bluuebunny/crossref_metadata_2025 huggingface dataset:
Retention of Phytochemical Compounds and Antioxidative Activity in Traditional Baked Dish “proja” Made from Pigmented Maize
Authors: Šimurina Olivera , Filipčev Bojana , Kiprovski Biljana , Nježić Zvonko , Janić Hajnal Elizabet , Đalović Ivica
Published: September 2024

Two genotypes of pigmented maize (black (BM) and red (RM)) were used as flour ingredients in several formulations of the traditional baked maize dish “proja”. This study investigated the stability of phytochemical compounds and antioxidant activity in proja as affected by baking and different acidity degrees of dough formulations. Compared to RM proja, all BM proja formulations were significantly higher in antioxidant compounds and exhibited the highest inhibitory activity (73–85%) against DPPH. There was a strong significant correlation between DPPH inhibition and total phenolics (r2 = 0.95), flavonoids (r2 = 0.96), and anthocyanins (r2 = 0.97) in baked proja. After baking, 67–85% of total phenolics were retained. The fate of flavonoids and anthocyanins after baking was variable: from 70% degradation to liberation. Dough acidity significantly and positively affected the content of phenolics, flavonoids, and anthocyanins in BM proja (r2 = 0.70, 0.82, and 0.47, respectively). Baking increased antioxidant activity against DPPH, •OH, and O2•− radicals in proja, except for ≈10% decline of DPPH inhibition in BM proja. In RM proja, retention of inhibitory capacity against O2•− was highly correlated to flavonoid retention (r2 = 0.71). Using pigmented maize flour in proja baking resulted in proja with appreciable content of total phenolics, flavonoids, anthocyanins, and high antioxidant activity, confirming the significant improvement of the nutrient profile of this traditional food.
Polyphenolic Content and Antimicrobial Effects of Plant Extracts as Adjuncts for Craft Herbal Beer Stabilization
Authors: Coronas Roberta , Bianco Angela , Niccolai Marta , Fancello Francesco , Sanna Anna Maria Laura , Asteggiano Alberto , Medana Claudio , Caboni Pierluigi , Budroni Marilena , Zara Giacomo
Published: September 2024

Extracts from locally grown aromatic plants can enhance the geographical characteristics and microbial stability of craft beers, which are often not pasteurized or filtered. Here, the chemical and antimicrobial properties of aqueous extracts from leaves of Myrtus communis L., Pistacia lentiscus L., Artemisia arborescens L., and floral wastes of Crocus sativus L., all cultivated in Sardinia (Italy), were assessed. P. lentiscus extract had the highest polyphenol content (111.20 mg GAE/g), followed by M. communis (56.80 mg GAE/g), C. sativus (32.80 mg GAE/g), and A. arborescens (8.80 mg GAE/g). Notably, only the M. communis extract demonstrated significant inhibitory activity against pathogenic and spoilage microorganisms, with minimum inhibitory concentrations of 0.18, 0.71, and 1.42 mg GAE/mL against Staphylococcus aureus, Lactiplantibacillus plantarum, and Lacticaseibacillus casei, respectively. Additionally, it reduced the growth of Levilactobacillus brevis and Fructilactobacillus lindneri at concentrations of 0.35 and 0.71 mg GAE/mL, respectively. Based on its significant antimicrobial activity, the M. communis extract was further characterized using high-resolution mass spectrometry, revealing high abundances of nonprenylated phloroglucinols, flavonoid derivatives (myricetin), and quinic acids. Lastly, adding M. communis extract (2.84 mg GAE/mL) to commercial beer effectively prevented the growth of L. brevis and F. lindneri, showing its potential to avoid beer’s microbial spoilage.
Aquatic Food Products: Processing Technology and Quality Control
Authors: Bi Jingran
Published: September 2024

Aquatic products have the characteristics of high protein, low fat, and good nutritional balance, and they have become an important source of support to solve world hunger and nutritional deficiencies [...]
Knockout, Knockdown, and the Schrödinger Paradox: Genetic Immunity to Phenotypic Recapitulation in Zebrafish
Authors: Arana Álvaro J. , Sánchez Laura
Published: September 2024

Previous research has highlighted significant phenotypic discrepancies between knockout and knockdown approaches in zebrafish, raising concerns about the reliability of these methods. However, our study suggests that these differences are not as pronounced as was once believed. By carefully examining the roles of maternal and zygotic gene contributions, we demonstrate that these factors significantly influence phenotypic outcomes, often accounting for the observed discrepancies. Our findings emphasize that morpholinos, despite their potential off-target effects, can be effective tools when used with rigorous controls. We introduce the concept of graded maternal contribution, which explains how the uneven distribution of maternal mRNA and proteins during gametogenesis impacts phenotypic variability. Our research categorizes genes into three types—susceptible, immune, and “Schrödinger” (conditional)—based on their phenotypic expression and interaction with genetic compensation mechanisms. This distinction provides new insights into the paradoxical outcomes observed in genetic studies. Ultimately, our work underscores the importance of considering both maternal and zygotic contributions, alongside rigorous experimental controls, to accurately interpret gene function and the mechanisms underlying disease. This study advocates for the continued use of morpholinos in conjunction with advanced genetic tools like CRISPR/Cas9, stressing the need for a meticulous experimental design to optimize the utility of zebrafish in genetic research and therapeutic development.
Implementation of the Expert Nursing Standard: Caregivers’ Oral Health Knowledge
Authors: Nitschke Ina , Schulz Felix , Ludwig Elmar , Jockusch Julia
Published: September 2024

