bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Predisposition to Colorectal Cancer: How Many and Which Genes to Test?
Authors: Rebuzzi Francesca , Ulivi Paola , Tedaldi Gianluca
Published: January 2023

Colorectal cancer is one of the most common tumors, and genetic predisposition is one of the key risk factors in the development of this malignancy. Lynch syndrome and familial adenomatous polyposis are the best-known genetic diseases associated with hereditary colorectal cancer. However, some other genetic disorders confer an increased risk of colorectal cancer, such as Li–Fraumeni syndrome (TP53 gene), MUTYH-associated polyposis (MUTYH gene), Peutz–Jeghers syndrome (STK11 gene), Cowden syndrome (PTEN gene), and juvenile polyposis syndrome (BMPR1A and SMAD4 genes). Moreover, the recent advances in molecular techniques, in particular Next-Generation Sequencing, have led to the identification of many new genes involved in the predisposition to colorectal cancers, such as RPS20, POLE, POLD1, AXIN2, NTHL1, MSH3, RNF43 and GREM1. In this review, we summarized the past and more recent findings in the field of cancer predisposition genes, with insights into the role of the encoded proteins and into the associated genetic disorders. Furthermore, we discussed the possible clinical utility of genetic testing in terms of prevention protocols and therapeutic approaches.
Role of Endothelial Progenitor Cells in Frailty
Authors: Komici Klara , Perna Angelica , Guerra Germano
Published: January 2023

Frailty is a clinical condition closely related to aging which is characterized by a multidimensional decline in biological reserves, a failure of physiological mechanisms and vulnerability to minor stressors. Chronic inflammation, the impairment of endothelial function, age-related endocrine system modifications and immunosenescence are important mechanisms in the pathophysiology of frailty. Endothelial progenitor cells (EPCs) are considered important contributors of the endothelium homeostasis and turn-over. In the elderly, EPCs are impaired in terms of function, number and survival. In addition, the modification of EPCs’ level and function has been widely demonstrated in atherosclerosis, hypertension and diabetes mellitus, which are the most common age-related diseases. The purpose of this review is to illustrate the role of EPCs in frailty. Initially, we describe the endothelial dysfunction in frailty, the response of EPCs to the endothelial dysfunction associated with frailty and, finally, interventions which may restore the EPCs expression and function in frail people.
Bioactive Compounds in Plasma as a Function of Sex and Sweetener Resulting from a Maqui-Lemon Beverage Consumption Using Statistical and Machine Learning Techniques
Authors: Hernández-Prieto Diego , Fernández Pablo S. , Agulló Vicente , García-Viguera Cristina , Egea Jose A.
Published: January 2023

The present study analyses the effect of a beverage composed of citrus and maqui (Aristotelia chilensis) with different sweeteners on male and female consumers. Beverages were designed and tested (140 volunteers) as a source of polyphenols, in a previous work. Plasma samples were taken before and after two months of daily intake. Samples were measured for bioactive-compound levels with metabolomics techniques, and the resulting data were analysed with advanced versions of ANOVA and clustering analysis, to describe the effects of sex and sweetener factors on bioactive compounds. To improve the results, machine learning techniques were applied to perform feature selection and data imputation. The results reflect a series of compounds which are more regulated for men, such as caffeic acid or 3,4-dihydroxyphenylacetic acid, and for women, trans ferulic acid (TFA) or naringenin glucuronide. Regulations are also observed with sweeteners, such as TFA with stevia in women, or vanillic acid with sucrose in men. These results show that there is a differential regulation of these two families of polyphenols by sex, and that this is influenced by sweeteners.
A Designed Host Defense Peptide for the Topical Treatment of MRSA-Infected Diabetic Wounds
Authors: Vargas Alex , Garcia Gustavo , Rivara Kathryn , Woodburn Kathryn , Clemens Louis Edward , Simon Scott I.
Published: January 2023

Diabetes mellitus is a chronic disease characterized by metabolic dysregulation which is frequently associated with diabetic foot ulcers that result from a severely compromised innate immune system. The high levels of blood glucose characteristic of diabetes cause an increase in circulating inflammatory mediators, which accelerate cellular senescence and dampen antimicrobial activity within dermal tissue. In diabetic wounds, bacteria and fungi proliferate in a protective biofilm forming a structure that a compromised host defense system cannot easily penetrate, often resulting in chronic infections that require antimicrobial intervention to promote the healing process. The designed host defense peptide (dHDP) RP557 is a synthesized peptide whose sequence has been derived from naturally occurring antimicrobial peptides (AMPs) that provide the first line of defense against invading pathogens. AMPs possess an amphipathic α-helix or β-sheet structure and a net positive charge that enables them to incorporate into pathogen membranes and perturb the barrier function of Gram-positive and Gram-negative bacteria along with fungi. The capacity of skin to resist infections is largely dependent upon the activity of endogenous AMPs that provided the basis for the design and testing of RP557 for the resolution of wound infections. In the current study, the topical application of RP557 stopped bacterial growth in the biofilm of methicillin-resistant Staphylococcus aureus (MRSA) USA300 infected wounds on the flanks of clinically relevant diabetic TALLYHO mice. Topical application of RP557 reduced bacterial load and accelerated wound closure, while wound size in control diabetic mice continued to expand. These studies demonstrate that RP557 reduces or eliminates an infection in its biofilm and restores wound-healing capacity.
Genome-Wide Characterization of B-Box Gene Family in Salvia miltiorrhiza
Authors: Li Yunyun , Tong Yunli , Ye Jun , Zhang Caijuan , Li Bin , Hu Suying , Xue Xiaoshan , Tian Qian , Wang Yueyue , Li Lin , Niu Junfeng , Cao Xiaoyan , Wang Donghao , Wang Zhezhi
Published: January 2023

