bluuebunny/crossref_metadata_2025 huggingface dataset:
Beads for Cell Immobilization: Comparison of Alternative Additive Manufacturing Techniques
Authors: Gatto Maria , Mengucci Paolo , Munteanu Daniel , Nasini Roberto , Tognoli Emanuele , Denti Lucia , Gatto Andrea
Published: January 2023

The attachment or entrapment of microbial cells and enzymes are promising solutions for various industrial applications. When the traps are beads, they are dispersed in a fluidized bed in a vessel where a pump guarantees fresh liquid inflow and waste outflow without washing out the cells. Scientific papers report numerous types of cell entrapment, but most of their applications remain at the laboratory level. In the present research, rigid polymer beads were manufactured by two different additive manufacturing (AM) techniques in order to verify the economy, reusability, and stability of the traps, with a view toward a straightforward industrial application. The proposed solutions allowed for overcoming some of the drawbacks of traditional manufacturing solutions, such as the limited mechanical stability of gel traps, and they guaranteed the possibility of producing parts of constant quality with purposely designed exchange surfaces, which are unfeasible when using conventional processes. AM proved to be a viable manufacturing solution for beads with complex shapes of two different size ranges. A deep insight into the production and characteristics of beads manufactured by AM is provided. The paper provides biotechnologists with a manufacturing perspective, and the results can be directly applied to transit from the laboratory to the industrial scale.
Planar Elliptical Inductor Design for Wireless Implantable Medical Devices
Authors: Farooq Muhammad , Amin Bilal , Elahi Adnan , Wijns William , Shahzad Atif
Published: January 2023

Wireless implantable medical devices (WIMDs) have seen unprecedented progress in the past three decades. WIMDs help clinicians in better-understanding diseases and enhance medical treatment by allowing for remote data collection and delivering tailored patient care. The wireless connectivity range between the external reader and the implanted device is considered one of the key design parameters in WIMD technology. One of the common modes of communication in battery-free WIMDs is inductive coupling, where the power and data between the reader and the implanted device are transmitted via magnetically coupled inductors. The design and shape of these inductors depend on the requirements of the application. Several studies have reported models of standard planar inductors such as circular, square, hexagonal, and octagonal in medical applications. However, for applications, constrained by narrow implantable locations, elliptical planar inductors may perform better than standard-shaped planar inductors. The aim of this study is to develop a numerical model for elliptical inductors. This model allows for the calculation of the inductance of the elliptical planar inductor and its parasitic components, which are key design parameters for the development of WIMDs powered by inductive coupling. An area transformation technique is used to transform and derive elliptical inductor formulas from standard circular inductor formulas. The proposed model is validated for various combinations of the number of turns, trace width, trace separation, and different inner and outer diameters of the elliptical planar inductor. For a thorough experimental validation of the proposed numerical model, more than 75 elliptical planar inductors were fabricated, measured, and compared with the numerical output of the proposed model. The mean error between the measured inductor parameters and numerical estimates using the proposed model is <5%, with a standard deviation of <3.18%. The proposed model provides an accurate analytical method for estimating and optimizing elliptical planar inductor parameters using a combination of current sheet expression and area transformation techniques. An elliptical planar inductor integrated with a sensing element can be used as a wireless implant to monitor the physiological signal from narrow implantation sites.
Effects of Genetic Mutation Sites in ADR Genes on Modern Chickens Produced and Domesticated by Artificial Selection
Authors: Komiyama Tomoyoshi
Published: January 2023

Associations between neurotransmitters, adrenergic receptor (ADR) mutations, and behaviors in chickens produced and domesticated by artificial selection remain unclear. This study investigates the association of neurotransmitters and ADR mutations with egg laying and cockfighting—behaviors associated with significantly different breeding backgrounds—in Shaver Brown and Shamo chickens. Accordingly, the whole sequences of nine ADR genes were determined, and nine amino acid-specific mutation sites from five genes (ADRα1A: S365G, ADRα1D: T440N, ADRα2A: D273E, ADRβ1: N443S, S445N, ADRβ3: R342C, Q404L, and P406S) were extracted. Evolutionary analysis showed that these mutations were not ancestrally derived. These results confirm that the mutations at these sites were artificially selected for domestication and are breed specific. NST population analysis confirmed a difference in the degree of genetic differentiation between the two populations in seven genes. The results further confirm differences in the degree of genetic differentiation between the two populations in Shaver Brown (ADRA1B and ADRA1D) and Shamo (ADRA1A and ADRA2B) chickens, indicating that the ADR gene differs between the two breeds. The effects of artificial selection, guided by the human-driven selection of desirable traits, are reflected in adrenaline gene mutations. Furthermore, certain gene mutations may affect domestication, while others may affect other traits in populations or individuals.
Quantitative Load Dependency Analysis of Local Trabecular Bone Microstructure to Understand the Spatial Characteristics in the Synthetic Proximal Femur
Authors: Kim Jisun , Chun Bong Ju , Kim Jung Jin
Published: January 2023

