bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic Effects of a Novel Form of Biotin on Propionic Acid-Induced Autistic Features in Rats
Authors: Sahin Kazim , Orhan Cemal , Karatoprak Serdar , Tuzcu Mehmet , Deeh Patrick Brice Defo , Ozercan Ibrahim Hanifi , Sahin Nurhan , Bozoglan Merve Yilmaz , Sylla Sarah , Ojalvo Sara Perez , Komorowski James R.
Published: March 2022

Magnesium biotinate (MgB) is a novel biotin complex with superior absorption and anti-inflammatory effects in the brain than D-Biotin. This study aimed to investigate the impact of different doses of MgB on social behavior deficits, learning and memory alteration, and inflammatory markers in propionic acid (PPA)-exposed rats. In this case, 35 Wistar rats (3 weeks old) were distributed into five groups: 1, Control; 2, PPA treated group; 3, PPA+MgBI (10 mg, HED); 4, PPA+MgBII (100 mg, HED); 5, PPA+MgBIII (500 mg, HED). PPA was given subcutaneously at 500 mg/kg/day for five days, followed by MgB for two weeks. PPA-exposed rats showed poor sociability and a high level of anxiety-like behaviors and cognitive impairments (p < 0.001). In a dose-dependent manner, behavioral and learning-memory disorders were significantly improved by MgB supplementation (p < 0.05). PPA decreased both the numbers and the sizes of Purkinje cells in the cerebellum. However, MgB administration increased the sizes and the densities of Purkinje cells. MgB improved the brain and serum Mg, biotin, serotonin, and dopamine concentrations, as well as antioxidant enzymes (CAT, SOD, GPx, and GSH) (p < 0.05). In addition, MgB treatment significantly regulated the neurotoxicity-related cytokines and neurotransmission-related markers. For instance, MgB significantly decreased the expression level of TNF-α, IL-6, IL-17, CCL-3, CCL-5, and CXCL-16 in the brain, compared to the control group (p < 0.05). These data demonstrate that MgB may ameliorate dysfunctions in social behavior, learning and memory and reduce the oxidative stress and inflammation indexes of the brain in a rat model.
Body Dissatisfaction and Disordered Eating Behaviors: The Mediation Role of Smartphone Addiction and Depression
Authors: Yang Fahui , Qi Le , Liu Shiyu , Hu Wen , Cao Qike , Liu Ying , Tang Man , Lv Zhuolan , Zhou Zhehan , Yang Yingkai
Published: March 2022

This study aimed to determine whether smartphone addiction and depression sequentially mediate the relationship between body dissatisfaction and disordered eating behaviors (e.g., restrained eating, emotional eating and external eating). A total of 5986 participants (54.1% females, average age = 19.8 years, age range = 17–32) completed the Satisfaction and Dissatisfaction with Body Parts Scale, the Three-Factor Eating Questionnaire, the Smartphone Addiction Scale and the Patient Health Questionnaire-9. Mediational analysis showed that, after controlling for age, sex and body mass index, body dissatisfaction was related to disordered eating behaviors through (a) the mediating effect of smartphone addiction, (b) the mediating effect of depression, and (c) the serial mediating effect of smartphone addiction and depression. In conclusion, our study showed for the first time that smartphone addiction and depression can be sequential mediator variables in the association between body dissatisfaction and disordered eating. However, this study is a cross-sectional study; future longitudinal studies could further test the causal associations between these study variables.
Effect of Copper and Selenium Supplementation on the Level of Elements in Rats’ Femurs under Neoplastic Conditions
Authors: Skrajnowska Dorota , Jagielska Agata , Ruszczyńska Anna , Idkowiak Jakub , Bobrowska-Korczak Barbara
Published: March 2022

A study was conducted to determine the effect of long-term supplementation with selenium and copper, administered at twice the level used in the standard diet of rats, on the content of selected elements in the femoral bones of healthy rats and rats with implanted LNCaP cancer cells. After an adaptation period, the animals were randomly divided into two experimental groups. The rats in the experimental group were implanted with prostate cancer cells. The rats in the control group were kept in the same conditions as those in the experimental group and fed the same diet, but without implanted cancer cells. The cancer cells (LNCaP) were intraperitoneally implanted in the amount of 1 × 106 (in PBS 0.4 mL) at the age of 90 days. The content of elements in the samples was determined by a quadrupole mass spectrometer with inductively coupled plasma ionization (ICP-MS). In the femoral bones of rats with implanted LNCaP cells, in the case of the standard diet and the copper-enriched diet, there was a marked decreasing trend in the content of the analysed elements relative to the control rats. This may indicate slow osteolysis taking place in the bone tissue. Contrasting results were obtained for the diet enriched with selenium; there was no significant reduction in the level of these elements, and there was even an increase in the concentrations of Fe and K in the bones of rats with implanted LNCaP cells. Particularly, numerous changes in the mineral composition of the bones were generated by enriching the diet with copper. The elements that most often underwent changes (losses) in the bones were cobalt, iron, manganese and molybdenum. The changes observed, most likely induced by the implantation of LNCaP cells, may indicate a disturbance of mineral homeostasis.
Liquiritigenin Inhibits Lipid Accumulation in 3T3-L1 Cells via mTOR-Mediated Regulation of the Autophagy Mechanism
Authors: Qin Hong , Song Ziyu , Zhao Chunyu , Yang Jinxin , Xia Fan , Wang Lewen , Ali Anwar , Zheng Wenya
Published: March 2022

