bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing the Yield of Mature Olive Trees via Comparative Fertilization Strategies, including a Foliar Application with Fulvic and Humic Acids, in Non-Irrigated Orchards with Calcareous and Non-Calcareous Soils
Authors: Sotiropoulos Stavros , Chatzissavvidis Christos , Papadakis Ioannis E. , Kavvadias Victor , Paschalidis Christos , Antonopoulou Chrysovalantou , Kiriakopoulos Sotirios
Published: February 2024

This study investigated the impact of fertilization treatments on mature, forty-year-old, fully productive olive trees (Olea europaea L. cv. Koroneiki) in two non-irrigated orchards featuring contrasting soil types: non-calcareous–acidic and calcareous–alkaline. Over three years (2019–2021), seven distinct treatments were applied, involving inorganic soil fertilizers (traditional strategy) and foliar applications of a liquid organic product containing fulvic and humic acids. Fertilization significantly influenced physiological parameters, such as mineral nutrition, photosynthetic pigments of olive leaves, fruit yield, and oil production per tree, revealing noteworthy effects influenced by soil types and their interactions with treatments. Statistical analysis highlighted specific treatments, indicating that the foliar application of the organic product once a year in alkaline soil or biannually in acidic soil resulted in the highest observed fruit yield and oil production per tree. Indeed, contrary to the control–unfertilized trees, specific fertilization strategies resulted in an average increase of up to 47% and 73% in fruit yield per tree and up to 96% and 100% in oil production per tree in acidic and alkaline soil, respectively. Furthermore, consistently high yields were correlated with constant high values of the chlorophyll a/chlorophyll b ratio (2.3–3.3 in August for acidic soil) and leaf chlorophyll a concentration (55–66 mg/100 g f.w. in August for alkaline soil). This novel finding underscores the crucial role of these factors as prerequisites for achieving superior fruit production. Our results emphasize the potential of integrating foliar organic fertilization as a complementary strategy to traditional soil-based approaches. This is particularly relevant under non-irrigated/rainfed cultural conditions, emphasizing the significance of considering alternative fertilization practices for optimized olive orchard management.
A Comparison of Statistical Methods to Construct Confidence Intervals and Fiducial Intervals for Measures of Health Disparities
Authors: Li Tengfei , Dragomir Anca D. , Luta George
Published: February 2024

Health disparities are differences in health status across different socioeconomic groups. Classical methods, e.g., the Delta method, have been used to estimate the standard errors of estimated measures of health disparities and to construct confidence intervals for these measures. However, the confidence intervals constructed using the classical methods do not have good coverage properties for situations involving sparse data. In this article, we introduce three new methods to construct fiducial intervals for measures of health disparities based on approximate fiducial quantities. Through a comprehensive simulation study, We compare the empirical coverage properties of the proposed fiducial intervals against two Monte Carlo simulation-based methods—utilizing either a truncated Normal distribution or the Gamma distribution—as well as the classical method. The findings of the simulation study advocate for the adoption of the Monte Carlo simulation-based method with the Gamma distribution when a unified approach is sought for all health disparity measures.
Equity in Cancer and Chronic Disease Prevention through a Multi-Pronged Network Intervention: Works-in-Progress
Authors: Molina Yamilé , Tsai Edward , Enqubahry Yalemzewod , Lee Eunhye , Siddiqi Faria , Gottesman Anna , Boylan Emma , Paz Kate , Wright Margaret E. , Abrol Ekas , Lofton Saria , Kim Sage J. , Patel Ajanta
Published: February 2024

The increasing rates of cancer incidence are disproportionately borne by populations that are ineligible for screening and historically marginalized populations. To address this need, our community-centered model seeks to catalyze the widespread diffusion of evidence-based information and resources (e.g., community-based organizations, federally qualified health centers) to reduce the risks of cancer, chronic disease, and other conditions. In this study, we tested whether improving personal health literacy (i.e., confidence in seeking information) and enabling successful information transfer (i.e., intention to share the specific information learned through the program) among community residents could contribute to greater diffusion intention (i.e., number of network members with whom residents plan to share information and resources). The current study used post-intervention surveys, which were administered to Chicago residents who were 18 years or older and had participated in the program. Among the 1499 diverse Chicago residents, improved personal health literacy was associated with greater diffusion intention (ORs = 2.00–2.68, 95% CI [1.27–4.39], p ≤ 0.003). Successful information transfer was associated with greater diffusion, especially for cancer and other chronic disease risk reductions (ORs = 3.43–3.73, 95% CI [1.95–6.68], p < 0.001). The findings highlight the potential gains for health equity through sustainable, scalable, multi-sectoral partnerships.
Plant-Origin Components: New Players to Combat Antibiotic Resistance in Klebsiella pneumoniae
Authors: Luna-Pineda Victor M. , Rodríguez-Martínez Griselda , Salazar-García Marcela , Romo-Castillo Mariana
Published: February 2024