Analysis of the dependency of the trabecular structure on loading conditions is essential for understanding and predicting bone structure formation. Although previous studies have investigated the relationship between loads and structural adaptations, there is a need for an in-depth analysis of this relationship based on the bone region and load specifics. In this study, the load dependency of the trabecular bone microstructure for twelve regions of interest (ROIs) in the synthetic proximal femur was quantitatively analyzed to understand the spatial characteristics under seven different loading conditions. To investigate the load dependency, a quantitative measure, called the load dependency score (LDS), was established based on the statistics of the strain energy density (SED) distribution. The results showed that for the global model and epiphysis ROIs, bone microstructures relied on the multiple-loading condition, whereas the structures in the metaphysis depended on single or double loads. These results demonstrate that a given ROI is predominantly dependent on a particular loading condition. The results confirm that the dependency analysis of the load effects for ROIs should be performed both qualitatively and quantitatively.
Exploring the Role of Immune System and Inflammatory Cytokines in SARS-CoV-2 Induced Lung Disease: A Narrative Review
Authors: Tirelli Claudio , De Amici Mara , Albrici Cristina , Mira Sabrina , Nalesso Giulia , Re Beatrice , Corsico Angelo Guido , Mondoni Michele , Centanni Stefano
Published: January 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative pathogen of coronavirus disease 19 (COVID-19). COVID-19 can manifest with a heterogenous spectrum of disease severity, from mild upper airways infection to severe interstitial pneumonia and devastating acute respiratory distress syndrome (ARDS). SARS-CoV-2 infection may induce an over activation of the immune system and the release of high concentrations of pro-inflammatory cytokines, leading to a “cytokine storm”, a recognized pathogenetic mechanism in the genesis of SARS-CoV-2-induced lung disease. This overproduction of inflammatory cytokines has been recognized as a poor prognostic factor, since it can lead to disease progression, organ failure, ARDS and death. Moreover, the immune system shows dysregulated activity, particularly through activated macrophages and T-helper cells and in the co-occurrent exhaustion of lymphocytes. We carried out a non-systematic literature review aimed at providing an overview of the current knowledge on the pathologic mechanisms played by the immune system and the inflammation in the genesis of SARS-CoV-2-induced lung disease. An overview on potential treatments for this harmful condition and for contrasting the “cytokine storm” has also been presented. Finally, a look at the experimented experimental vaccines against SARS-CoV-2 has been included.
Clinically Relevant Pancreatic Fistula after Pancreaticoduodenectomy: How We Do It
Authors: Enderes Jana , Pillny Christiane , Matthaei Hanno , Manekeller Steffen , Kalff Jörg C. , Glowka Tim R.
Published: January 2023

(1) Background: This study’s goals were to investigate possible risk factors for clinically relevant postoperative pancreatic fistula (POPF) grade B/C according to the updated definitions of the International Study Group of Pancreatic Surgery and to analyze possible treatment strategies; (2) Methods: Between 2017 and 2021, 200 patients were analyzed regarding the development of POPF grade B/C with an emphasis on postoperative outcome and treatment strategies; (3) Results: POPF grade B/C was observed in 39 patients (19.5%). These patients were younger, mainly male, had fewer comorbidities and showed a higher body mass index. Also, they had lower CA-19 levels, a smaller tumor size and softer pancreatic parenchyma. They experienced a worse outcome without affecting the overall mortality rate (10% vs. 6%, p = 0.481), however, this lead to a prolonged postoperative stay (28 (32–36) d vs. 20 (15–28) d, p ≤ 0.001). The majority of patients with POPF grade B/C were able to receive conservative treatment, followed by drainage placement, endoscopic vacuum-assisted therapy (EVT) and surgery. Conservative treatment resulted in a shorter length of the postoperative stay (24 (22–28) d vs. 34 (26–43) d, p = 0.012); (4) Conclusions: Patients developing POPF grade B/C had a worse outcome; however, this did not affect the overall mortality rate. The majority of the patients were able to receive conservative treatment, resulting in a shorter length of their hospital stay.
Behavior of Male Gamete Fusogen GCS1/HAP2 and the Regulation in Arabidopsis Double Fertilization
Authors: Shiba Yuka , Takahashi Taro , Ohashi Yukino , Ueda Minako , Mimuro Amane , Sugimoto Jin , Noguchi Yuka , Igawa Tomoko
Published: January 2023

In the sexual reproduction of flowering plants, two independent fertilization events occur almost simultaneously: two identical sperm cells fuse with either the egg cell or the central cell, resulting in embryo and endosperm development to produce a seed. GCS1/HAP2 is a sperm cell membrane protein essential for plasma membrane fusion with both female gametes. Other sperm membrane proteins, DMP8 and DMP9, are more important for egg cell fertilization than that of the central cell, suggesting its regulatory mechanism in GCS1/HAP2-driving gamete membrane fusion. To assess the GCS1/HAP2 regulatory cascade in the double fertilization system of flowering plants, we produced Arabidopsis transgenic lines expressing different GCS1/HAP2 variants and evaluated the fertilization in vivo. The fertilization pattern observed in GCS1_RNAi transgenic plants implied that sperm cells over the amount of GCS1/HAP2 required for fusion on their surface could facilitate membrane fusion with both female gametes. The cytological analysis of the dmp8dmp9 sperm cell arrested alone in an embryo sac supported GCS1/HAP2 distribution on the sperm surface. Furthermore, the fertilization failures with both female gametes were caused by GCS1/HAP2 secretion from the egg cell. These results provided a possible scenario of GCS1/HAP2 regulation, showing a potential scheme for capturing additional GCS1/HAP2-interacting proteins.
Prognostic Biomarker SPOCD1 and Its Correlation with Immune Infiltrates in Colorectal Cancer
Authors: Gan Lin , Yang Changjiang , Zhao Long , Wang Shan , Gao Zhidong , Ye Yingjiang
Published: January 2023

The biological role of the spen paralogue and orthologue C-terminal domain containing 1 (SPOCD1) has been investigated in human malignancies, but its function in colorectal cancer (CRC) is unclear. This study investigated the association between SPOCD1 expression and clinicopathological features of CRC cases, as well as its prognostic value and biological function based on large-scale databases and clinical samples. The results showed that the expression level of SPOCD1 was elevated in CRC, which was generally associated with shortened survival time and poor clinical indexes, including advanced T, N, and pathologic stages. Multivariate Cox regression analysis showed that elevated SPOCD1 expression was an independent factor for poor prognosis in CRC patients. Functional enrichment analysis of SPOCD1 and its co-expressed genes revealed that SPOCD1 could act as an oncogene by regulating gene expression in essential functions and pathways of tumorigenesis, such as extracellular matrix organization, chemokine signaling pathways, and calcium signaling pathways. In addition, immune cell infiltration results showed that SPOCD1 expression was associated with various immune cells, especially macrophages. Furthermore, our findings suggested a possible function for SPOCD1 in the polarization of macrophages from M1 to M2 in CRC. In conclusion, SPOCD1 is a promising diagnostic and prognostic marker for CRC, opening new avenues for research and treatment.
Structure-Guided Strategies of Targeted Therapies for Patients with EGFR-Mutant Non–Small Cell Lung Cancer
Authors: Du Zhenfang , Sun Jinghan , Zhang Yunkai , Hesilaiti Nigaerayi , Xia Qi , Cui Heqing , Fan Na , Xu Xiaofang
Published: January 2023

Oncogenic mutations within the EGFR kinase domain are well-established driver mutations in non–small cell lung cancer (NSCLC). Small-molecule tyrosine kinase inhibitors (TKIs) specifically targeting these mutations have improved treatment outcomes for patients with this subtype of NSCLC. The selectivity of these targeted agents is based on the location of the mutations within the exons of the EGFR gene, and grouping mutations based on structural similarities has proved a useful tool for conceptualizing the heterogeneity of TKI response. Structure-based analysis of EGFR mutations has influenced TKI development, and improved structural understanding will inform continued therapeutic development and further improve patient outcomes. In this review, we summarize recent progress on targeted therapy strategies for patients with EGFR-mutant NSCLC based on structure and function analysis.
Aquaporin-1 and Aquaporin-4 Expression in Ependyma, Choroid Plexus and Surrounding Transition Zones in the Human Brain
Authors: Bihlmaier Ronja , Deffner Felix , Mattheus Ulrich , Neckel Peter H. , Hirt Bernhard , Mack Andreas F.
Published: January 2023

The choroid plexus (CP) is a structure in the brain ventricles that produces the main part of the cerebrospinal fluid (CSF). It is covered with specialized cells which show epithelial characteristics and are the site of the blood–CSF barrier. These cells form a contiguous cell sheet with ventricle-lining ependymal cells which are known to express aquaporin-4 (AQP4). In contrast, CP epithelial cells express aquaporin-1 (AQP1) apically. We investigated the expression patterns of aquaporins in the CP-ependyma transition from human body donors using immunofluorescence and electron microscopy. Ependymal cells and subependymal astrocytes at the base of the CP showed a particularly high AQP4 immunoreactivity. Astrocytic processes formed a dense meshwork or glial plate around the blood vessels entering the CP. Interestingly, some of these astrocytic processes were in direct contact with the CP stroma, which contains fenestrated blood vessels, separated only by a basal lamina. Electron microscopy confirmed the continuity of the subastrocytic basal lamina with the CP epithelium. We also probed for components of the AQP4 anchoring dystrophin–dystroglycan complex. Immunolabeling for dystrophin and AQP4 showed an overlapping staining pattern in the glial plate but not in previously reported AQP4-positive CP epithelial cells. In contrast, dystroglycan expression was associated with laminin staining in the glial plate and the CP epithelium. This suggests different mechanisms for AQP4 anchoring in the cell membrane. The high AQP4 density in the connecting glial plate might facilitate the transport of water in and out of the CP stroma and could possibly serve as a drainage and clearing pathway for metabolites.
Practical Recommendations for a Selection of Inhaled Corticosteroids in COPD: A Composite ICO Chart
Authors: Oishi Keiji , Matsunaga Kazuto , Yamamoto Tasuku , Matsuda Kazuki , Murata Yoriyuki , Hirano Tsunahiko
Published: January 2023

The use of inhaled corticosteroids (ICS) for the maintenance of bronchodilator treatment in patients with chronic obstructive pulmonary disease (COPD) is controversial. While some patients achieve clinical benefits, such as fewer exacerbations and improved symptoms, others do not, and some experience undesired side effects, such as pneumonia. Thus, we reviewed the evidence related to predictors of ICS therapy treatment response in patients with COPD. The first priority clinical markers when considering the efficacy of ICS are type 2 inflammatory biomarkers, followed by a history of suspected asthma and recurrent exacerbations. It is also necessary to consider any potential infection risk associated with ICS, and several risk factors for pneumonia when using ICS have been clarified in recent years. In this article, based on the evidence supporting the selection of ICS for COPD, we propose an ICS composite that can be added to the COPD (ICO) chart for use in clinical practice. The chart divided the type 2 biomarkers into three ranges and provided recommendations (recommend, consider, and against) by combining the history of suspected asthma, history of exacerbations, and risk of infection.
Circular RNAs in Ischemic Stroke: Biological Role and Experimental Models
Authors: Siracusa Chiara , Sabatino Jolanda , Leo Isabella , Eyileten Ceren , Postuła Marek , De Rosa Salvatore
Published: January 2023