Liquiritigenin (LQG) is a natural flavonoid from the herb Glycyrrhiza uralensis Fisch that exhibits multiple biological activities. However, its specific role in antiobesity and its related underlying molecular mechanisms remain unknown. The primary purpose of this study is to explore the effects and regulatory mechanisms of LQG on lipid accumulation in 3T3-L1 adipocytes. The results show that LQG significantly reduced triglyceride levels and downregulated the expression of transcription factors such as CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ) in 3T3-L1 adipocytes. Additionally, the expression of sterol-regulatory element-binding protein 1c (SREBP1c), acetyl-CoA carboxylase 1 (ACC1), and fatty acid synthase (FASN) involved in lipogenesis was reduced by treatment with LQG. The protein expression levels of light chain 3B (LC3B), autophagy-related protein 7 (ATG7) and p62 were also modulated by LQG, leading to the suppression of autophagy. Further, LQG activated the phosphorylation of the mammalian target of rapamycin (mTOR), the inhibition of which was followed by the restored expression of autophagy-related proteins. Pretreatment with an mTOR inhibitor also reverted the expression of several genes or proteins involved in lipid synthesis. These results suggest that LQG inhibited lipid accumulation via mTOR-mediated autophagy in 3T3-L1 white adipocytes, indicating the role of LQG as a potential natural bioactive component for use in dietary supplements for preventing obesity.
Weight Gain and Nutrition during Pregnancy: An Analysis of Clinical Practice Guidelines in the Asia-Pacific Region
Authors: Aoyama Tomoko , Li Donglai , Bay Jacquie Lindsay
Published: March 2022

Nutrition and weight gain during pregnancy can influence the life-course health of offspring. Clinical practice guidelines play an important role in ensuring appropriate nutrition and weight gain among pregnant women. This study aims to identify clinical practice guidelines on gestational weight gain and/or maternal nutrition across the Asia-Pacific region and to determine the quality of the guidelines and variability in the recommendations. Through a systematic search of grey literature from 38 Asia-Pacific countries, 23 published guidelines were obtained. Of these, 10 eligible clinical practice guidelines reporting nutrition- or/and weight-related recommendations for pregnant women were selected and reviewed. Guideline quality was determined using the Assessment of Guidelines for Research Evaluation II (AGREE II) instrument. Of the 10 guidelines, 90% were classified as low-quality in the AGREE II appraisal. Several variations were found with respect to recommendations on gestational weight gain, including those specific to Asian populations. The recommendations on dietary advice, additional energy intake, and nutritional supplementation during pregnancy were varied. Clinical practice guidelines on weight gain and nutrition in pregnancy across the Asia-Pacific region are generally of poor quality, reflecting significant variation, and need to be improved to ensure pregnant women receive appropriate advice. (PROSPERO registration no. CRD42021291395).
Quality and Presence of Behaviour Change Techniques in Mobile Apps for the Mediterranean Diet: A Content Analysis of Android Google Play and Apple App Store Apps
Authors: McAleese Daniel , Linardakis Manolis , Papadaki Angeliki
Published: March 2022

Smartphone apps might represent an opportunity to promote adherence to the Mediterranean diet (MedDiet). This study aimed to evaluate the quality of commercially available apps for the MedDiet and the presence of behavioural change techniques (BCTs) used by these apps. A systematic search was conducted on the Apple App and Google Play stores in November 2021. Apps were included if they provided information on the MedDiet or if their objective was to promote a healthy lifestyle through adherence to the MedDiet. Eligible apps were independently evaluated by two reviewers with regard to their quality (engagement, functionality, aesthetics and information quality) using the 5-point Mobile App Rating Scale (MARS; with higher scores indicating higher quality), and the presence of BCTs using an established 26-item BCT taxonomy. Of the 55 analysed apps, 52 (94.5%) were free, 50 (90.9%) provided recipe ideas, 29 (52.7%) provided meal plans, and 22 (40%) provided information on the health benefits of the MedDiet. The overall quality mean MARS score was 2.84 (standard deviation (SD) = 0.42), with functionality being the highest scored MARS domain (mean = 3.58, SD = 0.44) and engagement the lowest (mean = 2.29, SD = 0.61). The average number of BCTs in the analysed apps was 2.3 (SD = 1.4; range: 0–6 per app). The number of BCTs was positively correlated with app information quality (rrho = 0.269, p = 0.047), overall MARS score (rrho = 0.267, p = 0.049), app subjective quality (rrho = 0.326, p = 0.015) and app-specific quality (rrho = 0.351, p = 0.009). These findings suggest that currently available apps might provide information on the MedDiet, but the incorporation of more BCTs is warranted to maximise the potential for behaviour change towards the MedDiet.
Lactobacillus paracasei CCFM1229 and Lactobacillus rhamnosus CCFM1228 Alleviated Depression- and Anxiety-Related Symptoms of Chronic Stress-Induced Depression in Mice by Regulating Xanthine Oxidase Activity in the Brain
Authors: Xu Mengshu , Tian Peijun , Zhu Huiyue , Zou Renying , Zhao Jianxin , Zhang Hao , Wang Gang , Chen Wei
Published: March 2022