Klebsiella pneumoniae (Kpn) is an opportunistic pathogen that causes intrahospital complications such as pneumonia, liver abscesses, soft tissue infections, urinary infections, bacteraemia, and, in some cases, death. Since this bacterium has a higher frequency than other Gram-negative pathogens, it has become an important pathogen to the health sector. The adaptative genome of Kpn likely facilitates increased survival of the pathogen in diverse situations. Therefore, several studies have been focused on developing new molecules, synergistic formulations, and biomaterials that make it possible to combat and control infections with and dispersion of this pathogen. Note that the uncontrolled antibiotic administration that occurred during the pandemic led to the emergence of new multidrug-resistant strains, and scientists were challenged to overcome them. This review aims to compile the latest information on Kpn that generates intrahospital infections, specifically their pathogenicity-associated factors. Furthermore, it explains the natural-product-based treatments (extracts and essential oils) developed for Kpn infection and dispersion control.
Methadone Requires the Co-Activation of μ-Opioid and Toll-Like-4 Receptors to Produce Extracellular DNA Traps in Bone-Marrow-Derived Mast Cells
Authors: Martínez-Cuevas Frida L. , Cruz Silvia L. , González-Espinosa Claudia
Published: February 2024

Methadone is an effective and long-lasting analgesic drug that is also used in medication-assisted treatment for people with opioid use disorders. Although there is evidence that methadone activates μ-opioid and Toll-like-4 receptors (TLR-4s), its effects on distinct immune cells, including mast cells (MCs), are not well characterized. MCs express μ-opioid and Toll-like receptors (TLRs) and constitute an important cell lineage involved in allergy and effective innate immunity responses. In the present study, murine bone-marrow-derived mast cells (BMMCs) were treated with methadone to evaluate cell viability by flow cytometry, cell morphology with immunofluorescence and scanning electron microscopy, reactive oxygen species (ROS) production, and intracellular calcium concentration ([Ca2+]i) increase. We found that exposure of BMMCs to 0.5 mM or 1 mM methadone rapidly induced cell death by forming extracellular DNA traps (ETosis). Methadone-induced cell death depended on ROS formation and [Ca2+]i. Using pharmacological approaches and TLR4-defective BMMC cultures, we found that µ-opioid receptors were necessary for both methadone-induced ROS production and intracellular calcium increase. Remarkably, TLR4 receptors were also involved in methadone-induced ROS production as it did not occur in BMMCs obtained from TLR4-deficient mice. Finally, confocal microscopy images showed a significant co-localization of μ-opioid and TLR4 receptors that increased after methadone treatment. Our results suggest that methadone produces MCETosis by a mechanism requiring a novel crosstalk pathway between μ-opioid and TLR4 receptors.
Endoribonuclease DNE1 Promotes Ethylene Response by Modulating EBF1/2 mRNA Processing in Arabidopsis
Authors: Yan Yan , Guo Hongwei , Li Wenyang
Published: February 2024

The gaseous phytohormone ethylene plays a crucial role in plant growth, development, and stress responses. In the ethylene signal transduction cascade, the F-box proteins EIN3-BINDING F-BOX 1 (EBF1) and EBF2 are identified as key negative regulators governing ethylene sensitivity. The translation and processing of EBF1/2 mRNAs are tightly controlled, and their 3′ untranslated regions (UTRs) are critical in these regulations. However, despite their significance, the exact mechanisms modulating the processing of EBF1/2 mRNAs remain poorly understood. In this work, we identified the gene DCP1-ASSOCIATED NYN ENDORIBONUCLEASE 1 (DNE1), which encodes an endoribonuclease and is induced by ethylene treatment, as a positive regulator of ethylene response. The loss of function mutant dne1-2 showed mild ethylene insensitivity, highlighting the importance of DNE1 in ethylene signaling. We also found that DNE1 colocalizes with ETHYLENE INSENSITIVE 2 (EIN2), the core factor manipulating the translation of EBF1/2, and targets the P-body in response to ethylene. Further analysis revealed that DNE1 negatively regulates the abundance of EBF1/2 mRNAs by recognizing and cleaving their 3′UTRs, and it also represses their translation. Moreover, the dne1 mutant displays hypersensitivity to 1,4-dithiothreitol (DTT)-induced ER stress and oxidative stress, indicating the function of DNE1 in stress responses. This study sheds light on the essential role of DNE1 as a modulator of ethylene signaling through regulation of EBF1/2 mRNA processing. Our findings contribute to the understanding of the intricate regulatory process of ethylene signaling and provide insights into the significance of ribonuclease in stress responses.
Enhanced Expression of Glycolytic Enzymes and Succinate Dehydrogenase Complex Flavoprotein Subunit A by Mesothelin Promotes Glycolysis and Mitochondrial Respiration in Myeloblasts of Acute Myeloid Leukemia
Authors: Jang Yunseon , Koh Jeong Suk , Park Jung-Hyun , Choi Suyoung , Duong Pham Thi Thuy , Heo Bu Yeon , Lee Sang Woo , Kim Jung Yeon , Lee Myung-Won , Kim Seok-Hwan , Song Ik-Chan
Published: February 2024