B-box (BBX) is a type of zinc finger transcription factor that contains a B-box domain. BBX transcription factors play important roles in plant photomorphogenesis, signal transduction, as well as abiotic and biological stress responses. However, the BBX gene family of Salvia miltiorrhiza has not been systematically investigated to date. For this study, based on the genomic data of Salvia miltiorrhiza, 27 SmBBXs genes were identified and clustered into five evolutionary branches according to phylogenetic analysis. The promoter analysis suggested that SmBBXs may be involved in the regulation of the light responses, hormones, stress signals, and tissue-specific development. Based on the transcriptome data, the expression patterns of SmBBXs under different abiotic stresses and plant hormones were analyzed. The results revealed that the expressions of the SmBBXs genes varied under different conditions and may play essential roles in growth and development. The transient expression analysis implied that SmBBX1, SmBBX4, SmBBX9, SmBBX20, and SmBBX27 were in the nucleus. A transcriptional activation assay showed SmBBX1, SmBBX4, SmBBX20, and SmBBX24 had transactivation activities, while SmBBX27 had none. These results provided a basis for further research on the role of SmBBXs in the development of Salvia miltiorrhiza.
Clinical Trials in Prader–Willi Syndrome: A Review
Authors: Mahmoud Ranim , Kimonis Virginia , Butler Merlin G.
Published: January 2023

Prader–Willi syndrome (PWS) is a complex, genetic, neurodevelopmental disorder. PWS has three molecular genetic classes. The most common defect is due to a paternal 15q11-q13 deletion observed in about 60% of individuals. This is followed by maternal disomy 15 (both 15 s from the mother), found in approximately 35% of cases. the remaining individuals have a defect of the imprinting center that controls the activity of imprinted genes on chromosome 15. Mild cognitive impairment and behavior problems in PWS include self-injury, anxiety, compulsions, and outbursts in childhood, impacted by genetic subtypes. Food seeking and hyperphagia can lead to morbid obesity and contribute to diabetes and cardiovascular or orthopedic problems. The control of hyperphagia and improving food-related behaviors are the most important unmet needs in PWS and could be addressed with the development of a new therapeutic agent, as currently no approved therapeutics exist for PWS treatment. The status of clinical trials with existing results for the management of obesity and hyperphagia in PWS will be discussed in this review, including treatments such as beloranib, setmelanotide, a diazoxide choline controlled-release tablet (DCCR), an unacylated ghrelin analogue, oxytocin and related compounds, glucagon-like peptide 1 receptor agonists, surgical intervention, and transcranial direct-current stimulation.
KIT-5 Structural and Textural Changes in Response to Different Methods of Functionalization with Sulfonic Groups
Authors: Chałupniczak Sylwia , Nowak Izabela , Wawrzyńczak Agata
Published: January 2023

In this project, KIT-5 materials were effectively functionalized with sulfonic groups introduced by grafting or the co-condensation method and tested as heterogeneous solid acid catalyst. A co-condensation procedure leading to the stable, –SO3H functionalized KIT-5 materials was successfully established. Moreover, the influence of both synthesis methods on the structural and textural parameters, as well as surface chemistry, morphology, and catalytic activity of –SO3H/KIT-5 materials was thoroughly investigated. The syntheses with 3-mepkaptopropyltrimethoxysilane (MPTMS) acting as a modifying agent resulted in samples in which functional groups were introduced into the structure and/or onto the mesoporous silica surface. The oxidation stage of –SH to –SO3H groups was carried out under mild conditions, using a “green” oxidant (H2O2). The application of different functionalization techniques and the introduction of different amounts of modifying agent allowed for an evaluation of the influence of these parameters on the ordering of the mesoporous structure of KIT-5 materials. The applied methods of assessment of the physicochemical parameters (XRD, low-temperature N2 sorption, TEM) showed that, especially when the co-condensation method was applied, as the number of functional groups increased, the ordering of structure characteristic of KIT-5 decreased. On the other hand, the samples modified by grafting had a stable structure, regardless of the amount of introduced MPTMS. Test reactions carried out on the basis of Friedel–Crafts alkylation process showed that the synthesized materials can be considered promising acid catalysts in heterogeneous catalysis reactions.
The Effect of the Tau Protein on D. melanogaster Lifespan Depends on GSK3 Expression and Sex
Authors: Veselkina Ekaterina R. , Trostnikov Mikhail V. , Roshina Natalia V. , Pasyukova Elena G.
Published: January 2023

