bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of a Single Nucleotide Variant in TERT with Airway Disease in Japanese Rheumatoid Arthritis Patients
Authors: Higuchi Takashi , Oka Shomi , Furukawa Hiroshi , Shimada Kota , Tsunoda Shinichiro , Ito Satoshi , Okamoto Akira , Fujimori Misuzu , Nakamura Tadashi , Katayama Masao , Saisho Koichiro , Shinohara Satoshi , Matsui Toshihiro , Migita Kiyoshi , Nagaoka Shouhei , Tohma Shigeto
Published: November 2023

Interstitial lung disease and airway disease (AD) are often complicated with rheumatoid arthritis (RA) and have a poor prognosis. Several studies reported genetic associations with interstitial lung disease in RA. However, few genetic studies have examined the susceptibility to AD in RA patients. Here, we investigated whether single nucleotide variants susceptible to idiopathic pulmonary fibrosis might be associated with interstitial lung disease or AD in Japanese RA patients. Genotyping of rs2736100 [C/A] in TERT and rs1278769 [G/A] in ATP11A was conducted in 98 RA patients with usual interstitial pneumonia, 120 with nonspecific interstitial pneumonia (NSIP), 227 with AD, and 422 without chronic lung disease using TaqMan assays. An association with AD in RA was found for rs2736100 (p = 0.0043, Pc = 0.0129, odds ratio [OR] 1.40, 95% confidence interval [CI] 1.11–1.77). ATP11A rs1278769 was significantly associated with NSIP in older RA patients (>65 years, p = 0.0010, OR 2.15, 95% CI 1.35–3.40). This study first reported an association of rs2736100 with AD in RA patients and ATP11A rs1278769 with NSIP in older RA patients.
Geophysical and Geomatic Methods for the Knowledge, Conservation, and Management of Jordanian Cultural Heritage
Authors: Angelini Andrea , Cozzolino Marilena , Gabrielli Roberto , Gentile Vincenzo , Mauriello Paolo
Published: November 2023

Jordan has a complex history that has left tangible traces in numerous archaeological sites scattered throughout the country. This unique heritage of inestimable cultural value must be documented, thoroughly researched, and protected in order to prevent its destruction and loss. In this context, knowledge and documentation can be achieved through the application of non-destructive geophysical and geomatic methods. This work represents a synthesis of the results of twenty years of projects carried out at the archaeological sites of Basta, Petra, Um-Hamat (Karak), Umm ar-Rasas, Wu’Ayra, Madaba, and Shawbak. This study enables the exploration of new buried structures in the ground and the documentation of the state of preservation of the structures. It provides an up-to-date overview of Jordan’s rich archaeological heritage and supports restoration projects.
“Learning a Way of Thinking”—World Café on Clinical Reasoning in Nursing and Midwifery Education and Practice across Five European Union Countries
Authors: Pađen Ljubiša , Pajnič Manca , Vettorazzi Renata , Pérez-Perdomo Ana , Stefaniak Małgorzata , Claes Nele , Franco Hugo , Vandervoort An , Ravljen Mirjam
Published: November 2023

Clinical reasoning is a key attribute of nursing and midwifery professionals. As a part of the Erasmus plus project, we designed a study with the aim of exploring the understanding of clinical reasoning as a concept, experiences of teaching clinical reasoning and practices related to using clinical reasoning in nursing and midwifery. A qualitative study was carried out using the World Café method, involving 44 participants from five European countries. The participants represented diverse professional backgrounds, including nurses, midwives and lecturers. Our analytical approach was based on a thematic analysis. We categorized the data into three main categories, namely, “Spiral of thinking”, “The learning and teaching of a way of thinking” and “Clinical reasoning in real life”, all under an overarching theme, “Learning a way of thinking”. This study highlighted areas of learning and teaching which can be improved in current nursing and midwifery education. Furthermore, it identified barriers, facilitators and practices from five European countries which can be used in the further development of nursing and midwifery curricula and courses with the aim of enhancing clinical reasoning competence and ultimately improving patient care.
Prevalence, Symptoms, and Triggering Factors of Panic Attacks among Dental Students in Riyadh Saudi Arabia—A Cross Sectional Survey
Authors: Khanagar Sanjeev B. , Altuwayjiri Reema Jamal , Albarqy Nadeen Mohammed , Alzahrani Ghida Ahmed , Alhusayni Hibah Ali , Alsaif Sarah Yousef
Published: November 2023

Panic disorder by definition is an anxiety disorder of unexpected and repeated episodes of intense fear. Panic attacks are usually diagnosed by four or more of a set of symptoms that include palpitations, sweating, trembling, shortness of breath, chest pain, nausea, dizziness, and hot flushes. They usually interfere with daily life situations and also interfere with education. Hence, the aim of this study was to assess the prevalence of panic attacks, their symptoms, and triggering factors among dental students in Riyadh, Saudi Arabia. Data were collected from 394 students using a structured and validated questionnaire. The prevalence of panic attacks among dental students in Riyadh, Saudi Arabia, was 42.9%. Most of the participants who experienced higher episodes of panic attacks were females (53.4%) when compared to males (24.5%). Third year students displayed greater (58.3%) episodes of panic attacks compared to their respective counterparts. The most reported symptom of panic attacks was rapid or pounding heartbeat followed by breathlessness, chest pain, and shaking or trembling. It was also noted that most of the participants (63.31%) encountered a panic attack for the first time after joining dental school. The situations where dental students frequently experienced panic attacks were during exams, clinic procedures, giving presentations, and especially while under a lot of stress. The high occurrence of panic attacks among dental students highlights the importance of providing support programs and implementing preventive measures to help students, particularly those who are most susceptible to higher levels of these psychological conditions. Dental students experiencing panic attacks should be provided with necessary counseling sessions or psychiatric consultation in order to overcome such scenarios. Dental schools should consider these findings when planning the dental curriculum. Hence, the role of the faculty members is essential in these situations to provide support for the affected students.
Health Behaviors of Cancer Survivors According to the Employment Status and Occupation: A Cross-Sectional Study
Authors: Bae Ka Ryeong , So Wi-Young , Lee Su Jung
Published: November 2023

