bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Metabolome and Transcriptome Analyses Reveal the Regulatory Mechanism of Purple Leafstalk Production in Taro (Colocasia esculenta L. Schott)
Authors: Jiang Shizheng , Guo Juxian , Khan Imran , Jahan Mohammad Shah , Tang Kang , Li Guihua , Yang Xian , Fu Mei
Published: January 2024

Taro is a plant in the Araceae family, and its leafstalk possesses significant botanical and culinary value owing to its noteworthy medicinal and nutritional attributes. Leafstalk colour is an essential attribute that significantly influences its desirability and appeal to both breeders and consumers. However, limited information is available about the underlying mechanism responsible for the taro plant’s colouration. Thus, the purpose of the current study was to elucidate the information on purple leafstalks in taro through comprehensive metabolome and transcriptome analysis. In total, 187 flavonoids, including 10 anthocyanins, were identified. Among the various compounds analysed, it was observed that the concentrations of five anthocyanins (keracyanin chloride (cyanidin 3-O-rutinoside chloride), cyanidin 3-O-glucoside, tulipanin (delphinidin 3-rutinoside chloride), idaein chloride (cyanidin 3-O-galactoside), and cyanidin chloride) were found to be higher in purple taro leafstalk compared to green taro leafstalk. Furthermore, a total of 3330 differentially expressed genes (DEGs) were identified by transcriptome analysis. Subsequently, the correlation network analysis was performed to investigate the relationship between the expression levels of these differentially expressed genes and the content of anthocyanin. There were 18 DEGs encoding nine enzymes detected as the fundamental structural genes contributing to anthocyanin biosynthesis, along with seven transcription factors (3 MYB and 4 bHLH) that may be promising candidate modulators of the anthocyanin biosynthesis process in purple taro leafstalk. The findings of the current investigation not only provide a comprehensive transcriptional code, but also give information on anthocyanin metabolites as well as beneficial insights into the colour mechanism of purple taro leafstalk.
Leptin and Leptin Receptor Polymorphisms in Infants and Their Parents: Correlation with Preterm Birth
Authors: Savino Francesco , Sardo Allegra , Gambarino Stefano , Dini Maddalena , Clemente Anna , Pau Anna , Galliano Ilaria , Bergallo Massimiliano
Published: January 2024

It has been proven that single-nucleotide polymorphisms (SNPs) in LEP and LEPR genes could predispose individuals to an increased risk of pregnancy adverse outcomes (PAOs) such as recurrent pregnancy loss (RPL) and pre-eclampsia. Preterm birth (PTB) is the leading cause of infant mortality. We decided to investigate the correlation between PTB and LEP and LEPR SNPs. The study cohort included families who underwent spontaneous PTB and control samples of families who had at-term-born (≥37 weeks of gestational age) children. Swabs were performed by rubbing the sticky end for about 30 s on the gum and on the inside of the cheek, allowing us to collect the flaking cells of the oral mucosa. Genotyping of the three SNPs—LEPRA668G, LEPG2548A and A19G—was carried out via an ARMS-MAMA real-time PCR procedure, as previously described. Regarding LEPG2548A, we found that the most expressed genotype in infants both in the preterm and the at-term group was AG; however, we did not discover any statistically significant difference (p = 0.97). Considering LEPA19G, none among the infants and parents were found to carry the AA genotype. No statistically significant differences were found between children, mothers and fathers belonging to preterm and at-term groups. We did not find a statistically significant association in newborns and their mother, but our results show a statistical correlation with the LEPRA668G genotype GG of the father. This fact can contribute to defining genetic risk factors for PTB. Further studies are certainly needed to better clarify the role of genetics in influencing preterm delivery.
Quality of Life and Incidence of Clinical Signs and Symptoms among Caregivers of Persons with Mental Disorders: A Cross-Sectional Study
Authors: Oikonomou Vasiliki , Gkintoni Evgenia , Halkiopoulos Constantinos , Karademas Evangelos C.
Published: January 2024

Background: Caring for individuals with mental disorders poses significant challenges for caregivers, often leading to compromised quality of life and mental health issues such as stress, anxiety, and depression. This study aims to assess the extent of these challenges among caregivers in Greece, identifying which demographic factors influence their well-being. Method: A total of 157 caregivers were surveyed using the SF-12 Health Survey for quality-of-life assessment and the DASS-21 questionnaire for evaluating stress, anxiety, and depression symptoms. t-tests, Kruskal–Wallis tests, Pearson’s correlation coefficients, and regression analyses were applied to understand the associations between demographics, quality of life, and mental health outcomes. Results: The study found that caregivers, especially women and younger individuals, faced high levels of mental health challenges. Marital status, educational level, and employment status also significantly influenced caregivers’ well-being. Depression was the most significant factor negatively correlating with the mental component of quality of life. The magnitude of the burden experienced by caregivers highlighted the urgency for targeted social and financial support, as well as strategic treatment programs that consider caregiver well-being. Conclusions: Caregivers of individuals with mental disorders endure significant stress, anxiety, and depression, influencing their quality of life. Demographic factors such as age, gender, marital status, education, and employment status have notable impacts. Findings emphasize the need for society-wide recognition of caregivers’ roles and the creation of comprehensive support and intervention programs to alleviate their burden, particularly in the context of the COVID-19 pandemic.
Overuse of Computed Tomography Pulmonary Angiography and Low Utilization of Clinical Prediction Rules in Suspected Pulmonary Embolism Patients at a Regional Australian Hospital
Authors: Chean Li Ning , Tan Clement , Hiskens Matthew I. , Rattenbury Marie , Sundaram Prahalath , Perara Jithmy , Smith Karen , Kumar Pranav
Published: January 2024

A pulmonary embolism (PE) is an obstruction in the pulmonary arterial system and may include non-specific signs and symptoms. Clinical prediction rules (CPRs) assess the pretest probability (PTP) of a PE to prevent the overuse of computed tomography pulmonary angiography (CTPA). CTPA overuse results in patient harm and health system waste. This study aimed to evaluate CTPA usage in an Australian regional hospital through analyzing CTPA encounters. A retrospective chart analysis was undertaken of 100 CTPAs conducted at an Australian regional hospital from April to May 2023. Analysis was undertaken for parameters including risk factors, signs and symptoms, investigations, and the use of CPRs. Overall, 86% of patients had signs and/or symptoms of a PE within a week of examination, and 6% of the population had signs of deep vein thrombosis. More than half of the population had no risk factors, while the most prevalent risk factors were a recent history of immobilization/trauma and/or having surgery that required general anesthesia in the last 4 weeks. The most common co-morbidity was chronic lung disease (11%). For the pre-test diagnostic workup, the ECG was the most ordered investigation. The Wells’ score was used at 10%, while most patients did not have any CPRs applied. The prevalence of PEs discovered on CTPAs was 9%. CPRs were under-utilized in this Australian regional hospital. The D-dimers for ruling out subjects with low PTP derived from CPRs were also underused. This led to the inappropriate overordering of CTPAs, resulting in negative implications for patients and unnecessary costs to the health system.
Perceived Factors Influencing Blue-Collar Workers’ Participation in Worksite Health Promotion Programs in Freight Transport: A Qualitative Investigation Using the TDF and COM-B
Authors: Damen Marc A. W. , Detaille Sarah I. , Engels Josephine A. , De Lange Annet H.
Published: January 2024

Blue-collar workers in the freight transport industry report a high risk of developing chronic diseases, partly due to an unhealthy lifestyle. Worksite health promotion programs (WHPPs) may be able to promote a healthier lifestyle, but participation among blue-collar workers in these programs is generally lower than among other workers. The current study aimed to further examine factors that can explain participation of blue-collar workers in these programs. A pragmatic, qualitative study was conducted, and semi-structured interviews were held with 32 blue-collar workers in freight transport in the Netherlands (94% men, 81% driver, mean age 48 (SD = 11)). The interview guide was based on the Theoretical Domains Framework (TDF) and Capability-Opportunity-Motivation-Behavior (COM-B) model, and was used to assess perceived determinants that influence participation. A combination of framework analysis and thematic analysis was conducted, which yielded the following nine main themes: (i) not being aware of WHPPs on offer, (ii) no clear picture of what to expect, (iii) (not) giving priority to health, (iv) expecting feedback and practical support, (v) being open and ready to change, (vi) preferring to be self-dependent, (vii) being offered a practical, fun and joint WHPP, (viii) having an employer who cares, thinks along and facilitates participation, and (ix) working and living in an environment in which a healthy lifestyle is not the norm. With these insights we were able to formulate recommendations to enhance the participation of blue-collar workers in WHPPs.
Missing Heritability in Albinism: Deep Characterization of a Hungarian Albinism Cohort Raises the Possibility of the Digenic Genetic Background of the Disease
Authors: Nagy Nikoletta , Pal Margit , Kun Jozsef , Galik Bence , Urban Peter , Medvecz Marta , Fabos Beata , Neller Alexandra , Abdolreza Aliasgari , Danis Judit , Szabo Viktoria , Yang Zhuo , Fenske Stefanie , Biel Martin , Gyenesei Attila , Adam Eva , Szell Marta
Published: January 2024

Albinism is characterized by a variable degree of hypopigmentation affecting the skin and the hair, and causing ophthalmologic abnormalities. Its oculocutaneous, ocular and syndromic forms follow an autosomal or X-linked recessive mode of inheritance, and 22 disease-causing genes are implicated in their development. Our aim was to clarify the genetic background of a Hungarian albinism cohort. Using a 22-gene albinism panel, the genetic background of 11 of the 17 Hungarian patients was elucidated. In patients with unidentified genetic backgrounds (n = 6), whole exome sequencing was performed. Our investigations revealed a novel, previously unreported rare variant (N687S) of the two-pore channel two gene (TPCN2). The N687S variant of the encoded TPC2 protein is carried by a 15-year-old Hungarian male albinism patient and his clinically unaffected mother. Our segregational analysis and in vitro functional experiments suggest that the detected novel rare TPCN2 variant alone is not a disease-causing variant in albinism. Deep genetic analyses of the family revealed that the patient also carries a phenotype-modifying R305W variant of the OCA2 protein, and he is the only family member harboring this genotype. Our results raise the possibility that this digenic combination might contribute to the observed differences between the patient and the mother, and found the genetic background of the disease in his case.
Buffering Mitigates Chondrocyte Oxidative Stress, Metabolic Dysfunction, and Death Induced by Normal Saline: Formulation of a Novel Arthroscopic Irrigant
Authors: Hlas Arman , Ganesh Venkateswaran , Marks Jaison , He Rui , Salem Aliasger K. , Buckwalter Joseph A. , Duchman Kyle R. , Shin Kyungsup , Martin James A. , Seol Dongrim
Published: January 2024