Acute myeloid leukemia (AML) is an aggressive malignancy characterized by rapid growth and uncontrolled proliferation of undifferentiated myeloid cells. Metabolic reprogramming is commonly observed in the bone marrow of AML patients, as leukemia cells require increased ATP supply to support disease progression. In this study, we examined the potential role of mesothelin as a metabolic modulator in myeloid cells in AML. Mesothelin is a well-known marker of solid tumors that promotes cancer cell proliferation and survival. We initially analyzed alterations in mesothelin expression in the myeloblast subpopulations, defined as SSC-Alow/CD45dim, obtained from the bone marrow of AML patients using flow cytometry. Our results showed overexpression of mesothelin in 34.8% of AML patients. Subsequently, metabolic changes in leukemia cells were evaluated by comparing the oxygen consumption rates (OCR) of bone marrow samples derived from adult AML patients. Notably, a higher OCR was observed in the mesothelin-positive compared to the mesothelin-low and non-expressing groups. Treatment with recombinant human mesothelin protein enhanced OCR and increased the mRNA expression of glycolytic enzymes and mitochondrial complex II in KG1α AML cells. Notably, siRNA targeting mesothelin in KG1α cells led to the reduction of glycolysis-related gene expression but had no effect on the mitochondrial complex gene. The collective results demonstrate that mesothelin induces metabolic changes in leukemia cells, facilitating the acquisition of a rapid supply of ATP for proliferation in AML. Therefore, the targeting of mesothelin presents a potentially promising approach to mitigating the progression of AML through the inhibition of glycolysis and mitochondrial respiration in myeloid cells.
Multi-Omics Approaches for Liver Reveal the Thromboprophylaxis Mechanism of Aspirin Eugenol Ester in Rat Thrombosis Model
Authors: Tao Qi , Ma Ning , Fan Liping , Ge Wenbo , Zhang Zhendong , Liu Xiwang , Li Jianyong , Yang Yajun
Published: February 2024

Aspirin eugenol ester (AEE) is a novel medicinal compound synthesized by esterifying aspirin with eugenol using the pro-drug principle. Pharmacological and pharmacodynamic experiments showed that AEE had excellent thromboprophylaxis and inhibition of platelet aggregation. This study aimed to investigate the effect of AEE on the liver of thrombosed rats to reveal its mechanism of thromboprophylaxis. Therefore, a multi-omics approach was used to analyze the liver. Transcriptome results showed 132 differentially expressed genes (DEGs) in the AEE group compared to the model group. Proteome results showed that 159 differentially expressed proteins (DEPs) were identified in the AEE group compared to the model group. Six proteins including fibrinogen alpha chain (Fga), fibrinogen gamma chain (Fgg), fibrinogen beta chain (Fgb), orosomucoid 1 (Orm1), hemopexin (Hpx), and kininogen-2 (Kng2) were selected for parallel reaction monitoring (PRM) analysis. The results showed that the expression of all six proteins was upregulated in the model group compared with the control group. In turn, AEE reversed the upregulation trend of these proteins to some degree. Metabolome results showed that 17 metabolites were upregulated and 38 were downregulated in the model group compared to the control group. AEE could reverse the expression of these metabolites to some degree and make them back to normal levels. The metabolites were mainly involved in metabolic pathways, including linoleic acid metabolism, arachidonic acid metabolism, and the tricarboxylic acid (TCA) cycle. Comprehensive analyses showed that AEE could prevent thrombosis by inhibiting platelet activation, decreasing inflammation, and regulating amino acid and energy metabolism. In conclusion, AEE can have a positive effect on thrombosis-related diseases.
The Role of Interleukin 6 in Periodontitis and Its Complications
Authors: Mazurek-Mochol Małgorzata , Bonsmann Tobias , Mochol Martyna , Poniewierska-Baran Agata , Pawlik Andrzej
Published: February 2024

Interleukin 6 (IL-6) is a pleomorphic pro-inflammatory cytokine that is strongly associated with local as well as systemic inflammatory processes. Its role in physiological and pathogenic processes throughout the human body has been the subject of numerous studies in recent years. Measurements of the IL-6 levels in gingival crevicular fluid (GFC), as well as in serum, can be important diagnostic and prognostic factors in periodontal diseases (PD) and in assessing their impact on a range of related inflammatory diseases. This narrative review explores the significant role of IL-6 in patients with periodontitis and its association with other widespread inflammatory pathologies.
Insights into the Medical Evaluation of Ekbom Syndrome: An Overview
Authors: Mindru Florina Madalina , Radu Andrei-Flavius , Bumbu Adrian Gheorghe , Radu Ada , Bungau Simona Gabriela
Published: February 2024

Ekbom syndrome, also known as delusional parasitosis (DP) or delusional infestation, is an uncommon psychiatric disorder distinguished by an enduring conviction of parasitic infestation, persisting notwithstanding the presence of medical evidence to the contrary. Primarily affecting middle-aged women, DP can manifest either as isolated psychological distress or as a component within a more intricate psychiatric framework, substantially influencing the quality of life for affected individuals. Its pathophysiological mechanism involves uncertain dopaminergic imbalances and dysfunction in the dopamine transporter system. Dermatologists often play a pivotal role in diagnosis, as patients first seek dermatological assessments of their signs and symptoms. However, DP frequently originates from underlying psychiatric disorders or medical variables, manifesting with neurological and infectious causative factors. The diagnostic complexity is attributed to patients’ resolute convictions, leading to delayed psychiatric intervention. First-line DP treatment involves antipsychotics, with newer agents demonstrating promising prospects, but the lack of standardized protocols poses a significant therapeutic challenge. In this narrative review, both a comprehensive approach to this uncommon pathology and an update on the state of knowledge in this medical subfield focused on optimizing the management of DP are provided. The complexity of DP underlying its uncommon nature and the incomplete understanding of its pathophysiology highlight the need for further research through multicenter studies and multidisciplinary teams to enhance therapeutic efficacy and safety.
Prostate Cancer and the Mevalonate Pathway
Authors: Guerrero-Ochoa Patricia , Rodríguez-Zapater Sergio , Anel Alberto , Esteban Luis Mariano , Camón-Fernández Alejandro , Espilez-Ortiz Raquel , Gil-Sanz María Jesús , Borque-Fernando Ángel
Published: February 2024

