bluuebunny/crossref_metadata_2025 huggingface dataset:
Do Preoperative Corticosteroid Injections Increase the Risk of Infection after Shoulder Arthroscopy or Shoulder Arthroplasty? A Systematic Review
Authors: Lucenti Ludovico , Panvini Flora Maria Chiara , de Cristo Claudia , Rapisarda Damiano , Sapienza Marco , Testa Gianluca , Pavone Vito
Published: February 2024

Introduction: Corticosteroid injections have demonstrated short-term benefits for shoulder pain. This symptomatic treatment method is used in various inflammatory conditions that affect the shoulder joint. Corticosteroid joint injections are not without risks and complications. Adverse effects have been documented, including damage to the articular cartilage, tendon rupture, and attenuation of the subject’s immune response. The aim of this study was to examine the timing of preoperative corticosteroid injections on infectious outcomes of shoulder arthroscopies and shoulder arthroplasty. Materials and Methods: In accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), the PubMed, Cochrane, and Science Direct databases were systematically reviewed by two independent authors in January 2024. After full-text reading and checking the reference lists, 11 article were included. Results: Patients who received a shoulder injection within three months prior to undergoing shoulder arthroplasty exhibited a markedly elevated incidence of infection. In addition, a significantly increased risk of periprosthetic joint infection (PJI) at 90 days postoperatively in patients who received CSIs (corticosteroid injections) within 1 month prior to shoulder arthroplasty was found. Different authors consider CSI injections within the 2 weeks prior to shoulder arthroscopy surgery principally associated with an increased risk of postoperative infection. Discussion: There is still no consensus on the correct timing of preoperative CSIs in both arthroscopic and arthroplasty procedures. The literature does not identify whether the number of preoperative injections could increase the risk of periprosthetic infection. Obesity, sex, and smoking did not have a significant effect on PJIs; alcohol abuse could be considered as a risk factor for PJIs with CSIs. Both in prosthetic surgeries and in arthroscopy procedures, modifiable and unmodifiable factors play secondary roles. The risk of postoperative infection is greater within 3 months, although it is almost comparable at one- and two-year follow-ups.
Whole Body Cryostimulation: A New Adjuvant Treatment in Central Sensitization Syndromes? An Expert Opinion
Authors: Alito Angelo , Verme Federica , Mercati Gian Paolo , Piterà Paolo , Fontana Jacopo Maria , Capodaglio Paolo
Published: February 2024

Central sensitisation is defined as a multifactorial etiopathogenetic condition involving an increase in the reactivity of nociceptive neurons and alterations in pain transmission and perception in the central nervous system. Patients may present with widespread chronic pain, fatigue, sleep disturbance, dizziness, psychological (e.g., depression, anxiety, and anger) and social impairment. Pain can be spontaneous in onset and persistence, characterised by an exaggerated response and spread beyond the site of origin, and sometimes triggered by a non-painful stimulus. Whole-body cryostimulation (WBC) could be an adjuvant therapy in the management of this type of pain because of its global anti-inflammatory effect, changes in cytokines and hormone secretion, reduction in nerve conduction velocity, autonomic modulation, and release of neurotransmitters involved in the pain pathway. In several conditions (e.g., fibromyalgia, rheumatoid arthritis, and chronic musculoskeletal pain), WBC affects physical performance, pain perception, and psychological aspects. Given its multiple targets and effects at different organs and levels, WBC appears to be a versatile adjuvant treatment for a wide range of conditions of rehabilitation interest. Further research is needed to fully understand the mechanisms of analgesic effect and potential actions on pain pathways, as well as to study long-term effects and potential uses in other chronic pain conditions.
Psychological Distress Associated with Enforced Hospital Isolation Due to COVID-19 during the “Flatten the Curve” Phase in Morocco: A Single-Center Cross-Sectional Study
Authors: Chadli Sarra , Nechba Bennis Rhita , Madani Naoufel , El Fahime ElMostafa , Abouqal Redouane , Belayachi Jihane
Published: February 2024

(1) Background: although much research has highlighted the mental health challenges faced by patients in hospital isolation during the COVID-19 pandemic, data from low–middle-income countries, including Morocco, are lacking. The main objective of this study was to assess the psychological distress of patients undergoing enforced hospital isolation during the initial phase of the COVID-19 pandemic in Morocco. (2) Methods: we conducted a cross-sectional study between 1 April and 1 May 2020, among patients hospitalized in isolation for suspected or confirmed COVID-19 at the Ibn Sina University Hospital of Rabat, Morocco. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). Binary logistic regression was performed to identify variables associated with anxiety and depression, with a cutoff of ≥8 used for both scales to create dichotomous variables. (3) Results: among 200 patients, 42.5% and 43% scored above the cut-off points for anxiety and depression, respectively. Multiple logistic regression identified female gender, a higher education level, a longer duration of isolation, and a poor understanding of the reasons for isolation as significant factors associated with anxiety. Conversely, female gender, chronic disease, a longer duration of isolation, and a poor understanding of the reasons for isolation were factors significantly associated with depression. (4) Conclusions: our study underscores high rates of anxiety and depression among patients forced into hospital isolation during the initial phase of COVID-19 in Morocco. We identified several factors associated with patients experiencing psychological distress that may inform future discussions on mental health and psychiatric crisis management.
Naples Yellow Revisited: Insights into Trades and Use in 17th-Century Sicily from the Macro X-ray Fluorescence Scanning of Matthias Stomer’s ‘The Mocking of Christ’
Authors: Botticelli Michela , Miliani Costanza , Ravan Eva Luna , Caliri Claudia , Romano Francesco Paolo
Published: February 2024

