bluuebunny/crossref_metadata_2025 huggingface dataset:
The Association between the School Environment and Adolescent Alcohol Drinking Behavior in Six Cities in China
Authors: Chi Ruixin , Lu Shijun , Zhang Na , Zhang Man , Guo Kaiwei , Du Songming , Guo Jing , Ma Guansheng
Published: January 2023

Drinking alcohol during adolescence has short-term and long-term effects on physical and mental health. At this stage, teenagers are greatly influenced by their schoolmates and friends. We conducted a multicenter cross-sectional study to investigate the association between school environment factors and adolescents’ drinking behavior in China. Using multistage stratified cluster sampling, the study investigated 27,762 middle school students from six cities in China. The logistic regression model was used to explore the association between the school environment and adolescent alcohol drinking behaviors after adjusting for confounders, including gender, age, city, location, and smoking status. Compared with students with none of their close friends drinking, students with more than half of their close friends drinking were more likely to drink in a year (OR = 20.148, 95% CI: 17.722–22.905, p < 0.001) and in a month (OR = 13.433, 95% CI: 11.779–15.319, p < 0.001). In addition, classmates’ drinking behaviors, friends’ persuasion, and attending parties were risk factors for adolescents’ drinking behavior, while the propaganda and regulations of banning drinking in school were protective factors. The school environment, especially friends drinking, is associated with students’ drinking behavior. It is necessary to mobilize the strength of schools and peers to strengthen the prevention and control of adolescent drinking.
Consumption of Eggs Alone or Enriched with Annatto (Bixa orellana L.) Does Not Increase Cardiovascular Risk in Healthy Adults—A Randomized Clinical Trial, the Eggant Study
Authors: Galvis Yeisson , Pineda Keilly , Zapata Juliana , Aristizabal Juan , Estrada Alejandro , Fernandez María Luz , Barona-Acevedo Jacqueline
Published: January 2023

Most atherosclerotic cardiovascular diseases can be prevented by modifying lifestyles, including unhealthy diets. Eggs contain important carotenoids that may impact cardiovascular risk. The lipid nature of eggs can improve the bioavailability of other carotenoids, such as Annatto (Bixa orellana L.), with reported antioxidant properties. Although numerous studies have shown that there is no association between egg consumption and cardiovascular risk, there is still controversy. In addition, there is limited information about Annatto’s effects on human health. This study evaluated the association between egg consumption and its enrichment with Annatto in lipid biomarkers of cardiovascular disease. In a parallel clinical trial, one hundred and five (n = 105) men and women were randomized by age, sex, and body mass index (BMI), and distributed into three groups. Subjects consumed daily, for 8 weeks, either two eggs, two eggs with Annatto, or two egg whites. Plasma lipids were measured by enzymatic colorimetric methods, plasma apolipoproteins and lipoprotein subfractions and size by nuclear magnetic resonance. There were no differences between groups in age, sex, and BMI. No significant changes were found over time or between groups in plasma triglycerides, LDL cholesterol, HDL cholesterol, apolipoprotein (apo) A1, apo B, or lipoprotein subfraction concentrations. In healthy adults, the intake of two eggs a day, or two eggs with Annatto for eight weeks, did not generate adverse changes in cardiovascular risk markers.
Interaction between SIDT2 and ABCA1 Variants with Nutrients on HDL-c Levels in Mexican Adults
Authors: León-Reyes Guadalupe , Argoty-Pantoja Anna D. , Rivera-Paredez Berenice , Hidalgo-Bravo Alberto , Flores Yvonne N. , Salmerón Jorge , Velázquez-Cruz Rafael
Published: January 2023

Previous studies have reported that the SIDT2 and ABCA1 genes are involved in lipid metabolism. We aimed to analyze the association—the gene x gene interaction between rs17120425 and rs1784042 on SIDT2 and rs9282541 on ABCA1 and their diet interaction on the HDL-c serum levels—in a cohort of 1982 Mexican adults from the Health Workers Cohort Study. Demographic and clinical data were collected through a structured questionnaire and standardized procedures. Genotyping was performed using a predesigned TaqMan assay. The associations and interactions of interest were estimated using linear and logistic regression. Carriers of the rs17120425-A and rs1784042-A alleles had slightly higher blood HDL-c levels compared to the non-carriers. In contrast, rs9282541-A was associated with low blood HDL-c levels (OR = 1.34, p = 0.013). The rs1784042 x rs9282541 interaction was associated with high blood HDL-c levels (p = 3.4 × 10−4). Premenopausal women who carried at least one rs17120425-A allele and consumed high dietary fat, protein, monounsaturated, or polyunsaturated fatty acids levels had higher HDL-c levels than the non-carriers. These results support the association between the genetic variants on SIDT2 and ABCA1 with HDL-c levels and suggest gene–gene and gene–diet interactions over HDL-c concentrations in Mexican adults. Our findings could be a platform for developing clinical and dietary strategies for improving the health of the Mexican population.
Bibliometric Analysis of Functional Crops and Nutritional Quality: Identification of Gene Resources to Improve Crop Nutritional Quality through Gene Editing Technology
Authors: Wei Xun , Long Yan , Yi Chenchen , Pu Aqing , Hou Quancan , Liu Chang , Jiang Yilin , Wu Suowei , Wan Xiangyuan
Published: January 2023

