bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of the Structure and Bioactivity of Polysaccharides from Different Parts of Stemona tuberosa Lour
Authors: Qiu Xiang , Ou Yanghui , Lu Shengjia , Liang Yibin , Zhang Yali , Li Mengjie , Li Gang , Ma Hongwei , Wu Yanting , He Zhaoyu , Zhang Zhensheng , Yao Hongliang , Chen Wen-Hua
Published: March 2024

The polysaccharides from Stemona tuberosa Lour, a kind of plant used in Chinese herbal medicine, have various pharmacological activities, such as anti-inflammatory and antioxidant properties. However, the effects of the extraction methods and the activity of polysaccharides from different parts are still unknown. Therefore, this study aimed to evaluate the effects of different extraction methods on the yields, chemical compositions, and bioactivity of polysaccharides extracted from different parts of Stemona tuberosa Lour. Six polysaccharides were extracted from the leaves, roots, and stems of Stemona tuberosa Lour through the use of hot water (i.e., SPS-L1, SPS-R1, and SPS-S1) and an ultrasound-assisted method (i.e., SPS-L2, SPS-R2, and SPS-S2). The results showed that the physicochemical properties, structural properties, and biological activity of the polysaccharides varied with the extraction methods and parts. SPS-R1 and SPS-R2 had higher extraction yields and total sugar contents than those of the other SPSs (SPS-L1, SPS-L2, SPS-S1, and SPS-S2). SPS-L1 had favorable antioxidant activity and the ability to downregulate MUC5AC expression. An investigation of the anti-inflammatory properties showed that SPS-R1 and SPS-R2 had greater anti-inflammatory activities, while SPS-R2 demonstrated the strongest anti-inflammatory potential. The results of this study indicated that SPS-L1 and SPS-L2, which were extracted from non-medicinal parts, may serve as potent natural antioxidants, but further study is necessary to explore their potential applications in the treatment of diseases. The positive anti-inflammatory effects of SPS-R1 and SPS-R2 in the roots may be further exploited in drugs for the treatment of inflammation.
An Intronic Heterozygous SYNE2 Splice Site Mutation: A Rare Cause for Myalgia and hyperCKemia?
Authors: Paulus Theresa , Young Natalie , Jessop Emily , Berwanger Carolin , Clemen Christoph Stephan , Schröder Rolf , Ploski Rafal , Hagel Christian , Hellenbroich Yorck , Moser Andreas , Karakesisoglou Iakowos
Published: March 2024

SYNE2 mutations have been associated with skeletal and cardiac muscle diseases, including Emery-Dreifuss muscular dystrophy (EDMD). Here, we present a 70-year-old male patient with muscle pain and elevated serum creatine kinase levels in whom whole-exome sequencing revealed a novel heterozygous SYNE2 splice site mutation (NM_182914.3:c.15306+2T>G). This mutation is likely to result in the loss of the donor splice site in intron 82. While a diagnostic muscle biopsy showed unspecific myopathological findings, immunofluorescence analyses of skeletal muscle and dermal cells derived from the patient showed nuclear shape alterations when compared to control cells. In addition, a significantly reduced nesprin-2 giant protein localisation to the nuclear envelope was observed in patient-derived dermal fibroblasts. Our findings imply that the novel heterozygous SYNE2 mutation results in a monoallelic splicing defect of nesprin-2, thereby leading to a rare cause of myalgia and hyperCKemia.
Optical Limiting Response of Porous Carbon Dispersions
Authors: Gao Bo , Zhao Xuhui , Yan Lihe , Yang Lijiao , Zhang Yue , Lin Tao , Si Jinhai
Published: March 2024

With the wide application of intense lasers, the protection of human eyes and detectors from laser damage is becoming more and more strict. In this paper, we study the nonlinear optical limiting (OL) properties of porous carbon with a super large specific surface area (2.9 × 103 m2/g) using the nanosecond Z-scan technique. Compared to the traditional OL material C60, the porous carbon material shows an excellent broadband limiting effect, and the limiting thresholds correspond to 0.11 J/cm2 for 532 nm and 0.25 J/cm2 for 1064 nm pulses, respectively. The nonlinear scattering experiments showed that the OL behavior was mainly attributed to the nonlinear scattering effect, which is caused by the rapid growth and expansion of bubbles in the dispersion induced by laser irradiation, and the scattered light distribution is consistent with the results of Mie’s scattering. These results suggest that porous carbon materials are expected to be applied to the field of laser protection in the future to further protect the human eye and precision optical instruments.
Circulating miRNAs as Novel Clinical Biomarkers in Temporal Lobe Epilepsy
Authors: Guarnieri Lorenza , Amodio Nicola , Bosco Francesca , Carpi Sara , Tallarico Martina , Gallelli Luca , Rania Vincenzo , Citraro Rita , Leo Antonio , De Sarro Giovambattista
Published: March 2024

