bluuebunny/crossref_metadata_2025 huggingface dataset:
Galectins as Emerging Glyco-Checkpoints and Therapeutic Targets in Glioblastoma
Authors: Videla-Richardson Guillermo A. , Morris-Hanon Olivia , Torres Nicolás I. , Esquivel Myrian I. , Vera Mariana B. , