bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution to Understanding the Mechanisms Involved in Biofilm Formation, Tolerance and Control
Authors: Simões Lúcia Chaves , Simões Manuel
Published: May 2023

Biofilms constitute a protected mode of growth that allows the colonizing microbial cells to survive in hostile environments, even when an antimicrobial agent is present. The scientific community has come to understand many things about the growth dynamics and behavior of microbial biofilms. It is now accepted that biofilm formation is a multifactorial process that starts with the adhesion of individual cells and (auto-)coaggregates of cells to a surface. Then, attached cells grow, reproduce and secrete insoluble extracellular polymeric substances. As the biofilm matures, biofilm detachment and growth processes come into balance, such that the total amount of biomass on the surface remains approximately constant in time. The detached cells retain the phenotype of the biofilm cells, which facilitates the colonization of neighboring surfaces. The most common practice to eliminate unwanted biofilms is the application of antimicrobial agents. However, conventional antimicrobial agents often show inefficacy in the control of biofilms. Much remains to be understood in the biofilm formation process and in the development of effective strategies for biofilm prevention and control. The articles contained in this Special Issue deal with biofilms of some important bacteria (including pathogens such as Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus) and fungi (Candida tropicalis), providing novel insights into their formation mechanisms and implications, together with novel methods (e.g., use of chemical conjugates and combinations of molecules) that can be used to disrupt the biofilm structure and kill the colonizing cells.
Evaluation of Antibacterial Mechanism of Action, Tyrosinase Inhibition, and Photocatalytic Degradation Potential of Sericin-Based Gold Nanoparticles
Authors: Das Gitishree , Patra Jayanta Kumar
Published: May 2023

In recent times, numerous natural materials have been used for the fabrication of gold nanoparticles (AuNPs). Natural resources used for the synthesis of AuNPs are more environment friendly than chemical resources. Sericin is a silk protein that is discarded during the degumming process for obtaining silk. The current research used sericin silk protein waste materials as the reducing agent for the manufacture of gold nanoparticles (SGNPs) by a one-pot green synthesis method. Further, the antibacterial effect and antibacterial mechanism of action, tyrosinase inhibition, and photocatalytic degradation potential of these SGNPs were evaluated. The SGNPs displayed positive antibacterial activity (8.45–9.58 mm zone of inhibition at 50 μg/disc) against all six tested foodborne pathogenic bacteria, namely, Enterococcus feacium DB01, Staphylococcus aureus ATCC 13565, Listeria monocytogenes ATCC 33090, Escherichia coli O157:H7 ATCC 23514, Aeromonas hydrophila ATCC 7966, and Pseudomonas aeruginosa ATCC 27583. The SGNPs also exhibited promising tyrosinase inhibition potential, with 32.83% inhibition at 100 μg/mL concentration as compared to 52.4% by Kojic acid, taken as a reference standard compound. The SGNPs also displayed significant photocatalytic degradation effects, with 44.87% methylene blue dye degradation after 5 h of incubation. Moreover, the antibacterial mode of action of the SGNPs was also investigated against E. coli and E. feacium, and the results show that due to the small size of the nanomaterials, they could have adhered to the surface of the bacterial pathogens, and could have released more ions and dispersed in the bacterial cell wall surrounding environment, thereby disrupting the cell membrane and ROS production, and subsequently penetrating the bacterial cells, resulting in lysis or damage to the cell by the process of structural damage to the membrane, oxidative stress, and damage to the DNA and bacterial proteins. The overall outcome of the current investigation concludes the positive effects of the obtained SGNPs and their prospective applications as a natural antibacterial agent in cosmetics, environmental, and foodstuff industries, and for the management of environmental contagion.
Recombinant SARS-CoV-2 Spike Protein Stimulates Secretion of Chymase, Tryptase, and IL-1β from Human Mast Cells, Augmented by IL-33
Authors: Tsilioni Irene , Theoharides Theoharis C.
Published: May 2023

SARS-CoV-2 infects cells via its spike (S) protein binding to its surface receptor angiotensin-converting enzyme 2 (ACE2) and results in the production of multiple proinflammatory cytokines, especially in the lungs, leading to what is known as COVID-19. However, the cell source and the mechanism of secretion of such cytokines have not been adequately characterized. In this study, we used human cultured mast cells that are plentiful in the lungs and showed that recombinant SARS-CoV-2 full-length S protein (1–10 ng/mL), but not its receptor-binding domain (RBD), stimulates the secretion of the proinflammatory cytokine interleukin-1β (IL-1β) as well as the proteolytic enzymes chymase and tryptase. The secretion of IL-1β, chymase, and tryptase is augmented by the co-administration of interleukin-33 (IL-33) (30 ng/mL). This effect is mediated via toll-like receptor 4 (TLR4) for IL-1β and via ACE2 for chymase and tryptase. These results provide evidence that the SARS-CoV-2 S protein contributes to inflammation by stimulating mast cells through different receptors and could lead to new targeted treatment approaches.
The Mechanism of Action and Clinical Efficacy of Low-Dose Long-Term Macrolide Therapy in Chronic Rhinosinusitis
Authors: Ryu Gwanghui , Lee Eunkyu , Park Song I , Park Minhae , Hong Sang Duk , Jung Yong Gi , Kim Hyo Yeol
Published: May 2023

