bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Combining Aerobic and Heavy Resistance Training on Body Composition, Muscle Hypertrophy, and Exercise Satisfaction in Physically Active Adults
Authors: Tan Jerrican , Krasilshchikov Oleksandr , Kuan Garry , Hashim Hairul Anuar , Aldhahi Monira I. , Al-Mhanna Sameer Badri , Badicu Georgian
Published: August 2023

This study investigated the effects of combined aerobic and heavy resistance training on the variables of body composition, muscle hypertrophy, and exercise satisfaction in physically active adults in comparison with heavy resistance training only (predominantly designed for hypertrophy). Twenty-two healthy male adults between the ages of 18 and 35, who had limited previous experience with muscle resistance training, participated in the intervention program while maintaining their physical activity level. The participants were randomly allocated into two groups: the resistance training group (control group) and the combined training group (experimental group), which involved both resistance training and aerobic training. Aerobic training consisted of 30 min aerobic interval training sessions three times a week with a total of 8 min work bouts in each at 60–70% of heart rate reserve (HRR). The intervention training program lasted for eight weeks. Resistance training consisted of a 3-day muscle group split (2–3 exercises per muscle group, 8 sets per muscle group, 6–12 repetition maximum (RM). Upon completion, body composition, muscle hypertrophy, and exercise satisfaction were analyzed using the mixed-design ANOVA. Variables selected for this study as markers of body composition responded differently to the different interventions and time; however, some trends were not statistically significant. Overall, it is not possible to state unequivocally that one training modality was superior to another in the body composition cluster, for significant improvements were observed within the groups from pre- to post-interventions, but no significant differences were observed between the resistance training and combined training groups, while, both interventions showed improvement with time in some variables of muscle hypertrophy. Compared to baseline, the exercise satisfaction post-intervention improved within the groups. From pre- to post-testing, both resistance and combined training groups improved exercise satisfaction (p < 0.05 in both groups). However, there was no significant difference in exercise satisfaction observed between the resistance training and combined training groups after the training intervention (p > 0.05).
Hub Gene Identification and Heat-Stress-Related Transcriptional Regulation Mechanism in Cabbage (Brassica oleracea L.)
Authors: Li Qiang , Zhang Guoli , Zhao Yuqian , Gu Liqiang , Wang Ying , Yu Xiaohui , Abdullah Shamsiah
Published: August 2023

Cabbage is a heat-stress-sensitive cool-season crop. When exposed to high temperatures, cabbage plants can experience reduced growth, wilting, leaf yellowing, and premature bolting (the formation of a flowering stem). The regulatory mechanism controlling heat stress is poorly understood in cabbage. To investigate this mechanism, physiological changes and transcriptional profiling for different heat treatment times were analyzed in this study. The results showed that superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities were enhanced under heat stress. In particular, the increase in SOD and POD activities after 12 h of heat treatment was greater than that after 4 h of heat treatment. With increasing heat treatment duration, the leaf CAT activity and H2O2 content decreased after the initial increase. The electrolyte leakage and malondialdehyde (MDA) content dropped significantly, while the proline content increased. Alongside that, 7007 and 5537 upregulated genes were identified in the experimental group treated with heat stress for the 4 h and 12 h treatments, respectively. We found that 10,479 DEGs were shared in the heat stress treatment, of which 1241 were associated with the heat treatment time. By integrating the expression patterns and functional annotations of genes related to heat stress, we identified 15 hub genes that respond to heat stress in cabbage. Meanwhile, we had constructed a physiological to molecular model of cabbage response to long-term heat stress. These findings provide new insights for the comprehensive analysis of cabbage response to heat stress and genetic resources for breeding new varieties of cabbage with heat tolerance via genetic engineering.
Physiotherapy Methods Applied in the Prevention of Functional Loss Associated with Human T-Lymphotropic Virus 1 Infection: An Overview
Authors: Assis Izabela Mendonça de , Callegari Bianca , Sousa Maisa Silva de
Published: August 2023

To achieve the objective of this study, we conducted a narrative review on physical therapeutic modalities applied to prevent functional losses associated with human T-lymphotropic virus 1 (HTLV-1) infections to promote health education and viable and accessible alternatives in the development of health education technology adapted to the home environment. This study comprised a qualitative stage of theoretical development to construct a digital booklet with an observational basis based on studies that reiterate themes about educational technologies as tools to conduct a home protocol of guided exercises without the direct supervision of professional physical therapists. Results indicate a lack of research on the development of health education technologies to assist patients with HTLV-1 without tropical spastic paraparesis or HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). We believe that this narrative review can initiate a theoretical framework to conduct a home exercise program aimed at people with HTLV-1 who have subtle symptoms, and also at people without the clinical definition of HAM/TSP, helping to train human resources for care and research on the subject and increase scientific production in physical therapy.
“Couch-to-5k or Couch to Ouch to Couch!?” Who Takes Part in Beginner Runner Programmes in the UK and Is Non-Completion Linked to Musculoskeletal Injury?
Authors: Relph Nicola , Taylor Sarah L. , Christian Danielle L. , Dey Paola , Owen Michael B.
Published: August 2023

