bluuebunny/crossref_metadata_2025 huggingface dataset:
Applying and Evaluating the Modified Method of the Rothermel Model under No-Wind Conditions for Pinus koraiensis Plantations
Authors: Guo Yan , Hu Haiqing , Hu Tongxin , Ren Menglin , Chen Boxuan , Fan Jiale , Man Ziyuan , Sun Long
Published: July 2024

Pinus koraiensis is one of the important tree species in Northeast China. Due to its high pine-needle-oil content and the density of human activities in its habitat, the forest-fire prevention situation is severe in the context of climate change. The rate of surface-fire spread is one of the key indicators for scientifically advancing early fire prevention and is crucial for guiding forest firefighting operations. In this study, we investigated how moisture content, load, and slope impact the surface-fire spread rate using indoor-simulated fire-spread experiments. Furthermore, we analyzed the limitations in the Rothermel model for predicting the surface-fire spread rate in P. koraiensis plantations and proposed modifications to the model by the modification method of priority to no-wind or slope conditions and slope conditions. Additionally, we evaluated the prediction accuracy of the original Rothermel model and two other modified models on the surface-fire spread rate. A high moisture content and low slope demonstrated an absolute inhibitory effect on the rate of surface-fire spread, whereas the promotional effect of a low moisture content and high slope was easily disturbed by the other factors. Under high-slope conditions, an overestimation situation was observed in the Rothermel model. Both of the modification methods involving priority to no-wind or slope conditions and slope conditions could improve this situation. Furthermore, the modification method demonstrated a better improvement effect on the prediction accuracy. Our findings provide valuable insights for refining the Rothermel model and offer guidance for improving the accuracy of predicting fire spread rates and behavior for Pinus koraiensis. This bears immense significance for advancing the understanding and calculation of the ROS of forest fires in the region.
Bamboo Breeding Strategies in the Context of “Bamboo as a Substitute for Plastic Initiative”
Authors: Li Xiaohua , Sun Huayu
Published: July 2024

Bamboo breeding strategies are essential in realizing “Bamboo as a Substitute for Plastic (BASP)”. This review article aims to explore the crucial role of breeding strategies in achieving the substitution of plastic products with bamboo as outlined under the BASP Initiative. Firstly, we address the issue of plastic pollution, along with the background of reducing the market share and demand for plastic products. It categorizes the types of bamboo products that can fully or partially replace plastic products in various categories, such as daily necessities, building materials, and industrial products. Then, we investigate which bamboo species can replace which plastic products and propose the need for bamboo improvement. Furthermore, it presents data from positioning observation research stations for bamboo forest ecosystems in China and outlines the essential traits necessary for bamboo substitution, including characteristics like long internode length, extended fiber length, thick culm wall, and optimal cellulose-to-lignin content ratio, among others. Finally, we discuss breeding methods and genetic improvement as key strategies to achieve bamboo substitution and suggest the potential of enhancing bamboo traits to serve as a viable replacement source for plastics. This comprehensive approach aims to enhance bamboo’s growth features and physical properties to meet the criteria for substituting bamboo for plastics effectively.
Contrasting Regeneration Patterns in Abies alba-Dominated Stands: Insights from Structurally Diverse Mountain Forests across Europe
Authors: Kolisnyk Bohdan , Wellstein Camilla , Czacharowski Marcin , Drozdowski Stanisław , Bielak Kamil
Published: July 2024

To maintain the ecosystem resilience to large-scale disturbances in managed forests, it is essential to adhere to the principles of close-to-nature silviculture, adapt practices to the traits of natural forest types, and utilize natural processes, including natural regeneration. This study examines the natural regeneration patterns in silver fir (Abies alba Mill.)-dominated forests, analyzing how the stand structure—tree size diversity, species composition, and stand density—affects the regeneration. We analyze the data from four sites in Poland, Germany, and Italy, employing generalized linear and zero-inflated models to evaluate the impact of the management strategies (even- vs. uneven-aged) and forester-controlled stand characteristics (structural diversity, broadleaf species admixture, and stand density) on the probability of regeneration, its density, and the developmental stages (seedling, small sapling, and tall sapling) across a climatic gradient. Our results indicate a significantly higher probability of regeneration in uneven-aged stands, particularly in areas with lower temperatures and lower overall regeneration density. The tree size diversity in the uneven-aged stands favors advancement from juveniles to more developed stages (seedling to sapling) in places with higher aridity. A denser stand layer (higher stand total basal area) leads to a lower density of natural regeneration for all the present species, except silver fir if considered separately, signifying that, by regulating the stand growing stock, we can selectively promote silver fir. A higher admixture of broadleaf species generally decreases the regeneration density across all the species, except in a water-rich site in the Bavarian Alps, where it had a strong positive impact. These findings underscore the complex interactions of forest ecosystems and provide a better understanding required for promoting silver fir regeneration, which is essential for a close-to-nature silviculture under climate change.
Groundwater Pollution: Sources, Mechanisms, and Prevention
Authors: Sidiropoulos Pantelis
Published: July 2024

Groundwater resources are vital for ecosystems and human health and prosperity [...]
Bidirectional Relationships between Sarcopenia and Pelvic Floor Disorders
Authors: Grosman Yacov , Kalichman Leonid
Published: July 2024