Various chronic inflammatory airway diseases can be treated with low-dose, long-term (LDLT) macrolide therapy. LDLT macrolides can be one of the therapeutic options for chronic rhinosinusitis (CRS) due to their immunomodulatory and anti-inflammatory actions. Currently, various immunomodulatory mechanisms of the LDLT macrolide treatment have been reported, as well as their antimicrobial properties. Several mechanisms have already been identified in CRS, including reduced cytokines such as interleukin (IL)-8, IL-6, IL-1β, tumor necrosis factor-α, transforming growth factor-β, inhibition of neutrophil recruitment, decreased mucus secretion, and increased mucociliary transport. Although some evidence of effectiveness for CRS has been published, the efficacy of this therapy has been inconsistent across clinical studies. LDLT macrolides are generally believed to act on the non-type 2 inflammatory endotype of CRS. However, the effectiveness of LDLT macrolide treatment in CRS is still controversial. Here, we reviewed the immunological mechanisms related to CRS in LDLT macrolide therapy and the treatment effects according to the clinical situation of CRS.
Expression of Ceramide-Metabolizing Enzymes in the Heart Adipose Tissue of Cardiovascular Disease Patients
Authors: Gruzdeva Olga , Dyleva Yulia , Belik Ekaterina , Uchasova Evgenia , Ponasenko Anastasia , Ivanov Sergey , Zinets Maxim , Stasev Alexander , Kutikhin Anton , Markova Victoria , Poddubnyak Alena , Gorbatovskaya Evgenia , Fanaskova Elena , Barbarash Olga
Published: May 2023

Here, we examined the expression of ceramide metabolism enzymes in the subcutaneous adipose tissue (SAT), epicardial adipose tissue (EAT) and perivascular adipose tissue (PVAT) of 30 patients with coronary artery disease (CAD) and 30 patients with valvular heart disease (VHD) by means of quantitative polymerase chain reaction and fluorescent Western blotting. The EAT of patients with CAD showed higher expression of the genes responsible for ceramide biosynthesis (SPTLC1, SPTLC2, CERS1, 5, 6, DEGS1, and SMPD1) and utilization (ASAH1, SGMS1). PVAT was characterized by higher mRNA levels of CERS3, CERS4, DEGS1, SMPD1, and ceramide utilization enzyme (SGMS2). In patients with VHD, there was a high CERS4, DEGS1, and SGMS2 expression in the EAT and CERS3 and CERS4 expression in the PVAT. Among patients with CAD, the expression of SPTLC1 in SAT and EAT, SPTLC2 in EAT, CERS2 in all studied AT, CERS4 and CERS5 in EAT, DEGS1 in SAT and EAT, ASAH1 in all studied AT, and SGMS1 in EAT was higher than in those with VHD. Protein levels of ceramide-metabolizing enzymes were consistent with gene expression trends. The obtained results indicate an activation of ceramide synthesis de novo and from sphingomyelin in cardiovascular disease, mainly in EAT, that contributes to the accumulation of ceramides in this location.
IPS (In-Plant System) Delivery of Double-Stranded Vitellogenin and Vitellogenin receptor via Hydroponics for Pest Control in Diaphorina citri Kuwayama (Hemiptera: Psyllidae)
Authors: Li Hailin , Mo Junlan , Wang Xiaoyun , Pan Biqiong , Xu Shu , Li Shuangrong , Zheng Xialin , Lu Wen
Published: May 2023

Diaphorina citri, a vector of citrus huanglongbing (HLB) disease, frequently leads to HLB outbreaks and reduces Rutaceae crop production. Recent studies have investigated the effects of RNA interference (RNAi) targeting the Vitellogenin (Vg4) and Vitellogenin receptor (VgR) genes, which are involved in egg formation in this pest, providing a theoretical foundation for developing new strategies to manage D. citri populations. This study presents RNAi methods for Vg4 and VgR gene expression interference and reveals that dsVgR is more effective than dsVg4 against D. citri. We demonstrated that dsVg4 and dsVgR persisted for 3–6 days in Murraya odorifera shoots when delivered via the in-plant system (IPS) and effectively interfered with Vg4 and VgR gene expression. Following Vg4 and VgR gene expression interference, egg length and width in the interference group were significantly smaller than those in the negative control group during the 10–30-day development stages. Additionally, the proportion of mature ovarian eggs in the interference group was significantly lower than that in the negative control group at the 10, 15, 20, 25, and 30-day developmental stages. DsVgR notably suppresses oviposition in D. citri, with fecundity decreasing by 60–70%. These results provide a theoretical basis for controlling D. citri using RNAi to mitigate the spread of HLB disease.
Effects of Tail Pinch on BDNF and trkB Expression in the Hippocampus of Roman Low- (RLA) and High-Avoidance (RHA) Rats
Authors: Serra Maria Pina , Sanna Francesco , Boi Marianna , Trucas Marcello , Fernández-Teruel Alberto , Corda Maria Giuseppa , Giorgi Osvaldo , Quartu Marina
Published: May 2023

In this article, we describe the effects of tail pinch (TP), a mild acute stressor, on the levels of brain-derived neurotrophic factor (BDNF) and its tyrosine kinase receptor B (trkB) proteins in the hippocampus (HC) of the outbred Roman High- (RHA) and Low-Avoidance (RLA) rats, one of the most validated genetic models for the study of fear/anxiety- and stress-related behaviors. Using Western blot (WB) and immunohistochemistry assays, we show for the first time that TP induces distinct changes in the levels of BDNF and trkB proteins in the dorsal (dHC) and ventral (vHC) HC of RHA and RLA rats. The WB assays showed that TP increases BDNF and trkB levels in the dHC of both lines but induces opposite changes in the vHC, decreasing BDNF levels in RHA rats and trkB levels in RLA rats. These results suggest that TP may enhance plastic events in the dHC and hinder them in the vHC. Immunohistochemical assays, carried out in parallel to assess the location of changes revealed by the WB, showed that, in the dHC, TP increases BDNF-like immunoreactivity (LI) in the CA2 sector of the Ammon’s horn of both Roman lines and in the CA3 sector of the Ammon’s horn of RLA rats while, in the dentate gyrus (DG), TP increases trkB-LI in RHA rats. In contrast, in the vHC, TP elicits only a few changes, represented by decreases of BDNF- and trkB-LI in the CA1 sector of the Ammon’s horn of RHA rats. These results support the view that the genotypic/phenotypic features of the experimental subjects influence the effects of an acute stressor, even as mild as TP, on the basal BDNF/trkB signaling, leading to different changes in the dorsal and ventral subdivisions of the HC.
Does EGFR Signaling Mediate Orexin System Activity in Sleep Initiation?
Authors: Kniazkina Marina , Dyachuk Vyacheslav
Published: May 2023

