bluuebunny/crossref_metadata_2025 huggingface dataset:
Ancient Aeolian Reservoirs of the East Siberia Craton
Authors: Shaldybin Michail V. , Kvachko Svetlana , Rudmin Maxim , Plyusnin Alexey , Kuznetsov Iliya
Published: July 2023

Fine-grained strata deposited on the Eastern Siberian craton are predominantly considered to mainly consist of Neoproterozoic sandstones. Clastic rocks near the unconformity border of the Ediacaran and the Riphean are represented by sandstone and siltstone layers with thicknesses of several tens of meters, belonging to the Nepa, Tira, and Byuk horizons in the Nepa–Botuoba region. These Neoproterozoic sandstones have features characteristic of aeolianites formed under the action of high wind velocity in the Ediacaran period. Sandstone samples near the Riphean–Ediacaran boundary were collected from five deep wells and characterized for granulometry and mineral composition using optical microscopy, XRD, SEM, and ICP-MS techniques. These sandstones have a high proportion of quartz (60–98%) with minor amounts of feldspars, carbonate, and sulfate cements. Thin sections of the sandy rocks feature bimodal distributions of the grains throughout many sections, with large well-rounded quartz grains being several orders of magnitude greater than the silt matrix grains. The monomineralic quartz rocks have an overgrowth of quartz grains. These rocks can be petroleum reservoirs with good porosity and permeability, but in most of the studied intervals, a high content of anhydrite and dolomite interstitial cement significantly reduces both. The porosity of the rocks is low, while the permeability is very low, which may be associated with a significant amount of clay and cement material. Aeolianites normally contain large amounts of bimodal quartz (due to its high stability and resistance to weathering) and possess the presence of heavy minerals.
The Association between Physical Activity and Anxiety in Aging: A Comparative Analysis
Authors: Dantas Estelio Henrique Martin , Figueira Olivia Andrade , Figueira Alan Andrade , Höekelmann Anita , Vale Rodrigo Gomes de Souza , Figueira Joana Andrade , Figueira Helena Andrade
Published: July 2023

(1) Background: As the worldwide aging population is growing, there is a need to embrace the role of physical activity in the anxiety of older people. Objectives: To analyze anxiety in older people practitioners and non-practitioners of physical activity; (2) Methods: ample composed of 690 older people of both genders, unselected volunteers, residing in Brazil, present (as participants or observers) in selected street races in the state of Rio de Janeiro, Brazil, between 30 October 2019, and 12 March 2020. An instrument composed of the sociodemographic questionnaire and questions from the Beck Anxiety Inventory, BAI, and the Physical Activity Inventory for older people, Baecke-Old. Design: Ex-post-facto observational analytical descriptive research; (3) Results: The average age of the sample was in the range of 65 to 69y, 74% female, 94% completed high school, 69% living with the family, 84% practicing physical activity. Anxiety levels were 26% (without), 35% (mild), 21% (moderate), and 18% (severe). The comparison of anxiety showed a difference between the groups of active and sedentary elderly. Logistic regression analysis considering anxiety (yes or no; dichotomous variable) and physical activity (yes or no; dichotomous variable) and Odds Ratio were performed to identify possible influences of the independent variables PA, gender, marital status, and education on anxiety. Only physical activity was associated with anxiety. (4) Conclusions: The sample data of this research point to the conclusion that physical activity influences anxiety levels with 98% certainty, and it is suggested that it be enriched in the future with different studies with different designs. The older people practitioners of physical activity with a high level of education presented as 26% without, 35% mild, 21% moderate, and 18% severe anxiety. More active individuals are less likely to develop anxiety.
The Internal Reliability and Construct Validity of the Evidence-Based Practice Questionnaire (EBPQ): Evidence from Healthcare Professionals in the Eastern Mediterranean Region
Authors: Youssef Naglaa , Saleeb Marina , Gebreal Assem , Ghazy Ramy Mohamed
Published: July 2023

Background: Fostering a culture of clinical effectiveness among healthcare professionals (HCPs) is crucial to achieving optimal patient health outcomes. To our knowledge, there is a lack of robust evidence-based practice (EBP) tools to assess the competence of HCPs in EBP in the Eastern Mediterranean Region (EMR). Aim: This study aims to comprehensively investigate the construct validity and internal reliability of the evidence-based practice questionnaire (EBPQ) among HCPs in the EMR. Methods: This multinational and multi-disciplinary cross-sectional study was conducted between 27 April and 11 May 2023. Convenience and snowball sampling methods were used to recruit a sample of HCPs (physicians, nurses, physiotherapists, dentists, and pharmacists) using an electronic survey questionnaire for data capture. To assess the reliability of the instrument, Cronbach’s alpha, inter-item reliability, and split-half reliability analyses were conducted. Furthermore, the convergent and discriminant validity of the questionnaire was ensured by calculating the average variance extracted (AVE) and the correlation coefficient between the different constructs, respectively. Factor loadings and cross-loadings of different indicators within each construct were calculated by performing both exploratory and confirmatory factor analyses. Results: A total of 1536 HCPs from 18 countries in the EMR (response rate = 96.786%) with a median age of 28 years participated; 47% were female, and 55% had Arabic as their first language. English was the most common language for a bachelor’s degree in science (54%). The construct validity of the EBPQ was investigated using exploratory factor analysis (EFA), which yielded four loaded factors. The confirmatory factor analysis (CFA) confirmed the four loaded factors. The CFA model showed that the root mean square error of approximation = 0.066, comparative fit index = 0.95, Tucker–Lewis’s index = 0.94, standardized root mean square residual = 0.033, normal fit index = 0.94, goodness of fit = 0.91, and χ2 test statistic= 22,553, with p < 0.001. The AVE values of the four factors were close to 1 (knowledge = 0.6, practice = 0.6, attitude = 0.5, and sharing = 0.7), thus supporting the convergent validity of the EBPQ. The four domains had Cronbach’s alpha coefficients and Omega ≥ 0.7 (knowledge = 0.9, practice = 0.9, attitude = 0.7, and sharing = 0.8), suggesting that the items within each domain had good internal consistency. These results support the discriminant validity of the EBPQ. Conclusions: The EBPQ is a robust questionnaire that can be completed in less than 10 min by EMR HCPs and can be used as a gold-standard questionnaire to collect valid data on the attitudes, knowledge, and proficiency of HCPs in making clinical decisions based on evidence. Future studies are recommended to investigate the retest reliability.
Looking Back, Looking Forward: A Study Protocol for a Mixed-Methods Multiple-Case Study to Examine Improvement Sustainability of Large-Scale Initiatives in Tertiary Hospitals
Authors: Moon Sarah E. J. , Hogden Anne , Eljiz Kathy , Siddiqui Nazlee
Published: July 2023

