bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammatory Mediators and Type 2 Diabetes Risk Factors before and in Response to Lifestyle Intervention among Latino Adolescents with Obesity
Authors: Peña Armando , Olson Micah L. , Ayers Stephanie L. , Sears Dorothy D. , Vega-López Sonia , Colburn Abigail T. , Shaibi Gabriel Q.
Published: May 2023

Obesity is associated with chronic inflammation that may contribute to T2D among youth. We examined the association between inflammatory biomarkers and insulin sensitivity and β-cell function and response to lifestyle intervention among Latino youth with obesity. Latino youth (n = 64) were randomized to six months of lifestyle intervention (INT, n = 40) or usual care (UC, n = 24). INT included nutrition education and physical activity. UC involved meeting with a pediatric endocrinologist and registered dietitian to discuss healthy lifestyles. At baseline, multiple linear regression assessed fasting serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), high-molecular weight adiponectin (HMW Adpn), IL-10, IL-1 receptor antagonist (IL-1ra) as predictors of insulin sensitivity (whole-body insulin sensitivity index, WBISI) and β-cell function (oral disposition index, oDI). Changes in outcomes between groups were assessed using covariance pattern models. At baseline, MCP-1 (β ± SE, −0.12 ± 0.05, p = 0.027) and IL-1ra (−0.03 ± 0.01, p = 0.005) were negatively associated with WBISI. Treatment effects were not observed for inflammatory markers. WBISI was significantly increased among both INT (from 1.8 ± 0.2 to 2.6 ± 0.4, p = 0.005) and UC (from 1.6 ± 0.2 to 2.8 ± 0.5, p = 0.002) with no significant differences between the groups. Obesity-related inflammatory mediators were associated with T2D risk factors but were unaffected by lifestyle intervention among Latino youth.
Complex Extract of Polygonatum sibiricum and Nelumbinis semen Improves Menopause Symptoms via Regulation of Estrogen Receptor Beta in an Ovariectomized Rat Model
Authors: Park Doori , Yoon Jee-Eun , Choi Boram , Lee Yoon-Jae , Ha In-Hyuk
Published: May 2023

Menopause is a hormone-deficiency state that causes facial flushing, vaginal dryness, depression, anxiety, insomnia, obesity, osteoporosis, and cardiovascular disease as ovarian function decreases. Hormone-replacement therapy is mainly used to treat menopause; however, its long-term use is accompanied by side effects such as breast cancer and endometriosis. To identify the effect of a complex extract of Polygonatum sibiricum (PS) and Nelumbinis semen (NS) on improving menopause without side effects, an ovariectomized rat model was established to analyze several menopause symptoms. Compared to single extracts, the complex extract restored vaginal epithelial cell thickness and decreased serotonin concentration by increasing the estrogen receptors ERα (ESR1) and ERβ (ESR2), depending on the ratio. Although the complex extract exerted a lower weight-loss effect than the single extracts, improved blood-lipid metabolism was observed after increasing high-density lipoprotein cholesterol levels and decreasing low-density lipoprotein cholesterol and triglyceride levels, and ovariectomy-induced osteoporosis was alleviated by suppressing osteoclast production. Thus, by increasing only ERβ expression without regulating ERα expression in the uterus, the complex extract of PS and NS may be a natural treatment for improving menopause symptoms without side effects, such as endometriosis.
Exposure to a Vitamin D Best Practices Toolkit, Model, and E-Tools Increases Knowledge, Confidence, and the Translation of Research to Public Health and Practice
Authors: Sanford Beth S. , Aliano Jennifer L. , Omary Courtney S. , McDonnell Sharon L. , Kimball Samantha M. , Grant William B.
Published: May 2023

Preventable vitamin D deficiency (VDD) is a global health concern. The prevention, early detection, and treatment of vitamin D deficiency aligning with serum 25-hydroxyvitamin D concentration recommendations of 40–60 ng/mL (100–150 nmol/L), provided by an international panel of 48 vitamin D researchers, would result in significant health benefits and cost savings to individuals and society. However, research shows that healthcare professionals lack knowledge and confidence in best practices with respect to vitamin D. A vitamin D toolkit was developed that included a model for decision-making support, e-tools, and accompanying resources and was implemented using an online, asynchronous learning management system. This pre-test, post-test, and follow-up survey study design aimed to increase nurses’ and dietitians’ levels of knowledge and confidence regarding vitamin D, aid in their translation of evidence into spheres of practice and influence, and help them identify translation barriers. The completion of the toolkit increased the participants’ (n = 119) knowledge from 31% to 65% (p < 0.001) and their confidence from 2.0 to 3.3 (p < 0.001) on a scale of 1–5. Respondents reported using the model (100%) as a framework to successfully guide the translation of vitamin D knowledge into their sphere of influence or practice (94%) and identifying translation barriers. The toolkit should be included in interdisciplinary continuing education, research/quality improvement initiatives, healthcare policy, and institutions of higher learning to increase the movement of research into practice.
Furanocoumarin Notopterol: Inhibition of Hepatocellular Carcinogenesis through Suppression of Cancer Stemness Signaling and Induction of Oxidative Stress-Associated Cell Death
Authors: Huang Ting-Yun , Yang Ching-Kuo , Chen Ming-Yao , Yadav Vijesh Kumar , Fong Iat-Hang , Yeh Chi-Tai , Cherng Yih-Giun
Published: May 2023