Sarcopenia and pelvic floor disorders (PFDs) are prevalent and often cooccurring conditions in the aging population. However, their bidirectional relationship and underlying mechanisms remain underexplored. This narrative review aims to elucidate this relationship by exploring potential causative interplays, shared pathophysiological mechanisms, and common risk factors. A comprehensive literature search was conducted to identify relevant studies focusing on epidemiological associations, interaction mechanisms, and implications for patient care. While epidemiological studies demonstrate associations between sarcopenia and PFDs, our findings reveal a cyclical relationship where sarcopenia may exacerbate PFDs through mechanisms such as decreased muscle strength and mobility. Conversely, the presence of PFDs often leads to reduced physical activity due to discomfort and mobility issues, which in turn exacerbate the muscle atrophy associated with sarcopenia. Additionally, shared risk factors such as physical inactivity, nutritional deficiencies, metabolic syndrome, and menopausal hormonal changes likely contribute to the onset and progression of both conditions. These interactions underscore the importance of concurrently integrated care approaches that address both conditions. Effective management requires comprehensive screening, the recognition of contributing factors, and tailored exercise regimens supported by a multidisciplinary approach. Future research should focus on longitudinal studies tracking disease progression and evaluating the efficacy of multidisciplinary care models in optimizing patient outcomes.
Functional Genomics in Psoriasis
Authors: Rossi Stefano , Richards Ellie Louise , Orozco Gisela , Eyre Stephen
Published: July 2024

Psoriasis is an autoimmune cutaneous condition that significantly impacts quality of life and represents a burden on society due to its prevalence. Genome-wide association studies (GWASs) have pinpointed several psoriasis-related risk loci, underlining the disease’s complexity. Functional genomics is paramount to unveiling the role of such loci in psoriasis and disentangling its complex nature. In this review, we aim to elucidate the main findings in this field and integrate our discussion with gold-standard techniques in molecular biology—i.e., Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)—and high-throughput technologies. These tools are vital to understanding how disease risk loci affect gene expression in psoriasis, which is crucial in identifying new targets for personalized treatments in advanced precision medicine.
Parotid Gland Tumors: Molecular Diagnostic Approaches
Authors: Vrinceanu Daniela , Dumitru Mihai , Bratiloveanu Miruna , Marinescu Andreea , Serboiu Crenguta , Manole Felicia , Palade Dragos Octavian , Costache Adrian , Costache Mariana , Patrascu Oana
Published: July 2024

Parotid gland pathology represents a web of differential diagnoses. There are many complex cases that require extensive diagnostic tests for a complete and correct final pathology diagnosis. Currently the official classification of parotid gland tumors extends over more than 40 subtypes. We performed a query of the PubMed database regarding the use of molecular biology tests in performing a better characterization of the tumors in specific cases. By using fluorescence in situ hybridization (FISH), reverse transcription polymerase chain reaction (RT-PCR) or next-generation sequencing, the team managing complex cases can offer a personalized therapeutic solution. We review the molecular differential diagnosis according to published articles in the last 5 years for many types of parotid gland tumors ranging from benign to borderline malign tumors to malign aggressive tumors. Mucoepidermoid carcinoma is a distinct subtype of parotid malignancy that was the subject of a consistent number of articles. However, the molecular biology diagnosis techniques helped more in excluding the diagnosis of mucoepidermoid carcinoma, and probably retrospectively limiting the number of cases with this final diagnosis. In Romania, the molecular biology diagnosis is available only in limited research facilities and should receive more consistent funding that will make it available on a larger scale. The novelty of this scoping review is that we propose an algorithm for molecular differential diagnosis of the tumors that could be encountered in the parotid gland.
B Cell Lymphocytes as a Potential Source of Breast Carcinoma Marker Candidates
Authors: Tkáčiková Soňa , Marcin Miroslav , Bober Peter , Kacírová Mária , Šuliková Michaela , Parnica Jozef , Tóth Dávid , Lenárt Marek , Radoňak Jozef , Urdzík Peter , Fedačko Ján , Sabo Ján
Published: July 2024

Despite advances in the genomic classification of breast cancer, current clinical tests and treatment decisions are commonly based on protein-level information. Nowadays breast cancer clinical treatment selection is based on the immunohistochemical (IHC) determination of four protein biomarkers: Estrogen Receptor 1 (ESR1), Progesterone Receptor (PGR), Human Epidermal Growth Factor Receptor 2 (HER2), and proliferation marker Ki-67. The prognostic correlation of tumor-infiltrating T cells has been widely studied in breast cancer, but tumor-infiltrating B cells have not received so much attention. We aimed to find a correlation between immunohistochemical results and a proteomic approach in measuring the expression of proteins isolated from B-cell lymphocytes in peripheral blood samples. Shotgun proteomic analysis was chosen for its key advantage over other proteomic methods, which is its comprehensive and untargeted approach to analyzing proteins. This approach facilitates better characterization of disease-associated changes at the protein level. We identified 18 proteins in B cell lymphocytes with a significant fold change of more than 2, which have promising potential to serve as breast cancer biomarkers in the future.
Lack of VEGFA/KDR Signaling in Conventional Renal Cell Carcinoma Explains the Low Efficacy of Target Therapy and Frequent Adverse Events
Authors: Peterfi Lehel , Yusenko Maria V. , Kovacs Gyula , Beothe Tamas
Published: July 2024