Ischemic stroke is among the leading causes of morbidity, disability, and mortality worldwide. Despite the recent progress in the management of acute ischemic stroke, timely intervention still represents a challenge. Hence, strategies to counteract ischemic brain injury during and around the acute event are still lacking, also due to the limited knowledge of the underlying mechanisms. Despite the increasing understanding of the complex pathophysiology underlying ischemic brain injury, some relevant pieces of information are still required, particularly regarding the fine modulation of biological processes. In this context, there is emerging evidence that the modulation of circular RNAs, a class of highly conserved non-coding RNA with a closed-loop structure, are involved in pathophysiological processes behind ischemic stroke, unveiling a number of potential therapeutic targets and possible clinical biomarkers. This paper aims to provide a comprehensive overview of experimental studies on the role of circular RNAs in ischemic stroke.
Functional Loss of Terminal Complement Complex Protects Rabbits from Injury-Induced Osteoarthritis on Structural and Cellular Level
Authors: Riegger Jana , Joos Helga , Möhler Valentin , Leucht Frank , Rading Katrin , Kubisch Christian , Ignatius Anita , Huber-Lang Markus , Brenner Rolf E.
Published: January 2023

The terminal complement complex (TCC) has been described as a potential driver in the pathogenesis of posttraumatic osteoarthritis (PTOA). However, sublytic TCC deposition might also play a crucial role in bone development and regeneration. Therefore, we elucidated the effects of TCC on joint-related tissues using a rabbit PTOA model. In brief, a C6-deficient rabbit breed was characterized on genetic, protein, and functional levels. Anterior cruciate ligament transection (ACLT) was performed in C6-deficient (C6−/−) and C6-sufficient (C6+/−) rabbits. After eight weeks, the progression of PTOA was determined histologically. Moreover, the structure of the subchondral bone was evaluated by µCT analysis. C6 deficiency could be attributed to a homozygous 3.6 kb deletion within the C6 gene and subsequent loss of the C5b binding site. Serum from C6−/− animals revealed no hemolytic activity. After ACLT surgery, joints of C6−/− rabbits exhibited significantly lower OA scores, including reduced cartilage damage, hypocellularity, cluster formation, and osteophyte number, as well as lower chondrocyte apoptosis rates and synovial prostaglandin E2 levels. Moreover, ACLT surgery significantly decreased the trabecular number in the subchondral bone of C6−/− rabbits. Overall, the absence of TCC protected from injury-induced OA progression but had minor effects on the micro-structure of the subchondral bone.
Identification of Activated Cdc42-Associated Kinase Inhibitors as Potential Anticancer Agents Using Pharmacoinformatic Approaches
Authors: Kumar Vikas , Kumar Raj , Parate Shraddha , Danishuddin  , Lee Gihwan , Kwon Moonhyuk , Jeong Seong-Hee , Ro Hyeon-Su , Lee Keun Woo , Kim Seon-Won
Published: January 2023

Background: Activated Cdc42-associated kinase (ACK1) is essential for numerous cellular functions, such as growth, proliferation, and migration. ACK1 signaling occurs through multiple receptor tyrosine kinases; therefore, its inhibition can provide effective antiproliferative effects against multiple human cancers. A number of ACK1-specific inhibitors were designed and discovered in the previous decade, but none have reached the clinic. Potent and selective ACK1 inhibitors are urgently needed. Methods: In the present investigation, the pharmacophore model (PM) was rationally built utilizing two distinct inhibitors coupled with ACK1 crystal structures. The generated PM was utilized to screen the drug-like database generated from the four chemical databases. The binding mode of pharmacophore-mapped compounds was predicted using a molecular docking (MD) study. The selected hit-protein complexes from MD were studied under all-atom molecular dynamics simulations (MDS) for 500 ns. The obtained trajectories were ranked using binding free energy calculations (ΔG kJ/mol) and Gibb’s free energy landscape. Results: Our results indicate that the three hit compounds displayed higher binding affinity toward ACK1 when compared with the known multi-kinase inhibitor dasatinib. The inter-molecular interactions of Hit1 and Hit3 reveal that compounds form desirable hydrogen bond interactions with gatekeeper T205, hinge region A208, and DFG motif D270. As a result, we anticipate that the proposed scaffolds might help in the design of promising selective ACK1 inhibitors.
Biomacromolecular Profile in Human Primary Retinal Pigment Epithelial Cells—A Study of Oxidative Stress and Autophagy by Synchrotron-Based FTIR Microspectroscopy
Authors: Josifovska Natasha , Andjelic Sofija , Lytvynchuk Lyubomyr , Lumi Xhevat , Dučić Tanja , Petrovski Goran
Published: January 2023