Physical activity has mental and physical health benefits; however, globally, three-quarters of the population do not meet physical activity guidelines. The Couch-to-5k is a beginner runner programme aimed at increasing physical activity. However, this programme lacks an evidence base, and it is unclear who is attracted to the programme; running also has a high rate of musculoskeletal (MSK) injuries. The aims of this study were to identify the characteristics of people taking part and the incidence of MSK injuries as well as exploring the experiences of people who dropped out of a modified 9-week Couch-to-5k programme. A total of 110 runners (average age was 47.1 ± 13.7 years) participated in the study, which involved completion of questionnaires (running experience and footwear information, quality of life (EQ-5D-5L), physical activity level (IPAQ-short form), MSK injury history and knee condition (SNAPPS and KOOS-PS)) at the start, middle and end of the programme and collecting sociodemographic information (age, gender, social economic status, relationship status, education level), as well as body mass index, running experience, footwear information, quality of life, physical activity levels, MSK injuries and knee condition. Fifteen drop-outs were interviewed to explore experiences of the programme. Runners were mainly females (81.8%) with an average age 47.1 years, average body mass index of 28.1 kg.m2, mainly from high socio-economic levels, married and educated to degree level. In total, 64% of the sample had previous running experience and were classified as active. Half the sample self-reported pain/discomfort and 37.2% reported anxiety/depression at the start of the programme via the EQ-5D-5L scale. Self-reported health scores increased (p = 0.047) between baseline (73.1 ± 18.8 out of 100) and at the midpoint (81.2 ± 11.6), but there were no significant differences between any other time points (end point 79.7 ± 17.5, p > 0.05). Twenty-one injuries were reported during the programme (19%). Previous injury increased the risk of new injury (OR 7.56 95% CI from 2.06 to 27.75). Only 27.3% completed the programme. Three themes emerged from interviews; MSK injury, negative emotions linked to non-completion and design of the programme. The Couch-to-5k may not attract diverse inactive populations, but future work with larger sample sizes is needed to substantiate this finding. Dropping out was linked to MSK injury and progressive design, so future programmes should consider including injury prevention advice and more flexible designs.
Mental Health Challenges during COVID-19 Pandemic: Experiences of Primary Healthcare Nurses in Durban, South Africa
Authors: Onwubu Stanley Chibuzor , Sibiya Maureen Nokuthula , Makgobole Mokgadi Ursula.
Published: August 2023

The COVID-19 pandemic had a significant impact on the mental health of individuals globally, and primary healthcare (PHC) nurses play a critical role in providing mental healthcare services. However, limited research has explored the experiences of PHC nurses in providing mental healthcare services during the COVID-19 pandemic. This study explored the experiences of PHC nurses in providing mental healthcare services during the pandemic in Durban, South Africa. The aim was to identify the challenges faced by healthcare providers and the potential for innovative approaches to improve access to care. A qualitative, exploratory design guided the study, and data were collected through in-depth interviews with twelve PHC nurses purposively selected. Thematic analysis was used to analyze the data. Findings from interviews with PHC nurses reveal that the pandemic exacerbated existing challenges, including medication adherence issues, fear and uncertainty among patients, vaccine hesitancy, decreased clinic visits, and the mental and emotional toll on both patients and healthcare workers. PHC nurses adapted their services by increasing outreach efforts, prioritizing patient care, and utilizing technology and non-governmental organizations’ (NGOs) support. Challenges included reduced patient visits, complexities in healthcare provision, and a lack of adequate support. Positive changes observed include increased mental health awareness among healthcare professionals and younger generations. Recommendations include implementing outreach and awareness campaigns, providing accurate information about COVID-19 and vaccinations, and promoting cultural sensitivity in mental healthcare provision.
Maternal, Fetal and Neonatal Outcomes Related to Recreational Cannabis Use during Pregnancy: Analysis of a Real-World Clinical Data Warehouse between 2010 and 2019
Authors: Bouquet Emilie , Blouin Pascal , Pérault-Pochat Marie-Christine , Carlier-Guérin Caroline , Millot Frédéric , Ricco Jean-Baptiste , De Keizer Joe , Pain Stéphanie , Guétarni Farid
Published: August 2023

Background: Cannabis is the main illicit psychoactive substance used in French childbearing women and very few data are available about adverse events (AEs) related to its use during pregnancy. The aim of this study was to evaluate the association between recreational cannabis use during pregnancy and adverse outcomes from a real-world clinical data warehouse. Methods: Data from the Poitiers University Hospital warehouse were analyzed between 1 January 2010 and 31 December 2019. Logistic regression models were used to evaluate associations between outcomes in three prenatal user groups: cannabis alone ± tobacco (C ± T) (n = 123), tobacco alone (T) (n = 191) and controls (CTRL) (n = 355). Results: Pregnant women in the C ± T group were younger (mean age: 25.5 ± 5.7 years), had lower pre-pregnancy body mass index (22.8 ± 5.5 kg/m2), more psychiatric history (17.5%) and were more likely to benefit from universal free health-care coverage (18.2%) than those in the T and CTRL groups. Cannabis use increases the occurrence of voluntary interruption of pregnancy, at least one AE during pregnancy, at least one neonatal AE, the composite adverse pregnancy outcome over 28, prematurity and small for gestational age. Conclusion: Given the trivialization of recreational cannabis use during pregnancy, there is an urgent need to communicate on AEs of cannabis use during pregnancy.
Comment on Calugi et al. The Role of Weight Suppression in Intensive Enhanced Cognitive Behavioral Therapy for Adolescents with Anorexia Nervosa: A Longitudinal Study. Int. J. Environ. Res. Public Health 2023, 20, 3221
Authors: Meule Adrian
Published: August 2023

Calugi and colleagues [...]
Violence in the Nursing Workplace in the Context of Primary Health Care: A Qualitative Study
Authors: Carvalho Kisa Valladão , Araujo Priscila Norié de , Santos Felipe Lima dos , Oliveira Poliana Silva de , Silva Janaina Pereira da , Santos Karen da Silva , Viana Angelina Lettiere , Fortuna Cinira Magali
Published: August 2023

Violence demands considerable attention due to its complexity and social consequences. The objective of this study was to analyze violence in the nursing professional workplace in the context of primary health care in Brazil. It is a qualitative study with theoretical and methodological reference to institutional analysis. It was carried out in basic health units in Brazil. Nursing professionals (N = 11) participated in semi-structured interviews and discussion groups, in addition to a research diary and participant observation. Data collection took place from October to December 2021. The results are presented in five categories: types of violence and aggressors from the perspective of nursing professionals; the causes of violence reported by professionals; strategies for the management of violence; professionals’ proposals for preventing violence in health contexts; the consequences of violence in the workplace. Nursing professionals make up a large part of the workforce and have reported verbal, physical, moral, and psychological violence. The main causes are associated with user access to services. For the prevention of violence, professionals do not see themselves as protagonists of change. The consequences are the loss of quality of work and the health of professionals who requested sick leave and transfers. The study’s findings can help in the development of public policies and educational and management actions.
Chinese Modern Architectural Heritage Resources: Perspectives of Spatial Distribution and Influencing Factors
Authors: Liao Yidan , Cenci Jeremy , Zhang Jiazhen
Published: August 2023

Architectural heritage refers to buildings, complexes, and sites with historical, cultural, artistic, technological, and geographical values, including ancient buildings, historical buildings, places of interest, dwellings, and industrial sites. China’s 20th-Century Architectural Heritage List is a state-level list that includes architecture of historical, cultural, technological, and artistic value in China in the 20th century. It is the carrier of the past century and the monument to witnessing the change in human knowledge, culture, technology, and even art. This list is from China, a country with a vast land area, a densely populated population, and numerous architectural relics. This study used ArcGIS to analyze 597 cases in 6 batches in China’s 20th-Century Architectural Heritage List. Its spatial structure was studied by calculating the nearest neighbor index, Gini coefficient, imbalance index, and kernel density. The results showed that the distribution of the Chinese modern architectural heritage resources is cohesive and uneven in China. Next, the geographical detector model was used to analyze its influencing factors from the perspective of 12 factors. This study found that the spatial distribution of this type of resource was condensed. The provincial level showed a distribution pattern of seven centers with one core and multiple scattered points. Its distribution in 34 administrative regions is extremely uneven, with 57.29% being located in North and East China. It also focused on analyzing five influencing factors, namely, topography, regional status, culture and education, social and economic development level, and external contact. Exploring its spatial structure and influencing factors will not only enable a comprehensive understanding of the development context and current situation of 20th-century architectural heritage, but also provide a reference for its protection and sustainable use.
EGF, TGF-α and Amphiregulin Differently Regulate Endometrium-Derived Mesenchymal Stromal/Stem Cells
Authors: Kamentseva Rimma Sergeevna , Kharchenko Marianna Viktorovna , Gabdrahmanova Gulnara Vladikovna , Kotov Michael Alexandrovich , Kosheverova Vera Vladislavovna , Kornilova Elena Sergeevna
Published: August 2023

The prototypical receptor tyrosine kinase epidermal growth factor receptor (EGFR) is regulated by a set of its ligands, which determines the specificity of signaling and intracellular fate of the receptor. The EGFR signaling system is well characterized in immortalized cell lines such as HeLa derived from tumor tissues, but much less is known about EGFR function in untransformed multipotent stromal/stem cells (MSCs). We compared the effect of epidermal growth factor (EGF), transforming growth factor-α (TGF-α) and amphiregulin (AREG) on physiological responses in endometrial MSCs (enMSC) and HeLa cells. In addition, using Western blotting and confocal microscopy, we studied the internalization and degradation of EGFR stimulated by the three ligands in these cell lines. We demonstrated that unlike HeLa, EGF and TGF-α, but not AREG, stimulated enMSC proliferation and prevented decidual differentiation in an EGFR-dependent manner. In HeLa cells, EGF targeted EGFR for degradation, while TGF-α stimulated its recycling. Surprisingly, in enMSC, both ligands caused EGFR degradation. In both cell lines, AREG-EGFR internalization was not registered. In HeLa cells, EGFR was degraded within 2 h, restoring its level in 24 h, while in enMSC, degradation took more than 4–8 h, and the low EGFR level persisted for several days. This indicates that EGFR homeostasis in MSCs may differ significantly from that in immortalized cell lines.
The Role of Biomarkers, Metabolomics, and COVID-19 in Venous Thromboembolism—A Review of Literature
Authors: Della Corte Vittoriano , Riolo Renata , Scaglione Stefania , Pecoraro Rosaria , Tuttolomondo Antonino
Published: August 2023