Background: Hepatocellular carcinoma (HCC) remains an aggressive malignancy with a poor prognosis and a leading cause of cancer-related mortality globally. Cumulative evidence suggests critical roles for endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in chronic liver diseases. However, the role of ER stress in HCC pathogenesis, aggressiveness and therapy response remains unclear and understudied. Objectives: Against this background, the present study evaluated the therapeutic efficacy and feasibility of notopterol (NOT), a furanocoumarin and principal component of Notopterygium incisum, in the modulation of ER stress and cancer stemness, and the subsequent effect on liver oncogenicity. Methods: An array of biomolecular methods including Western blot, drug cytotoxicity, cell motility, immunofluorescence, colony and tumorsphere formation, flow-cytometric mitochondrial function, GSH/GSSG ratio, and tumor xenograft ex vivo assays were used in the study. Results: Herein, we demonstrated that NOT significantly suppresses the viability, migration, and invasion capacity of the human HCC HepJ5 and Mahlavu cell lines by disrupting ATF4 expression, inhibiting JAK2 activation, and downregulating the GPX1 and SOD1 expression in vitro. NOT also markedly suppressed the expression of vimentin (VIM), snail, b-catenin, and N-cadherin in the HCC cells, dose-dependently. Treatment with NOT significantly attenuated cancer stem cells (CSCs)-like phenotypes, namely colony and tumorsphere formation, with the concomitant downregulation of stemness markers OCT4, SOX2, CD133, and upregulated PARP-1 cleavage, dose-dependently. We also demonstrated that NOT anticancer activity was strongly associated with increased cellular reactive oxidative stress (ROS) but, conversely, reduced mitochondrial membrane potential and function in the HepJ5 and Mahlavu cells in vitro. Our tumor xenograft studies showed that compared with sorafenib, NOT elicited greater tumor growth suppression without adverse changes in mice body weights. Compared with the untreated control and sorafenib-treated mice, NOT-treated mice exhibited markedly greater apoptosis ex vivo, and this was associated with the co-suppression of stemness and drug-resistance markers OCT4, SOX2, ALDH1, and the upregulation of endoplasmic reticulum stress and oxidative stress factors PERK and CHOP. Conclusions: In summary, we demonstrated for the first time that NOT exhibits strong anticancer activity via the suppression of cancer stemness, enhanced endoplasmic reticulum stress and increased oxidative stress thus projecting NOT as a potentially effective therapeutic agent against HCC.
Silver Carp (Hypophthalmichthys molitrix) Scale Collagen Peptides-1 (SCPs1) Inhibit Melanogenesis through Downregulation of the cAMP-CREB Signaling Pathway
Authors: Li Hai-Lan , Li Mei-Jin , Xiong Guang-Quan , Cai Jun , Liao Tao , Zu Xiao-Yan
Published: May 2023

The mechanism of silver carp scale collagen peptides (SCPs1) on melanogenesis and its mechanism of action were examined in mouse melanoma cells (B16). The cell viability and effects of SCPs1 on intracellular tyrosinase (TYR) activity and melanin, reactive oxygen species (ROS), glutathione (GSH) and cyclic adenosine monophosphate (cAMP) content were examined. The regulatory mechanism of SCPs1 on the cAMP response element-binding protein (CREB) signaling pathway was analyzed. The cell viability of the SCPs1 group was >80% (0.01–1 mg/mL) and the inhibitory rate of SCPs1 on B16 cell melanin increased in a dose-dependent manner. The highest inhibitory rate of SCPs1 on melanin content reaching 80.24%. SCPs1 significantly increased the GSH content and decreased the tyrosinase activity, as well as the content of ROS and cAMP. Western blot analysis showed that SCPs1 significantly inhibited melanocortin-1 receptor (MC1R) expression and CREB phosphorylation in the cAMP-CREB signaling pathway, leading to downregulation of microphthalmia-associated transcription factor (MITF) and the expression of TYR, TYR-related protein-1 (TRP-1) and TRP-2. SCPs1 also inhibited the expression of MC1R, MITF, TYR, TRP-1 and TRP-2 at the transcriptional level. Taken together, SCPs1 inhibited melanin synthesis through the downregulation of the cAMP-CREB signaling pathway. Fish-derived collagen peptides could potentially be applied in skin whitening products.
Factors Associated with Dietary Patterns of Schoolchildren: A Systematic Review
Authors: de Menezes Laura Rangel Drummond , e Souza Rafaela Cristina Vieira , Cardoso Pollyanna Costa , dos Santos Luana Caroline
Published: May 2023

The evaluation of food consumption in childhood is essential to help understand the effect of food choices on health. The objective of this study was to conduct a systematic review of studies that identified the dietary patterns in schoolchildren (7–10 years old) and their associated factors. Observational studies published in the last ten years were searched in the databases BVS (Virtual Health Library), Embase, PubMed, Scopus, and Web of Science. The Newcastle Ottawa Scale was adopted to evaluate the articles’ quality. The studies covered schoolchildren, children, and adolescents as part of the sample. We selected 16 studies, 75% of which were considered good/very good and seven mentioned three food patterns. A dietary pattern considered unhealthy was identified in 93.75% of the studies, having as associated factors to its consumption: higher screen time, low bone mass, gain of weight and fat in children, and meal skipping. The children who usually had breakfast showed greater adherence to the dietary pattern consisting of healthier foods. The children’s dietary patterns were related to their behavior, nutritional status, and family environment habits. Food and nutrition education’s effective actions, as well as the regularization of the marketing of ultra-processed foods, must be stimulated and inserted in public policies as a way to promote and protect children’s health.
Exercise Is Medicine for Nonalcoholic Fatty Liver Disease: Exploration of Putative Mechanisms
Authors: Heinle James Westley , DiJoseph Kara , Sabag Angelo , Oh Sechang , Kimball Scot R. , Keating Shelley , Stine Jonathan G.
Published: May 2023