It is acknowledged that conventional renal cell carcinoma (cRCC), which makes up 85% of renal malignancies, is a highly vascular tumor. Humanized monoclonal antibodies were developed to inhibit tumor neo-angiogenesis, which is driven by VEGFA/KDR signaling. The results largely met our expectations, and in several cases, adverse events occurred. Our study aimed to analyze the expression of VEGFA and its receptor KDR by immunohistochemistry in tissue multi-array containing 811 cRCC and find a correlation between VEGFA/KDR signaling and new vessel formation. None of the 811 cRCC displayed VEGFA-positive immunostaining. However, each glomerulus in normal kidney showed VEGFA-positive endothelial cells. KDR expression in endothelial meshwork was found in only 9% of cRCC, whereas 2% of the cRCC displayed positive KDR reaction in the cytoplasm of tumor cells. Our results disclose the involvement of VEGFA/KDR signaling in the neo-vascularization of cRCC and explain the frequent resistance to drugs targeting the VEGFA/KDR signaling and the high frequency of adverse events.
Genetic Links between Reproductive Traits and Amino Acid Pairwise Distances of Swine Leukocyte Antigen Alleles among Mating Partners in Microminipigs
Authors: Ando Asako , Matsubara Tatsuya , Suzuki Shingo , Imaeda Noriaki , Takasu Masaki , Shigenari Atsuko , Miyamoto Asuka , Ohshima Shino , Kametani Yoshie , Shiina Takashi , Kulski Jerzy K. , Kitagawa Hitoshi
Published: July 2024

Previously, we found that a greater dissimilarity in swine leukocyte antigen (SLA) class I and class II alleles between mating partners resulted in increased farrowing rates in a highly inbred population of Microminipigs (MMPs). In this follow-up study, we have analyzed the effects of dissimilarity in SLA alleles between mating partners for seven different reproductive traits, including litter size and the number of stillborn and live or dead weaned piglets. We determined the relationships among reproductive traits within each mating event and the amino acid distances of SLA alleles as markers of diversity between mating partners. Our results indicate that mating partners with greater amino acid pairwise genetic distances in the SLA-1 class I gene or DQB1 class II gene alleles were associated with significantly larger litter sizes and higher numbers of live piglets at birth and weaning. Also, partners with greater pairwise distances in the SLA-2 class I gene alleles exhibited fewer pre-weaning deaths. These findings suggest that the dissimilarity in SLA class I and class II alleles between mating partners may affect not only farrowing rates but also other key reproductive traits such as litter size and improved piglet survival rates. Consequently, SLA alleles could serve as valuable genetic markers for selecting mating partners in breeding programs and for conducting epistatic studies on various reproductive traits in MMPs.
Arctigenin from Forsythia viridissima Fruit Inhibits the Replication of Human Coronavirus
Authors: So Jaeyeon , Kim Jang Hoon , Lee Siyun , Kim Chansoo , Park Rackhyun , Park Junsoo
Published: July 2024

Coronavirus can cause various diseases, from mild symptoms to the recent severe COVID-19. The coronavirus RNA genome is frequently mutated due to its RNA nature, resulting in many pathogenic and drug-resistant variants. Therefore, many medicines should be prepared to respond to the various coronavirus variants. In this report, we demonstrated that Forsythia viridissima fruit ethanol extract (FVFE) effectively reduces coronavirus replication. We attempted to identify the active compounds and found that actigenin from FVFE effectively reduces human coronavirus replication. Arctigenin treatment can reduce coronavirus protein expression and coronavirus-induced cytotoxicity. These results collectively suggest that arctigenin is a potent natural compound that prevents coronavirus replication.
Thyroid Hormone Signaling in Retinal Development and Function: Implications for Diabetic Retinopathy and Age-Related Macular Degeneration
Authors: Nicolini Giuseppina , Casini Giovanni , Posarelli Chiara , Amato Rosario , Lulli Matteo , Balzan Silvana , Forini Francesca
Published: July 2024

Thyroid Hormones (THs) play a central role in the development, cell growth, differentiation, and metabolic homeostasis of neurosensory systems, including the retina. The coordinated activity of various components of TH signaling, such as TH receptors (THRs) and the TH processing enzymes deiodinases 2 and 3 (DIO2, DIO3), is required for proper retinal maturation and function of the adult photoreceptors, Müller glial cells, and pigmented epithelial cells. Alterations of TH homeostasis, as observed both in frank or subclinical thyroid disorders, have been associated with sight-threatening diseases leading to irreversible vision loss i.e., diabetic retinopathy (DR), and age-related macular degeneration (AMD). Although observational studies do not allow causal inference, emerging data from preclinical models suggest a possible correlation between TH signaling imbalance and the development of retina disease. In this review, we analyze the most important features of TH signaling relevant to retinal development and function and its possible implication in DR and AMD etiology. A better understanding of TH pathways in these pathological settings might help identify novel targets and therapeutic strategies for the prevention and management of retinal disease.
Rapid Screening of Chemical Components in Salvia miltiorrhiza with the Potential to Inhibit Skin Inflammation
Authors: He Kehang , Hu Yikao , Bai Xiaolin , Liao Xun
Published: July 2024