Food security and hidden hunger are two worldwide serious and complex challenges nowadays. As one of the newly emerged technologies, gene editing technology and its application to crop improvement offers the possibility to relieve the pressure of food security and nutrient needs. In this paper, we analyzed the research status of quality improvement based on gene editing using four major crops, including rice, soybean, maize, and wheat, through a bibliometric analysis. The research hotspots now focus on the regulatory network of related traits, quite different from the technical improvements to gene editing in the early stage, while the trends in deregulation in gene-edited crops have accelerated related research. Then, we mined quality-related genes that can be edited to develop functional crops, including 16 genes related to starch, 15 to lipids, 14 to proteins, and 15 to other functional components. These findings will provide useful reference information and gene resources for the improvement of functional crops and nutritional quality based on gene editing technology.
Vitamin A- and D-Deficient Diets Disrupt Intestinal Antimicrobial Peptide Defense Involving Wnt and STAT5 Signaling Pathways in Mice
Authors: Filipe Rosa Louisa , Petersen Patricia P. , Görtz Lisa F. , Stolzer Iris , Kaden-Volynets Valentina , Günther Claudia , Bischoff Stephan C.
Published: January 2023

Vitamin A and D deficiencies are associated with immune modulatory effects and intestinal barrier impairment. However, the underlying mechanisms remain unclear. C57BL/6J mice were fed either a diet lacking in vitamin A (VAd), vitamin D (VDd) or a control diet (CD) for 12 weeks. Gut barrier function, antimicrobial peptide (AMP) defense and regulatory pathways were assessed. VAd mice compared to CD mice showed a reduced villus length in the ileum (p < 0.01) and decreased crypt depth in the colon (p < 0.05). In both VAd- and VDd-fed mice, ileal α-defensin 5 (p < 0.05/p < 0.0001 for VAd/VDd) and lysozyme protein levels (p < 0.001/p < 0.0001) were decreased. Moreover, mRNA expression of lysozyme (p < 0.05/p < 0.05) and total cryptdins (p < 0.001/p < 0.01) were reduced compared to controls. Furthermore, matrix metalloproteinase-7 (Mmp7) mRNA (p < 0.0001/p < 0.001) as well as components of the Wnt signaling pathway were decreased. VAd- and VDd-fed mice, compared to control mice, exhibited increased expression of pro-inflammatory markers and β-defensins in the colon. Organoid cell culture confirmed that vitamins A and D regulate AMP expression, likely through the Jak/STAT5 signaling pathway. In conclusion, our data show that vitamin A and D regulate intestinal antimicrobial peptide defense through Wnt and STAT5 signaling pathways.
Joint Effects of Prenatal Folic Acid Supplement with Prenatal Multivitamin and Iron Supplement on Obesity in Preschoolers Born SGA: Sex Specific Difference
Authors: Lu Qing , Strodl Esben , Liang Yang , Huang Li-Hua , Hu Bing-Jie , Chen Wei-Qing
Published: January 2023

Prenatal maternal nutrient supplementation has been reported to be associated with offspring obesity, but the reports are inconsistent and have mainly ignored the differences between the total children population and children born small for gestational age (SGA). This study aimed to examine the joint effects of folic acid, iron, and multivitamin supplementation during pregnancy on the risk of obesity in preschoolers born SGA. A total of 8918 children aged 3–6.5 years born SGA were recruited from Longhua District in Shenzhen of China in 2021. Their mothers completed a structured questionnaire about the child’s and parents’ socio-demographic characteristics, maternal prepregnant obesity, and mothers’ prenatal supplementation of folic acid, iron, and multivitamin. In addition, the children’s current weight and height were measured by trained nurses. Logistic regression models were used to analyze the associations between prenatal supplementations and the current presence of childhood obesity. After controlling for potential confounders, the results of the logistic regression analysis showed that prenatal supplement of folic acid (OR = 0.72, 95% CI = 0.55~0.93) was associated with a lower likelihood of being an obese preschooler born SGA. In contrast, the ingestion of multivitamin or iron supplements during pregnancy did not seem to be related to the likelihood of childhood obesity in preschoolers born SGA. Moreover, cross-over analysis of prenatal folic acid and multivitamin obtained significant negative associations of prenatal folic acid supplement only (OR = 0.73, 95% CI = 0.55~0.97) and combination supplement of folic acid and multivitamin (OR = 0.67, 95% CI = 0.50~0.90) with obesity of preschoolers born SGA; while the cross-over analysis of prenatal folic acid and iron observed significant negative associations between obesity of preschoolers born SGA and a combination supplement of folic acid and iron (OR = 0.70, 95% CI = 0.52~0.96). Furthermore, the aforementioned significant associations were only found in girls and not in boys when the analyses were stratified by sex. Our findings suggest that the prenatal folic acid supplementation may decrease the risk of obesity in preschool girls born SGA, and that this effect may be modified by prenatal multivitamin or iron supplementation.
Is Curcumine Useful in the Treatment and Prevention of the Tendinopathy and Myotendinous Junction Injury? A Scoping Review
Authors: Córdova Alfredo , Drobnic Franchek , Noriega-González David , Caballero-García Alberto , Roche Enrique , Alvarez-Mon Melchor
Published: January 2023

Physical activity in general and sports in particular, is a mechanism that produces stress and generates great force in the tendon and in the muscle-tendon unit, which increases the risk of injury (tendinopathies). Eccentric and repetitive contraction of the muscle precipitates persistent microtraumatism in the tendon unit. In the development of tendinopathies, the cellular process includes inflammation, apoptosis, vascular, and neuronal changes. Currently, treatments with oral supplements are frequently used. Curcumin seems to preserve, and even repair, damaged tendons. In this systematic review, we focus more especially on the benefits of curcumin. The biological actions of curcumin are diverse, but act around three systems: (a) inflammatory, (b) nuclear factor B (NF-κB) related apoptosis pathways, and (c) oxidative stress systems. A bibliographic search is conducted under the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) as a basis for reporting reliable systematic reviews to perform a Scoping review. After analysing the manuscripts, we can conclude that curcumin is a product that demonstrates a significant biological antialgic, anti-inflammatory, and antioxidant power. Therefore, supplementation has a positive effect on the inflammatory and regenerative response in tendinopathies. In addition, curcumin decreases and modulates the cell infiltration, activation, and maturation of leukocytes, as well as the production of pro-inflammatory mediators at the site of inflammation.
Pharmacological and Molecular Insight on the Cardioprotective Role of Apigenin
Authors: Thomas Shilu Deepa , Jha Niraj Kumar , Jha Saurabh Kumar , Sadek Bassem , Ojha Shreesh
Published: January 2023