In recent years, the field of venous thromboembolism has undergone numerous innovations, starting from the recent discoveries on the role of biomarkers, passing through the role of metabolomics in expanding our knowledge on pathogenic mechanisms, which have opened up new therapeutic targets. A variety of studies have contributed to characterizing the metabolic phenotype that occurs in venous thromboembolism, identifying numerous pathways that are altered in this setting. Among these pathways are the metabolism of carnitine, tryptophan, purine, and fatty acids. Furthermore, new evidence has emerged with the recent COVID-19 pandemic. Hypercoagulability phenomena induced by this viral infection appear to be related to altered von Willebrand factor activity, alteration of the renin–angiotensin–aldosterone system, and dysregulation of both innate and adaptive immunity. This is the first literature review that brings together the most recent evidence regarding biomarkers, metabolomics, and COVID-19 in the field of venous thromboembolism, while also mentioning current therapeutic protocols.
Expression Variation of CPT1A Induces Lipid Reconstruction in Goat Intramuscular Precursor Adipocytes
Authors: Tang Yinmei , Zhang Wenyang , Wang Yinggui , Li Haiyang , Zhang Changhui , Wang Yong , Lin Yaqiu , Shi Hengbo , Xiang Hua , Huang Lian , Zhu Jiangjiang
Published: August 2023

Intramuscular fat (IMF) deposition is one of the most important factors affecting meat quality and is closely associated with the expression of carnitine palmitoyl transferase 1A (CPT1A) which facilitates the transfer of long-chain fatty acids (LCFAs) into the mitochondria. However, the role of how CPT1A regulates the IMF formation remains unclear. Herein, we established the temporal expression profile of CPT1A during the differentiation of goat intramuscular precursor adipocytes. Functionally, the knockdown of CPT1A by siRNA treatment significantly increased the mRNA expression of adipogenic genes and promoted lipid deposition in goat intramuscular precursor adipocytes. Meanwhile, a CPT1A deficiency inhibited cell proliferation and promoted cell apoptosis significantly. CPT1A was then supported by the overexpression of CPT1A which significantly suppressed the cellular triglyceride deposition and promoted cell proliferation although the cell apoptosis also was increased. For RNA sequencing, a total of 167 differential expression genes (DEGs), including 125 upregulated DEGs and 42 downregulated DEGs, were observed after the RNA silencing of CPT1A compared to the control, and were predicted to enrich in the focal adhesion pathway, cell cycle, apoptosis and the MAPK signaling pathway by KEGG analysis. Specifically, blocking the MAPK signaling pathway by a specific inhibitor (PD169316) rescued the promotion of cell proliferation in CPT1A overexpression adipocytes. In conclusion, the expression variation of CPT1A may reconstruct the lipid distribution between cellular triglyceride deposition and cell proliferation in goat intramuscular precursor adipocyte. Furthermore, we demonstrate that CPT1A promotes the proliferation of goat adipocytes through the MAPK signaling pathway. This work widened the genetic regulator networks of IMF formation and delivered theoretical support for improving meat quality from the aspect of IMF deposition.
Single-Cell Analysis of Contractile Forces in iPSC-Derived Cardiomyocytes: Paving the Way for Precision Medicine in Cardiovascular Disease
Authors: Turnbull Irene C. , Bajpai Apratim , Jankowski Katherine B. , Gaitas Angelo
Published: August 2023

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) hold enormous potential in cardiac disease modeling, drug screening, and regenerative medicine. Furthermore, patient-specific iPSC-CMS can be tested for personalized medicine. To provide a deeper understanding of the contractile force dynamics of iPSC-CMs, we employed Atomic Force Microscopy (AFM) as an advanced detection tool to distinguish the characteristics of force dynamics at a single cell level. We measured normal (vertical) and lateral (axial) force at different pacing frequencies. We found a significant correlation between normal and lateral force. We also observed a significant force–frequency relationship for both types of forces. This work represents the first demonstration of the correlation of normal and lateral force from individual iPSC-CMs. The identification of this correlation is relevant because it validates the comparison across systems and models that can only account for either normal or lateral force. These findings enhance our understanding of iPSC-CM properties, thereby paving the way for the development of therapeutic strategies in cardiovascular medicine.
Effect of Composition and Size on Surface Properties of Anti-Cancer Nanoparticles
Authors: Mishra Ina , Garrett Meredith , Curry Stephen , Jameson Jeffrey , Kastellorizios Michail
Published: August 2023