The microtubule-associated conserved protein tau has attracted significant attention because of its essential role in the formation of pathological changes in the nervous system, which can reduce longevity. The study of the effects caused by tau dysfunction and the molecular mechanisms underlying them is complicated because different forms of tau exist in humans and model organisms, and the changes in protein expression can be multidirectional. In this article, we show that an increase in the expression of the main isoform of the Drosophila melanogaster tau protein in the nervous system has differing effects on lifespan depending on the sex of individuals but has no effect on the properties of the nervous system, in particular, the synaptic activity and distribution of another microtubule-associated protein, Futsch, in neuromuscular junctions. Reduced expression of tau in the nervous system does not affect the lifespan of wild-type flies, but it does increase the lifespan dramatically shortened by overexpression of the shaggy gene encoding the GSK3 (Glycogen Synthase Kinase 3) protein kinase, which is one of the key regulators of tau phosphorylation levels. This effect is accompanied by the normalization of the Futsch protein distribution impaired by shaggy overexpression. The results presented in this article demonstrate that multidirectional changes in tau expression can lead to effects that depend on the sex of individuals and the expression level of GSK3.
The Lung Microbiome: A New Frontier for Lung and Brain Disease
Authors: Chen Jiawen , Li Ting , Ye Chun , Zhong Jiasheng , Huang Jian-Dong , Ke Yiquan , Sun Haitao
Published: January 2023

Due to the limitations of culture techniques, the lung in a healthy state is traditionally considered to be a sterile organ. With the development of non-culture-dependent techniques, the presence of low-biomass microbiomes in the lungs has been identified. The species of the lung microbiome are similar to those of the oral microbiome, suggesting that the microbiome is derived passively within the lungs from the oral cavity via micro-aspiration. Elimination, immigration, and relative growth within its communities all contribute to the composition of the lung microbiome. The lung microbiome is reportedly altered in many lung diseases that have not traditionally been considered infectious or microbial, and potential pathways of microbe–host crosstalk are emerging. Recent studies have shown that the lung microbiome also plays an important role in brain autoimmunity. There is a close relationship between the lungs and the brain, which can be called the lung–brain axis. However, the problem now is that it is not well understood how the lung microbiota plays a role in the disease—specifically, whether there is a causal connection between disease and the lung microbiome. The lung microbiome includes bacteria, archaea, fungi, protozoa, and viruses. However, fungi and viruses have not been fully studied compared to bacteria in the lungs. In this review, we mainly discuss the role of the lung microbiome in chronic lung diseases and, in particular, we summarize the recent progress of the lung microbiome in multiple sclerosis, as well as the lung–brain axis.
How Organ-on-a-Chip Technology Can Assist in Studying the Role of the Glymphatic System in Neurodegenerative Diseases
Authors: Spitz Sarah , Ko Eunkyung , Ertl Peter , Kamm Roger D.
Published: January 2023

The lack of a conventional lymphatic system that permeates throughout the entire human brain has encouraged the identification and study of alternative clearance routes within the cerebrum. In 2012, the concept of the glymphatic system, a perivascular network that fluidically connects the cerebrospinal fluid to the lymphatic vessels within the meninges via the interstitium, emerged. Although its exact mode of action has not yet been fully characterized, the key underlying processes that govern solute transport and waste clearance have been identified. This review briefly describes the perivascular glial-dependent clearance system and elucidates its fundamental role in neurodegenerative diseases. The current knowledge of the glymphatic system is based almost exclusively on animal-based measurements, but these face certain limitations inherent to in vivo experiments. Recent advances in organ-on-a-chip technology are discussed to demonstrate the technology’s ability to provide alternative human-based in vitro research models. Herein, the specific focus is on how current microfluidic-based in vitro models of the neurovascular system and neurodegenerative diseases might be employed to (i) gain a deeper understanding of the role and function of the glymphatic system and (ii) to identify new opportunities for pharmacological intervention.
Utilizing the 1H-15N NMR Methods for the Characterization of Isomeric Human Milk Oligosaccharides
Authors: Garádi Zsófia , Tóth András , Gáti Tamás , Dancsó András , Béni Szabolcs
Published: January 2023

Human milk oligosaccharides (HMOs) are structurally complex unconjugated glycans that are the third largest solid fraction in human milk after lactose and lipids. HMOs are in the forefront of research since they have been proven to possess beneficial health effects, especially on breast-fed neonates. Although HMO research is a trending topic nowadays, readily available analytical methods suitable for the routine investigation of HMOs are still incomplete. NMR spectroscopy provides detailed structural information that can be used to indicate subtle structural differences, particularly for isomeric carbohydrates. Herein, we propose an NMR-based method to identify the major isomeric HMOs containing GlcNAc and/or Neu5Ac building blocks utilizing their amide functionality. Experimental conditions were optimized (H2O:D2O 9:1 v/v solvent at pH 3.0) to obtain 1H-15N HSQC and 1H-15N HSQC-TOCSY NMR spectra of the aforementioned building blocks in HMOs. Four isomeric HMO pairs, LNT/LNnT, 3’SL/6’SL, LNFP II/LNFP III, and LSTa/LSTb, were investigated, and complete NMR resonance assignments were provided. In addition, 1H and 15N NMR resonances were found to be indicative of various linkages, thereby facilitating the distinction of isomeric tri-, tetra-, and pentasaccharide HMOs. The rapid growth of HMO products (from infant formulas and dietary supplements to cosmetics) undoubtedly requires expanding the range of applicable analytical methods. Thus, our work provides a 15N NMR-based method to advance this challenging field of carbohydrate analysis.
GxxxG Motif Stabilize Ion-Channel like Pores through Cα―H···O Interaction in Aβ (1-40)
Authors: Rando Carola , Grasso Giuseppe , Sarkar Dibakar , Sciacca Michele Francesco Maria , Cucci Lorena Maria , Cosentino Alessia , Forte Giuseppe , Pannuzzo Martina , Satriano Cristina , Bhunia Anirban , La Rosa Carmelo
Published: January 2023