Apigenin is a naturally occurring dietary flavonoid found abundantly in fruits and vegetables. It possesses a wide range of biological properties that exert antioxidant, anti-inflammatory, anticancer, and antibacterial effects. These effects have been reported to be beneficial in the treatment of atherosclerosis, stroke, hypertension, ischemia/reperfusion-induced myocardial injury, and diabetic cardiomyopathy, and provide protection against drug-induced cardiotoxicity. These potential therapeutic effects advocate the exploration of the cardioprotective actions of apigenin. This review focuses on apigenin, and the possible pharmacological mechanisms involved in the protection against cardiovascular diseases. We further discuss its therapeutic uses and highlight its potential applications in the treatment of various cardiovascular disorders. Apigenin displays encouraging results, which may have implications in the development of novel strategies for the treatment of cardiovascular diseases. With the commercial availability of apigenin as a dietary supplement, the outcomes of preclinical studies may provide the investigational basis for future translational strategies evaluating the potential of apigenin in the treatment of cardiovascular disorders. Further preclinical and clinical investigations are required to characterize the safety and efficacy of apigenin and establish it as a nutraceutical as well as a therapeutic agent to be used alone or as an adjuvant with current drugs.
Maternal Iodine Status and Birth Outcomes: A Systematic Literature Review and Meta-Analysis
Authors: Greenwood Darren C. , Webster James , Keeble Claire , Taylor Elizabeth , Hardie Laura J.
Published: January 2023

Background & aims: Iodine is important for thyroid function during pregnancy to support fetal growth, but studies of maternal iodine status and birth outcomes are conflicting. We aimed to quantify the association between iodine status and birth outcomes, including potential threshold effects using nonlinear dose–response curves. Methods: We systematically searched Medline and Embase to 10 October 2022 for relevant cohort studies. We conducted random-effects meta-analyses of urinary iodine concentration (UIC), iodine:creatinine ratio (I:Cr), and iodide intake for associations with birth weight, birth weight centile, small for gestational age (SGA), preterm delivery, and other birth outcomes. Study quality was assessed using the Newcastle-Ottawa scale. Results: Meta-analyses were conducted on 23 cohorts with 42269 participants. Birth weight was similar between UIC ≥ 150 μg/L and <150 μg/L (difference = 30 g, 95% CI −22 to 83, p = 0.3, n = 13, I2 = 89%) with no evidence of linear trend (4 g per 50 μg/L, −3 to 10, p = 0.2, n = 12, I2 = 80%). I:Cr was similar, but with nonlinear trend suggesting I:Cr up to 200 μg/g associated with increasing birthweight (p = 0.02, n = 5). Birthweight was 2.0 centiles (0.3 to 3.7, p = 0.02, n = 4, I2 = 0%) higher with UIC ≥ 150 μg/g, but not for I:Cr. UIC ≥ 150 μg/L was associated with lower risk of SGA (RR = 0.85, 0.75 to 0.96, p = 0.01, n = 13, I2 = 0%), but not with I:Cr. Conclusions: The main risk of bias was adjustment for confounding, with variation in urine sample collection and exposure definition. There were modest-sized associations between some measures of iodine status, birth weight, birth weight centile, and SGA. In pregnancy, we recommend that future studies report standardised measures of birth weight that take account of gestational age, such as birth weight centile and SGA. Whilst associations were modest-sized, we recommend maintaining iodine sufficiency in the population, especially for women of childbearing age on restricted diets low in iodide.
Five Days of Tart Cherry Supplementation Improves Exercise Performance in Normobaric Hypoxia
Authors: Horiuchi Masahiro , Fukuoka Yoshiyuki , Koyama Katsuhiro , Oliver Samuel J.
Published: January 2023

Previous studies have shown tart cherry (TC) to improve exercise performance in normoxia. The effect of TC on hypoxic exercise performance is unknown. This study investigated the effects of 5 days of tart cherry (TC) or placebo (PL) supplementation on hypoxic exercise performance. Thirteen healthy participants completed an incremental cycle exercise test to exhaustion (TTE) under two conditions: (i) hypoxia (13% O2) with PL and (ii) hypoxia with TC (200 mg anthocyanin per day for 4 days and 100 mg on day 5). Pulmonary gas exchange variables, peripheral arterial oxygen saturation (SpO2), deoxygenated hemoglobin (HHb), and tissue oxygen saturation (StO2) assessed by near-infrared spectroscopy in the vastus lateralis muscle were measured at rest and during exercise. Urinary 8-hydro-2′ deoxyguanosine (8-OHdG) excretion was evaluated pre-exercise and 1 and 5 h post-exercise. The TTE after TC (940 ± 84 s, mean ± standard deviation) was longer than after PL (912 ± 63 s, p < 0.05). During submaximal hypoxic exercise, HHb was lower and StO2 and SpO2 were higher after TC than PL. Moreover, a significant interaction (supplements × time) in urinary 8-OHdG excretion was found (p < 0.05), whereby 1 h post-exercise increases in urinary 8-OHdG excretion tended to be attenuated after TC. These findings indicate that short-term dietary TC supplementation improved hypoxic exercise tolerance, perhaps due to lower HHb and higher StO2 in the working muscles during submaximal exercise.
Prolonged High-Fat Diet Consumption throughout Adulthood in Mice Induced Neurobehavioral Deterioration via Gut-Brain Axis
Authors: Wu Haicui , Zhang Wenxiu , Huang Mingyue , Lin Xueying , Chiou Jiachi
Published: January 2023