Depression is a common mood disorder that affects around 350 million people worldwide. We studied the effect of supplementation with Lactobacillus strains for the treatment of depression. Except for control group (n = 8), C57BL/6J mice were treated with Lactobacillus during six weeks of chronic unpredictable stress (depression group: n = 9, Lactobacillus intervention group: n = 7). L. paracasei CCFM1229 and L. rhamnosus CCFM1228 significantly reduced depressive behaviour in the forced swimming test and tail suspension test, significantly reduced anxiety behaviour in the open field test, and reduced anxiety behaviour in the marble burying test and light/dark box test. L. paracasei CCFM1229 and L. rhamnosus CCFM1228 significantly increased the brain serotonin and brain-derived neurotrophic factor concentrations, and CCFM1229 significantly decreased the serum corticosterone concentration, all of which are closely associated with the relief of depressive symptoms. Furthermore, CCFM1229 and CCFM1228 were shown to regulate purine metabolism in mice, as indicated by decreases in brain xanthine oxidase activity and an increase in liver adenosine deaminase activity. Anxiety- and depression-related indicators were significantly associated with xanthine oxidase activity in the cerebral cortex. The strains CCFM1229 and CCFM1228 reduced anxiety- and depression-related behaviour in a mouse model of chronic stress-induced depression, which may be achieved by regulating the activity of brain xanthine oxidase.
Relation of Alcohol Intake to Kidney Function and Mortality Observational, Population-Based, Cohort Study
Authors: Cirillo Massimo , Bilancio Giancarlo , Secondulfo Carmine , Iesce Gennaro , Ferrara Carmela , Terradura-Vagnarelli Oscar , Laurenzi Martino
Published: March 2022

Data are conflicting about the effects of alcohol intake on kidney function. This population-based study investigated associations of alcohol intake with kidney function and mortality. The study cohort included adult participants in Exam-1, Exam-2 (6-year follow-up), and Exam-3 (20-year follow-up) of the Gubbio study. Kidney function was evaluated as estimated glomerular filtration rate (eGFR, CKD-Epi equation, mL/min × 1.73 m2). Daily habitual alcohol intake was assessed by questionnaires. Wine intake accounted for >94% of total alcohol intake at all exams. Alcohol intake significantly tracked over time (R > 0.66, p < 0.001). Alcohol intake distribution was skewed at all exams (skewness > 2) and was divided into four strata for analyses (g/day = 0, 1–24, 25–48, and >48). Strata of alcohol intake differed substantially for lab markers of alcohol intake (p < 0.001). In multivariable regression, strata of alcohol intake related cross-sectionally to eGFR at all exams (Exam-1: B = 1.70, p < 0.001; Exam-2: B = 1.03, p < 0.001; Exam-3: B = 0.55, p = 0.010) and related longitudinally to less negative eGFR change from Exam-1 to Exam-2 (B = 0.133, p = 0.002) and from Exam-2 to Exam-3 (B = 0.065, p = 0.004). In multivariable Cox models, compared to no intake, intakes > 24 g/day were not associated with different mortality while an intake of 1–24 g/day was associated with lower mortality in the whole cohort (HR = 0.77, p = 0.003) and in the subgroup with eGFR < 60 mL/min × 1.73 m2 (HR = 0.69, p = 0.033). These data indicate a positive independent association of alcohol intake with kidney function not due to a mortality-related selection.
Plant-Based Diets and Peritoneal Dialysis: A Review
Authors: Liebman Scott E. , Joshi Shivam
Published: March 2022

Whole food plant-based diets are gaining popularity as a preventative and therapeutic modality for numerous chronic health conditions, including chronic kidney disease, but their role and safety in end-stage kidney disease patients on peritoneal dialysis (PD) is unclear. Given the general public’s increased interest in this dietary pattern, it is likely that clinicians will encounter individuals on PD who are either consuming, considering, or interested in learning more about a diet with more plants. This review explores how increasing plant consumption might affect those on PD, encompassing potential benefits, including some specific to the PD population, and potential concerns.
Dietary Recommendations for Post-COVID-19 Syndrome
Authors: Barrea Luigi , Grant William B. , Frias-Toral Evelyn , Vetrani Claudia , Verde Ludovica , de Alteriis Giulia , Docimo Annamaria , Savastano Silvia , Colao Annamaria , Muscogiuri Giovanna
Published: March 2022

At the beginning of the coronavirus disease (COVID-19) pandemic, global efforts focused on containing the spread of the virus and avoiding contagion. Currently, it is evident that health professionals should deal with the overall health status of COVID-19 survivors. Indeed, novel findings have identified post-COVID-19 syndrome, which is characterized by malnutrition, loss of fat-free mass, and low-grade inflammation. In addition, the recovery might be complicated by persistent functional impairment (i.e., fatigue and muscle weakness, dysphagia, appetite loss, and taste/smell alterations) as well as psychological distress. Therefore, the appropriate evaluation of nutritional status (assessment of dietary intake, anthropometrics, and body composition) is one of the pillars in the management of these patients. On the other hand, personalized dietary recommendations represent the best strategy to ensure recovery. Therefore, this review aimed to collect available evidence on the role of nutrients and their supplementation in post-COVID-19 syndrome to provide a practical guideline to nutritionists to tailor dietary interventions for patients recovering from COVID-19 infections.
Household Food Insecurity Is Associated with Symptoms of Emotional Dysregulation in Children with Attention Deficit Hyperactivity Disorder: The MADDY Study
Authors: Hatsu Irene E. , Eiterman Leanna , Stern Madeline , Lu Stacy , Johnstone Jeanette M. , Leung Brenda M. Y. , Srikanth Priya , Robinette Lisa , Tost Gabriella , Odei James B. , Gracious Barbara L. , Arnold L. Eugene
Published: March 2022