Sleep–wake cycle disorders are an important symptom of many neurological diseases, including Parkinson’s disease, Alzheimer’s disease, and multiple sclerosis. Circadian rhythms and sleep–wake cycles play a key role in maintaining the health of organisms. To date, these processes are still poorly understood and, therefore, need more detailed elucidation. The sleep process has been extensively studied in vertebrates, such as mammals and, to a lesser extent, in invertebrates. A complex, multi-step interaction of homeostatic processes and neurotransmitters provides the sleep–wake cycle. Many other regulatory molecules are also involved in the cycle regulation, but their functions remain largely unclear. One of these signaling systems is epidermal growth factor receptor (EGFR), which regulates the activity of neurons in the modulation of the sleep–wake cycle in vertebrates. We have evaluated the possible role of the EGFR signaling pathway in the molecular regulation of sleep. Understanding the molecular mechanisms that underlie sleep–wake regulation will provide critical insight into the fundamental regulatory functions of the brain. New findings of sleep-regulatory pathways may provide new drug targets and approaches for the treatment of sleep-related diseases.
Cloning and Functional Characterization of Cold-Inducible MYB-like 17 Transcription Factor in Rapeseed (Brassica napus L.)
Authors: Luo Dan , Raza Ali , Cheng Yong , Zou Xiling , Lv Yan
Published: May 2023

Rapeseed (Brassica napus L.) is an important crop for edible oil, vegetables, and biofuel. Rapeseed growth and development require a minimum temperature of ~1–3 °C. Notably, frost damage occurs during overwintering, posing a serious threat to the productivity and yield of rapeseed. MYB proteins are important transcription factors (TFs) in plants, and have been proven to be involved in the regulation of stress responses. However, the roles of the MYB TFs in rapeseed under cold stress conditions are yet to be fully elucidated. To better understand the molecular mechanisms of one MYB-like 17 gene, BnaMYBL17, in response to low temperature, the present study found that the transcript level of BnaMYBL17 is induced by cold stress. To characterize the gene’s function, the 591 bp coding sequence (CDS) from rapeseed was isolated and stably transformed into rapeseed. The further functional analysis revealed significant sensitivity in BnaMYBL17 overexpression lines (BnaMYBL17-OE) after freezing stress, suggesting its involvement in freezing response. A total of 14,298 differentially expressed genes relative to freezing response were found based on transcriptomic analysis of BnaMYBL17-OE. Overall, 1321 candidate target genes were identified based on differential expression, including Phospholipases C1 (PLC1), FCS-like zinc finger 8 (FLZ8), and Kinase on the inside (KOIN). The qPCR results confirmed that the expression levels of certain genes showed fold changes ranging from two to six when compared between BnaMYBL17-OE and WT lines after exposure to freezing stress. Furthermore, verification indicated that BnaMYBL17 affects the promoter of BnaPLC1, BnaFLZ8, and BnaKOIN genes. In summary, the results suggest that BnaMYBL17 acts as a transcriptional repressor in regulating certain genes related to growth and development during freezing stress. These findings provide valuable genetic and theoretical targets for molecular breeding to enhance freezing tolerance in rapeseed.
The Small RNA-Binding Protein CcaF1 Promotes Formation of Photosynthetic Complexes in Rhodobacter sphaeroides
Authors: Grützner Julian , Börner Janek , Jäger Andreas , Klug Gabriele
Published: May 2023

In natural habitats, bacteria frequently need to adapt to changing environmental conditions. Regulation of transcription plays an important role in this process. However, riboregulation also contributes substantially to adaptation. Riboregulation often acts at the level of mRNA stability, which is determined by sRNAs, RNases, and RNA-binding proteins. We previously identified the small RNA-binding protein CcaF1, which is involved in sRNA maturation and RNA turnover in Rhodobacter sphaeroides. Rhodobacter is a facultative phototroph that can perform aerobic and anaerobic respiration, fermentation, and anoxygenic photosynthesis. Oxygen concentration and light conditions decide the pathway for ATP production. Here, we show that CcaF1 promotes the formation of photosynthetic complexes by increasing levels of mRNAs for pigment synthesis and for some pigment-binding proteins. Levels of mRNAs for transcriptional regulators of photosynthesis genes are not affected by CcaF1. RIP-Seq analysis compares the binding of CcaF1 to RNAs during microaerobic and photosynthetic growth. The stability of the pufBA mRNA for proteins of the light-harvesting I complex is increased by CcaF1 during phototrophic growth but decreased during microaerobic growth. This research underlines the importance of RNA-binding proteins in adaptation to different environments and demonstrates that an RNA-binding protein can differentially affect its binding partners in dependence upon growth conditions.
Fangs in the Ghats: Preclinical Insights into the Medical Importance of Pit Vipers from the Western Ghats
Authors: Khochare Suyog , Senji Laxme R. R. , Jaikumar Priyanka , Kaur Navneet , Attarde Saurabh , Martin Gerard , Sunagar Kartik
Published: May 2023