Synchrotron radiation-based Fourier Transform Infrared (SR-FTIR) microspectroscopy is a non-destructive and chemically sensitive technique for the rapid detection of changes in the different components of the cell’s biomacromolecular profile. Reactive oxygen species and oxidative stress may cause damage to the DNA, RNA, and proteins in the retinal pigment epithelium (RPE), which can further lead to age-related macular degeneration (AMD) and visual loss in the elderly. In this study, human primary RPEs (hRPEs) were used to study AMD pathogenesis by using an established in vitro cellular model of the disease. Autophagy—a mechanism of intracellular degradation, which is altered during AMD, was studied in the hRPEs by using the autophagy inducer rapamycin and treated with the autophagy inhibitor bafilomycin A1. In addition, oxidative stress was induced by the hydrogen peroxide (H2O2) treatment of hRPEs. By using SR-FTIR microspectroscopy and multivariate analyses, the changes in the phosphate groups of nucleic acids, Amide I and II of the proteins, the carbonyl groups, and the lipid status in the hRPEs showed a significantly different pattern under oxidative stress/autophagy induction and inhibition. This biomolecular fingerprint can be evaluated in future drug discovery studies affecting autophagy and oxidative stress in AMD.
Mesenchymal Stem/Stromal Cells in Three-Dimensional Cell Culture: Ion Homeostasis and Ouabain-Induced Apoptosis
Authors: Shatrova Alla N. , Domnina Alisa P. , Pugovkina Natalia A. , Alekseenko Larisa L. , Marakhova Irina I.
Published: January 2023

This study describes the changes in ion homeostasis of human endometrial mesenchymal stem/stromal cells (eMSCs) during the formation of three-dimensional (3D) cell structures (spheroids) and investigates the conditions for apoptosis induction in 3D eMSCs. Detached from the monolayer culture, (2D) eMSCs accumulate Na+ and have dissipated transmembrane ion gradients, while in compact spheroids, eMSCs restore the lower Na+ content and the high K/Na ratio characteristic of functionally active cells. Organized as spheroids, eMSCs are non-proliferating cells with an active Na/K pump and a lower K+ content per g cell protein, which is typical for quiescent cells and a mean lower water content (lower hydration) in 3D eMSCs. Further, eMSCs in spheroids were used to evaluate the role of K+ depletion and cellular signaling context in the induction of apoptosis. In both 2D and 3D eMSCs, treatment with ouabain (1 µM) results in inhibition of pump-mediated K+ uptake and severe K+ depletion as well as disruption of the mitochondrial membrane potential. In 3D eMSCs (but not in 2D eMSCs), ouabain initiates apoptosis via the mitochondrial pathway. It is concluded that, when blocking the Na/K pump, cardiac glycosides prime mitochondria to apoptosis, and whether a cell enters the apoptotic pathway depends on the cell-specific signaling context, which includes the type of apoptotic protein expressed.
Evidence of Improvement of Lower Limb Functioning Using Hydrotherapy on Spinal Cord Injury Patients
Authors: Stanciu Liliana Elena , Iliescu Madalina Gabriela , Vlădăreanu Liliana , Ciota Alexandra Ecaterina , Ionescu Elena-Valentina , Mihailov Claudia Ileana
Published: January 2023

Background: Spinal cord injury (SCI) is a devastating problem for modern society, whether it affects young people in the most productive period of their lives or the elderly. The spinal cord injury is currently without curative treatment and the therapeutic intervention aims to minimize secondary complications and maximize residual function through rehabilitation medicine. The main objective of this scientific paper is to determine whether there is evidence in the literature regarding the importance and/or use of hydrotherapy, as part of the therapeutic management of the SCI patient, in order to decrease the degree of spasticity, of pain symptoms, increase or maintain range of motion, improve respiratory, cardiovascular, and metabolic status, as well as improve function and psychological benefits. Methods: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) procedures, the following databases were analyzed between 2000 and 2021: Pub Med, Pub Med Central, Science Direct, Scopus, and SpringerLink. Initial keywords: rehabilitation treatment, spinal cord injury. Additional keywords: hydrotherapy, aqua therapy, spasticity, human. For the scientific quality of the included articles, risk of bias was assessed using the Downs and Black Appraisal Modified Scale. Results: Our research used only four publications as per PRISMA protocol, assessed with Downs and Black Scale. The study models used in the individual studies included in the research are the following: two systematic reviews, one experimental non-randomized control, and one individual semi-structured interview. Due to the low number of studies, despite two of them being reviews, there is the necessity for a more standardized methodology to prove the benefits hydrotherapy for SCI patients for the improvement of lower limb functioning. Conclusion: Hydrotherapy is an important component of the treatment of an SCI patient, despite the limited number of scientific studies that support this aspect. Clinical trials in the future are required.
An Insight on Functioning Pancreatic Neuroendocrine Neoplasms
Authors: Bevere Michele , Gkountakos Anastasios , Martelli Filippo Maria , Scarpa Aldo , Luchini Claudio , Simbolo Michele
Published: January 2023