Background Hospitals invest extensive resources in large-scale initiatives to improve patient safety and quality at an organizational level. However, initial success, if any, does not guarantee longer-term improvement. Empirical and theoretical knowledge that informs hospitals on how to attain sustained improvement from large-scale change is lacking. Aim The proposed study aims to examine improvement sustainability of two large-scale initiatives in an Australian tertiary hospital and translate the lessons into strategies for achieving sustained improvement from large-scale change in hospital settings. Design and Methods The study employs a single-site, multiple-case study design to evaluate the initiatives separately and comparatively using mixed methods. Semi-structured staff interviews will be conducted in stratified cohorts across the organizational hierarchy to capture different perspectives from various staff roles involved in the initiatives. The output and impact of the initiatives will be examined through organizational documents and relevant routinely collected organizational indicators. The obtained data will be analyzed thematically and statistically before being integrated for a synergic interpretation. Implications Capturing a comprehensive organizational view of large-scale change, the findings will have the potential to guide the practice and contribute to the theoretical understandings for achieving meaningful and longer-term organizational improvement in patient safety and quality.
Predicting Multimorbidity Using Saudi Health Indicators (Sharik) Nationwide Data: Statistical and Machine Learning Approach
Authors: Albagmi Faisal Mashel , Hussain Mehwish , Kamal Khurram , Sheikh Muhammad Fahad , AlNujaidi Heba Yaagoub , Bah Sulaiman , Althumiri Nora A. , BinDhim Nasser F.
Published: July 2023

The Saudi population is at high risk of multimorbidity. The risk of these morbidities can be reduced by identifying common modifiable behavioural risk factors. This study uses statistical and machine learning methods to predict factors for multimorbidity in the Saudi population. Data from 23,098 Saudi residents were extracted from the “Sharik” Health Indicators Surveillance System 2021. Participants were asked about their demographics and health indicators. Binary logistic models were used to determine predictors of multimorbidity. A backpropagation neural network model was further run using the predictors from the logistic regression model. Accuracy measures were checked using training, validation, and testing data. Females and smokers had the highest likelihood of experiencing multimorbidity. Age and fruit consumption also played a significant role in predicting multimorbidity. Regarding model accuracy, both logistic regression and backpropagation algorithms yielded comparable outcomes. The backpropagation method (accuracy 80.7%) was more accurate than the logistic regression model (77%). Machine learning algorithms can be used to predict multimorbidity among adults, particularly in the Middle East region. Different testing methods later validated the common predicting factors identified in this study. These factors are helpful and can be translated by policymakers to consider improvements in the public health domain.
Detecting Surface Defects of Achacha Fruit (Garcinia humilis) with Hyperspectral Images
Authors: Nguyen Ngo Minh Tri , Liou Nai-Shang
Published: July 2023

Hyperspectral imaging data within the wavelength range of 400–1000 nm were used to classify the common skin conditions (i.e., normal, scar, decay, and insect bite) of achacha fruits. The band ratio (BR) and spectral angle mapper (SAM) algorithms were used in a binary classification. Furthermore, SAM, support vector machine (SVM), and artificial neural network (ANN) models were used in a multiclass classification. The performances of the binary and multiclass classification models were assessed. For the binary-classification approach, the three defective classes were merged into one, and the accuracies of the BR (990 nm/600 nm) and SAM were 78.70% and 75.02%, respectively. Furthermore, the SAM, SVM, and ANN accuracies in the four class problems were 58.36%, 83.59%, and 99.88%, respectively. A principal component analysis (PCA) was used for the data reduction. Nine characteristic wavelengths were extracted from the weighting-coefficient curves of the first four principal components. Using only the nine selected bands, the accuracies of the SAM, SVM, and ANN models were 51.49%, 80.76%, and 96.85%, respectively. Compared with the models using full bands, the classification accuracies of the models using only nine characteristic bands decreased slightly; however, the gain in classification speed and the potential data-acquisition speed can expedite the classification of achacha fruits.
Impact of Liquidity and Investors Sentiment on Herd Behavior in Cryptocurrency Market
Authors: Bogdan Siniša , Brmalj Natali , Mujačević Elvis
Published: July 2023