Hyaluronidase possesses the capacity to degrade high-molecular-weight hyaluronic acid into smaller fragments, subsequently initiating a cascade of inflammatory responses and activating dendritic cells. In cases of bacterial infections, substantial quantities of HAase are generated, potentially leading to severe conditions such as cellulitis. Inhibiting hyaluronidase activity may offer anti-inflammatory benefits. Salvia miltiorrhiza Bunge, a traditional Chinese medicine, has anti-inflammatory properties. However, its effects on skin inflammation are not well understood. This study screened and evaluated the active components of S. miltiorrhiza that inhibit skin inflammation, using ligand fishing, enzyme activity assays, drug combination analysis, and molecular docking. By combining magnetic nanomaterials with hyaluronidase functional groups, we immobilized hyaluronidase on magnetic nanomaterials for the first time in the literature. We then utilized an immobilized enzyme to specifically adsorb the ligand; two ligands were identified as salvianolic acid B and rosmarinic acid by HPLC analysis after desorption of the dangling ligands, to complete the rapid screening of potential anti-inflammatory active ingredients in S. miltiorrhiza roots. The median-effect equation and combination index results indicated that their synergistic inhibition of hyaluronidase at a fixed 3:2 ratio was enhanced with increasing concentrations. Kinetic studies revealed that they acted as mixed-type inhibitors of hyaluronidase. Salvianolic acid B had Ki and Kis values of 0.22 and 0.96 μM, respectively, while rosmarinic acid had values of 0.54 and 4.60 μM. Molecular docking revealed that salvianolic acid B had a higher affinity for hyaluronidase than rosmarinic acid. In addition, we observed that a 3:2 combination of SAB and RA significantly decreased the secretion of TNF-α, IL-1, and IL-6 inflammatory cytokines in UVB-irradiated HaCaT cells. These findings identify salvianolic acid B and rosmarinic acid as key components with the potential to inhibit skin inflammation, as found in S. miltiorrhiza. This research is significant for developing skin inflammation treatments. It demonstrates the effectiveness and broad applicability of the magnetic nanoparticle-based ligand fishing approach for screening enzyme inhibitors derived from herbal extracts.
Extracellular Vesicles: The Next Generation of Biomarkers and Treatment for Central Nervous System Diseases
Authors: Zanirati Gabriele , dos Santos Paula Gabrielli , Alcará Allan Marinho , Bruzzo Fernanda , Ghilardi Isadora Machado , Wietholter Vinicius , Xavier Fernando Antônio Costa , Gonçalves João Ismael Budelon , Marinowic Daniel , Shetty Ashok K. , da Costa Jaderson Costa
Published: July 2024

It has been widely established that the characterization of extracellular vesicles (EVs), particularly small EVs (sEVs), shed by different cell types into biofluids, helps to identify biomarkers and therapeutic targets in neurological and neurodegenerative diseases. Recent studies are also exploring the efficacy of mesenchymal stem cell-derived extracellular vesicles naturally enriched with therapeutic microRNAs and proteins for treating various diseases. In addition, EVs released by various neural cells play a crucial function in the modulation of signal transmission in the brain in physiological conditions. However, in pathological conditions, such EVs can facilitate the spread of pathological proteins from one brain region to the other. On the other hand, the analysis of EVs in biofluids can identify sensitive biomarkers for diagnosis, prognosis, and disease progression. This review discusses the potential therapeutic use of stem cell-derived EVs in several central nervous system diseases. It lists their differences and similarities and confers various studies exploring EVs as biomarkers. Further advances in EV research in the coming years will likely lead to the routine use of EVs in therapeutic settings.
Effects of Dietary Protein Intake Levels on Peripheral Circadian Rhythm in Mice
Authors: Han Yerim , Shon Jinyoung , Kwon So Young , Park Yoon Jung
Published: July 2024

The regulation of the circadian clock plays an important role in influencing physiological conditions. While it is reported that the timing and quantity of energy intake impact circadian regulation, the underlying mechanisms remain unclear. This study investigated the impact of dietary protein intake on peripheral clocks. Firstly, transcriptomic analysis was conducted to investigate molecular targets of low-protein intake. Secondly, mPer2::Luc knock-in mice, fed with either a low-protein, normal, or high-protein diet for 6 weeks, were analyzed for the oscillation of PER2 expression in peripheral tissues and for the expression profiles of circadian and metabolic genes. Lastly, the candidate pathway identified by the in vivo analysis was validated using AML12 cells. As a result, using transcriptomic analysis, we found that the low-protein diet hardly altered the circadian rhythm in the central clock. In animal experiments, expression levels and period lengths of PER2 were different in peripheral tissues depending on dietary protein intake; moreover, mRNA levels of clock-controlled genes and endoplasmic reticulum (ER) stress genes were affected by dietary protein intake. Induction of ER stress in AML12 cells caused an increased amplitude of Clock and Bmal1 and an advanced peak phase of Per2. This result shows that the intake of different dietary protein ratios causes an alteration of the circadian rhythm, especially in the peripheral clock of mice. Dietary protein intake modifies the oscillation of ER stress genes, which may play key roles in the regulation of the circadian clock.
Modulation of Bronchial Epithelial Barrier Integrity by Low Molecular Weight Components from Birch Pollen
Authors: Sudharson Srinidhi , Kalic Tanja , Eckl-Dorna Julia , Lengger Nina , Breiteneder Heimo , Hafner Christine
Published: July 2024

