bluuebunny/crossref_metadata_2025 huggingface dataset:
Healthy Patients, Workforce and Environment: Coupling Climate Adaptation and Mitigation to Wellbeing in Healthcare
Authors: de Souza Mark , Lee Aunty Bilawara , Cook Stephen
Published: November 2023

Climate change threatens the health of all Australians: without adaptation, many areas may become unlivable, in particular the tropical north. The Northern Territory (NT) health workforce is already under colliding operational pressures worsened by extreme weather events, regional staff shortages and infrastructure that is poorly adapted to climate change. The H3 Project (Healthy Patients, Workforce and Environment) explores nature-based interventions in the NT health sector aiming to strengthen the resilience and responsiveness of health infrastructure and workforce in our climate-altered future. The H3 Project engaged the health workforce, climate researchers and the wider community, in recognition that meaningful and timely climate action requires both organization-led and grassroots engagement. We recruited campus greening volunteers and sustainability champions to Royal Darwin Hospital (RDH) to develop strategies that enhance climate adaptation, build climate and health literacy, and incentivize active mobility. We implemented low-cost biophilic design within the constraints of legacy healthcare infrastructure, creating cool and restorative outdoor spaces to mitigate the impacts of heat on RDH campus users and adapt to projected warming. This case study demonstrated substantial cooling impacts and improved local biodiversity and hospital campus aesthetics. We collaborated with Indigenous healers and plant experts to harness the synergy between Aboriginal people’s traditional knowledge and connectedness to land and the modern concept of biophilic design, while seeking to improve hospital outcomes for Indigenous patients who are both disconnected from their homelands and disproportionately represented in NT hospitals.
Browning of Mammary Fat Suppresses Pubertal Mammary Gland Development of Mice via Elevation of Serum Phosphatidylcholine and Inhibition of PI3K/Akt Pathway
Authors: Lang Limin , Zheng Jisong , Liang Shuyi , Zhang Fenglin , Fu Yiming , Deng Kaixin , Li Fan , Yang Xiaohua , Wang Junfeng , Luo Yuexiang , Zhang Shilei , Zhu Xiaotong , Wang Lina , Gao Ping , Zhu Canjun , Shu Gang , Xi Qianyun , Zhang Yongliang , Jiang Qingyan , Wang Songbo
Published: November 2023

Mammary fat plays a profound role in the postnatal development of mammary glands. However, the specific types (white, brown, or beige) of adipocytes in mammary fat and their potential regulatory effects on modulating mammary gland development remain poorly understood. This study aimed to investigate the role of the browning of mammary fat on pubertal mammary gland development and explore the underlying mechanisms. Thus, the mammary gland development and the serum lipid profile were evaluated in mice treated with CL316243, a β3-adrenoceptor agonist, to induce mammary fat browning. In addition, the proliferation of HC11 cells co-cultured with brown adipocytes or treated with the altered serum lipid metabolite was determined. Our results showed that the browning of mammary fat by injection of CL316243 suppressed the pubertal development of mice mammary glands, accompanied by the significant elevation of serum dioleoylphosphocholine (DOPC). In addition, the proliferation of HC11 was repressed when co-cultured with brown adipocytes or treated with DOPC. Furthermore, DOPC suppressed the activation of the PI3K/Akt pathway, while the DOPC-inhibited HC11 proliferation was reversed by SC79, an Akt activator, suggesting the involvement of the PI3K/Akt pathway in the DOPC-inhibited proliferation of HC11. Together, the browning of mammary fat suppressed the development of the pubertal mammary gland, which was associated with the elevated serum DOPC and the inhibition of the PI3K/Akt pathway.
Unbiased Phosphoproteome Mining Reveals New Functional Sites of Metabolite-Derived PTMs Involved in MASLD Development
Authors: Moltó Eduardo , Pintado Cristina , Louzada Ruy Andrade , Bernal-Mizrachi Ernesto , Andrés Antonio , Gallardo Nilda , Bonzon-Kulichenko Elena
Published: November 2023

Post-translational modifications (PTMs) of proteins are paramount in health and disease. Phosphoproteome analysis by enrichment techniques is becoming increasingly attractive for biomedical research. Recent findings show co-enrichment of other phosphate-containing biologically relevant PTMs, but these results were obtained by closed searches focused on the modifications sought. Open searches are a breakthrough in high-throughput PTM analysis (OS-PTM), identifying practically all PTMs detectable by mass spectrometry, even unknown ones, with their modified sites, in a hypothesis-free and deep manner. Here we reanalyze liver phosphoproteome by OS-PTM, demonstrating its extremely complex nature. We found extensive Lys glycerophosphorylations (pgK), as well as modification with glycerylphosphorylethanolamine on Glu (gpetE) and flavin mononucleotide on His (fmnH). The functionality of these metabolite-derived PTMs is demonstrated during metabolic dysfunction-associated steatotic liver disease (MASLD) development in mice. MASLD elicits specific alterations in pgK, epgE and fmnH in the liver, mainly on glycolytic enzymes and mitochondrial proteins, suggesting an increase in glycolysis and mitochondrial ATP production from the early insulin-resistant stages. Thus, we show new possible mechanisms based on metabolite-derived PTMs leading to intrahepatic lipid accumulation during MASLD development and reinforce phosphoproteome enrichment as a valuable tool with which to study the functional implications of a variety of low-abundant phosphate-containing PTMs in cell physiology.
WRKY Transcriptional Factor IlWRKY70 from Iris laevigata Enhances Drought and Salinity Tolerances in Nicotiana tabacum
Authors: Shi Gongfa , Liu Guiling , Liu Huijun , Xu Nuo , Yang Qianqian , Song Ziyi , Ye Wangbin , Wang Ling
Published: November 2023