Neuropsychiatric disorders have been one of the worldwide health problems contributing to profound social and economic consequences. It is reported that consumption of an excessive high-fat diet (HFD) in middle age could induce cognitive and emotional dysfunctions, whereas the mechanisms of the effects of long-term HFD intake on brain disorders have not been fully investigated. We propose a hypothesis that prolonged HFD intake throughout adulthood could lead to neurobehavioral deterioration via gut-brain axis. In this study, the adult C57BL/6J mice consuming long-term HFD (24 weeks) exhibited more anxiety-like, depression-like, and disruptive social behaviors and poorer performance in learning and memory than control mice fed with a normal diet (ND). In addition, the homeostasis of gut microbiota was impaired by long-term HFD consumption. Changes in some flora, such as Prevotellaceae_NK3B31_group and Ruminococcus, within the gut communities, were correlated to neurobehavioral alterations. Furthermore, the gut permeability was increased after prolonged HFD intake due to the decreased thickness of the mucus layer and reduced expression of tight junction proteins in the colon. The mRNA levels of genes related to synaptic-plasticity, neuronal development, microglia maturation, and activation in the hippocampus and prefrontal cortex of HFD-fed mice were lower than those in mice fed with ND. Interestingly, the transcripts of genes related to tight junction proteins, ZO-1 and Occludin involved in blood-brain-barrier (BBB), were decreased in both hippocampus and prefrontal cortex after long-term HFD consumption. Those results indicated that chronic consumption of HFD in mice resulted in gut microbiota dysbiosis, which induced decreased expression of mucus and tight junction proteins in the colon, in turn leading to local and systemic inflammation. Those changes could further contribute to the impairment of brain functions and neurobehavioral alterations, including mood, sociability, learning and memory. In short, long-term HFD intake throughout adulthood could induce behavioral phenotypes related to neuropsychiatric disorders via gut-brain axis. The observations of this study provide potential intervention strategies to reduce the risk of HFD via targeting the gut or manipulating gut microbiota.
Emergence of Hadron Mass and Structure
Authors: Ding Minghui , Roberts Craig , Schmidt Sebastian
Published: January 2023

Visible matter is characterised by a single mass scale; namely, the proton mass. The proton’s existence and structure are supposed to be described by quantum chromodynamics (QCD); yet, absent Higgs boson couplings, chromodynamics is scale-invariant. Thus, if the Standard Model is truly a part of the theory of Nature, then the proton mass is an emergent feature of QCD; and emergent hadron mass (EHM) must provide the basic link between theory and observation. Nonperturbative tools are necessary if such connections are to be made; and in this context, we sketch recent progress in the application of continuum Schwinger function methods to an array of related problems in hadron and particle physics. Special emphasis is given to the three pillars of EHM—namely, the running gluon mass, process-independent effective charge, and running quark mass; their role in stabilising QCD; and their measurable expressions in a diverse array of observables.
β-Defensin-1 Regulates Influenza Virus Infection in Human Bronchial Epithelial Cells through the STAT3 Signaling Pathway
Authors: Othumpangat Sreekumar , Noti John D.
Published: January 2023

Understanding the host response to influenza A virus (IAV) infection is vital for developing intervention strategies. The primary barriers for invading respiratory pathogens are the respiratory tract epithelial cells and antimicrobial proteins generated by these cells. The antimicrobial peptide, β-defensin-1, has antiviral activity against both enveloped and non-enveloped viruses. Significant downregulation of β-defensin1 gene (DEFB1) expression was observed when human bronchial epithelial cells (HBEpCs) were exposed to IAV. HBEpCs overexpressing DEFB1 caused a significant reduction in IAV, that was confirmed by IAV matrix gene analysis, plaque assay, and confocal microscopy. DEFB1 expression after transfection with two micro RNAs (miRNAs), hsa-miR-186-5p and hsa-miR-340-5p, provided evidence that DEFB1 expression could be modulated by these miRNAs and hsa-miR-186-5p had a higher binding efficiency with DEFB1. Overexpression of DEFB1 in IAV-infected HBEpCs led to increased NF-κB expression. In a PCR array analysis of 84 transcription factors, either overexpressing DEFB1 or siRNA silencing of DEFB1 expression significantly modulated the expression of signal transducer and activator of transcription 3 (STAT3). In addition, Ingenuity Pathway Analysis (IPA) integrated with PCR array data showed that the JAK1/STAT3 pathway was significantly altered in cells overexpressing DEFB1, suggesting this to be one of the pathways by which defensin regulates IAV replication in HBEpCs. In conclusion, the reduction in IAV copy number in DEFB1 overexpressing cells suggests that β-defensin-1 plays a key role in regulating IAV survival through STAT3 and is a potential target for antiviral drug development.
Triazine-Based Small Molecules: A Potential New Class of Compounds in the Antifungal Toolbox
Authors: Conrad Karen A. , Kim Hyunjeong , Qasim Mohammad , Djehal Amel , Hernday Aaron D. , Désaubry Laurent , Rauceo Jason M.
Published: January 2023