Aβ (1-40) can transfer from the aqueous phase to the bilayer and thus form stable ion-channel-like pores where the protein has alpha-helical conformation. The stability of the pores is due to the presence of the GXXXG motif. It has been reported that these ion-channel-like pores are stabilized by a Cα―H···O hydrogen bond that is established between a glycine of the GXXXG sequence of an alpha-helix and another amino acid of a vicinal alpha-helix. However, conflicting data are reported in the literature. Some authors have suggested that hydrogen bonding does not have a stabilizing function. Here we synthesized pentapeptides having a GXXXG motif to explore its role in pore stability. We used molecular dynamics simulations, quantum mechanics, and experimental biophysical techniques to determine whether hydrogen bonding was formed and had a stabilizing function in ion-channel-like structures. Starting from our previous molecular dynamics data, molecular quantum mechanics simulations, and ATR data showed that a stable ion-channel-like pore formed and a band centered at 2910 cm−1 was attributed to the interaction between Gly 7 of an alpha-helix and Asp 23 of a vicinal alpha-helix.
Molecular Mechanisms of Carcinogenesis in Pediatric Airways Tumors
Authors: Soloperto Davide , Gazzini Sandra , Cerullo Raffaele
Published: January 2023

Primary tumors of the airways in the pediatric population are very rare entities. For this reason, little is known about the pathogenesis of these neoplasms. Understanding the biology has different practical implications: for example, it could help in the differential diagnosis, have a prognostic significance, or may lead to the development of a targeted therapy. The aim of this article is to present the current knowledge about pediatric airways tumors, focusing on the molecular mechanisms that cause the onset and progression of these neoplasms. After a brief introduction of epidemiology and clinical presentation, the tumorigenesis of the most frequent pediatric airways tumors will be described: Juvenile-onset recurrent respiratory papillomatosis (JORRP), Subglottic Hemangiona (SH), Rhabdomyosarcoma (RMS), and Mucoepidermoid carcinoma (MEC).
Potential Roles of YAP/TAZ Mechanotransduction in Spaceflight-Induced Liver Dysfunction
Authors: Li Wang , Shu Xinyu , Zhang Xiaoyu , Zhang Ziliang , Sun Shujin , Li Ning , Long Mian
Published: January 2023

Microgravity exposure during spaceflight causes the disordered regulation of liver function, presenting a specialized mechano-biological coupling process. While YAP/TAZ serves as a typical mechanosensitive pathway involved in hepatocyte metabolism, it remains unclear whether and how it is correlated with microgravity-induced liver dysfunction. Here, we discussed liver function alterations induced by spaceflight or simulated effects of microgravity on Earth. The roles of YAP/TAZ serving as a potential bridge in connecting liver metabolism with microgravity were specifically summarized. Existing evidence indicated that YAP/TAZ target gene expressions were affected by mechanotransductive pathways and phase separation, reasonably speculating that microgravity might regulate YAP/TAZ activation by disrupting these pathways via cytoskeletal remodeling or nuclear deformation, or disturbing condensates formation via diffusion limit, and then breaking liver homeostasis.
The Cell-Specific Role of SHP2 in Regulating Bone Homeostasis and Regeneration Niches
Authors: Zhang Jie , Ye Chengxinyue , Zhu Yufan , Wang Jun , Liu Jin
Published: January 2023

Src homology-2 containing protein tyrosine phosphatase (SHP2), encoded by PTPN11, has been proven to participate in bone-related diseases, such as Noonan syndrome (NS), metachondromatosis and osteoarthritis. However, the mechanisms of SHP2 in bone remodeling and homeostasis maintenance are complex and undemonstrated. The abnormal expression of SHP2 can influence the differentiation and maturation of osteoblasts, osteoclasts and chondrocytes. Meanwhile, SHP2 mutations can act on the immune system, vasculature and nervous system, which in turn affect bone development and remodeling. Signaling pathways regulated by SHP2, such as mitogen-activated protein kinase (MAPK), Indian hedgehog (IHH) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT), are also involved in the proliferation, differentiation and migration of bone functioning cells. This review summarizes the recent advances of SHP2 on osteogenesis-related cells and niche cells in the bone marrow microenvironment. The phenotypic features of SHP2 conditional knockout mice and underlying mechanisms are discussed. The prospective applications of the current agonists or inhibitors that target SHP2 in bone-related diseases are also described. Full clarification of the role of SHP2 in bone remodeling will shed new light on potential treatment for bone related diseases.
Prenatal Sex Hormone Exposure Is Associated with the Development of Autism Spectrum Disorder
Authors: Li Mengwei , Usui Noriyoshi , Shimada Shoichi
Published: January 2023

