in solution, demonstrating the potential of display methods to generate LPS-specific binding molecules.
Insights into Hyperparathyroidism–Jaw Tumour Syndrome: From Endocrine Acumen to the Spectrum of CDC73 Gene and Parafibromin-Deficient Tumours
Authors: Gheorghe Ana-Maria , Sima Oana-Claudia , Florescu Alexandru Florin , Ciuche Adrian , Nistor Claudiu , Sandru Florica , Carsote Mara
Published: February 2024

A total of 1 out of 10 patients with primary hyperparathyroidism (PHP) presents an underlying genetic form, such as multiple endocrine neoplasia types 1, 2A, etc., as well as hyperparathyroidism–jaw tumour syndrome (HJT). We aimed to summarise the recent data, thus raising more awareness regarding HJT, from the clinical perspective of PHP in association with the challenges and pitfalls of CDC73 genetic testing and parafibromin staining. This narrative review included a sample-focused analysis from the past decade according to a PubMed search. We identified 17 original human studies (≥4 patients per article). The mean age at disease onset was between 20.8 and 39.5 years, while the largest study found that 71% of patients had HJT recognised before the age of 30. Males and females seemed to be equally affected, in contrast with sporadic PHP. PHP represented the central manifestation of HJT, occurring as the first manifestation in up to 85% of HJT cases. A biochemistry panel found a mean serum calcium level above the level of 12 mg/dL in PHP. PTH was elevated in HJT as well, with average values of at least 236.6 pg/mL. The most frequent pathological type in PHP was a parathyroid adenoma, but the incidence of a parathyroid carcinoma was much higher than in non-HJT cases (15% of all parathyroid tumours), with the diagnosis being established between the age of 15 and 37.5. In some families up to 85% of carriers suffered from a parathyroid carcinoma thus indicating that certain CDC73 pathogenic variants may harbour a higher risk. An important issue in HJT was represented by the parafibromin profile in the parathyroid tumours since in HJT both parathyroid adenomas and carcinomas might display a deficient immunoreactivity. Another frequent manifestation in HJT was ossifying fibromas of the jaw (affecting 5.4% to 50% of patients; the largest study found a prevalence of 15.4%). HJT was associated with a wide variety of kidney lesion (mostly: kidney cysts, with a prevalence of up to 75%, and renal tumours involved in 19% of patients). The risk of uterine lesions seemed increased in HJT, especially with concern to leiomyomas, adenofibromas, and adenomyosis. The underlying pathogenic mechanisms and the involvement of CDC73 pathogenic variants and parafibromin expression are yet to be explored. Currently, the heterogeneous expression of parafibromin status and, the wide spectrum of CDC73 mutations including the variety of clinical presentations in HJT, make it difficult to predict the phenotype based on the genotype. The central role of HJT-PHP is, however, the main clinical element, while the elevated risk of parathyroid carcinoma requires a special awareness.
SUMOylation Inhibition Enhances Protein Transcription under CMV Promoter: A Lesson from a Study with the F508del-CFTR Mutant
Authors: Borgo Christian , D’Amore Claudio , Capurro Valeria , Tomati Valeria , Pedemonte Nicoletta , Bosello Travain Valentina , Salvi Mauro
Published: February 2024

Cystic fibrosis (CF) is a genetic disorder caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), a selective anion channel expressed in the epithelium of various organs. The most frequent mutation is F508del. This mutation leads to a misfolded CFTR protein quickly degraded via ubiquitination in the endoplasmic reticulum. Although preventing ubiquitination stabilizes the protein, functionality is not restored due to impaired plasma membrane transport. However, inhibiting the ubiquitination process can improve the effectiveness of correctors which act as chemical chaperones, facilitating F508del CFTR trafficking to the plasma membrane. Previous studies indicate a crosstalk between SUMOylation and ubiquitination in the regulation of CFTR. In this study, we investigated the potential of inhibiting SUMOylation to increase the effects of correctors and enhance the rescue of the F508del mutant across various cell models. In the widely used CFBE41o-cell line expressing F508del-CFTR, inhibiting SUMOylation substantially boosted F508del expression, thereby increasing the efficacy of correctors. Interestingly, this outcome did not result from enhanced stability of the mutant channel, but rather from augmented cytomegalovirus (CMV) promoter-mediated gene expression of F508del-CFTR. Notably, CFTR regulated by endogenous promoters in multiple cell lines or patient cells was not influenced by SUMOylation inhibitors.
Nicotinic Receptors in Human Chromaffin Cells: Characterization, Functional and Physical Interactions between Subtypes and Regulation
Authors: Jiménez-Pompa Amanda , Albillos Almudena
Published: February 2024