Invasive fungal infections caused by Candida species remain a significant public health problem worldwide. The increasing prevalence of drug-resistant infections and a limited arsenal of antifungal drugs underscore the need for novel interventions. Here, we screened several classes of pharmacologically active compounds against mammalian diseases for antifungal activity. We found that the synthetic triazine-based compound melanogenin (Mel) 56 is fungicidal in Candida albicans laboratory and clinical strains with minimal inhibitory concentrations of 8–16 µg/mL. Furthermore, Mel56 has general antifungal activity in several non-albicans Candida species and the non-pathogenic yeast Saccharomyces cerevisiae. Surprisingly, Mel56 inhibited the yeast-to-hyphae transition at sublethal concentrations, revealing a new role for triazine-based compounds in fungi. In human cancer cell lines, Mel56 targets the inner mitochondrial integral membrane prohibitin proteins, PHB1 and PHB2. However, Mel56 treatment did not impact C. albicans mitochondrial activity, and antifungal activity was similar in prohibitin single, double, and triple homozygous mutant strains compared to the wild-type parental strain. These results suggests that Mel56 has a novel mechanism-of-action in C. albicans. Therefore, Mel56 is a promising antifungal candidate warranting further analyses.
Orthosiphon aristatus (Blume) Miq Alleviates Non-Alcoholic Fatty Liver Disease via Antioxidant Activities in C57BL/6 Obese Mice and Palmitic–Oleic Acid-Induced Steatosis in HepG2 Cells
Authors: Alshehade Salah Abdalrazak , Al Zarzour Raghdaa Hamdan , Mathai Michael , Giribabu Nelli , Seyedan Atefehalsadat , Kaur Gurjeet , Al-Suede Fouad Saleih Resq , Majid Amin Malik Shah Abdul , Murugaiyah Vikneswaran , Almoustafa Hassan , Alshawsh Mohammed Abdullah
Published: January 2023

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of liver disease. Orthosiphon aristatus (Blume) Miq, a traditional plant in South Asia, has previously been shown to attenuate obesity and hyperglycaemic conditions. Eight weeks of feeding C57BL/6 mice with the standardized O. aristatus extract (400 mg/kg) inhibited the progression of NAFLD. Liver enzymes including alanine aminotransferase and aspartate transaminase were significantly reduced in treated mice by 74.2% ± 7.69 and 52.8% ± 7.83, respectively. Furthermore, the treated mice showed a reduction in serum levels of glucose (50% ± 5.71), insulin (70.2% ± 12.09), total cholesterol (27.5% ± 15.93), triglycerides (63.2% ± 16.5), low-density lipoprotein (62.5% ± 4.93) and atherogenic risk index relative to the negative control. Histologically, O. aristatus reversed hepatic fat accumulation and reduced NAFLD severity. Notably, our results showed the antioxidant activity of O. aristatus via increased superoxide dismutase activity and a reduction of hepatic malondialdehyde levels. In addition, the levels of serum pro-inflammatory mediators (IL-6 and TNFα) decreased, indicating anti-inflammatory activity. The aqueous, hydroethanolic and ethanolic fractions of O. aristatus extract significantly reduced intracellular fat accumulation in HepG2 cells that were treated with palmitic–oleic acid. Together, these findings suggest that antioxidant activities are the primary mechanism of action of O. aristatus underlying the anti-NAFLD effects.
Three Members of Transmembrane-4-Superfamily, TM4SF1, TM4SF4, and TM4SF5, as Emerging Anticancer Molecular Targets against Cancer Phenotypes and Chemoresistance
Authors: Rahim Nur Syafiqah , Wu Yuan Seng , Sim Maw Shin , Velaga Appalaraju , Bonam Srinivasa Reddy , Gopinath Subash C. B. , Subramaniyan Vetriselvan , Choy Ker Woon , Teow Sin-Yeang , Fareez Ismail M. , Samudi Chandramathi , Sekaran Shamala Devi , Sekar Mahendran , Guad Rhanye Mac
Published: January 2023

There are six members of the transmembrane 4 superfamily (TM4SF) that have similar topology and sequence homology. Physiologically, they regulate tissue differentiation, signal transduction pathways, cellular activation, proliferation, motility, adhesion, and angiogenesis. Accumulating evidence has demonstrated, among six TM4SF members, the regulatory roles of transmembrane 4 L6 domain family members, particularly TM4SF1, TM4SF4, and TM4SF5, in cancer angiogenesis, progression, and chemoresistance. Hence, targeting derailed TM4SF for cancer therapy has become an emerging research area. As compared to others, this review aimed to present a focused insight and update on the biological roles of TM4SF1, TM4SF4, and TM4SF5 in the progression, metastasis, and chemoresistance of various cancers. Additionally, the mechanistic pathways, diagnostic and prognostic values, and the potential and efficacy of current anti-TM4SF antibody treatment were also deciphered. It also recommended the exploration of other interactive molecules to be implicated in cancer progression and chemoresistance, as well as potential therapeutic agents targeting TM4SF as future perspectives. Generally, these three TM4SF members interact with different integrins and receptors to significantly induce intracellular signaling and regulate the proliferation, migration, and invasion of cancer cells. Intriguingly, gene silencing or anti-TM4SF antibody could reverse their regulatory roles deciphered in different preclinical models. They also have prognostic and diagnostic value as their high expression was detected in clinical tissues and cells of various cancers. Hence, TM4SF1, TM4SF4, and TM4SF5 are promising therapeutic targets for different cancer types preclinically and deserve further investigation.
Ciclopirox Olamine Induces Proliferation Inhibition and Protective Autophagy in Hepatocellular Carcinoma
Authors: Wan Xinyan , Xiang Junqi , Fan Hui , Jiang Ying , Lu Yiting , Zhang Chundong , Zhang Ying , Chen Quanmei , Lei Yunlong
Published: January 2023