Temporal lobe epilepsy (TLE) represents the most common form of refractory focal epilepsy. The identification of innovative clinical biomarkers capable of categorizing patients with TLE, allowing for improved treatment and outcomes, still represents an unmet need. Circulating microRNAs (c-miRNAs) are short non-coding RNAs detectable in body fluids, which play crucial roles in the regulation of gene expression. Their characteristics, including extracellular stability, detectability through non-invasive methods, and responsiveness to pathological changes and/or therapeutic interventions, make them promising candidate biomarkers in various disease settings. Recent research has investigated c-miRNAs in various bodily fluids, including serum, plasma, and cerebrospinal fluid, of TLE patients. Despite some discrepancies in methodologies, cohort composition, and normalization strategies, a common dysregulated signature of c-miRNAs has emerged across different studies, providing the basis for using c-miRNAs as novel biomarkers for TLE patient management.
Betanin Attenuates Epigenetic Mechanisms and UV-Induced DNA Fragmentation in HaCaT Cells: Implications for Skin Cancer Chemoprevention
Authors: Zand Afshin , Enkhbilguun Sodbuyan , Macharia John M. , Varajti Krisztina , Szabó Istvan , Gerencsér Gellért , Tisza Boglárka Bernadett , Raposa Bence L. , Gyöngyi Zoltán , Varjas Timea
Published: March 2024

Dermal photoaging refers to the skin’s response to prolonged and excessive ultraviolet (UV) exposure, resulting in inflammation, changes to the tissue, redness, swelling, and discomfort. Betanin is the primary betacyanin in red beetroot (Beta vulgaris) and has excellent antioxidant properties. Yet, the specific molecular mechanisms of betanin in HaCaT cells have not been fully clarified. The objective of this study was to investigate the activity of betanin and the underlying mechanisms in HaCaT cells; furthermore, in this study, we explored the protective effect of various concentrations of betanin against UVB irradiation on HaCaT cells. Additionally, we assessed its influence on the transcription of various epigenetic effectors, including members of the DNA methyltransferase (DNMT) and histone deacetylase (HDAC) families. Our findings demonstrate a notable downregulation of genes in HaCaT cells, exhibiting diverse patterns upon betanin intake. We considered the involvement of DNMT and HDAC genes in distinct stages of carcinogenesis and the limited exploration of the effects of daily exposure dosages. Our results indicate that betanin may protect the skin from damage caused by UV exposure. Further investigation is essential to explore these potential associations.
Investigating the Metabolism of Estrogens in Ligilactobacillus salivarius Strains Isolated from Human Milk and Vaginal Microbiota
Authors: Aragón Alberto , Jurado Rubén , Jara Josué , Rodríguez Juan Miguel , Orgaz Belén
Published: March 2024

The interplay between enterohepatic circulation and the gut microbiota is the main driver determining systemic levels of estrogens and their metabolites. Nevertheless, the role of potentially probiotic microorganisms in estrogen metabolism has not been investigated so far. In this work, we have explored the ability of six Ligilactobacillus salivarius strains isolated from human milk and vaginal samples to degrade and/or conjugate parental estrogens in vitro and under aerobic conditions. The quantification of estrogens and their derivatives was carried out in cell-free supernatants by LC-QQQ-MS. All the tested L. salivarius strains achieved an average degradation rate of estrone and estriol of 98% and 55%, respectively, whereas 17β-estradiol was preferentially conjugated (up to 40%). The presence of seven out of ten genes encoding enzymes relevant for estrogen metabolism was further confirmed by PCR, highlighting their genetic potential for degrading, conjugating and/or deconjugating estrogens. The tested L. salivarius strains may be considered potential probiotics affecting the fate of endogenous estrogens. Clinical trials targeting populations with estrogen-dependent conditions will be required to elucidate the true potential of these strains for the restoration and maintenance of a healthy host estrobolome.
Exploring the Role of Serum Osteonectin and Hsp27 in Pediatric MAFLD Diagnosis and Cardiometabolic Health
Authors: Bălănescu Anca , Bălănescu Paul-Cristian , Codreanu Ioana Florentina , Stan Iustina-Violeta , Comanici Valentina-Daniela , Robu Alina Maria , Ciomârtan Tatiana
Published: March 2024

Background: Childhood obesity is one of the major challenges of public health policies. The problem of fatty liver in childhood, known as MAFLD (metabolic dysfunction-associated fatty liver disease), is of particular interest as the gold standard diagnosis technique is invasive (liver biopsy). Hence, efforts are made to discover more specific biomarkers for the MAFLD signature. Therefore, the aim of the study was to evaluate Osteonectin and Hsp27 as biomarkers for MAFLD diagnosis and to assess their links with auxological and biochemical profiles of overweight and obese pediatric subjects. Methods: A cross-sectional study in which we (re)analyzed data from the MR PONy cohort comprising 71 pediatric subjects. Auxological data, liver ultrasonography and biochemical serum profile were recorded. Lipid-derived indices and body composition indices were calculated. Nevertheless, serum Osteonectin and Hsp27 levels were assessed using an ELISA approach. Results: MAFLD prevalence was 40.8%. Higher Osteonectin levels were noted in MAFLD subjects versus non-MAFLD subjects and in dyslipidemic children regardless of their liver function status. Lipid-derived indices had good diagnostic capacity for MAFLD. Conclusions: We confirm Osteonectin as a MAFLD diagnosis biomarker in children. Also, lipid-derived indices are useful as metabolic-associated organ impairment markers in children even before the onset of obesity.
Adherence to the Planetary Health Diet and Its Association with Diet Quality in the Young Adult Population of Türkiye: A Large Cross-Sectional Study
Authors: Mortaş Hande , Navruz-Varlı Semra , Bilici Saniye
Published: March 2024