Drought and high salinity greatly affect plant growth and development. WRKY transcription factors play a key role in plant tolerance to abiotic stress, but the functions of WRKYs in the ornamental monocotyledon Iris laevigata remain largely unexplored. In this study, we cloned IlWRKY70 and found that it is a Group III WRKY localized in the nucleus. The expression of IlWRKY70 was induced by NaCl and PEG-6000, which reached peaks (4.38 and 5.65 times) after 3 h and 1 h, respectively. The exogenous overexpression of IlWRKY70 in N. tabacum significantly improved the resistance under NaCl and drought treatments, as evidenced by higher germination rates, longer root lengths, and increased fresh weights compared to those of control plants. In addition, transgenic seedlings showed significantly reduced wilting, higher photosynthetic performance, higher Fv/Fm and chlorophyll content, and lower stomatal conductance. Moreover, transgenic lines showed higher antioxidant enzymatic activities, lower reactive oxygen species (ROS), and lower malondialdehyde contents. Accordingly, we also found higher expressions of antioxidant defense genes, including SOD, CAT, and POD, in transgenic lines compared to controls under salt and drought stresses. Thus, IlWRKY70 enhances the abilities of salt and drought tolerances in plants, at least partially, via ROS regulation and can be used for breeding I. laevigata possessing enhanced salt and drought resistances.
Anti-Incretin Gut Features Induced by Feed Supplementation with Alpha-Amylase: Studies on EPI Pigs
Authors: Pierzynowska Kateryna , Wychowański Piotr , Zaworski Kamil , Woliński Jarosław , Donaldson Janine , Pierzynowski Stefan
Published: November 2023

The acini-islet-acinar (AIA) axis concept justifies the anatomical placement of the Langerhans islets within the exocrine pancreatic parenchyma and explains the existence of the pancreas as a single organ. Amylase has been suggested to play a key role as an anti-incretin factor. Oral glucose tolerance tests (OGTT) were performed on 18 piglets in both a healthy (prior to pancreatic duct ligation (PDL) surgery, study Day 10) and an exocrine pancreatic insufficient (EPI) state (30 days after PDL, study Day 48)). Amylase (4000 units/feeding) or Creon® (100,000 units/feeding) was administered to pigs with the morning and evening meals, according to study design randomization, for 37 days following the first OGTT. Blood glucose levels, as well as plasma levels of insulin, GLP-1, and GIP, were measured, and the HOMA-IR index was calculated. EPI status did not affect the area under the curve (AUC) of insulin release, fasting insulin levels, or the HOMA-IR index, while amylase supplementation led to a significant (p < 0.05) decrease in the above-mentioned parameters. At the same time, EPI led to a significant (p < 0.05) increase in GLP-1 levels, and neither amylase nor Creon® supplementation had any effects on this EPI-related increase. Fasting plasma levels of GIP were not affected by EPI; however, the GIP response in EPI and Amylase-treated EPI animals was significantly lower (p < 0.05) when compared to that of the intact, healthy pigs. Orally administered amylase induces gut anti-incretin action, normalizing glucose homeostasis and reducing HOMA-IR as a long-term outcome, thus lowering the risk of diabetes type II development. Amylase has long-lasting anti-incretin effects, and one could consider the existence of a long-lasting gut memory for amylase, which decreases hyperinsulinemia and hyperglycemia for up to 16 h after the last exposure of the gut to amylase.
Carnivorous Plant Biology: From Gene to Traps
Authors: Płachno Bartosz J.
Published: November 2023

Carnivorous plants (approximately 850 species) are specific mixotrophic plants which all perform photosynthesis but need mainly nitrogen and phosphorous from animal or protist bodies [...]
Towards Polycaprolactone-Based Scaffolds for Alveolar Bone Tissue Engineering: A Biomimetic Approach in a 3D Printing Technique
Authors: Stafin Krzysztof , Śliwa Paweł , Piątkowski Marek
Published: November 2023

The alveolar bone is a unique type of bone, and the goal of bone tissue engineering (BTE) is to develop methods to facilitate its regeneration. Currently, an emerging trend involves the fabrication of polycaprolactone (PCL)-based scaffolds using a three-dimensional (3D) printing technique to enhance an osteoconductive architecture. These scaffolds are further modified with hydroxyapatite (HA), type I collagen (CGI), or chitosan (CS) to impart high osteoinductive potential. In conjunction with cell therapy, these scaffolds may serve as an appealing alternative to bone autografts. This review discusses research gaps in the designing of 3D-printed PCL-based scaffolds from a biomimetic perspective. The article begins with a systematic analysis of biological mineralisation (biomineralisation) and ossification to optimise the scaffold’s structural, mechanical, degradation, and surface properties. This scaffold-designing strategy lays the groundwork for developing a research pathway that spans fundamental principles such as molecular dynamics (MD) simulations and fabrication techniques. Ultimately, this paves the way for systematic in vitro and in vivo studies, leading to potential clinical applications.
Genome-Wide Characterization of the Aux/IAA Gene Family in Orchardgrass and a Functional Analysis of DgIAA21 in Responding to Drought Stress
Authors: Wang Miaoli , Feng Guanyan , Yang Zhongfu , Wu Jiahui , Liu Bingyan , Xu Xiaoheng , Nie Gang , Huang Linkai , Zhang Xinquan
Published: November 2023