Antineoplastic therapies for prostate cancer (PCa) have traditionally centered around the androgen receptor (AR) pathway, which has demonstrated a significant role in oncogenesis. Nevertheless, it is becoming progressively apparent that therapeutic strategies must diversify their focus due to the emergence of resistance mechanisms that the tumor employs when subjected to monomolecular treatments. This review illustrates how the dysregulation of the lipid metabolic pathway constitutes a survival strategy adopted by tumors to evade eradication efforts. Integrating this aspect into oncological management could prove valuable in combating PCa.
Arsenic Impairs Wound Healing Processes in Dermal Fibroblasts and Mice
Authors: Dresler Sara R. , Pinto Bronson I. , Salanga Matthew C. , Propper Catherine R. , Berry Savannah R. , Kellar Robert S.
Published: February 2024

Inorganic arsenic (NaAsO2) is a naturally occurring metalloid found in water resources globally and in the United States at concentrations exceeding the U.S. Environmental Protection Agency Maximum Contamination Level of 10 ppb. While exposure to arsenic has been linked to cancer, cardiovascular disease, and skin lesions, the impact of arsenic exposure on wound healing is not fully understood. Cultured dermal fibroblasts exposed to NaAsO2 displayed reduced migration (scratch closure), proliferation, and viability with a lowest observable effect level (LOEL) of 10 µM NaAsO2 following 24 h exposure. An enrichment of Matrix Metalloproteinase 1 (MMP1) transcripts was observed at a LOEL of 1 µM NaAsO2 and 24 h exposure. In vivo, C57BL/6 mice were exposed to 10 µM NaAsO2 in their drinking water for eight weeks, then subjected to two full thickness dorsal wounds. Wounds were evaluated for closure after 6 days. Female mice displayed a significant reduction in wound closure and higher erythema levels, while males showed no effects. Gene expression analysis from skin excised from the wound site revealed significant enrichment in Arsenic 3-Methyltransferase (As3mt) and Estrogen Receptor 2 (Esr2) mRNA in the skin of female mice. These results indicate that arsenic at environmentally relevant concentrations may negatively impact wound healing processes in a sex-specific manner.
Periosteum Containing Implicit Stem Cells: A Progressive Source of Inspiration for Bone Tissue Regeneration
Authors: Zhang Xinyuan , Deng Chen , Qi Shengcai
Published: February 2024

The periosteum is known as the thin connective tissue covering most bone surfaces. Its extrusive bone regeneration capacity was confirmed from the very first century-old studies. Recently, pluripotent stem cells in the periosteum with unique physiological properties were unveiled. Existing in dynamic contexts and regulated by complex molecular networks, periosteal stem cells emerge as having strong capabilities of proliferation and multipotential differentiation. Through continuous exploration of studies, we are now starting to acquire more insight into the great potential of the periosteum in bone formation and repair in situ or ectopically. It is undeniable that the periosteum is developing further into a more promising strategy to be harnessed in bone tissue regeneration. Here, we summarized the development and structure of the periosteum, cell markers, and the biological features of periosteal stem cells. Then, we reviewed their pivotal role in bone repair and the underlying molecular regulation. The understanding of periosteum-related cellular and molecular content will help enhance future research efforts and application transformation of the periosteum.
Nanotechnology as a Promising Method in the Treatment of Skin Cancer
Authors: Adamus-Grabicka Angelika A. , Hikisz Pawel , Sikora Joanna
Published: February 2024

The incidence of skin cancer continues to grow. There are an estimated 1.5 million new cases each year, of which nearly 350,000 are melanoma, which is often fatal. Treatment is challenging and often ineffective, with conventional chemotherapy playing a limited role in this context. These disadvantages can be overcome by the use of nanoparticles and may allow for the early detection and monitoring of neoplastic changes and determining the effectiveness of treatment. This article briefly reviews the present understanding of the characteristics of skin cancers, their epidemiology, and risk factors. It also outlines the possibilities of using nanotechnology, especially nanoparticles, for the transport of medicinal substances. Research over the previous decade on carriers of active substances indicates that drugs can be delivered more accurately to the tumor site, resulting in higher therapeutic efficacy. The article describes the application of liposomes, carbon nanotubes, metal nanoparticles, and polymer nanoparticles in existing therapies. It discusses the challenges encountered in nanoparticle therapy and the possibilities of improving their performance. Undoubtedly, the use of nanoparticles is a promising method that can help in the fight against skin cancer.
Fibroblasts in Diabetic Foot Ulcers
Authors: Voza Francesca A. , Huerta Carlos Theodore , Le Nga , Shao Hongwei , Ribieras Antoine , Ortiz Yulexi , Atkinson Carl , Machuca Tiago , Liu Zhao-Jun , Velazquez Omaida C.
Published: February 2024