Exercise remains a key component of nonalcoholic fatty liver disease (NAFLD) treatment. The mechanisms that underpin improvements in NAFLD remain the focus of much exploration in our attempt to better understand how exercise benefits patients with NAFLD. In this review, we summarize the available scientific literature in terms of mechanistic studies which explore the role of exercise training in modulating fatty acid metabolism, reducing hepatic inflammation, and improving liver fibrosis. This review highlights that beyond simple energy expenditure, the activation of key receptors and pathways may influence the degree of NAFLD-related improvements with some pathways being sensitive to exercise type, intensity, and volume. Importantly, each therapeutic target of exercise training in this review is also the focus of previous or ongoing drug development studies in patients with nonalcoholic steatohepatitis (NASH), and even when a regulatory-agency-approved drug comes to market, exercise will likely remain an integral component in the clinical management of patients with NAFLD and NASH.
RAASi Therapy Attenuates the Association between 24-h Urinary Potassium Excretion and Dietary Potassium Intake in CKD Patients
Authors: Giannese Domenico , D’Alessandro Claudia , Pellegrino Nicola , Panichi Vincenzo , Cupisti Adamasco
Published: May 2023

The aim of this study was to evaluate urinary potassium (K) excretion as a reliable marker of dietary K intake, in a cohort of CKD patients with or without Renin-Angiotensin-Aldosterone System (RAAS) inhibitor therapy. One hundred and thirty-eight consecutive out-patients (51 f and 87 m) aged 60 ± 13 years and affected by CKD stage 3–4, who were metabolically and nutritionally stable, entered the study between November 2021 and October 2022. No difference was observed between patients with (n = 85) or without (n = 53) RAAS inhibitor therapy, regarding dietary intakes, blood biochemistry, and 24-h urine excretion parameters. Considering all patients, urinary K showed a weak relationship with eGFR (r = 0.243, p < 0.01), and with dietary K intake (r = 0.184, p < 0.05). Serum K was not associated with dietary K intake, but an inverse relationship was observed with eGFR (r = −0.269, p < 0.01). When patients were examined depending on whether they were receiving RAAS inhibitor therapy, the weak inverse relationship between serum K and eGFR was maintained in both groups. Conversely, urinary K excretion remained positively associated with dietary K intake only in the no RAAS inhibitor group. In conclusion, 24-h urine K excretion may be used as a surrogate of K intake, but RAAS inhibitor therapy reduces the association between 24-h urine K excretion and dietary K intake in CKD patients.
Synergistic Effect of Diet and Physical Activity on a NAFLD Cohort: Metabolomics Profile and Clinical Variable Evaluation
Authors: Calabrese Francesco Maria , Celano Giuseppe , Bonfiglio Caterina , Campanella Angelo , Franco Isabella , Annunziato Alessandro , Giannelli Gianluigi , Osella Alberto Ruben , De Angelis Maria
Published: May 2023

Together with its comorbidities, nonalcoholic fatty liver disease (NAFLD) is likely to rise further with the obesity epidemic. However, the literature’s evidence shows how its progression can be reduced by the administration of calorie-restrictive dietary interventions and physical activity regimens. The liver function and the gut microbiota have been demonstrated to be closely related. With the aim of ascertaining the impact of a treatment based on the combination of diet and physical activity (versus physical activity alone), we recruited 46 NAFLD patients who were divided into two groups. As a result, we traced the connection between volatile organic compounds (VOCs) from fecal metabolomics and a set of statistically filtered clinical variables. Additionally, we identified the relative abundances of gut microbiota taxa obtained from 16S rRNA gene sequencing. Statistically significant correlations emerged between VOCs and clinical parameters, as well as between VOCs and gut microbiota taxa. In comparison with a physical activity regimen alone, we disclose how ethyl valerate and pentanoic acid butyl ester, methyl valerate, and 5-hepten-2-one, 6-methyl changed because of the positive synergistic effect exerted by the combination of the Mediterranean diet and physical activity regimens. Moreover, 5-hepten-2-one, 6-methyl positively correlated with Sanguinobacteroides, as well as the two genera Oscillospiraceae-UCG002 and Ruminococcaceae UCG010 genera.
Focus of Sustainable Healthy Diets Interventions in Primary School-Aged Children: A Systematic Review
Authors: Patra Elena , Kokkinopoulou Anna , Pagkalos Ioannis
Published: May 2023

Research and public policy interest regarding Sustainable Healthy Diets (SHDs) have increased during the last decades, as nutrition recommendations and diet practices should align with growing environmental concerns. SHDs encompass sociocultural, economic and environmental components of nutrition and health and raising awareness across all these dimensions, as well as providing relevant education, especially to young children, is important for adopting SHD practices. Primary school students (5–12 years old) are often the target population for interventions, as they are considered agents of change for educating the community. The objective of this systematic review is to map the SHD indicators addressed by such interventions in order to identify gaps and opportunities for future interventions in this population. Scopus, PubMed and Web of Science were searched for available publications, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA 2020) methodology. After screening for eligibility, thirteen intervention studies were included and reviewed. Results showed that indicator definitions and measuring methods were not harmonized across research efforts. Implemented SHD interventions address predominantly food waste and diet quality, while social and economic indicators are underrepresented. The standardization of SHD, focusing on measurable harmonized indicators, should be a priority for policy actors in order to enable impactful research efforts. Future interventions should incorporate clear SHD indicators to raise awareness and consider the application of composite tools or indexes to evaluate outcomes and maximize impact in the community.
The Role of Emotional Regulation in the Relationship between Nurses’ Creative Style and Innovation Behaviors: A Cross-Sectional Study
Authors: Toscano Ferdinando , Giusino Davide , Diana Raffaello , Rahimi Pordanjani Tayebe
Published: May 2023