To advance both human health and environmental sustainability, it’s crucial to assess the adaptation to new dietary trends emerging in this field. This study aimed to explore the relationship between diet quality and the principles of planetary health diet in young adults studying at university. This cross-sectional study consisted of 945 young adults with a mean age of 20.1 ± 1.34 y (582 females, 363 males). A questionnaire form containing socio-demographic information (age, gender, education level), anthropometric measurements (body weight and height), and a 24 h dietary record form for three consecutive days was applied. The scores of the Planetary Health Diet Index (PHDI) and the Healthy Eating Index-2020 (HEI-2020) were calculated according to the dietary records. The mean total scores of the PHDI and HEI-2020 were 59.9 ± 14.16 and 54.2 ± 10.87, respectively. The association between the HEI-2020 score and the PHDI score was significant (p = 0.003). A one-unit increase in the unadjusted HEI-2020 score caused a 0.429 unit decrease in the PHDI score (95% CI: −0.709; −0.149). The findings underscore the imperative for targeted interventions and educational programs to enhance the PHDI and HEI-2020 scores, promoting individual well-being and environmental sustainability in the university.
Glycomacropeptide as an Efficient Agent to Fight Pathophysiological Mechanisms of Metabolic Syndrome
Authors: Sauvé Mathilde Foisy , Feldman Francis , Sané Alain Théophile , Koudoufio Mireille , Patey Natalie , Spahis Schohraya , Butcher James , Duan Haonan , Figeys Daniel , Marcil Valérie , Stintzi Alain , Levy Emile
Published: March 2024

There is currently a growing interest in the use of nutraceuticals as a means of preventing the development of complex diseases. Given the considerable health potential of milk-derived peptides, the aim of this study was to investigate the protective effects of glycomacropeptide (GMP) on metabolic syndrome. Particular emphasis was placed on the potential mechanisms mitigating cardiometabolic disorders in high-fat, high-fructose diet-fed mice in the presence of GMP or Bipro, an isocaloric control. The administration of GMP for 12 weeks reduced obesity, hyperglycemia and hyperinsulinemia caused by a high-fat, high-fructose diet, resulting in a decline in insulin resistance. GMP also lessened systemic inflammation, as indicated by decreased circulating inflammatory cytokines. In the intestinal and hepatic tissues, GMP improved homeostasis by increasing insulin sensitivity and attenuating high-fat, high-fructose-induced inflammation, oxidative stress and endoplasmic reticulum stress. Biochemical and histological analyses revealed improved hepatic steatosis and fatty acid composition in the livers of high-fat, high-fructose diet-fed mice treated with GMP compared to Bipro. A trend toward a decrease in bile acids without any marked changes in intestinal microbiota composition characterized GMP-treated animals compared to those administered Bipro. GMP offers considerable potential for fighting metabolic syndrome-related components and complications given its beneficial effects on risk factors such as inflammation, oxidative stress and endoplasmic reticulum stress without involving the intestinal microbiota.
Ferroptosis Altered microRNAs Expression in HT-1080 Fibrosarcoma Cells Based on Small RNA Sequencing and Bioinformatics Analysis
Authors: Zhang Qian , Wang Qiwen , Ding Haoxuan , Hu Caihong , Feng Jie
Published: March 2024

Iron is an essential trace element in the human body. However, excess iron is harmful and may cause ferroptosis. The expression and role of microRNAs (miRNAs) in ferroptosis remain largely unknown. A model of ferroptosis induced by ferric ammonium citrate in HT-1080 cells was established in this study. The miRNAs expression profiles of the control and iron groups were obtained using small RNA sequencing and verified using qRT-PCR. A total of 1346 known miRNAs and 80 novel miRNAs were identified, including 12 up-regulated differentially expressed miRNAs (DE-miRNAs) and 16 down-regulated DE-miRNAs. SP1 was the most important upstream transcription factor regulating DE-miRNAs. The downstream target genes of DE-miRNAs were predicted based on miRDB, TargetScan, and miRBase databases, and 403 common target genes were screened. GO annotation and KEGG analysis revealed that the target genes were mainly involved in various biological processes and regulatory pathways, especially the MAPK signaling pathway and PI3K-Akt signaling pathway. Afterwards, a target genes network was constructed using STRING and Cytoscape, and the hub genes were compared with the ferroptosis database (FerrDb V2) to discover the hub genes related to ferroptosis. EGFR, GSK3B, PARP1, VCP, and SNCA were screened out. Furthermore, a DE-miRNAs-target genes network was constructed to explore key DE-miRNAs. hsa-miR-200c-3p, hsa-miR-26b-5p, and hsa-miR-7-5p were filtered out. Comprehensive bioinformatics analysis of miRNAs and its upstream and downstream regulation in ferroptosis in HT-1080 cells using small RNA sequencing is helpful for understanding the role of miRNAs in iron overload-related diseases and ferroptosis-targeted therapy for cancer.
Dietary Intakes of Long-Chain Polyunsaturated Fatty Acids and Impulsivity: Comparing Non-Restricted, Vegetarian, and Vegan Diets
Authors: Byrne Mitchell K. , Cook Rebecca , Murta Janina C. D. , Bressington Daniel , Meyer Barbara J.
Published: March 2024