Drought stress is an important factor that reduces plant biomass production and quality. As one of the most important economic forage grasses, orchardgrass (Dactylis glomerata) has high drought tolerance. Auxin/indole-3-acetic acid (Aux/IAA) is one of the early responsive gene families of auxin and plays a key role in the response to drought stress. However, the characteristics of the Aux/IAA gene family in orchardgrass and their potential function in responding to drought stress remain unclear. Here, 30 Aux/IAA members were identified in orchardgrass. Segmental duplication may be an important driving force in the evolution of the Aux/IAA gene family in orchardgrass. Some Aux/IAA genes were induced by IAA, drought, salt, and temperature stresses, implying that these genes may play important roles in responding to abiotic stresses. Heterologous expression in yeast revealed that DgIAA21 can reduce drought tolerance. Similarly, the overexpression of DgIAA21 also reduced drought tolerance in transgenic Arabidopsis, which was supported by lower total chlorophyll content and relative water content as well as higher relative electrolyte leakage and malondialdehyde content (MDA) than Col-0 plants under drought conditions. The results of this study provided valuable insight into the function of DgIAAs in response to drought stress, which can be further used to improve forage grass breeding programs.
Evaluation of the Antimicrobial Activity of a Formulation Containing Ascorbic Acid and Eudragit FS 30D Microparticles for the Controlled Release of a Curcumin–Boric Acid Solid Dispersion in Turkey Poults Infected with Salmonella enteritidis: A Therapeutic Model
Authors: Hernandez-Patlan Daniel , Solis-Cruz Bruno , Latorre Juan D. , Maguey-Gonzalez Jesus A. , Castellanos-Huerta Inkar , Beyssac Eric , Garrait Ghislain , Vázquez-Durán Alma , López-Arellano Raquel , Méndez-Albores Abraham , Hargis Billy M. , Tellez-Isaias Guillermo
Published: November 2023

The selection of components within a formulation or for treatment must stop being arbitrary and must be focused on scientific evidence that supports the inclusion of each one. Therefore, the objective of the present study was to obtain a formulation based on ascorbic acid (AA) and Eudragit FS 30D microparticles containing curcumin–boric acid (CUR–BA) considering interaction studies between the active components carried out via Fourier transform infrared spectrometry (FTIR) and differential scanning calorimetry (DSC) to minimize antagonistic effects, and comprehensively and effectively treat turkey poults infected with Salmonella enteritidis (S. enteritidis). The DSC and FTIR studies clearly demonstrated the interactions between AA, BA, and CUR. Consequently, the combination of AA with CUR and/or BA should be avoided, but not CUR and BA. Furthermore, the Eudragit FS 30D microparticles containing CUR–BA (SD CUR–BA MP) showed a limited release of CUR–BA in an acidic medium, but they were released at a pH 6.8–7.0, which reduced the interactions between CUR–BA and AA. Finally, in the S. enteritidis infection model, turkey poults treated with the combination of AA and SD CUR–BA MP presented lower counts of S. enteritidis in cecal tonsils after 10 days of treatment. These results pointed out that the use of an adequate combination of AA and CUR–BA as an integral treatment of S. enteritidis infections could be a viable option to replace the indiscriminate use of antibiotics.
Identification of a Novel Oxidative Stress- and Anoikis-Related Prognostic Signature and Its Immune Landscape Analysis in Non-Small Cell Lung Cancer
Authors: Zhao Hanqing , Huang Ying , Tong Guoshun , Wu Wei , Ren Yangwu
Published: November 2023

The objective of this study was to identify a kind of prognostic signature based on oxidative stress- and anoikis-related genes (OARGs) for predicting the prognosis and immune landscape of NSCLC. Initially, We identified 47 differentially expressed OARGs that primarily regulate oxidative stress and epithelial cell infiltration through the PI3K-Akt pathway. Subsequently, 10 OARGs related to prognosis determined two potential clusters. A cluster was associated with a shorter survival level, lower immune infiltration, higher stemness index and tumor mutation burden. Next, The best risk score model constructed by prognostic OARGs was the Random Survival Forest model, and it included SLC2A1, LDHA and PLAU. The high-risk group was associated with cluster A and poor prognosis, with a higher tumor mutation burden, stemness index and proportion of M0-type macrophages, and a lower immune checkpoint expression level, immune function score and IPS score. The calibration curve and decision-making curve showed that the risk score combined with clinical pathological characteristics could be used to construct a nomogram for guiding the clinical treatment strategies. Finally, We found that all three hub genes were highly expressed in tumor tissues, and LDHA expression was mainly regulated by has-miR-338-3p, has-miR-330-5p and has-miR-34c-5p. Altogether, We constructed an OARG-related prognostic signature to reveal potential relationships between the signature and clinical characteristics, TME, stemness, tumor mutational burden, drug sensitivity and immune landscape in NSCLC patients.
Keratinocytes Exposed to Blue or Red Light: Proteomic Characterization Showed Cytoplasmic Thioredoxin Reductase 1 and Aldo-Keto Reductase Family 1 Member C3 Triggered Expression
Authors: Lazzarini Raffaella , Tartaglione Maria Fiorella , Ciarapica Veronica , Piva Francesco , Giulietti Matteo , Fulgenzi Gianluca , Martelli Margherita , Ledda Caterina , Vitale Ermanno , Malavolta Marco , Santarelli Lory , Bracci Massimo
Published: November 2023

Several cell-signaling mechanisms are activated by visible light radiation in human keratinocytes, but the key regulatory proteins involved in this specific cellular response have not yet been identified. Human keratinocytes (HaCaT cells) were exposed to blue or red light at low or high irradiance for 3 days in cycles of 12 h of light and 12 h of dark. The cell viability, apoptotic rate and cell cycle progression were analyzed in all experimental conditions. The proteomic profile, oxidative stress and mitochondrial morphology were additionally evaluated in the HaCaT cells following exposure to high-irradiance blue or red light. Low-irradiance blue or red light exposure did not show an alteration in the cell viability, cell death or cell cycle progression. High-irradiance blue or red light reduced the cell viability, induced cell death and cell cycle G2/M arrest, increased the reactive oxygen species (ROS) and altered the mitochondrial density and morphology. The proteomic profile revealed a pivotal role of Cytoplasmic thioredoxin reductase 1 (TXNRD1) and Aldo-keto reductase family 1 member C3 (AKR1C3) in the response of the HaCaT cells to high-irradiance blue or red light exposure. Blue or red light exposure affected the viability of keratinocytes, activating a specific oxidative stress response and inducing mitochondrial dysfunction. Our results can help to address the targets for the therapeutic use of light and to develop adequate preventive strategies for skin damage. This in vitro study supports further in vivo investigations of the biological effects of light on human keratinocytes.
Analysis of Growth Trajectories and Verification of Related SNPs in Populus deltoides
Authors: Wang Yaolin , Wang Zesen , Zhu Sheng , Pan Huixin , Ding Changjun , Xu Meng
Published: November 2023