Sexual differentiation is a major developmental process. Sex differences resulting from sexual differentiation have attracted the attention of researchers. Unraveling what contributes to and underlies sex differences will provide valuable insights into the development of neurodevelopmental disorders that exhibit sex biases. Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects an individual’s social interaction and communication abilities, and its male preponderance has been consistently reported in clinical studies. The etiology of male preponderance remains unclear, but progress has been made in studying prenatal sex hormone exposure. The present review examined studies that focused on the association between prenatal testosterone exposure and ASD development, as well as sex-specific behaviors in individuals with ASD. This review also included studies on maternal immune activation-induced developmental abnormalities that also showed striking sex differences in offspring and discussed its possible interacting roles in ASD so as to present a potential approach for future studies on sex biases in ASD.
Non-Coding RNAs in Cell-to-Cell Communication: Exploiting Physiological Mechanisms as Therapeutic Targets in Cardiovascular Pathologies
Authors: Laura Francés Javier , Musolino Elettra , Papait Roberto , Pagiatakis Christina
Published: January 2023

Cardiovascular disease, the leading cause of death worldwide, has been characterized at the molecular level by alterations in gene expression that contribute to the etiology of the disease. Such alterations have been shown to play a critical role in the development of atherosclerosis, cardiac remodeling, and age-related heart failure. Although much is now known about the cellular and molecular mechanisms in this context, the role of epigenetics in the onset of cardiovascular disease remains unclear. Epigenetics, a complex network of mechanisms that regulate gene expression independently of changes to the DNA sequence, has been highly implicated in the loss of homeostasis and the aberrant activation of a myriad of cellular pathways. More specifically, non-coding RNAs have been gaining much attention as epigenetic regulators of various pathologies. In this review, we will provide an overview of the ncRNAs involved in cell-to-cell communication in cardiovascular disease, namely atherosclerosis, cardiac remodeling, and cardiac ageing, and the potential use of epigenetic drugs as novel therapeutic targets.
Behavioral and Sensory Deficits Associated with Dysfunction of GABAergic System in a Novel shank2-Deficient Zebrafish Model
Authors: Wang Yi , Liu Chunxue , Deng Jingxin , Xu Qiong , Lin Jia , Li Huiping , Hu Meixin , Hu Chunchun , Li Qiang , Xu Xiu
Published: January 2023

Hyper-reactivity to sensory inputs is a common and debilitating symptom of autism spectrum disorder (ASD), but the underlying neural abnormalities remain unclear. Two of three patients in our clinical cohort screen harboring de novo SHANK2 mutations also exhibited high sensitivity to visual, auditory, and tactile stimuli, so we examined whether shank2 deficiencies contribute to sensory abnormalities and other ASD-like phenotypes by generating a stable shank2b-deficient zebrafish model (shank2b−/−). The adult shank2b−/− zebrafish demonstrated reduced social preference and kin preference as well as enhanced behavioral stereotypy, while larvae exhibited hyper-sensitivity to auditory noise and abnormal hyperactivity during dark-to-light transitions. This model thus recapitulated the core developmental and behavioral phenotypes of many previous genetic ASD models. Expression levels of γ-aminobutyric acid (GABA) receptor subunit mRNAs and proteins were also reduced in shank2b−/− zebrafish, and these animals exhibited greater sensitivity to drug-induced seizures. Our results suggest that GABAergic dysfunction is a major contributor to the sensory hyper-reactivity in ASD, and they underscore the need for interventions that target sensory-processing disruptions during early neural development to prevent disease progression.
Antibacterial and Healing Effect of Chicha Gum Hydrogel (Sterculia striata) with Nerolidol
Authors: Lima Idglan Sá de , Ferreira Maria Onaira Gonçalves , Barros Esmeralda Maria Lustosa , Rizzo Marcia dos Santos , Santos Jailson de Araújo , Ribeiro Alessandra Braga , Anteveli Osajima Furtini Josy , C. Silva-Filho Edson , Estevinho Leticia M.
Published: January 2023

Chicha gum is a natural polymer obtained from the Sterculia striata plant. The hydroxyl groups of its structure have a chemical affinity to form hydrogels, which favors the association with biologically active molecules, such as nerolidol. This association improves the biological properties and allows the material to be used in drug delivery systems. Chicha gum hydrogels associated with nerolidol were produced at two concentrations: 0.01 and 0.02 g mL−1. Then, the hydrogels were characterized by thermogravimetry (TG), Fourier Transform Infrared spectroscopy (FTIR), and rheological analysis. The antibacterial activity was tested against Staphylococcus aureus and Escherichia coli. The cytotoxicity was evaluated against Artemia salina. Finally, an in vivo healing assay was carried out. The infrared characterization indicated that interactions were formed during the gel reticulation. This implies the presence of nerolidol in the regions at 3100–3550 cm−1. The rheological properties changed with an increasing concentration of nerolidol, which resulted in less viscous materials. An antibacterial 83.6% growth inhibition effect was observed using the hydrogel with 0.02 g mL−1 nerolidol. The in vivo healing assay showed the practical activity of the hydrogels in the wound treatment, as the materials promoted efficient re-epithelialization. Therefore, it was concluded that the chicha hydrogels have the potential to be used as wound-healing products.
miRNA Molecules—Late Breaking Treatment for Inflammatory Bowel Diseases?
Authors: Aggeletopoulou Ioanna , Mouzaki Athanasia , Thomopoulos Konstantinos , Triantos Christos
Published: January 2023