The association of household food insecurity with symptoms of attention deficit hyperactivity disorder (ADHD) and emotional dysregulation in children was examined in this study. We utilized baseline data from 134 children aged 6–12 years who were enrolled in a clinical trial investigating multinutrient supplementation as a treatment for ADHD and emotional dysregulation. Household food security status was assessed using the 18-item US Household Food Security Survey Module. The symptoms of ADHD and emotional dysregulation disorders (oppositional defiant disorder (ODD) and disruptive mood dysregulation disorder (DMDD)) were assessed using the Child and Adolescent Symptom Inventory-5 and other comorbid emotional dysregulation symptoms were assessed using the Strengths and Difficulties Questionnaire (SDQ). Multiple linear regression determined associations between household food security status and symptoms of ADHD, ODD and DMDD, emotional symptoms and conduct problems. Household food insecurity was associated with more severe emotional symptoms (β = 2.30; 95% CI = 0.87–3.73; p = 0.002), conduct problems (β = 1.15; 95% CI = 0.01–2.30; p = 0.049) and total difficulties scores (β = 4.59; 95% CI = 1.82–7.37; p = 0.001) after adjusting for covariates (child’s sex, parent marital status, household income, parental anxiety and other parental psychopathology). In unadjusted analyses, household food insecurity was also associated with increased ODD (β = 0.58; 95% CI = 0.21–0.95; p = 0.003) and DMDD symptoms (β = 0.69; 95% CI = 0.20–1.19; p = 0.006), but these associations attenuated to non-significance after adjusting for all covariates. Household food insecurity was associated with more severe emotional dysregulation symptoms. Discussing and addressing food insecurity may be appropriate initial steps for youths with ADHD and emotional dysregulation.
Selected Organ and Endocrine Complications According to BMI and the Metabolic Category of Obesity: A Single Endocrine Center Study
Authors: Milewska Ewa Malwina , Szczepanek-Parulska Ewelina , Marciniak Martyna , Krygier Aleksandra , Dobrowolska Agnieszka , Ruchala Marek
Published: March 2022

Obesity is a chronic and complex disease associated with metabolic, organ and endocrine complications. In the study, we analyzed a group of 105 patients suffering from obesity without any other previously recognized serious disorders who had been referred to a single endocrine center. The study aimed to assess the prevalence of selected organ and endocrine complications by subdividing the group, firstly according to body mass index (BMI) and secondly with regard to metabolic syndrome (MetS), pre-MetS and the metabolically healthy obesity (MHO) category. We have observed that in our groups, the prevalence of hyperlipidemia, hypertension, asthma, obstructive sleep apnea (OSA) depended on BMI category, whereas the incidence of hyperlipidemia, hypertension, OSA, hypothyroidism, non-alcoholic fatty liver disease, prediabetes, and type 2 diabetes was related to the metabolic category. We concluded that the distribution of particular organ and endocrine complications change significantly with increased BMI and with the shift from MHO to pre-MetS and MetS. Thus, to determine the risk of organ and endocrine complications more effectively, BMI and metabolic status should be assessed during the examination of patients with obesity.
Bronchoscopy and Lung Fine-Needle Aspiration for Antemortem Evaluation of Pulmonary Involvement in Dogs with Naturally Occurring Canine Leishmaniosis
Authors: Kavarnos Ioannis , Pardali Dimitra , Brellou Georgia D. , Papadopoulos Elias , Kritsepi-Konstantinou Maria , Adamama-Moraitou Katerina K.
Published: March 2022

Clinical manifestations from the lower respiratory tract are rare in canine leishmaniosis (CanL), making bronchoscopy and lung fine-needle aspiration (FNA) seldomly justified. The aim of this prospective study was to investigate the involvement of Leishmania infantum in the lungs of dogs with naturally occurring CanL by bronchoscopy and examination of bronchoalveolar lavage fluid (BALF), bronchial mucosa biopsies, and FNA, using immunodiagnostics. Dogs with relevant concurrent diseases and azotemia were excluded. Cough was detected in 5/31 (16.1%) dogs. Lesions (hyperemia, edema, mucosal granularity, secretions) were identified upon bronchoscopy in 19/31 (61.3%) dogs. The cytology of BALF revealed histiocytic inflammation in 14/31 (45.2%) dogs; the parasite was identified in one dog (3.2%). The immunofluorescence antibody test in BALF was positive in 15/31 (48.4%) dogs. Histopathology of bronchial mucosa and/or adjacent alveoli revealed lesions (mononuclear cell infiltration, fibrosis, edema, thickening of the inter-alveolar septa) in 24/31 (77.4%) dogs, with no Leishmania amastigotes. Positive antigen staining was observed within the cytoplasm of mononuclear cells in immunocytochemistry and immunohistochemistry. Μononuclear cells showed antigenic positivity in bronchial mucosa (27/31; 87.1%), BALF (30/31; 96.8%), and lung FNA (27/31; 87.1%). In conclusion, lungs seem to be affected from CanL more commonly than previously believed, and bronchoscopy allows obtaining valuable samples for antemortem diagnosis.
A Review of SARS-CoV-2 Disease (COVID-19): Pandemic in Our Time
Authors: Al-Awwal Nasruddeen , Dweik Ferris , Mahdi Samira , El-Dweik Majed , Anderson Stephen H.
Published: March 2022

Development and deployment of biosensors for the rapid detection of the 2019 novel severe acute respiratory syndrome—coronavirus 2 (SARS-CoV-2) are of utmost importance and urgency during this recent outbreak of coronavirus pneumonia (COVID-19) caused by SARS-CoV-2 infection, which spread rapidly around the world. Cases now confirmed in February 2022 indicate that more than 170 countries worldwide are affected. Recent evidence indicates over 430 million confirmed cases with over 5.92 million deaths scattered across the globe, with the United States having more than 78 million confirmed cases and over 920,000 deaths. The US now has many more cases than in China where coronavirus cases were first reported in late December 2019. During the initial outbreak in China, many leaders did not anticipate it could reach the whole world, spreading to many countries and posing severe threats to global health. The objective of this review is to summarize the origin of COVID-19, its biological nature, comparison with other coronaviruses, symptoms, prevention, treatment, potential, available methods for SARS-CoV-2 detection, and post-COVID-19 symptoms.
Trash to Treasure: How Insect Protein and Waste Containers Can Improve the Environmental Footprint of Mosquito Egg Releases
Authors: Allman Megan J. , Slack Aidan J. , Abello Nigel P. , Lin Ya-Hsun , O’Neill Scott L. , Robinson Andrea J. , Flores Heather A. , Joubert D. Albert
Published: March 2022