The promotion of oral health in nursing care is essential for preventing oral diseases and maintaining health in elderly vulnerable populations. There is a need for standardized guidelines and education. The aim of this study was to collect data on the attitudes and hopes of caregivers regarding the implementation of the German Expert Nursing Standard “Promotion of Oral Health in Nursing” (GENS-POHN) and to evaluate their oral healthcare knowledge before implementation. A cross-sectional study was conducted in five different care settings in Germany. A self-administered questionnaire was used to collect data on the attitudes and hopes of nursing assistants regarding the GENS-POHN. Oral healthcare knowledge was evaluated before implementation. Most participants had a positive attitude towards the GENS-POHN and hoped that its implementation would lead to greater safety and competence in daily oral healthcare tasks. Few participants currently use screening or assessment instruments for oral care. There is a need for further education and training, as well as the development and implementation of standardized guidelines and tools for screening and assessment, in oral care. The GENS-POHN as an expert standard could be made accessible to an international audience by translating it into other respective national languages, thereby enhancing its usability for a wider range of users.
How We Treat Hemolytic Anemia Due to Pyruvate Kinase Deficiency
Authors: Tama-Shekan Sara , Moreno Valeria , Saba Ludovic , Chaulagain Chakra P.
Published: September 2024

Background: Pyruvate kinase (PK) deficiency is an inherited red blood cell (RBC) enzyme disorder that results in non-immune chronic hemolytic anemia. Characteristic symptoms of PK deficiency include anemia, fatigue, splenomegaly, jaundice, gallstones, thrombosis, and transfusional iron overload. Previously, treatments aimed at symptomatic management with RBC transfusions, phototherapy, folic acid supplementation, splenectomy, and iron chelation therapy when iron overload was documented. Mitapivat, a recently approved medication for treatment of PK-deficiency hemolytic anemia, is an oral allosteric activator of wild-type and mutant RBC PK enzymes. In this paper, we describe three cases of PK-deficiency anemia treated with mitapivat and describe modern management of this rare hemolytic disorder. Methods: A retrospective healthcare database analysis was conducted to extract relevant information. Both quantitative and qualitative methods were integrated to provide a more comprehensive understanding of the cases. Results: Two patients responded well to treatment with mitapivat, noted by an increase in hemoglobin levels, improvements in hemolytic markers, less frequent or no RBC transfusion requirements, and improvements in fatigue. One patient carrying two non-missense mutations of the PKLR gene did not respond to treatment with mitapivat. As variations in patient-specific factors (including genotype) can lead to different clinical manifestations and responses to treatment, we recommend considering both the phenotype (clinical symptoms and signs) and the genotype of the PKLR gene when making therapeutic decisions about starting a patient on mitapivat. Conclusions: While mitapivat addresses the previously unmet needs of most patients with PK deficiency as the first and only disease-modifying medication to receive approval for this condition, not all patients with PK deficiency are amenable to treatment with mitapivat.
Genetic Characteristics and Volatile Organic Compounds of Leaves and Fruit Edible Parts of Citrus depressa Hayata from Different Geographic Origins
Authors: Oe Moena , Asikin Yonathan , Kashima Misaki , Yamamoto Masashi , Mitsube Fumimasa , Lin Shu-Yen , Takara Kensaku , Wada Koji
Published: September 2024

Citrus depressa Hayata is a citrus cultivar grown in Japan and Taiwan. To assess the differences in genetic characteristics and volatile organic components (VOCs) in the leaves and edible parts of the fruits of 23 C. depressa accessions from different geographic origins, the tissues were analyzed using cleaved amplified polymorphic sequence markers and gas chromatography-mass spectrometry. A phylogenetic cluster analysis demonstrated that Kagoshima accessions had a close genetic relationship with one another, with Okinawan “Izumi kugani-like” being the most distinct accession. The predominant volatiles in the leaves were γ-terpinene, p-cymene, limonene, and linalool. Multivariate analysis and volcano plots revealed distinct volatiles in the leaves of each cultivation region: piperitone and citronellal (Kagoshima); 5,9,9-trimethyl-spiro[3.5]non-5-en-1-one (Okinawa); and hexanal (Taiwan). Furthermore, the edible parts of Taiwanese fruits contained abundant amounts of monoterpenes, including linalool and 1,8-cineole. In contrast, Kagoshima and Okinawa accessions were rich in aldehydes and esters, respectively. In conclusion, the genetic and volatile profiles of 23 C. depressa accessions of different origins could be distinguished, and multivariate analysis suggested that C. depressa contains diverse VOCs depending on where it is cultivated. These findings demonstrate the exclusivity of C. depressa resources in each region, which could assist farmers and agro-industries in promoting food products derived from C. depressa fruits.
Impact of CO2 Enrichment on Growth, Yield and Fruit Quality of F1 Hybrid Strawberry Grown under Controlled Greenhouse Condition
Authors: Osman Mohamed , Qaryouti Muein , Alharbi Saif , Alghamdi Budour , Al-Soqeer Abdulrahman , Alharbi Abdulaziz , Almutairi Khalid , Abdelaziz Mohamed Ewis
Published: September 2024