Fibroblasts are stromal cells ubiquitously distributed in the body of nearly every organ tissue. These cells were previously considered to be “passive cells”, solely responsible for ensuring the turnover of the extracellular matrix (ECM). However, their versatility, including their ability to switch phenotypes in response to tissue injury and dynamic activity in the maintenance of tissue specific homeostasis and integrity have been recently revealed by the innovation of technological tools such as genetically modified mouse models and single cell analysis. These highly plastic and heterogeneous cells equipped with multifaceted functions including the regulation of angiogenesis, inflammation as well as their innate stemness characteristics, play a central role in the delicately regulated process of wound healing. Fibroblast dysregulation underlies many chronic conditions, including cardiovascular diseases, cancer, inflammatory diseases, and diabetes mellitus (DM), which represent the current major causes of morbidity and mortality worldwide. Diabetic foot ulcer (DFU), one of the most severe complications of DM affects 40 to 60 million people. Chronic non-healing DFU wounds expose patients to substantial sequelae including infections, gangrene, amputation, and death. A complete understanding of the pathophysiology of DFU and targeting pathways involved in the dysregulation of fibroblasts are required for the development of innovative new therapeutic treatments, critically needed for these patients.
Deregulated Transcriptome as a Platform for Adrenal Huntington’s Disease-Related Pathology
Authors: Olechnowicz Anna , Blatkiewicz Małgorzata , Jopek Karol , Isalan Mark , Mielcarek Michal , Rucinski Marcin
Published: February 2024

Huntington’s disease (HD) is a neurodegenerative disorder that affects mainly the central nervous system (CNS) by inducing progressive deterioration in both its structure and function. In recent years, there has been growing interest in the impact of HD on peripheral tissue function. Herein, we used the R6/2 mouse model of HD to investigate the influence of the disease on adrenal gland functioning. A transcriptomic analysis conducted using a well-established quantitative method, an Affymetrix array, revealed changes in gene expression in the R6/2 model compared to genetic background controls. For the first time, we identified disruptions in cholesterol and sterol metabolism, blood coagulation, and xenobiotic metabolism in HD adrenal glands. This study showed that the disrupted expression of these genes may contribute to the underlying mechanisms of Huntington’s disease. Our findings may contribute to developing a better understanding of Huntington’s disease progression and aid in the development of novel diagnostic or therapeutic approaches.
Quantiferon Monitor Testing Sheds Light on Immune System Disparities between Multiple Sclerosis Patients and Healthy Individuals
Authors: Součková Ilona , Souček Ondřej , Krejsek Jan , Vyšata Oldřich , Matyáš David , Peterka Marek , Novotný Michal , Kunc Pavel , Pavelek Zbyšek
Published: February 2024

The aim of this study was to conduct QuantiFERON Monitor (QFM) testing in patients with multiple sclerosis (MS), which is used to monitor the state of the immune system through the non-specific stimulation of leukocytes followed by determining the level of interferon-gamma (IFN-γ) released from activated cells. Additionally, we tested the level of selected cytokines (IFN-α, IFN-γ, IL-1α, IL-1β, IL-1ra, IL-2, IL-3, IL-4, IL-6, IL-7, IL-10, IL-15, IL-33, VEGF) from stimulated blood samples to further understand the immune response. This study builds upon a previously published study, utilizing activated serum samples that were initially used for IFN-γ determination. However, our current focus shifts from IFN-γ to exploring other cytokines that could provide further insights into the immune response. A screening was conducted using Luminex technology, which yielded promising results. These results were then further elaborated upon using ELISA to provide a more detailed understanding of the cytokine profiles involved. This study, conducted from August 2019 to June 2023, included 280 participants: 98 RRMS patients treated with fingolimod (fMS), 96 untreated patients with progressive MS (pMS), and 86 healthy controls (HC). Our results include Violin plots showing elevated IL-1α in pMS and fMS. Statistical analysis indicated significant differences in the interleukin levels between groups, with IL-1ra and age as key predictors in differentiating HC from pMS and IL-1ra, IL-1α, age, and EDSS in distinguishing pMS from fMS. These findings suggest cytokines’ potential as biomarkers in MS progression and treatment response.
Sex-Hormone-Binding Globulin Gene Polymorphisms and Breast Cancer Risk in Caucasian Women of Russia
Authors: Ponomarenko Irina , Pasenov Konstantin , Churnosova Maria , Sorokina Inna , Aristova Inna , Churnosov Vladimir , Ponomarenko Marina , Reshetnikov Evgeny , Churnosov Mikhail
Published: February 2024

In our work, the associations of GWAS (genome-wide associative studies) impact for sex-hormone-binding globulin (SHBG)-level SNPs with the risk of breast cancer (BC) in the cohort of Caucasian women of Russia were assessed. The work was performed on a sample of 1498 women (358 BC patients and 1140 control (non BC) subjects). SHBG correlated in previously GWAS nine polymorphisms such as rs780093 GCKR, rs17496332 PRMT6, rs3779195 BAIAP2L1, rs10454142 PPP1R21, rs7910927 JMJD1C, rs4149056 SLCO1B1, rs440837 ZBTB10, rs12150660 SHBG, and rs8023580 NR2F2 have been genotyped. BC risk effects of allelic and non-allelic SHBG-linked gene SNPs interactions were detected by regression analysis. The risk genetic factor for BC developing is an SHBG-lowering allele variant C rs10454142 PPP1R21 ([additive genetic model] OR = 1.31; 95%CI = 1.08–1.65; pperm = 0.024; power = 85.26%), which determines 0.32% of the cancer variance. Eight of the nine studied SHBG-related SNPs have been involved in cancer susceptibility as part of nine different non-allelic gene interaction models, the greatest contribution to which is made by rs10454142 PPP1R21 (included in all nine models, 100%) and four more SNPs—rs7910927 JMJD1C (five models, 55.56%), rs17496332 PRMT6 (four models, 44.44%), rs780093 GCKR (four models, 44.44%), and rs440837 ZBTB10 (four models, 44.44%). For SHBG-related loci, pronounced functionality in the organism (including breast, liver, fibroblasts, etc.) was predicted in silico, having a direct relationship through many pathways with cancer pathophysiology. In conclusion, our results demonstrated the involvement of SHBG-correlated genes polymorphisms in BC risk in Caucasian women in Russia.
Chemical Hypoxia Induces Pyroptosis in Neuronal Cells by Caspase-Dependent Gasdermin Activation
Authors: Park Chan Ho , Park Jun Young , Cho Won Gil
Published: February 2024