Background: Research suggests a link between deficiencies in omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) and impulsivity among psychiatric populations. However, this association is less evident in non-clinical populations. As omega-3 LCPUFAs are predominantly sourced through fish consumption, non-fish dieters may be more vulnerable to higher impulsivity. Methods: This cross-sectional observational study explored the association between lower intakes of omega-3 LCPUFA food sources and higher self-reported measures of impulsivity among healthy adults consuming non-restricted, vegetarian, and vegan diets. Results: The results from the validated Food Frequency Questionnaire showed significantly lower estimated omega-3 LCPUFA intakes among vegans and vegetarians when compared with people consuming non-restricted diets. Furthermore, although all groups scored within the normal range of impulsivity measures, vegans scored comparatively higher. Vegans also scored significantly higher in impulsivity control relating to attention than those consuming non-restricted diets. Conclusions: The significantly lower omega-3 LCPUFA dietary intakes in the vegan diets were associated with higher scores in the second-order attentional aspect of self-reported impulsiveness.
Time-Restricted Eating and Bone Health: A Systematic Review with Meta-Analysis
Authors: Fernández-Rodríguez Rubén , Garrido-Miguel Miriam , Bizzozero-Peroni Bruno , Díaz-Goñi Valentina , Rodríguez-Gutiérrez Eva , Guzmán-Pavón María José , Meseguer-Henarejos Ana Belén , Torres-Costoso Ana
Published: March 2024

Time-restricted eating (TRE) has emerged as a dietary strategy that restricts food consumption to a specific time window and is commonly applied to facilitate weight loss. The benefits of TRE on adipose tissue have been evidenced in human trials and animal models; however, its impact on bone tissue remains unclear. To systematically synthesize and examine the evidence on the impact of TRE on bone health (bone mineral content (BMC), bone mineral density (BMD), and bone turnover factors), PubMed, Scopus, Cochrane CENTRAL, and Web of Science databases were systematically explored from inception to 1 October 2023 searching for randomized controlled trials (RCTs) aimed at determining the effects of TRE on bone health in adults (≥18 years). The Cochrane Handbook and the PRISMA recommendations were followed. A total of seven RCTs involving 313 participants (19 to 68 years) were included, with an average length of 10.5 weeks (range: 4 to 24 weeks). Despite the significant weight loss reported in five out of seven studies when compared to the control, our meta-analysis showed no significant difference in BMD (g/cm2) between groups (MD = −0.009, 95% CI: −0.026 to 0.009, p = 0.328; I2 = 0%). BMC and bone turnover markers between TRE interventions and control conditions were not meta-analyzed because of scarcity of studies (less than five). Despite its short-term benefits on cardiometabolic health, TRE did not show detrimental effects on bone health outcomes compared to those in the control group. Nevertheless, caution should be taken when interpreting our results due to the scarcity of RCTs adequately powered to assess changes in bone outcomes.
Role of Dietary Factors on DNA Methylation Levels of TNF-Alpha Gene and Proteome Profiles in Obese Men
Authors: Boonrong Chayanisa , Roytrakul Sittiruk , Shantavasinkul Prapimporn Chattranukulchai , Sritara Piyamitr , Sirivarasai Jintana
Published: March 2024

Integrated omics-based platforms from epigenomics and proteomics technologies are used to identify several important mechanisms in obesity etiology, food components, dietary intake, regulation of biological pathways, and potential new intervention targets. Therefore, this study aimed to analyze whether dietary factors involved in the methylation of tumor necrosis factor (TNF)-α are implicated in differential protein expression in people with normal weight and obesity. Methods: The participants were classified into the non-obese (N = 100) and obese (N = 133) groups. DNA methylation levels of the TNF-alpha gene and proteomics were analyzed using the pyrosequencing method and LC-MS-MS, respectively. Results: Comparison between geometric means of DNA methylation of TNF-α showed lower levels in subjects with obesity than in those without obesity (p < 0.05). There were associations between dietary factors and some metabolic syndrome components and TNF-α DNA methylation levels. Proteomic analysis showed important signaling pathways related to obesity, with 95 significantly downregulated proteins and 181 upregulated proteins in the non-obese group compared with the obese group. Conclusion: This study shows an association between the dietary factors involved in the methylation of TNF-α and differential protein expression related to obesity. However, a large sample size in future studies is required to confirm our results.
Mental Health Nursing Student’s Perception of Clinical Simulation about Patients at Risk of Suicide: A Qualitative Study
Authors: Del Pozo-Herce Pablo , Tovar-Reinoso Alberto , Martínez-Sabater Antonio , Chover-Sierra Elena , Pacheco-Tabuenca Teresa , Carrasco-Yubero Jorge , Sánchez-González Juan Luis , González-Fernández Silvia , Santolalla-Arnedo Iván , Sufrate-Sorzano Teresa , Juárez-Vela Raúl , García-Carpintero Blas Eva
Published: March 2024

Suicide is a serious public health problem, with a global mortality rate of 1.4% of all deaths worldwide and the leading cause of unnatural death in Spain. Clinical simulation has proven to be a beneficial tool in training nursing students. Such experiences allow them to develop cognitive and affective skills that are fundamental for the detection of warning signs and the use of interventions in cases of people who want to take their own lives. Working in a mental health environment can be difficult for nursing students; therefore, the purpose of this study was to explore the perceptions of nursing students on the approach, management, and intervention of suicidal crisis through clinical mental health simulation. Methods: qualitative descriptive phenomenological study through focus groups and reflective narratives in a sample of 45 students. A thematic analysis was performed using ATLAS-ti. Results: After the analysis, three themes were obtained: (a) management and handling of emotions, (b) identification of suicide motives, and (c) intervention in suicidal crisis. Discussion: Clinical simulation in mental health allows students to exercise clinical judgment reasoning, detect warning signs for a better treatment approach, and provide tools for effective intervention and management of patient care. The results of this study indicate that nursing students face challenges in approaching mental health clinical simulation due to a lack of prior exposure.
Investigation of the In Vitro Immunomodulatory Effects of Extracts from Green-Lipped Mussels (Perna canaliculus)
Authors: Lessa Roberta Cardim , Ebrahimi Belgheis , Li Hui , Guan Xiao , Li Yan , Lu Jun
Published: March 2024