For decades, surgeons have utilized 0.9% normal saline (NS) for joint irrigation to improve visualization during arthroscopic procedures. This continues despite mounting evidence that NS exposure impairs chondrocyte metabolism and compromises articular cartilage function. We hypothesized that chondrocyte oxidative stress induced by low pH is the dominant factor driving NS toxicity, and that buffering NS to increase its pH would mitigate these effects. Effects on chondrocyte viability, reactive oxygen species (ROS) production, and overall metabolic function were assessed. Even brief exposure to NS caused cell death, ROS overproduction, and disruption of glycolysis, pentose phosphate, and tricarboxylic acid (TCA) cycle pathways. NS also stimulated ROS overproduction in synovial cells that could adversely alter the synovial function and subsequently the entire joint health. Buffering NS with 25 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) significantly increased chondrocyte viability, reduced ROS production, and returned metabolite levels to near control levels while also reducing ROS production in synovial cells. These results confirm that chondrocytes and synoviocytes are vulnerable to insult from the acidic pH of NS and demonstrate that adding a buffering agent to NS averts many of its most harmful effects.
Ischemia-Reperfusion Programming of Alzheimer’s Disease-Related Genes—A New Perspective on Brain Neurodegeneration after Cardiac Arrest
Authors: Pluta Ryszard , Czuczwar Stanisław J.
Published: January 2024

The article presents the latest data on pathological changes after cerebral ischemia caused by cardiac arrest. The data include amyloid accumulation, tau protein modification, neurodegenerative and cognitive changes, and gene and protein changes associated with Alzheimer’s disease. We present the latest data on the dysregulation of genes related to the metabolism of the amyloid protein precursor, tau protein, autophagy, mitophagy, apoptosis, and amyloid and tau protein transport genes. We report that neuronal death after cerebral ischemia due to cardiac arrest may be dependent and independent of caspase. Moreover, neuronal death dependent on amyloid and modified tau protein has been demonstrated. Finally, the results clearly indicate that changes in the expression of the presented genes play an important role in acute and secondary brain damage and the development of post-ischemic brain neurodegeneration with the Alzheimer’s disease phenotype. The data indicate that the above genes may be a potential therapeutic target for brain therapy after ischemia due to cardiac arrest. Overall, the studies show that the genes studied represent attractive targets for the development of new therapies to minimize ischemic brain injury and neurological dysfunction. Additionally, amyloid-related genes expression and tau protein gene modification after cerebral ischemia due to cardiac arrest are useful in identifying ischemic mechanisms associated with Alzheimer’s disease. Cardiac arrest illustrates the progressive, time- and area-specific development of neuropathology in the brain with the expression of genes responsible for the processing of amyloid protein precursor and the occurrence of tau protein and symptoms of dementia such as those occurring in patients with Alzheimer’s disease. By carefully examining the common genetic processes involved in these two diseases, these data may help unravel phenomena associated with the development of Alzheimer’s disease and neurodegeneration after cerebral ischemia and may lead future research on Alzheimer’s disease or cerebral ischemia in new directions.
Ionic Liquid-Based Polymer Matrices for Single and Dual Drug Delivery: Impact of Structural Topology on Characteristics and In Vitro Delivery Efficiency
Authors: Niesyto Katarzyna , Keihankhadiv Shadi , Mazur Aleksy , Mielańczyk Anna , Neugebauer Dorota
Published: January 2024

Previously reported amphiphilic linear and graft copolymers, derived from the ionic liquid [2-(methacryloyloxy)ethyl]trimethylammonium chloride (TMAMA_Cl‾), along with their conjugates obtained through modification either before or after polymerization with p-aminosalicylate anions (TMAMA_PAS‾), were employed as matrices in drug delivery systems (DDSs). Based on the counterion type in TMAMA units, they were categorized into single drug systems, manifesting as ionic polymers with chloride counterions and loaded isoniazid (ISO), and dual drug systems, featuring ISO loaded in self-assembled PAS conjugates. The amphiphilic nature of these copolymers was substantiated through the determination of the critical micelle concentration (CMC), revealing an increase in values post-ion exchange (from 0.011–0.063 mg/mL to 0.027–0.181 mg/mL). The self-assembling properties were favorable for ISO encapsulation, with drug loading content (DLC) ranging between 15 and 85% in both single and dual systems. In vitro studies indicated ISO release percentages between 16 and 61% and PAS release percentages between 20 and 98%. Basic cytotoxicity assessments using the 2,5-diphenyl-2H-tetrazolium bromide (MTT) test affirmed the non-toxicity of the studied systems toward human non-tumorigenic lung epithelial cell line (BEAS-2B) cell lines, particularly in the case of dual systems bearing both ISO and PAS simultaneously. These results confirmed the effectiveness of polymeric carriers in drug delivery, demonstrating their potential for co-delivery in combination therapy.
Density Functional Theory Calculations: A Useful Tool to Investigate Mechanisms of 1,3-Dipolar Cycloaddition Reactions
Authors: Chiacchio Maria Assunta , Legnani Laura
Published: January 2024

The present review contains a representative sampling of mechanistic studies, which have appeared in the literature in the last 5 years, on 1,3-dipolar cycloaddition reactions, using DFT calculations. Attention is focused on the mechanistic insights into 1,3-dipoles of propargyl/allenyl type and allyl type such as aza-ylides, nitrile oxides and azomethyne ylides and nitrones, respectively. The important role played by various metal–chiral–ligand complexes and the use of chiral eductors in promoting the site-, regio-, diastereo- and enatioselectivity of the reaction are also outlined.
Vitamin D/Bone Mineral Density and Triglyceride Paradoxes Seen in African Americans: A Cross-Sectional Study and Review of the Literature
Authors: Stevens Christopher M. , Jain Sushil K.
Published: January 2024