In a recent non-destructive analytical campaign at Museo Civico, Castello Ursino, in Catania, Italy, several paintings in the permanent collection were investigated by MA-XRF scanning, with a special focus on Matthias Stomer’s production. On one depiction of the Mocking of Christ (ca. 1640) donated to the municipality of Catania by G.B. Finocchiaro in 1826, the analysis documented the use of Naples yellow. Sb with Pb was detected in yellow areas of the Mocking of Christ, but not in his work Tobias healing his father. This finding possibly suggested an early use of lead antimonate yellow in South Italy, although it is generally accepted that this pigment was introduced in painting in the eighteenth century. Further details on his technique and later conservation treatments are provided, as well as literary comparisons with the artistic production during the same period, in Sicily and elsewhere. A systematic study of Stomer’s works, for example examining paintings produced while he was in Naples or Rome, might determine whether this material choice depended on local availability. Overall, it would shed light on his technique, as well as on the history of Naples yellow in southern Italy and beyond, before this pigment became so popular in the eighteenth century.
Dendropanax morbifera Leveille Extract-Induced Alteration of Metabolic Profile in Whitening Effects
Authors: Bu Ting , Kim Dongwon , Kim Sooah
Published: February 2024

This study aimed to evaluate the potential of Dendropanax morbifera Leveille (D. morbifera) extract as a natural melanin depigmentation agent to achieve skin whitening. Treating α-MSH-stimulated B16-F10 cells with the extract effectively inhibited melanin production and tyrosinase activity. The cellular metabolic profiles were analyzed to understand the mechanisms underlying the whitening-related metabolic processes. We identified 29 metabolites that were significantly altered in the α-MSH-stimulated B16-F10 cells. The melanin-synthesis-related pathways that were downregulated included phenylalanine, tyrosine, and tryptophan biosynthesis and phenylalanine metabolism. Simultaneously, alanine, aspartate, and glutamate metabolism; arginine and proline metabolism; arginine biosynthesis; butanoate metabolism; glutathione metabolism; and glyoxylate and dicarboxylate metabolism were upregulated. We found that the optimal extract concentration of 0.2 mg/mL showed the highest efficacy in reversing the alterations to the metabolite levels and metabolic pathways. Moreover, D. morbifera extract exerted low cytotoxicity and high efficacy in inhibiting melanin production. Thus, D. morbifera extract is a potential melanin inhibitor with application in the development of whitening cosmetics.
Differential Tolerance of Primary Metabolism of Annona emarginata (Schltdl.) H. Rainer to Water Stress Modulates Alkaloid Production
Authors: Honório Ana Beatriz Marques , De-la-Cruz-Chacón Ivan , da Silva Gustavo Cabral , Mimi Carolina Ovile , Campos Felipe Girotto , da Silva Magali Ribeiro , Boaro Carmen Silvia Fernandes , Ferreira Gisela
Published: February 2024

Annona emarginata produces alkaloids of ecological and pharmacological interest and is tolerant to water and biotic stress, so it is used as rootstock for other Annonaceae fruits. There are few reports in the literature on how contrasting water stress impacts the production of specialized metabolites in Annonaceae and how primary metabolism adjusts to support such production. The objective of this investigation was to evaluate how drought and flooding stress affect alkaloid concentration and the primary metabolism of young A. emarginata plants. Three water levels (flooding, field capacity, and drought) were studied at two moments (stress and recovery). Variables analyzed were gas exchange levels, chlorophyll a fluorescence, leaf sugars, total alkaloid content, alkaloid profile, and Liriodenine concentration. The photosynthetic metabolism of A. emarginata was affected by water stress, with plants having a greater ability to adapt to drought conditions than to flooding. During the drought, a reduction in photosynthetic efficiency with subsequent recovery, higher starch and trehalose concentrations in leaves, and total alkaloids in roots (480 µg.g−1) were observed. Under flooding, there was a reduction in photochemical efficiency during stress, indicating damage to the photosynthetic apparatus, without reversal during the recovery period, as well as a higher concentration of total sugars, reducing sugars, sucrose, glucose, and fructose in leaves, and Liriodenine in roots (100 µg.g−1), with a lower concentration of total alkaloids (90 µg.g−1). It could be concluded that there is differential tolerance of A. emarginata to water stress, inducing the modulation of alkaloid production, while drought promotes a higher concentration of total alkaloids and flooding leads to an increase in the Liriodenine concentration.
Reach, Acceptability, and Sustainability of the Native Changing High-Risk Alcohol Use and Increasing Contraception Effectiveness Study (CHOICES) Intervention: A Qualitative Evaluation of an Alcohol-Exposed Pregnancy Prevention Program
Authors: London Sara M. , Hanson Jessica D. , Sarche Michelle , Oziel Kyra , Buchwald Dedra
Published: February 2024