The socioeconomic impact of snakebites in India is largely attributed to a subset of snake species commonly known as the ‘big four’. However, envenoming by a range of other clinically important yet neglected snakes, a.k.a. the ‘neglected many’, also adds to this burden. The current approach of treating bites from these snakes with the ‘big four’ polyvalent antivenom is ineffective. While the medical significance of various species of cobras, saw-scaled vipers, and kraits is well-established, the clinical impact of pit vipers from regions such as the Western Ghats, northeastern India, and the Andaman and Nicobar Islands remains poorly understood. Amongst the many species of snakes found in the Western Ghats, the hump-nosed (Hypnale hypnale), Malabar (Craspedocephalus malabaricus), and bamboo (Craspedocephalus gramineus) pit vipers can potentially inflict severe envenoming. To evaluate the severity of toxicity inflicted by these snakes, we characterised their venom composition, biochemical and pharmacological activities, and toxicity- and morbidity-inducing potentials, including their ability to damage kidneys. Our findings highlight the therapeutic inadequacies of the Indian and Sri Lankan polyvalent antivenoms in neutralising the local and systemic toxicity resulting from pit viper envenomings.
Transcriptome Revealed the Macrophages Inflammatory Response Mechanism and NOD-like Receptor Characterization in Siberian Sturgeon (Acipenser baerii)
Authors: Chen Defang , Chen Yinqiu , Lu Lu , Zhu Hao , Zhang Xin , Huang Xiaoli , Li Zhiqiong , Ouyang Ping , Zhang Xiaoli , Li Liangyu , Geng Yi
Published: May 2023

Nucleotide-binding and oligomerization domain-like receptors (NOD-like receptors, NLRs) can regulate the inflammatory response to eliminate pathogens and maintain the host’s homeostasis. In this study, the head kidney macrophages of Siberian sturgeon were treated with lipopolysaccharide (LPS) to induce inflammation by evaluating the expression of cytokines. The high-throughput sequencing for macrophages after 12 h treatment showed that 1224 differentially expressed genes (DEGs), including 779 upregulated and 445 downregulated, were identified. DEGs mainly focus on pattern recognition receptors (PRRs) and the adaptor proteins, cytokines, and cell adhesion molecules. In the NOD-like receptor signaling pathway, multiple NOD-like receptor family CARD domains containing 3-like (NLRC3-like) were significantly downregulated, and pro-inflammatory cytokines were upregulated. Based on the transcriptome database, 19 NLRs with NACHT structural domains were mined and named in Siberian sturgeon, including 5 NLR-A, 12 NLR-C, and 2 other NLRs. The NLR-C subfamily had the characteristics of expansion of the teleost NLRC3 family and lacked the B30.2 domain compared with other fish. This study revealed the inflammatory response mechanism and NLRs family characterization in Siberian sturgeon by transcriptome and provided basic data for further research on inflammation in teleost.
NK Cells in Cancer: Mechanisms of Dysfunction and Therapeutic Potential
Authors: Portale Federica , Di Mitri Diletta
Published: May 2023

Natural killer cells (NK) are innate lymphocytes endowed with the ability to recognize and kill cancer cells. Consequently, adoptive transfer of autologous or allogeneic NK cells represents a novel opportunity in cancer treatment that is currently under clinical investigation. However, cancer renders NK cells dysfunctional, thus restraining the efficacy of cell therapies. Importantly, extensive effort has been employed to investigate the mechanisms that restrain NK cell anti-tumor function, and the results have offered forthcoming solutions to improve the efficiency of NK cell-based therapies. The present review will introduce the origin and features of NK cells, summarize the mechanisms of action and causes of dysfunction of NK cells in cancer, and frame NK cells in the tumoral microenvironment and in the context of immunotherapies. Finally, we will discuss therapeutic potential and current limitations of NK cell adoptive transfer in tumors.
Chondrocyte Thrombomodulin Protects against Osteoarthritis
Authors: Kang Lin , Yang Ai-Lun , Lai Chao-Han , Chen Tsan-Ju , Lin Sung-Yen , Wang Yan-Hsiung , Wang Chau-Zen , Conway Edward M. , Wu Hua-Lin , Ho Mei-Ling , Chang Je-Ken , Chen Chung-Hwan , Cheng Tsung-Lin
Published: May 2023

Osteoarthritis (OA) is a prevalent form of arthritis that affects over 32.5 million adults worldwide, causing significant cartilage damage and disability. Unfortunately, there are currently no effective treatments for OA, highlighting the need for novel therapeutic approaches. Thrombomodulin (TM), a glycoprotein expressed by chondrocytes and other cell types, has an unknown role in OA. Here, we investigated the function of TM in chondrocytes and OA using various methods, including recombinant TM (rTM), transgenic mice lacking the TM lectin-like domain (TMLeD/LeD), and a microRNA (miRNA) antagomir that increased TM expression. Results showed that chondrocyte-expressed TM and soluble TM [sTM, like recombinant TM domain 1 to 3 (rTMD123)] enhanced cell growth and migration, blocked interleukin-1β (IL-1β)-mediated signaling and protected against knee function and bone integrity loss in an anterior cruciate ligament transection (ACLT)-induced mouse model of OA. Conversely, TMLeD/LeD mice exhibited accelerated knee function loss, while treatment with rTMD123 protected against cartilage loss even one-week post-surgery. The administration of an miRNA antagomir (miR-up-TM) also increased TM expression and protected against cartilage damage in the OA model. These findings suggested that chondrocyte TM plays a crucial role in counteracting OA, and miR-up-TM may represent a promising therapeutic approach to protect against cartilage-related disorders.
Production of Mare Chorionic Girdle Organoids That Secrete Equine Chorionic Gonadotropin
Authors: Thompson Riley E. , Meyers Mindy A. , Palmer Jennifer , Veeramachaneni D. N. Rao , Magee Christianne , de Mestre Amanda M. , Antczak Douglas F. , Hollinshead Fiona K.
Published: May 2023