Innovation is crucial to an effective healthcare system, and nurses are key figures in the innovation process. A potential factor behind innovation in nursing is the creative style of nurses. Creativity is an essential component of innovation. However, the relationship between creative style and innovation is complex and involves many different factors. Among them, given the nature of the nursing profession, we propose emotional regulation, or the ability to effectively manage one’s emotions. In this study, we hypothesize that two specific emotion-regulation strategies, positive reappraisal and putting into perspective, play a role in the relationship between nurses’ creative style and innovative behaviors. We tested a moderated mediation model using cross-sectional data from 187 nurses working in 3 university hospitals in Bojnord, Iran, in 2019. Our results show that positive reappraisal completely mediates the relationship between creative style and innovative behaviors, while putting into perspective moderates the relationship between positive reappraisal and innovative behaviors. These results suggest that nurses with a flair for creativity may be able to implement innovative behaviors in the workplace due to their ability to understand work-related situations and events positively. This may be especially true for nurses who can adopt alternative viewpoints. Our study discusses these findings by highlighting the importance of emotional regulation mechanisms in transforming nurses’ creativity into effective innovation. Finally, we provide suggestions for healthcare organizations to promote innovation as an added value in the healthcare environment and services provided.
Molecular Characterization of Porcine Reproductive and Respiratory Syndrome Virus in Korea from 2018 to 2022
Authors: Lee Min-A , Jayaramaiah Usharani , You Su-Hwa , Shin Eun-Gyeong , Song Seung-Min , Ju Lanjeong , Kang Seok-Jin , Hyun Bang-Hun , Lee Hyang-Sim
Published: May 2023

Porcine reproductive and respiratory syndrome (PRRS) is an endemic disease in the Republic of Korea. Surveillance of PRRS virus (PRRSV) types is critical to tailor control measures. This study collected 5062 serum and tissue samples between 2018 and 2022. Open reading frame 5 (ORF5) sequences suggest that subgroup A (42%) was predominant, followed by lineage 1 (21%), lineage 5 (14%), lineage Korea C (LKC) (9%), lineage Korea B (LKB) (6%), and subtype 1C (5%). Highly virulent lineages 1 (NADC30/34/MN184) and 8 were also detected. These viruses typically mutate or recombine with other viruses. ORF5 and non-structural protein 2 (NSP2) deletion patterns were less variable in the PRRSV-1. Several strains belonging to PRRSV-2 showed differences in NSP2 deletion and ORF5 sequences. Similar vaccine-like isolates to the PRRSV-1 subtype 1C and PRRSV-2 lineage 5 were also found. The virus is evolving independently in the field and has eluded vaccine protection. The current vaccine that is used in Korea offers only modest or limited heterologous protection. Ongoing surveillance to identify the current virus strain in circulation is necessary to design a vaccine. A systemic immunization program with region-specific vaccinations and stringent biosecurity measures is required to reduce PRRSV infections in the Republic of Korea.
Fluconazole Resistance and Virulence in In Vitro Induced-Fluconazole Resistant Strains and in Clinical Fluconazole Resistant Strain of Cryptococcus deuterogattii
Authors: Bertout Sébastien , Laroche Laetitia , Roger Frédéric , Krasteva Donika , Drakulovski Pascal , Bellet Virginie
Published: May 2023

Neuromeningeal cryptococcosis is a life-threatening infection of the central nervous system, caused by encapsulated yeast belonging to the Cryptococcus neoformans and Cryptococcus gattii species complexes. Recent data showed that virulence and antifungal resistance are variable for yeasts belonging to the C. gattii species complex. There is an increase in resistance to fluconazole for yeasts of the C. gattii species complex and the virulence is variable according to the genotype. In the present study, (i) we explored and compared the mechanisms of resistance to fluconazole between C. deuterogattii clinically resistant strains and induced fluconazole-resistant strains by exposure to fluconazole in vitro, and (ii) we studied their virulence in the Galleria mellonella study model. We demonstrated that the fluconazole resistance mechanisms involved were different between clinically resistant strains and induced resistant strains. We also demonstrated that fluconazole-induced resistant strains are less virulent when compared to the original susceptible strains. On the contrary, the clinically resistant strain tested maintains its virulence compared to fluconazole-susceptible strains of the same sequence type.
Lungworms of Non-Ruminant Terrestrial Mammals and Humans in Iran
Authors: Mohtasebi Sina , Sazmand Alireza , Zafari Salman , Verocai Guilherme G. , Otranto Domenico
Published: May 2023