Hypoxia-induced neuronal death is a major cause of neurodegenerative diseases. Pyroptosis is a type of inflammatory programmed cell death mediated by elevated intracellular levels of reactive oxygen species (ROS). Therefore, we hypothesized that hypoxia-induced ROS may trigger pyroptosis via caspase-dependent gasdermin (GSDM) activation in neuronal cells. To test this, we exposed SH-SY5Y neuronal cells to cobalt chloride (CoCl2) to trigger hypoxia and then evaluated the cellular and molecular responses to hypoxic conditions. Our data revealed that CoCl2 induced cell growth inhibition and the expression of hypoxia-inducible factor-1α in SH-SY5Y cells. Exposure to CoCl2 elicits excessive accumulation of cytosolic and mitochondrial ROS in SH-SY5Y cells. CoCl2-induced hypoxia not only activated the intrinsic (caspases-3, -7, and -9) apoptotic pathway but also induced caspase-3/GSDME-dependent and NLRP3/caspase-1/GSDMD-mediated pyroptosis in SH-SY5Y cells. Importantly, inhibition of caspase-3 and -1 using selective inhibitors ameliorated pyroptotic cell death and downregulated GSDM protein expression. Additionally, treatment with a ROS scavenger significantly suppressed caspase- and pyroptosis-related proteins in CoCl2-treated SH-SY5Y cells. Our findings indicate that hypoxia-mediated ROS production plays an important role in the activation of both apoptosis and pyroptosis in SH-SY5Y neuronal cells, thus providing a potential therapeutic strategy for hypoxia-related neurological diseases.
Aldehyde Dehydrogenase 2 (ALDH2) Deficiency, Obesity, and Atrial Fibrillation Susceptibility: Unraveling the Connection
Authors: Hsu Lung-An , Yeh Yung-Hsin , Chang Chi-Jen , Chen Wei-Jan , Tsai Hsin-Yi , Chang Gwo-Jyh
Published: February 2024

Atrial fibrillation (AF), characterized by structural remodeling involving atrial myocardial degradation and fibrosis, is linked with obesity and transforming growth factor beta 1 (TGF-β1). Aldehyde dehydrogenase 2 (ALDH2) deficiency, highly prevalent in East Asian people, is paradoxically associated with a lower AF risk. This study investigated the impact of ALDH2 deficiency on diet-induced obesity and AF vulnerability in mice, exploring potential compensatory upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme-oxygenase 1 (HO-1). Wild-type (WT) and ALDH2*2 knock-in (KI) mice were administered a high-fat diet (HFD) for 16 weeks. Despite heightened levels of reactive oxygen species (ROS) post HFD, the ALDH2*2 KI mice did not exhibit a greater propensity for AF compared to the WT controls. The ALDH2*2 KI mice showed equivalent myofibril degradation in cardiomyocytes compared to WT after chronic HFD consumption, indicating suppressed ALDH2 production in the WT mice. Atrial fibrosis did not proportionally increase with TGF-β1 expression in ALDH2*2 KI mice, suggesting compensatory upregulation of the Nrf2 and HO-1 pathway, attenuating fibrosis. In summary, ALDH2 deficiency did not heighten AF susceptibility in obesity, highlighting Nrf2/HO-1 pathway activation as an adaptive mechanism. Despite limitations, these findings reveal a complex molecular interplay, providing insights into the paradoxical AF–ALDH2 relationship in the setting of obesity.
Sex-Specific Effects of Long-Term Antipsychotic Drug Treatment on Adipocyte Tissue and the Crosstalk to Liver and Brain in Rats
Authors: Fehsel Karin , Bouvier Marie-Luise
Published: February 2024

Antipsychotic drug (APD) medication can lead to metabolic dysfunctions and weight gain, which together increase morbidity and mortality. Metabolically active visceral adipose tissue (VAT) in particular plays a crucial role in the etiopathology of these metabolic dysregulations. Here, we studied the effect of 12 weeks of drug medication by daily oral feeding of clozapine and haloperidol on the perirenal fat tissue as part of VAT of male and female Sprague Dawley rats in the context of complex former investigations on brain, liver, and blood. Adipocyte area values were determined, as well as triglycerides, non-esterified fatty acids (NEFAs), glucose, glycogen, lactate, malondialdehyde equivalents, ferric iron and protein levels of Perilipin-A, hormone-sensitive-lipase (HSL), hepcidin, glucose transporter-4 (Glut-4) and insulin receptor-ß (IR-ß). We found increased adipocyte mass in males, with slightly higher adipocyte area values in both males and females under clozapine treatment. Triglycerides, NEFAs, glucose and oxidative stress in the medicated groups were unchanged or slightly decreased. In contrast to controls and haloperidol-medicated rats, perirenal adipocyte mass and serum leptin levels were not correlated under clozapine. Protein expressions of perilipin-A, Glut-4 and HSL were decreased under clozapine treatment. IR-ß expression changed sex-specifically in the clozapine-medicated groups associated with higher hepcidin levels in the perirenal adipose tissue of clozapine-treated females. Taken together, clozapine and haloperidol had a smaller effect than expected on perirenal adipose tissue. The perirenal adipose tissue shows only weak changes in lipid and glucose metabolism. The main changes can be seen in the proteins examined, and probably in their effect on liver metabolism.
Isolation and Identification of a Tibetan Pig Porcine Epidemic Diarrhoea Virus Strain and Its Biological Effects on IPEC-J2 Cells
Authors: Li Mei , Wang Meng , Xi Yao , Qiu Shantong , Zeng Qiaoying , Pan Yangyang
Published: February 2024