This study aimed to identify differences in health behaviors according to the employment status and occupation of cancer survivors, as well as to identify risk factors. Using data from the Korea National and Health Nutrition Examination Survey (2008–2018), 1023 cancer survivors aged 19–60 years were classified based on their employment status and occupation, and their health behaviors were comparatively assessed. To investigate the impact of occupational status on the health behaviors of cancer survivors, we performed multivariate adjusted logistic regression analysis. Five hundred fifty-six (54.3%) cancer survivors were engaged in economic activities. After adjusting for various factors, white- and blue-collar workers exhibited an increased risk of obesity. The blue-collar group had a 1.45 times higher risk of non-practice with cancer screening, while the white-collar group had a 0.50 times lower risk of non-practice with health screening. The results provide evidence of the need to support cancer survivors in practicing healthy behaviors according to their employment status and occupation. As cancer survivors’ economic activities increase, it is necessary to help them manage their health by predicting any possible health-behavior failures.
Targeted Metabolome and Transcriptome Analyses Reveal the Molecular Mechanism of Color Variation between Sepals and Petals in Fuchsia hybrida
Authors: Lei Shutong , Li Jingjing , Wang Jiaying , Deng Chengyan
Published: November 2023

The sepal color of Fuchsia hybrida is colorful instead of green and usually varies from the petal colors, which greatly increases its ornamental value and attract customers’ preference. However, the potential molecular mechanism underlying the color variation between sepals and petals remains unclear. The present study collected F. hybrida with red sepals and purple petals to explore the key pigments and genes involved in color development using a targeted metabolome and transcriptome. A total of 43 metabolites with diverse hydroxylation, glycosylation, methylation and acylation patterns were isolated and identified by UPLC-MS/MS. The quantification analysis showed that peonidin-3,5-O-diglucoside and malvidin-3,5-O-diglucoside were the most abundant anthocyanins accumulating in the sepals and petals, respectively. Then, six libraries from the sepals and petals were constructed for the transcriptome and 70,135 unigenes were generated. The transcript level of FhF3′H was significantly higher in the sepals, while Fh3′5′H showed more abundant expression in the petals, which can account for the abundant peonidin and malvidin accumulation in the sepals and petals, respectively. The subsequent multiomics analysis showed that both the differentially accumulated anthocyanins and expressed unigenes were enriched in the anthocyanin biosynthesis pathway. Additionally, FhMYBs potentially regulating anthocyanin biosynthesis were screened out by correlation analysis and protein interaction prediction. These findings help to elucidate the molecular mechanisms underlying the color variation between the sepals and petals in F. hybrida.
Indigenous Voices Against Suicide: A Meta-Synthesis Advancing Prevention Strategies
Authors: Richardson Meenakshi , Waters Sara F.
Published: November 2023

Rates of suicidality amongst Indigenous Peoples are linked to historical and ongoing settler-colonialism including land seizures, spiritual oppression, cultural disconnection, forced enculturation, and societal alienation. Consistent with decolonial practices, Indigenous voices and perspectives must be centered in the development and evaluation of suicide prevention programs for Indigenous Peoples in the United States to ensure efficacy. The current study is a meta-synthesis of qualitative research on suicide prevention among Indigenous populations in the United States. Findings reveal little evidence for the centering of participant voices within existing suicide prevention programs. Applied thematic analysis of synthesis memos developed for each article in the final sample surfaced four primary themes: (1) support preferences; (2) challenges to suicide prevention; (3) integration of culture as prevention; and (4) grounding relationships in prevention. The need for culturally centered programming and the inadequacy of ‘pan-Indian’ approaches are highlighted. Sub-themes with respect to resiliency, kinship connection, and safe spaces to share cultural knowledge also emerge. Implications of this work to further the decolonization of suicide prevention and aid in the promotion of culturally grounded prevention science strategies are discussed.
Association between Japanese Diet Adherence and Muscle Weakness in Japanese Adults Aged ≥50 Years: Findings from the JSTAR Cohort Study
Authors: Shimizu Akio , Okada Kiwako , Tomata Yasutake , Uno Chiharu , Kawase Fumiya , Momosaki Ryo
Published: November 2023