Hepatocellular carcinoma is one of the most common fatal malignancies worldwide. Thus far, the hepatocellular carcinoma prognosis has been bleak due to deficiencies in the identification and diagnosis of early hepatocellular carcinoma. Ciclopirox olamine (CPX) is a synthetic antifungal agent and has been considered as an anti-cancer candidate drug recently, though the detailed mechanisms related to its anti-cancer effect in hepatocellular carcinoma have not yet been revealed. Here, we found that CPX could inhibit proliferation in HCC cells but not in intrahepatic cholangiocarcinoma cells by arresting the cell cycle. Moreover, the anti-cancer effects of CPX in HCC cells were also attributed to CPX-triggered ROS accumulation and DJ-1 downregulation. Additionally, CPX could promote complete autophagic flux, which alleviated the anti-cancer effect of CPX in HCC cells, whereas the ROS scavenger (NAC) would attenuate CPX-induced protective autophagy. Interestingly, CPX could also induce glycogen clustering in HCC cells. Altogether, this study provides a new insight into the detailed molecular mechanisms of CPX as an anti-cancer therapy and a strategy for treating hepatocellular carcinoma.
Formulation and Characterisation of Carbamazepine Orodispersible 3D-Printed Mini-Tablets for Paediatric Use
Authors: Hu Jiayu , Fitaihi Rawan , Abukhamees Shorooq , Abdelhakim Hend E.
Published: January 2023

One of the main challenges to paediatric drug administration is swallowing difficulties, hindering the acceptability of the medicine and hence clinical outcomes. This study aims at developing a child-appropriate dosage form, the orodispersible mini-tablet (ODMT), using the model drug carbamazepine (CBZ). This dosage form was prepared and 3D-printed via a semi-solid extrusion technique. Design of Experiment methods were applied for optimising the formulation. The formulation with 40% (w/w) of SSG (superdisintegrant) and 5% (w/w) of PVP K30 (binder) was selected and loaded with CBZ. The drug-loaded tablets were characterised by a mean hardness of 18.5 N and a disintegrating time of 84 s, along with acceptable friability. The mean drug loading ratio of the tablets was tested as 90.56%, and the drug release rate in 0.1 M HCl reached 68.3% at 45 min. Excipients showed proper compatibility with the drug in physical form analysis. Taste assessment via an E-tongue was also conducted, where the drug did not show bitter taste signals at a low concentration in the taste assessment, and the sweetener also blocked bitterness signals in the testing. To this end, ODMTs were found to be potential candidates for child-appropriate dosage forms delivering CBZ.
Are Natural Compounds a Promising Alternative to Synthetic Cross-Linking Agents in the Preparation of Hydrogels?
Authors: Sapuła Paulina , Bialik-Wąs Katarzyna , Malarz Katarzyna
Published: January 2023

The main aim of this review is to assess the potential use of natural cross-linking agents, such as genipin, citric acid, tannic acid, epigallocatechin gallate, and vanillin in preparing chemically cross-linked hydrogels for the biomedical, pharmaceutical, and cosmetic industries. Chemical cross-linking is one of the most important methods that is commonly used to form mechanically strong hydrogels based on biopolymers, such as alginates, chitosan, hyaluronic acid, collagen, gelatin, and fibroin. Moreover, the properties of natural cross-linking agents and their advantages and disadvantages are compared relative to their commonly known synthetic cross-linking counterparts. Nowadays, advanced technologies can facilitate the acquisition of high-purity biomaterials from unreacted components with no additional purification steps. However, while planning and designing a chemical process, energy and water consumption should be limited in order to reduce the risks associated with global warming. However, many synthetic cross-linking agents, such as N,N′-methylenebisacrylamide, ethylene glycol dimethacrylate, poly (ethylene glycol) diacrylates, epichlorohydrin, and glutaraldehyde, are harmful to both humans and the environment. One solution to this problem could be the use of bio-cross-linking agents obtained from natural resources, which would eliminate their toxic effects and ensure the safety for humans and the environment.
Emerging Antimicrobial and Immunomodulatory Fiber-Based Scaffolding Systems for Treating Diabetic Foot Ulcers
Authors: Felgueiras Helena P.
Published: January 2023

Diabetic foot ulcers (DFUs) are one of the main complications of diabetes and are characterized by their complexity and severity, which are frequently aggravated by overexpressed inflammatory factors and polymicrobial infections. Most dressing systems offer a passive action in the treatment of DFUs, being frequently combined with antibiotic or immunomodulatory therapies. However, in many instances due to these combined therapies’ inability to properly fight microbial presence, and provide a suitable, breathable and moist environment that is also capable of protecting the site from secondary microbial invasions or further harm, aggravation of the wound state is unavoidable and lower limb amputations are necessary. Considering these limitations and knowing of the urgent demand for new and more effective therapeutic systems for DFU care that will guarantee the quality of life for patients, research in this field has boomed in the last few years. In this review, the emerging innovations in DFU dressing systems via fiber-based scaffolds modified with bioactive compounds have been compiled; data focused on the innovations introduced in the last five years (2017–2022). A generalized overview of the classifications and constraints associated with DFUs healing and the bioactive agents, both antimicrobial and immunomodulatory, that can contribute actively to surpass such issues, has also been provided.
Nanotechnology-Based Approaches for Voriconazole Delivery Applied to Invasive Fungal Infections
Authors: de Almeida Campos Laís , Fin Margani Taise , Santos Kelvin Sousa , de Lima Gualque Marcos William , Freire Cabral Ana Karla Lima , Khalil Najeh Maissar , Fusco-Almeida Ana Marisa , Mainardes Rubiana Mara , Mendes-Giannini Maria José Soares
Published: January 2023