As an important timber genus with high economic and ecological values, Populus is a model for dissecting the genetic architecture of growth traits in perennial forest trees. However, the genetic mechanisms of longitudinal growth traits in poplar remain incompletely understood. In this study, we conducted longitudinal genetic analysis of height and diameter at breast height (DBH) in eleven-year poplar clones using ultra-deep sequencing datasets. We compared four S-shaped growth models, including asymptotic, Gompertz, logistic, and Richard, on eleven-year height and DBH records in terms of five metrics. We constructed the best-fitting growth model (Richard) and determined poplar ontogenetic stages by virtue of growth curve fitting and likelihood ratio testing. This study provides some scientific clues for temporal variation of longitudinal growth traits in Populus species.
Advances in Intercellular Communication Mediated by Exosomal ncRNAs in Cardiovascular Disease
Authors: Zhang Xiaoyan , Sun Shengjie , Ren Gang , Liu Wujun , Chen Hong
Published: November 2023

Cardiovascular diseases are a leading cause of worldwide mortality, and exosomes have recently gained attention as key mediators of intercellular communication in these diseases. Exosomes are double-layered lipid vesicles that can carry biomolecules such as miRNAs, lncRNAs, and circRNAs, and the content of exosomes is dependent on the cell they originated from. They can be involved in the pathophysiological processes of cardiovascular diseases and hold potential as diagnostic and monitoring tools. Exosomes mediate intercellular communication, stimulate or inhibit the activity of target cells, and affect myocardial hypertrophy, injury and infarction, ventricular remodeling, angiogenesis, and atherosclerosis. Exosomes can be released from various types of cells, including endothelial cells, smooth muscle cells, cardiomyocytes, fibroblasts, platelets, adipocytes, immune cells, and stem cells. In this review, we highlight the communication between different cell-derived exosomes and cardiovascular cells, with a focus on the roles of RNAs. This provides new insights for further exploring targeted therapies in the clinical management of cardiovascular diseases.
Ions-Induced Alginate Gelation According to Elemental Analysis and a Combinatorial Approach
Authors: Zueva Olga S. , Khair Tahar , Kazantseva Mariia A. , Latypova Larisa , Zuev Yuriy F.
Published: November 2023

This study considers the potential of elemental analysis of polysaccharide ionotropic gels in elucidating the junction zones for different divalent cations. The developed algorithm ensures the correct separation of contributions from physically adsorbed and structure-forming ionic compounds, with the obtained results scaled to alginate C12 block. Possible versions of chain association into dimers and their subsequent integration into flat junction zones were analyzed within the framework of the “egg-box” model. The application of combinatorial analysis made it possible to derive theoretical relations to find the probability of various types of egg-box cell occurrences for alginate chains with arbitrary monomeric units ratio μ = M/G, which makes it possible to compare experimental data for alginates of different origins. Based on literature data and obtained chemical formulas, the possible correspondence of concrete biopolymer cells to those most preferable for filling by alkaline earth cations was established. The identified features of elemental composition suggest the formation of composite hydrated complexes with the participation of transition metal cations. The possibility of quantitatively assessing ordered secondary structures formed due to the physical sorption of ions and molecules from environment, correlating with the sorption capabilities of Me2+ alginate, was established.
Characterization of a Vibriophage Infecting Pathogenic Vibrio harveyi
Authors: Li Yingying , Yun Huayi , Chen Ruo , Jiao Nianzhi , Zheng Qiang , Yang Yunlan , Zhang Rui
Published: November 2023

Bacterial diseases caused by Vibrio spp. are prevalent in aquaculture and can lead to high mortality rates among aquatic species and significant economic losses. With the increasing emergence of multidrug-resistant Vibrio strains, phage therapy is being explored as a potential alternative to antibiotics for biocontrol of infectious diseases. Here, a new lytic phage named vB_VhaS_R21Y (R21Y) was isolated against Vibrio harveyi BVH1 obtained from seawater from a scallop-farming area in Rongcheng, China. Its morphology, infection cycle, lytic profile, phage stability, and genetic features were characterized. Transmission electronic microscopy indicated that R21Y is siphovirus-like, comprising an icosahedral head (diameter 73.31 ± 2.09 nm) and long noncontractile tail (205.55 ± 0.75 nm). In a one-step growth experiment, R21Y had a 40-min latent period and a burst size of 35 phage particles per infected cell. R21Y was highly species-specific in the host range test and was relatively stable at pH 4–10 and 4–55 °C. Genomic analysis showed that R21Y is a double-stranded DNA virus with a genome size of 82,795 bp and GC content of 47.48%. Its high tolerance and lytic activity indicated that R21Y may be a candidate for phage therapy in controlling vibriosis in aquacultural systems.
Cytokine Profile in Development of Glioblastoma in Relation to Healthy Individuals
Authors: Jarmuzek Pawel , Defort Piotr , Kot Marcin , Wawrzyniak-Gramacka Edyta , Morawin Barbara , Zembron-Lacny Agnieszka
Published: November 2023