Japanese diet adherence has been inversely correlated with muscle weakness. In this study, we aimed to validate that association. Longitudinal data from 1699 individuals aged ≥50 years (mean age 62.5 ± 6.9 years, 50.4% female) at two time points (2007 and 2011) were used. Participants without muscle weakness from several regions in Japan were included. The 12-component revised Japanese Diet Index (rJDI12) classified by tertiles assessed adherence to the Japanese dietary pattern. Muscle weakness was defined as a handgrip strength of ˂18 kg for females and ˂28 kg for males based on the Asian Working Group for Sarcopenia criteria 2019. A multivariate logistic approach was used to determine the relationship between rJDI12 tertile and the occurrence of muscle weakness by calculating the odds ratio (OR) and its 95% confidence interval (95% CI) throughout the observation period. Muscle weakness was negatively correlated with the highest rJDI12 tertile (OR [95% CI] 0.891 [0.814, 0.973] for T3). This association was consistent in sensitivity analyses with multiple imputations of missing values. Closely following the Japanese dietary pattern appears to reduce the occurrence of muscle weakness among the aging population in this study, suggesting it may prevent frailty and sarcopenia in the aging population.
The Brief Health Literacy Scale for Adults: Adaptation and Validation of the Health Literacy for School-Aged Children Questionnaire
Authors: Rasmussen Stinne Eika , Aaby Anna , Søjbjerg Anne , Mygind Anna , Maindal Helle Terkildsen , Paakkari Olli , Christensen Kaj Sparle
Published: November 2023

The Health Literacy for School-Aged Children (HLSAC) is a brief, generic instrument measuring health literacy among school-aged children. Given its brevity and broad conceptualization of health literacy, the HLSAC is a potentially valuable measuring instrument among adults as well. This validation study aimed to adapt the HLSAC questionnaire to an adult population through assessment of content validity and subsequently determine the structural validity of the adapted instrument, the Brief Health Literacy scale for Adults (B-HLA). The content validity of the HLSAC was assessed through interviews with respondents and experts, and the structural validity of the adapted instrument (B-HLA) was evaluated using Rasch analysis. The content validity assessment (n = 25) gave rise to adjustments in the wording of five items. The B-HLA demonstrated an overall misfit to the Rasch model (n = 290). Items 6 and 8 had the poorest individual fits. We found no signs of local dependency or differential item functioning concerning sex, age, education, and native language. The B-HLA demonstrated unidimensionality and ability to discriminate across health literacy levels (PSI = 0.80). Discarding items 6 or 8 resulted in an overall model fit and individual fit of all items. In conclusion, the B-HLA appears to be a valid and reliable instrument for assessing health literacy among adults.
Preclinical Models and Technologies in Glioblastoma Research: Evolution, Current State, and Future Avenues
Authors: Slika Hasan , Karimov Ziya , Alimonti Paolo , Abou-Mrad Tatiana , De Fazio Emerson , Alomari Safwan , Tyler Betty
Published: November 2023

Glioblastoma is the most common malignant primary central nervous system tumor and one of the most debilitating cancers. The prognosis of patients with glioblastoma remains poor, and the management of this tumor, both in its primary and recurrent forms, remains suboptimal. Despite the tremendous efforts that are being put forward by the research community to discover novel efficacious therapeutic agents and modalities, no major paradigm shifts have been established in the field in the last decade. However, this does not mirror the abundance of relevant findings and discoveries made in preclinical glioblastoma research. Hence, developing and utilizing appropriate preclinical models that faithfully recapitulate the characteristics and behavior of human glioblastoma is of utmost importance. Herein, we offer a holistic picture of the evolution of preclinical models of glioblastoma. We further elaborate on the commonly used in vitro and vivo models, delving into their development, favorable characteristics, shortcomings, and areas of potential improvement, which aids researchers in designing future experiments and utilizing the most suitable models. Additionally, this review explores progress in the fields of humanized and immunotolerant mouse models, genetically engineered animal models, 3D in vitro models, and microfluidics and highlights promising avenues for the future of preclinical glioblastoma research.
Gene Cloning and Characterization of Transcription Factor FtNAC10 in Tartary Buckwheat (Fagopyrum tataricum (L.) Gaertn.)
Authors: Li Jinghuan , Li Xiaohua , Jia Caihua , Liu Dahui
Published: November 2023

NAC transcription factors play a significant role in plant stress responses. In this study, an NAC transcription factor, with a CDS of 792 bp encoding 263 amino acids, was cloned from Fagopyrum tataricum (L.) Gaertn. (F. tataricum), a minor cereal crop, which is rich in flavonoids and highly stress resistant. The transcription factor was named FtNAC10 (NCBI accession number: MK614506.1) and characterized as a member of the NAP subgroup of NAC transcriptions factors. The gene exhibited a highly conserved N-terminal, encoding about 150 amino acids, and a highly specific C-terminal. The resulting protein was revealed to be hydrophilic, with strong transcriptional activation activity. FtNAC10 expression occurred in various F. tataricum tissues, most noticeably in the root, and was regulated differently under various stress treatments. The over-expression of FtNAC10 in transgenic Arabidopsis thaliana (A. thaliana) seeds inhibited germination, and the presence of FtNAC10 enhanced root elongation under saline and drought stress. According to phylogenetic analysis and previous reports, our experiments indicate that FtNAC10 may regulate the stress response or development of F. tataricum through ABA-signaling pathway, although the mechanism is not yet known. This study provides a reference for further analysis of the regulatory function of FtNAC10 and the mechanism that underlies stress responses in Tartary buckwheat.
Structural Insights into Protein–Aptamer Recognitions Emerged from Experimental and Computational Studies
Authors: Troisi Romualdo , Balasco Nicole , Autiero Ida , Vitagliano Luigi , Sica Filomena
Published: November 2023