Liposomal formulations offer significant advantages as anticancer drug carriers for targeted drug delivery; however, due to their complexity, clinical translation has been challenging. In addition, liposomal product manufacturing has been interrupted in the past, as was the case for Doxil® (doxorubicin hydrochloride liposome injection). Here, interfacial tension (IFT) measurements were investigated as a potential physicochemical characterization tool to aid in liposomal product characterization during development and manufacturing. A pendant drop method using an optical tensiometer was used to measure the interfacial tension of various analogues of Doxil® liposomal suspensions in air and in dodecane. The effect of liposome concentration, formulation (PEG and cholesterol content), presence of encapsulated drug, as well as average particle size was analyzed. It was observed that Doxil® analog liposomes demonstrate surfactant-like behavior with a sigmoidal-shape interfacial tension vs. concentration curve. This behavior was heavily dependent on PEG content, with a complete loss of surfactant-like behavior when PEG was removed from the formulation. In addition to interfacial tension, three data analyses were identified as able to distinguish between formulations with variations in PEG, cholesterol, and particle size: (i) polar and non-polar contribution to interfacial tension, (ii) liposomal concentration at which the polar and non-polar components were equal, and (iii) rate of interfacial tension decay after droplet formation, which is indicative of how quickly liposomes migrate from the bulk of the solution to the surface. We demonstrate for the first time that interfacial tension can be used to detect certain liposomal formulation changes, such as PEG content, encapsulated drug presence, and size variability, and may make a useful addition to physicochemical characterization during development and manufacturing of liposomal products.
Evaluating the In Vitro and In Vivo Prebiotic Effects of Different Xylo-Oligosaccharides Obtained from Bamboo Shoots by Hydrothermal Pretreatment Combined with Endo-Xylanase Hydrolysis
Authors: Deng Junping , Yun Jinyan , Gu Yang , Yan Bowen , Yin Baishuang , Huang Caoxing
Published: August 2023

Xylo-oligosaccharides (XOS) enriched with high fractions of X2-X3 are regarded as an effective prebiotic for regulating the intestinal microflora. In this study, the original XOS solution was obtained from bamboo shoots through hydrothermal pretreatment under optimized conditions. Subsequently, enzymatic hydrolysis with endo-xylanase was performed on the original XOS solution to enhance the abundance of the X2-X3 fractions. The results demonstrated that hydrothermal pretreatment yielded 21.24% of XOS in the hydrolysate solution, and subsequent enzymatic hydrolysis significantly increased the proportion of the X2-X3 fractions from 38.87% to 68.21%. Moreover, the XOS solutions with higher amounts of X2-X3 fractions exhibited superior performance in promoting the growth of probiotics such as Bifidobacterium adolescentis and Lactobacillus acidophilus in vitro, leading to increased production of short-chain fatty acids. In the in vivo colitis mouse model, XOS solutions with higher contents of X2-X3 fractions demonstrated enhanced efficacy against intestinal inflammation. Compared with the colitis mice (model group), the XOS solution with higher X2-X3 fractions (S1 group) could significantly increase the number of Streptomyces in the intestinal microflora, while the original XOS solution (S2 group) could significantly increase the number of Bacteroides in the intestinal microflora of colitis mice. In addition, the abundances of Alcaligenes and Pasteurella in the intestinal microflora of the S1 and S2 groups were much lower than in the model group. This effect was attributed to the ability of these XOS solutions to enhance species diversity, reversing the imbalance and disorder within the intestinal microflora. Overall, this work highlights the outstanding potential of XOS enriched with high contents of X2-X3 fractions as a regulator of the intestinal microbiota and as an anti-colitis agent.
Lactiplantibacillus plantarum P101 Attenuated Cyclophosphamide-Induced Liver Injury in Mice by Regulating the Nrf2/ARE Signaling Pathway
Authors: You Tao , Zhao Yu , Liu Shanji , Xu Hengyi
Published: August 2023

Cyclophosphamide causes side effects in cancer patients, including hepatotoxicity. Probiotics have recently emerged as potential approaches for the administration of many diseases. This study aimed to evaluate the protective effects of Lactiplantibacillus plantarum P101 against cyclophosphamide-induced liver injury and elucidate the underlying mechanism. In this study, Lactiplantibacillus plantarum P101 or Lactobacillus rhamnosus GG were pre-administered to mice with varying duration (1 week, 2 weeks, and 3 weeks) before being intraperitoneally injected with cyclophosphamide at a dose of 30 mg/kg/day for 7 days to induce liver injury. Results demonstrated that cyclophosphamide-induced liver injury was characterized by histopathological disorders, including irregular central venous shape and hepatic vascular rupture, as well as a severe inflammation response and oxidative stress. The administration of probiotics for 3 weeks exerted the most significant improvements in alleviating liver injury, oxidative stress, and inflammation when compared to the shorter intervention duration. Notably, Lactiplantibacillus plantarum P101 exhibited more pronounced effects than Lactobacillus rhamnosus GG. Furthermore, Lactiplantibacillus plantarum P101 enhanced the antioxidant defense system by activating the Nrf2/ARE signaling pathway, ultimately alleviating hepatotoxicity and hepatocyte apoptosis. In conclusion, this study highlighted the potential of Lactiplantibacillus plantarum P101 to alleviate cyclophosphamide-induced hepatotoxicity.
Phytochemical Screening on Phenolic, Flavonoid Contents, and Antioxidant Activities of Six Indigenous Plants Used in Traditional Thai Medicine
Authors: Tiranakwit Tanawuth , Puangpun Wimonwan , Tamprasit Kawintra , Wichai Natthapong , Siriamornpun Sirithon , Srisongkram Tarapong , Weerapreeyakul Natthida
Published: August 2023