Release and subsequent establishment of Wolbachia-infected Aedes aegypti in native mosquito populations has successfully reduced mosquito-borne disease incidence. While this is promising, further development is required to ensure that this method is scalable and sustainable. Egg release is a beneficial technique that requires reduced onsite resources and increases community acceptance; however, its incidental ecological impacts must be considered to ensure sustainability. In this study, we tested a more environmentally friendly mosquito rearing and release approach through the encapsulation of diet and egg mixtures and the subsequent utilization of waste containers to hatch and release mosquitoes. An ecologically friendly diet mix was specifically developed and tested for use in capsules, and we demonstrated that using either cricket or black soldier fly meal as a substitute for beef liver powder had no adverse effects on fitness or Wolbachia density. We further encapsulated both the egg and diet mixes and demonstrated no loss in viability. To address the potential of increased waste generation through disposable mosquito release containers, we tested reusing commonly found waste containers (aluminum and tin cans, PET, and glass bottles) as an alternative, conducting a case study in Kiribati to assess the concept’s cultural, political, and economic applicability. Our results showed that mosquito emergence and fitness was maintained with a variety of containers, including when tested in the field, compared to control containers, and that there are opportunities to implement this method in the Pacific Islands in a way that is culturally considerate and cost-effective.
Use of Early Donated COVID-19 Convalescent Plasma Is Optimal to Preserve the Integrity of Lymphatic Endothelial Cells
Authors: Amri Nada , Bégin Rémi , Tessier Nolwenn , Vachon Laurent , Villeneuve Louis , Bégin Philippe , Bazin Renée , Loubaki Lionel , Martel Catherine
Published: March 2022

Convalescent plasma therapy (CPT) has gained significant attention since the onset of the coronavirus disease 2019 (COVID-19) pandemic. However, clinical trials designed to study the efficacy of CPT based on antibody concentrations were inconclusive. Lymphatic transport is at the interplay between the immune response and the resolution of inflammation from peripheral tissues, including the artery wall. As vascular complications are a key pathogenic mechanism in COVID-19, leading to inflammation and multiple organ failure, we believe that sustaining lymphatic vessel function should be considered to define optimal CPT. We herein sought to determine what specific COVID-19 convalescent plasma (CCP) characteristics should be considered to limit inflammation-driven lymphatic endothelial cells (LEC) dysfunction. CCP donated 16 to 100 days after the last day of symptoms was characterized and incubated on inflammation-elicited adult human dermal LEC (aHDLEC). Plasma analysis revealed that late donation correlates with higher concentration of circulating pro-inflammatory cytokines. Conversely, extracellular vesicles (EVs) derived from LEC are more abundant in early donated plasma (r = −0.413, p = 0.004). Thus, secretion of LEC-EVs by an impaired endothelium could be an alarm signal that instigate the self-defense of peripheral lymphatic vessels against an excessive inflammation. Indeed, in vitro experiments suggest that CCP obtained rapidly following the onset of symptoms does not damage the aHDLEC junctions as much as late-donated plasma. We identified a particular signature of CCP that would counteract the effects of an excessive inflammation on the lymphatic endothelium. Accordingly, an easy and efficient selection of convalescent plasma based on time of donation would be essential to promote the preservation of the lymphatic and immune system of infected patients.
Cannabidiol on the Path from the Lab to the Cancer Patient: Opportunities and Challenges
Authors: Olivas-Aguirre Miguel , Torres-López Liliana , Villatoro-Gómez Kathya , Perez-Tapia Sonia Mayra , Pottosin Igor , Dobrovinskaya Oxana
Published: March 2022

Cannabidiol (CBD), a major non-psychotropic component of cannabis, is receiving growing attention as a potential anticancer agent. CBD suppresses the development of cancer in both in vitro (cancer cell culture) and in vivo (xenografts in immunodeficient mice) models. For critical evaluation of the advances of CBD on its path from laboratory research to practical application, in this review, we wish to call the attention of scientists and clinicians to the following issues: (a) the biological effects of CBD in cancer and healthy cells; (b) the anticancer effects of CBD in animal models and clinical case reports; (c) CBD’s interaction with conventional anticancer drugs; (d) CBD’s potential in palliative care for cancer patients; (e) CBD’s tolerability and reported side effects; (f) CBD delivery for anticancer treatment.
Enantioselectivity of Pentedrone and Methylone on Metabolic Profiling in 2D and 3D Human Hepatocyte-like Cells
Authors: Silva Bárbara , Rodrigues Joana Saraiva , Almeida Ana Sofia , Lima Ana Rita , Fernandes Carla , Guedes de Pinho Paula , Miranda Joana Paiva , Remião Fernando
Published: March 2022