American Indian (AI) women are at risk of alcohol-exposed pregnancy (AEP) due to the higher prevalence of alcohol use disorders (AUDs) and risky drinking. The Native Changing High-Risk Alcohol Use and Increasing Contraception Effectiveness Study (Native CHOICES) was implemented in partnership with a Northern Plains Tribal community to address the effectiveness of a brief, motivational interviewing-based intervention to reduce AEP risk among adult AI women. A subgroup of the participants shared their perspectives in a qualitative interview conducted following the completion of the six-month post-baseline data collection. These interviews solicited participant perspectives on the Native CHOICES intervention and its satisfaction, reach, acceptability, and sustainability. The participants were delighted with Native CHOICES, felt the intervention helped them learn about AEP prevention and goal setting, learned valuable lessons, and believed Native CHOICES would be well-received by other women in their community and should be continued. The participants also shared how the COVID-19 pandemic affected their choices about drinking and birth control. The findings showed the receptivity to and acceptance of Native CHOICES among AI women. The interview findings offered a glimpse into the effectiveness of Native CHOICES and how it contributed to participants making healthier choices surrounding drinking and sexual health.
Assessing Energy Mutual Funds: Performance, Risks, and Managerial Skills
Authors: Malhotra Davinder , Nippani Srinivas
Published: February 2024

This study investigates the risk-adjusted performance of energy equity mutual funds across a 23-year period, employing the Cumulative Wealth Index (CWI) to gauge their long-term performance relative to benchmark indices. Despite inherent volatility due to the energy sector’s cyclical nature, these funds consistently outperformed benchmarks based on monthly returns, showcasing resilience amid market fluctuations. However, challenges emerged during the COVID-19 pandemic, with notable improvements post-vaccination. Utilizing a multi-factor model, the research highlights the interconnectivity of energy equity mutual funds with broader market movements and systemic factors. Despite their primary focus on the energy sector, these funds exhibit sensitivity to larger market trends, rendering them susceptible to market dynamics. Additionally, an assessment of portfolio manager expertise reveals some proficiency in security selection post-vaccinations against COVID-19.
Validating Enteroid-Derived Monolayers from Murine Gut Organoids for Toxicological Testing of Inorganic Particles: Proof-of-Concept with Food-Grade Titanium Dioxide
Authors: Malaisé Yann , Casale Eva , Pettes-Duler Aurélie , Cartier Christel , Gaultier Eric , Martins Breyner Natalia , Houdeau Eric , Evariste Lauris , Lamas Bruno
Published: February 2024

Human exposure to foodborne inorganic nanoparticles (NPs) is a growing concern. However, identifying potential hazards linked to NP ingestion often requires long-term exposure in animals. Owing these constraints, intestinal organoids are a promising alternative to in vivo experiments; as such, an in vitro approach should enable a rapid and reliable assessment of the effects of ingested chemicals on the gut. However, this remains to be validated for inorganic substances. In our study, a transcriptomic analysis and immunofluorescence staining were performed to compare the effects of food-grade TiO2 (fg-TiO2) on enteroid-derived monolayers (EDMs) from murine intestinal organoids to the known impacts of TiO2 on intestinal epithelium. After their ability to respond to a pro-inflammatory cytokine cocktail was validated, EDMs were exposed to 0, 0.1, 1, or 10 µg fg-TiO2/mL for 24 h. A dose-related increase of the muc2, vilin 1, and chromogranin A gene markers of cell differentiation was observed. In addition, fg-TiO2 induced apoptosis and dose-dependent genotoxicity, while a decreased expression of genes encoding for antimicrobial peptides, and of genes related to tight junction function, was observed. These results validated the use of EDMs as a reliable model for the toxicity testing of foodborne NPs likely to affect the intestinal barrier.
The Auditory Pathway in Congenitally Cytomegalovirus-Infected Human Fetuses
Authors: Gabrielli Liliana , Bonasoni Maria Paola , Piccirilli Giulia , Petrisli Evangelia , Venturoli Simona , Cantiani Alessia , Pavoni Matteo , Marsico Concetta , Capretti Maria Grazia , Simonazzi Giuliana , Lazzarotto Tiziana
Published: February 2024

Congenital cytomegalovirus (CMV) infection is the main cause of non-hereditary sensorineural hearing loss (SNHL). In order to shed light on SNHL pathophysiology, we examined the auditory pathway in CMV-infected fetuses; the temporal lobe, in particular the auditory cortex, and the inner ear. We investigated both inner ears and temporal lobes of 20 human CMV-infected fetuses at 21 weeks of gestation. As a negative group, five fetuses from spontaneous miscarriages without CMV infection were studied. Inner ears and temporal lobes were histologically examined, immunohistochemistry for CMV and CMV-PCR were performed. On the auditory cortex, we evaluated the local microglial reaction to the infection. CMV-positive cells were found in 14/20 brains and the damage was classified as severe, moderate, or mild, according to histological features. Fetuses with severe brain damage had a statistically higher temporal lobe viral load and a higher number of activated microglial cells in the auditory cortex compared to fetuses with mild brain damage (p: 0.01; p: 0.01). In the inner ears, the marginal cells of the stria vascularis were the most CMV positive. In our study, CMV affected the auditory pathway, suggesting a tropism for this route. In addition, in the auditory cortex, microglial activation may favor further tissue damage contributing to hearing loss.
Caffeic Acid O-Methyltransferase Gene Family in Mango (Mangifera indica L.) with Transcriptional Analysis under Biotic and Abiotic Stresses and the Role of MiCOMT1 in Salt Tolerance
Authors: Wang Huiliang , Chen Zhuoli , Luo Ruixiong , Lei Chen , Zhang Mengting , Gao Aiping , Pu Jinji , Zhang He
Published: February 2024