With over 300 terrestrial and aquatic mammalian species, Iran is considered a country with an ample mastofauna. Although many studies have assessed the distribution of gastrointestinal helminth parasites in animals and humans in Iran, lungworms have not received adequate attention. Following a previous article in which we reviewed the diversity and prevalence of lungworm infections in pastoral and wild ruminants of Iran, this report compiles the available scientific information about the occurrence of lungworms in non-ruminant mammals and humans from 1980 to 2022 to provide insights into the epidemiology of these infections. International and national scientific databases were searched, and twenty-six articles in peer-reviewed journals, one conference paper, and one D.V.M. thesis were included in the study. In total, 10 species belonging to seven genera, including Dictyocaulus, Deraiophoronema, Protostrongylus, Crenosoma, Eucoleus, Aelurostrongylus, and Metastrongylus, were reported in the respiratory tract or feces of humans, domestic animals (i.e., camels, equids, dogs, and cats), and wildlife species (i.e., hedgehogs, wild boars, and hares). Most of the studies (22/28) were performed using post-mortem examinations. The overall prevalence of respiratory nematode infection varied according to animal species in camels (14.83%), equids (13.31%), dogs (5%), wild boars (45.66%), hedgehogs (42.57%), and hares (1.6%). In addition, pulmonary capillariasis caused by Eucoleus aerophilus was reported in a 9 year old child. The prevalence of lungworm species in domestic camels, equids, and dogs, combined with a lack of labeled anthelmintic products, supports the need to improve our understanding of these important nematode parasites and inform the development of sustainable control strategies. From a zoo and wildlife medicine point of view, there is a shortage of information about the presence and prevalence of lungworm infections in the majority of mammalian species, pending epidemiological studies that integrate classical parasitology and molecular methods.
Compounded Effervescent Magnesium for Familial Hypomagnesemia: A Case Report
Authors: Bennati Giada , Cirino Mario , Benericetti Giulia , Maximova Natalia , Zanier Monica , Pigato Federico , Parzianello Anna , Maestro Alessandra , Barbi Egidio , Zanon Davide
Published: May 2023

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive disorder affecting <1/1,000,000 people. It is caused by mutations in the CLDN16 (FHHNC Type 1) or CLDN19 (FHHNC Type 2) genes, which are located on Chromosomes 3q27 and 1p34.2, respectively. There are no drug therapies for this condition. Although magnesium salts represent an important class of compounds and exhibit various therapeutic actions as a supplement for magnesium deficiency in FHHNC, various formulations on the market have different bioavailability. We report the case of a patient with FHNNC first treated, in our Pediatric Institute, with high doses of magnesium pidolate and magnesium and potassium citrate. The patient began to neglect this therapy after experiencing frequent daily episodes of diarrhoea. Our pharmacy received a request for an alternative magnesium supplement that would better comply by ensuring a good magnesium intake which will result in adequate blood magnesium levels. In response, we developed a galenic compound in the form of effervescent magnesium. Here, we report on the promise of this formulation not only for better compliance than pidolate, but also for better bioavailability.
Innate Vascular Failure by Application of Neuroleptics, Amphetamine, and Domperidone Rapidly Induced Severe Occlusion/Occlusion-like Syndromes in Rats and Stable Gastric Pentadecapeptide BPC 157 as Therapy
Authors: Strbe Sanja , Smoday Ivan Maria , Krezic Ivan , Kalogjera Luka , Vukovic Vlasta , Zizek Helena , Gojkovic Slaven , Vranes Hrvoje , Barisic Ivan , Sikiric Suncana , Tepes Marijan , Oroz Katarina , Brkic Filip , Drinkovic Martin , Beketic Oreskovic Lidija , Popic Jelena , Boban Blagaic Alenka , Skrtic Anita , Staresinic Mario , Seiwerth Sven , Sikiric Predrag
Published: May 2023

Even before behavioral disturbances, neuroleptics, amphetamine, and domperidone application rapidly emerged severe occlusion/occlusion-like syndrome, shared innate vascular and multiorgan failure in rats, comparable to occlusion/occlusion-like syndrome described with vessel(s) occlusion or similar noxious procedures application. As therapy, i.e., activation of the collateral pathways, “bypassing key” (activated azygos vein pathway, direct blood flow delivery), the stable gastric pentadecapeptide BPC 157 is a novel solution. Recently, BPC 157 therapy particularly counteracted neuroleptic- or L-NAME-induced catalepsy, lithium intoxication, and schizophrenia positive and negative symptoms (amphetamine/methamphetamine/apomorphine/ketamine). In rats with complete calvariectomy, medication (BPC 157 10 µg/kg, 10 ng/kg ip or ig) was given 5 min after distinctive dopamine agents (mg/kg ip) (haloperidol (5), fluphenazine (5), clozapine (10), risperidone (5), olanzapine (10), quetiapine (10), or aripiprazole (10), domperidone (25), amphetamine (10), and combined amphetamine and haloperidol) and assessed at 15 min thereafter. All neuroleptic-, domperidone-, and amphetamine-induced comparable vascular and multiorgan failure severe syndrome was alleviated with BPC 157 therapy as before major vessel(s) occlusion or other similar noxious procedures. Specifically, all severe lesions in the brain (i.e., immediate swelling, hemorrhage), heart (i.e., congestion, arrhythmias), and lung (i.e., congestion, hemorrhage), as well as congestion in the liver, kidney, and gastrointestinal (stomach) tract, were resolved. Intracranial (superior sagittal sinus), portal, and caval hypertension and aortal hypotension were attenuated or eliminated. BPC 157 therapy almost annihilated arterial and venous thrombosis, peripherally and centrally. Thus, rapidly acting Virchow triad circumstances that occur as dopamine central/peripheral antagonists and agonist essential class-points, fully reversed by BPC 157 therapy, might be overwhelming for both neuroleptics and amphetamine.
Exploring the Potential of Nanotechnology in Pediatric Healthcare: Advances, Challenges, and Future Directions
Authors: Omidian Hossein , Mfoafo Kwadwo
Published: May 2023