Pentedrone and methylone can express stereoselectivity in toxicokinetic and toxicodynamic processes. Similarly, their chiral discrimination in metabolism, which was not yet evaluated, can result in different metabolic profiles and subsequent hepatotoxic effects. Therefore, the aim of this work was to assess, for the first time, both the hepatic cytotoxic and metabolic profile of pentedrone and methylone enantiomers using physiologically relevant in vitro models. The hepatotoxicity of these compounds was observed in a concentration-dependent manner in human stem-cell-derived hepatocyte-like cells (HLCs) cultured under 3D (3D-HLCs) and 2D (2D-HLCs) conditions. Enantioselectivity, on the other hand, was only shown for pentedrone (1 mM) in 3D-HLCs, being R-(−)-pentedrone the most cytotoxic. Furthermore, the metabolic profile was initially evaluated in human liver microsomes (HLM) and further demonstrated in 3D-HLCs and 2D-HLCs applying a gas chromatography coupled to a mass spectrometer (GC–MS) technique. Methylone and pentedrone showed distinct and preferential metabolic routes for their enantiomers, resulting in the production of differentiated metabolites; R-(+)-methylone and R-(−)-pentedrone are the most metabolized enantiomers. In conclusion, the results demonstrated enantioselectivity for pentedrone and methylone in the metabolic processes, with enantioselectivity in cytotoxicity for pentedrone.
Design and Development of Levodopa Loaded Polymeric Nanoparticles for Intranasal Delivery
Authors: Ahmad Mohd Zulhelmy , Sabri Akmal Hidyat Bin , Anjani Qonita Kurnia , Domínguez-Robles Juan , Abdul Latip Normala , Hamid Khuriah Abdul
Published: March 2022

Intranasal delivery is an alternative administration route to deliver levodopa (L-Dopa) to the brain. This drug delivery route offers high drug permeability across the nasal epithelium and rapid absorption into the central nervous system (CNS) while bypassing first-pass metabolism. In this study, we developed a library of polymeric nanocarrier systems for L-Dopa utilising poly(lactic-co-glycolic acid) (PLGA) and chitosan. A total of three PLGA nanoparticles formulations (P1, P2 and P3) were prepared using a modified water-in-oil-in-water (W/O/W) solvent evaporation technique, while four formulations of chitosan nanoparticles (C1, C2, C3 and C4) were prepared by ionic gelation method with sodium tripolyphosphate (TPP) as a cross-linking agent. Upon characterising nanocarriers developed, it was discovered that C2 demonstrated the best results with regard to droplet size (553 ± 52 nm), polydispersity index (0.522), zeta potential (+46.2 ± 2.3 mV), and encapsulation efficiency (82.38% ± 1.63). Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) further corroborated the particle size analysis highlighting that C2 displayed uniform particle size with spherical morphology. Additionally, X-ray diffraction analysis (XRD) revealed that C2 was in an amorphous state while Fourier transform infrared (FTIR) analysis showed that there were no chemical interactions that might change the chemical structure of L-Dopa within the polymeric nanoparticle matrix. Lastly, an in-vivo intranasal study in male Wistar rats showed that the absorption of L-Dopa when formulated as chitosan nanoparticles was significantly enhanced (p < 0.05) by approximately two-fold compared to unmodified L-Dopa. Therefore, this work illustrates that formulating L-Dopa into chitosan nanoparticles for intranasal delivery is a potentially viable formulation strategy to improve the bioavailability of the drug for the treatment of Parkinson’s disease.
Up-to-Date Overview of the Use of Natural Ingredients in Sunscreens
Authors: Resende Diana I. S. P. , Jesus Ana , Sousa Lobo José M. , Sousa Emília , Cruz Maria T. , Cidade Honorina , Almeida Isabel F.
Published: March 2022

The photoprotective skincare segment is in high demand to meet consumer concerns on UV-induced skin damage, with a recent trend towards sunscreen alternatives with a natural origin. In this study, the use of natural ingredients, either from terrestrial or marine origin, in a panel of 444 sunscreen commercial formulations (2021) was analyzed. Ingredients from terrestrial organisms represent the large majority found in the analyzed sunscreen formulations (48%), whereas marine ingredients are present only in 13% of the analyzed products. A deeper analysis regarding the most prevalent families of ingredients from terrestrial and marine organisms used as top ingredients is also presented, as well as their mechanisms of action. This study provides an up-to-date overview of the sunscreen market regarding the use of natural ingredients, which is of relevance for scientists involved in the development of new sunscreens to identify opportunities for innovation.
Polymorphic and Higher-Order G-Quadruplexes as Possible Transcription Regulators: Novel Perspectives for Future Anticancer Therapeutic Applications
Authors: Rigo Riccardo , Groaz Elisabetta , Sissi Claudia
Published: March 2022

In the past two decades, significant efforts have been put into designing small molecules to target selected genomic sites where DNA conformational rearrangements control gene expression. G-rich sequences at oncogene promoters are considered good points of intervention since, under specific environmental conditions, they can fold into non-canonical tetrahelical structures known as G-quadruplexes. However, emerging evidence points to a frequent lack of correlation between small molecule targeting of G-quadruplexes at gene promoters and the expression of the associated protein, which hampers pharmaceutical applications. The wide genomic localization of G-quadruplexes along with their highly polymorphic behavior may account for this scenario, suggesting the need for more focused drug design strategies. Here, we will summarize the G4 structural features that can be considered to fulfill this goal. In particular, by comparing a telomeric sequence with the well-characterized G-rich domain of the KIT promoter, we will address how multiple secondary structures might cooperate to control genome architecture at a higher level. If this holds true, the link between drug–DNA complex formation and the associated cellular effects will need to be revisited.
New Applications of JAK/STAT Inhibitors in Pediatrics: Current Use of Ruxolitinib
Authors: Marcuzzi Annalisa , Rimondi Erika , Melloni Elisabetta , Gonelli Arianna , Grasso Antonio Giacomo , Barbi Egidio , Maximova Natalia
Published: March 2022