Aptamers are synthetic nucleic acids that are developed to target with high affinity and specificity chemical entities ranging from single ions to macromolecules and present a wide range of chemical and physical properties. Their ability to selectively bind proteins has made these compounds very attractive and versatile tools, in both basic and applied sciences, to such an extent that they are considered an appealing alternative to antibodies. Here, by exhaustively surveying the content of the Protein Data Bank (PDB), we review the structural aspects of the protein–aptamer recognition process. As a result of three decades of structural studies, we identified 144 PDB entries containing atomic-level information on protein–aptamer complexes. Interestingly, we found a remarkable increase in the number of determined structures in the last two years as a consequence of the effective application of the cryo-electron microscopy technique to these systems. In the present paper, particular attention is devoted to the articulated architectures that protein–aptamer complexes may exhibit. Moreover, the molecular mechanism of the binding process was analyzed by collecting all available information on the structural transitions that aptamers undergo, from their protein-unbound to the protein-bound state. The contribution of computational approaches in this area is also highlighted.
FMRP Enhances the Translation of 4EBP2 mRNA during Neuronal Differentiation
Authors: Yu Jinbae , Woo Youngsik , Kim Heesun , An Sihyeon , Park Sang Ki , Jang Sung Key
Published: November 2023

FMRP is a multifunctional protein encoded by the Fragile X Messenger Ribonucleoprotein 1 gene (FMR1). The inactivation of the FMR1 gene results in fragile X syndrome (FXS), a serious neurodevelopmental disorder. FMRP deficiency causes abnormal neurite outgrowth, which is likely to lead to abnormal learning and memory capabilities. However, the mechanism of FMRP in modulating neuronal development remains unknown. We found that FMRP enhances the translation of 4EBP2, a neuron-specific form of 4EBPs that inactivates eIF4E by inhibiting the interaction between eIF4E and eIF4G. Depletion of 4EBP2 results in abnormal neurite outgrowth. Moreover, the impairment of neurite outgrowth upon FMRP depletion was overcome by the ectopic expression of 4EBP2. These results suggest that FMRP controls neuronal development by enhancing 4EBP2 expression at the translational level. In addition, treatment with 4EGI-1, a chemical that blocks eIF4E activity, restored neurite length in FMRP-depleted and 4EBP2-depleted cells. In conclusion, we discovered that 4EBP2 functions as a key downstream regulator of FMRP activity in neuronal development and that FMRP represses eIF4E activity by enhancing 4EBP2 translation.
In Vitro Cytotoxic Effects of Ferruginol Analogues in Sk-MEL28 Human Melanoma Cells
Authors: Shao Luying , González-Cardenete Miguel A. , Prieto-Garcia Jose M.
Published: November 2023

Ferruginol is a promising abietane-type antitumor diterpene able to induce apoptosis in SK-Mel-28 human malignant melanoma. We aim to increase this activity by testing the effect of a small library of ferruginol analogues. After a screening of their antiproliferative activity (SRB staining, 48 h) on SK-Mel-28 cells the analogue 18-aminoferruginol (GI50 ≈ 10 µM) was further selected for mechanistic studies including induction of apoptosis (DAPI staining, p < 0.001), changes in cell morphology associated with the treatment (cell shrinkage and membrane blebbing), induction of caspase-3/7 activity (2.5 at 48 h, 6.5 at 72 h; p < 0.0001), changes in the mitochondrial membrane potential (not significant) and in vitro effects on cell migration and cell invasion (Transwell assays, not significant). The results were compared to those of the parent molecule (ferruginol, GI50 ≈ 50 µM, depolarisation of mitochondrial membrane p < 0.01 at 72 h; no caspases 3/7 activation) and paclitaxel (GI50 ≈ 10 nM; caspases 3/7 activation p < 0.0001) as a reference drug. Computational studies of the antiproliferative activity of 18-aminoferruginol show a consistent improvement in the activity over ferruginol across a vast majority of cancer cells in the NCI60 panel. In conclusion, we demonstrate here that the derivatisation of ferruginol into 18-aminoferruginol increases its antiproliferative activity five times in SK-MEL-28 cells and changes the apoptotic mechanism of its parent molecule, ferruginol.
Peptoids: Smart and Emerging Candidates for the Diagnosis of Cancer, Neurological and Autoimmune Disorders
Authors: Giorgio Anna , Del Gatto Annarita , Pennacchio Simone , Saviano Michele , Zaccaro Laura
Published: November 2023

Early detection of fatal and disabling diseases such as cancer, neurological and autoimmune dysfunctions is still desirable yet challenging to improve quality of life and longevity. Peptoids (N-substituted glycine oligomers) are a relatively new class of peptidomimetics, being highly versatile and capable of mimicking the architectures and the activities of the peptides but with a marked resistance to proteases and a propensity to cross the cellular membranes over the peptides themselves. For these properties, they have gained an ever greater interest in applications in bioengineering and biomedical fields. In particular, the present manuscript is to our knowledge the only review focused on peptoids for diagnostic applications and covers the last decade’s literature regarding peptoids as tools for early diagnosis of pathologies with a great impact on human health and social behavior. The review indeed provides insights into the peptoid employment in targeted cancer imaging and blood-based screening of neurological and autoimmune diseases, and it aims to attract the scientific community’s attention to continuing and sustaining the investigation of these peptidomimetics in the diagnosis field considering their promising peculiarities.
Role of ST6GAL1 in Thyroid Cancers: Insights from Tissue Analysis and Genomic Datasets
Authors: Gunjača Ivana , Benzon Benjamin , Pleić Nikolina , Babić Leko Mirjana , Pešutić Pisac Valdi , Barić Ana , Kaličanin Dean , Punda Ante , Polašek Ozren , Vukojević Katarina , Zemunik Tatijana
Published: November 2023