MicroRNAs (miRNAs) are a group of non-coding RNAs that play a critical role in regulating epigenetic mechanisms in inflammation-related diseases. Inflammatory bowel diseases (IBDs), which primarily include ulcerative colitis (UC) and Crohn’s disease (CD), are characterized by chronic recurrent inflammation of intestinal tissues. Due to the multifactorial etiology of these diseases, the development of innovative treatment strategies that can effectively maintain remission and alleviate disease symptoms is a major challenge. In recent years, evidence for the regulatory role of miRNAs in the pathogenetic mechanisms of various diseases, including IBD, has been accumulating. In light of these findings, miRNAs represent potential innovative candidates for therapeutic application in IBD. In this review, we discuss recent findings on the role of miRNAs in regulating inflammatory responses, maintaining intestinal barrier integrity, and developing fibrosis in clinical and experimental IBD. The focus is on the existing literature, indicating potential therapeutic application of miRNAs in both preclinical experimental IBD models and translational data in the context of clinical IBD. To date, a large and diverse data set, which is growing rapidly, supports the potential use of miRNA-based therapies in clinical practice, although many questions remain unanswered.
Lipid Biomarkers and Atherosclerosis—Old and New in Cardiovascular Risk in Childhood
Authors: Močnik Mirjam , Marčun Varda Nataša
Published: January 2023

Lipids are a complex group of molecules in the body, essential as structural, functional and metabolic components. When disbalanced, they are regarded as a cardiovascular risk factor, traditionally in cholesterol level evaluation. However, due to their complex nature, much research is still needed for a comprehensive understanding of their role in atherosclerosis, especially in the young. Several new lipid biomarkers are emerging, some already researched to a point, such as lipoproteins and apolipoproteins. Other lipid molecules are also being increasingly researched, including oxidized forms due to oxidative inflammation in atherosclerosis, and sphingolipids. For many, even those less new, the atherogenic potential is not clear and no clinical recommendations are in place to aid the clinician in using them in everyday clinical practice. Moreover, lipids’ involvement in atherogenesis in children has yet to be elucidated. This review summarizes the current knowledge on lipids as biomarkers of cardiovascular risk in the paediatric population.
Phillygenin Attenuated Colon Inflammation and Improved Intestinal Mucosal Barrier in DSS-induced Colitis Mice via TLR4/Src Mediated MAPK and NF-κB Signaling Pathways
Authors: Xue Huan-Huan , Li Jing-Jing , Li Shi-Fei , Guo Jing , Yan Rui-Ping , Chen Ting-Gui , Shi Xiang-Hua , Wang Jin-Dong , Zhang Li-Wei
Published: January 2023

Ulcerative colitis (UC) is a chronic, relapsing, and nonspecific inflammatory bowel disease (IBD). Phillygenin (PHI), a natural bioactive ingredient, isolated from Forsythiae Fructus, exhibits anti-inflammatory, anti-oxidative, and hepatoprotective activities. However, few reports provide direct evidence on the efficacy of PHI in improving colitis mice. The present study elucidated that the symptoms of DSS-induced colitis mice were alleviated after PHI administration, including body weight loss, the disease activity index, colon length shortening, colonic pathological damage, splenomegaly, and hepatomegaly. PHI treatment improved the intestinal mucosal barrier by protecting goblet cells, promoting gene expressions of Clca1, Slc26a3, and Aqp8, increasing tight junction proteins (TJs), and reducing epithelial cell apoptosis. In addition, the levels of oxidative stress (MPO, SOD, and MDA) and inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-10) were reversed by PHI in colitis mice. According to transcriptome and network pharmacology analysis, inflammatory pathway might be an important mechanism for PHI to improve colitis. Western blotting displayed that the PHI inhibited the activation of tyrosine kinase Src mediated by TLR4, and then reduced the phosphorylation of downstream proteins p38, JNK, and NF-κB in colitis mice. In summary, our results suggested that PHI might be an appropriate and effective drug candidate to protect colitis.
S100B Affects Gut Microbiota Biodiversity
Authors: Romano Spica Vincenzo , Valeriani Federica , Orsini Massimiliano , Clementi Maria Elisabetta , Seguella Luisa , Gianfranceschi Gianluca , Di Liddo Rosa , Di Sante Gabriele , Ubaldi Francesca , Ria Francesco , Esposito Giuseppe , Michetti Fabrizio
Published: January 2023

This in vivo study in mice addresses the relationship between the biodiversity of the microbiota and the levels of S100B, a protein present in enteroglial cells, but also in foods such as milk. A positive significant correlation was observed between S100B levels and Shannon values, which was reduced after treatment with Pentamidine, an inhibitor of S100B function, indicating that the correlation was influenced by the modulation of S100B activity. Using the bootstrap average method based on the distribution of the S100B concentration, three groups were identified, exhibiting a significant difference between the microbial profiles. Operational taxonomic units, when analyzed by SIMPER analysis, showed that genera regarded to be eubiotic were mainly concentrated in the intermediate group, while genera potentially harboring pathobionts often appeared to be more concentrated in groups where the S100B amounts were very low or high. Finally, in a pilot experiment, S100B was administered orally, and the microbial profiles appeared to be modified accordingly. These data may open novel perspectives involving the possibility of S100B-mediated regulation in the intestinal microbiota.
A Review of Insect Pest Management in Vegetable Crop Production in Nigeria
Authors: Ofuya Thomas I. , Okunlola Adeyela I. , Mbata George N.
Published: January 2023