The antioxidant activity of a traditional Thai formula has been studied and compared to each plant. The formula comprised the roots of Caesalpinia digyna Rottler, Huberantha cerasoides (Roxb.) Benth), Oxyceros horridus Lour, Antidesma ghaesembilla Gaerth, Combretum quadrangulare Kurz, and Ziziphus cambodiana Pierre. The stem was also studied in comparison. The ethanolic extract from each plant part and the mixed plants mimicking the traditional formula were prepared and investigated for antioxidant capability in vitro via DPPH radical scavenging and ferric-reducing antioxidant power assays. The phytochemical constituents were determined by chemical screening, total phenolic (TPC) and flavonoid contents (TFC), and high-performance liquid chromatography. The relationship between antioxidant activity and the contributed phytochemicals was determined using correlation analysis and principal component analysis (PCA). Results showed that extracts from both parts of the plant formula showed the highest antioxidant activity compared to a single plant extract. Among the six plants, C. digyna exhibited the highest TPC and antioxidant activity. TPC had a strong positive correlation with antioxidant activity. PCA revealed that gallic acid contributed to the antioxidant activity. In conclusion, the ethanolic extracts of the traditional formula and C. digyna have the potential for further chemical characterization and study related to antioxidant activity.
Rimonabant and Cannabidiol Rewrite the Interactions between Breast Cancer Cells and Tumor Microenvironment
Authors: Proto Maria Chiara , Fiore Donatella , Bifulco Maurizio , Gazzerro Patrizia
Published: August 2023

The spread of breast cancer to distant sites is the major cause of death in breast cancer patients. Increasing evidence supports the role of the tumor microenvironment (TME) in breast cancers, and its pathologic assessment has become a diagnostic and therapeutic tool. In the TME, a bidirectional interplay between tumor and stromal cells occurs, both at the primary and metastatic site. Hundreds of molecules, including cytokines, chemokines, and growth factors, contribute to this fine interaction to promote tumor spreading. Here, we investigated the effects of Rimonabant and Cannabidiol, known for their antitumor activity, on reprogramming the breast TME. Both compounds directly affect the activity of several pathways involved in breast cancer progression. To mimic tumor–stroma interactions during breast-to-lung metastasis, we investigated the effect of the compounds on growth factor secretion from metastatic breast cancer cells and normal and activated lung fibroblasts. In this setting, we demonstrated the anti-metastatic potential of the two compounds, and the membrane array analyses highlighted their ability to alter the release of factors involved in the autocrine and paracrine regulation of tumor proliferation, angiogenesis, and immune reprogramming. The results enforce the antitumor potential of Rimonabant and Cannabidiol, providing a novel potential tool for breast cancer TME management.
Modeling Side Chains in the Three-Dimensional Structure of Proteins for Post-Translational Modifications
Authors: Petrovskiy Denis V. , Nikolsky Kirill S. , Rudnev Vladimir R. , Kulikova Liudmila I. , Butkova Tatiana V. , Malsagova Kristina A. , Kopylov Arthur T. , Kaysheva Anna L.
Published: August 2023

Amino acid substitutions and post-translational modifications (PTMs) play a crucial role in many cellular processes by directly affecting the structural and dynamic features of protein interaction. Despite their importance, the understanding of protein PTMs at the structural level is still largely incomplete. The Protein Data Bank contains a relatively small number of 3D structures having post-translational modifications. Although recent years have witnessed significant progress in three-dimensional modeling (3D) of proteins using neural networks, the problem related to predicting accurate PTMs in proteins has been largely ignored. Predicting accurate 3D PTM models in proteins is closely related to another fundamental problem: predicting the correct side-chain conformations of amino acid residues in proteins. An analysis of publications as well as the paid and free software packages for modeling three-dimensional structures showed that most of them focus on working with unmodified proteins and canonical amino acid residues; the number of articles and software packages placing emphasis on modeling three-dimensional PTM structures is an order of magnitude smaller. This paper focuses on modeling the side-chain conformations of proteins containing PTMs (nonstandard amino acid residues). We collected our own libraries comprising the most frequently observed PTMs from the PDB and implemented a number of algorithms for predicting the side-chain conformation at modification points and in the immediate environment of the protein. A comprehensive analysis of both the algorithms per se and compared to the common Rosetta and FoldX structure modeling packages was also carried out. The proposed algorithmic solutions are comparable in their characteristics to the well-known Rosetta and FoldX packages for the modeling of three-dimensional structures and have great potential for further development and optimization. The source code of algorithmic solutions has been deposited to and is available at the GitHub source.
Novel Insights into the Molecular Mechanisms of Atherosclerosis
Authors: Wojtasińska Armanda , Frąk Weronika , Lisińska Wiktoria , Sapeda Natalia , Młynarska Ewelina , Rysz Jacek , Franczyk Beata
Published: August 2023

Atherosclerosis is one of the most fatal diseases in the world. The associated thickening of the arterial wall and its background and consequences make it a very composite disease entity with many mechanisms that lead to its creation. It is an active process, and scientists from various branches are engaged in research, including molecular biologists, cardiologists, and immunologists. This review summarizes the available information on the pathophysiological implications of atherosclerosis, focusing on endothelium dysfunction, inflammatory factors, aging, and uric acid, vitamin D, and miRNA expression as recent evidence of interactions of the molecular and cellular elements. Analyzing new discoveries for the underlying causes of this condition assists the general research to improve understanding of the mechanism of pathophysiology and thus prevention of cardiovascular diseases.
TRIM67 Implicates in Regulating the Homeostasis and Synaptic Development of Mitral Cells in the Olfactory Bulb
Authors: Cai Chunyu , Luo Qihui , Jia Lanlan , Xia Yu , Lan Xinting , Wei Xiaoli , Shi Shuai , Liu Yucong , Wang Yao , Xiong Zongliang , Shi Riyi , Huang Chao , Chen Zhengli
Published: August 2023