This review summarizes our research on nicotinic acetylcholine receptors in human chromaffin cells. Limited research has been conducted in this field on human tissue, primarily due to the difficulties associated with obtaining human cells. Receptor subtypes were characterized here using molecular biology and electrophysiological patch-clamp techniques. However, the most significant aspect of this study refers to the cross-talk between the two main subtypes identified in these cells, the α7- and α3β4* subtypes, aiming to avoid their desensitization. The article also reviews other aspects, including the regulation of their expression, function or physical interaction by choline, Ca2+, and tyrosine and serine/threonine phosphatases. Additionally, the influence of sex on their expression is also discussed.
The Potential Role of Probiotics, Especially Butyrate Producers, in the Management of Gastrointestinal Mucositis Induced by Oncologic Chemo-Radiotherapy
Authors: Cazzaniga Massimiliano , Cardinali Marco , Di Pierro Francesco , Zonzini Giordano Bruno , Palazzi Chiara Maria , Gregoretti Aurora , Zerbinati Nicola , Guasti Luigina , Bertuccioli Alexander
Published: February 2024

Many clinical studies have now highlighted how the composition of the intestinal microbiota can regulate the effects of many oncological therapies. In particular, the modulation of microbial composition has been shown to enhance their efficacy and reduce potential side effects. Numerous adverse events induced by chemotherapy and radiotherapy appear to be strongly associated with an alteration in the intestinal microbiota caused by these treatments. This supports the hypothesis that the modulation or correction of the microbiota may decrease the toxic impact of therapies, improving patient compliance and quality of life. Among the most debilitating disorders related to oncological treatments is certainly mucositis, and recent clinical data highlight how the deficiency of short-chain fatty acids, especially butyrate, and specifically the lack of certain bacterial groups responsible for its production (butyrate producers), is strongly associated with this disorder. It is hypothesized that restoring these elements may influence the onset and severity of adverse events. Therefore, the intake of probiotics, especially butyrate producers, and specifically Clostridium butyricum (CBM588), currently the only cultivable and usable strain with a history of data proving its safety, could be a valuable ally in oncological therapies, reducing the associated discomfort and improving compliance, efficacy, and quality of life for patients.
Whole-Transcriptome Profiling and Functional Prediction of Long Non-Coding RNAs Associated with Cold Tolerance in Japonica Rice Varieties
Authors: Wang Hao , Jia Yan , Bai Xu , Gong Weibin , Liu Ge , Wang Haixing , Xin Junying , Wu Yulong , Zheng Hongliang , Liu Hualong , Wang Jingguo , Zou Detang , Zhao Hongwei
Published: February 2024

Low-temperature chilling is a major abiotic stress leading to reduced rice yield and is a significant environmental threat to food security. Low-temperature chilling studies have focused on physiological changes or coding genes. However, the competitive endogenous RNA mechanism in rice at low temperatures has not been reported. Therefore, in this study, antioxidant physiological indices were combined with whole-transcriptome data through weighted correlation network analysis, which found that the gene modules had the highest correlation with the key antioxidant enzymes superoxide dismutase and peroxidase. The hub genes of the superoxide dismutase-related module included the UDP-glucosyltransferase family protein, sesquiterpene synthase and indole-3-glycerophosphatase gene. The hub genes of the peroxidase-related module included the WRKY transcription factor, abscisic acid signal transduction pathway-related gene plasma membrane hydrogen-ATPase and receptor-like kinase. Therefore, we selected the modular hub genes and significantly enriched the metabolic pathway genes to construct the key competitive endogenous RNA networks, resulting in three competitive endogenous RNA networks of seven long non-coding RNAs regulating three co-expressed messenger RNAs via four microRNAs. Finally, the negative regulatory function of the WRKY transcription factor OsWRKY61 was determined via subcellular localization and validation of the physiological indices in the mutant.
Dysregulation of Glucocorticoid Receptor Homeostasis and Glucocorticoid-Associated Genes in Umbilical Cord Endothelial Cells of Diet-Induced Obese Pregnant Sheep
Authors: Mata-Greenwood Eugenia , Chow Wendy L. , Anti Nana A. O. , Sands LeeAnna D. , Adeoye Olayemi , Ford Stephen P. , Nathanielsz Peter W.
Published: February 2024