Carbon dioxide enrichment inside a greenhouse is a sustainable approach to increasing crop production worldwide. Recently, the F1 hybrid strawberry became an alternative to runner-propagated cultivation as an innovative method to shorten the production period and increase strawberry production. This work aims to present CO2 enrichment as a sustainable tool that improves the yield in a controlled greenhouse and addresses the efficiency of three F1 hybrid strawberry varieties grown under Saudi Arabian conditions. A greenhouse experiment was conducted at the National Research and Development Center for Sustainable Agriculture (Estidamah), KSA, to study the impact of two CO2 levels (400 ppm (“ambient”) and 600 ppm (“enrichment”)) on the growth, photosynthesis traits, fruit yield and fruit quality of three F1 hybrid strawberry varieties grown under soilless culture conditions. The results show that CO2 enrichment significantly improved the phenotyping of strawberry growth traits at 60 days post-transplanting. The physiological response of the varieties to CO2 enrichment reveals a significant increase in the photosynthetic rate (129.7%) and intercellular CO2 (43.7%) in the leaves of strawberry exposed to CO2 enrichment rather than in ambient conditions, combined with a significant increase in the number of fruits per plant (27.5%) and total fruit yield (42.2%). A similar pattern was observed with varieties D and S in terms of fruit number, length and diameter. However, CO2 at 600 ppm promoted total soluble solid accumulation and vitamin C for the tested varieties. In contrast, CO2 enrichment significantly decreased nitrogen, phosphorus, potassium and magnesium accumulation in the leaves of the exposed plants in comparison to 400 ppm of CO2. These results suggest that increasing CO2 enrichment could contribute to an increase in strawberry yield and nutritional value and demonstrate that understanding the response of each variety to CO2 enrichment is important to support selecting suitable greenhouse strawberry varieties to improve crop yield.
Mechanistic Insights on Metformin and Arginine Implementation as Repurposed Drugs in Glioblastoma Treatment
Authors: Barciszewska Anna-Maria , Belter Agnieszka , Barciszewski Jakub F. , Gawrońska Iwona , Giel-Pietraszuk Małgorzata , Naskręt-Barciszewska Mirosława Z.
Published: September 2024

As the most common and aggressive primary malignant brain tumor, glioblastoma is still lacking a satisfactory curative approach. The standard management consisting of gross total resection followed by radiotherapy and chemotherapy with temozolomide only prolongs patients’ life moderately. In recent years, many therapeutics have failed to give a breakthrough in GBM treatment. In the search for new treatment solutions, we became interested in the repurposing of existing medicines, which have established safety profiles. We focused on the possible implementation of well-known drugs, metformin, and arginine. Metformin is widely used in diabetes treatment, but arginine is mainly a cardiovascular protective drug. We evaluated the effects of metformin and arginine on total DNA methylation, as well as the oxidative stress evoked by treatment with those agents. In glioblastoma cell lines, a decrease in 5-methylcytosine contents was observed with increasing drug concentration. When combined with temozolomide, both guanidines parallelly increased DNA methylation and decreased 8-oxo-deoxyguanosine contents. These effects can be explained by specific interactions of the guanidine group with m5CpG dinucleotide. We showed that metformin and arginine act on the epigenetic level, influencing the foreground and potent DNA regulatory mechanisms. Therefore, they can be used separately or in combination with temozolomide, in various stages of disease, depending on desired treatment effects.
Green Leaf Volatiles: A New Player in the Protection against Abiotic Stresses?
Authors: Engelberth Jurgen
Published: September 2024

To date, the role of green leaf volatiles (GLVs) has been mainly constrained to protecting plants against pests and pathogens. However, increasing evidence suggests that among the stresses that can significantly harm plants, GLVs can also provide significant protection against heat, cold, drought, light, and salinity stress. But while the molecular basis for this protection is still largely unknown, it seems obvious that a common theme in the way GLVs work is that most, if not all, of these stresses are associated with physical damage to the plants, which, in turn, is the major event responsible for the production of GLVs. Here, I summarize the current state of knowledge on GLVs and abiotic stresses and provide a model explaining the multifunctionality of these compounds.
The Application of Green Solvents in the Synthesis of S-Heterocyclic Compounds—A Review
Authors: Kosmalski Tomasz , Kołodziejska Renata , Przybysz Monika , Szeleszczuk Łukasz , Pawluk Hanna , Mądra-Gackowska Katarzyna , Studzińska Renata
Published: September 2024

Cyclic organic compounds containing sulfur atoms constitute a large group, and they play an important role in the chemistry of heterocyclic compounds. They are valuable intermediates for the synthesis of other compounds or biologically active compounds themselves. The synthesis of heterocyclic compounds poses a major challenge for organic chemists, especially in the context of applying the principles of “green chemistry”. This work is a review of the methods of synthesis of various S-heterocyclic compounds using green solvents such as water, ionic liquids, deep eutectic solvents, glycerol, ethylene glycol, polyethylene glycol, and sabinene. The syntheses of five-, six-, and seven-membered heterocyclic compounds containing a sulfur atom or atoms, as well as those with other heteroatoms and fused-ring systems, are described. It is shown that using green solvents determines the attractiveness of conditions for many reactions; for others, such use constitutes a real compromise between efficiency and mild reaction conditions.
Spatiotemporal Dysregulation of Neuron–Glia Related Genes and Pro-/Anti-Inflammatory miRNAs in the 5xFAD Mouse Model of Alzheimer’s Disease
Authors: Ianni Marta , Corraliza-Gomez Miriam , Costa-Coelho Tiago , Ferreira-Manso Mafalda , Inteiro-Oliveira Sara , Alemãn-Serrano Nuno , Sebastião Ana M. , Garcia Gonçalo , Diógenes Maria José , Brites Dora
Published: September 2024