Insect pest infestations and damage can limit the production of vegetables in the farming systems in Nigeria. This review looks at integrated insect pest management as a possible panacea for resolving insect pest issues in vegetable crops. The main vegetable crops which include okra, tomatoes, chilli peppers, cucumbers, green amaranth, carrots and onions are highlighted. The major insect pests of the various vegetables which include foliage beetles, caterpillars, aphids, fruit flies, stink bugs, and grasshoppers are also mentioned. The various control measures that have been empirically verified for the mitigation of the impact of these insect pests, including the application of synthetic insecticides, modification of agronomic practices, use of resistant varieties, application of botanicals, biological and mechanical controls, are discussed. Studies which have been carried out attempting to integrate two or more of the control strategies for better insect pest control are also reviewed. Strategies that can be put in place for the integrated pest management of vegetable insect pests in Nigeria are considered. Among the IPM (Integrated Pest Management) practices instituted for the mitigation of pest infestations on vegetable crops in Nigeria, intercropping of suitable vegetables in combination with the application of aqueous extracts of Azadirachta indica and Piper guineense seeds under good farm hygiene and sanitation proved to be most successful.
Quantifying the Aerodynamic Power Required for Flight and Testing for Adaptive Wind Drift in Passion-Vine Butterflies Heliconius sara (Lepidoptera: Nymphalidae)
Authors: Srygley Robert B. , Dudley Robert , Hernandez Edgar J. , Kainz Franz , Riveros Andre J. , Ellington Charlie P.
Published: January 2023

Although theoretical work on optimal migration has been largely restricted to birds, relevant free-flight data are now becoming available for migratory insects. Here we report, for the first time in passion-vine butterflies, that Heliconius sara migrates directionally. To test optimal migration models for insects, we quantified the aerodynamic power curve for free-flying H. sara as they migrated across the Panama Canal. Using synchronized stereo-images from high-speed video cameras, we reconstructed three-dimensional flight kinematics of H. sara migrating naturally across the Panama Canal. We also reconstructed flight kinematics from a single-camera view of butterflies flying through a flight tunnel. We calculated the power requirements for flight for H. sara over a range of flight velocities. The relationship between aerodynamic power and velocity was “J”-shaped across the measured velocities with a minimum power velocity of 0.9 m/s and a maximum range velocity of 2.25 m/s. Migrating H. sara did not compensate for crosswind drift. Changes in airspeed with tailwind drift were consistent with the null hypothesis that H. sara did not compensate for tailwind drift, but they were also not significantly different from those predicted to maximize the migratory range of the insects.
The Role of Platelets in the Pathogenesis and Pathophysiology of Adenomyosis
Authors: Guo Sun-Wei
Published: January 2023

Widely viewed as an enigmatic disease, adenomyosis is a common gynecological disease with bewildering pathogenesis and pathophysiology. One defining hallmark of adenomyotic lesions is cyclic bleeding as in eutopic endometrium, yet bleeding is a quintessential trademark of tissue injury, which is invariably followed by tissue repair. Consequently, adenomyotic lesions resemble wounds. Following each bleeding episode, adenomyotic lesions undergo tissue repair, and, as such, platelets are the first responder that heralds the subsequent tissue repair. This repeated tissue injury and repair (ReTIAR) would elicit several key molecular events crucial for lesional progression, eventually leading to lesional fibrosis. Platelets interact with adenomyotic cells and actively participate in these events, promoting the lesional progression and fibrogenesis. Lesional fibrosis may also be propagated into their neighboring endometrial–myometrial interface and then to eutopic endometrium, impairing endometrial repair and causing heavy menstrual bleeding. Moreover, lesional progression may result in hyperinnervation and an enlarged uterus. In this review, the role of platelets in the pathogenesis, progression, and pathophysiology is reviewed, along with the therapeutic implication. In addition, I shall demonstrate how the notion of ReTIAR provides a much needed framework to tether to and piece together many seemingly unrelated findings and how it helps to make useful predictions.
Application of Nonlinear Models Combined with Conventional Laboratory Indicators for the Diagnosis and Differential Diagnosis of Ovarian Cancer
Authors: Zhang Tongshuo , Pang Aibo , Lyu Jungang , Ren Hefei , Song Jiangnan , Zhu Feng , Liu Jinlong , Cui Yuntao , Ling Cunbao , Tian Yaping
Published: January 2023