The immune system plays a crucial role in defending the body against foreign invaders, and the balance of various polyunsaturated fatty acids, such as alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), can impact immune cell functions and overall immune responses. This study aimed to assess the effectiveness of mussel oil extracts in modulating inflammatory responses by analysing their effects on immune cell lines and cytokine expression. Four different mussel oil extracts were obtained using two extraction methods (organic solvent and supercritical CO2 extraction) from two tissue sources (fresh and commercial). These extracts were then tested at various concentrations on T lymphocyte (Jurkat) cells, monocytes, and macrophages (THP-1 and U-937). Cytokine levels were quantified using ELISA. The results showed that the solvent-extracted samples had a dose-dependent effect on tumour necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) cytokine secretion in THP-1 and U937 cells, with the extract from a commercial mussel powder being more efficient than the extract from fresh powder. However, supercritical CO2 samples showed elevated cytokine secretion levels despite their high omega-3 content. Furthermore, 100 ug/mL extract from fresh powder successfully reduced interleukin-2 (IL-2) secretion while maintaining cell viability after stimulation. The study demonstrated that solvent-extracted mussel oil can effectively regulate cytokine secretion, modulate immune cell activation, and alleviate inflammation. These findings offer valuable insights into using mussel oil extracts to treat inflammatory disorders and enhance immune responses.
The Re-Emergence of Rift Valley Fever in Mananjary District, Madagascar in 2021: A Call for Action
Authors: Harimanana Aina Nirina , Andriamandimby Soa Fy , Ranoaritiana Dany Bakoly , Randrianasolo Laurence , Irinantenaina Judickaelle , Ranoelison Nirina Nantenaina , Rafisandrantatsoa Jean Théophile , Ankasitrahana Miamina Fidy , Raherinandrasana Antso Hasina , Andriamahatana Manuela Vololoniaina , Tantely Michael Luciano , Girod Romain , Dussart Philippe , Lacoste Vincent , Randremanana Rindra Vatosoa
Published: March 2024

An epizootic of rift valley fever (RVF) was suspected on 21 February 2021 in various districts of Madagascar, with a lab confirmation on 1 April 2021. A cross-sectional survey aiming to detect cases of RVF in humans and to study the circulation of rift valley fever virus (RVFV) in animals was conducted from 22 April to 4 May 2021 in the district of Mananjary. Blood samples from cattle and humans were tested using serological and molecular techniques. In cattle, the circulation of RVFV was confirmed between 5 February and 4 May 2021. The positivity rates of anti-RVFV IgG and IgM were 60% and 40%, respectively. In humans, the circulation of RVFV was observed from 1 April to 5 May 2021. The positivity rate of RVFV was estimated to be 11.7% by combining the results of the molecular and serological approaches. Of the 103 individuals who agreed to participate in the survey, 3 were determined to be positive by RT-PCR, and 10 had anti-RVFV IgM. Among them, one was positive for both. Given that previous studies have reported the circulation of RVFV during inter-epidemic periods and the occurrence of outbreaks due to imported RVFV in Madagascar, our findings suggest the importance of strengthening RVF surveillance from a “One Health” perspective by conducting syndromic and risk-based surveillance at the national and regional levels.
Comparison of Glutathione Nanoparticles, CoEnzyme Q10, and Fish Oil for Prevention of Oxygen-Induced Retinopathy in Neonatal Rats
Authors: Bashir Sidra , Cai Charles L. , Marcelino Matthew , Aranda Jacob V. , Beharry Kay D.
Published: March 2024

Notch ligands and receptors are important for cell specification and angiogenesis, but their role in oxygen-induced retinopathy (OIR) is not well studied. Delta-like ligand (DLL)-4/Notch inhibits angiogenesis, while Jagged-1/Notch promotes angiogenesis. We tested the hypothesis that early supplementation with antioxidants and/or fish oil curtails severe OIR by inducing DLL-4/Notch and reducing Jagged-1/Notch. Newborn rats were exposed to brief intermittent hypoxia (IH) during hyperoxia, during which they received daily oral supplements of (1) fish oil, (2) coenzyme Q10 (CoQ10) in olive oil (OO), (3) glutathione nanoparticles (nGSH), (4) fish oil + CoQ10, or (5) OO (controls) from birth (P0) to P14. At P14, the pups were placed in room air (RA) until P21, with no further treatment. Oxidative stress, apoptosis, ocular histopathology, and Notch signaling were assessed. Neonatal IH resulted in severe retinal damage consistent with retinopathy of prematurity (ROP). Retinal damage was associated with induced oxidative stress and Jagged-1/Notch signaling, as well as reduced DLL-4/Notch signaling. All treatments reversed these outcomes, but nGSH produced the most beneficial outcomes. Severe OIR promoted the induction of Jagged-1/Notch and curtailed DLL-4/Notch, which was an effect that could be reversed with nGSH supplementation. These findings may indicate a potential alternate pathway for ROP treatment and/or prevention.
Absorption Distribution Metabolism Excretion and Toxicity Property Prediction Utilizing a Pre-Trained Natural Language Processing Model and Its Applications in Early-Stage Drug Development
Authors: Jung Woojin , Goo Sungwoo , Hwang Taewook , Lee Hyunjung , Kim Young-Kuk , Chae Jung-woo , Yun Hwi-yeol , Jung Sangkeun
Published: March 2024