Janus kinases (JAK) are a family of tyrosine kinases (JAK1, JAK2, JAK3, and TYK2) that transduce cytokine-mediated signals through the JAK–STAT metabolic pathway. These kinases act by regulating the transcription of specific genes capable of inducing biological responses in several immune cell subsets. Inhibition of Janus kinases interferes with the JAK–STAT signaling pathway. Besides being used in the treatment of cancer and inflammatory diseases, in recent years, they have also been used to treat inflammatory conditions, such as graft-versus-host disease (GVHD) and cytokine release syndrome as complications of allogeneic hematopoietic stem cell transplantation and cell therapy. Recently, the FDA approved the use of ruxolitinib, a JAK1/2 inhibitor, in the treatment of acute steroid-refractory GVHD (SR-aGVHD), highlighting the role of JAK inhibition in this immune deregulation. Ruxolitinib was initially used to treat myelofibrosis and true polycythemia in a high-dose treatment and caused hematological toxicity. Since a lower dosage often could not be effective, the use of ruxolitinib was suspended. Subsequently, ruxolitinib was evaluated in adult patients with SR-aGVHD and was found to achieve a rapid and effective response. In addition, its early low-dose use in pediatric patients affected by GVHD has proved effective, safe, and reasonably preventive. The review aims to describe the potential properties of ruxolitinib to identify new therapeutic strategies.
Targeting Wnt/Beta-Catenin Signaling in HPV-Positive Head and Neck Squamous Cell Carcinoma
Authors: Brkic Faris F. , Stoiber Stefan , Maier Tobias , Gurnhofer Elisabeth , Kenner Lukas , Heiduschka Gregor , Kadletz-Wanke Lorenz
Published: March 2022

Wnt/Beta-Catenin signaling is involved in the carcinogenesis of different solid malignant tumors. The interaction of Creb-binding protein (CBP) with Beta-Catenin is a pivotal component of the Wnt/Beta-Catenin signaling pathway. The first aim of this study was to evaluate the association of CBP expression with survival in patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC). Second, the in vitro effects of the inhibition of CBP/Beta-Catenin interaction were analyzed. In particular, the effects of ICG-001, an inhibitor of CBP/Beta-Catenin interaction, on proliferation, cell death, modulation of Wnt/Beta-Catenin target expression, and cell migration were examined in vitro. High CBP expression is significantly associated with better survival on mRNA and protein levels. Furthermore, we observed cytotoxic as well as anti-migratory effects of ICG-001. These effects were particularly more potent in the HPV-positive than in the -negative cell line. Mechanistically, ICG-001 treatment induced apoptosis and led to a downregulation of CBP, c-MYC, and Cyclin D1 in HPV-positive cells, indicating inhibition of Wnt/Beta-Catenin signaling. In conclusion, high CBP expression is observed in HPV-positive HNSCC patients with a good prognosis, and ICG-001 showed a promising antineoplastic potential, particularly in HPV-positive HNSCC cells. Therefore, ICG-001 may potentially become an essential component of treatment de-escalation regimens for HPV-positive HNSCC. Further studies are warranted for additional assessment of the mechanistic background of our in vitro findings.
Linearity-Enhanced Dual-Parallel Mach–Zehnder Modulators Based on a Thin-Film Lithium Niobate Platform
Authors: Huang Xingrui , Liu Yang , Tu Donghe , Yu Zhiguo , Wei Qingquan , Li Zhiyong
Published: March 2022

In this work, we report a linearity-enhanced dual-parallel Mach–Zehnder modulator (MZM) on a thin-film lithium niobate platform. By setting the optical and electrical splitting ratios at a specific condition, the third-order intermodulation distortions (IMD3) of the child MZMs cancel with each other, whereas the first-order harmonics (FH) reach the maximum. Passive devices instead of thermo-optical switches are used to control the optical power and phase of the child MZMs, which greatly improve the device stability and simplify the operation complexity. To the best of our knowledge, the experimental results show a record-high spurious-free dynamic range on a thin-film lithium niobate platform (110.7 dB·Hz2/3 at 1 GHz). The E-O response decayed about 1.9 dB from 10 MHz to 40 GHz, and the extrapolated E-O 3 dB bandwidth is expected to be 70 GHz. A half-wave voltage of 2.8 V was also achieved. The proposed modulator provides a promising solution for high-bandwidth and low-voltage analog optical links.
NLP2-NR Module Associated NO Is Involved in Regulating Seed Germination in Rice under Salt Stress
Authors: Yi Yake , Peng Yaqiong , Song Tao , Lu Siqiong , Teng Zhenning , Zheng Qin , Zhao Fankai , Meng Shuan , Liu Bohang , Peng Yan , Chen Guanghui , Zhang Jianhua , Ye Nenghui
Published: March 2022

Salt stress has the most severe impact on plant growth and development, including seed germination. However, little is known about the mechanism of NR (nitrate reductase)-associated nitric oxide (NO) regulates salt tolerance during seed germination in rice. Herein, we shown that inhibition of seed germination by salt stress was significantly impaired by sodium nitroferricyanide (SNP), a NO donor. Then a triple mutant, nr1/nr2/nr3, was generated. Results shown that germination of triple mutants were delayed and were much more sensitive to salt stress than WT plant, which can be rescued by application of SNP. qPCR analysis revealed that expressions of abscisic acid (ABA) catabolism gene, OsABA8ox1, was suppressed in triple mutants under salt stress, resulting in an elevated ABA content. Similar to SNP, application of nitrate also rescued seed germination under salt stress, which, however, was blocked in the triple mutants. Further study revealed that a nitrate responsive transcript factor, OsNLP2, was induced by salt stress, which thus up-regulates the expression of OsNRs and NR activity, resulting in promoted salt tolerance during seed germination. In addition, nitrate-mediated salt tolerance was impaired in mutant of aba8ox1, a target gene for NLP2. Transient trans-activation assays further revealed NLP2 can significantly activate the expression of OsABA8ox1 and OsNR1, suggesting that NLP2 activates expression of ABA catabolism gene directly or indirectly via NR-associated NO. Taken together, our results demonstrate that NLP2-NR associated NO was involved in salt response by increasing ABA catabolism during seed germination and highlight the importance of NO for stress tolerance of plants.
Identification of Genes in Xanthomonas euvesicatoria pv. rosa That Are Host Limiting in Tomato
Authors: Fan Qiurong , Bibi Shaheen , Vallad Gary E. , Goss Erica M. , Hurlbert Jason C. , Paret Matthews L. , Jones Jeffrey B. , Timilsina Sujan
Published: March 2022