Caffeic acid O-methyltransferase (COMT) participates in various physiological activities in plants, such as positive responses to abiotic stresses and the signal transduction of phytohormones. In this study, 18 COMT genes were identified in the chromosome-level reference genome of mango, named MiCOMTs. A phylogenetic tree containing nine groups (I-IX) was constructed based on the amino acid sequences of the 71 COMT proteins from seven species. The phylogenetic tree indicated that the members of the MiCOMTs could be divided into four groups. Quantitative real-time PCR showed that all MiCOMT genes have particularly high expression levels during flowering. The expression levels of MiCOMTs were different under abiotic and biotic stresses, including salt and stimulated drought stresses, ABA and SA treatment, as well as Xanthomonas campestris pv. mangiferaeindicae and Colletotrichum gloeosporioides infection, respectively. Among them, the expression level of MiCOMT1 was significantly up-regulated at 6–72 h after salt and stimulated drought stresses. The results of gene function analysis via the transient overexpression of the MiCOMT1 gene in Nicotiana benthamiana showed that the MiCOMT1 gene can promote the accumulation of ABA and MeJA, and improve the salt tolerance of mango. These results are beneficial to future researchers aiming to understand the biological functions and molecular mechanisms of MiCOMT genes.
Therapeutic Approach in Pigmented Purpuric Dermatoses—A Scoping Review
Authors: Kimak Agnieszka , Żebrowska Agnieszka
Published: February 2024

Pigmented purpuric dermatoses (PPD) encompass a group of chronic skin conditions characterized by the presence of petechiae, purpura, and pigmentation changes. While generally benign, these dermatoses can be persistent and aesthetically bothersome. Key clinical features include red to brownish patches with a distinctive “cayenne pepper” appearance, predominantly localized on the lower extremities, particularly the shins. Subtypes include Schamberg disease, Majocchi’s disease, Gougerot–Blum disease, Ducas and Kapetanakis pigmented purpura, and lichen aureus. Diagnosis relies primarily on clinical evaluation of skin lesions, with biopsy as a confirmatory tool. Although the exact cause of PPD remains unclear, capillary fragility and red blood cell extravasation are implicated. Treatment strategies for PPD aim to alleviate symptoms, considering the generally benign and chronic nature of the condition. As there is no standardized treatment, various methods with varying efficacy are employed. After searching SCOPUS and PubMed databases, we assessed 42 original articles to present current knowledge regarding therapy of PPD. This review will compare treatment approaches specifically in Schamberg disease and other manifestations of pigmented purpuric dermatoses.
Sex-Biased Expression and Response of microRNAs in Neurological Diseases and Neurotrauma
Authors: Geleta Urim , Prajapati Paresh , Bachstetter Adam , Nelson Peter T. , Wang Wang-Xia
Published: February 2024

Neurological diseases and neurotrauma manifest significant sex differences in prevalence, progression, outcome, and therapeutic responses. Genetic predisposition, sex hormones, inflammation, and environmental exposures are among many physiological and pathological factors that impact the sex disparity in neurological diseases. MicroRNAs (miRNAs) are a powerful class of gene expression regulator that are extensively involved in mediating biological pathways. Emerging evidence demonstrates that miRNAs play a crucial role in the sex dimorphism observed in various human diseases, including neurological diseases. Understanding the sex differences in miRNA expression and response is believed to have important implications for assessing the risk of neurological disease, defining therapeutic intervention strategies, and advancing both basic research and clinical investigations. However, there is limited research exploring the extent to which miRNAs contribute to the sex disparities observed in various neurological diseases. Here, we review the current state of knowledge related to the sexual dimorphism in miRNAs in neurological diseases and neurotrauma research. We also discuss how sex chromosomes may contribute to the miRNA sexual dimorphism phenomenon. We attempt to emphasize the significance of sexual dimorphism in miRNA biology in human diseases and to advocate a gender/sex-balanced science.
Molecular Classifications in Gastric Cancer: A Call for Interdisciplinary Collaboration
Authors: Díaz del Arco Cristina , Fernández Aceñero María Jesús , Ortega Medina Luis
Published: February 2024

Gastric cancer (GC) is a heterogeneous disease, often diagnosed at advanced stages, with a 5-year survival rate of approximately 20%. Despite notable technological advancements in cancer research over the past decades, their impact on GC management and outcomes has been limited. Numerous molecular alterations have been identified in GC, leading to various molecular classifications, such as those developed by The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG). Other authors have proposed alternative perspectives, including immune, proteomic, or epigenetic-based classifications. However, molecular stratification has not yet transitioned into clinical practice for GC, and little attention has been paid to alternative molecular classifications. In this review, we explore diverse molecular classifications in GC from a practical point of view, emphasizing their relationships with clinicopathological factors, prognosis, and therapeutic approaches. We have focused on classifications beyond those of TCGA and the ACRG, which have been less extensively reviewed previously. Additionally, we discuss the challenges that must be overcome to ensure their impact on patient treatment and prognosis. This review aims to serve as a practical framework to understand the molecular landscape of GC, facilitate the development of consensus molecular categories, and guide the design of innovative molecular studies in the field.
Quantifying the Dynamics of Bacterial Biofilm Formation on the Surface of Soft Contact Lens Materials Using Digital Holographic Tomography to Advance Biofilm Research
Authors: Buzalewicz Igor , Kaczorowska Aleksandra , Fijałkowski Wojciech , Pietrowska Aleksandra , Matczuk Anna Karolina , Podbielska Halina , Wieliczko Alina , Witkiewicz Wojciech , Jędruchniewicz Natalia
Published: February 2024