Machine learning techniques are extensively employed in drug discovery, with a significant focus on developing QSAR models that interpret the structural information of potential drugs. In this study, the pre-trained natural language processing (NLP) model, ChemBERTa, was utilized in the drug discovery process. We proposed and evaluated four core model architectures as follows: deep neural network (DNN), encoder, concatenation (concat), and pipe. The DNN model processes physicochemical properties as input, while the encoder model leverages the simplified molecular input line entry system (SMILES) along with NLP techniques. The latter two models, concat and pipe, incorporate both SMILES and physicochemical properties, operating in parallel and with sequential manners, respectively. We collected 5238 entries from DrugBank, including their physicochemical properties and absorption, distribution, metabolism, excretion, and toxicity (ADMET) features. The models’ performance was assessed by the area under the receiver operating characteristic curve (AUROC), with the DNN, encoder, concat, and pipe models achieved 62.4%, 76.0%, 74.9%, and 68.2%, respectively. In a separate test with 84 experimental microsomal stability datasets, the AUROC scores for external data were 78% for DNN, 44% for the encoder, and 50% for concat, indicating that the DNN model had superior predictive capabilities for new data. This suggests that models based on structural information may require further optimization or alternative tokenization strategies. The application of natural language processing techniques to pharmaceutical challenges has demonstrated promising results, highlighting the need for more extensive data to enhance model generalization.
Effect of Matricaria aurea Essential Oils on Biofilm Development, Virulence Factors and Quorum Sensing-Dependent Genes of Pseudomonas aeruginosa
Authors: Qaralleh Haitham , Saghir Sultan Ayesh Mohammed , Al-limoun Muhamad O. , Dmor Saif M. , Khleifat Khaled , Al-Ahmad Basma Ezzat Mustafa , Al-Omari Laila , Tabana Yasser , Mothana Ramzi A. , Al-Yousef Hanan M. , Alqahtani Abdulaziz M.
Published: March 2024

The emergence of drug-resistant microorganisms presents a substantial global public health threat. The increase in pathogens resistant to commonly prescribed antibiotics underscores the urgent requirement to explore alternative treatment strategies. This study adopts a novel approach by harnessing natural resources, specifically essential oils (EO), to combat bacterial pathogenicity. The primary aim of this research was to analyze the chemical composition of the aerial part of the Matricaria aurea (M. aureas) EO and evaluate its potential for inhibiting quorum sensing (QS) and disrupting biofilm formation in Pseudomonas aeruginosa (P. aeruginosa). The gas chromatography-mass spectrometry (GCMS) analysis unveiled that α-bisabolol oxide A constituted the predominant portion, comprising 64.8% of the total, with β-bisabolene at 6.3% and α-farnesene at 4.8% following closely behind. The antibiofilm efficacy was observed at concentrations of 0.3, 0.15, and 0.08 mg/mL, demonstrating negligible effects on cell viability. Furthermore, the EO from M. aurea effectively inhibited the formation of P. aeruginosa biofilms by diminishing aggregation, hydrophobicity, and swarming motility. Significantly, the EO treatment resulted in a conspicuous decrease in the production of pyocyanin, rhamnolipid, and extracellular polymeric substances (EPS), along with a reduction in the enzymatic activity of protease and chitinase. The EO effectively hindered QS by disrupting QS mechanisms, resulting in a marked decline in the secretion of N-Acyl homoserine lactone (AHL) molecules and the expression of phazA1 and aprA genes. This investigation offers compelling evidence supporting the potential of M. aurea EO as a promising therapeutic candidate for addressing infectious diseases induced by biofilm formation.
Target Development towards First Production of High-Molar- Activity 44gSc and 47Sc by Mass Separation at CERN-MEDICIS
Authors: Mamis Edgars , Duchemin Charlotte , Berlin Valentina , Bernerd Cyril , Bovigny Mathieu , Chevallay Eric , Crepieux Bernard , Gadelshin Vadim Maratovich , Heinke Reinhard , Hernandez Ronaldo Mendez , Johnson Jake David , Kalniņa Patrīcija , Koliatos Alexandros , Lambert Laura , Rossel Ralf Erik , Rothe Sebastian , Thiboud Julien , Weber Felix , Wendt Klaus , Zabolockis Rudolfs Jānis , Pajuste Elīna , Stora Thierry
Published: March 2024