The utilization of nanotechnology has brought about notable advancements in the field of pediatric medicine, providing novel approaches for drug delivery, disease diagnosis, and tissue engineering. Nanotechnology involves the manipulation of materials at the nanoscale, resulting in improved drug effectiveness and decreased toxicity. Numerous nanosystems, including nanoparticles, nanocapsules, and nanotubes, have been explored for their therapeutic potential in addressing pediatric diseases such as HIV, leukemia, and neuroblastoma. Nanotechnology has also shown promise in enhancing disease diagnosis accuracy, drug availability, and overcoming the blood–brain barrier obstacle in treating medulloblastoma. It is important to acknowledge that while nanotechnology offers significant opportunities, there are inherent risks and limitations associated with the use of nanoparticles. This review provides a comprehensive summary of the existing literature on nanotechnology in pediatric medicine, highlighting its potential to revolutionize pediatric healthcare while also recognizing the challenges and limitations that need to be addressed.
Improved Therapeutic Delivery Targeting Clinically Relevant Orthotopic Human Pancreatic Tumors Engrafted in Immunocompromised Pigs Using Ultrasound-Induced Cavitation: A Pilot Study
Authors: Imran Khan Mohammad , Tintera Benjamin , Morrison Holly A. , Tupik Juselyn D. , Nagai-Singer Margaret A. , Ivester Hannah , Council-Troche McAlister , Edwards Michael , Coutermarsh-Ott Sheryl , Byron Christopher , Clark-Deener Sherrie , Uh Kyungjun , Lee Kiho , Boulos Paul , Rowe Cliff , Coviello Christian , Allen Irving C.
Published: May 2023

Pancreatic tumors can be resistant to drug penetration due to high interstitial fluid pressure, dense stroma, and disarrayed vasculature. Ultrasound-induced cavitation is an emerging technology that may overcome many of these limitations. Low-intensity ultrasound, coupled with co-administered cavitation nuclei consisting of gas-stabilizing sub-micron scale SonoTran Particles, is effective at increasing therapeutic antibody delivery to xenograft flank tumors in mouse models. Here, we sought to evaluate the effectiveness of this approach in situ using a large animal model that mimics human pancreatic cancer patients. Immunocompromised pigs were surgically engrafted with human Panc-1 pancreatic ductal adenocarcinoma (PDAC) tumors in targeted regions of the pancreas. These tumors were found to recapitulate many features of human PDAC tumors. Animals were intravenously injected with the common cancer therapeutics Cetuximab, gemcitabine, and paclitaxel, followed by infusion with SonoTran Particles. Select tumors in each animal were targeted with focused ultrasound to induce cavitation. Cavitation increased the intra-tumor concentrations of Cetuximab, gemcitabine, and paclitaxel by 477%, 148%, and 193%, respectively, compared to tumors that were not targeted with ultrasound in the same animals. Together, these data show that ultrasound-mediated cavitation, when delivered in combination with gas-entrapping particles, improves therapeutic delivery in pancreatic tumors under clinically relevant conditions.
Prediction of CYP-Mediated Drug Interaction Using Physiologically Based Pharmacokinetic Modeling: A Case Study of Salbutamol and Fluvoxamine
Authors: Marques Lara , Vale Nuno
Published: May 2023

Drug–drug interactions (DDIs) represent a significant concern in healthcare, particularly for patients undergoing polytherapy. DDIs can lead to a range of outcomes, from decreased therapeutic effectiveness to adverse effects. Salbutamol, a bronchodilator recommended for the treatment of respiratory diseases, is metabolized by cytochrome P450 (CYP) enzymes, which can be inhibited or induced by co-administered drugs. Studying DDIs involving salbutamol is crucial for optimizing drug therapy and preventing adverse outcomes. Here, we aimed to investigate CYP-mediated DDIs between salbutamol and fluvoxamine through in silico approaches. The physiologically based pharmacokinetic (PBPK) model of salbutamol was developed and validated using available clinical PK data, whereas the PBPK model of fluvoxamine was previously verified by GastroPlus. Salbutamol–fluvoxamine interaction was simulated according to different regimens and patient’s characteristics (age and physiological status). The results demonstrated that co-administering salbutamol with fluvoxamine enhanced salbutamol exposure in certain situations, especially when fluvoxamine dosage increased. To sum up, this study demonstrated the utility of PBPK modeling in predicting CYP-mediated DDIs, making it a pioneer in PK DDI research. Furthermore, this study provided insights into the relevance of regular monitoring of patients taking multiple medications, regardless of their characteristics, to prevent adverse outcomes and for the optimization of the therapeutic regimen, in cases where the therapeutic benefit is no longer experienced.
Reviewing the Impact of Powder Cohesion on Continuous Direct Compression (CDC) Performance
Authors: Jones-Salkey Owen , Chu Zoe , Ingram Andrew , Windows-Yule Christopher R. K.
Published: May 2023