Alzheimer’s disease (AD), the leading cause of dementia, is a multifactorial disease influenced by aging, genetics, and environmental factors. miRNAs are crucial regulators of gene expression and play significant roles in AD onset and progression. This exploratory study analyzed the expression levels of 28 genes and 5 miRNAs (miR-124-3p, miR-125b-5p, miR-21-5p, miR-146a-5p, and miR-155-5p) related to AD pathology and neuroimmune responses using RT-qPCR. Analyses were conducted in the prefrontal cortex (PFC) and the hippocampus (HPC) of the 5xFAD mouse AD model at 6 and 9 months old. Data highlighted upregulated genes encoding for glial fibrillary acidic protein (Gfap), triggering receptor expressed on myeloid cells (Trem2) and cystatin F (Cst7), in the 5xFAD mice at both regions and ages highlighting their roles as critical disease players and potential biomarkers. Overexpression of genes encoding for CCAAT enhancer-binding protein alpha (Cebpa) and myelin proteolipid protein (Plp) in the PFC, as well as for BCL2 apoptosis regulator (Bcl2) and purinergic receptor P2Y12 (P2yr12) in the HPC, together with upregulated microRNA(miR)-146a-5p in the PFC, prevailed in 9-month-old animals. miR-155 positively correlated with miR-146a and miR-21 in the PFC, and miR-125b positively correlated with miR-155, miR-21, while miR-146a in the HPC. Correlations between genes and miRNAs were dynamic, varying by genotype, region, and age, suggesting an intricate, disease-modulated interaction between miRNAs and target pathways. These findings contribute to our understanding of miRNAs as therapeutic targets for AD, given their multifaceted effects on neurons and glial cells.
X-ray Radiotherapy Impacts Cardiac Dysfunction by Modulating the Sympathetic Nervous System and Calcium Transients
Authors: Feat-Vetel Justyne , Suffee Nadine , Bachelot Florence , Dos Santos Morgane , Mougenot Nathalie , Delage Elise , Saliou Florian , Martin Sabrina , Brunet Isabelle , Sicard Pierre , Monceau Virginie
Published: September 2024

Recent epidemiological studies have shown that patients with right-sided breast cancer (RBC) treated with X-ray irradiation (IR) are more susceptible to developing cardiovascular diseases, such as arrhythmias, atrial fibrillation, and conduction disturbances after radiotherapy (RT). Our aim was to investigate the mechanisms induced by low to moderate doses of IR and to evaluate changes in the cardiac sympathetic nervous system (CSNS), atrial remodeling, and calcium homeostasis involved in cardiac rhythm. To mimic the RT of the RBC, female C57Bl/6J mice were exposed to X-ray doses ranging from 0.25 to 2 Gy targeting 40% of the top of the heart. At 60 weeks after RI, Doppler ultrasound showed a significant reduction in myocardial strain, ejection fraction, and atrial function, with a significant accumulation of fibrosis in the epicardial layer and apoptosis at 0.5 mGy. Calcium transient protein expression levels, such as RYR2, NAK, Kir2.1, and SERCA2a, increased in the atrium only at 0.5 Gy and 2 Gy at 24 h, and persisted over time. Interestingly, 3D imaging of the cleaned hearts showed an early reduction of CSNS spines and dendrites in the ventricles and a late reorientation of nerve fibers, combined with a decrease in SEMA3a expression levels. Our results showed that local heart IR from 0.25 Gy induced late cardiac and atrial dysfunction and fibrosis development. After IR, ventricular CSNS and calcium transient protein expression levels were rearranged, which affected cardiac contractility. The results are very promising in terms of identifying pro-arrhythmic mechanisms and preventing arrhythmias during RT treatment in patients with RBC.
Psychobiotic Properties of Lactiplantibacillus plantarum in Neurodegenerative Diseases
Authors: Di Chiano Mariagiovanna , Sallustio Fabio , Fiocco Daniela , Rocchetti Maria Teresa , Spano Giuseppe , Pontrelli Paola , Moschetta Antonio , Gesualdo Loreto , Gadaleta Raffaella Maria , Gallone Anna
Published: September 2024

Neurodegenerative disorders are the main cause of cognitive and physical disabilities, affect millions of people worldwide, and their incidence is on the rise. Emerging evidence pinpoints a disturbance of the communication of the gut–brain axis, and in particular to gut microbial dysbiosis, as one of the contributors to the pathogenesis of these diseases. In fact, dysbiosis has been associated with neuro-inflammatory processes, hyperactivation of the neuronal immune system, impaired cognitive functions, aging, depression, sleeping disorders, and anxiety. With the rapid advance in metagenomics, metabolomics, and big data analysis, together with a multidisciplinary approach, a new horizon has just emerged in the fields of translational neurodegenerative disease. In fact, recent studies focusing on taxonomic profiling and leaky gut in the pathogenesis of neurodegenerative disorders are not only shedding light on an overlooked field but are also creating opportunities for biomarker discovery and development of new therapeutic and adjuvant strategies to treat these disorders. Lactiplantibacillus plantarum (LBP) strains are emerging as promising psychobiotics for the treatment of these diseases. In fact, LBP strains are able to promote eubiosis, increase the enrichment of bacteria producing beneficial metabolites such as short-chain fatty acids, boost the production of neurotransmitters, and support the homeostasis of the gut–brain axis. In this review, we summarize the current knowledge on the role of the gut microbiota in the pathogenesis of neurodegenerative disorders with a particular focus on the benefits of LBP strains in Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, autism, anxiety, and depression.
Loss of JCAD/KIAA1462 Protects the Lung from Acute and Chronic Consequences of Chronic Obstructive Pulmonary Disease
Authors: Suraya Ratoe , Nagano Tatsuya , Yumura Masako , Hara Tetsuya , Akashi Masaya , Yamamoto Masatsugu , Tachihara Motoko , Nishimura Yoshihiro , Kobayashi Kazuyuki
Published: September 2024