Vitamin D is known to have a positive effect on bone health. Despite the greater frequency of vitamin D deficiency in African Americans (AA), they have a higher bone mineral density (BMD) compared to whites, demonstrating a disconnect between BMD and vitamin D levels in AA. Another intriguing relationship seen in AA is the triglyceride (TG) paradox, an unusual phenomenon in which a normal TG status is observed even when patients house conditions known to be characterized by high TG levels, such as Type II diabetes. To the best of our knowledge, no study has examined whether these two paradoxical relationships exist simultaneously in AA subjects with Type II diabetes. In this study, we compared levels of blood markers, including HbA1c, TG, and vitamin D, measured as serum 25-hydroxyvitamin D [25(OH)VD] µM/mL, [25(OH)VD]/TG, calcium, and BMD in AA (n = 56) and white (n = 26) subjects with Type II diabetes to see whether these relationships exist concurrently. We found that AA subjects had significantly lower TG and [25(OH)VD] levels and a significantly higher BMD status compared to white subjects, even when the ages, BMI, duration of diabetes, HbA1c, and calcium levels were similar between the two groups. This demonstrates that these two paradoxical relationships exist simultaneously in Type II diabetic AA subjects. In addition to these findings, we discuss the current hypotheses in the literature that attempt to explain why these two intriguing relationships exist. This review also discusses four novel hypotheses, such as altered circulating levels and the potential role of estrogen and hydrogen sulfide on BMD and HMG-CoA reductase as a possible contributor to the TG paradox in AA subjects. This manuscript demonstrates that there are still many unanswered questions regarding these two paradoxical relationships and further research is needed to determine why they exist and how they can be implemented to improve healthcare.
Molecular Insights into the Synergistic Effects of Putrescine and Ammonium on Dinoflagellates
Authors: Wang Yanfei , Coyne Kathryn J.
Published: January 2024

Ammonium and polyamines are essential nitrogen metabolites in all living organisms. Crosstalk between ammonium and polyamines through their metabolic pathways has been demonstrated in plants and animals, while no research has been directed to explore this relationship in algae or to investigate the underlying molecular mechanisms. Previous research demonstrated that high concentrations of ammonium and putrescine were among the active substances in bacteria-derived algicide targeting dinoflagellates, suggesting that the biochemical inter-connection and/or interaction of these nitrogen compounds play an essential role in controlling these ecologically important algal species. In this research, putrescine, ammonium, or a combination of putrescine and ammonium was added to cultures of three dinoflagellate species to explore their effects. The results demonstrated the dose-dependent and species-specific synergistic effects of putrescine and ammonium on these species. To further explore the molecular mechanisms behind the synergistic effects, transcriptome analysis was conducted on dinoflagellate Karlodinium veneficum treated with putrescine or ammonium vs. a combination of putrescine and ammonium. The results suggested that the synergistic effects of putrescine and ammonium disrupted polyamine homeostasis and reduced ammonium tolerance, which may have contributed to the cell death of K. veneficum. There was also transcriptomic evidence of damage to chloroplasts and impaired photosynthesis of K. veneficum. This research illustrates the molecular mechanisms underlying the synergistic effects of the major nitrogen metabolites, ammonium and putrescine, in dinoflagellates and provides direction for future studies on polyamine biology in algal species.
APRF1 Interactome Reveals HSP90 as a New Player in the Complex That Epigenetically Regulates Flowering Time in Arabidopsis thaliana
Authors: Isaioglou Ioannis , Podia Varvara , Velentzas Athanassios D. , Kapolas Georgios , Beris Despoina , Karampelias Michael , Plitsi Panagiota Konstantinia , Chatzopoulos Dimitris , Samakovli Despina , Roussis Andreas , Merzaban Jasmeen , Milioni Dimitra , Stravopodis Dimitrios J. , Haralampidis Kosmas
Published: January 2024

WD40 repeat proteins (WDRs) are present in all eukaryotes and include members that are implicated in numerous cellular activities. They act as scaffold proteins and thus as molecular “hubs” for protein–protein interactions, which mediate the assembly of multifunctional complexes that regulate key developmental processes in Arabidopsis thaliana, such as flowering time, hormonal signaling, and stress responses. Despite their importance, many aspects of their putative functions have not been elucidated yet. Here, we show that the late-flowering phenotype of the anthesis promoting factor 1 (aprf1) mutants is temperature-dependent and can be suppressed when plants are grown under mild heat stress conditions. To gain further insight into the mechanism of APRF1 function, we employed a co-immunoprecipitation (Co-IP) approach to identify its interaction partners. We provide the first interactome of APRF1, which includes proteins that are localized in several subcellular compartments and are implicated in diverse cellular functions. The dual nucleocytoplasmic localization of ARRF1, which was validated through the interaction of APRF1 with HEAT SHOCK PROTEIN 1 (HSP90.1) in the nucleus and with HSP90.2 in the cytoplasm, indicates a dynamic and versatile involvement of APRF1 in multiple biological processes. The specific interaction of APRF1 with the chaperon HSP90.1 in the nucleus expands our knowledge regarding the epigenetic regulation of flowering time in A. thaliana and further suggests the existence of a delicate thermoregulated mechanism during anthesis.
Mitochondrial Glutathione in Cellular Redox Homeostasis and Disease Manifestation
Authors: Chen Tsung-Hsien , Wang Hsiang-Chen , Chang Chia-Jung , Lee Shih-Yu
Published: January 2024