Xanthomonas euvesicatoria pv. rosa strain Xer07 causes a leaf spot on a Rosa sp. and is closely related to X. euvesicatoria pv. euvesicatoria (Xee) and X. perforans (Xp), causal agents of bacterial spot of tomato. However, Xer07 is not pathogenic on tomato and elicits a hypersensitive reaction (HR). We compared the genomes of the three bacterial species to identify the factors that limit Xer07 on tomato. Comparison of pathogenicity associated factors including the type III secretion systems identified two genes, xopA and xer3856, in Xer07 that have lower sequence homology in tomato pathogens. xer3856 is a homolog of genes in X. citri (xac3856) and X. fuscans pv. aurantifolii, both of which have been reported to elicit HRs in tomato. When xer3856 was expressed in X. perforans and infiltrated in tomato leaflets, the transconjugant elicited an HR and significantly reduced bacterial populations compared to the wildtype X. perforans strain. When xer3856 was mutated in Xer07, the mutant strain still triggered an HR in tomato leaflets. The second gene identified codes for type III secreted effector XopA, which contains a harpin domain that is distinct from the xopA homologs in Xee and Xp. The Xer07-xopA, when expressed in X. perforans, did not elicit an HR in tomato leaflets, but significantly reduced bacterial populations. This indicates that xopA and xer3856 genes in combination with an additional factor(s) limit Xer07 in tomato.
Effect of Salinity on Growth, Ion Accumulation and Mineral Nutrition of Different Accessions of a Crop Wild Relative Legume Species, Trifolium fragiferum
Authors: Jēkabsone Astra , Andersone-Ozola Una , Karlsons Andis , Romanovs Māris , Ievinsh Gederts
Published: March 2022

Crop wild relatives represent a valuable resource for the breeding of new crop varieties suitable for sustainable productivity in conditions of climate change. The aim of the present study was to assess salt tolerance of several wild accessions of T. fragiferum from habitats with different salinity levels in controlled conditions. Decrease of plant biomass and changes in partitioning between different organs was a characteristic response of plants with increasing substrate salinity, but these responses were genotype-specific. In several accessions, salinity stimulated reproductive development. The major differences in salinity responses between various T. fragiferum genotypes were at the level of dry biomass accumulation as well as water accumulation in plant tissues, resulting in relatively more similar effect on fresh mass. Na+ and Cl− accumulation capacity were organ-specific, with leaf petioles accumulating more, followed by leaf blades and stolons. Responses of mineral nutrition clearly were both genotype- and organ-specific, but several elements showed a relatively general pattern, such as increase in Zn concentration in all plant parts, and decrease in Ca and Mg concentration. Alterations in mineralome possibly reflect a reprogramming of the metabolism to adapt to changes in growth, morphology and ion accumulation resulting from effect of NaCl. High intraspecies morphological and physiological variability in responses of T. fragiferum accessions to salinity allow to describe them as ecotypes.
Genetic Diversity, Population Structure and Linkage Disequilibrium Analyses in Tropical Maize Using Genotyping by Sequencing
Authors: Kumar Bhupender , Rakshit Sujay , Kumar Sonu , Singh Brijesh Kumar , Lahkar Chayanika , Jha Abhishek Kumar , Kumar Krishan , Kumar Pardeep , Choudhary Mukesh , Singh Shyam Bir , Amalraj John J. , Prakash Bhukya , Khulbe Rajesh , Kamboj Mehar Chand , Chirravuri Neeraja N. , Hossain Firoz
Published: March 2022

Several maize breeding programs in India have developed numerous inbred lines but the lines have not been characterized using high-density molecular markers. Here, we studied the molecular diversity, population structure, and linkage disequilibrium (LD) patterns in a panel of 314 tropical normal corn, two sweet corn, and six popcorn inbred lines developed by 17 research centers in India, and 62 normal corn from the International Maize and Wheat Improvement Center (CIMMYT). The 384 inbred lines were genotyped with 60,227 polymorphic single nucleotide polymorphisms (SNPs). Most of the pair-wise relative kinship coefficients (58.5%) were equal or close to 0, which suggests the lack of redundancy in the genomic composition in the majority of inbred lines. Genetic distance among most pairs of lines (98.3%) varied from 0.20 to 0.34 as compared with just 1.7% of the pairs of lines that differed by <0.20, which suggests greater genetic variation even among sister lines. The overall average of 17% heterogeneity was observed in the panel indicated the need for further inbreeding in the high heterogeneous genotypes. The mean nucleotide diversity and frequency of polymorphic sites observed in the panel were 0.28 and 0.02, respectively. The model-based population structure, principal component analysis, and phylogenetic analysis revealed three to six groups with no clear patterns of clustering by centers-wise breeding lines, types of corn, kernel characteristics, maturity, plant height, and ear placement. However, genotypes were grouped partially based on their source germplasm from where they derived.