Thyroid cancer is the predominant endocrine-related malignancy. ST6 β-galactoside α2,6-sialyltransferase 1 (ST6GAL1) has been studied in various types of cancers; however, the expression and function of ST6GAL1 in thyroid cancer has not been investigated so far. Previously, we conducted two genome-wide association studies and have identified the association of the ST6GAL1 gene with plasma thyroglobulin (Tg) levels. Since Tg levels are altered in thyroid pathologies, in the current study, we wanted to evaluate the expression of ST6GAL1 in thyroid cancer tissues. We performed an immunohistochemical analysis using human thyroid tissue from 89 patients and analyzed ST6GAL1 protein expression in papillary thyroid cancer (including follicular variant and microcarcinoma) and follicular thyroid cancer in comparison to normal thyroid tissue. Additionally, ST6GAL1 mRNA levels from The Cancer Genome Atlas (TCGA, n = 572) and the Genotype-Tissue Expression (GTEx) project (n = 279) were examined. The immunohistochemical analysis revealed higher ST6GAL1 protein expression in all thyroid tumors compared to normal thyroid tissue. TCGA data revealed increased ST6GAL1 mRNA levels in both primary and metastatic tumors versus controls. Notably, the follicular variant of papillary thyroid cancer exhibited significantly higher ST6GAL1 mRNA levels than classic papillary thyroid cancer. High ST6GAL1 mRNA levels significantly correlated with lymph node metastasis status, clinical stage, and reduced survival rate. ST6GAL1 emerges as a potential cancer-associated glycosyltransferase in thyroid malignancies, offering valuable insights into its diagnostic and prognostic significance.
FTO Sensitizes Oral Squamous Cell Carcinoma to Ferroptosis via Suppressing ACSL3 and GPX4
Authors: Wang Ziyi , Li Hongyu , Cai Hongshi , Liang Jianfeng , Jiang Yaoqi , Song Fan , Hou Chen , Hou Jinsong
Published: November 2023

Ferroptosis is a newly established form of regulated cell death characterized by intracellular lipid peroxidation and iron accumulation that may be a promising cancer treatment strategy. However, the function and therapeutic value of ferroptosis in oral squamous cell carcinoma (OSCC) remain inadequately understood. In the present study, we investigated the biological role of the fat mass and obesity-associated gene (FTO) in ferroptosis in the context of OSCC. We found that OSCC had greater potential for ferroptosis, and FTO is associated with ferroptosis. Furthermore, higher FTO expression sensitized OSCC cells to ferroptosis in vitro and in vivo. Mechanistically, FTO suppressed the expression of anti-ferroptotic factors, acyl-CoA synthetase long-chain family member 3 (ACSL3) and glutathione peroxidase 4 (GPX4), by demethylating the m6A modification on the mRNA of ACSL3 and GPX4 and decreasing their stability. Taken together, our findings revealed that FTO promotes ferroptosis through ACSL3 and GPX4 regulation. Thus, ferroptosis activation in OSCC with high FTO levels may serve as a potential therapeutic target.
STAT3 Signalling Drives LDH Up-Regulation and Adiponectin Down-Regulation in Cachectic Adipocytes
Authors: Mannelli Michele , Bartoloni Bianca , Cantini Giulia , Nencioni Elena , Magherini Francesca , Luconi Michaela , Modesti Alessandra , Gamberi Tania , Fiaschi Tania
Published: November 2023

Cachexia is a devastating pathology that worsens the quality of life and antineoplastic treatment outcomes of oncologic patients. Herein, we report that the secretome from murine colon carcinoma CT26 induces cachectic features in both murine and human adipocytes that are associated with metabolic alterations such as enhanced lactate production and decreased oxygen consumption. The use of oxamate, which inhibits lactate dehydrogenase activity, hinders the effects induced by CT26 secretome. Interestingly, the CT26 secretome elicits an increased level of lactate dehydrogenase and decreased expression of adiponectin. These modifications are driven by the STAT3 signalling cascade since the inhibition of STAT3 with WP1066 impedes the formation of the cachectic condition and the alteration of lactate dehydrogenase and adiponectin levels. Collectively, these findings show that STAT3 is responsible for the altered lactate dehydrogenase and adiponectin levels that, in turn, could participate in the worsening of this pathology and highlight a step forward in the comprehension of the mechanisms underlying the onset of the cachectic condition in adipocytes.
Intravital Microscopy of Lipopolysaccharide-Induced Inflammatory Changes in Different Organ Systems—A Scoping Review
Authors: Scott Cassidy , Neira Agonh Daniel , White Hannah , Sultana Saki , Lehmann Christian
Published: November 2023

Intravital microscopy (IVM) is a powerful imaging tool that captures biological processes in real-time. IVM facilitates the observation of complex cellular interactions in vivo, where ex vivo and in vitro experiments lack the physiological environment. IVM has been used in a multitude of studies under healthy and pathological conditions in different organ systems. IVM has become essential in the characterization of the immune response through visualization of leukocyte–endothelial interactions and subsequent changes within the microcirculation. Lipopolysaccharide (LPS), a common inflammatory trigger, has been used to induce inflammatory changes in various studies utilizing IVM. In this review, we provide an overview of IVM imaging of LPS-induced inflammation in different models, such as the brain, intestines, bladder, and lungs.
Hepatic NLRP3-Derived Hsp70 Binding to TLR4 Mediates MASLD to MASH Progression upon Inhibition of PP2A by Harmful Algal Bloom Toxin Microcystin, a Second Hit
Authors: Roy Subhajit , Saha Punnag , Bose Dipro , Trivedi Ayushi , More Madhura , Xiao Shuo , Diehl Anna Mae , Chatterjee Saurabh
Published: November 2023