Cytokines play an essential role in the control of tumor cell development and multiplication. However, the available literature provides ambiguous data on the involvement of these proteins in the formation and progression of glioblastoma (GBM). This study was designed to evaluate the inflammatory profile and to investigate its potential for the identification of molecular signatures specific to GBM. Fifty patients aged 66.0 ± 10.56 years with newly diagnosed high-grade gliomas and 40 healthy individuals aged 71.7 ± 4.9 years were included in the study. White blood cells were found to fall within the referential ranges and were significantly higher in GBM than in healthy controls. Among immune cells, neutrophils showed the greatest changes, resulting in elevated neutrophil-to-lymphocyte ratio (NLR). The neutrophil count inversely correlated with survival time expressed by Spearman’s coefficient rs = −0.359 (p = 0.010). The optimal threshold values corresponded to 2.630 × 103/µL for NLR (the area under the ROC curve AUC = 0.831, specificity 90%, sensitivity 76%, the relative risk RR = 7.875, the confidence intervals 95%CI 3.333–20.148). The most considerable changes were recorded in pro-inflammatory cytokines interleukin IL-1β, IL-6, and IL-8, which were approx. 1.5–2-fold higher, whereas tumor necrosis factor α (TNFα) and high mobility group B1 (HMGB1) were lower in GBM than healthy control (p < 0.001). The results of the ROC, AUC, and RR analysis of IL-1β, IL-6, IL-8, and IL-10 indicate their high diagnostics potential for clinical prognosis. The highest average RR was observed for IL-6 (RR = 2.923) and IL-8 (RR = 3.151), which means there is an approx. three-fold higher probability of GBM development after exceeding the cut-off values of 19.83 pg/mL for IL-6 and 10.86 pg/mL for IL-8. The high values of AUC obtained for the models NLR + IL-1β (AUC = 0.907), NLR + IL-6 (AUC = 0.908), NLR + IL-8 (AUC = 0.896), and NLR + IL-10 (AUC = 0.887) prove excellent discrimination of GBM patients from healthy individuals and may represent GBM-specific molecular signatures.
MicroRNAs: Midfielders of Cardiac Health, Disease and Treatment
Authors: Asjad Emman , Dobrzynski Halina
Published: November 2023

MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that play a role in post-transcriptional gene regulation. It is generally accepted that their main mechanism of action is the negative regulation of gene expression, through binding to specific regions in messenger RNA (mRNA) and repressing protein translation. By interrupting protein synthesis, miRNAs can effectively turn genes off and influence many basic processes in the body, such as developmental and apoptotic behaviours of cells and cardiac organogenesis. Their importance is highlighted by inhibiting or overexpressing certain miRNAs, which will be discussed in the context of coronary artery disease, atrial fibrillation, bradycardia, and heart failure. Dysregulated levels of miRNAs in the body can exacerbate or alleviate existing disease, and their omnipresence in the body makes them reliable as quantifiable markers of disease. This review aims to provide a summary of miRNAs as biomarkers and their interactions with targets that affect cardiac health, and intersperse it with current therapeutic knowledge. It intends to succinctly inform on these topics and guide readers toward more comprehensive works if they wish to explore further through a wide-ranging citation list.
Comparison between [68Ga]Ga-PSMA-617 and [18F]FET PET as Imaging Biomarkers in Adult Recurrent Glioblastoma
Authors: Brighi Caterina , Puttick Simon , Woods Amanda , Keall Paul , Tooney Paul A. , Waddington David E. J. , Sproule Vicki , Rose Stephen , Fay Michael
Published: November 2023

The aim of this prospective clinical study was to evaluate the potential of the prostate specific membrane antigen (PSMA) targeting ligand, [68Ga]-PSMA–Glu–NH–CO–NH–Lys-2-naphthyl-L-Ala-cyclohexane-DOTA ([68Ga]Ga-PSMA-617) as a positron emission tomography (PET) imaging biomarker in recurrent glioblastoma patients. Patients underwent [68Ga]Ga-PSMA-617 and O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F]FET) PET scans on two separate days. [68Ga]Ga-PSMA-617 tumour selectivity was assessed by comparing tumour volume delineation and by assessing the intra-patient correlation between tumour uptake on [68Ga]Ga-PSMA-617 and [18F]FET PET images. [68Ga]Ga-PSMA-617 tumour specificity was evaluated by comparing its tumour-to-brain ratio (TBR) with [18F]FET TBR and its tumour volume with the magnetic resonance imaging (MRI) contrast-enhancing (CE) tumour volume. Ten patients were recruited in this study. [68Ga]Ga-PSMA-617-avid tumour volume was larger than the [18F]FET tumour volume (p = 0.063). There was a positive intra-patient correlation (median Pearson r = 0.51; p < 0.0001) between [68Ga]Ga-PSMA-617 and [18F]FET in the tumour volume. [68Ga]Ga-PSMA-617 had significantly higher TBR (p = 0.002) than [18F]FET. The [68Ga]Ga-PSMA-617-avid tumour volume was larger than the CE tumour volume (p = 0.0039). Overall, accumulation of [68Ga]-Ga-PSMA-617 beyond [18F]FET-avid tumour regions suggests the presence of neoangiogenesis in tumour regions that are not overly metabolically active yet. Higher tumour specificity suggests that [68Ga]-Ga-PSMA-617 could be a better imaging biomarker for recurrent tumour delineation and secondary treatment planning than [18F]FET and CE MRI.
Carnosine, Zinc and Copper: A Menage a Trois in Bone and Cartilage Protection
Authors: Ciaffaglione Valeria , Rizzarelli Enrico
Published: November 2023