The increase in bacterial resistance to antibiotics in recent years demands innovative strategies for the detection and combating of biofilms, which are notoriously resilient. Biofilms, particularly those on contact lenses, can lead to biofilm-related infections (e.g., conjunctivitis and keratitis), posing a significant risk to patients. Non-destructive and non-contact sensing techniques are essential in addressing this threat. Digital holographic tomography emerges as a promising solution. This allows for the 3D reconstruction of the refractive index distribution in biological samples, enabling label-free visualization and the quantitative analysis of biofilms. This tool provides insight into the dynamics of biofilm formation and maturation on the surface of transparent materials. Applying digital holographic tomography for biofilm examination has the potential to advance our ability to combat the antibiotic bacterial resistance crisis. A recent study focused on characterizing biofilm formation and maturation on six soft contact lens materials (three silicone hydrogels, three hydrogels), with a particular emphasis on Staphylococcus epidermis and Pseudomonas aeruginosa, both common culprits in ocular infections. The results revealed species- and time-dependent variations in the refractive indexes and volumes of biofilms, shedding light on cell dynamics, cell death, and contact lens material-related factors. The use of digital holographic tomography enables the quantitative analysis of biofilm dynamics, providing us with a better understanding and characterization of bacterial biofilms.
Liquid Biopsy: A Game Changer for Type 2 Diabetes
Authors: Gradisteanu Pircalabioru Gratiela , Musat Madalina , Elian Viviana , Iliescu Ciprian
Published: February 2024

As the burden of type 2 diabetes (T2D) continues to escalate globally, there is a growing need for novel, less-invasive biomarkers capable of early diabetes detection and monitoring of disease progression. Liquid biopsy, recognized for its minimally invasive nature, is increasingly being applied beyond oncology, and nevertheless shows its potential when the collection of the tissue biopsy is not possible. This diagnostic approach involves utilizing liquid biopsy markers such as cell-free nucleic acids, extracellular vesicles, and diverse metabolites for the molecular diagnosis of T2D and its related complications. In this context, we thoroughly examine recent developments in T2D liquid biopsy research. Additionally, we discuss the primary challenges and future prospects of employing liquid biopsy in the management of T2D. Prognosis, diagnosis and monitoring of T2D through liquid biopsy could be a game-changing technique for personalized diabetes management.
Effect of Caffeine on the Inflammatory-Dependent Changes in the GnRH/LH Secretion in a Female Sheep Model
Authors: Herman Andrzej Przemysław , Tomczyk Monika , Wójcik Maciej , Bochenek Joanna , Antushevich Hanna , Herman Anna , Wiechetek Wiktoria , Szczepkowska Aleksandra , Marciniak Elżbieta , Tomaszewska-Zaremba Dorota
Published: February 2024

Caffeine is one of the most widely consumed psychoactive drugs in the world. It easily crosses the blood–brain barrier, and caffeine-interacting adenosine and ryanodine receptors are distributed in various areas of the brain, including the hypothalamus and pituitary. Caffeine intake may have an impact on reproductive and immune function. Therefore, in the present study performed on the ewe model, we decided to investigate the effect of peripheral administration of caffeine (30 mg/kg) on the secretory activity of the hypothalamic–pituitary unit which regulates the reproductive function in females during both a physiological state and an immune/inflammatory challenge induced by lipopolysaccharide (LPS; 400 ng/kg) injection. It was found that caffeine stimulated (p < 0.01) the biosynthesis of gonadotropin-releasing hormone (GnRH) in the hypothalamus of ewe under both physiological and inflammatory conditions. Caffeine also increased (p < 0.05) luteinizing hormone (LH) secretion in ewes in a physiological state; however, a single administration of caffeine failed to completely release the LH secretion from the inhibitory influence of inflammation. This could result from the decreased expression of GnRHR in the pituitary and it may also be associated with the changes in the concentration of neurotransmitters in the median eminence (ME) where GnRH neuron terminals are located. Caffeine and LPS increased (p < 0.05) dopamine in the ME which may explain the inhibition of GnRH release. Caffeine treatment also increased (p < 0.01) cortisol release, and this stimulatory effect was particularly evident in sheep under immunological stress. Our studies suggest that caffeine affects the secretory activity of the hypothalamic–pituitary unit, although its effect appears to be partially dependent on the animal’s immune status.
The Complete Chloroplast Genomes of Bulbophyllum (Orchidaceae) Species: Insight into Genome Structure Divergence and Phylogenetic Analysis
Authors: Wu Yuwei , Zeng Meng-Yao , Wang Huan-Xin , Lan Siren , Liu Zhong-Jian , Zhang Shibao , Li Ming-He , Guan Yunxiao
Published: February 2024