Mitochondria are critical for providing energy to maintain cell viability. Oxidative phosphorylation involves the transfer of electrons from energy substrates to oxygen to produce adenosine triphosphate. Mitochondria also regulate cell proliferation, metastasis, and deterioration. The flow of electrons in the mitochondrial respiratory chain generates reactive oxygen species (ROS), which are harmful to cells at high levels. Oxidative stress caused by ROS accumulation has been associated with an increased risk of cancer, and cardiovascular and liver diseases. Glutathione (GSH) is an abundant cellular antioxidant that is primarily synthesized in the cytoplasm and delivered to the mitochondria. Mitochondrial glutathione (mGSH) metabolizes hydrogen peroxide within the mitochondria. A long-term imbalance in the ratio of mitochondrial ROS to mGSH can cause cell dysfunction, apoptosis, necroptosis, and ferroptosis, which may lead to disease. This study aimed to review the physiological functions, anabolism, variations in organ tissue accumulation, and delivery of GSH to the mitochondria and the relationships between mGSH levels, the GSH/GSH disulfide (GSSG) ratio, programmed cell death, and ferroptosis. We also discuss diseases caused by mGSH deficiency and related therapeutics.
Do Cuticular Gaps Make It Possible to Study the Composition of the Cell Walls in the Glands of Drosophyllum lusitanicum?
Authors: Płachno Bartosz J. , Kapusta Małgorzata , Stolarczyk Piotr , Świątek Piotr
Published: January 2024

Carnivorous plants can survive in poor habitats because they have the ability to attract, capture, and digest prey and absorb animal nutrients using modified organs that are equipped with glands. These glands have terminal cells with permeable cuticles. Cuticular discontinuities allow both secretion and endocytosis. In Drosophyllum lusitanicum, these emergences have glandular cells with cuticular discontinuities in the form of cuticular gaps. In this study, we determined whether these specific cuticular discontinuities were permeable enough to antibodies to show the occurrence of the cell wall polymers in the glands. Scanning transmission electron microscopy was used to show the structure of the cuticle. Fluorescence microscopy revealed the localization of the carbohydrate epitopes that are associated with the major cell wall polysaccharides and glycoproteins. We showed that Drosophyllum leaf epidermal cells have a continuous and well-developed cuticle, which helps the plant inhibit water loss and live in a dry environment. The cuticular gaps only partially allow us to study the composition of cell walls in the glands of Drosophyllum. We recoded arabinogalactan proteins, some homogalacturonans, and hemicelluloses. However, antibody penetration was only limited to the cell wall surface. The localization of the wall components in the cell wall ingrowths was missing. The use of enzymatic digestion improves the labeling of hemicelluloses in Drosophyllum glands.
Interferon-β Overexpression in Adipose Tissue-Derived Stem Cells Induces HepG2 and Macrophage Cell Death in Liver Tumor Organoids via Induction of TNF-Related Apoptosis-Inducing Ligand Expression
Authors: Yoon Yongdae , Kim Chang Wan , Kim Moon Young , Baik Soon Koo , Jung Pil Young , Eom Young Woo
Published: January 2024

Liver tumor organoids derived from liver tumor tissues and pluripotent stem cells are used for liver tumor research but have several challenges in primary cell isolation and stem cell differentiation. Here, we investigated the potential of HepG2-based liver tumor organoids for screening anticancer drugs by evaluating their responsiveness to IFN-β produced by mesenchymal stem cells (MSCs). Liver tumor organoids were prepared in three days on Matrigel using HepG2, primary liver sinusoidal epithelial cells (LSECs), LX-2 human hepatic stellate cells, and THP-1-derived macrophages at a ratio of 4:4:1:1, with 105 total cells. Hepatocyte-related and M2 macrophage-associated genes increased in liver tumor organoids. IFN-β treatment decreased the viability of liver tumor organoids and increased M1 macrophage marker expression (i.e., TNF-α and iNOS) and TRAIL. TRAIL expression was increased in all four cell types exposed to IFN-β, but cell death was only observed in HepG2 cells and macrophages. Further, MSCs overexpressing IFN-β (ASC-IFN-β) also expressed TRAIL, contributing to the reduced viability of liver tumor organoids. In summary, IFN-β or ASC-IFN-β can induce TRAIL-dependent HepG2 and macrophage cell death in HepG2-based liver tumor organoids, highlighting these liver tumor organoids as suitable for anticancer drug screening and mechanistic studies.
Pancreatic Neuroendocrine Tumors: Signaling Pathways and Epigenetic Regulation
Authors: Saleh Zena , Moccia Matthew C. , Ladd Zachary , Joneja Upasana , Li Yahui , Spitz Francis , Hong Young Ki , Gao Tao
Published: January 2024

Pancreatic neuroendocrine tumors (PNETs) are characterized by dysregulated signaling pathways that are crucial for tumor formation and progression. The efficacy of traditional therapies is limited, particularly in the treatment of PNETs at an advanced stage. Epigenetic alterations profoundly impact the activity of signaling pathways in cancer development, offering potential opportunities for drug development. There is currently a lack of extensive research on epigenetic regulation in PNETs. To fill this gap, we first summarize major signaling events that are involved in PNET development. Then, we discuss the epigenetic regulation of these signaling pathways in the context of both PNETs and commonly occurring—and therefore more extensively studied—malignancies. Finally, we will offer a perspective on the future research direction of the PNET epigenome and its potential applications in patient care.
Circulating Monocyte Chemoattractant Protein-1 (MCP-1) in Patients with Primary Biliary Cholangitis
Authors: Bauer Alicja , Rawa Tomasz
Published: January 2024