In recent years, olfactory dysfunction has attracted increasingly more attention as a hallmark symptom of neurodegenerative diseases (ND). Deeply understanding the molecular basis underlying the development of the olfactory bulb (OB) will provide important insights for ND studies and treatments. Now, with a genetic knockout mouse model, we show that TRIM67, a new member of the tripartite motif (TRIM) protein family, plays an important role in regulating the proliferation and development of mitral cells in the OB. TRIM67 is abundantly expressed in the mitral cell layer of the OB. The genetic deletion of TRIM67 in mice leads to excessive proliferation of mitral cells in the OB and defects in its synaptic development, resulting in reduced olfactory function in mice. Finally, we show that TRIM67 may achieve its effect on mitral cells by regulating the Semaphorin 7A/Plexin C1 (Sema7A/PlxnC1) signaling pathway.
In Vitro Evaluation of Biological and Anticancer Activities Exhibited by Five Varieties of Vitis vinifera L.
Authors: Darwiche Linda , Mesmar Joelle , Baydoun Elias , El Kayal Walid
Published: August 2023

Vitis vinifera commonly known as grapevine is one of the most important fruit crops worldwide. Its cultivation started more than 7000 years ago in the Near East, and over the millennia was followed by the development of thousands of cultivars that were further selected and characterized for specific purposes. Its important pharmacological value and its richness in phytoconstituents were the triggers to perform this project. Seven extracts were prepared from five different V. vinifera varieties (V. vinifera ‘Black Pearl’ (BP), V. vinifera ‘Red Glob’ (RG), V. vinifera ‘Crimson’ (CR), V. vinifera ‘Beitamouni’ (BE) and V. vinifera ‘Superior’ (SU)) by separating the pulp from the seeds, followed by methanolic extraction. The phytochemical analysis showed that red colored grapes (RE, BP and CR), the seeds from V. vinifera ‘Black Pearl’ and V. vinifera ‘Red Globe’ contain higher amounts of primary and secondary metabolites such as polyphenols, anthocyanins and reducing sugars. In addition to their richness in phytoconstituents, these varieties/seeds possess an important antioxidant activity. The results of the cell viability assays showed that the red varieties have a potential anticancer activity against Capan-2 pancreatic cancer and MDA-MB231(TNBC) breast cancer cell lines, with the greatest promise when combined with the seeds.
Sex Differences in Glomerular Lesions, in Atherosclerosis Progression, and in the Response to Angiotensin-Converting Enzyme Inhibitors in the ApoE−/− Mice Model
Authors: Mallén Adrián , Rodriguez-Urquia Ronny , Alvarez Rafael , Dorca-Duch Eduard , Navarro Estanis , Hueso Miguel
Published: August 2023

This study analyzes sex-based differences in renal structure and the response to the Angiotensin-Converting Enzyme (ACE) inhibitor enalapril in a mouse model of atherosclerosis. Eight weeks old ApoE−/− mice received enalapril (5 mg/kg/day, subcutaneous) or PBS (control) for an additional 14 weeks. Each group consisted of six males and six females. Females exhibited elevated LDL-cholesterol levels, while males presented higher creatinine levels and proteinuria. Enalapril effectively reduced blood pressure in both groups, but proteinuria decreased significantly only in females. Plaque size analysis and assessment of kidney inflammation revealed no significant sex-based differences. However, males displayed more severe glomerular injury, with increased mesangial expansion, mesangiolysis, glomerular foam cells, and activated parietal epithelial cells (PECs). Enalapril mitigated mesangial expansion, glomerular inflammation (particularly in the female group), and hypertrophy of the PECs in males. This study demonstrates sex-based differences in the response to enalapril in a mouse model of atherosclerosis. Males exhibited more severe glomerular injury, while enalapril provided renal protection, particularly in females. These findings suggest potential sex-specific considerations for ACE inhibitor therapy in chronic kidney disease and atherosclerosis cardiovascular disease. Further research is needed to elucidate the underlying mechanism behind these observations.
Creation of Chemically Tri-Layered Collagen Crosslinked Membranes and Their Comparison with Ionically Tri-Layered Chitosan Crosslinked Membranes to Study Human Skin Properties
Authors: Galán-Navea Larry , Guerle-Cavero Rocío , Balfagón-Costa Albert , Artalejo-Ortega Beatriz
Published: August 2023