Pollen, in addition to allergens, comprise low molecular weight components (LMC) smaller than 3 kDa. Emerging evidence indicates the relevance of LMC in allergic immune responses. However, the interaction of birch pollen (BP)-derived LMC and epithelial cells has not been extensively studied. We investigated epithelial barrier modifications induced by exposure to BP LMC, using the human bronchial epithelial cell line 16HBE14o-. Epithelial cell monolayers were apically exposed to the major BP allergen Bet v 1, aqueous BP extract or BP-derived LMC. Barrier integrity after the treatments was monitored by measuring transepithelial electrical resistance at regular intervals and by using the xCELLigence Real-Time Cell Analysis system. The polarized release of cytokines 24 h following treatment was measured using a multiplex immunoassay. Epithelial barrier integrity was significantly enhanced upon exposure to BP LMC. Moreover, BP LMC induced the repair of papain-mediated epithelial barrier damage. The apical release of CCL5 and TNF-α was significantly reduced after exposure to BP LMC, while the basolateral release of IL-6 significantly increased. In conclusion, the results of our study demonstrate that BP-derived LMC modify the physical and immunological properties of bronchial epithelial cells and thus regulate airway epithelial barrier responses.
Transcriptome Analysis Reveals Cross-Talk between the Flagellar Transcriptional Hierarchy and Secretion System in Plesiomonas shigelloides
Authors: Yan Junxiang , Zhang Zixu , Shi Hongdan , Xue Xinke , Li Ang , Ding Peng , Guo Xi , Wang Jinzhong , Wang Ying , Cao Boyang
Published: July 2024

Plesiomonas shigelloides, a Gram-negative bacillus, is the only member of the Enterobacteriaceae family able to produce polar and lateral flagella and cause gastrointestinal and extraintestinal illnesses in humans. The flagellar transcriptional hierarchy of P. shigelloides is currently unknown. In this study, we identified FlaK, FlaM, FliA, and FliAL as the four regulators responsible for polar and lateral flagellar regulation in P. shigelloides. To determine the flagellar transcription hierarchy of P. shigelloides, the transcriptomes of the WT and ΔflaK, ΔflaM, ΔfliA, and ΔfliAL were carried out for comparison in this study. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and luminescence screening assays were used to validate the RNA-seq results, and the Electrophoretic Mobility Shift Assay (EMSA) results revealed that FlaK can directly bind to the promoters of fliK, fliE, flhA, and cheY, while the FlaM protein can bind directly to the promoters of flgO, flgT, and flgA. Meanwhile, we also observed type VI secretion system (T6SS) and type II secretion system 2 (T2SS-2) genes downregulated in the transcriptome profiles, and the killing assay revealed lower killing abilities for ΔflaK, ΔflaM, ΔfliA, and ΔfliAL compared to the WT, indicating that there was a cross-talk between the flagellar hierarchy system and bacterial secretion system. Invasion assays also showed that ΔflaK, ΔflaM, ΔfliA, and ΔfliAL were less effective in infecting Caco-2 cells than the WT. Additionally, we also found that the loss of flagellar regulators causes the differential expression of some of the physiological metabolic genes of P. shigelloides. Overall, this study aims to reveal the transcriptional hierarchy that controls flagellar gene expression in P. shigelloides, as well as the cross-talk between motility, virulence, and physiological and metabolic activity, laying the groundwork for future research into P. shigelloides’ coordinated survival in the natural environment and the mechanisms that infect the host.
Associations of Circulating Biomarkers with Disease Risks: A Two-Sample Mendelian Randomization Study
Authors: Elmas Abdulkadir , Spehar Kevin , Do Ron , Castellano Joseph M. , Huang Kuan-Lin
Published: July 2024

Circulating biomarkers play a pivotal role in personalized medicine, offering potential for disease screening, prevention, and treatment. Despite established associations between numerous biomarkers and diseases, elucidating their causal relationships is challenging. Mendelian Randomization (MR) can address this issue by employing genetic instruments to discern causal links. Additionally, using multiple MR methods with overlapping results enhances the reliability of discovered relationships. Here, we report an MR study using multiple methods, including inverse variance weighted, simple mode, weighted mode, weighted median, and MR-Egger. We use the MR-base resource (v0.5.6) from Hemani et al. 2018 to evaluate causal relationships between 212 circulating biomarkers (curated from UK Biobank analyses by Neale lab and from Shin et al. 2014, Roederer et al. 2015, and Kettunen et al. 2016 and 99 complex diseases (curated from several consortia by MRC IEU and Biobank Japan). We report novel causal relationships found by four or more MR methods between glucose and bipolar disorder (Mean Effect Size estimate across methods: 0.39) and between cystatin C and bipolar disorder (Mean Effect Size: −0.31). Based on agreement in four or more methods, we also identify previously known links between urate with gout and creatine with chronic kidney disease, as well as biomarkers that may be causal of cardiovascular conditions: apolipoprotein B, cholesterol, LDL, lipoprotein A, and triglycerides in coronary heart disease, as well as lipoprotein A, LDL, cholesterol, and apolipoprotein B in myocardial infarction. This Mendelian Randomization study not only corroborates known causal relationships between circulating biomarkers and diseases but also uncovers two novel biomarkers associated with bipolar disorder that warrant further investigation. Our findings provide insight into understanding how biological processes reflecting circulating biomarkers and their associated effects may contribute to disease etiology, which can eventually help improve precision diagnostics and intervention.
Detection and Characterization of Methylated Circulating Tumor DNA in Gastric Cancer
Authors: Seo Seung Young , Youn Sang Hee , Bae Jin-Han , Lee Sung-Hun , Lee Sun Young
Published: July 2024