Invasive fungal infections increase mortality and morbidity rates worldwide. The treatment of these infections is still limited due to the low bioavailability and toxicity, requiring therapeutic monitoring, especially in the most severe cases. Voriconazole is an azole widely used to treat invasive aspergillosis, other hyaline molds, many dematiaceous molds, Candida spp., including those resistant to fluconazole, and for infections caused by endemic mycoses, in addition to those that occur in the central nervous system. However, despite its broad activity, using voriconazole has limitations related to its non-linear pharmacokinetics, leading to supratherapeutic doses and increased toxicity according to individual polymorphisms during its metabolism. In this sense, nanotechnology-based drug delivery systems have successfully improved the physicochemical and biological aspects of different classes of drugs, including antifungals. In this review, we highlighted recent work that has applied nanotechnology to deliver voriconazole. These systems allowed increased permeation and deposition of voriconazole in target tissues from a controlled and sustained release in different routes of administration such as ocular, pulmonary, oral, topical, and parenteral. Thus, nanotechnology application aiming to delivery voriconazole becomes a more effective and safer therapeutic alternative in the treatment of fungal infections.
Photostress Recovery Time after Flash-Lighting Is Increased in Myopic Eyes
Authors: Ávila Francisco J. , Casado Pilar , Ares Jorge
Published: January 2023

Background: It is well-known that non-pathological axial myopic eyes present physiological and functional differences in comparison with emmetropic eyes due to altered retinal anatomy. Photostress tests have shown very significant capabilities to discriminate a normal retina from an abnormal retina. Accordingly, the aim of this work was to investigate the differences between myopic and emmetropic eyes in the measured photostress recovery time (PSRT) after retinal light-flashing in a population of young healthy subjects. Methods: A coaxial illumination total disability glare instrument was employed to measure the recovery time after photostress was induced by a 240 milliseconds flash-lighting (535 nm) exposure on 66 myopic and 66 emmetropic eyes. The measurements were carried out for different combinations of glare angles and contrasts of the visual stimuli. Results: In general terms, PSRT in myopic eyes was found at a statistically higher than in emmetropic eyes (Bonferroni correction). For both groups, the measured recovery strongly depends on the contrast of the test object used to measure baseline recovery function and markedly less on the source of glare angles explored. When the PSRTs obtained for different glare angles are averaged, the differences between PSRTs drastically increase with the reduction in the contrast of the stimuli between both groups of study. Conclusions: PSRT is higher for myopic than for young healthy emmetropic eyes (1.2 s and 0.2 s for 5% and 100% contrast test object, respectively). Though seemingly small, the magnitude of this finding can be relevant when flash-lighting happens while driving a car or while performing actions where the reaction time after a visual stimulus can be critical.
Neutral Spores—An Easier Way to Cultivate Pyropia leucosticta (Thuret) Neefus & J.Brodie, 2011 (Bangiales, Rhodophyta) along the Romanian Black Sea Shore
Authors: Marin Oana Alina , Coatu Valentina , Stoica Elena
Published: January 2023

Macroalgal cultures are currently of great interest worldwide. Although along the Romanian Black Sea coast, there is no tradition in this sense, currently, a major interest in developing this direction exists, taking into consideration that the overexploitation of wild seaweed resources involves the disturbance of the marine environment, with implications that can sometimes be irreversible. Porphyra and Pyropia species (also known as nori algae) are considered the world’s most valuable mariculture algal products due to their high nutritional value and multiple active principles, considered unique representatives of marine algae. Considering these aspects, attention was focused on the only nori species from the Romanian Black Sea coast, namely, Pyropia leucosticta. The species was cultivated in controlled laboratory conditions for 5.5 months by manipulating its reproductive elements. The aim was to establish a simple, low-cost method by avoiding the complicated conchocelis phase of the species; therefore, reproduction and further species development were achieved by collecting the released neutral spores and isolating them in culture vessels, ensuring, at the same time, proper nutrient conditions, using sterile enriched seawater and mimicking ambient conditions. At the end of the experiment, specimens of almost 80−90 mm were obtained, making this method suitable for obtaining ex situ P. leucosticta blades on the Romanian Black Sea shore.
Potential Anti-Cholinesterase Activity of Bioactive Compounds Extracted from Cassia grandis L.f. and Cassia timoriensis DC.
Authors: Alhawarri Maram B. , Dianita Roza , Rawa Mira Syahfriena Amir , Nogawa Toshihiko , Wahab Habibah A.
Published: January 2023