Even with recent advances in pathobiology and treatment options, chronic obstructive pulmonary disease (COPD) remains a major contributor to morbidity and mortality. To develop new ways of combating this disease, breakthroughs in our understanding of its mechanisms are sorely needed. Investigating the involvement of underanalyzed lung cell types, such as endothelial cells (ECs), is one way to further our understanding of COPD. JCAD is a junctional protein in endothelial cells (ECs) arising from the KIAA1462 gene, and a mutation in this gene has been implicated in the risk of developing COPD. In our study, we induced inflammation and emphysema in mice via the global knockout of KIAA1462/JCAD (JCAD-KO) and confirmed it in HPMECs and A549 to examine how the loss of JCAD could affect COPD development. We found that KIAA1462/JCAD loss reduced acute lung inflammation after elastase treatment. Even after 3 weeks of elastase, JCAD-KO mice demonstrated a preserved lung parenchymal structure and vasculature. In vitro, after KIAA1462 expression is silenced, both endothelial and epithelial cells showed alterations in pro-inflammatory gene expression after TNF-α treatment. We concluded that JCAD loss could ameliorate COPD through its anti-inflammatory and anti-angiogenic effects, and that KIAA1462/JCAD could be a novel target for COPD therapy.
Recent Advances: Heterocycles in Drugs and Drug Discovery
Authors: Pibiri Ivana
Published: September 2024

Interest and research focusing on the design of novel pharmaceutical agents is always growing [...]
Lemairamin (Wgx-50) Attenuates DSS-Induced Intestinal Inflammation in Zebrafish
Authors: Zhang Ling , Liu Huiru , Zhang Haoyi , Yuan Hao , Ren Dalong
Published: September 2024

Inflammatory bowel disease (IBD) is a chronic non-specific intestinal inflammatory disease that affects millions of people worldwide, and current treatment methods have certain limitations. This study aimed to explore the therapeutic potential and mechanism of action of lemairamin (Wgx-50) in inflammatory bowel disease (IBD). We used dextran sulfate sodium (DSS)-treated zebrafish as an inflammatory bowel disease model, and observed the effect of Wgx-50 on DSS-induced colitis inflammation. The results of the study showed that Wgx-50 could reduce the expression of pro-inflammatory cytokines induced by DSS and inhibit the recruitment of neutrophils to the site of intestinal injury. Further experiments revealed that Wgx-50 exerted its anti-inflammatory effect by regulating the activation of the Akt pathway. These research findings indicate that Wgx-50 possesses anti-inflammatory activity.
Reverse Gradient Distributions of Drug and Polymer Molecules within Electrospun Core–Shell Nanofibers for Sustained Release
Authors: Chen Yaoning , Gong Wenjian , Zhang Zhiyuan , Zhou Jianfeng , Yu Deng-Guang , Yi Tao
Published: September 2024

Core–shell nanostructures are powerful platforms for the development of novel nanoscale drug delivery systems with sustained drug release profiles. Coaxial electrospinning is facile and convenient for creating medicated core–shell nanostructures with elaborate designs with which the sustained-release behaviors of drug molecules can be intentionally adjusted. With resveratrol (RES) as a model for a poorly water-soluble drug and cellulose acetate (CA) and PVP as polymeric carriers, a brand-new electrospun core–shell nanostructure was fabricated in this study. The guest RES and the host CA molecules were designed to have a reverse gradient distribution within the core–shell nanostructures. Scanning electron microscope and transmission electron microscope evaluations verified that these nanofibers had linear morphologies, without beads or spindles, and an obvious core–shell double-chamber structure. The X-ray diffraction patterns and Fourier transform infrared spectroscopic results indicated that the involved components were highly compatible and presented in an amorphous molecular distribution state. In vitro dissolution tests verified that the new core–shell structures were able to prevent the initial burst release, extend the continuous-release time period, and reduce the negative tailing-off release effect, thus ensuring a better sustained-release profile than the traditional blended drug-loaded nanofibers. The mechanism underlying the influence of the new core–shell structure with an RES/CA reverse gradient distribution on the behaviors of RES release is proposed. Based on this proof-of-concept demonstration, a series of advanced functional nanomaterials can be similarly developed based on the gradient distributions of functional molecules within electrospun multi-chamber nanostructures.
Effect of Sodium Thiosulfate Pre-Treatment on Renal Ischemia-Reperfusion Injury in Kidney Transplantation
Authors: Nelson Pierce , Dugbartey George J. , McFarlane Liam , McLeod Patrick , Major Sally , Jiang Jifu , O’Neil Caroline , Haig Aaron , Sener Alp
Published: September 2024

We recently reported in a rat model of kidney transplantation that the addition of sodium thiosulfate (STS) to organ preservation solution improved renal graft quality and prolonged recipient survival. The present study investigates whether STS pre-treatment would produce a similar effect. In vitro, rat kidney epithelial cells were treated with 150 μM STS before and/or during exposure to hypoxia followed by reoxygenation. In vivo, donor rats were treated with PBS or 2.4 mg/kg STS 30 min before donor kidneys were procured and stored in UW or UW+150 μM STS solution at 4 °C for 24 h. Renal grafts were then transplanted into bilaterally nephrectomised recipient rats which were then sacrificed on post-operative day 3. STS pre-treatment significantly reduced cell death compared to untreated and other treated cells in vitro (p < 0.05), which corresponded with our in vivo result (p < 0.05). However, no significant differences were observed in other parameters of tissue injury. Our results suggest that STS pre-treatment may improve renal graft function after transplantation.
Activation of G Protein-Coupled Estrogen Receptor 1 (GPER) Attenuates Obesity-Induced Asthma by Switching M1 Macrophages to M2 Macrophages
Authors: Son So-Eun , Im Dong-Soon
Published: September 2024