The equine chorionic girdle is comprised of specialized invasive trophoblast cells that begin formation approximately 25 days after ovulation (day 0) and invade the endometrium to become endometrial cups. These specialized trophoblast cells transition from uninucleate to differentiated binucleate trophoblast cells that secrete the glycoprotein hormone equine chorionic gonadotropin (eCG; formerly known as pregnant mare serum gonadotropin or PMSG). This eCG has LH-like activity in the horse but variable LH- and FSH-like activity in other species and has been utilized for these properties both in vivo and in vitro. To produce eCG commercially, large volumes of whole blood must be collected from pregnant mares, which negatively impacts equine welfare due to repeated blood collections and the birth of an unwanted foal. Attempts to produce eCG in vitro using long-term culture of chorionic girdle explants have not been successful beyond 180 days, with peak eCG production at 30 days of culture. Organoids are three-dimensional cell clusters that self-organize and can remain genetically and phenotypically stable throughout long-term culture (i.e., months). Human trophoblast organoids have been reported to successfully produce human chorionic gonadotropin (hCG) and proliferate long-term (>1 year). The objective of this study was to evaluate whether organoids derived from equine chorionic girdle maintain physiological functionality. Here we show generation of chorionic girdle organoids for the first time and demonstrate in vitro production of eCG for up to 6 weeks in culture. Therefore, equine chorionic girdle organoids provide a physiologically representative 3D in vitro model for chorionic girdle development of early equine pregnancy.
Inflammatory Mesenchymal Stem Cells Express Abundant Membrane-Bound and Soluble Forms of C-Type Lectin-like CD248
Authors: Payet Melissa , Ah-Pine Franck , Guillot Xavier , Gasque Philippe
Published: May 2023

CD248 (endosialin) belongs to a glycoprotein family that also includes thrombomodulin (CD141), CLEC14A, and CD93 (AA4) stem cell markers. We analyzed the regulated expression of CD248 in vitro using skin (HFFF) and synovial (FLS) mesenchymal stem cell lines, and in fluid and tissue samples of rheumatoid arthritis (RA) and osteoarthritis (OA) patients. Cells were incubated with either rhVEGF165, bFGF, TGF-β1, IL1-β, TNF-α, TGFβ1, IFN-γ, or PMA (Phorbol ester). There was no statistically significant change in membrane expression. A soluble (s) form of cleaved CD248 (sCD248) was detected after cell treatment with IL1-β and PMA. Matrix metalloprotease (MMP) MMP-1 and MMP-3 mRNAs were significantly up-regulated by IL1-β and PMA. A broad MMP inhibitor blocked the release of soluble CD248. In RA synovial tissue, we identified CD90+ perivascular MSCs double-stained for CD248 and VEGF. High sCD248 levels were detected in synovial fluid from RA. In culture, subpopulations of CD90+ CD14− RA MSCs were either identified as CD248+ or CD141+ cells but CD93−. CD248 is abundantly expressed by inflammatory MSCs and shed in an MMP-dependent manner in response to cytokines and pro-angiogenic growth factors. Both membrane-bound and soluble CD248 (acting as a decoy receptor) may contribute to RA pathogenesis.
Functional Characterisation of the Rare SCN5A p.E1225K Variant, Segregating in a Brugada Syndrome Familial Case, in Human Cardiomyocytes from Pluripotent Stem Cells
Authors: Salvarani Nicolò , Peretto Giovanni , Silvia Crasto , Villatore Andrea , Thairi Cecilia , Santoni Anna , Galli Camilla , Carrera Paola , Sala Simone , Benedetti Sara , Di Pasquale Elisa , Di Resta Chiara
Published: May 2023

Brugada syndrome (BrS) is an inherited autosomal dominant cardiac channelopathy. Pathogenic rare mutations in the SCN5A gene, encoding the alpha-subunit of the voltage-dependent cardiac Na+ channel protein (Nav1.5), are identified in 20% of BrS patients, affecting the correct function of the channel. To date, even though hundreds of SCN5A variants have been associated with BrS, the underlying pathogenic mechanisms are still unclear in most cases. Therefore, the functional characterization of the SCN5A BrS rare variants still represents a major hurdle and is fundamental to confirming their pathogenic effect. Human cardiomyocytes (CMs) differentiated from pluripotent stem cells (PSCs) have been extensively demonstrated to be reliable platforms for investigating cardiac diseases, being able to recapitulate specific traits of disease, including arrhythmic events and conduction abnormalities. Based on this, in this study, we performed a functional analysis of the BrS familial rare variant NM_198056.2:c.3673G>A (NP_932173.1:p.Glu1225Lys), which has been never functionally characterized before in a cardiac-relevant context, as the human cardiomyocyte. Using a specific lentiviral vector encoding a GFP-tagged SCN5A gene carrying the specific c.3673G>A variant and CMs differentiated from control PSCs (PSC-CMs), we demonstrated an impairment of the mutated Nav1.5, thus suggesting the pathogenicity of the rare BrS detected variant. More broadly, our work supports the application of PSC-CMs for the assessment of the pathogenicity of gene variants, the identification of which is increasing exponentially due to the advances in next-generation sequencing methods and their massive use in genetic testing.
Capacitive Electrode-Based Electric Field Treatments on Redox-Toxic Iron Deposits in Transgenic AD Mouse Models: The Electroceutical Targeting of Alzheimer’s Disease Feasibility Study
Authors: Choi Younshick , Lee Won-Seok , Lee Jaemeun , Park Sun-Hyun , Kim Sunwoung , Kim Ki-Hong , Park Sua , Kim Eun Ho , Kim Jong-Ki
Published: May 2023