Dysregulated metal homeostasis is associated with many pathological conditions, including arthritic diseases. Osteoarthritis and rheumatoid arthritis are the two most prevalent disorders that damage the joints and lead to cartilage and bone destruction. Recent studies show that the levels of zinc (Zn) and copper (Cu) are generally altered in the serum of arthritis patients. Therefore, metal dyshomeostasis may reflect the contribution of these trace elements to the disease’s pathogenesis and manifestations, suggesting their potential for prognosis and treatment. Carnosine (Car) also emerged as a biomarker in arthritis and exerts protective and osteogenic effects in arthritic joints. Notably, its zinc(II) complex, polaprezinc, has been recently proposed as a drug-repurposing candidate for bone fracture healing. On these bases, this review article aims to provide an overview of the beneficial roles of Cu and Zn in bone and cartilage health and their potential application in tissue engineering. The effects of Car and polaprezinc in promoting cartilage and bone regeneration are also discussed. We hypothesize that polaprezinc could exchange Zn for Cu, present in the culture media, due to its higher sequestering ability towards Cu. However, future studies should unveil the potential contribution of Cu in the beneficial effects of polaprezinc.
Non-Coding RNAs in Human Cancer and Other Diseases: Overview of the Diagnostic Potential
Authors: Beňačka Roman , Szabóová Daniela , Guľašová Zuzana , Hertelyová Zdenka , Radoňak Jozef
Published: November 2023

Non-coding RNAs (ncRNAs) are abundant single-stranded RNA molecules in human cells, involved in various cellular processes ranging from DNA replication and mRNA translation regulation to genome stability defense. MicroRNAs are multifunctional ncRNA molecules of 18–24 nt in length, involved in gene silencing through base-pair complementary binding to target mRNA transcripts. piwi-interacting RNAs are an animal-specific class of small ncRNAs sized 26–31 nt, responsible for the defense of genome stability via the epigenetic and post-transcriptional silencing of transposable elements. Long non-coding RNAs are ncRNA molecules defined as transcripts of more than 200 nucleotides, their function depending on localization, and varying from the regulation of cell differentiation and development to the regulation of telomere-specific heterochromatin modifications. The current review provides recent data on the several forms of small and long non-coding RNA’s potential to act as diagnostic, prognostic or therapeutic target for various human diseases.
Strain Variation Can Significantly Modulate the miRNA Response to Zika Virus Infection
Authors: Ramphan Suwipa , Chumchanchira Chanida , Sornjai Wannapa , Chailangkarn Thanathom , Jongkaewwattana Anan , Assavalapsakul Wanchai , Smith Duncan R.
Published: November 2023

Zika virus (ZIKV) is a mosquito-transmitted virus that has emerged as a major public health concern due to its association with neurological disorders in humans, including microcephaly in fetuses. ZIKV infection has been shown to alter the miRNA profile in host cells, and these changes can contain elements that are proviral, while others can be antiviral in action. In this study, the expression of 22 miRNAs in human A549 cells infected with two different ZIKV isolates was investigated. All of the investigated miRNAs showed significant changes in expression at at least one time point examined. Markedly, 18 of the miRNAs examined showed statistically significant differences in expression between the two strains examined. Four miRNAs (miR-21, miR-34a, miR-128 and miR-155) were subsequently selected for further investigation. These four miRNAs were shown to modulate antiviral effects against ZIKV, as downregulation of their expression through anti-miRNA oligonucleotides resulted in increased virus production, whereas their overexpression through miRNA mimics reduced virus production. However, statistically significant changes were again seen when comparing the two strains investigated. Lastly, candidate targets of the miRNAs miR-34a and miR-128 were examined at the level of the mRNA and protein. HSP70 was identified as a target of miR-34a, but, again, the effects were strain type-specific. The two ZIKV strains used in this study differ by only nine amino acids, and the results highlight that consideration must be given to strain type variation when examining the roles of miRNAs in ZIKV, and probably other virus infections.
The Exposure to Lead (Pb) Exacerbates Immunological Abnormalities in BTBR T+ Itpr3tf/J Mice through the Regulation of Signaling Pathways Relevant to T Cells
Authors: Assiri Mohammed A. , Albekairi Thamer H. , Ansari Mushtaq A. , Nadeem Ahmed , Attia Sabry M. , Bakheet Saleh A. , Shahid Mudassar , Aldossari Abdullah A. , Almutairi Mohammed M. , Almanaa Taghreed N. , Alwetaid Mohammad Y. , Ahmad Sheikh F.
Published: November 2023

Autism spectrum disorder (ASD) is a common neurodevelopmental illness characterized by abnormal social interactions, communication difficulties, and repetitive and limited behaviors or interests. The BTBR T+ Itpr3tf/J (BTBR) mice have been used extensively to research the ASD-like phenotype. Lead (Pb) is a hazardous chemical linked to organ damage in the human body. It is regarded as one of the most common metal exposure sources and has been connected to the development of neurological abnormalities. We used flow cytometry to investigate the molecular mechanism behind the effect of Pb exposure on subsets of CD4+ T cells in the spleen expressing IFN-γ, T-bet, STAT1, STAT4, IL-9, IRF4, IL-22, AhR, IL-10, and Foxp3. Furthermore, using RT-PCR, we studied the effect of Pb on the expression of numerous genes in brain tissue, including IFN-γ, T-bet, STAT1, STAT4, IL-9, IRF4, IL-22, AhR, IL-10, and Foxp3. Pb exposure increased the population of CD4+IFN-γ+, CD4+T-bet+, CD4+STAT1+, CD4+STAT4+, CD4+IL-9+, CD4+IRF4+, CD4+IL-22+, and CD4+AhR+ cells in BTBR mice. In contrast, CD4+IL-10+ and CD4+Foxp3+ cells were downregulated in the spleen cells of Pb-exposed BTBR mice compared to those treated with vehicle. Furthermore, Pb exposure led to a significant increase in IFN-γ, T-bet, STAT1, STAT4, IL-9, IRF4, IL-22, and AhR mRNA expression in BTBR mice. In contrast, IL-10 and Foxp3 mRNA expression was significantly lower in those treated with the vehicle. Our data suggest that Pb exposure exacerbates immunological dysfunctions associated with ASD. These data imply that Pb exposure may increase the risk of ASD.
Induction of Autophagy and Its Role in Peripheral Nerve Regeneration after Peripheral Nerve Injury
Authors: Yon Dong Keon , Kim Yong Jun , Park Dong Choon , Jung Su Young , Kim Sung Soo , Yeo Joon Hyung , Lee Jeongmin , Lee Jae Min , Yeo Seung Geun
Published: November 2023