Gastric cancer is the fifth most common disease in the world and the fourth most common cause of death. It is diagnosed through esophagogastroduodenoscopy with biopsy; however, there are limitations in finding lesions in the early stages. Recently, research has been actively conducted to use liquid biopsy to diagnose various cancers, including gastric cancer. Various substances derived from cancer are reflected in the blood. By analyzing these substances, it was expected that not only the presence or absence of cancer but also the type of cancer can be diagnosed. However, the amount of these substances is extremely small, and even these have various variables depending on the characteristics of the individual or the characteristics of the cancer. To overcome these, we collected methylated DNA fragments using MeDIP and compared them with normal plasma to characterize gastric cancer tissue or patients’ plasma. We attempted to diagnose gastric cancer using the characteristics of cancer reflected in the blood through the cancer tissue and patients’ plasma. As a result, we confirmed that the consistency of common methylated fragments between tissue and plasma was approximately 41.2% and we found the possibility of diagnosing and characterizing cancer using the characteristics of the fragments through SFR and 5′end-motif analysis.
The Role of Short Chain Fatty Acids in Inflammation and Body Health
Authors: Du Yuhang , He Changhao , An Yongcheng , Huang Yan , Zhang Huilin , Fu Wanxin , Wang Menglu , Shan Ziyi , Xie Jiamei , Yang Yang , Zhao Baosheng
Published: July 2024

Short chain fatty acids (SCFAs), mainly including acetate, propionate and butyrate, are produced by intestinal bacteria during the fermentation of partially digested and indigestible polysaccharides. SCFAs play an important role in regulating intestinal energy metabolism and maintaining the homeostasis of the intestinal environment and also play an important regulatory role in organs and tissues outside the gut. In recent years, many studies have shown that SCFAs can regulate inflammation and affect host health, and two main signaling mechanisms have also been identified: the activation of G-protein coupled receptors (GPCRs) and inhibition of histone deacetylase (HDAC). In addition, a growing body of evidence highlights the importance of every SCFA in influencing health maintenance and disease development. In this review, we summarized the recent advances concerning the biological properties of SCFAs and their signaling pathways in inflammation and body health. Hopefully, it can provide a systematic theoretical basis for the nutritional prevention and treatment of human diseases.
Progranulin, sICAM-1, and sVCAM-1 May Predict an Increased Risk for Ventricular Arrhythmias in Patients with Systemic Sclerosis
Authors: Sebestyén Veronika , Ratku Balázs , Ujvárosy Dóra , Lőrincz Hajnalka , Tari Dóra , Végh Lilla , Majai Gyöngyike , Somodi Sándor , Páll Dénes , Szűcs Gabriella , Harangi Mariann , Szabó Zoltán
Published: July 2024

In systemic sclerosis (SSc), fibrosis of the myocardium along with ongoing autoimmune inflammation can alter the electric function of the cardiac myocytes, which may increase the risk for ventricular arrhythmias and sudden cardiac death. We analyzed the electrocardiographic (ECG) variables describing ventricular repolarization such as QT interval, QT dispersion (QTd), T wave peak-to-end interval (Tpe), and arrhythmogeneity index (AIX) of 26 patients with SSc and 36 healthy controls. Furthermore, echocardiographic and laboratory parameters were examined, with a focus on inflammatory proteins like C-reactive ptotein (CRP), soluble intracellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), and progranulin (PGRN). The CRP, sICAM-1, and sVCAM-1 levels were positively correlated with the length of the QT interval. Although the serum PGRN levels were not increased in the SSc group compared to the controls, in SSc patients, the PGRN levels were positively correlated with the QT interval and the AIX. According to our results, we conclude that there may be a potential association between autoimmune inflammation and the risk for ventricular arrhythmias in patients with SSc. We emphasize that the measurement of laboratory parameters of inflammatory activity including CRP, PGRN, sVCAM-1, and sICAM-1 could be helpful in the prediction of sudden cardiac death in patients with SSc.
DHXT1, a Virulence Factor of Dactylellina haptotyla, Regulates Pathogenicity by Participating in Trap Formation and Metabolite Synthesis
Authors: Wen Xing-Fu , Shi Ting-Ting , Zhang Ya-Qi , Wang Si-Han , Xiang Chun-Mei , Zhao Pei-Ji
Published: July 2024

The capsule-associated protein 10 gene (CAP10) is indispensable due to its involvement in pod formation and virulence maintenance in Cryptococcus neoformans. The function of the CAP10 gene in nematode-predatory fungi remains unreported. As a typical nematode-trapping fungus, Dactylellina haptotyla efficiently captures nematodes using adhesive knobs, which has potential applications in the biological control of plant-parasitic nematodes. In this study, we investigated the function of DHXT1 (a CAP10 homologous protein) in D. haptotyla–nematode interactions based on the disruption and overexpression of DHXT1, phenotypic analysis and metabolomic analysis. As a result, it was shown that the disruption of the DHXT1 gene causes a marked decrease in the number of adhesive knobs, and on the contrary, the overexpression of the DHXT1 gene causes a substantial increase in the number of adhesive knobs. Interestingly, the variety of metabolites increased with the disruption of the DHXT1 and decreased with the overexpression of the DHXT1 gene. The results suggest that DHXT1 effects pathogenicity through its involvement in adhesive knobs’ formation and metabolite synthesis and serves as a key virulence factor in D. haptotyla.
Protective Effect of Arzanol against H2O2-Induced Oxidative Stress Damage in Differentiated and Undifferentiated SH-SY5Y Cells
Authors: Piras Franca , Sogos Valeria , Pollastro Federica , Rosa Antonella
Published: July 2024