Iron accumulation in the brain accelerates Alzheimer’s disease progression. To cure iron toxicity, we assessed the therapeutic effects of noncontact transcranial electric field stimulation to the brain on toxic iron deposits in either the Aβ fibril structure or the Aβ plaque in a mouse model of Alzheimer’s disease (AD) as a pilot study. A capacitive electrode-based alternating electric field (AEF) was applied to a suspension of magnetite (Fe3O4) to measure field-sensitized reactive oxygen species (ROS) generation. The increase in ROS generation compared to the untreated control was both exposure-time and AEF-frequency dependent. The frequency-specific exposure of AEF to 0.7–1.4 V/cm on a magnetite-bound Aβ-fibril or a transgenic Alzheimer’s disease (AD) mouse model revealed the degradation of the Aβ fibril or the removal of the Aβ-plaque burden and ferrous magnetite compared to the untreated control. The results of the behavioral tests show an improvement in impaired cognitive function following AEF treatment on the AD mouse model. Tissue clearing and 3D-imaging analysis revealed no induced damage to the neuronal structures of normal brain tissue following AEF treatment. In conclusion, our results suggest that the effective degradation of magnetite-bound amyloid fibrils or plaques in the AD brain by the electro-Fenton effect from electric field-sensitized magnetite offers a potential electroceutical treatment option for AD.
Current Advancements and Future Perspectives of Immunotherapy in Breast Cancer Treatment
Authors: Vasileiou Maria , Papageorgiou Savvas , Nguyen Nam P.
Published: May 2023

Breast cancer is the most commonly diagnosed cancer in women and is a leading cause of cancer death in women worldwide. Despite the available treatment options, such as surgery, chemotherapy, radiotherapy, endocrine therapy and molecular targeted therapy, breast cancer treatment remains a challenge. The advent of immunotherapy has revolutionized the treatment of breast cancer as it utilizes the host’s immune system to directly target tumor cells. In this literature review, we aim to summarize the recent advancements made in using immunotherapy for treating breast cancer patients. We discuss the different types of existing immunotherapies for breast cancer, including targeted therapy using monoclonal antibodies against breast cancer specific antigens and the use of immune checkpoint inhibitors to elicit an immune response against cancer cells. Finally, we consider the development of breast cancer vaccines that train the immune system to specifically recognize cancer cells and the future perspectives of immunotherapy for breast cancer.
Gene Co-Expression Network Analysis Reveals Key Regulatory Genes in Metisa plana Hormone Pathways
Authors: Vengatharajuloo Vinothienii , Goh Hoe-Han , Hassan Maizom , Govender Nisha , Sulaiman Suhaila , Afiqah-Aleng Nor , Harun Sarahani , Mohamed-Hussein Zeti-Azura
Published: May 2023

Metisa plana Walker (Lepidoptera: Psychidae) is a major oil palm pest species distributed across Southeast Asia. M. plana outbreaks are regarded as serious ongoing threats to the oil palm industry due to their ability to significantly reduce fruit yield and subsequent productivity. Currently, conventional pesticide overuses may harm non-target organisms and severely pollute the environment. This study aims to identify key regulatory genes involved in hormone pathways during the third instar larvae stage of M. plana gene co-expression network analysis. A weighted gene co-expression network analysis (WGCNA) was conducted on the M. plana transcriptomes to construct a gene co-expression network. The transcriptome datasets were obtained from different development stages of M. plana, i.e., egg, third instar larvae, pupa, and adult. The network was clustered using the DPClusO algorithm and validated using Fisher’s exact test and receiver operating characteristic (ROC) analysis. The clustering analysis was performed on the network and 20 potential regulatory genes (such as MTA1-like, Nub, Grn, and Usp) were identified from ten top-most significant clusters. Pathway enrichment analysis was performed to identify hormone signalling pathways and these pathways were identified, i.e., hormone-mediated signalling, steroid hormone-mediated signalling, and intracellular steroid hormone receptor signalling as well as six regulatory genes Hnf4, Hr4, MED14, Usp, Tai, and Trr. These key regulatory genes have a potential as important targets in future upstream applications and validation studies in the development of biorational pesticides against M. plana and the RNA interference (RNAi) gene silencing method.
Geant4 Simulation of Muon Absorption in Concrete Layers
Authors: Joffe David , Perez Christian
Published: May 2023

Muography requires a detailed understanding of the absorption of muons in the material situated between the muon source and the detector. A large-statistics (>3 billion event) Geant4 simulation was run to simulate the absorption of muons in different thicknesses of concrete layers and to determine the effect of the material on the energies of muons that were not absorbed. The Geant4 simulation included a simple detector placed directly behind the absorbing material. A Geant4 simulation was also run for the same detector for alpha sources with no absorbing material and the results of this simulation were compared to the signals from the physical detector built in the laboratory and measured using standard alpha sources. The large-statistics simulations using muons of different energies were compared to the predictions of muon absorption from existing literature. The results of the simulations were in good agreement with both the measured signals from the laboratory as well as the predictions from the literature and the general method is found to be well-suited for studies used for muography involving material layers of uniform thickness.
Dry Eye Disease following LASIK, PRK, and LASEK: An Observational Cross-Sectional Study
Authors: Yahalomi Tal , Achiron Asaf , Arnon Roee , Stanescu Nir , Pikkel Joseph
Published: May 2023