This research addresses the impact of individual investors on the cryptocurrency market, focusing specifically on the development of herd behavior. Although the phenomenon of herd behavior has been studied extensively in the stock market, it has received limited research in the context of cryptocurrencies. This study aims to fill this research gap by examining the impact of liquidity and sentiment on herd behavior using the CSAD model, considering small, medium, and large cryptocurrencies. The results show different outcomes for cryptocurrencies of different sizes, consistently demonstrating that the herding effect is more pronounced under conditions of lower liquidity, as determined by the turnover volume and liquidity ratio of cryptocurrencies. Proxy measures such as the Twitter Hedonometer and CBOE VIX were used to measure investor sentiment and show the prevalence of herding behavior in optimistic times for all cryptocurrencies, regardless of their market capitalization. Consequently, this study provides valuable insights into the manifestation of herd behavior in the cryptocurrency market and highlights the importance of liquidity and sentiment as influencing factors. These findings improve our understanding of investor behavior and provide guidance to market participants and policymakers on how to effectively manage the risks associated with herd effects.
Hydrazinolysis Products of Selected Sugar Lactones—Crystal Structure and Microbiological Activity
Authors: Samaszko-Fiertek Justyna , Sikorski Artur , Dmochowska Barbara , Szweda Piotr , Madaj Janusz
Published: July 2023

Commercially available lactones, as well as those synthesized by us, turned out to be good substrates for the synthesis of sugar hydrazides. The exception was L-ascorbic acid, whose hydrazinolysis led to the formation of a hydrazinium salt, not the hydrazide as expected. The structure of all compounds was confirmed by NMR and X-ray analyses. The lower durability of hydrazinium L-ascorbate was additionally confirmed by thermogravimetric tests. All products were tested for biological activity against Gram-negative bacteria strains Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853 and against Gram-positive Staphylococcus aureus ATCC 25923 and Staphylococcus aureus ATCC 29213. Their antifungal activity against Candida albicans SC5314, Candida glabrata DSM 11226 SM 11226, Candida krusei DSM 6128, and Candida parapsilosis DSM 5784 was also tested. The most interesting results of microbiological activity were obtained for D-gluconic acid hydrazide and hydrazinium L-ascorbate. The results of the latter encourage more extensive testing.
Antioxidant Activity of a Sicilian Almond Skin Extract Using In Vitro and In Vivo Models
Authors: Arangia Alessia , Ragno Agnese , Cordaro Marika , D’Amico Ramona , Siracusa Rosalba , Fusco Roberta , Marino Merlo Francesca , Smeriglio Antonella , Impellizzeri Daniela , Cuzzocrea Salvatore , Mandalari Giuseppina , Di Paola Rosanna
Published: July 2023

Almond skins are known for their antioxidative and anti-inflammatory properties, which are mainly due to the presence of polyphenols. The aim of the present study was to evaluate the antioxidant and anti-inflammatory effects of almond skin extract (ASE) obtained from the Sicilian cultivar “Fascionello” and to evaluate the possible mechanisms of action using an in vitro model of human monocytic U937 cells as well as an in vivo model of carrageenan (CAR)-induced paw edema. The in vitro studies demonstrated that pretreatment with ASE inhibited the formation of ROS and apoptosis. The in vivo studies showed that ASE restored the CAR-induced tissue changes; restored the activity of endogenous antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione; and decreased neutrophil infiltration, lipid peroxidation, and the release of proinflammatory mediators. The anti-inflammatory and antioxidant effects of ASE could be associated with the inhibition of the pro-inflammatory nuclear NF-κB and the activation of the nuclear factor-erythroid 2-related factor 2 (Nrf2) antioxidant pathways. In conclusion, almond skin could reduce the levels of inflammation and oxidative stress and could be beneficial in the treatment of several disorders.
Novel Matrix Metalloproteinase-9 (MMP-9) Inhibitors in Cancer Treatment
Authors: Rashid Zainab Ahmed , Bardaweel Sanaa K.
Published: July 2023

Matrix metalloproteinases (MMPs) belong to a family of zinc-dependent proteolytic metalloenzymes. MMP-9, a member of the gelatinase B family, is characterized as one of the most intricate MMPs. The crucial involvement of MMP-9 in extracellular matrix (ECM) remodeling underscores its significant correlation with each stage of cancer pathogenesis and progression. The design and synthesis of MMP-9 inhibitors is a potentially attractive research area. Unfortunately, to date, there is no effective MMP-9 inhibitor that passes the clinical trials and is approved by the FDA. This review primarily focuses on exploring the diverse strategies employed in the design and advancement of MMP-9 inhibitors, along with their anticancer effects and selectivity. To illuminate the essential structural characteristics necessary for the future design of novel MMP-9 inhibitors, the current narrative review highlights several recently discovered MMP-9 inhibitors exhibiting notable selectivity and potency.
Accelerating the Screening of Small Peptide Ligands by Combining Peptide-Protein Docking and Machine Learning
Authors: Codina Josep-Ramon , Mascini Marcello , Dikici Emre , Deo Sapna K. , Daunert Sylvia
Published: July 2023