Pancreatic neuroendocrine neoplasms (PanNENs) are rare neoplasms arising from islets of the Langerhans in the pancreas. They can be divided into two groups, based on peptide hormone secretion, functioning and nonfunctioning PanNENs. The first group is characterized by different secreted peptides causing specific syndromes and is further classified into subgroups: insulinoma, gastrinoma, glucagonoma, somatostatinoma, VIPoma and tumors producing serotonin and adrenocorticotrophic hormone. Conversely, the second group does not release peptides and is usually associated with a worse prognosis. Today, although the efforts to improve the therapeutic approaches, surgery remains the only curative treatment for patients with PanNENs. The development of high-throughput techniques has increased the molecular knowledge of PanNENs, thereby allowing us to understand better the molecular biology and potential therapeutic vulnerabilities of PanNENs. Although enormous advancements in therapeutic and molecular aspects of PanNENs have been achieved, there is poor knowledge about each subgroup of functioning PanNENs.Therefore, we believe that combining high-throughput platforms with new diagnostic tools will allow for the efficient characterization of the main differences among the subgroups of functioning PanNENs. In this narrative review, we summarize the current landscape regarding diagnosis, molecular profiling and treatment, and we discuss the future perspectives of functioning PanNENs.
Role of Hyaluronic Acid in Selected Malignant Neoplasms in Women
Authors: Markowska Anna , Antoszczak Michał , Markowska Janina , Huczyński Adam
Published: January 2023

Hyaluronic acid (HA) is a significant glycosaminoglycan component of the extracellular matrix, playing an essential role in cell localization and proliferation. However, high levels of HA may also correlate with multidrug resistance of tumor cells, an increased tendency to metastasize, or cancer progression, and thus represent a very unfavorable prognosis for cancer patients. The purpose of this review article is to summarize the results of studies describing the relationship between HA, the main ligand of the CD44 receptor, or other components of the HA signaling pathway. In addition, we review the course of selected female malignancies, i.e., breast, cervical, endometrial, and ovarian cancer, with the main focus on the mechanisms oriented to CD44. We also analyze reports on the beneficial use of HA-containing preparations in adjuvant therapy among patients with these types of cancer. Data from the literature suggest that HA and its family members may be critical prognostic biomarkers of selected malignancies among women. Nevertheless, the results of the available studies are inconclusive, and the actual clinical significance of HA expression analysis is still quite enigmatic. In our opinion, the HA-CD44 signaling pathway should be an attractive target for future research related to targeted therapy in gynecological cancers.
Metformin Alleviates Diabetes-Associated Hypertension by Attenuating the Renal Epithelial Sodium Channel
Authors: Scindia Yogesh M. , Gholam Mohammed F. , Waleed Alina , Liu Lauren P. , Chacko Kevin M. , Desai Dhruv , Lopez Juliana Pena , Malik Zeeshan , Schramm Whitney C. , Morales Angelica G. , Carson-Marino Morgan , Alli Abdel A.
Published: January 2023

Diabetic nephropathy is the primary cause of morbidity in type 2 diabetes mellitus (T2DM) patients. New data indicate that hypertension, a common comorbidity in T2DM, can worsen outcomes of diabetic nephropathy. While metformin is a commonly prescribed drug for treating type 2 diabetes, its blood pressure regulating ability is not well documented. The aim of this study was to investigate the effect of metformin on normalizing blood pressure in salt-loaded hypertensive diabetic db/db mice. Sixteen-week-old male and female diabetic db/db mice were individually placed in metabolic cages and then randomized to a control vehicle (saline) or metformin treatment group. We evaluated the blood pressure reducing ability of metformin in salt-induced hypertension and progression of nephropathy in db/db mice. We observed that metformin- normalized systolic blood pressure in hypertensive diabetic mice. Mechanistically, metformin treatment reduced renal cathepsin B expression. Low cathepsin B expression was associated with reduced expression and activity of the epithelial sodium channel (ENaC), sodium retention, and thus control of hypertension. In addition, we identified that urinary extracellular vesicles (EVs) from the diabetic mice are enriched in cathepsin B. Compared to treatment with urinary EVs of vehicle-treated hypertensive diabetic mice, the amiloride-sensitive transepithelial current was significantly attenuated upon exposure of renal collecting duct cells to urinary EVs isolated from metformin-treated db/db mice or cathepsin B knockout mice. Collectively, our study identifies a novel blood pressure reducing role of metformin in diabetic nephropathy by regulating the cathepsin B-ENaC axis.
Role of the Endocannabinoid System in Metabolic Control Processes and in the Pathogenesis of Metabolic Syndrome: An Update
Authors: Dörnyei Gabriella , Vass Zsolt , Juhász Csilla Berta , Nádasy György L. , Hunyady László , Szekeres Mária
Published: January 2023

Metabolic syndrome is a complex disease state, which appears mostly as a consequence of an unhealthy, sedentary lifestyle. Metabolic complications include insulin resistance (IR), diabetes, dyslipidemia, hypertension, and atherosclerosis, impairing life standards and reducing life expectancy. The endocannabinoid system (ECS) has an important role in signalization processes, not only in the central nervous system, but also in the peripheral tissues. Several physiological functions are affected, and overexpression or downregulation contributes to several diseases. A better understanding of the functions of cannabinoid (CB) receptors may propose potential therapeutic effects by influencing receptor signaling and enzymes involved in downstream pathways. In this review, we summarize recent information regarding the roles of the ECS and the CB1 receptor signaling in the physiology and pathophysiology of energy and metabolic homeostasis, in the development of obesity by enhancing food intake, upregulating energy balance and fat accumulation, increasing lipogenesis and glucose production, and impairing insulin sensitivity and secretion. By analyzing the roles of the ECS in physiological and pathophysiological mechanisms, we introduce some recently identified signaling pathways in the mechanism of the pathogenesis of metabolic syndrome. Our review emphasizes that the presence of such recently identified ECS signaling steps raises new therapeutic potential in the treatment of complex metabolic diseases such as diabetes, insulin resistance, obesity, and hypertension.
mRNA—From COVID-19 Treatment to Cancer Immunotherapy
Authors: Krause Werner
Published: January 2023