The pharmaceutical industry is undergoing a paradigm shift towards continuous processing from batch, where continuous direct compression (CDC) is considered to offer the most straightforward implementation amongst powder processes due to the relatively low number of unit operations or handling steps. Due to the nature of continuous processing, the bulk properties of the formulation will require sufficient flowability and tabletability in order to be processed and transported effectively to and from each unit operation. Powder cohesion presents one of the greatest obstacles to the CDC process as it inhibits powder flow. As a result, there have been many studies investigating potential manners in which to overcome the effects of cohesion with, to date, little consideration of how these controls may affect downstream unit operations. The aim of this literature review is to explore and consolidate this literature, considering the impact of powder cohesion and cohesion control measures on the three-unit operations of the CDC process (feeding, mixing, and tabletting). This review will also cover the consequences of implementing such control measures whilst highlighting subject matter which could be of value for future research to better understand how to manage cohesive powders for CDC manufacture.
Dendrimers in Corneal Drug Delivery: Recent Developments and Translational Opportunities
Authors: Dhull Anubhav , Yu Carson , Wilmoth Alex Hunter , Chen Minjie , Sharma Anjali , Yiu Samuel
Published: May 2023

Dendrimers are biocompatible organic nanomaterials with unique physicochemical properties, making them the focus of recent research in drug delivery. The cornea of the human eye presents a challenge for drug transit due to its inherently impenetrable nature, requiring nanocarrier-mediated targeted drug delivery. This review intends to examine recent advancements in the use of dendrimers for corneal drug delivery, including their properties and their potential for treating various ocular diseases. The review will also highlight the benefit of the novel technologies that have been developed and applied in the field, such as corneal targeting, drug release kinetics, treatments for dry eye disease, antibacterial drug delivery, corneal inflammation, and corneal tissue engineering. The review seeks to provide a comprehensive overview of the current state of research in this field, along with the translational developments in the field of dendrimer-based therapeutics and imaging agents and inspire the potential for future developments and translational opportunities in dendrimers based corneal drug delivery.
Invasive Plant Alternanthera philoxeroides Benefits More Competition Advantage from Rhizosphere Bacteria Regardless of the Host Source
Authors: Li Xu , Zhang Yi , Kong Fang-Li , Naz Misbah , Zhou Jian-Yu , Qi Shan-Shan , Dai Zhi-Cong , Du Dao-Lin
Published: May 2023

The rhizosphere plays a vital role in the exchange of materials in the soil–plant ecosystem, and rhizosphere microorganisms are crucial for plant growth and development. In this study, we isolated two strains of Pantoea rhizosphere bacteria separately from invasive Alternanthera philoxeroides and native A. sessilis. We conducted a control experiment to test the effects of these bacteria on the growth and competition of the two plant species using sterile seedlings. Our findings showed that the rhizobacteria strain isolated from A. sessilis significantly promoted the growth of invasive A. philoxeroides in monoculture compared to native A. sessilis. Both strains significantly enhanced the growth and competitiveness of invasive A. philoxeroides under competition conditions, regardless of their host source. Our study suggests that rhizosphere bacteria, including those from different host sources, can contribute to the invasion of A. philoxeroides by significantly enhancing its competitiveness.
Inflorescence Emergence and Flowering Response of Olive Cultivars Grown in Olive Reference Collection of Portugal (ORCP)
Authors: Inês Carla , Gomez-Jimenez Maria C. , Cordeiro António M.
Published: May 2023

In olive trees, fluctuations in the onset of phenological stages have been reported due to weather conditions. The present study analyses the reproductive phenology of 17 olive cultivars grown in Elvas (Portugal) in 3 consecutive years (2012–2014). Through 2017–2022, the phenological observations continued with four cultivars. The phenological observations followed the BBCH scale. Over the course of the observations, the bud burst (stage 51) occurred gradually later; a few cultivars did not follow this trend in 2013. The flower cluster totally expanded phase (stage 55) was achieved gradually earlier, and the period between stages 51–55 was shortened, especially in 2014. Date of bud burst showed a negative correlation with minimum temperature (Tmin) of November–December, and, in ‘Arbequina’ and ‘Cobrançosa’, the interval stage 51–55 showed a negative correlation with both the Tmin of February and the Tmax of April, whereas in ‘Galega Vulgar’ and ‘Picual’ there was instead a positive correlation with the Tmin of March. These two seemed to be more responsive to early warm weather, whereas ‘Arbequina’ and ‘Cobrançosa’ were less sensitive. This investigation revealed that olive cultivars behaved differently under the same environmental conditions and, in some genotypes, the ecodormancy release may be linked to endogenous factors in a stronger way.
Human Settlement and Landscape Anthropization of Remote Oceanic Islands: A Comparison between Rapa Nui (Pacific Ocean) and the Azores (Atlantic Ocean)
Authors: Rull Valentí
Published: May 2023

The flora and vegetation of oceanic islands have been deeply affected by human settlement and further landscape modifications during prehistoric and historical times. The study of these transformations is of interest not only for understanding how current island biotas and ecological communities have been shaped but also for informing biodiversity and ecosystem conservation. This paper compares two oceanic insular entities of disparate geographical, environmental, biological, historical and cultural characteristics—Rapa Nui (Pacific Ocean) and the Azores Islands (Atlantic Ocean)—in terms of human settlement and further landscape anthropization. The similarities and differences between these islands/archipelagos are discussed considering their permanent colonization, the possibility of earlier settlements, the removal of the original forests and the further landscape transformations leading to either full floristic/vegetational degradation (Rapa Nui) or major replacement (Azores). This comparison uses evidence from varied disciplines, notably paleoecology, archaeology, anthropology and history, to obtain a holistic view of the development of the respective socioecological systems from a human ecodynamic perspective. The most relevant issues still to be resolved are identified and some prospects for future research are suggested. The cases of Rapa Nui and Azores Islands may help set a conceptual basis for ocean-wide global comparisons among oceanic islands/archipelagos.
Mycorrhizal Colonization of Wheat by Intact Extraradical Mycelium of Mn-Tolerant Native Plants Induces Different Biochemical Mechanisms of Protection
Authors: Faria Jorge M. S. , Barrulas Pedro , Pinto Ana Paula , Brito Isabel , Teixeira Dora Martins
Published: May 2023