This research introduces a novel pipeline that couples machine learning (ML), and molecular docking for accelerating the process of small peptide ligand screening through the prediction of peptide-protein docking. Eight ML algorithms were analyzed for their potential. Notably, Light Gradient Boosting Machine (LightGBM), despite having comparable F1-score and accuracy to its counterparts, showcased superior computational efficiency. LightGBM was used to classify peptide-protein docking performance of the entire tetrapeptide library of 160,000 peptide ligands against four viral envelope proteins. The library was classified into two groups, ‘better performers’ and ‘worse performers’. By training the LightGBM algorithm on just 1% of the tetrapeptide library, we successfully classified the remaining 99%with an accuracy range of 0.81–0.85 and an F1-score between 0.58–0.67. Three different molecular docking software were used to prove that the process is not software dependent. With an adjustable probability threshold (from 0.5 to 0.95), the process could be accelerated by a factor of at least 10-fold and still get 90–95% concurrence with the method without ML. This study validates the efficiency of machine learning coupled to molecular docking in rapidly identifying top peptides without relying on high-performance computing power, making it an effective tool for screening potential bioactive compounds.
Oxidative Stress and Antioxidant Defense in the Brain of Bat Species with Different Feeding Habits
Authors: Rampelotto Pabulo Henrique , Giannakos Nikolas Raphael Oliveira , Mena Canata Diego Antonio , Pereira Francielly Dias , Hackenhaar Fernanda Schäfer , Pereira María João Ramos , Benfato Mara Silveira
Published: July 2023

Assessing the levels of oxidative stress markers and antioxidant enzymes in the brain is crucial in evaluating its antioxidant capacity and understanding the influence of various dietary patterns on brain well-being. This study aimed to investigate the antioxidant status and oxidative damage in the brain of bat species with different feeding habits to gain insights into their protective mechanisms against oxidative stress and their interspecific variation. The levels of oxidative damage markers and the activities of antioxidants were measured in the brain of four bat species with different feeding habits, namely insectivorous, frugivorous, nectarivorous, and hematophagous. Insectivorous bats showed higher levels of SOD and fumarase compared to the other groups, while hematophagous bats showed lower levels of these enzymes. On the other hand, the activities of glutathione peroxidase and glutathione S-transferase were higher in hematophagous bats and lower in insectivorous bats. The carbonyl groups and malondialdehyde levels were lower in frugivores, while they were similar in the other feeding guilds. Nitrite and nitrate levels were higher in the hematophagous group and relatively lower in all other groups. The GSSG/GSH ratio was higher in the hematophagous group and lower in frugivores. Overall, our results indicate that the levels of oxidative stress markers and the activities of antioxidant enzymes in the brain vary significantly among bat species with different feeding habitats. The findings suggest that the antioxidant status of the brain is influenced by diet and feeding habits.
Practices, Potential, and Perspectives for Detecting Predisease Using Raman Spectroscopy
Authors: Oshima Yusuke , Haruki Takayuki , Koizumi Keiichi , Yonezawa Shota , Taketani Akinori , Kadowaki Makoto , Saito Shigeru
Published: July 2023

Raman spectroscopy shows great potential for practical clinical applications. By analyzing the structure and composition of molecules through real-time, non-destructive measurements of the scattered light from living cells and tissues, it offers valuable insights. The Raman spectral data directly link to the molecular composition of the cells and tissues and provides a “molecular fingerprint” for various disease states. This review focuses on the practical and clinical applications of Raman spectroscopy, especially in the early detection of human diseases. Identifying predisease, which marks the transition from a healthy to a disease state, is crucial for effective interventions to prevent disease onset. Raman spectroscopy can reveal biological processes occurring during the transition states and may eventually detect the molecular dynamics in predisease conditions.
Identification of EGF Receptor and Thrombospondin-1 as Endogenous Targets of ER-Associated Degradation Enhancer EDEM1 in HeLa Cells
Authors: Miura Kohta , Katsuki Riko , Yoshida Shusei , Ohta Ren , Tamura Taku
Published: July 2023

Secretory and membrane proteins are vital for cell activities, including intra- and intercellular communication. Therefore, protein quality control in the endoplasmic reticulum (ER) is an essential and crucial process for eukaryotic cells. Endoplasmic reticulum-associated degradation (ERAD) targets misfolded proteins during the protein maturation process in the ER and leads to their disposal. This process maintains the ER productive function and prevents misfolded protein stress (i.e., ER stress). The ERAD-stimulating factor ER degradation-enhancing α mannosidase-like 1 protein (EDEM1) acts on misfolded proteins to accelerate ERAD, thereby maintaining the productivity of the ER. However, the detail mechanism underlying the function of EDEM1 in ERAD is not completely understood due to a lack of established physiological substrate proteins. In this study, we attempted to identify substrate proteins for EDEM1 using siRNA. The matrix component thrombospondin-1 (TSP1) and epidermal growth factor receptor (EGFR) were identified as candidate targets of EDEM1. Their protein maturation status and cellular localization were markedly affected by knockdown of EDEM1. We also showed that EDEM1 physically associates with EGFR and enhances EGFR degradation via ERAD. Our data highlight the physiological role of EDEM1 in maintaining specific target proteins and provide a potential approach to the regulation of expression of clinically important proteins.
Delivery of Immunostimulatory Cargos in Nanocarriers Enhances Anti-Tumoral Nanovaccine Efficacy
Authors: Schunke Jenny , Mailänder Volker , Landfester Katharina , Fichter Michael
Published: July 2023

Finding a long-term cure for tumor patients still represents a major challenge. Immunotherapies offer promising therapy options, since they are designed to specifically prime the immune system against the tumor and modulate the immunosuppressive tumor microenvironment. Using nucleic-acid-based vaccines or cellular vaccines often does not achieve sufficient activation of the immune system in clinical trials. Additionally, the rapid degradation of drugs and their non-specific uptake into tissues and cells as well as their severe side effects pose a challenge. The encapsulation of immunomodulatory molecules into nanocarriers provides the opportunity of protected cargo transport and targeted uptake by antigen-presenting cells. In addition, different immunomodulatory cargos can be co-delivered, which enables versatile stimulation of the immune system, enhances anti-tumor immune responses and improves the toxicity profile of conventional chemotherapeutic agents.
Nuclear Expression of TDP-43 Is Linked with Morphology and Ubiquitylation of Cytoplasmic Aggregates in Amyotrophic Lateral Sclerosis
Authors: Yabata Hiroyuki , Riku Yuichi , Miyahara Hiroaki , Akagi Akio , Sone Jun , Urushitani Makoto , Yoshida Mari , Iwasaki Yasushi
Published: July 2023