This review provides an overview covering mRNA from its use in the COVID-19 pandemic to cancer immunotherapy, starting from the selection of appropriate antigens, tumor-associated and tumor-specific antigens, neoantigens, the basics of optimizing the mRNA molecule in terms of stability, efficacy, and tolerability, choosing the best formulation and the optimal route of administration, to summarizing current clinical trials of mRNA vaccines in tumor therapy.
Cancer Is Associated with the Emergence of Placenta-Reactive Autoantibodies
Authors: Khorami Sarvestani Sara , Shojaeian Sorour , Sarrami-Forooshani Ramin , Yekaninejad Mir Saeed , Gilany Kambiz , Ghaderi Abbas , Hashemnejad Maryam , Olfatbakhsh Asiie , Notash Haghighat Farzane , Montazeri Samaneh , Stensballe Allan , Jeddi-Tehrani Mahmood , Zarnani Amir-Hassan
Published: January 2023

Placenta-specific antigens are minimally expressed or unexpressed in normal adult tissues, while they are widely expressed in cancer. In the course of carcinogenesis, a vast array of autoantibodies (AAbs) is produced. Here, we used a quantitative approach to determine the reactivity of AAbs in the sera of patients with breast (BrC: N = 100, 100% female, median age: 51 years), gastric (GC: N = 30, 46.6% female, median age: 57 years), bladder (BC: N = 29, 34.4% female, median age: 57 years), and colorectal (CRC: N = 34, 41.1% female, median age: 51 years) cancers against first-trimester (FTP) and full-term placental proteome (TP) in comparison with age- and sex-matched non-cancer individuals. Human-on-human immunohistochemistry was used to determine reactive target cells in FTP. The effect of pregnancy on the emergence of placenta-reactive autoantibodies was tested using sera from pregnant women at different trimesters of pregnancy. Except for BC, patients with BrC (p < 0.0284), GC (p < 0.0002), and CRC (p < 0.0007) had significantly higher levels of placenta-reactive AAbs. BrC (p < 0.0001) and BC (p < 0.0409) in the early stages triggered higher autoantibody reactivity against FTP. The reactivities of BrC sera with FTP did not show an association with ER, PR, or HER2 expression. Pregnancy in the third trimester was associated with the induction of TP- and not FTP-reactive autoantibodies (=0.018). The reactivity of BrC sera with placental proteins was found to be independent of gravidity or abortion. BrC sera showed a very strong and specific pattern of reactivity with scattered cells beneath the syncytiotrophoblast layer. Our results reinforce the concept of the coevolution of placentation and cancer and shed light on the future clinical application of the placental proteome for the non-invasive early detection and treatment of cancer.
A High-Quality Diet, as Measured by the DASH Score, Is Associated with a Lower Risk of Metabolic Syndrome and Visceral Obesity
Authors: Konikowska Klaudia , Bombała Wojciech , Szuba Andrzej , Różańska Dorota , Regulska-Ilow Bożena
Published: January 2023

The current study was designed to examine the relationship between diet quality, as measured by the Dietary Approaches to Stop Hypertension (DASH) score, and the prevalence of metabolic syndrome (MetS) and its components. The study was cross-sectional in design and enrolled 535 people, including 215 with MetS and 320 without MetS. Using a validated food frequency questionnaire, the DASH diet quality score was counted. The mean age of the MetS group and control subjects was 58.48 ± 14.65 and 58.33 ± 9.26 years, respectively. The study showed that the MetS group had a significantly lower mean total DASH score than the control group (23.13 ± 5.44 vs. 24.62 ± 5.07, p = 0.0023). In addition, it was found that an increase in the total DASH score was associated with a lower risk of MetS (odds ratio [OR] = 0.95, 95% confidence interval [CI] = 0.91–0.99, p = 0.009). In the correlation analysis of the total population, a better-quality diet (higher DASH score) was positively correlated with high-density lipoprotein cholesterol (HDL-c), and negatively correlated with triglyceride (TG) concentration and waist circumference. It was also found that an increase in the total DASH score was associated with a lower risk of abdominal obesity (OR = 0.93, 95% CI = 0.88–0.99, p = 0.017). The results from the analyzed data highlight the potential benefits of following a healthy diet such as DASH.
The Impact of Treatment with IL-17/IL-23 Inhibitors on Subclinical Atherosclerosis in Patients with Plaque Psoriasis and/or Psoriatic Arthritis: A Systematic Review
Authors: Tsiogka Aikaterini , Gregoriou Stamatios , Stratigos Alexander , Soulaidopoulos Stergios , Rompoti Natalia , Panagakis Pantelis , Papoutsaki Marina , Kostakis Panagiotis , Kontochristopoulos George , Tsioufis Konstantinos , Campanati Anna , Offidani Annamaria , Vlachopoulos Charalambos , Rigopoulos Dimitrios
Published: January 2023