The prevalence of obesity-induced asthma increases in women after menopause. We hypothesized that the increase in obese asthma in middle-aged women results from estrogen loss. In particular, we focused on the acute action of estrogen through the G protein-coupled estrogen receptor 1 (GPER), previously known as GPR30. We investigated whether GPER activation ameliorates obesity-induced asthma with a high-fat diet (HFD) using G-1, the GPER agonist, and G-36, the GPER antagonist. Administration of G-1 (0.5 mg/kg) suppressed HFD-induced airway hypersensitivity (AHR), and increased immune cell infiltration, whereas G-36 co-treatment blocked it. Histological analysis showed that G-1 treatment inhibited HFD-induced inflammation, fibrosis, and mucus hypersecretion in a GPER-dependent manner. G-1 inhibited the HFD-induced rise in the mRNA levels of pro-inflammatory cytokines in the gonadal white adipose tissue and lungs, whereas G-36 co-treatment reversed this effect. G-1 increased anti-inflammatory M2 macrophages and inhibited the HFD-induced rise in pro-inflammatory M1 macrophages in the lungs. In addition, G-1 treatment reversed the HFD-induced increase in leptin expression and decrease in adiponectin expression in the lungs and gonadal white adipose tissue. The results suggest that activation of GPER could be a therapeutic option for obesity-induced asthma.
Investigating the Role of Cannabinoid Type 1 Receptors in Vascular Function and Remodeling in a Hypercholesterolemic Mouse Model with Low-Density Lipoprotein–Cannabinoid Type 1 Receptor Double Knockout Animals
Authors: Vass Zsolt , Shenker-Horváth Kinga , Bányai Bálint , Vető Kinga Nóra , Török Viktória , Gém Janka Borbála , Nádasy György L. , Kovács Kinga Bernadett , Horváth Eszter Mária , Jakus Zoltán , Hunyady László , Szekeres Mária , Dörnyei Gabriella
Published: September 2024

Hypercholesterolemia forms the background of several cardiovascular pathologies. LDL receptor-knockout (LDLR-KO) mice kept on a high-fat diet (HFD) develop high cholesterol levels and atherosclerosis (AS). Cannabinoid type 1 receptors (CB1Rs) induce vasodilation, although their role in cardiovascular pathologies is still controversial. We aimed to reveal the effects of CB1Rs on vascular function and remodeling in hypercholesterolemic AS-prone LDLR-KO mice. Experiments were performed on a newly established LDLR and CB1R double-knockout (KO) mouse model, in which KO and wild-type (WT) mice were kept on an HFD or a control diet (CD) for 5 months. The vascular functions of abdominal aorta rings were tested with wire myography. The vasorelaxation effects of acetylcholine (Ach, 1 nM–1 µM) were obtained after phenylephrine precontraction, which was repeated with inhibitors of nitric oxide synthase (NOS) and cyclooxygenase (COX), Nω-nitro-L-arginine (LNA), and indomethacin (INDO), respectively. Blood pressure was measured with the tail-cuff method. Immunostaining of endothelial NOS (eNOS) was carried out. An HFD significantly elevated the cholesterol levels in the LDLR-KO mice more than in the corresponding WT mice (mean values: 1039 ± 162 mg/dL vs. 91 ± 18 mg/dL), and they were not influenced by the presence of the CB1R gene. However, with the defect of the CB1R gene, damage to the Ach relaxation ability was moderated. The blood pressure was higher in the LDLR-KO mice compared to their WT counterparts (systolic/diastolic values: 110/84 ± 5.8/6.8 vs. 102/80 ± 3.3/2.5 mmHg), which was significantly elevated with an HFD (118/96 ± 1.9/2 vs. 100/77 ± 3.4/3.1 mmHg, p < 0.05) but attenuated in the CB1R-KO HFD mice. The expression of eNOS was depressed in the HFD WT mice compared to those on the CD, but it was augmented if CB1R was knocked out. This newly established double-knockout mouse model provides a tool for studying the involvement of CB1Rs in the development of hypercholesterolemia and atherosclerosis. Our results indicate that knocking out the CB1R gene significantly attenuates vascular damage in hypercholesterolemic mice.
Plastome Evolution and Comparative Analyses of a Recently Radiated Genus Vanda (Aeridinae, Orchidaceae)
Authors: Lei Wanshun , Zhou Peng , Pei Zelong , Liu Yizhen , Luo Yan , Xiang Xiaoguo
Published: September 2024