Soil with excess Mn induces toxicity and impairs crop growth. However, with the development in the soil of an intact extraradical mycelia (ERM) from arbuscular mycorrhizal fungi (AMF) symbiotic to native Mn-tolerant plants, wheat growth is promoted due to a stronger AMF colonization and subsequent increased protection against Mn toxicity. To determine the biochemical mechanisms of protection induced by this native ERM under Mn toxicity, wheat grown in soil from previously developed Lolium rigidum (LOL) or Ornithopus compressus (ORN), both strongly mycotrophic plants, was compared to wheat grown in soil from previously developed Silene gallica (SIL), a non-mycotrophic plant. Wheat grown after LOL or ORN had 60% higher dry weight, ca. two-fold lower Mn levels and almost double P contents. Mn in the shoots was preferentially translocated to the apoplast along with Mg and P. The activity of catalase increased; however, guaiacol peroxidase (GPX) and superoxide dismutase (SOD) showed lower activities. Wheat grown after ORN differed from that grown after LOL by displaying slightly higher Mn levels, higher root Mg and Ca levels and higher GPX and Mn-SOD activities. The AMF consortia established from these native plants can promote distinct biochemical mechanisms for protecting wheat against Mn toxicity.
Arbuscular Mycorrhizal Fungi as an Important Factor Enabling the Adaptation of Anthyllis vulneraria L. to Zn-Pb-Polluted Tailings
Authors: Sujkowska-Rybkowska Marzena , Lisek Anna , Sumorok Beata , Derkowska Edyta , Szymańska Magdalena , Sas-Paszt Lidia
Published: May 2023

The old Zn-Pb-contaminated (calamine) tailings in southern Poland are spontaneously colonized by metal-tolerant Anthyllis vulneraria L. (Fabaceae), which can form simultaneously symbiotic association with nitrogen-fixing rhizobia and phosphorus-acquiring arbuscular mycorrhizal fungi (AMF). So far, fungal colonization and the AMF diversity of calamine-inhabiting legumes have been poorly studied. Thus, we determined AMF spore density in the substratum and the mycorrhizal status of nodulated A. vulneraria plants occurring on calamine tailings (M) and on a reference non-metallicolous (NM) site. The results indicate the presence of the Arum-type of arbuscular mycorrhiza in the roots of both Anthyllis ecotypes. Despite the presence of AM fungi in M plant roots, the dark septate endophyte (DSE) fungi (hyphae and microsclerotia) were occasionally also detected. Metal ions were accumulated mainly in the nodules and intraradical fungal structures rather than thick plant cell walls. Mycorrhization parameters (frequency of mycorrhization and intensity of root cortex colonization) for M plants were markedly higher and differed in a statistically significant manner from the parameters for NM plants. Heavy metal excess had no negative effect on the number of AMF spores, the amounts of glomalin-related soil proteins and AMF species composition. Molecular identification of AMF using PCR-DGGE analysis based on the 18S rDNA ribosomal gene by nested-PCR with primers AM1/NS31 and NS31-GC/Glo1 revealed similar genera/species of AMF in the roots of both Anthyllis ecotypes: Rhizophagus sp., R. fasciculatus, and R. iranicus. The results of this work indicate the presence of unique fungal symbionts, which may enhance A. vulneraria tolerance to heavy metal stress and plant adaptation to extreme conditions on calamine tailings.
Application of Cold Storage and Short In Vitro Germination for Somatic Embryos of Pinus radiata and P. sylvestris
Authors: Reeves Cathie , Tikkinen Mikko , Aronen Tuija , Krajnakova Jana
Published: May 2023

Somatic embryogenesis (SE) is an advanced vegetative propagation technology that, when used in combination with breeding and cryopreservation, offers the forest industry a powerful tool for the deployment of elite genotypes. Germination and acclimatization are critical and cost-intensive phases in the production of somatic plants. The efficient conversion of somatic embryos into robust plants is a necessity if a propagation protocol is to be successfully adopted by the industry. In this work, these late phases of the SE protocol of two pine species were investigated. A shortened germination protocol and more controlled acclimatization were investigated for Pinus radiata, testing embryos from 18 embryogenic cell lines. A more simplified protocol, including a cold storage phase, was also compared among 10 of these cell lines. A shortened germination period and more controlled protocols significantly improved the acclimatization of somatic embryos directly from the lab to the glasshouse. When results for all cell lines were pooled, there were significant improvements in all growth characteristics (shoot height, root length, root collar diameter, and root quadrant score). When the more simplified protocol involving cold storage was tested, improvements were seen in the root architecture. For Pinus sylvestris, the late phases of somatic embryogenesis were investigated on seven cell lines in a set of two trials (four to seven cell lines per trial). During the germination phase, a shortened and simplified in vitro period, a cold storage option and basal media were explored. Viable plants were obtained from all treatments. However, there is still the need to improve germination and related protocols together with growing regimes for Pinus sylvestris. The improvements to protocols presented here, particularly for Pinus radiata, result in greater survival and quality of somatic emblings, leading to reduced costs and increased confidence in the technology. Simplified protocols using a cold storage option show great promise and, with some further research, could lead to reductions in the cost of the technology.