The radionuclides 43Sc,  44g/mSc, and 47Sc can be produced cost-effectively in sufficient yield for medical research and applications by irradiating  natTi and  natV target materials with protons. Maximizing the production yield of the therapeutic 47Sc in the highest cross section energy range of 24–70 MeV results in the co-production of long-lived, high-γ-ray-energy 46Sc and 48Sc contaminants if one does not use enriched target materials. Mass separation can be used to obtain high molar activity and isotopically pure Sc radionuclides from natural target materials; however, suitable operational conditions to obtain relevant activity released from irradiated  natTi and  natV have not yet been established at CERN-MEDICIS and ISOLDE. The objective of this work was to develop target units for the production, release, and purification of Sc radionuclides by mass separation as well as to investigate target materials for the mass separation that are compatible with high-yield Sc radionuclide production in the 9–70 MeV proton energy range. In this study, the in-target production yield obtained at MEDICIS with 1.4 GeV protons is compared with the production yield that can be reached with commercially available cyclotrons. The thick-target materials were irradiated at MEDICIS and comprised of metallic  natTi,  natV metallic foils, and  natTiC pellets. The produced radionuclides were subsequently released, ionized, and extracted from various target and ion source units and mass separated. Mono-atomic Sc laser and molecule ionization with forced-electron-beam-induced arc-discharge ion sources were investigated. Sc radionuclide production in thick  natTi and  natV targets at MEDICIS is equivalent to low- to medium-energy cyclotron-irradiated targets at medically relevant yields, furthermore benefiting from the mass separation possibility. A two-step laser resonance ionization scheme was used to obtain mono-atomic Sc ion beams. Sc radionuclide release from irradiated target units most effectively could be promoted by volatile scandium fluoride formation. Thus, isotopically pure  44g/mSc, 46Sc, and 47Sc were obtained as mono-atomic and molecular ScF 2+ ion beams and collected for the first time at CERN-MEDICIS. Among all the investigated target materials,  natTiC is the most suitable target material for Sc mass separation as molecular halide beams, due to high possible operating temperatures and sustained release.
Nanomedicine for the Treatment of Viral Diseases: Smaller Solution to Bigger Problems
Authors: Ghorai Suvankar , Shand Harshita , Patra Soumendu , Panda Kingshuk , Santiago Maria J. , Rahman Md. Sohanur , Chinnapaiyan Srinivasan , Unwalla Hoshang J.
Published: March 2024

The continuous evolution of new viruses poses a danger to world health. Rampant outbreaks may advance to pandemic level, often straining financial and medical resources to breaking point. While vaccination remains the gold standard to prevent viral illnesses, these are mostly prophylactic and offer minimal assistance to those who have already developed viral illnesses. Moreover, the timeline to vaccine development and testing can be extensive, leading to a lapse in controlling the spread of viral infection during pandemics. Antiviral therapeutics can provide a temporary fix to tide over the time lag when vaccines are not available during the commencement of a disease outburst. At times, these medications can have negative side effects that outweigh the benefits, and they are not always effective against newly emerging virus strains. Several limitations with conventional antiviral therapies may be addressed by nanotechnology. By using nano delivery vehicles, for instance, the pharmacokinetic profile of antiviral medications can be significantly improved while decreasing systemic toxicity. The virucidal or virus-neutralizing qualities of other special nanomaterials can be exploited. This review focuses on the recent advancements in nanomedicine against RNA viruses, including nano-vaccines and nano-herbal therapeutics.
Fundamentals and Applications of Focused Ultrasound-Assisted Cancer Immune Checkpoint Inhibition for Solid Tumors
Authors: Jahangiri Sepideh , Yu François
Published: March 2024

Despite spectacular clinical successes across several cancer types, immune checkpoint inhibition is effective only in subgroups of patients and suffers from significant systemic toxicities, highlighting the need to understand and locally overcome the mechanisms of therapeutic resistance. Similarly to other therapeutics, immunotherapies face delivery challenges (for example, antibodies need to reach their targets) and immunological barriers that are unique to solid tumors and their microenvironment. Interestingly, focused ultrasound (FUS), with or without microbubbles, which has been shown to enhance gene and drug delivery, notably in oncology, has been recently found to trigger immunological responses. In recent years, there has been a strong emphasis on understanding the biological and immunological effects of FUS for cancer therapy, and FUS is now emerging as an approach that can improve cancer immunotherapy. We herein review: (1) the immunological barriers implicated in ICI resistance; (2) the fundamentals of FUS +/− MB and the current knowledge on leveraging FUS +/− MB bioeffects for improving ICI therapy efficacy; (3) the immune profile of tumor models that have been successfully treated with FUS and ICI; and finally, (4) we discuss the challenges ahead for translating FUS and MB treatments to the clinic, highlighting the exciting perspectives for this new research area.
Trypanocidal and Anti-Inflammatory Effects of Three ent-Kaurane Diterpenoids from Gymnocoronis spilanthoides var. subcordata (Asteraceae)
Authors: Selener Mariana G. , Borgo Jimena , Sarratea Maria Belen , Delfino Maria Alicia , Laurella Laura C. , Cerny Natacha , Gomez Jessica , Coll Mauro , Malchiodi Emilio L. , Bivona Augusto E. , Barrera Patricia , Redko Flavia C. , Catalán César A. N. , Alberti Andrés Sánchez , Sülsen Valeria P.
Published: March 2024