Harmful algal bloom toxin microcystin has been associated with metabolic dysfunction-associated steatotic liver disease (MASLD) progression and hepatocellular carcinoma, though the mechanisms remain unclear. Using an established mouse model of MASLD, we show that the NLRP3–Hsp70–TLR4 axis drives in part the inflammation of the liver lobule that results in the progression of MASLD to metabolic dysfunction-associated steatohepatitis (MASH). Results showed that mice deficient in NLRP3 exhibited decreased MASH pathology, blocked Hsp70 expression, and co-binding with NLRP3, a crucial protein component of the liver inflammasome. Hsp70, both in the liver lobule and extracellularly released in the liver vasculature, acted as a ligand to TLR4 in the liver, primarily in hepatocytes to activate the NF-κB pathway, ultimately leading to hepatic cell death and necroptosis, a crucial pathology of MASH progression. The above studies show a novel insight into an inflammasome-triggered Hsp70-mediated inflammation that may have broader implications in MASLD pathology. MASLD to MASH progression often requires multiple hits. One of the mediators of progressive MASLD is environmental toxins. In this research report, we show for the first time a novel mechanism where microcystin-LR, an environmental toxin, advances MASLD to MASH by triggering the release of Hsp70 as a DAMP to activate TLR4-induced inflammation in the liver.
An Overview of Recent Developments in the Management of Burn Injuries
Authors: Radzikowska-Büchner Elżbieta , Łopuszyńska Inga , Flieger Wojciech , Tobiasz Michał , Maciejewski Ryszard , Flieger Jolanta
Published: November 2023

According to the World Health Organization (WHO), around 11 million people suffer from burns every year, and 180,000 die from them. A burn is a condition in which heat, chemical substances, an electrical current or other factors cause tissue damage. Burns mainly affect the skin, but can also affect deeper tissues such as bones or muscles. When burned, the skin loses its main functions, such as protection from the external environment, pathogens, evaporation and heat loss. Depending on the stage of the burn, the patient’s condition and the cause of the burn, we need to choose the most appropriate treatment. Personalization and multidisciplinary collaboration are key to the successful management of burn patients. In this comprehensive review, we have collected and discussed the available treatment options, focusing on recent advances in topical treatments, wound cleansing, dressings, skin grafting, nutrition, pain and scar tissue management.
Bioinformatic Assessment and Expression Profiles of the AP2/ERF Superfamily in the Melastoma dodecandrum Genome
Authors: Zhou Yuzhen , Zheng Ruiyue , Peng Yukun , Chen Jiemin , Zhu Xuanyi , Xie Kai , Su Qiuli , Huang Ruiliu , Zhan Suying , Peng Donghui , Zhao Kai , Liu Zhong-Jian
Published: November 2023

AP2/ERF transcription factors play crucial roles in various biological activities, including plant growth, development, and responses to biotic and abiotic stressors. However, limited research has been conducted on the AP2/ERF genes of Melastoma dodecandrum for breeding of this potential fruit crop. Leveraging the recently published whole genome sequence, we conducted a comprehensive assessment of this superfamily and explored the expression patterns of AP2/ERF genes at a genome-wide level. A significant number of genes, totaling 218, were discovered to possess the AP2 domain sequence and displayed notable structural variations among five subfamilies. An uneven distribution of these genes was observed on 12 pseudochromosomes as the result of gene expansion facilitated by segmental duplications. Analysis of cis-acting elements within promoter sites and 87.6% miRNA splicing genes predicted their involvement in multiple hormone responses and abiotic stresses through transcriptional and post-transcriptional regulations. Transcriptome analysis combined with qRT-PCR results indicated that certain candidate genes are involved in tissue formation and the response to developmental changes induced by IAA hormones. Overall, our study provides valuable insights into the evolution of ERF genes in angiosperms and lays a solid foundation for future breeding investigations aimed at improving fruit quality and enhancing adaptation to barren land environments.
APOA1 Is a Novel Marker for Preeclampsia
Authors: Liu Zhenzhen , Pei Jiangnan , Zhang Xiaoyue , Wang Chengjie , Tang Yao , Liu Haiyan , Yu Yi , Luo Shouling , Gu Weirong
Published: November 2023

Preeclampsia (PE) is one of the pregnancy complications, leading to major maternal and fetal morbidity and mortality; however, the underlying mechanisms of PE still remain unclear. We aimed to explore the role of apolipoprotein A1 (APOA1) in the pathophysiology of PE. The expression of APOA1 was elevated in both plasma and placental tissues, as detected by Western blotting, immunohistochemistry, and a qRT-PCR assay. Importantly, we detected the concentration of APOA1 using the ELISA assay in normal control women (n = 30) and women with preeclampsia (n = 29) from a prospective cohort study. The concentration of APOA1 was not significantly altered in plasma during early and mid-term gestation of the PE patients compared to the NP patients; however, it was elevated during late gestation. Additionally, the concentration of APOA1 was positively associated with systolic blood pressure during late gestation. The proliferation and invasion of trophoblast were all increased in HTR8/SVneo cells transfected with APOA1 siRNA and decreased in HTR8/SVneo cells treated with the recombinant human APOA1 protein (rhAPOA1). Additionally, we used public datasets to investigate the downstream genes of APOA1 and qRT-PCR for validation. Furthermore, we explored the transcriptional activity of peroxisome proliferator-activated receptor gamma (PPARγ) in APOA1 by using a luciferase assay, which showed that the APOA1 promoter was activated by PPARγ. Additionally, the inhibitory effect of rhAPOA1 on the ability of trophoblast invasion and proliferation can be rescued by the PPARγ inhibitor. Our findings suggest the crucial role of APOA1 in PE, which might provide a new strategy for the prevention and treatment of PE.
Oxidative Stress and Antioxidant Defense in the Heart, Liver, and Kidney of Bat Species with Different Feeding Habits
Authors: Pereira Francielly Dias , Mena Canata Diego Antonio , Salomon Tiago Boeira , Hackenhaar Fernanda Schäfer , Pereira María João Ramos , Benfato Mara Silveira , Rampelotto Pabulo Henrique
Published: November 2023