Vanda R.Br. is an epiphytic orchid genus with significant horticultural and ornamental value. Previous molecular studies expanded Vanda including some members from five other genera. However, the interspecific relationships of this recently radiated genus have remained unclear based on several DNA markers until now. In this study, the complete plastome has been used to infer the phylogenetic relationships of Vanda s.l. The five newly obtained plastomes ranged from 146,340 bp to 149,273 bp in length, with a GC content ranging from 36.5% to 36.7%. The five plastomes contained 74 protein-coding genes (CDSs), 38 tRNAs, and 8 rRNAs, and their ndh genes underwent loss or pseudogenization. Comparative plastome analyses of 13 Vanda species revealed high conservation in terms of genome size, structure, and gene order, except for a large inversion from trnGGCC to ycf3 in V. coerulea. Moreover, six CDSs and five non-CDSs were selected as candidate DNA barcodes. Our phylogenetic analyses demonstrated that Vanda s.l. is a monophyletic group with high supporting values based on five different datasets (complete plastome with one IR, 68 CDSs, LSC, five hypervariable non-CDSs, and six hypervariable CDSs), while the phylogenetic relationships among species were fully resolved based on the complete plastome with one IR dataset. Our results confirmed that the complete plastome has a great power in resolving the phylogenetic relationships of recently radiated lineages.
Peripheral Inflammation Featuring Eosinophilia or Neutrophilia Is Associated with the Survival and Infiltration of Eosinophils within the Tumor among Various Histological Subgroups of Patients with NSCLC
Authors: Alashkar Alhamwe Bilal , Yuskaeva Kadriya , Wulf Friederike , Trinkmann Frederik , Kriegsmann Mark , Thomas Michael , Keber Corinna Ulrike , Strandmann Elke Pogge von , Herth Felix J. , Kolahian Saeed , Renz Harald , Muley Thomas
Published: September 2024

Immune activation status determines non-small cell lung cancer (NSCLC) prognosis, with reported positive/negative associations for T helper type 2 (TH2) responses, including allergen-specific IgE and eosinophils. Our study seeks to explore the potential impact of these comorbid immune responses on the survival rates of patients with NSCLC. Our retrospective study used data from the Data Warehouse of the German Center for Lung Research (DZL) and Lung Biobank at Thoraxklinik Heidelberg. We estimated the association of blood eosinophilia and neutrophilia on survival rates in an inflammatory cohort of 3143 patients with NSCLC. We also tested sensitization to food and inhalants and high-sensitivity C-reactive protein (hs-CRP) in a comorbidity cohort of 212 patients with NSCLC. Finally, we estimated the infiltration of immune-relevant cells including eosinophils, T-cells, and mast cells in a tissue inflammatory sub-cohort of 60 patients with NSCLC. Sensitization to at least one food or inhalant (sIgE) was higher in patients with adenocarcinoma (adeno-LC) than the non-adenocarcinoma (non-adeno-LC). Furthermore, hs-CRP was higher in non-adeno-LC compared with adeno-LC. Peripheral inflammation, particularly eosinophilia and neutrophilia, was associated with poor survival outcomes in NSCLC with a clear difference between histological subgroups. Finally, blood eosinophilia was paralleled by significant eosinophil infiltration into the peritumoral tissue in the lung. This study provides novel perspectives on the crucial role of peripheral inflammation, featuring eosinophilia and neutrophilia, with overall survival, underscoring distinctions between NSCLC subgroups (adeno-LC vs. non-adeno-LC). Peripheral eosinophilia enhances eosinophil infiltration into tumors. This sheds light on the complex interplay between inflammation, eosinophil infiltration, and NSCLC prognosis among various histological subtypes. Further studies are required to underscore the role of eosinophils in NSCLC among different histological subgroups and their role in shaping the tumor microenvironment.
Raman Spectroscopy of Optically Trapped Living Human T Cell Subsets and Monocytes
Authors: Nötzel Martin , Mahamid Maria , Kronstein-Wiedemann Romy , Ziemssen Tjalf , Akgün Katja
Published: September 2024

In recent years, Raman spectroscopy has garnered growing interest in the field of biomedical research. It offers a non-invasive and label-free approach to defining the molecular fingerprint of immune cells. We utilized Raman spectroscopy on optically trapped immune cells to investigate their molecular compositions. While numerous immune cell types have been studied in the past, the characterization of living human CD3/CD28-stimulated T cell subsets remains incomplete. In this study, we demonstrate the capability of Raman spectroscopy to readily distinguish between naïve and stimulated CD4 and CD8 cells. Additionally, we compared these cells with monocytes and discovered remarkable similarities between stimulated T cells and monocytes. This paper contributes to expanding our knowledge of Raman spectroscopy of immune cells and serves as a launching point for future clinical applications.
Crucial Parameters for Immunopeptidome Characterization: A Systematic Evaluation
Authors: Juanes-Velasco Pablo , Arias-Hidalgo Carlota , García-Vaquero Marina L. , Sotolongo-Ravelo Janet , Paíno Teresa , Lécrevisse Quentin , Landeira-Viñuela Alicia , Góngora Rafael , Hernández Ángela-Patricia , Fuentes Manuel
Published: September 2024

Immunopeptidomics is the area of knowledge focused on the study of peptides assembled in the major histocompatibility complex (MHC), or human leukocyte antigen (HLA) in humans, which could activate the immune response via specific and selective T cell recognition. Advances in high-sensitivity mass spectrometry have enabled the detailed identification and quantification of the immunopeptidome, significantly impacting fields like oncology, infections, and autoimmune diseases. Current immunopeptidomics approaches primarily focus on workflows to identify immunopeptides from HLA molecules, requiring the isolation of the HLA from relevant cells or tissues. Common critical steps in these workflows, such as cell lysis, HLA immunoenrichment, and peptide isolation, significantly influence outcomes. A systematic evaluation of these steps led to the creation of an ‘Immunopeptidome Score’ to enhance the reproducibility and robustness of these workflows. This score, derived from LC-MS/MS datasets (ProteomeXchange identifier PXD038165), in combination with available information from public databases, aids in optimizing the immunopeptidome characterization process. The ‘Immunopeptidome Score’ has been applied in a systematic analysis of protein extraction, HLA immunoprecipitation, and peptide recovery yields across several tumor cell lines enabling the selection of peptides with optimal features and, therefore, the identification of potential biomarker and therapeutic targets.
Simultaneous Detection of Collagen I Alpha II and Cytokeratin 19 mRNA by Multiplex qPCR in Liquid Biopsy in Diagnosis of Patients with Resectable Solid Tumors
Authors: Estévez Pérez Lara Sofía , Alén Begoña O. , Otero Alén María , Hormaetxe Saioa Domínguez , Simón Laureano , Concha Ángel
Published: September 2024