No matter what treatment is used after nerve transection, a complete cure is impossible, so basic and clinical research is underway to find a cure. As part of this research, autophagy is being investigated for its role in nerve regeneration. Here, we review the existing literature regarding the involvement and significance of autophagy in peripheral nerve injury and regeneration. A comprehensive literature review was conducted to assess the induction and role of autophagy in peripheral nerve injury and subsequent regeneration. Studies were included if they were prospective or retrospective investigations of autophagy and facial or peripheral nerves. Articles not mentioning autophagy or the facial or peripheral nerves, review articles, off-topic articles, and those not written in English were excluded. A total of 14 peripheral nerve studies that met these criteria, including 11 involving sciatic nerves, 2 involving facial nerves, and 1 involving the inferior alveolar nerve, were included in this review. Studies conducted on rats and mice have demonstrated activation of autophagy and expression of related factors in peripheral nerves with or without stimulation of autophagy-inducing factors such as rapamycin, curcumin, three-dimensional melatonin nerve scaffolds, CXCL12, resveratrol, nerve growth factor, lentinan, adipose-derived stem cells and melatonin, basic fibroblast growth factor, and epothilone B. Among the most studied of these factors in relation to degeneration and regeneration of facial and sciatic nerves are LC3II/I, PI3K, mTOR, Beclin-1, ATG3, ATG5, ATG7, ATG9, and ATG12. This analysis indicates that autophagy is involved in the process of nerve regeneration following facial and sciatic nerve damage. Inadequate autophagy induction or failure of autophagy responses can result in regeneration issues after peripheral nerve damage. Animal studies suggest that autophagy plays an important role in peripheral nerve degeneration and regeneration.
Transcriptome Analysis Revealed the Advantages of Room Temperature Preservation of Concentrated Oocystis borgei Cultures for Use in Aquaculture
Authors: Zhang Ning , Deng Chengcheng , Hong Ting , Ren Jiajia , Zhang Yulei , Li Feng , Dong Zhongdian , Hu Zhangxi , Huang Xianghu , Li Changling
Published: November 2023

Oocystis borgei, a microalgae species employed for regulating the quality of aquaculture water, demonstrates the capacity to adsorb noxious substances, curtail the growth of detrimental bacteria, and outcompete blooming cyanobacteria. It can be concentrated by natural sedimentation and stored at room temperature, making it costless and simple to transport and use. To study the mechanism of adaptation to room temperature preservation, O. borgei was concentrated (1.19 × 107−1.21 × 107 cell/mL) and stored for 50 days at low (5 °C, LT), normal (25 °C, NT), and high (35 °C, HT) temperatures, respectively. Polysaccharide content, lipid content, cell survival, and resuscitation were evaluated. RNA-Seq was also used to examine how concentrated O. borgei responded to temperature. During storage, there was an increase in polysaccharide content and a decrease in lipid content, with both being significantly upregulated in the LT and HT groups. Survival and cell density were highest in the NT group. The RNA-Seq analysis revealed extensive differences in transcript levels. ATP synthesis was inhibited in the LT group due to the reduced expression of PsaD, PsaE, PsaF, PsaK, and PsaL. Under HT, the formation of reactive oxygen species (ROS) was facilitated by low levels of redox-related genes (nirA) and high levels of oxidative genes (gdhA, glna, and glts). The findings suggest that storing concentrated O. borgei at room temperature is optimal for microalgae preservation, enhancing theoretical research in this field. Our study provides further theoretical and practical support for the development of O. borgei as a live ecological preparation for aquaculture microalgae ecology management.
Modulating Stress Proteins in Response to Therapeutic Interventions for Parkinson’s Disease
Authors: Silvestro Serena , Raffaele Ivana , Mazzon Emanuela
Published: November 2023

Parkinson’s disease (PD) is a neurodegenerative illness characterized by the degeneration of dopaminergic neurons in the substantia nigra, resulting in motor symptoms and without debilitating motors. A hallmark of this condition is the accumulation of misfolded proteins, a phenomenon that drives disease progression. In this regard, heat shock proteins (HSPs) play a central role in the cellular response to stress, shielding cells from damage induced by protein aggregates and oxidative stress. As a result, researchers have become increasingly interested in modulating these proteins through pharmacological and non-pharmacological therapeutic interventions. This review aims to provide an overview of the preclinical experiments performed over the last decade in this research field. Specifically, it focuses on preclinical studies that center on the modulation of stress proteins for the treatment potential of PD. The findings display promise in targeting HSPs to ameliorate PD outcomes. Despite the complexity of HSPs and their co-chaperones, proteins such as HSP70, HSP27, HSP90, and glucose-regulated protein-78 (GRP78) may be efficacious in slowing or preventing disease progression. Nevertheless, clinical validation is essential to confirm the safety and effectiveness of these preclinical approaches.
Membrane Localization and Phosphorylation of Indoleamine 2,3-Dioxygenase 2 (IDO2) in A549 Human Lung Adenocarcinoma Cells: First Steps in Exploring Its Signaling Function
Authors: Suvieri Chiara , De Marchis Francesca , Mandarano Martina , Ambrosino Sara , Rossini Sofia , Mondanelli Giada , Gargaro Marco , Panfili Eleonora , Orabona Ciriana , Pallotta Maria Teresa , Belladonna Maria Laura , Volpi Claudia
Published: November 2023