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that leads to the destruction of the intrahepatic bile ducts. While the inflammatory process can be mediated by monocyte chemotactic protein-1 (MCP-1), the importance of circulating MCP-1 as a biomarker is unclear. Our aim was to assess the diagnostic significance of the serum concentrations of MCP-1 in PBC patients. We compared circulating MCP-1 with biochemical, immunological and histological parameters. Serum samples were collected from 120 PBC patients, 60 pathologic controls and 30 healthy donors. MCP-1 levels were determined by using commercial enzyme-linked immunosorbent assay (ELISA). Elevated serum MCP-1 levels were detected in 66% of PBC patients with a specificity of 97%. Significantly higher levels of MCP-1 protein were found in the sera of patients with PBC than in the group of healthy individuals—410.2 pg/mL vs. 176.0 pg/mL, p < 0.01). Patients with higher concentrations of alkaline phosphatase also had higher levels of MCP-1 (r = 0.4, p < 0.01). In accordance with Ludwig’s classification, a positive correlation of serum MCP-1 concentration with the degree of fibrosis was observed, OR = 6.1, p = 0.0003. We compared the MCP-1 with procollagen type III, hyaluronic acid (HA), FIB-4 index, APRI and collagen type IV when predicting the advance of liver fibrosis. Circulating MCP-1 is better correlated with liver fibrosis and is also associated with the occurrence of specific antimitochondrial autoantibodies and specific anti-nuclear autoantibodies—anti-gp210. MPC-1 can be considered to be a tool for diagnosing the degree of fibrosis in PBC, and combinations of MCP-1 and other specific biomarkers could support the diagnosis of PBC.
The Efficacy and Safety of Transvaginal Ethanol Sclerotherapy in the Treatment of Endometrial Cysts—A Systematic Review
Authors: Frankowska Karolina , Dymanowska-Dyjak Izabela , Abramiuk Monika , Polak Grzegorz
Published: January 2024

Endometriosis, as a chronic disorder that is a source of severe pain ailments and infertility, requires a comprehensive therapeutic approach. Sclerotherapy, consisting of the administration of sclerosing agents into the cyst, is a constantly evolving minimally invasive treatment method for this disease. Hence, the main objective of this systematic review was to evaluate the impact of its most often used variant, transvaginal ethanol sclerotherapy, on endometriosis-related symptoms, endometrial cyst recurrence rate, ovarian reserve, assisted reproductive technology (ART) outcomes, and pregnancy outcomes, as well as to assess potential complications resulting from this treatment. This systematic review was undertaken using PubMed, Scopus, Web of Science, and Cochrane Library databases on 24 November 2023. The risk of bias in included studies was assessed with the use of the Newcastle–Ottawa scale (NOS) and the revised Cochrane risk of bias 2.0 tool for randomized controlled trials. From the 1141 records obtained from all databases, 16 studies have been included in this review. The use of ethanol sclerotherapy was characterized by a low rate of post-procedural complications. The recurrence rate of endometrial cysts after the procedure depended on the ethanol instillation time within the cyst. Although ethanol sclerotherapy had negligible influence on ovarian reserves when compared to laparoscopic cystectomy, the effects of both these methods on pregnancy outcomes were comparable. This review identifies that sclerotherapy is safe, provides significant relief of symptoms, and does not impair the reproductive potential of the patients.
Cyclobutanone Inhibitors of Diaminopimelate Desuccinylase (DapE) as Potential New Antibiotics
Authors: Habeeb Mohammad Thahani S. , Kelley Emma H. , Reidl Cory T. , Konczak Katherine , Beulke Megan , Javier Janielle , Olsen Kenneth W. , Becker Daniel P.
Published: January 2024

Based on our previous success in using cyclobutanone derivatives as enzyme inhibitors, we have designed and prepared a 37-member library of α-aminocyclobutanone amides and sulfonamides, screened for inhibition of the bacterial enzyme diaminopimelate desuccinylase (DapE), which is a promising antibiotic target, and identified several inhibitors with micromolar inhibitory potency. Molecular docking suggests binding of the deprotonated hydrate of the strained cyclobutanone, and thermal shift analysis with the most potent inhibitor (3y, IC50 = 23.1 µM) enabled determination of a Ki value of 10.2 +/− 0.26 µM and observed two separate Tm values for H. influenzae DapE (HiDapE).
Effects of TiO2 Nanotubes and Reduced Graphene Oxide on Streptococcus mutans and Preosteoblastic Cells at an Early Stage
Authors: Ji Min-Kyung , Kim Hyeonji , Jeong Geonwoo , Kim Won-Jae , Ryu Je-Hwang , Cho Hoonsung , Lim Hyun-Pil
Published: January 2024