The early detection of tumors is one of the key factors in increasing overall survival in cancer patients. A wide range of cancers still do not have a system of early diagnosis; therefore, the development of new non-invasive tools in this line is essential. Accordingly, the objective of our work was to develop a non-invasive screening method for the early detection of various carcinomas in plasma using a panel that combines two markers using RT-qPCR. A retrospective case-control study was conducted to develop a cancer screening test based on the detection of stromal and epithelial biomarkers (COL1A2 and KRT19) in plasma. The expression of biomarkers was evaluated using multiplex quantitative PCR applied to 47 cases with non-metastatic tumors and 13 control participants. For both biomarkers, a cut-off value was stablished using Youden’s J index through ROC curve analysis and areas under the curve (AUC) were calculated. The plasma mRNA expression level of both biomarkers was significantly higher in diseased versus healthy patients. Moreover, ROC curve analysis showed an AUC value of 0.897 for the combined model. This model also resulted in a cutoff value of 0.664, as well as a sensitivity of 83% and a specificity of 84.6%. These results suggest that the plasma expression levels of COL1A2 and KRT19 could a have potential role in detecting various types of cancer at the early stages. The combined analysis of both stromal and epithelial biomarkers would provide a non-invasive screening method that would allow us to differentiate patients with an active neoplastic process.
Using MRI Texture Analysis Machine Learning Models to Assess Graft Interstitial Fibrosis and Tubular Atrophy in Patients with Transplanted Kidneys
Authors: Trojani Valeria , Monelli Filippo , Besutti Giulia , Bertolini Marco , Verzellesi Laura , Sghedoni Roberto , Iori Mauro , Ligabue Guido , Pattacini Pierpaolo , Giorgi Rossi Paolo , Ottone Marta , Piccinini Alessia , Alfano Gaetano , Donati Gabriele , Fontana Francesco
Published: September 2024

Objective: Interstitial fibrosis/tubular atrophy (IFTA) is a common, irreversible, and progressive form of chronic kidney allograft injury, and it is considered a critical predictor of kidney allograft outcomes. The extent of IFTA is estimated through a graft biopsy, while a non-invasive test is lacking. The aim of this study was to evaluate the feasibility and accuracy of an MRI radiomic-based machine learning (ML) algorithm to estimate the degree of IFTA in a cohort of transplanted patients. Approach: Patients who underwent MRI and renal biopsy within a 6-month interval from 1 January 2012 to 1 March 2021 were included. Stable MRI sequences were selected, and renal parenchyma, renal cortex and medulla were segmented. After image filtering and pre-processing, we computed radiomic features that were subsequently selected through a LASSO algorithm for their highest correlation with the outcome and lowest intercorrelation. Selected features and relevant patients’ clinical data were used to produce ML algorithms using 70% of the study cases for feature selection, model training and validation with a 10-fold cross-validation, and 30% for model testing. Performances were evaluated using AUC with 95% confidence interval. Main results: A total of 70 coupled tests (63 patients, 35.4% females, mean age 52.2 years) were included and subdivided into a wider cohort of 50 for training and a smaller cohort of 20 for testing. For IFTA ≥ 25%, the AUCs in test cohort were 0.60, 0.59, and 0.54 for radiomic features only, clinical variables only, and a combined radiomic–clinical model, respectively. For IFTA ≥ 50%, the AUCs in training cohort were 0.89, 0.84, and 0.96, and in the test cohort, they were 0.82, 0.83, and 0.86, for radiomic features only, clinical variables only, and the combined radiomic–clinical model, respectively. Significance: An ML-based MRI radiomic algorithm showed promising discrimination capacity for IFTA > 50%, especially when combined with clinical variables. These results need to be confirmed in larger cohorts.
Review of Modern Forest Fire Detection Techniques: Innovations in Image Processing and Deep Learning
Authors: Özel Berk , Alam Muhammad Shahab , Khan Muhammad Umer
Published: September 2024

Fire detection and extinguishing systems are critical for safeguarding lives and minimizing property damage. These systems are especially vital in combating forest fires. In recent years, several forest fires have set records for their size, duration, and level of destruction. Traditional fire detection methods, such as smoke and heat sensors, have limitations, prompting the development of innovative approaches using advanced technologies. Utilizing image processing, computer vision, and deep learning algorithms, we can now detect fires with exceptional accuracy and respond promptly to mitigate their impact. In this article, we conduct a comprehensive review of articles from 2013 to 2023, exploring how these technologies are applied in fire detection and extinguishing. We delve into modern techniques enabling real-time analysis of the visual data captured by cameras or satellites, facilitating the detection of smoke, flames, and other fire-related cues. Furthermore, we explore the utilization of deep learning and machine learning in training intelligent algorithms to recognize fire patterns and features. Through a comprehensive examination of current research and development, this review aims to provide insights into the potential and future directions of fire detection and extinguishing using image processing, computer vision, and deep learning.