Indoleamine 2,3-dioxygenase 2 (IDO2) is a paralog of Indoleamine 2,3-dioxygenase 1 (IDO1), a tryptophan-degrading enzyme producing immunomodulatory molecules. However, the two proteins are unlikely to carry out the same functions. IDO2 shows little or no tryptophan catabolic activity and exerts contrasting immunomodulatory roles in a context-dependent manner in cancer and autoimmune diseases. The recently described potential non-enzymatic activity of IDO2 has suggested its possible involvement in alternative pathways, resulting in either pro- or anti-inflammatory effects in different models. In a previous study on non-small cell lung cancer (NSCLC) tissues, we found that IDO2 expression revealed at the plasma membrane level of tumor cells was significantly associated with poor prognosis. In this study, the A549 human cell line, basally expressing IDO2, was used as an in vitro model of human lung adenocarcinoma to gain more insights into a possible alternative function of IDO2 different from the catalytic one. In these cells, immunocytochemistry and isopycnic sucrose gradient analyses confirmed the IDO2 protein localization in the cell membrane compartment, and the immunoprecipitation of tyrosine-phosphorylated proteins revealed that kinase activities can target IDO2. The different localization from the cytosolic one and the phosphorylation state are the first indications for the signaling function of IDO2, suggesting that the IDO2 non-enzymatic role in cancer cells is worthy of deeper understanding.
A Vicious NGF-p75NTR Positive Feedback Loop Exacerbates the Toxic Effects of Oxidative Damage in the Human Retinal Epithelial Cell Line ARPE-19
Authors: Tringali Giuseppe , Pizzoferrato Michela , Lisi Lucia , Marinelli Silvia , Buccarello Lucia , Falsini Benedetto , Cattaneo Antonino , Navarra Pierluigi
Published: November 2023

In spite of its variety of biological activities, the clinical exploitation of human NGF (hNGF) is currently limited to ocular pathologies. It is therefore interesting to test the effects of hNGF in preclinical models that may predict their efficacy and safety in the clinical setting of ocular disorders and compare the effects of hNGF with those of its analogs. We used a human retinal pigment cell line, ARPE-19 cells, to investigate the effects of hNGF and its analogs, mouse NGF (mNGF) and painless NGF (pNGF), on cell viability under basal conditions and after exposure to oxidative stimuli, i.e., hydrogen peroxide (H2O2) and ultraviolet (UV)-A rays. The effects of hNGF and pNGF were also tested on the gene expression and protein synthesis of the two NGF receptor subtypes, p75 neurotrophic receptors (p75NTR) and tyrosine kinase A (TrkA) receptors. We drew the following conclusions: (i) the exposure of ARPE-19 cells to H2O2 or UV-A causes a dose-dependent decrease in the number of viable cells; (ii) under baseline conditions, hNGF, but not pNGF, causes a concentration-dependent decrease in cell viability in the range of doses 1–100 ng/mL; (iii) hNGF, but not pNGF, significantly potentiates the toxic effects of H2O2 or of UV-A on ARPE-19 cells in the range of doses 1–100 ng/mL, while mNGF at the same doses presents an intermediate behavior; (iv) 100 ng/mL of hNGF triggers an increase in p75NTR expression in H2O2-treated ARPE-19 cells, while pNGF at the same dose does not; (v) pNGF, but not hNGF (both given at 100 ng/mL), increases the total cell fluorescence intensity for TrkA receptors in H2O2-treated ARPE-19 cells. The present findings suggest a vicious positive feedback loop through which NGF-mediated upregulation of p75NTR contributes to worsening the toxic effects of oxidative damage in the human retinal epithelial cell line ARPE-19. Looking at the possible clinical relevance of these findings, one can postulate that pNGF might show a better benefit/risk ratio than hNGF in the treatment of ocular disorders.
OsmiRNA5488 Regulates the Development of Embryo Sacs and Targets OsARF25 in Rice (Oryza sativa L.)
Authors: Guo Shengyuan , Zheng Chuanjiang , Wang Yan , Xu Yangwen , Wu Jinwen , Wang Lan , Liu Xiangdong , Chen Zhixiong
Published: November 2023

Small RNAs are a class of non-coding RNAs that typically range from 20 to 24 nucleotides in length. Among them, microRNAs (miRNAs) are particularly important regulators for plant development. The biological function of the conserved miRNAs has been studied extensively in plants, while that of the species-specific miRNAs has been studied in-depth. In this study, the regulatory role of a rice-specific OsmiRNA5488 (OsmiR5488) was characterized with the miR5488-overexpressed line (miR5488-OE) and miR5488-silenced line (STTM-5488). The seed-setting rate was notably reduced in miR5488-OE lines, but not in STTM-5488 lines. Cytological observation demonstrated the different types of abnormal mature embryo sacs, including the degeneration of embryo sacs and other variant types, in miR5488-OE lines. The percentage of the abnormal mature embryo sacs accounted for the reduced value of the seed-setting rate. Furthermore, OsARF25 was identified as a target of OsmiR5488 via RNA ligase-mediated 3′-amplifification of cDNA ends, dual luciferase assays, and transient expression assays. The primary root length was decreased with the increases in auxin concentrations in miR5488-OE lines compared to wild-type rice. Summarily, our results suggested that OsmiR5488 regulates the seed-setting rate and down-regulates the targeted gene OsARF25.