Dry eye disease is the most frequent non-refractive postoperative complication following refractive surgery. This prospective study investigated the development of dry eye disease after three common refractive laser surgeries: laser in situ keratomileusis (LASIK), photorefractive keratectomy (PRK), and laser-assisted sub-epithelial keratectomy (LASEK). Patients who underwent uneventful refractive surgery in a single private medical center between May 2017 and September 2020 were included. Ocular surface disease was graded according to the Dry Eye Workshop severity (DEWS) classification. Patients were examined 6 months following refractive surgery. The analysis included 251 eyes of 137 patients: 64 eyes (36 patients) after LASEK, 90 eyes (48 patients) after PRK, and 97 eyes (53 patients) after LASIK. At 6 months post-surgery, the DEWS score was higher for the LASIK than the PRK and LASEK groups (p = 0.01). For the total cohort, severe DEWS score (grades 3 and 4) at 6 months post-surgery was correlated with female gender (p = 0.01) and to the amount of refractive correction (p < 0.001), but not to age (p = 0.87). In conclusion, LASIK surgery and female gender were associated with dry eye. Patients, particularly those with high myopia, should be counseled about the risk of developing dry eye after refractive surgeries.
Using Type I Collagen Gel to Prevent Postoperative Intrauterine Adhesion: A Multicenter Retrospective Study
Authors: Lee Kwang Beom , Chon Seung Joo , Kim Sunghoon , Kim Dae Yeon , Park Chan Woo , Shin So Jin , Kim Seok Mo , Lee Ki Hwan , Ji Yong Il
Published: May 2023

We evaluated the clinical outcomes of using type 1 collagen gel after therapeutic resectoscopy; overall, 150 women aged > 20 who planned to undergo therapeutic resectoscopy were enrolled. The patients were randomly assigned to either of the anti-adhesive treatment groups: the type 1 collagen gel (Collabarrier®) (study group; N = 75) or the sodium hyaluronate and sodium carboxymethylcellulose gel group (control group; N = 75) after resectoscopy. One month after applying anti-adhesive materials, postoperative intrauterine adhesions were evaluated using second-look hysteroscopy; the incidence rate of postoperative intrauterine adhesions examined through second-look hysteroscopy showed no significant differences between the groups. There were no statistical differences between the frequency and mean scores of the type and intensity of adhesions in both groups. Finally, no significant differences in adverse events, serious adverse events, adverse device effects, and serious adverse device effects were noted between the two groups; type 1 collagen gel can be effectively and safely used in intrauterine surgery to minimize postoperative adhesions, thereby eventually decreasing the prevalence of infertility, secondary amenorrhea, and recurrent pregnancy loss in reproductive women.
Development of a Statistical Shape Model and Assessment of Anatomical Shape Variations in the Hemipelvis
Authors: van Veldhuizen Willemina A. , van der Wel Hylke , Kuipers Hennie Y. , Kraeima Joep , ten Duis Kaj , Wolterink Jelmer M. , de Vries Jean-Paul P. M. , Schuurmann Richte C. L. , IJpma Frank F. A.
Published: May 2023

Knowledge about anatomical shape variations in the pelvis is mandatory for selection, fitting, positioning, and fixation in pelvic surgery. The current knowledge on pelvic shape variation mostly relies on point-to-point measurements on 2D X-ray images and computed tomography (CT) slices. Three-dimensional region-specific assessments of pelvic morphology are scarce. Our aim was to develop a statistical shape model of the hemipelvis to assess anatomical shape variations in the hemipelvis. CT scans of 200 patients (100 male and 100 female) were used to obtain segmentations. An iterative closest point algorithm was performed to register these 3D segmentations, so a principal component analysis (PCA) could be performed, and a statistical shape model (SSM) of the hemipelvis was developed. The first 15 principal components (PCs) described 90% of the total shape variation, and the reconstruction ability of this SSM resulted in a root mean square error of 1.58 (95% CI: 1.53–1.63) mm. In summary, an SSM of the hemipelvis was developed, which describes the shape variations in a Caucasian population and is able to reconstruct an aberrant hemipelvis. Principal component analyses demonstrated that, in a general population, anatomical shape variations were mostly related to differences in the size of the pelvis (e.g., PC1 describes 68% of the total shape variation, which is attributed to size). Differences between the male and female pelvis were most pronounced in the iliac wing and pubic rami regions. These regions are often subject to injuries. Future clinical applications of our newly developed SSM may be relevant for SSM-based semi-automatic virtual reconstruction of a fractured hemipelvis as part of preoperative planning. Lastly, for companies, using our SSM might be interesting in order to assess which sizes of pelvic implants should be produced to provide proper-fitting implants for most of the population.
The Effect of Metformin on Plasma Prolactin Levels in Young Women with Autoimmune Thyroiditis
Authors: Krysiak Robert , Kowalcze Karolina , Madej Andrzej , Okopień Bogusław
Published: May 2023