Porcine epidemic diarrhoea virus (PEDV) is a coronavirus that can cause severe watery diarrhoea in piglets, with high morbidity and mortality rates, seriously hindering the healthy development of the global swine industry. In this study, we isolated a strain of PEDV from Tibetan pigs and named it CH/GS/2022. Subsequently, we screened the apoptosis signals of PEDV-infected IPEC-J2 cells and studied the correlation between apoptosis signals and cell apoptosis. The results showed that different infections of PEDV induced different degrees of apoptosis in cells, and PEDV-induced cell apoptosis was dose-dependent. We then detected the expression of the p53, p38, JNK, Bax, and Bcl-2 genes in the apoptosis signal pathway. The results showed that 24 h after PEDV infection, the expression of the p53, p38, JNK, and Bax genes in IPEC-J2 cells increased significantly, while the expression of the Bcl-2 gene decreased significantly (p < 0.05). Subsequently, we used Western blot to detect the protein levels of these five genes, and the results showed that PEDV infection upregulated the expression of p53, p38, JNK, and Bax proteins (p < 0.05) while downregulating the expression of Bcl-2 protein (p < 0.05). Thus, it was initially inferred that PEDV infection could regulate cell apoptosis by activating the p53, p38, and JNK signalling pathways. Finally, we further investigated the apoptosis of the cells through the use of inhibitors. The results indicated that the p53 inhibitor Pifithrin-α has a significant inhibitory effect on the expression of the p53 protein after PEDV infection and can reverse the expression levels of Bax and Bcl-2 proteins. This suggested that p53 is involved in PEDV-induced cell apoptosis. Similarly, the p38 MAPK inhibitor SB203580 has an inhibitory effect on the expression of the p38 protein and can reverse the expression levels of Bax and Bcl-2 proteins. This suggested that p38 is also involved in PEDV-induced cell apoptosis. On the other hand, the JNK inhibitor SP600125 has no inhibitory effect on the expression of the JNK protein after PEDV infection, but the expression levels of Bax and Bcl-2 proteins have changed. Furthermore, it is noteworthy that SP600125 can inhibit the activity of apoptotic proteins but not their levels, resulting in reduced cell apoptosis. These preliminary results indicated that JNK may be involved in PEDV-induced IPEC-J2 cell apoptosis.
Effect of Mexican Propolis on Wound Healing in a Murine Model of Diabetes Mellitus
Authors: Canales-Alvarez Octavio , Canales-Martinez Maria Margarita , Dominguez-Verano Pilar , Balderas-Cordero Daniela , Madrigal-Bujaidar Eduardo , Álvarez-González Isela , Rodriguez-Monroy Marco Aurelio
Published: February 2024

Diabetes mellitus (DM) affects the wound healing process, resulting in impaired healing or aberrant scarring. DM increases reactive oxygen species (ROS) production, fibroblast senescence and angiogenesis abnormalities, causing exacerbated inflammation accompanied by low levels of TGF—β and an increase in Matrix metalloproteinases (MMPs). Propolis has been proposed as a healing alternative for diabetic patients because it has antimicrobial, anti-inflammatory, antioxidant and proliferative effects and important properties in the healing process. An ethanolic extract of Chihuahua propolis (ChEEP) was obtained and fractionated, and the fractions were subjected to High–Performance Liquid Chromatography with diode–array (HPLC–DAD), High–Performance Liquid Chromatography–Mass Spectrometry (HPLC–MS) and Gas Chromatography–Mass Spectrometry (GC–MS) analyses and 46 compounds were detected. Deep wounds were made in a murine DM model induced by streptozotocin, and the speed of closure and the wound tensile strength were evaluated by the tensiometric method, which showed that ChEEP had similar activity to Recoveron, improving the speed of healing and increasing the wound tensile strength needed to open the wound again. A histological analysis of the wounds was performed using H&E staining, and when Matrix metalloproteinase 9 (MMP9) and α—actin were quantified by immunohistochemistry, ChEEP was shown to be associated with improved histological healing, as indicated by the reduced MMP9 and α—actin expression. In conclusion, topical ChEEP application enhances wound healing in diabetic mice.
Clostridioides difficile Flagella
Authors: Marvaud Jean-Christophe , Bouttier Sylvie , Saunier Johanna , Kansau Imad
Published: February 2024