The transactive response DNA-binding protein of 43 kDa (TDP-43) is a pathological protein of amyotrophic lateral sclerosis (ALS). TDP-43 pathology is characterized by a combination of the cytoplasmic aggregation and nuclear clearance of this protein. However, the mechanisms underlying TDP-43 pathology have not been fully clarified. The aim of this study was to evaluate the relationships between the expression level of nuclear TDP-43 and the pathological properties of cytoplasmic aggregates in autopsied ALS cases. We included 22 consecutively autopsied cases with sporadic TDP-43-related ALS. The motor neuron systems were neuropathologically assessed. We identified 790 neurons with cytoplasmic TDP-43 inclusions from the lower motor neuron system of included cases. Nuclear TDP-43 disappeared in 84% (n = 660) and expressed in 16% (n = 130) of neurons with cytoplasmic inclusions; the former was defined as TDP-43 cytoplasmic immunoreactivity (c-ir), and the latter was defined as nuclear and cytoplasmic immunoreactivity (n/c-ir). Morphologically, diffuse cytoplasmic inclusions were significantly more prevalent in TDP-43 n/c-ir neurons than in c-ir neurons, while skein-like and round inclusions were less prevalent in n/c-ir neurons. The cytoplasmic inclusions of TDP-43 n/c-ir neurons were phosphorylated but poorly ubiquitylated when compared with those of c-ir neurons. TDP-43 n/c-ir neurons became less dominant than the c-ir neurons among cases with a prolonged disease duration. The expression level of nuclear TDP-43 was significantly lower in n/c-ir neurons than in normal neurons without cytoplasmic inclusions. Our results indicate that the maturation of cytoplasmic TDP-43 inclusions correlates with the depletion of nuclear TDP-43 in each affected neuron. This finding supports the view that an imbalance between nuclear and cytoplasmic TDP-43 may be an essential pathway to TDP-43 pathology.
SPARC Is Highly Expressed in Young Skin and Promotes Extracellular Matrix Integrity in Fibroblasts via the TGF-β Signaling Pathway
Authors: Ham Seung Min , Song Min Ji , Yoon Hyun-Sun , Lee Dong Hun , Chung Jin Ho , Lee Seung-Taek
Published: July 2023

The matricellular secreted protein acidic and rich in cysteine (SPARC; also known as osteonectin), is involved in the regulation of extracellular matrix (ECM) synthesis, cell-ECM interactions, and bone mineralization. We found decreased SPARC expression in aged skin. Incubating foreskin fibroblasts with recombinant human SPARC led to increased type I collagen production and decreased matrix metalloproteinase-1 (MMP-1) secretion at the protein and mRNA levels. In a three-dimensional culture of foreskin fibroblasts mimicking the dermis, SPARC significantly increased the synthesis of type I collagen and decreased its degradation. In addition, SPARC also induced receptor-regulated SMAD (R-SMAD) phosphorylation. An inhibitor of transforming growth factor-beta (TGF-β) receptor type 1 reversed the SPARC-induced increase in type I collagen and decrease in MMP-1, and decreased SPARC-induced R-SMAD phosphorylation. Transcriptome analysis revealed that SPARC modulated expression of genes involved in ECM synthesis and regulation in fibroblasts. RT-qPCR confirmed that a subset of differentially expressed genes is induced by SPARC. These results indicated that SPARC enhanced ECM integrity by activating the TGF-β signaling pathway in fibroblasts. We inferred that the decline in SPARC expression in aged skin contributes to process of skin aging by negatively affecting ECM integrity in fibroblasts.
The Effects of a Curcumin Derivative and Osimertinib on Fatty Acyl Metabolism and Mitochondrial Functions in HCC827 Cells and Tumors
Authors: Hsieh Min-Tsang , Lee Pei-Chih , Chiang Yi-Ting , Lin Hui-Yi , Lee Der-Yen
Published: July 2023

Drug combination therapy is a key approach in cancer treatments, aiming to improve therapeutic efficacy and overcome drug resistance. Evaluation of intracellular response in cancer cells to drug treatment may disclose the underlying mechanism of drug resistance. In this study, we aimed to investigate the effect of osimertinib, a tyrosine kinase inhibitor (TKI), and a curcumin derivative, 35d, on HCC827 cells and tumors by analyzing alterations in metabolome and related regulations. HCC827 tumor-bearing SCID mice and cultured HCC827 cells were separately examined. The treatment comprised four conditions: vehicle-only, 35d-only, osimertinib-only, and a combination of 35d and osimertinib. The treated tumors/cells were subsequently subjected to metabolomics profiling, fatty acyl analysis, mitochondrial potential measurement, and cell viability assay. Osimertinib induced changes in the ratio of short-chain (SC) to long-chain (LC) fatty acyls, particularly acylcarnitines (ACs), in both tumors and cells. Furthermore, 35d enhanced this effect by further lowering the SC/LC ratio of most ACs. Osimertinib and 35d also exerted detrimental effects on mitochondria through distinct mechanisms. Osimertinib upregulated the expression of carnitine palmitoyltransferase I (CPTI), while 35d induced the expression of heat shock protein 60 (HSP60). The alterations in ACs and CPTI were correlated with mitochondrial dysfunction and inhibited cell growth. Our results suggest that osimertinib and 35d disrupted the fatty acyl metabolism and induced mitochondrial stress in cancer cells. This study provides insights into the potential application of fatty acyl metabolism inhibitors, such as osimertinib or other TKIs, and mitochondrial stress inducers, such as curcumin derivatives, as combination therapy for cancer.
Using Normalized Carcinoembryonic Antigen and Carbohydrate Antigen 19 to Predict and Monitor the Efficacy of Neoadjuvant Chemotherapy in Locally Advanced Gastric Cancer
Authors: Tang Xiao-Huan , Wu Xiao-Long , Gan Xue-Jun , Wang Yi-Ding , Jia Fang-Zhou , Wang Yi-Xue , Zhang Yan , Gao Xiang-Yu , Li Zi-Yu
Published: July 2023

Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are established prognostic biomarkers for patients with gastric cancer. However, their potential as predictive markers for neoadjuvant chemotherapy (NACT) efficacy has not been fully elucidated. Methods: We conducted a retrospective analysis to determine values of CEA and CA19-9 prior to NACT (pre-NACT) and after NACT (post-NACT) in 399 patients with locally advanced gastric cancer (LAGC) who received intended NACT and surgery. Results: Among the 399 patients who underwent NACT plus surgery, 132 patients (33.1%) had elevated pre-NACT CEA/CA19-9 values. Furthermore, either pre-NACT or post-NACT CEA /CA19-9 levels were significantly associated with prognosis (p = 0.0023) compared to patients with non-elevated levels. Moreover, among the patients, a significant proportion (73/132, 55.3%) achieved normalized CEA/CA19-9 following NACT, which is a strong marker of a favorable treatment response and survival benefits. In addition, the patients with normalized CEA/CA19-9 also had a prolonged survival compared to those who underwent surgery first (p = 0.0140), which may be attributed to the clearance of micro-metastatic foci. Additionally, the magnitude of CEA/CA19-9 changes did not exhibit a statistically significant prognostic value. Conclusions: Normalization of CEA/CA19-9 is a strong biomarker for the effectiveness of treatment, and can thus be exploited to prolong the long-term survival of patients with LAGC.
HIV-1–Host Interaction in Gut-Associated Lymphoid Tissue (GALT): Effects on Local Environment and Comorbidities
Authors: Moretti Sonia , Schietroma Ivan , Sberna Giuseppe , Maggiorella Maria Teresa , Sernicola Leonardo , Farcomeni Stefania , Giovanetti Marta , Ciccozzi Massimo , Borsetti Alessandra
Published: July 2023

HIV-1 replication in the gastrointestinal (GI) tract causes severe CD4+ T-cell depletion and disruption of the protective epithelial barrier in the intestinal mucosa, causing microbial translocation, the main driver of inflammation and immune activation, even in people living with HIV (PLWH) taking antiretroviral drug therapy. The higher levels of HIV DNA in the gut compared to the blood highlight the importance of the gut as a viral reservoir. CD4+ T-cell subsets in the gut differ in phenotypic characteristics and differentiation status from the ones in other tissues or in peripheral blood, and little is still known about the mechanisms by which the persistence of HIV is maintained at this anatomical site. This review aims to describe the interaction with key subsets of CD4+ T cells in the intestinal mucosa targeted by HIV-1 and the role of gut microbiome and its metabolites in HIV-associated systemic inflammation and immune activation that are crucial in the pathogenesis of HIV infection and related comorbidities.
Changes in Multiple microRNA Levels with Antidepressant Treatment Are Associated with Remission and Interact with Key Pathways: A Comprehensive microRNA Analysis
Authors: Funatsuki Toshiya , Ogata Haruhiko , Tahara Hidetoshi , Shimamoto Akira , Takekita Yoshiteru , Koshikawa Yosuke , Nonen Shinpei , Higasa Koichiro , Kinoshita Toshihiko , Kato Masaki
Published: July 2023

Individual treatment outcomes to antidepressants varies widely, yet the determinants to this difference remain elusive. MicroRNA (miRNA) gene expression regulation in major depressive disorder (MDD) has attracted interest as a biomarker. This 4-week randomized controlled trial examined changes in the plasma miRNAs that correlated with the treatment outcomes of mirtazapine (MIR) and selective serotonin reuptake inhibitor (SSRI) monotherapy. Pre- and post- treatment, we comprehensively analyzed the miRNA levels in MDD patients, and identified the gene pathways linked to these miRNAs in 46 patients. Overall, 141 miRNA levels significantly demonstrated correlations with treatment remission after 4 weeks of MIR, with miR-1237-5p showing the most robust and significant correlation after Bonferroni correction. These 141 miRNAs displayed a negative correlation with remission, indicating a decreasing trend. These miRNAs were associated with 15 pathways, including TGF-β and MAPK. Through database searches, the genes targeted by these miRNAs with the identified pathways were compared, and it was found that MAPK1, IGF1, IGF1R, and BRAF matched. Alterations in specific miRNAs levels before and after MIR treatment correlated with remission. The miRNAs mentioned in this study have not been previously reported. No other studies have investigated treatment with MIR. The identified miRNAs also correlated with depression-related genes and pathways.
Foliar Application of Chelated Sugar Alcohol Calcium Improves Photosynthesis and Tuber Quality under Drought Stress in Potatoes (Solanum tuberosum L.)
Authors: Wang Yihao , Qin Tianyuan , Pu Zhuanfang , Dekomah Simon Dontoro , Yao Panfeng , Sun Chao , Liu Yuhui , Bi Zhenzhen , Bai Jiangping
Published: July 2023