Oxidative stress can damage neuronal cells, greatly contributing to neurodegenerative diseases (NDs). In this study, the protective activity of arzanol, a natural prenylated α-pyrone-phloroglucinol heterodimer, was evaluated against the H2O2-induced oxidative damage in trans-retinoic acid-differentiated (neuron-like) human SH-SY5Y cells, widely used as a neuronal cell model of neurological disorders. The pre-incubation (for 2 and 24 h) with arzanol (5, 10, and 25 μM) significantly preserved differentiated SH-SY5Y cells from cytotoxicity (MTT assay) and morphological changes induced by 0.25 and 0.5 mM H2O2. Arzanol reduced the generation of reactive oxygen species (ROS) induced by 2 h oxidation with H2O2 0.5 mM, established by 2′,7′-dichlorodihydrofluorescein diacetate assay. The 2 h incubation of differentiated SH-SY5Y cells with H2O2 determined a significant increase in the number of apoptotic cells versus control cells, evaluated by propidium iodide fluorescence assay (red fluorescence) and NucView® 488 assay (green fluorescence). Arzanol pre-treatment (2 h) exerted a noteworthy significant protective effect against apoptosis. In addition, arzanol was tested, for comparison, in undifferentiated SH-SY5Y cells for cytotoxicity and its ability to protect against H2O2-induced oxidative stress. Furthermore, the PubChem database and freely accessible web tools SwissADME and pkCSM-pharmacokinetics were used to assess the physicochemical and pharmacokinetic properties of arzanol. Our results qualify arzanol as an antioxidant agent with potential neuroprotective effects against neuronal oxidative stress implicated in NDs.
Dissimilar Changes in Serum Cortisol after Epileptic and Psychogenic Non-Epileptic Seizures: A Promising Biomarker in the Differential Diagnosis of Paroxysmal Events?
Authors: Rider Flora , Turchinets Alexander , Druzhkova Tatyana , Kustov Georgii , Guekht Alla , Gulyaeva Natalia
Published: July 2024

The hypothalamic–pituitary–adrenal axis is known to be involved in the pathogenesis of epilepsy and psychiatric disorders. Epileptic seizures (ESs) and psychogenic non-epileptic seizures (PNESs) are frequently differentially misdiagnosed. This study aimed to evaluate changes in serum cortisol and prolactin levels after ESs and PNESs as possible differential diagnostic biomarkers. Patients over 18 years with ESs (n = 29) and PNESs with motor manifestations (n = 45), captured on video-EEG monitoring, were included. Serum cortisol and prolactin levels as well as hemograms were assessed in blood samples taken at admission, during the first hour after the seizure, and after 6, 12, and 24 h. Cortisol and prolactine response were evident in the ES group (but not the PNES group) as an acute significant increase within the first hour after seizure. The occurrence of seizures in patients with ESs and PNESs demonstrated different circadian patterns. ROC analysis confirmed the accuracy of discrimination between paroxysmal events based on cortisol response: the AUC equals 0.865, with a prediction accuracy at the cutoff point of 376.5 nmol/L 0.811 (sensitivity 86.7%, specificity 72.4%). Thus, assessments of acute serum cortisol response to a paroxysmal event may be regarded as a simple, fast, and minimally invasive laboratory test contributing to differential diagnosis of ESs and PNESs.
The Interaction of Vasopressin with Hormones of the Hypothalamo–Pituitary–Adrenal Axis: The Significance for Therapeutic Strategies in Cardiovascular and Metabolic Diseases
Authors: Szczepanska-Sadowska Ewa , Czarzasta Katarzyna , Bogacki-Rychlik Wiktor , Kowara Michał
Published: July 2024

A large body of evidence indicates that vasopressin (AVP) and steroid hormones are frequently secreted together and closely cooperate in the regulation of blood pressure, metabolism, water–electrolyte balance, and behavior, thereby securing survival and the comfort of life. Vasopressin cooperates with hormones of the hypothalamo–pituitary–adrenal axis (HPA) at several levels through regulation of the release of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and multiple steroid hormones, as well as through interactions with steroids in the target organs. These interactions are facilitated by positive and negative feedback between specific components of the HPA. Altogether, AVP and the HPA cooperate closely as a coordinated functional AVP-HPA system. It has been shown that cooperation between AVP and steroid hormones may be affected by cellular stress combined with hypoxia, and by metabolic, cardiovascular, and respiratory disorders; neurogenic stress; and inflammation. Growing evidence indicates that central and peripheral interactions between AVP and steroid hormones are reprogrammed in cardiovascular and metabolic diseases and that these rearrangements exert either beneficial or harmful effects. The present review highlights specific mechanisms of the interactions between AVP and steroids at cellular and systemic levels and analyses the consequences of the inappropriate cooperation of various components of the AVP-HPA system for the pathogenesis of cardiovascular and metabolic diseases.
Mechanisms and Functions of Sweet Reception in Oral and Extraoral Organs
Authors: Yoshida Ryusuke , Ninomiya Yuzo
Published: July 2024

The oral detection of sugars relies on two types of receptor systems. The first is the G-protein-coupled receptor TAS1R2/TAS1R3. When activated, this receptor triggers a downstream signaling cascade involving gustducin, phospholipase Cβ2 (PLCβ2), and transient receptor potential channel M5 (TRPM5). The second type of receptor is the glucose transporter. When glucose enters the cell via this transporter, it is metabolized to produce ATP. This ATP inhibits the opening of KATP channels, leading to cell depolarization. Beside these receptor systems, sweet-sensitive taste cells have mechanisms to regulate their sensitivity to sweet substances based on internal and external states of the body. Sweet taste receptors are not limited to the oral cavity; they are also present in extraoral organs such as the gastrointestinal tract, pancreas, and brain. These extraoral sweet receptors are involved in various functions, including glucose absorption, insulin release, sugar preference, and food intake, contributing to the maintenance of energy homeostasis. Additionally, sweet receptors may have unique roles in certain organs like the trachea and bone. This review summarizes past and recent studies on sweet receptor systems, exploring the molecular mechanisms and physiological functions of sweet (sugar) detection in both oral and extraoral organs.
Cytokine Profiling in Cerebrospinal Fluid of Patients with Newly Diagnosed Relapsing-Remitting Multiple Sclerosis (RRMS): Associations between Inflammatory Biomarkers and Disease Activity
Authors: Gębka-Kępińska Barbara , Adamczyk Bożena , Gębka Dorota , Czuba Zenon , Szczygieł Jarosław , Adamczyk-Sowa Monika
Published: July 2024