Bulbophyllum is one of the largest genera and presents some of the most intricate taxonomic problems in the family Orchidaceae, including species of ornamental and medical importance. The lack of knowledge regarding the characterization of Bulbophyllum chloroplast (cp) genomes has imposed current limitations on our study. Here, we report the complete cp genomes of seven Bulbophyllum species, including B. ambrosia, B. crassipes, B. farreri, B. hamatum, B. shanicum, B. triste, and B. violaceolabellum, and compared with related taxa to provide a better understanding of their genomic information on taxonomy and phylogeny. A total of 28 Bulbophyllum cp genomes exhibit typical quadripartite structures with lengths ranging from 145,092 bp to 165,812 bp and a GC content of 36.60% to 38.04%. Each genome contained 125–132 genes, encompassing 74–86 protein-coding genes, 38 tRNA genes, and eight rRNA genes. The genome arrangements, gene contents, and length were similar, with differences observed in ndh gene composition. It is worth noting that there were exogenous fragment insertions in the IR regions of B. crassipes. A total of 18–49 long repeats and 38–80 simple sequence repeats (SSRs) were detected and the single nucleotide (A/T) was dominant in Bulbophyllum cp genomes, with an obvious A/T preference. An analysis of relative synonymous codon usage (RSCU) revealed that leucine (Leu) was the most frequently used codon, while cysteine (Cys) was the least used. Six highly variable regions (rpl32-trnLUAG > trnTUGU-trnLUAA > trnFGAA-ndhJ > rps15-ycf1 > rbcL-accD > psbI-trnSGCU) and five coding sequences (ycf1 > rps12 > matK > psbK > rps15) were identified as potential DNA markers based on nucleotide diversity. Additionally, 31,641 molecular diagnostic characters (MDCs) were identified in complete cp genomes. A phylogenetic analysis based on the complete cp genome sequences and 68 protein-coding genes strongly supported that 28 Bulbophyllum species can be divided into four branches, sects. Brachyantha, Cirrhopetalum, and Leopardinae, defined by morphology, were non-monophyly. Our results enriched the genetic resources of Bulbophyllum, providing valuable information to illustrate the complicated taxonomy, phylogeny, and evolution process of the genus.
Identification of Viruses Infecting Phalaenopsis Orchids Using Nanopore Sequencing and Development of an RT-RPA-CRISPR/Cas12a for Rapid Visual Detection of Nerine Latent Virus
Authors: Lee Hyo-Jeong , Kim Hae-Jun , Cho In-Sook , Jeong Rae-Dong
Published: February 2024

Phalaenopsis orchids are one of the most popular ornamental plants. More than thirty orchid viruses have been reported, and virus-infected Phalaenopsis orchids significantly lose their commercial value. Therefore, the development of improved viral disease detection methods could be useful for quality control in orchid cultivation. In this study, we first utilized the MinION, a portable sequencing device based on Oxford Nanopore Technologies (ONT) to rapidly detect plant viruses in Phalaenopsis orchids. Nanopore sequencing revealed the presence of three plant viruses in Phalaenopsis orchids: odontoglossum ringspot virus, cymbidium mosaic virus, and nerine latent virus (NeLV). Furthermore, for the first time, we detected NeLV infection in Phalaenopsis orchids using nanopore sequencing and developed the reverse transcription–recombinase polymerase amplification (RT-RPA)-CRISPR/Cas12a method for rapid, instrument-flexible, and accurate diagnosis. The developed RT-RPA-CRISPR/Cas12a technique can confirm NeLV infection in less than 20 min and exhibits no cross-reactivity with other viruses. To determine the sensitivity of RT-RPA-CRISPR/Cas12a for NeLV, we compared it with RT-PCR using serially diluted transcripts and found a detection limit of 10 zg/μL, which is approximately 1000-fold more sensitive. Taken together, the ONT platform offers an efficient strategy for monitoring plant viral pathogens, and the RT-RPA-CRISPR/Cas12a method has great potential as a useful tool for the rapid and sensitive diagnosis of NeLV.
Structural Variant Disrupting the Expression of the Remote FOXC1 Gene in a Patient with Syndromic Complex Microphthalmia
Authors: Plaisancié Julie , Chesneau Bertrand , Fares-Taie Lucas , Rozet Jean-Michel , Pechmeja Jacmine , Noero Julien , Gaston Véronique , Bailleul-Forestier Isabelle , Calvas Patrick , Chassaing Nicolas
Published: February 2024

Ocular malformations (OMs) arise from early defects during embryonic eye development. Despite the identification of over 100 genes linked to this heterogeneous group of disorders, the genetic cause remains unknown for half of the individuals following Whole-Exome Sequencing. Diagnosis procedures are further hampered by the difficulty of studying samples from clinically relevant tissue, which is one of the main obstacles in OMs. Whole-Genome Sequencing (WGS) to screen for non-coding regions and structural variants may unveil new diagnoses for OM individuals. In this study, we report a patient exhibiting a syndromic OM with a de novo 3.15 Mb inversion in the 6p25 region identified by WGS. This balanced structural variant was located 100 kb away from the FOXC1 gene, previously associated with ocular defects in the literature. We hypothesized that the inversion disrupts the topologically associating domain of FOXC1 and impairs the expression of the gene. Using a new type of samples to study transcripts, we were able to show that the patient presented monoallelic expression of FOXC1 in conjunctival cells, consistent with the abolition of the expression of the inverted allele. This report underscores the importance of investigating structural variants, even in non-coding regions, in individuals affected by ocular malformations.
Roles of lncRNAs in NF-κB-Mediated Macrophage Inflammation and Their Implications in the Pathogenesis of Human Diseases
Authors: Shin Jae-Joon , Park Jeongkwang , Shin Hyeung-Seob , Arab Imene , Suk Kyoungho , Lee Won-Ha
Published: February 2024