The aim of this study was to compare the oxidative metabolism of four neotropical bat species with different feeding habits and investigate the relationship between their feeding habits and oxidative status. In terms of oxidative damage, our findings revealed major differences among the four bat species. In particular, hematophagous bats had lower levels of oxidative damage in the heart but higher levels in the liver. Nectarivorous bats had lower levels of carbonyl groups in the kidneys compared to insectivorous and hematophagous bats. The activity of various antioxidant and non-antioxidant enzymes in the heart, liver, and kidney also showed significant differences among the bat species. H2O2 consumption was lower in the heart of hematophagous bats, while insectivorous bats exhibited the highest enzymatic activity in the kidney. SOD activity was lower in the heart of hematophagous bats and lower in nectarivorous bats in the liver. Fumarase activity was higher in the heart of frugivorous/insectivorous and lower in nectarivorous/hematophagous bats. GPx activity was higher in the heart of nectarivorous/insectivorous and higher in the kidney of insectivorous bats. GST activity was higher in the heart of nectarivorous and lower in hematophagous bats. The correlation analysis between oxidative markers and enzymatic/non-enzymatic antioxidants in the heart, liver, and kidney exhibited distinct patterns of correlations due to variations in antioxidant defense mechanisms and oxidative stress responses in different organs. The observed differences in oxidative damage, antioxidant enzyme activities, and correlations between oxidative markers and antioxidants highlight the adaptability and complexity of the antioxidant defense systems in these bats. Each organ appears to have specific demands and adaptations to cope with oxidative stress based on its physiological functions and exposure to dietary components. Our results have major significance for the conservation and management of bats, which are threatened species despite being crucial components of ecosystems. Our study’s implications go beyond bat biology and offer valuable insights into comparative oxidative physiology.
Transcriptome Profiling Provides Insights into the Early Development of Tiller Buds in High- and Low-Tillering Orchardgrass Genotypes
Authors: Feng Guangyan , Xu Xiaoheng , Liu Wen , Hao Feigxiang , Yang Zhongfu , Nie Gang , Huang Linkai , Peng Yan , Bushman Shaun , He Wei , Zhang Xinquan
Published: November 2023

Orchardgrass (Dactylis glomerata L.) is among the most economically important perennial cool-season grasses, and is considered an excellent hay, pasture, and silage crop in temperate regions worldwide. Tillering is a vital feature that dominates orchardgrass regeneration and biomass yield. However, transcriptional dynamics underlying early-stage bud development in high- and low-tillering orchardgrass genotypes are unclear. Thus, this study assessed the photosynthetic parameters, the partially essential intermediate biomolecular substances, and the transcriptome to elaborate the early-stage profiles of tiller development. Photosynthetic efficiency and morphological development significantly differed between high- (AKZ-NRGR667) and low-tillering genotypes (D20170203) at the early stage after tiller formation. The 206.41 Gb of high-quality reads revealed stage-specific differentially expressed genes (DEGs), demonstrating that signal transduction and energy-related metabolism pathways, especially photosynthetic-related processes, influence tiller induction and development. Moreover, weighted correlation network analysis (WGCNA) and functional enrichment identified distinctively co-expressed gene clusters and four main regulatory pathways, including chlorophyll, lutein, nitrogen, and gibberellic acid (GA) metabolism pathways. Therefore, photosynthesis, carbohydrate synthesis, nitrogen efficient utilization, and phytohormone signaling pathways are closely and intrinsically linked at the transcriptional level. These findings enhance our understanding of tillering in orchardgrass and perennial grasses, providing a new breeding strategy for improving forage biomass yield.
Key Genes of the Immune System and Predisposition to Acquired Hemophilia A: Evidence from a Spanish Cohort of 49 Patients Using Next-Generation Sequencing
Authors: Pardos-Gea Jose , Martin-Fernandez Laura , Closa Laia , Ferrero Ainara , Marzo Cristina , Rubio-Rivas Manuel , Mitjavila Francesca , González-Porras José Ramón , Bastida José María , Mateo José , Carrasco Marina , Bernardo Ángel , Astigarraga Itziar , Aguinaco Reyes , Corrales Irene , Garcia-Martínez Iris , Vidal Francisco
Published: November 2023