Existing biomarkers for ovarian cancer lack sensitivity and specificity. We compared the diagnostic efficacy of nonlinear machine learning and linear statistical models for diagnosing ovarian cancer using a combination of conventional laboratory indicators. We divided 901 retrospective samples into an ovarian cancer group and a control group, comprising non-ovarian malignant gynecological tumor (NOMGT), benign gynecological disease (BGD), and healthy control subgroups. Cases were randomly assigned to training and internal validation sets. Two linear (logistic regression (LR) and Fisher’s linear discriminant (FLD)) and three nonlinear models (support vector machine (SVM), random forest (RF), and artificial neural network (ANN)) were constructed using 22 conventional laboratory indicators and three demographic characteristics. Model performance was compared. In an independent prospectively recruited validation set, the order of diagnostic efficiency was RF, SVM, ANN, FLD, LR, and carbohydrate antigen 125 (CA125)-only (AUC, accuracy: 0.989, 95.6%; 0.985, 94.4%; 0.974, 93.4%; 0.915, 82.1%; 0.859, 80.1%; and 0.732, 73.0%, respectively). RF maintained satisfactory classification performance for identifying different ovarian cancer stages and for discriminating it from NOMGT-, BGD-, or CA125-positive control. Nonlinear models outperformed linear models, indicating that nonlinear machine learning models can efficiently use conventional laboratory indicators for ovarian cancer diagnosis.
Incidence of Orbital Side Effects in Zygomaticomaxillary Complex and Isolated Orbital Walls Fractures: A Retrospective Study in South Italy and a Brief Review of the Literature
Authors: Committeri Umberto , Arena Antonio , Carraturo Emanuele , Austoni Martina , Germano Cristiana , Salzano Giovanni , De Riu Giacomo , Giovacchini Francesco , Maglitto Fabio , Abbate Vincenzo , Bonavolontà Paola , Califano Luigi , Piombino Pasquale
Published: January 2023

Zygomaticomaxillary complex and isolated orbital walls fractures are one of the most common fractures of the midface, often presenting orbital symptoms and complications. Our study was born with the aim of understanding the trend in the incidence of orbital presurgical symptoms, specifically diplopia, enophthalmos and exophthalmos, in the Campania Region in southern Italy. We conducted a retrospective, monocentric observational study at the Maxillofacial Surgery Unit of the Federico II University Hospital of Naples, enrolling 402 patients who reported a fracture of the zygomaticomaxillary complex and orbital floor region from 1 January 2012 to 1 January 2022. Patients were evaluated by age, gender, etiology, type of fracture, preoperative orbital side effects and symptoms. Pre-surgical side effects were studied, and 16% of patients (n = 66) developed diplopia. Diplopia was most common in patients previously operated on for orbital wall fractures (100%), and least common in patients who reported trauma after interpersonal violence (15%) and road traffic accidents (11%). Exophthalmos appeared only in 1% (six cases); whereas it did not appear in 99% (396 cases). Enophthalmos was present in 4% (sixteen cases), most commonly in interpersonal violence cases (two cases). The frequency of orbital complications in patients with zygomaticomaxillary complex and isolated orbital walls fractures suggests how diplopia remains the most common pre-surgical orbital side effect.
Epidemiology and Clinical Burden of Meningococcal Disease in France: Scoping Review
Authors: Baloche Alexiane , Dussart Claude , Bedouch Pierrick , Carrouel Florence , Mick Gérard
Published: January 2023

Invasive meningococcal disease (IMD) remains a significant health concern due to its unpredictable nature and its rapid progression. Even if occurrence of IMD is strictly monitored by a national surveillance network, no information on long-term sequelae is reported, making it difficult to assess the entire clinical burden of IMD in France. The aim of this scoping review was to analyze the epidemiology and the clinical burden of IMD in France by reporting the main epidemiological parameters, and by describing the clinical consequences and the care pathway of patients. The process of the review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension to the Scoping Reviews guidelines. In France, the incidence of IMD cases has been fluctuating over time, characterized by an overall downward trend linked to a decrease in Sg B cases and the introduction of mandatory vaccination against Sg C. Sg W cases increased in recent years (from 5% to 21% in 2019). The case fatality rate remained constant (6–12.9%). The most frequently reported sequelae were severe neurological disorder, epilepsy, and anxiety. However, data on sequelae and care pathways were scarce. Further research should concentrate on providing robust identification of sequelae and the subsequent impact on quality of life, as well as on the organization of optimal care and support for patients and their families.
Gastroduodenal Stenting with a Flexible Stent Demonstrates Favorable Clinical Effectiveness despite Gradual Expansion: A Multicenter Prospective Study
Authors: Shigoka Hiroaki , Toki Masao , Takahashi Sho , Takahara Naminatsu , Kitamura Katsuya , Iwasaki Eisuke , Nakahara Kazunari , Isayama Hiroyuki , Nakai Yousuke , Maetani Iruru
Published: January 2023

Aims: This study aimed to evaluate the effectiveness and safety of stenting with a flexible braided self-expandable metal stent (SEMS) for unresectable malignant gastric outlet obstruction (GOO). Methods: Palliative stenting was prospectively carried out at seven university hospitals between October 2017 and August 2020. All procedures were performed using a flexible branded SEMS of the same brand. The primary endpoint was clinical success rate at 7 days after stenting. Secondary endpoints were procedural success rate, adverse events, recurrent gastric outlet obstruction (RGOO), and patient survival time. Results: Sixty patients were enrolled. The procedural and clinical success rates were 100% and 90%, respectively. RGOO occurred in 15 cases (25%). Adverse events other than RGOO were found in seven cases (12%). The 50% survival time was 75.5 days (range: 52–97 days). Median expansion rates at 1, 3, and 7 days after stenting were 55%, 65%, and 75%, respectively. Conclusions: A flexible braided stent woven with relatively thin wires was used for malignant GOO. Despite a gradual expansion with slightly lower expansile force, the stent functioned sufficiently well and showed favorable results. Clinical Trials Registry ID: UMIN000029496.