Chagas disease, caused by the protozoan Trypanosoma cruzi, affects 6–7 million people worldwide. The dichloromethane extract obtained from the aerial parts of Gymnocoronis spilanthoides var subcordata showed trypanocidal activity in vitro. The fractionation of the dewaxed organic extract via column chromatography led to the isolation of three diterpenoids: ent-9α,11α-dihydroxy-15-oxo-kaur-16-en-19-oic acid or adenostemmoic acid B, (16R)-ent-11α-hydroxy-15-oxokauran-19-oic acid and ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic acid. These compounds showed IC50 values of 10.6, 15.9 and 4.8 µM against T. cruzi epimastigotes, respectively. When tested against amastigotes, the diterpenoids afforded IC50 values of 6.1, 19.5 and 60.6 µM, respectively. The cytotoxicity of the compounds was tested on mammalian cells using an MTT assay, resulting in CC50s of 321.8, 23.3 and 14.8 µM, respectively. The effect of adenostemmoic acid B on T. cruzi was examined at the ultrastructural level using transmission microscopy. Treatment with 20 μM for 48 h stimulated the formation of abnormal cytosolic membranous structures in the parasite. This compound also showed an anti-inflammatory effect in murine macrophages stimulated with LPS and other TLR agonists. Treatment of macrophages with adenostemmoic acid B was able to reduce TNF secretion and nitric oxide production, while increasing IL-10 production. The combination of adenostemmoic acid B with benznidazole resulted in greater inhibition of NF-kB and a decrease in nitrite concentration. The administration of adenostemmoic acid B to mice infected with trypomastigotes of T. cruzi at the dose of 1 mg/kg/day for five days produced a significant decrease in parasitemia levels and weight loss. Treatment with the association with benznidazole increased the survival time of the animals. In view of these results, adenostemmoic acid B could be considered a promising candidate for further studies in the search for new treatments for Chagas disease.
Medication Lubricants for Oral Delivery of Drugs: Oral Processing Reduces Thickness, Changes Characteristics, and Improves Dissolution Profile
Authors: Malouh Marwa A. , Cichero Julie A. Y. , Sun Yu , Lau Esther T. L. , Nissen Lisa M. , Steadman Kathryn J.
Published: March 2024

Swallowing oral solid dosage forms is challenging for those who have medication swallowing difficulties, including patients with dysphagia. One option is to mix the drug (whole or crushed) with a thick vehicle (medication lubricant). Previous in vitro studies consistently suggest that thick vehicles could impact the dissolution of solid dosage forms, potentially influencing their therapeutic effectiveness, but do not account for changes that happen during oral processing and swallowing. This study aims to investigate the potential impact of medication lubricants on drug release and examine the effect of oral processing. In vitro dissolution of whole and crushed paracetamol tablets mixed with five commercially available medication lubricants (two IDDSI level 2, two IDDSI level 3, and one IDDSI level 4) were tested with and without oral processing; a medication lubricant with/without paracetamol was placed in the mouth (five healthy volunteers), prepared for swallowing, but then expectorated and assessed for physical characteristics and drug release. Medication lubricants, both alone and mixed with crushed paracetamol tablets, showed a significant decrease in viscosity after oral processing. Without oral processing, IDDSI level 3 and 4 lubricants significantly delayed the dissolution of paracetamol tablets. After oral processing, particularly with crushed tablets, there was a substantial increase in the dissolution rate. These findings suggest that dissolution testing overestimates the impact of medication lubricants on drug dissolution. Therefore, using in vitro dissolution tests to predict the dissolution rate of medications mixed with thick vehicles is discouraged. It is essential to consider ways to incorporate the effects of the oral environment and oral processing on thick vehicles used for oral medication administration.
Comparative Evaluation of Transient Protein Expression Efficiency in Tissues across Soybean Varieties Using the Tsukuba System
Authors: Fuhrmann-Aoyagi Martina Bianca , Igarashi Saki , Miura Kenji
Published: March 2024

Transient protein expression is a versatile tool with diverse applications and can be used in soybeans to study gene function, obtain mutants, and produce proteins for commercial use. However, soybeans are considered recalcitrant for agroinfiltration. Subsequent studies on soybeans have demonstrated a green fluorescent protein (GFP) expression in seedpods, but not in leaves, using syringe agroinfiltration. To evaluate agroinfiltration-based transient protein expression levels in plant cells, we used the transient expression vector pTKB3 harboring the GFP gene. Using Agrobacterium tumefaciens, vacuum agroinfiltration of the leaves and needle agroinfiltration of the seedlings of different soybean varieties were performed. GFP was transiently expressed in all of the samples. However, the Enrei and Williams 82 varieties presented better results than the other varieties in the leaf tissue, with results confirmed by immunoblot analysis, demonstrating that both varieties are good candidates for molecular biological studies. GFP expression in the seedlings was less extensive than that in the leaves, which may be due to the tissue characteristics, with Enrei showing the best results. Based on this observation, we conclude that the Tsukuba system is an effective tool that can be used for different tissues and soybean varieties.
The Receptor Kinases DRUS1 and DRUS2 Behave Distinctly in Osmotic Stress Tolerance by Modulating the Root System Architecture via Auxin Signaling
Authors: Latif Ammara , Yang Chen-Guang , Zhang Lan-Xin , Yang Xin-Yu , Liu Xin-Ye , Ai Lian-Feng , Noman Ali , Pu Cui-Xia , Sun Ying
Published: March 2024

Receptor kinases DRUS1 (Dwarf and Runtish Spikelet1) and DRUS2 are orthologues of the renowned Arabidopsis thaliana gene FERONIA, which play redundant roles in rice growth and development. Whether the two duplicated genes perform distinct functions in response to environmental stress is largely unknown. Here, we found that osmotic stress (OS) and ABA increased DRUS1 expression while decreasing DRUS2. When subjected to osmotic stress, the increased DRUS1 in drus2 mutants suppresses the OsIAA repressors, resulting in a robust root system with an increased number of adventitious and lateral roots as well as elongated primary, adventitious, and lateral roots, conferring OS tolerance. In contrast, the decreased DRUS2 in drus1-1 mutants are not sufficient to suppress OsIAA repressors, leading to a feeble root system with fewer adventitious and lateral roots and hindering seminal root growth, rendering OS intolerance. All these findings offer valuable insights into the biological significance of the duplication of two homologous genes in rice, wherein, if one is impaired, the other one is able to continue auxin-signaling-mediated root growth and development to favor resilience to environmental stress, such as water shortage.