Drought stress is a major threat to sustainable crop production worldwide. Despite the positive role of calcium (Ca2+) in improving plant drought tolerance in different crops, little attention has been paid to its role in mitigating drought stress in potatoes. In the present study, we studied the effect of foliar chelated sugar alcohol calcium treatments on two potato cultivars with different drought responses applied 15 and 30 days after limiting soil moisture. The results showed that the foliar application of calcium treatments alleviated the SPAD chlorophyll loss of the drought-sensitive cultivar ‘Atlantic’ (Atl) and reduced the inhibition of photosynthetic parameters, leaf anatomy deformation, and MDA and H2O2 content of both cultivars under drought stress. The Ca2+ treatments changed the expression of several Calcium-Dependent Protein Kinase (StCDPK) genes involved in calcium sensing and signaling and significantly increased antioxidant enzyme activities, average tuber weight per plant, and tuber quality of both cultivars. We conclude that calcium spray treatments improved the drought tolerance of both potato cultivars and were especially effective for the drought-sensitive cultivar. The present work suggests that the foliar application of calcium is a promising strategy to improve commercial potato yields and the economic efficiency of potato production under drought stress conditions.
Disintegrin-like Protein Strategy to Inhibit Aggressive Triple-Negative Breast Cancer
Authors: Limam Inès , Abdelkarim Mohamed , El Ayeb Mohamed , Crepin Michel , Marrakchi Naziha , Di Benedetto Mélanie
Published: July 2023

Venoms are a rich source of bioactive compounds, and among them is leberagin-C (Leb-C), a disintegrin-like protein derived from the venom of Macrovipera lebetina transmediterrannea snakes. Leb-C has shown promising inhibitory effects on platelet aggregation. Previous studies have demonstrated that this SECD protein specifically targets α5β1, αvβ3, and αvβ6 integrins through a mimic mechanism of RGD disintegrins. In our current study, we focused on exploring the potential effects of Leb-C on metastatic breast cancer. Our findings revealed that Leb-C disrupted the adhesion, migration, and invasion capabilities of MDA-MB-231 breast cancer cells and its highly metastatic D3H2LN sub-population. Additionally, we observed significant suppression of adhesion, migration, and invasion of human umbilical vein endothelial cells (HUVECs). Furthermore, Leb-C demonstrated a strong inhibitory effect on fibroblast-growth-factor-2-induced proliferation of HUVEC. We conducted in vivo experiments using nude mice and found that treatment with 2 µM of Leb-C resulted in a remarkable 73% reduction in D3H2LN xenograft tumor size. Additionally, quantification of intratumor microvessels revealed a 50% reduction in tumor angiogenesis in xenograft after 21 days of twice-weekly treatment with 2 µM of Leb-C. Collectively, these findings suggest the potential utility of this disintegrin-like protein for inhibiting aggressive and resistant metastatic breast cancer.
Microbial Consortia for Plant Protection against Diseases: More than the Sum of Its Parts
Authors: Maciag Tomasz , Kozieł Edmund , Rusin Piotr , Otulak-Kozieł Katarzyna , Jafra Sylwia , Czajkowski Robert
Published: July 2023

Biological plant protection presents a promising and exciting alternative to chemical methods for safeguarding plants against the increasing threats posed by plant diseases. This approach revolves around the utilization of biological control agents (BCAs) to suppress the activity of significant plant pathogens. Microbial BCAs have the potential to effectively manage crop disease development by interacting with pathogens or plant hosts, thereby increasing their resistance. However, the current efficacy of biological methods remains unsatisfactory, creating new research opportunities for sustainable plant cultivation management. In this context, microbial consortia, comprising multiple microorganisms with diverse mechanisms of action, hold promise in terms of augmenting the magnitude and stability of the overall antipathogen effect. Despite scientific efforts to identify or construct microbial consortia that can aid in safeguarding vital crops, only a limited number of microbial consortia-based biocontrol formulations are currently available. Therefore, this article aims to present a complex analysis of the microbial consortia-based biocontrol status and explore potential future directions for biological plant protection research with new technological advancements.
Effect of Granulocyte Colony-Stimulating Factor on the Development of Spermatogenesis in the Adulthood of Juvenile AML Mice Model Treated with Cytarabine
Authors: Khaleel Bara’ah , Lunenfeld Eitan , Kapelushnik Joseph , Huleihel Mahmoud
Published: July 2023