The effects of TiO2 nanotube (TNT) and reduced graphene oxide (rGO) deposition onto titanium, which is widely used in dental implants, on Streptococcus mutans (S. mutans) and preosteoblastic cells were evaluated. TNTs were formed through anodic oxidation on pure titanium, and rGO was deposited using an atmospheric plasma generator. The specimens used were divided into a control group of titanium specimens and three experimental groups: Group N (specimens with TNT formation), Group G (rGO-deposited specimens), and Group NG (specimens under rGO deposition after TNT formation). Adhesion of S. mutans to the surface was assessed after 24 h of culture using a crystal violet assay, while adhesion and proliferation of MC3T3-E1 cells, a mouse preosteoblastic cell line, were evaluated after 24 and 72 h through a water-soluble tetrazolium salt assay. TNT formation and rGO deposition on titanium decreased S. mutans adhesion (p < 0.05) and increased MC3T3-E1 cell adhesion and proliferation (p < 0.0083). In Group NG, S. mutans adhesion was the lowest (p < 0.05), while MC3T3-E1 cell proliferation was the highest (p < 0.0083). In this study, TNT formation and rGO deposition on a pure titanium surface inhibited the adhesion of S. mutans at an early stage and increased the initial adhesion and proliferation of preosteoblastic cells.
The Risk Function of Breast and Ovarian Cancers in the Avrami–Dobrzyński Cellular Phase-Transition Model
Authors: Zawadzka Anna , Brzozowska Beata , Matyjanka Anna , Mikula Michał , Reszczyńska Joanna , Tartas Adrianna , Fornalski Krzysztof W.
Published: January 2024

Specifying the role of genetic mutations in cancer development is crucial for effective screening or targeted treatments for people with hereditary cancer predispositions. Our goal here is to find the relationship between a number of cancerogenic mutations and the probability of cancer induction over the lifetime of cancer patients. We believe that the Avrami–Dobrzyński biophysical model can be used to describe this mechanism. Therefore, clinical data from breast and ovarian cancer patients were used to validate this model of cancer induction, which is based on a purely physical concept of the phase-transition process with an analogy to the neoplastic transformation. The obtained values of model parameters established using clinical data confirm the hypothesis that the carcinogenic process strongly follows fractal dynamics. We found that the model’s theoretical prediction and population clinical data slightly differed for patients with the age below 30 years old, and that might point to the existence of an ancillary protection mechanism against cancer development. Additionally, we reveal that the existing clinical data predict breast or ovarian cancers onset two years earlier for patients with BRCA1/2 mutations.
MicroRNA Profiling of the Inflammatory Response after Early and Late Asthmatic Reaction
Authors: Duecker Ruth P. , Alemdar Oguzhan , Wimmers Andreas , Gronau Lucia , Chiocchetti Andreas G. , Valesky Eva M. , Donath Helena , Trischler Jordis , Blumchen Katharina , Zielen Stefan , Schubert Ralf
Published: January 2024

A high proportion of house dust mite (HDM)-allergic asthmatics suffer from both an early asthmatic reaction (EAR) and a late asthmatic reaction (LAR) which follows it. In these patients, allergic inflammation is more relevant. MiRNAs have been shown to play an important role in the regulation of asthma’s pathology. The aim of this study was to analyze the miRNA profile in patients with mild asthma and an HDM allergy after bronchial allergen provocation (BAP). Seventeen patients with EAR/no LAR and 17 patients with EAR plus LAR, determined by a significant fall in FEV1 after BAP, were differentially analyzed. As expected, patients with EAR plus LAR showed a more pronounced allergic inflammation and FEV1 delta drop after 24 h. NGS-miRNA analysis identified the down-regulation of miR-15a-5p, miR-15b-5p, and miR-374a-5p after BAP with the highest significance in patients with EAR plus LAR, which were negatively correlated with eNO and the maximum decrease in FEV1. These miRNAs have shared targets like CCND1, VEGFA, and GSK3B, which are known to be involved in airway remodeling, basement membrane thickening, and Extracellular Matrix deposition. NGS-profiling identified miRNAs involved in the inflammatory response after BAP with HDM extract, which might be useful to predict a LAR.
The Efficacy of Continuous Serratus Anterior and Erector Spinae Plane Blocks vs Intercostal Nerve Block in Uniportal-Vats Surgery: A Propensity-Matched Prospective Trial
Authors: Nachira Dania , Punzo Giovanni , Calabrese Giuseppe , Sessa Flaminio , Congedo Maria Teresa , Beccia Giovanna , Aceto Paola , Kuzmych Khrystyna , Cambise Chiara , Sassorossi Carolina , Nocera Adriana , Senatore Alessia , Vita Maria Letizia , Meacci Elisa , Sollazzi Liliana , Margaritora Stefano
Published: January 2024

Background: To evaluate the analgesic efficacy of continuous erector spinae plane block(c-ESPB) and serratus anterior plane block(c-SAPB) versus the intercostal nerve block (ICNB) in Uniportal-VATS in terms of pain control, drug consumption, and complications. Methods: Ninety-three consecutive patients, undergone one of the three peripheral nerve blocks after Uniportal-VATS, were prospectively enrolled. A 1:1 propensity score matching was used to minimize bias. Results: C-ESPB and c-SAPB groups had no difference in morphine request upon awakening compared to ICNB. A higher VAS-score was recorded in c-ESPB compared to ICNB in the first 12 h after surgery. A significantly lower consumption of paracetamol in II postoperative day (p.o.d.) and tramadol in I and II p.o.d. was recorded in the c-ESPB group compared to the ICNB group. A higher dynamic VAS score was recorded at 24 h and 48 h in the ICNB group compared to the c-SAPB. No difference was found in safety, VAS-score and drug consumption between c-ESPB and c-SAPB at any given time, except for a higher tramadol request in c-SAPB in II p.o.d. Conclusions: C-ESPB and c-SAPB appear to have the same safety and analgesic efficacy when compared between them and to ICNB in Uniportal-VATS approach. C-ESPB showed a delayed onset of analgesic effect and a lower postoperative drug consumption compared to ICNB.
The Effect of an Active Break Intervention on Nonspecific Low Back Pain and Musculoskeletal Discomfort during Prolonged Sitting among Young People—Protocol for a Randomized Controlled Trial
Authors: Plandowska Magdalena , Labecka Marta Kinga , Truszczyńska-Baszak Aleksandra , Płaszewski Maciej , Rajabi Reza , Makaruk Beata , Różańska Dorota
Published: January 2024