Maternal obesity (MO) is associated with offspring cardiometabolic diseases that are hypothesized to be partly mediated by glucocorticoids. Therefore, we aimed to study fetal endothelial glucocorticoid sensitivity in an ovine model of MO. Rambouillet/Columbia ewes were fed either 100% (control) or 150% (MO) National Research Council recommendations from 60 d before mating until near-term (135 days gestation). Sheep umbilical vein and artery endothelial cells (ShUVECs and ShUAECs) were used to study glucocorticoid receptor (GR) expression and function in vitro. Dexamethasone dose–response studies of gene expression, activation of a glucocorticoid response element (GRE)-dependent luciferase reporter vector, and cytosolic/nuclear GR translocation were used to assess GR homeostasis. MO significantly increased basal GR protein levels in both ShUVECs and ShUAECs. Increased GR protein levels did not result in increased dexamethasone sensitivity in the regulation of key endothelial gene expression such as endothelial nitric oxide synthase, plasminogen activator inhibitor 1, vascular endothelial growth factor, or intercellular adhesion molecule 1. In ShUVECs, MO increased GRE-dependent transactivation and FKBP prolyl isomerase 5 (FKBP5) expression. ShUAECs showed generalized glucocorticoid resistance in both dietary groups. Finally, we found that ShUVECs were less sensitive to dexamethasone-induced activation of GR than human umbilical vein endothelial cells (HUVECs). These findings suggest that MO-mediated effects in the offspring endothelium could be further mediated by dysregulation of GR homeostasis in humans as compared with sheep.
Trained Innate Immunity in Animal Models of Cardiovascular Diseases
Authors: Kleimann Patricia , Irschfeld Lisa-Marie , Grandoch Maria , Flögel Ulrich , Temme Sebastian
Published: February 2024

Acquisition of immunological memory is an important evolutionary strategy that evolved to protect the host from repetitive challenges from infectious agents. It was believed for a long time that memory formation exclusively occurs in the adaptive part of the immune system with the formation of highly specific memory T cells and B cells. In the past 10–15 years, it has become clear that innate immune cells, such as monocytes, natural killer cells, or neutrophil granulocytes, also have the ability to generate some kind of memory. After the exposure of innate immune cells to certain stimuli, these cells develop an enhanced secondary response with increased cytokine secretion even after an encounter with an unrelated stimulus. This phenomenon has been termed trained innate immunity (TI) and is associated with epigenetic modifications (histone methylation, acetylation) and metabolic alterations (elevated glycolysis, lactate production). TI has been observed in tissue-resident or circulating immune cells but also in bone marrow progenitors. Risk-factors for cardiovascular diseases (CVDs) which are associated with low-grade inflammation, such as hyperglycemia, obesity, or high salt, can also induce TI with a profound impact on the development and progression of CVDs. In this review, we briefly describe basic mechanisms of TI and summarize animal studies which specifically focus on TI in the context of CVDs.
Epidermal Growth Factor Receptor Inhibitors in Glioblastoma: Current Status and Future Possibilities
Authors: Ezzati Shawyon , Salib Samuel , Balasubramaniam Meenakshisundaram , Aboud Orwa
Published: February 2024