Over the past century, molecular biology’s focus has transitioned from proteins to DNA, and now to RNA. Once considered merely a genetic information carrier, RNA is now recognized as both a vital element in early cellular life and a regulator in complex organisms. Long noncoding RNAs (lncRNAs), which are over 200 bases long but do not code for proteins, play roles in gene expression regulation and signal transduction by inducing epigenetic changes or interacting with various proteins and RNAs. These interactions exhibit a range of functions in various cell types, including macrophages. Notably, some macrophage lncRNAs influence the activation of NF-κB, a crucial transcription factor governing immune and inflammatory responses. Macrophage NF-κB is instrumental in the progression of various pathological conditions including sepsis, atherosclerosis, cancer, autoimmune disorders, and hypersensitivity. It orchestrates gene expression related to immune responses, inflammation, cell survival, and proliferation. Consequently, its malfunction is a key contributor to the onset and development of these diseases. This review aims to summarize the function of lncRNAs in regulating NF-κB activity in macrophage activation and inflammation, with a particular emphasis on their relevance to human diseases and their potential as therapeutic targets. The insights gained from studies on macrophage lncRNAs, as discussed in this review, could provide valuable knowledge for the development of treatments for various pathological conditions involving macrophages.
Clinically Effective Molecules of Natural Origin for Obesity Prevention or Treatment
Authors: Hidalgo-Lozada Gladys Maribel , Villarruel-López Angelica , Nuño Karla , García-García Abel , Sánchez-Nuño Yaír Adonaí , Ramos-García César Octavio
Published: February 2024

The prevalence and incidence of obesity and the comorbidities linked to it are increasing worldwide. Current therapies for obesity and associated pathologies have proven to cause a broad number of adverse effects, and often, they are overpriced or not affordable for all patients. Among the alternatives currently available, natural bioactive compounds stand out. These are frequently contained in pharmaceutical presentations, nutraceutical products, supplements, or functional foods. The clinical evidence for these molecules is increasingly solid, among which epigallocatechin-3-gallate, ellagic acid, resveratrol, berberine, anthocyanins, probiotics, carotenoids, curcumin, silymarin, hydroxy citric acid, and α-lipoic acid stand out. The molecular mechanisms and signaling pathways of these molecules have been shown to interact with the endocrine, nervous, and gastroenteric systems. They can regulate the expression of multiple genes and proteins involved in starvation–satiety processes, activate the brown adipose tissue, decrease lipogenesis and inflammation, increase lipolysis, and improve insulin sensitivity. This review provides a comprehensive view of nature-based therapeutic options to address the increasing prevalence of obesity. It offers a valuable perspective for future research and subsequent clinical practice, addressing everything from the molecular, genetic, and physiological bases to the clinical study of bioactive compounds.
Special Issue “Computer-Aided Drug Discovery and Treatment”
Authors: Ilan Yaron
Published: February 2024

This Special Issue aims to highlight some of the latest developments in drug discovery [...]
Ciprofloxacin-, Cefazolin-, and Methicilin-Soaked Graphene Paper as an Antibacterial Medium Suppressing Cell Growth
Authors: Nasiłowska Barbara , Bombalska Aneta , Kutwin Marta , Lange Agata , Jaworski Sławomir , Narojczyk Kamila , Olkowicz Klaudia , Bogdanowicz Zdzisław
Published: February 2024

This paper presents the results of research on the impact of graphene paper on selected bacterial strains. Graphene oxide, from which graphene paper is made, has mainly bacteriostatic properties. Therefore, the main goal of this research was to determine the possibility of using graphene paper as a carrier of a medicinal substance. Studies of the degree of bacterial inhibition were performed on Staphylococcus aureus and Pseudomonas aeruginosa strains. Graphene paper was analyzed not only in the state of delivery but also after the incorporation of the antibiotics ciprofloxacin, cefazolin, and methicillin into its structures. In addition, Fourier-Transform Infrared Spectroscopy, contact angle, and microscopic analysis of bacteria on the surface of the examined graphene paper samples were also performed. Studies have shown that graphene paper with built-in ciprofloxacin had a bactericidal effect on the strains of Staphylococcus aureus and Pseudomonas aeruginosa. In contrast, methicillin, as well as cefazolin, deposited on graphene paper acted mainly locally. Studies have shown that graphene paper can be used as a carrier of selected medicinal substances.
Oral Ingestion of Yuzu Seed Oil Suppresses the Development of Atopic Dermatitis-like Skin Lesions in NC/Nga Mice
Authors: Asano Kimito , Watanabe Yoshiya , Miyamoto Mio , Toutani Mochifumi , Mizobuchi Shunji
Published: February 2024

Long-term oral ingestion of unheated yuzu seed oil in humans reduces lipid peroxides in the blood. Moreover, yuzu seed oil contains limonin, which can induce antioxidant and anti-inflammatory effects by activating the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). Previously, Nrf2 has been shown to reduce atopic dermatitis (AD). Therefore, we hypothesized that ingesting unheated yuzu seed oil can regulate AD through Nrf2. An AD model was established using NC/Nga mice through repeated local exposure to mite antigens. Unheated and purified yuzu seed oil (100 µL/mice) or water (control, 100 µL/mice) was administered orally once a day using a gastric cannula for rodents for 28 days. On day 28, mice in the unheated yuzu seed oil group exhibited significantly lower clinical skin severity scores and ear thickness than those in the purified yuzu seed oil and water groups. Serum histamine levels remained unaltered among the three AD-induced groups. Serum Dermatophagoides farina body (Dfb)-specific immunoglobulin E (IgE) levels were significantly lower in the unheated yuzu seed oil group. Oral ingestion of yuzu seed oil in NC/Nga AD model mice significantly suppressed dermatitis deterioration and decreased serum IgE levels. Clinical trials (n = 41) have already confirmed that unheated yuzu oil is safe for long-term intake, further suggesting its potential use in improving AD symptoms.
Independent and Combined Effects of Prenatal Alcohol Exposure and Prenatal Stress on Fetal HPA Axis Development
Authors: Bakhireva Ludmila N. , Solomon Elizabeth , Roberts Melissa H. , Ma Xingya , Rai Rajani , Wiesel Alexandria , Jacobson Sandra W. , Weinberg Joanne , Milligan Erin D.
Published: February 2024