Metformin decreases elevated prolactin levels, which are frequently found in patients with thyroid disorders. The aim of this study was to investigate whether thyroid autoimmunity modulates the impact of metformin on lactotrope secretory function. This study compared two matched groups of young women with prediabetes and mild-to-moderate prolactin excess: 28 subjects with coexisting euthyroid autoimmune thyroiditis (group 1) and 28 individuals without thyroid disorders (group 2), treated for six months with metformin (3 g daily). Thyroid antibody titers, glucose homeostasis markers, prolactin, thyrotropin, free thyroid hormones, FSH, LH, ACTH, IGF-1 and hsCRP were assessed at the beginning and at the end of the study. At entry, the study groups differed in antibody titers and hsCRP levels. Although the improvement in glucose homeostasis and the decrease in hsCRP levels were observed in both study groups, they were more pronounced in group 2. Only in group 2 did metformin reduce circulating prolactin levels (both total and monomeric). Prolactin-lowering properties of metformin positively correlated with baseline prolactin levels, baseline antibody titers (in group 1) and with the degree of reduction in hsCRP levels. The obtained results suggest that autoimmune thyroiditis may attenuate the impact of metformin on lactotrope secretory function.
Treatment of Peritoneal Surface Malignancies by Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Spain: Results of the National Registry of the Spanish Group of Peritoneal Oncologic Surgery (REGECOP)
Authors: Manzanedo Israel , Pereira Fernando , Cascales-Campos Pedro , Muñoz-Casares Cristobal , Asensio Enrique , Torres-Melero Juan , Prada-Villaverde Arancha , Caravaca-García Ibán , Gutiérrez-Calvo Alberto , Vaqué Javier , Ortega Gloria , Titos-García Alberto , González-Sánchez Laura , Pérez-Viejo Estíbalitz , Serrano Ángel , Martínez-Torres Beatriz ,   REGECOP Group
Published: May 2023

Introduction: Treatment of Peritoneal Surface Malignancies (PSM) with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has achieved results never seen before in these patients, which classically have a poor prognosis. The possibility of conducting clinical trials in these diseases is complicated, since some of them are rare, so the analysis of large databases provides very valuable scientific information. The aim of this study is to analyze the global results of the National Registry of the Spanish Group of Peritoneal Oncologic Surgery (REGECOP), whose objective is to register all patients scheduled for HIPEC nationwide. Methods: This is a retrospective analysis of the data recorded in the REGECOP from 36 Spanish hospitals from 2001 to 2021. There were 4159 surgical interventions in 3980 patients. Results: 66% are women and 34% are men with a median age of 59 years (range 17–86). 41.5% of the patients were treated for Peritoneal Metastases (PM) of colorectal cancer (CRC); 32.4% were women with ovarian cancer (OC) with PM; 12.8% were treated for pseudomyxoma peritonei (PMP); 6.2% had PM from gastric cancer (GC); 4.9% had PM of non-conventional origin; and, finally, 2.1% of cases were patients diagnosed with peritoneal mesothelioma. The median Peritoneal Cancer Index (PCI) was 9 (0–39), and complete cytoreduction was achieved in 81.7% of the procedures. Severe morbidity (Dindo–Clavien grade III–IV) was observed in 17.7% of surgeries, with 2.1% mortality. Median hospital stay was 11 days (0–259). Median overall survival (OS) was 41 months for CRC patients, 55 months for women with OC, was not reached in PMP patients, was 14 months for GC patients, and 66 months in mesothelioma patients. Conclusions: large databases provide extremely useful data. CRS with HIPEC in referral centers is a safe treatment with encouraging oncologic results in PSM.
Full-Right Full-Left Split Liver Transplantation for Two Adult Recipients: A Single-Center Experience in China
Authors: Ding Limin , Yu Xizhi , Zhang Rui , Qian Junjie , Zhang Wu , Wu Qinchuan , Zhou Lin , Yang Zhe , Zheng Shusen
Published: May 2023

Background: The most effective treatment for end-stage liver diseases is liver transplantation, which is impeded by the shortage of donor livers. Split liver transplantation (SLT) is important for addressing the donor liver shortage. However, full-right full-left SLT for two adult recipients is globally rarely conducted. This study aimed to investigate the clinical outcomes of this technique. Methods: We retrospectively analyzed the clinical data of 22 recipients who underwent full-right full-left SLT at Shulan (Hangzhou) Hospital between January, 2021 and September, 2022. The graft-to-recipient weight ratio (GRWR), cold ischemia time, operation time, length of the anhepatic phase, intraoperative blood loss, and red blood cell transfusion amount were all analyzed. The differences in liver function recovery after transplantation were compared between the left and right hemiliver groups. The postoperative complications and prognosis of the recipients were also analyzed. Results: The livers of 11 donors were transplanted into 22 adult recipients. The GRWR ranged from 1.16–1.65%, the cold ischemia time was 282.86 ± 134.87 min, the operation time was 371.32 ± 75.36 min, the anhepatic phase lasted 60.73 ± 19.00 min, the intraoperative blood loss was 759.09 ± 316.84 mL, and the red blood cell transfusion amount was 695.45 ± 393.67 mL. No significant difference in the levels of liver function markers, total bilirubin, aspartate aminotransferase, or alanine aminotransferase between left and right hemiliver groups at 1, 3, 5, 7, 14, and 28 d postoperatively was observed (both p > 0.05). One recipient developed bile leakage 10 d after transplantation, which improved with endoscopic retrograde cholangiopancreatography-guided nasobiliary drainage and stent placement. Another developed portal vein thrombosis 12 d after transplantation and underwent portal vein thrombolytic therapy and stenting to restore portal vein blood flow. A color Doppler ultrasound performed 2 d after transplantation revealed hepatic artery thrombosis in one patient, and thrombolytic therapy was administered to restore hepatic artery blood flow. The liver function of other patients recovered quickly after transplantation. Conclusions: Full-right full-left SLT for two adult patients is an efficient way to increase the donor pool. It is safe and feasible with careful donor and recipient selection. Transplant hospitals with highly experienced surgeons in SLT are recommended to promote using full-right full-left SLT for two adult recipients.