Cytokines regulate immune responses and are crucial to MS pathogenesis. This study evaluated pro-inflammatory and anti-inflammatory cytokine concentrations in the CSF of de novo diagnosed RRMS patients compared to healthy controls. We assessed cytokine levels in the CSF of 118 de novo diagnosed RRMS patients and 112 controls, analyzing relationships with time from symptom onset to diagnosis, MRI lesions, and serum vitamin D levels. Elevated levels of IL-2, IL-4, IL-6, IL-13, FGF-basic, and GM-CSF, and lower levels of IL-1β, IL-1RA, IL-5, IL-7, IL-9, IL-10, IL-12p70, IL-15, G-CSF, PDGF-bb, and VEGF were observed in RRMS patients compared to controls. IL-2, IL-4, IL-12p70, PDGF, G-CSF, GM-CSF, and FGF-basic levels increased over time, while IL-10 decreased. IL-1β, IL-1RA, IL-6, TNF-α, and PDGF-bb levels negatively correlated with serum vitamin D. TNF-α levels positively correlated with post-contrast-enhancing brain lesions. IL-15 levels negatively correlated with T2 and Gd(+) lesions in C-spine MRI, while TNF-α, PDGF-bb, and FGF-basic correlated positively with T2 lesions in C-spine MRI. IL-6 levels positively correlated with post-contrast-enhancing lesions in Th-spine MRI. Distinct cytokine profiles in the CSF of de novo diagnosed MS patients provide insights into MS pathogenesis and guide immunomodulatory therapy strategies.
TGF-β Modulated Pathways in Colorectal Cancer: New Potential Therapeutic Opportunities
Authors: Fasano Morena , Pirozzi Mario , Miceli Chiara Carmen , Cocule Mariateresa , Caraglia Michele , Boccellino Mariarosaria , Vitale Pasquale , De Falco Vincenzo , Farese Stefano , Zotta Alessia , Ciardiello Fortunato , Addeo Raffaele
Published: July 2024

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, with 20% of patients presenting with metastatic disease at diagnosis. TGF-β signaling plays a crucial role in various cellular processes, including growth, differentiation, apoptosis, epithelial-mesenchymal transition (EMT), regulation of the extracellular matrix, angiogenesis, and immune responses. TGF-β signals through SMAD proteins, which are intracellular molecules that transmit TGF-β signals from the cell membrane to the nucleus. Alterations in the TGF-β pathway and mutations in SMAD proteins are common in metastatic CRC (mCRC), making them critical factors in CRC tumorigenesis. This review first analyzes normal TGF-β signaling and then investigates its role in CRC pathogenesis, highlighting the mechanisms through which TGF-β influences metastasis development. TGF-β promotes neoangiogenesis via VEGF overexpression, pericyte differentiation, and other mechanisms. Additionally, TGF-β affects various elements of the tumor microenvironment, including T cells, fibroblasts, and macrophages, promoting immunosuppression and metastasis. Given its strategic role in multiple processes, we explored different strategies to target TGF-β in mCRC patients, aiming to identify new therapeutic options.
Cholinesterase Inhibition and Antioxidative Capacity of New Heteroaromatic Resveratrol Analogs: Synthesis and Physico—Chemical Properties
Authors: Mlakić Milena , Talić Stanislava , Odak Ilijana , Barić Danijela , Šagud Ivana , Škorić Irena
Published: July 2024

The targeted compounds in this research, resveratrol analogs 1–14, were synthesized as mixtures of isomers by the Wittig reaction using heterocyclic triphenylphosphonium salts and various benzaldehydes. The planned compounds were those possessing the trans-configuration as the biologically active trans-resveratrol. The pure isomers were obtained by repeated column chromatography in various isolated yields depending on the heteroaromatic ring. It was found that butyrylcholinesterase (BChE) was more sensitive to the heteroaromatic resveratrol analogs than acetylcholinesterase (AChE), except for 6, the methylated thiophene derivative with chlorine, which showed equal inhibition toward both enzymes. Compounds 5 and 8 achieved the highest BChE inhibition with IC50 values of 22.9 and 24.8 μM, respectively. The same as with AChE and BChE, methylated thiophene subunits of resveratrol analogs showed better enzyme inhibition than unmethylated ones. Two antioxidant spectrophotometric methods, DPPH and CUPRAC, were applied to determine the antioxidant potential of new heteroaromatic resveratrol analogs. The molecular docking of these compounds was conducted to visualize the ligand-active site complexes’ structure and identify the non-covalent interactions responsible for the complex’s stability, which influence the inhibitory potential. As ADME properties are crucial in developing drug product formulations, they have also been addressed in this work. The potential genotoxicity is evaluated by in silico studies for all compounds synthesized.