Pediatric acute myeloid leukemia (AML) generally occurs de novo. The treatment of AML includes cytarabine (CYT) and other medications. The granulocyte-colony stimulating factor (GCSF) is used in the clinic in cases of neutropenia after chemotherapies. We show that the administration of GCSF in combination with CYT in AML-diagnosed mice (AML+CYT+GCSF) extended the survival of mice for additional 20 days. However, including GCSF in all treatment modalities does not affect the testis’ weight or the histology of the seminiferous tubules (STs). We show that GCSF does not affect normal ST histology from AML-, CYT-, or (AML+CYT)-treated groups compared to the relevant treated group without GCSF 2, 4, and 5 weeks post-injection. However, when comparing the percentages of normal STs between the AML+CYT+GCSF-treated groups and those without GCSF, we observe an increase of 17%–42% in STs at 4 weeks and 5.5 weeks post-injection. Additionally, we show that the injection of GCSF into the normal, AML-alone, or CYT-alone groups, or in combination with AML, significantly decreases the percentage of STs with apoptotic cells compared to the relevant groups without GCSF and to the CT (untreated mice) only 2 weeks post-injection. We also show that injection of GCSF into the CT group increases the examined spermatogonial marker PLZF within 2 weeks post-injection. However, GCSF does not affect the count of meiotic cells (CREM) but decreases the post-meiotic cells (ACROSIN) within 4 weeks post-injection. Furthermore, GCSF not only extends the survival of the AML+CYT-treated group, but it also leads to the generation of sperm (1.2 ± 0.04 × 106/mL) at 5.5 weeks post-injection. In addition, we demonstrate that the injection of GCSF into the CT group increases the RNA expression level of IL-10 but not IL-6 compared to CT 2 weeks post-treatment. However, the injection of GCSF into the AML-treated group reverses the expression levels of both IL-10 and IL-6 to normal levels compared to CT 2 weeks post-injection. Thus, we suggest that the addition of GCSF to the regimen of AML after CYT may assist in the development of future therapeutic strategies to preserve male fertility in AML prepubertal patients.
Functional Study of Amorpha fruticosa WRKY20 Gene in Response to Drought Stress
Authors: Li Danni , Gu Baoxiang , Huang Chunxi , Shen Jiayi , Wang Xin , Guo Jianan , Yu Ruiqiang , Mou Sirui , Guan Qingjie
Published: July 2023

The WRKY gene family in plants regulates the plant’s response to drought through regulatory networks and hormone signaling. AfWRKY20 (MT859405) was cloned from Amorpha fruticosa (A. fruticosa) seedlings using RT-PCR. The binding properties of the AfWRKY20 protein and the W-box (a DNA cis-acting element) were verified both in vivo and in vitro using EMSA and Dual-Luciferase activity assays. RT-qPCR detected that the total expression level of AfWRKY20 in leaves and roots was 22 times higher in the 30% PEG6000 simulated drought treatment compared to the untreated group. Under the simulated drought stress treatments of sorbitol and abscisic acid (ABA), the transgenic tobacco with the AfWRKY20 gene showed enhanced drought resistance at the germination stage, with significantly increased germination rate, green leaf rate, fresh weight, and root length compared to the wild-type (WT) tobacco. In addition, the superoxide dismutase (SOD) activity, chlorophyll content, and Fv/Fm ratio of AfWRKY20 transgenic tobacco were significantly higher than those of the WT tobacco under natural drought stress, while the malondialdehyde (MDA) content and 3,3′-diaminobenzidine (DAB) and nitroblue tetrazolium (NBT) staining levels were lower. The expression levels of oxidation kinase genes (NbSOD, NbPOD, and NbCAT) in transgenic tobacco under drought stress were significantly higher than those in WT tobacco. This enhancement in gene expression improved the ability of transgenic tobacco to detoxify reactive oxygen species (ROS). The survival rate of transgenic tobacco after natural drought rehydration was four times higher than that of WT tobacco. In summary, this study revealed the regulatory mechanism of AfWRKY20 in response to drought stress-induced ABA signaling, particularly in relation to ROS. This finding provides a theoretical basis for understanding the pathways of WRKY20 involved in drought stress, and offers genetic resources for molecular plant breeding aimed at enhancing drought resistance.
Coronavirus Disease Pathophysiology: Biomarkers, Potential New Remedies, Comorbidities, Long COVID-19, Post Pandemic Epidemiological Surveillance
Authors: Kubiak Jacek Z. , Kloc Małgorzata
Published: July 2023

The toughest challenge modern biomedical research ever faced was the rapid understanding of the SARS-CoV-2 physiopathology [...]
Differential Role of Aldosterone and Transforming Growth Factor Beta-1 in Cardiac Remodeling
Authors: Kmieć Piotr , Rosenkranz Stephan , Odenthal Margarete , Caglayan Evren
Published: July 2023

Angiotensin II, a major culprit in cardiovascular disease, activates mediators that are also involved in pathological cardiac remodeling. In this context, we aimed at investigating the effects of two of them: aldosterone (Ald) and transforming growth factor beta-1 (TGF-β1) in an in vivo model. Six-week-old male wild-type (WT) and TGF-β1-overexpressing transgenic (TGF-β1-TG) mice were infused with subhypertensive doses of Ald for 2 weeks and/or treated orally with eplerenone from postnatal day 21. Thehearts’ ventricles were examined by morphometry, immunoblotting to assess the intracellular signaling pathways and RT qPCR to determine hypertrophy and fibrosis marker genes. The TGF-β1-TG mice spontaneously developed cardiac hypertrophy and interstitial fibrosis and exhibited a higher baseline phosphorylation of p44/42 and p38 kinases, fibronectin and ANP mRNA expression. Ald induced a comparable increase in the ventricular-heart-weight-to-body-weight ratio and cardiomyocyte diameter in both strains, but a less pronounced increase in interstitial fibrosis in the transgenic compared to the WT mice (23.6% vs. 80.9%, p < 0.005). Ald increased the phosphorylation of p44/42 and p38 in the WT but not the TGF-β1-TG mice. While the eplerenone-enriched chow partially prevented Ald-induced cardiac hypertrophy in both genotypes and interstitial fibrosis in the WT controls, it completely protected against additional fibrosis in transgenic mice. Ald appears to induce cardiac hypertrophy independently of TGF-β1, while in the case of fibrosis, the downstream signaling pathways of these two factors probably converge.