In 2009, a new European regulation came into force that forbade the use of animals in the cosmetics industry. As a result, new alternatives were sought, taking into account the new ethical considerations. The main objective of this article is to continue a line of research that aims to build a physical model of skin from a biomaterial scaffold composed of collagen, chitosan or a combination to investigate whether they offer similar behavior to human skin. Collagen, the major component in the dermis, was crosslinked with glutaraldehyde (GTA) to develop three formulations for studying some properties of the skin through rheological tests like swelling index, elasticity or water loss. In addition, this article makes a comparison with the results obtained in the previous article where the membranes were made of chitosan and tripolyphosphate (TPP). The results obtained highlight that the tri-layered membranes scaffold better than the mono-layered ones to increase the elastic modulus (G′) and the permeability. Furthermore, they offer a protective effect against water loss compared to mono-layered membranes. As regards chitosan membranes, these have a higher G′ modulus than collagen membranes when the degree of deacetylation (DDA) is 85%. However, collagen membranes are more elastic when the DDA of chitosan is 76%, and their linear viscoelastic limit (LVL) doubles that of chitosan membranes, both for the degree of acetylation of 76 and 85%.
CRISPR/Cas-Based Techniques for Live-Cell Imaging and Bioanalysis
Authors: Huang Shuo , Dai Rui , Zhang Zhiqi , Zhang Han , Zhang Meng , Li Zhangjun , Zhao Kangrui , Xiong Wenjun , Cheng Siyu , Wang Buhua , Wan Yi
Published: August 2023

CRISPR/Cas systems have found widespread applications in gene editing due to their high accuracy, high programmability, ease of use, and affordability. Benefiting from the cleavage properties (trans- or cis-) of Cas enzymes, the scope of CRISPR/Cas systems has expanded beyond gene editing and they have been utilized in various fields, particularly in live-cell imaging and bioanalysis. In this review, we summarize some fundamental working mechanisms and concepts of the CRISPR/Cas systems, describe the recent advances and design principles of CRISPR/Cas mediated techniques employed in live-cell imaging and bioanalysis, highlight the main applications in the imaging and biosensing of a wide range of molecular targets, and discuss the challenges and prospects of CRISPR/Cas systems in live-cell imaging and biosensing. By illustrating the imaging and bio-sensing processes, we hope this review will guide the best use of the CRISPR/Cas in imaging and quantifying biological and clinical elements and inspire new ideas for better tool design in live-cell imaging and bioanalysis.
Guidongnins I–J: Two New 6,7-seco-7,20-Olide-ent-kaurene Diterpenes with Unusual Structures from Isodon rubescens
Authors: Zou Juan , Ye Jianghai , Zhao Chenliang , Zhang Jingjie , Liu Yahua , Pan Lutai , He Kang , Zhang Hongjie
Published: August 2023

Two undescribed ent-kaurene diterpenes, named guidongnins I (1) and J (2), were isolated from the medicinal plant Isodon rubescens. Compound 1 was determined to contain an unprecedented 23 carbons in the skeleton by bearing an extra isopropyl group at C-17 out of the diterpenoid parent structure, and compound 2 was the first example of 6,7-seco-7,20-olide-ent-kaurenes with two fused-tetrahydrofuran rings formed between C-6 and C-19/C-20 through oxygen bridges. Their structures, including their absolute configurations, were determined using the analyses of the spectroscopic and X-ray diffraction data. Guidongnins I (1) and J (2) were assessed for their anti-cancer activities against the growth of various cancer cell lines, and 2 displayed cytotoxic potency against HepG2 at IC50 27.14 ± 3.43 μM.
Hydroxytyrosol–Donepezil Hybrids Play a Protective Role in an In Vitro Induced Alzheimer’s Disease Model and in Neuronal Differentiated Human SH-SY5Y Neuroblastoma Cells
Authors: Maiuolo Jessica , Costanzo Paola , Masullo Mariorosario , D’Errico Antonio , Nasso Rosarita , Bonacci Sonia , Mollace Vincenzo , Oliverio Manuela , Arcone Rosaria
Published: August 2023

Alzheimer’s disease (AD) is the most common neurodegenerative pathology among progressive dementias, and it is characterized by the accumulation in the brain of extracellular aggregates of beta-amyloid proteins and neurofibrillary intracellular tangles consisting of τ-hyperphosphorylated proteins. Under normal conditions, beta-amyloid peptides exert important trophic and antioxidant roles, while their massive presence leads to a cascade of events culminating in the onset of AD. The fibrils of beta-amyloid proteins are formed by the process of fibrillogenesis that, starting from individual monomers of beta-amyloid, can generate polymers of this protein, constituting the hypothesis of the “amyloid cascade”. To date, due to the lack of pharmacological treatment for AD without toxic side effects, chemical research is directed towards the realization of hybrid compounds that can act as an adjuvant in the treatment of this neurodegenerative pathology. The hybrid compounds used in this work include moieties of a hydroxytyrosol, a nitrohydroxytyrosol, a tyrosol, and a homovanillyl alcohol bound to the N-benzylpiperidine moiety of donepezil, the main drug used in AD. Previous experiments have shown different properties of these hybrids, including low toxicity and antioxidant and chelating activities. The purpose of this work was to test the effects of hybrid compounds mixed with Aβ 1–40 to induce fibrillogenesis and mimic AD pathogenesis. This condition has been studied both in test tubes and by an in vitro model of neuronal differentiated human SH-SY5Y neuroblastoma cells. The results obtained from test tube experiments showed that some hybrids inhibit the activity of the enzymes AChE, BuChE, and BACE-1. Cell experiments suggested that hybrids could inhibit fibrillogenesis, negatively modulating caspase-3. They were also shown to exert antioxidant effects, and the acetylated hybrids were found to be more functional and efficient than nonacetylated forms.