Glioblastoma, a grade 4 glioma as per the World Health Organization, poses a challenge in adult primary brain tumor management despite advanced surgical techniques and multimodal therapies. This review delves into the potential of targeting epidermal growth factor receptor (EGFR) with small-molecule inhibitors and antibodies as a treatment strategy. EGFR, a mutationally active receptor tyrosine kinase in over 50% of glioblastoma cases, features variants like EGFRvIII, EGFRvII and missense mutations, necessitating a deep understanding of their structures and signaling pathways. Although EGFR inhibitors have demonstrated efficacy in other cancers, their application in glioblastoma is hindered by blood–brain barrier penetration and intrinsic resistance. The evolving realm of nanodrugs and convection-enhanced delivery offers promise in ensuring precise drug delivery to the brain. Critical to success is the identification of glioblastoma patient populations that benefit from EGFR inhibitors. Tools like radiolabeled anti-EGFR antibody 806i facilitate the visualization of EGFR conformations, aiding in tailored treatment selection. Recognizing the synergistic potential of combination therapies with downstream targets like mTOR, PI3k, and HDACs is pivotal for enhancing EGFR inhibitor efficacy. In conclusion, the era of precision oncology holds promise for targeting EGFR in glioblastoma, contingent on tailored treatments, effective blood–brain barrier navigation, and the exploration of synergistic therapies.
Unveiling the Role of Endothelial Dysfunction: A Possible Key to Enhancing Catheter Ablation Success in Atrial Fibrillation
Authors: Zakynthinos George E. , Tsolaki Vasiliki , Oikonomou Evangelos , Pantelidis Panteleimon , Gialamas Ioannis , Kalogeras Konstantinos , Zakynthinos Epaminondas , Vavuranakis Manolis , Siasos Gerasimos
Published: February 2024

Atrial fibrillation, a prevalent type of arrhythmia, is increasingly contributing to the economic burden on healthcare systems. The development of innovative treatments, notably catheter ablation, has demonstrated both impressive and promising outcomes. However, these treatments have not yet fully replaced pharmaceutical approaches, primarily due to the relatively high incidence of atrial fibrillation recurrence post-procedure. Recent insights into endothelial dysfunction have shed light on its role in both the onset and progression of atrial fibrillation. This emerging understanding suggests that endothelial function might significantly influence the effectiveness of catheter ablation. Consequently, a deeper exploration into endothelial dynamics could potentially elevate the status of catheter ablation, positioning it as a primary treatment option for atrial fibrillation.
CSDE1 Intracellular Distribution as a Biomarker of Melanoma Prognosis
Authors: Indacochea Alberto , Guitart Tanit , Boada Aram , Peg Vicente , Quer Ariadna , Laayouni Hafid , Condal Laura , Espinosa Pablo , Manzano Jose Luis , Gebauer Fátima
Published: February 2024

RNA-binding proteins are emerging as critical modulators of oncogenic cell transformation, malignancy and therapy resistance. We have previously found that the RNA-binding protein Cold Shock Domain containing protein E1 (CSDE1) promotes invasion and metastasis of melanoma, the deadliest form of skin cancer and also a highly heterogeneous disease in need of predictive biomarkers and druggable targets. Here, we design a monoclonal antibody useful for IHC in the clinical setting and use it to evaluate the prognosis potential of CSDE1 in an exploratory cohort of 149 whole tissue sections including benign nevi and primary tumors and metastasis from melanoma patients. Contrary to expectations for an oncoprotein, we observed a global decrease in CSDE1 levels with increasing malignancy. However, the CSDE1 cytoplasmic/nuclear ratio exhibited a positive correlation with adverse clinical features of primary tumors and emerged as a robust indicator of progression free survival in cutaneous melanoma, highlighting the potential of CSDE1 as a biomarker of prognosis. Our findings provide a novel feature for prognosis assessment and highlight the intricacies of RNA-binding protein dynamics in cancer progression.
The Sphingolipid-Modulating Drug Opaganib Protects against Radiation-Induced Lung Inflammation and Fibrosis: Potential Uses as a Medical Countermeasure and in Cancer Radiotherapy
Authors: Maines Lynn W. , Keller Staci N. , Smith Ryan A. , Green Cecelia L. , Smith Charles D.
Published: February 2024