Prenatal alcohol exposure (PAE) and prenatal stress (PS) are highly prevalent conditions known to affect fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis. The objectives of this study were to assess the effect of light PAE, PS, and PAE-PS interaction on fetal HPA axis activity assessed via placental and umbilical cord blood biomarkers. Participants of the ENRICH-2 cohort were recruited during the second trimester and classified into the PAE and unexposed control groups. PS was assessed by the Perceived Stress Scale. Placental tissue was collected promptly after delivery; gene and protein analysis for 11β-HSD1, 11β-HSD2, and pCRH were conducted by qPCR and ELISA, respectively. Umbilical cord blood was analyzed for cortisone and cortisol. Pearson correlation and multivariable linear regression examined the association of PAE and PS with HPA axis biomarkers. Mean alcohol consumption in the PAE group was ~2 drinks/week. Higher PS was observed in the PAE group (p < 0.01). In multivariable modeling, PS was associated with pCRH gene expression (β = 0.006, p < 0.01), while PAE was associated with 11β-HSD2 protein expression (β = 0.56, p < 0.01). A significant alcohol-by-stress interaction was observed with respect to 11β-HSD2 protein expression (p < 0.01). Results indicate that PAE and PS may independently and in combination affect fetal programming of the HPA axis.
Simultaneous Determination of Enantiomeric Purity and Organic Impurities of Dexketoprofen Using Reversed-Phase Liquid Chromatography—Enhancing Enantioselectivity through Hysteretic Behavior and Temperature-Dependent Enantiomer Elution Order Reversal on Polysaccharide Chiral Stationary Phases
Authors: Dobó Máté , Dombi Gergely , Köteles István , Fiser Béla , Kis Csenge , Szabó Zoltán-István , Tóth Gergő
Published: February 2024

A reversed-phase high-performance liquid chromatographic (HPLC) method was developed for the simultaneous determination of the potential impurities of dexketoprofen, including the distomer R-ketoprofen. After screening the separation capability of four polysaccharide columns (Lux Amylose-1, Lux Amylose-2, Lux Cellulose-1 and Lux Cellulose-2) in polar organic and in reversed-phase modes, appropriate enantioseparation was observed only on the Lux Amylose-2 column in an acidified acetonitrile/water mixture. A detailed investigation of the mobile phase composition and temperature for enantio- and chemoselectivity showed many unexpected observations. It was observed that both the resolution and the enantiomer elution order can be fine-tuned by varying the temperature and mobile phase composition. Moreover, hysteresis of the retention times and enantioselectivity was also observed in reversed-phase mode using methanol/water mixtures on amylose-type columns. This could indicate that the three-dimensional structure of the amylose column can change by transitioning from a polar organic to a reversed-phase mode, which affects the enantioseparation process. Temperature-dependent enantiomer elution order and rare enthalpic/entropic controlled enantioseparation in the operative temperature range were also observed in reversed-phase mode. To find the best methodological conditions for the determination of dexketoprofen impurities, a full factorial optimization design was performed. Using the optimized parameters (Lux Amylose-2 column with water/acetonitrile/acetic acid 50/50/0.1 (v/v/v) at a 1 mL/min flow rate at 20 °C), baseline separations were achieved between all compounds within 15 min. Our newly developed HPLC method was validated according to the current guidelines, and its application was tested on commercially available pharmaceutical formulations. According to the authors’ knowledge, this is the first study to report hysteretic behavior on polysaccharide columns in reversed-phase mode.
Transcriptomic and Physiological Analysis of the Effects of Exogenous Phloretin and Pterostilbene on Resistance Responses of Stylosanthes against Anthracnose
Authors: Zhang Shizi , Xu Yunfeng , Wang Fang , Yang Liyun , Luo Lijuan , Jiang Lingyan
Published: February 2024

Anthracnose caused by Colletotrichum gloeosporioides is a destructive disease of Stylosanthes (stylo). Combination treatment of phloretin and pterostilbene (PP) has been previously shown to effectively inhibit the conidial germination and mycelial growth of C. gloeosporioides in vitro. In this study, the effects of PP treatment on the growth of C. gloeosporioides in vivo and the biocontrol mechanisms were investigated. We found that exogenous PP treatment could limit the growth of C. gloeosporioides and alleviate the damage of anthracnose in stylo. Comparative transcriptome analysis revealed that 565 genes were up-regulated and 239 genes were down-regulated upon PP treatment during the infection by C. gloeosporioides. The differentially expressed genes were mainly related to oxidative stress and chloroplast organization. Further physiological analysis revealed that application of PP after C. gloeosporioides inoculation significantly reduced the accumulation of O2•− level and increased the accumulation of antioxidants (glutathione, ascorbic acid and flavonoids) as well as the enzyme activity of total antioxidant capacity, superoxide dismutase, catalase, glutathione reductase, peroxidase and ascorbate peroxidase. PP also reduced the decline of chlorophyll a + b and increased the content of carotenoid in response to C. gloeosporioides infection. These results suggest that PP treatment alleviates anthracnose by improving antioxidant capacity and reducing the damage of chloroplasts, providing insights into the biocontrol mechanisms of PP on the stylo against anthracnose.