Background: The most recent evidence has shown that the pandemic of COVID-19 caused an increasing problem with spinal pain in the population of teenagers and young adults. This may be explained by prolonged sitting times in flexed positions with electronic devices. Positions maintained for a prolonged time cause overloading of soft tissue and discogenic symptoms. This study aims to evaluate the effectiveness of the active break program in reducing musculoskeletal discomfort and LBP (low back pain) among young people. Methods: This will be a randomized controlled study. The participants will be recruited from Bachelor’s course students of the Physical Education Department aged 18–25 years. The participants will be assigned to an experimental group (with an active break) and a control group. The group with an active break with lumbar and hip extension exercises will be recommended to take a break for every 30 min of sitting. The control group will receive self-care recommendations. The primary outcomes will be pain intensity (Visual Analogue Scale), disability index (Oswestry Disability Index), and perceived musculoskeletal discomfort during prolonged sitting (Borg scale), assessed at baseline and after the intervention, and the Global Perceived Effect, only assessed after the 12-week intervention. The secondary outcome will be a Post-Intervention Questionnaire (a 5-item self-completed questionnaire), only assessed after the 12-week intervention. Results: Our main research outcome—exercise protocols and interventions—will lead to the development of recommendations and protocols for the LBP population. It is important to determine the effect of interventions that are feasible and effective in addressing LBP and perceived musculoskeletal discomfort in young people. Conclusions: This is the first study examining the effect of active breaks with proposed lumbar and hip extension exercises on reducing or decreasing LBP in students based on a search of the literature. Exercises and recommendations will be the basis for developing proprietary preventative and therapeutic programs, which will be implemented in selected educational institutions.
Cervical Multifidus and Longus Colli Ultrasound Differences among Patients with Cervical Disc Bulging, Protrusion and Extrusion and Asymptomatic Controls: A Cross-Sectional Study
Authors: Javanshir Khodabakhsh , Ghafouri-Rouzbehani Payam , Zohrehvand Amirhossein , Naeimi Arvin , Fernández-de-las-Peñas César , Nikbakht Hossein-Ali , Mousavi-Khatir Seyedeh Roghayeh , Valera-Calero Juan Antonio
Published: January 2024

The aim of this study was to analyze the differences in morphological and histological features of the cervical multifidus (CM) and longus colli (LC) muscles among patients with cervical disc bulging, protrusion, or extrusion. Fifteen patients with cervical disc bulging (20% male, mean age: 48.5, standard deviation (SD) 7.5 years), fifteen with cervical disc protrusion (6% male, mean age: 43, SD 7.8 years), and fifteen with cervical disc extrusion (40% male, mean age: 44, SD 8 years) diagnosed via clinical and imaging findings participated in this study. Additionally, fifteen asymptomatic controls (40% male, mean age: 40.4, SD 9.7 years) were also included. The following ultrasound measurements, cross-sectional area (CSA), anterior–posterior distance (APD), lateral dimension (LD), and mean echo-intensity (EI) of the CM and LC at C5-C6 level were examined by an assessor blinded to the subject’s condition. The results revealed no group ×side significant differences among the groups (p > 0. 00625). However, group effects were found for APD and MEI of the CM (p = 0.006 and p < 0.001, respectively) and CSA, APD and MEI of the LC (all, p < 0.001). The LD of the LC muscle and the APD and LD of the CM were negatively associated with related disability (p < 0.01; p < 0.05 and p < 0.01, respectively), and pain intensity was negatively associated with LC APD and LD (both p < 0.05). These results suggest that US can be used to detect bilateral morphological changes in deep cervical flexors and extensors to discriminate patients with cervical disc alterations.
Association between Psychological Distress and Possible, Probable, and Definite Sleep Bruxism—A Comparison of Approved Diagnostic Procedures
Authors: Walentek Nicole Pascale , Schäfer Ralf , Bergmann Nora , Franken Michael , Ommerborn Michelle Alicia
Published: January 2024

(1) Background: The relationship between sleep bruxism (SB) and psychological distress has been investigated in numerous studies and is heterogeneous. Different diagnostic procedures have been applied to determine SB. The aim of this study was to directly compare the association between psychological distress and SB diagnosed by different accepted methods. (2) Methods: Data of N = 45 subjects were analyzed, including group comparisons and correlation analyses. Following diagnostic methods for the determination of SB were used in one sample: self-report, clinical assessment, polysomnography with audio–video recording and a novel diagnostic sheet with analyzing software. Psychological distress was measured using the global severity index (GSI) of the Symptom Checklist-90-Standard (SCL-90-S). (3) Results: The GSI did not differ significantly between subjects with and without SB, regardless of the underlying diagnostic classification (p > 0.05). In-depth correlation analyses of self-report and clinical data revealed a weak-to-medium correlation with the GSI (r = 0.12–0.44). Due to non-normally distributed data, a test of statistical significance was not possible. Variables of instrumental methods such as the SB index (amount of SB activity per hour) of polysomnography (PSG) showed almost no correlation with psychological distress (r = −0.06–0.05). (4) Conclusions: Despite these limitations, the results provide an indication that the choice of diagnostic procedure may elucidate the variance in the correlation between SB and psychological distress.