Fibrosis is a chronic pathology resulting from excessive deposition of extracellular matrix components that leads to the loss of tissue function. Pulmonary fibrosis can follow a variety of diverse insults including ischemia, respiratory infection, or exposure to ionizing radiation. Consequently, treatments that attenuate the development of debilitating fibrosis are in desperate need across a range of conditions. Sphingolipid metabolism is a critical regulator of cell proliferation, apoptosis, autophagy, and pathologic inflammation, processes that are all involved in fibrosis. Opaganib (formerly ABC294640) is the first-in-class investigational drug targeting sphingolipid metabolism for the treatment of cancer and inflammatory diseases. Opaganib inhibits key enzymes in sphingolipid metabolism, including sphingosine kinase-2 and dihydroceramide desaturase, thereby reducing inflammation and promoting autophagy. Herein, we demonstrate in mouse models of lung damage following exposure to ionizing radiation that opaganib significantly improved long-term survival associated with reduced lung fibrosis, suppression of granulocyte infiltration, and reduced expression of IL-6 and TNFα at 180 days after radiation. These data further demonstrate that sphingolipid metabolism is a critical regulator of fibrogenesis, and specifically show that opaganib suppresses radiation-induced pulmonary inflammation and fibrosis. Because opaganib has demonstrated an excellent safety profile during clinical testing in other diseases (cancer and COVID-19), the present studies support additional clinical trials with this drug in patients at risk for pulmonary fibrosis.
Effects of Pharmaceutical Substances with Obesogenic Activity on Male Reproductive Health
Authors: Mascarenhas Caio , Sousa Ana C. A. , Rato Luís
Published: February 2024

Obesogens have been identified as a significant factor associated with increasing obesity rates, particularly in developed countries. Substances with obesogenic traits are prevalent in consumer products, including certain pharmaceuticals. Specific classes of pharmaceuticals have been recognized for their ability to induce weight gain, often accompanied by hormonal alterations that can adversely impact male fertility. Indeed, research has supplied evidence underscoring the crucial role of obesogens and therapeutic agents in the normal functioning of the male reproductive system. Notably, sperm count and various semen parameters have been closely linked to a range of environmental and nutritional factors, including chemicals and pharmacological agents exhibiting obesogenic properties. This review aimed to explore studies focused on analyzing male fertility parameters, delving into the intricacies of sperm quality, and elucidating the direct and adverse effects that pharmacological agents may have on these aspects.
Structural Complications Following ST-Elevation Myocardial Infarction: An Analysis of the National Inpatient Sample 2016 to 2020
Authors: Kwok Chun Shing , Qureshi Adnan I. , Will Maximillian , Schwarz Konstantin , Lip Gregory Y. H. , Borovac Josip A.
Published: February 2024

ST-elevation myocardial infarction (STEMI) is a life-threatening emergency that can result in cardiac structural complications without timely revascularization. A retrospective study from the National Inpatient Sample included all patients with a diagnosis of STEMI between 2016 and 2020. Primary outcomes of interest were in-hospital mortality, length of stay (LoS), and healthcare costs for patients with and without structural complications. There were 994,300 hospital admissions included in the analysis (median age 64 years and 32.2% female). Structural complications occurred in 0.78% of patients. There was a three-fold increase in patients with cardiogenic shock (41.6% vs. 13.6%) and in-hospital mortality (30.6% vs. 10.7%) in the group with structural complications. The median LoS was longer (5 days vs. 3 days), and the median cost was significantly greater (USD 32,436 vs. USD 20,241) for patients with structural complications. After adjustments, in-hospital mortality was significantly greater for patients with structural complications (OR 1.99, 95% CI 1.73–2.30), and both LoS and costs were greater. There was a significant increase in mortality with ruptured cardiac wall (OR 9.16, 95% CI 5.91–14.20), hemopericardium (OR 3.20, 95% CI 1.91–5.35), and ventricular septal rupture (OR 2.57, 95% CI 1.98–3.35) compared with those with no complication. In conclusion, structural complications in STEMI patients are rare but potentially catastrophic events.