Acetylcholinesterase (AChE) inhibitors remain the primary therapeutic drug that can alleviate Alzheimer’s disease’s (AD) symptoms. Several Cassia species have been shown to exert significant anti-AChE activity, which can be an alternative remedy for AD. Cassia timoriensis and Cassia grandis are potential plants with anti-AChE activity, but their phytochemical investigation is yet to be further conducted. The aims of this study were to identify the phytoconstituents of C. timoriensis and C. grandis and evaluate their inhibitory activity against AChE and butyrylcholinesterase (BChE). Two compounds were isolated for the first time from C. timoriensis: arachidyl arachidate (1) and luteolin (2). Five compounds were identified from C. grandis: β-sitosterol (3), stigmasterol (4), cinnamic acid (5), 4-hydroxycinnamic acid (6), and hydroxymethylfurfural (7). Compound 2 showed significant inhibition towards AChE (IC50: 20.47 ± 1.10 µM) and BChE (IC50: 46.15 ± 2.20 µM), followed by 5 (IC50: 40.5 ± 1.28 and 373.1 ± 16.4 µM) and 6 (IC50: 43.4 ± 0.61 and 409.17 ± 14.80 µM) against AChE and BChE, respectively. The other compounds exhibited poor to slightly moderate AChE inhibitory activity. Molecular docking revealed that 2 showed good binding affinity towards TcAChE (PDB ID: 1W6R) and HsBChE (PDB ID: 4BDS). It formed a hydrogen bond with TYR121 at the peripheral anionic site (PAS, 2.04 Å), along with hydrophobic interactions with the anionic site and PAS (TRP84 and TYR121, respectively). Additionally, 2 formed three H-bonds with the binding site residues: one bond with catalytic triad, HIS438 at distance 2.05 Å, and the other two H-bonds with GLY115 and GLU197 at distances of 2.74 Å and 2.19 Å, respectively. The evidence of molecular interactions of 2 may justify the relevance of C. timoriensis as a cholinesterase inhibitor, having more promising activity than C. grandis.
Indigenous-Amazonian Traditional Medicine’s Usage of the Tobacco Plant: A Transdisciplinary Ethnopsychological Mixed-Methods Case Study
Authors: Berlowitz Ilana , García Torres Ernesto , Maake Caroline , Wolf Ursula , Martin-Soelch Chantal
Published: January 2023

Harmful usage of tobacco is a global public health problem associated with adverse health effects and addiction. Yet, in the Peruvian Amazon, the native region of Nicotiana rustica L., this plant is used in remarkably different manners: it is considered a potent medicinal plant, applied in liquid form for oral ingestion to treat mental health problems, a common and ancient healing practice in this region. Using a transdisciplinary field research approach with mixed ethnopsychological methods, this work aimed to report for the first time a case study in this context. The intervention took place in the Peruvian Amazon (Loreto) and involved ritual tobacco ingestion in a weeklong retreat-like frame, administered by a specialized traditional Amazonian healer. The patient was a 37-year-old woman with diagnosed mood, anxiety, and attention deficit disorders, as well as a chronic somatic condition. We applied qualitative experience-sampling during and quantitative symptom assessments pre- and post-treatment. Our findings offer a detailed description of the experiential therapeutic process during the treatment week and suggest clinically relevant improvements in patient well-being. This work is significant in view of the globally prevalent harmful uses of tobacco and the current scientific trend of revisiting herbal psychoactives (e.g., cannabis, psilocybin) for their therapeutic potentials.
A Tight Interaction between the Native Seagrass Cymodocea nodosa and the Exotic Halophila stipulacea in the Aegean Sea Highlights Seagrass Holobiont Variations
Authors: Conte Chiara , Apostolaki Eugenia T. , Vizzini Salvatrice , Migliore Luciana
Published: January 2023

Seagrasses harbour bacterial communities with which they constitute a functional unit called holobiont that responds as a whole to environmental changes. Epiphytic bacterial communities rapidly respond to both biotic and abiotic factors, potentially contributing to the host fitness. The Lessepsian migrant Halophila stipulacea has a high phenotypical plasticity and harbours a highly diverse epiphytic bacterial community, which could support its invasiveness in the Mediterranean Sea. The current study aimed to evaluate the Halophila/Cymodocea competition in the Aegean Sea by analysing each of the two seagrasses in a meadow zone where these intermingled, as well as in their monospecific zones, at two depths. Differences in holobionts were evaluated using seagrass descriptors (morphometric, biochemical, elemental, and isotopic composition) to assess host changes, and 16S rRNA gene to identify bacterial community structure and composition. An Indicator Species Index was used to identify bacteria significantly associated with each host. In mixed meadows, native C. nodosa was shown to be affected by the presence of exotic H. stipulacea, in terms of both plant descriptors and bacterial communities, while H. stipulacea responded only to environmental factors rather than C. nodosa proximity. This study provided evidence of the competitive advantage of H. stipulacea on C. nodosa in the Aegean Sea and suggests the possible use of associated bacterial communities as an ecological seagrass descriptor.
MYB Transcription Factor Family in Pearl Millet: Genome-Wide Identification, Evolutionary Progression and Expression Analysis under Abiotic Stress and Phytohormone Treatments
Authors: Chanwala Jeky , Khadanga Badrinath , Jha Deepak Kumar , Sandeep Inavolu Sriram , Dey Nrisingha
Published: January 2023

Transcription factors (TFs) are the regulatory proteins that act as molecular switches in controlling stress-responsive gene expression. Among them, the MYB transcription factor family is one of the largest TF family in plants, playing a significant role in plant growth, development, phytohormone signaling and stress-responsive processes. Pearl millet (Pennisetum glaucum L.) is one of the most important C4 crop plants of the arid and semi-arid regions of Africa and Southeast Asia for sustaining food and fodder production. To explore the evolutionary mechanism and functional diversity of the MYB family in pearl millet, we conducted a comprehensive genome-wide survey and identified 279 MYB TFs (PgMYB) in pearl millet, distributed unevenly across seven chromosomes of pearl millet. A phylogenetic analysis of the identified PgMYBs classified them into 18 subgroups, and members of the same group showed a similar gene structure and conserved motif/s pattern. Further, duplication events were identified in pearl millet that indicated towards evolutionary progression and expansion of the MYB family. Transcriptome data and relative expression analysis by qRT-PCR identified differentially expressed candidate PgMYBs (PgMYB2, PgMYB9, PgMYB88 and PgMYB151) under dehydration, salinity, heat stress and phytohormone (ABA, SA and MeJA) treatment. Taken together, this study provides valuable information for a prospective functional characterization of the MYB family members of pearl millet and their application in the genetic improvement of crop plants.