Accumulating evidence considers psoriasis a systemic inflammatory disorder that is associated with comorbidities such as psoriatic arthritis, cardiovascular disease, and metabolic syndrome. Although the precise pathogenetic links between psoriasis and atherosclerosis warrants further investigation, it is believed that chronic systemic inflammation along with the T helper (Th)-1 and Th17 polarization are associated with endothelial dysfunction and subsequent acceleration of atherosclerosis. Considering the above, several studies have evaluated if optimal control of the inflammation in psoriasis by inhibiting interleukins targeting the Interleukin (IL)-23/Th17 axis could subsequently reduce the atherosclerotic process during anti-psoriatic treatment by using a variety of surrogate markers of subclinical atherosclerosis. This systematic review summarizes current knowledge on the pathogenetic mechanisms and diagnostic evaluation of atherosclerosis in the context of psoriasis and provides a systematic review of the literature on the impact of treatment with biologics targeting the IL-23/Th17 axis on subclinical atherosclerosis in patients with plaque psoriasis and/or psoriatic arthritis.
A Fluorescent Biosensor for Streptavidin Detection Based on Double-Hairpin DNA-Templated Copper Nanoparticles
Authors: Xiao Qiangsheng , Chen Mingjian , Nie Wanpin , Xie Fengjiao , Yu Xiao , Ma Changbei
Published: January 2023

In this paper, we developed a sensitive, label-free and facile fluorescent strategy for detecting streptavidin (SA) based on double-hairpin DNA-templated copper nanoparticles (CuNPs) and terminal protection of small molecule-linked DNA. Herein, a special DNA hairpin probe was designed and synthesized, which contained two poly T single-stranded loops and a nick point in the middle of the stem. Inspired by the concept of the terminal protection interaction, the specific binding of SA to the biotinylated DNA probe can prevent the exonuclease degradation and keep the integrity of DNA probe, which can be used for synthesizing fluorescent CuNPs as a template. Conversely, the DNA probe would be digested by exonucleases and therefore, would fail to form CuNPs without SA. After systematic optimization, the detection range of SA concentration is from 0.5 to 150 nM with a low detection limit of 0.09 nM. Additionally, the proposed method was also successfully applied in the biological samples. Finally, the proposed method is sensitive, effective and simple, and can be potentially applied for predicting diseases and discovering new drugs.
Two-Dimensional Transition Metal Dichalcogenide Based Biosensors: From Fundamentals to Healthcare Applications
Authors: Mia Abdul Kaium , Meyyappan M. , Giri P. K.
Published: January 2023

There has been an exponential surge in reports on two-dimensional (2D) materials ever since the discovery of graphene in 2004. Transition metal dichalcogenides (TMDs) are a class of 2D materials where weak van der Waals force binds individual covalently bonded X–M–X layers (where M is the transition metal and X is the chalcogen), making layer-controlled synthesis possible. These individual building blocks (single-layer TMDs) transition from indirect to direct band gaps and have fascinating optical and electronic properties. Layer-dependent opto-electrical properties, along with the existence of finite band gaps, make single-layer TMDs superior to the well-known graphene that paves the way for their applications in many areas. Ultra-fast response, high on/off ratio, planar structure, low operational voltage, wafer scale synthesis capabilities, high surface-to-volume ratio, and compatibility with standard fabrication processes makes TMDs ideal candidates to replace conventional semiconductors, such as silicon, etc., in the new-age electrical, electronic, and opto-electronic devices. Besides, TMDs can be potentially utilized in single molecular sensing for early detection of different biomarkers, gas sensors, photodetector, and catalytic applications. The impact of COVID-19 has given rise to an upsurge in demand for biosensors with real-time detection capabilities. TMDs as active or supporting biosensing elements exhibit potential for real-time detection of single biomarkers and, hence, show promise in the development of point-of-care healthcare devices. In this review, we provide a historical survey of 2D TMD-based biosensors for the detection of bio analytes ranging from bacteria, viruses, and whole cells to molecular biomarkers via optical, electronic, and electrochemical sensing mechanisms. Current approaches and the latest developments in the study of healthcare devices using 2D TMDs are discussed. Additionally, this review presents an overview of the challenges in the area and discusses the future perspective of 2D TMDs in the field of biosensing for healthcare devices.
Novel Wearable Optical Sensors for Vital Health Monitoring Systems—A Review
Authors: Kaur Baljinder , Kumar Santosh , Kaushik Brajesh Kumar
Published: January 2023

Wearable sensors are pioneering devices to monitor health issues that allow the constant monitoring of physical and biological parameters. The immunity towards electromagnetic interference, miniaturization, detection of nano-volumes, integration with fiber, high sensitivity, low cost, usable in harsh environments and corrosion-resistant have made optical wearable sensor an emerging sensing technology in the recent year. This review presents the progress made in the development of novel wearable optical sensors for vital health monitoring systems. The details of different substrates, sensing platforms, and biofluids used for the detection of target molecules are discussed in detail. Wearable technologies could increase the quality of health monitoring systems at a nominal cost and enable continuous and early disease diagnosis. Various optical sensing principles, including surface-enhanced Raman scattering, colorimetric, fluorescence, plasmonic, photoplethysmography, and interferometric-based sensors, are discussed in detail for health monitoring applications. The performance of optical wearable sensors utilizing two-dimensional materials is also discussed. Future challenges associated with the development of optical wearable sensors for point-of-care applications and clinical diagnosis have been thoroughly discussed.