Acquired hemophilia A (AHA) is a rare bleeding disorder caused by the presence of autoantibodies against factor VIII (FVIII). As with other autoimmune diseases, its etiology is complex and its genetic basis is unknown. The aim of this study was to identify the immunogenetic background that predisposes individuals to AHA. HLA and KIR gene clusters, as well as KLRK1, were sequenced using next-generation sequencing in 49 AHA patients. Associations between candidate genes involved in innate and adaptive immune responses and AHA were addressed by comparing the alleles, genotypes, haplotypes, and gene frequencies in the AHA cohort with those in the donors’ samples or Spanish population cohort. Two genes of the HLA cluster, as well as rs1049174 in KLRK1, which tags the natural killer (NK) cytotoxic activity haplotype, were found to be linked to AHA. Specifically, A*03:01 (p = 0.024; odds ratio (OR) = 0.26[0.06–0.85]) and DRB1*13:03 (p = 6.8 × 103, OR = 7.56[1.64–51.40]), as well as rs1049174 (p = 0.012), were significantly associated with AHA. In addition, two AHA patients were found to carry one copy each of the low-frequency allele DQB1*03:09 (nallele = 2, 2.04%), which was completely absent in the donors. To the best of our knowledge, this is the first time that the involvement of these specific alleles in the predisposition to AHA has been proposed. Further molecular and functional studies will be needed to unravel their specific contributions. We believe our findings expand the current knowledge on the genetic factors involved in susceptibility to AHA, which will contribute to improving the diagnosis and prognosis of AHA patients.
Some Structural Elements of Bacterial Protein MF3 That Influence Its Ability to Induce Plant Resistance to Fungi, Viruses, and Other Plant Pathogens
Authors: Erokhin Denis , Popletaeva Sophya , Sinelnikov Igor , Rozhkova Alexandra , Shcherbakova Larisa , Dzhavakhiya Vitaly
Published: November 2023

The ability of the MF3 protein from Pseudomonas fluorescens to protect plants by inducing their resistance to pathogenic fungi, bacteria, and viruses is well confirmed both in greenhouses and in the field; however, the molecular basis of this phenomenon remains unexplored. To find a relationship between the primary (and spatial) structure of the protein and its target activity, we analyzed the inducing activity of a set of mutants generated by alanine scanning and an alpha-helix deletion (ahD) in the part of the MF3 molecule previously identified by our group as a 29-amino-acid peptide working as the inducer on its own. Testing the mutants’ inducing activity using the “tobacco–tobacco mosaic virus” pathosystem revealed that some of them showed an almost threefold (V60A and V62A) or twofold (G51A, L58A, ahD) reduction in inducing activity compared to the wild-type MF3 type. Interestingly, these mutations demonstrated close proximity in the homology model, probably contributing to MF3 reception in a host plant.
The Wheat Annexin TaAnn12 Plays Positive Roles in Plant Disease Resistance by Regulating the Accumulation of Reactive Oxygen Species and Callose
Authors: Shi Beibei , Liu Weijian , Ma Qing
Published: November 2023

(1) Annexins are proteins that bind phospholipids and calcium ions in cell membranes and mediate signal transduction between Ca2+ and cell membranes. They play key roles in plant immunity. (2) In this study, virus mediated gene silencing and the heterologous overexpression of TaAnn12 in Arabidopsis thaliana Col-0 trials were used to determine whether the wheat annexin TaAnn12 plays a positive role in plant disease resistance. (3) During the incompatible interaction between wheat cv. Suwon 11 and the Puccinia striiformis f. sp. tritici (Pst) race CYR23, the expression of TaAnn12 was significantly upregulated at 24 h post inoculation (hpi). Silencing TaAnn12 in wheat enhanced the susceptibility to Pst. The salicylic acid hormone contents in the TaAnn12-silenced plants were significantly reduced. The overexpression of TaAnn12 in A. thaliana significantly increased resistance to Pseudomonas syringae pv. tomato DC3000, and the symptoms of the wild-type plants were more serious than those of the transgenic plants; the amounts of bacteria were significantly lower than those in the control group, the accumulation of Reactive Oxygen Species (ROS)and callose deposition increased, and the expression of resistance-related genes (AtPR1, AtPR2, and AtPR5) significantly increased. (4) Our results suggest that wheat TaAnn12 resisted the invasion of pathogens by inducing the production and accumulation of ROS and callose.
Behçet’s Disease: A Comprehensive Review on the Role of HLA-B*51, Antigen Presentation, and Inflammatory Cascade
Authors: Khoshbakht Saba , Başkurt Defne , Vural Atay , Vural Seçil
Published: November 2023

Behçet’s disease (BD) is a complex, recurring inflammatory disorder with autoinflammatory and autoimmune components. This comprehensive review aims to explore BD’s pathogenesis, focusing on established genetic factors. Studies reveal that HLA-B*51 is the primary genetic risk factor, but non-HLA genes (ERAP1, IL-10, IL23R/IL-12RB2), as well as innate immunity genes (FUT2, MICA, TLRs), also contribute. Genome-wide studies emphasize the significance of ERAP1 and HLA-I epistasis. These variants influence antigen presentation, enzymatic activity, and HLA-I peptidomes, potentially leading to distinct autoimmune responses. We conducted a systematic review of the literature to identify studies exploring the association between HLA-B*51 and BD and further highlighted the roles of innate and adaptive immunity in BD. Dysregulations in Th1/Th2 and Th17/Th1 ratios, heightened clonal cytotoxic (CD8+) T cells, and reduced T regulatory cells characterize BD’s complex immune responses. Various immune cell types (neutrophils, γδ T cells, natural killer cells) further contribute by releasing cytokines (IL-17, IL-8, GM-CSF) that enhance neutrophil activation and mediate interactions between innate and adaptive immunity. In summary, this review advances our understanding of BD pathogenesis while acknowledging the research limitations. Further exploration of genetic interactions, immune dysregulation, and immune cell roles is crucial. Future studies may unveil novel diagnostic and therapeutic strategies, offering improved management for this complex disease.