Clostridioides difficile is an important pathogen for humans with a lead in nosocomial infection, but it is also more and more common in communities. Our knowledge of the pathology has historically been focused on the toxins produced by the bacteria that remain its major virulence factors. But the dysbiosis of the intestinal microbiota creating the conditions for the colonization appears to be fundamental for our understanding of the disease. Colonization implies several steps for the bacteria that do or do not use their capacity of motility with the synthesis of flagella. In this review, we focus on the current understanding of different topics on the C. difficile flagellum, ranging from its genetic organization to the vaccinal interest in it.
Trace DNA Transfer in Co-Working Spaces: The Importance of Background DNA Analysis
Authors: Onofri Martina , Tommolini Federica , Severini Simona , Gambelunghe Cristiana , Lancia Massimo , Carlini Luigi , Carnevali Eugenia
Published: February 2024

The presence of background DNA (bgDNA) can hinder the evaluation of DNA evidence at the activity level, especially when the suspect is expected to be retrieved due to their habitual occupation of the investigated environment. Based on real-life casework circumstances, this study investigates the prevalence, composition, origin, and probable transfer routes of bgDNA found on personal items in situations where their owner and person of interest (POI) share the same workspace. Baseline values of bgDNA were evaluated on the participants’ personal items. Secondary and higher degree transfer scenarios of non-self DNA deposition were also investigated. The DNA from co-workers and co-inhabiting partners can be recovered from an individual’s personal belongings. Non-self DNA present on the hands and deposited on a sterile surface can generate uninformative profiles. The accumulation of foreign DNA on surfaces over time appears to be crucial for the recovery of comparable profiles, resulting in detectable further transfer onto other surfaces. For a thorough evaluation of touch DNA traces at the activity level, it is necessary to collect information not only about DNA transfer probabilities but also about the presence of the POI as part of the ‘baseline’ bgDNA of the substrates involved.
Comorbidity Genes of Alzheimer’s Disease and Type 2 Diabetes Associated with Memory and Cognitive Function
Authors: Cho Seong Beom
Published: February 2024

Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) are comorbidities that result from the sharing of common genes. The molecular background of comorbidities can provide clues for the development of treatment and management strategies. Here, the common genes involved in the development of the two diseases and in memory and cognitive function are reviewed. Network clustering based on protein–protein interaction network identified tightly connected gene clusters that have an impact on memory and cognition among the comorbidity genes of AD and T2DM. Genes with functional implications were intensively reviewed and relevant evidence summarized. Gene information will be useful in the discovery of biomarkers and the identification of tentative therapeutic targets for AD and T2DM.
COVID-19, Possible Hepatic Pathways and Alcohol Abuse—What Do We Know up to 2023?
Authors: Michalak Agata , Lach Tomasz , Szczygieł Karolina , Cichoż-Lach Halina
Published: February 2024

The pandemic period due to coronavirus disease 2019 (COVID-19) revolutionized all possible areas of global health. Significant consequences were also related to diverse extrapulmonary manifestations of this pathology. The liver was found to be a relatively common organ, beyond the respiratory tract, affected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple studies revealed the essential role of chronic liver disease (CLD) in the general outcome of coronavirus infection. Present concerns in this field are related to the direct hepatic consequences caused by COVID-19 and pre-existing liver disorders as risk factors for the severe course of the infection. Which mechanism has a key role in this phenomenon—previously existing hepatic disorder or acute liver failure due to SARS-CoV-2—is still not fully clarified. Alcoholic liver disease (ALD) constitutes another not fully elucidated context of coronavirus infection. Should the toxic effects of ethanol or already developed liver cirrhosis and its consequences be perceived as a causative or triggering factor of hepatic impairment in COVID-19 patients? In the face of these discrepancies, we decided to summarize the role of the liver in the whole picture of coronavirus infection, paying special attention to ALD and focusing on the pathological pathways related to COVID-19, ethanol toxicity and liver cirrhosis.
The Influence of the Cu Foam on the Electrochemical Reduction of Carbon Dioxide
Authors: Lee Yuan-Gee , Chiao Hui-Hsuan , Weng Yu-Ching , Lay Chyi-How
Published: February 2024

Unlike the flat Cu sheet, we employed Cu foam to explore the specific porous effect on the expanding specific area. We found that the foam structure is superior to the sheet feature in the specific location from the morphology investigation. In the practical measurement of surface area, we found that the adsorbate could aptly agglomerate, resulting in a consequential block in the transport path. The specific location of the Cu foam was underestimated because the channels of the deep foam layer were blocked by the agglomerated adsorbate. To explore the protonation process of the electro-reduction, we adopted the carbonate electrolyte as the control group in contrast to the experimental group, the bicarbonate electrolyte. In the carbonate electrolyte, the primary intermediate was shown to be CO molecules, as verified using XPS spectra. In the bicarbonate electrolyte, the intermediate CO disappeared; instead, it was hydrogenated as a hydrocarbon intermediate, CHO*. The bicarbonate ion was also found to suppress electrocatalysis in the deep structure of the Cu foam because its high-molecular-weight intermediates accumulated in the diffusion paths. Furthermore, we found a promotion of the oxidation valence on the electrode from Cu2O to CuO, when the electrode structure transformed from sheet to foam. Cyclic voltammograms demonstrate a succession of electro-reduction consequences: at low reduction potential, hydrogen liberated by the decomposition of water; at elevated reduction potential, formic acid and CO produced; and at high reduction potential, CH4 and C2H4 were formed from −1.4 V to −1.8 V.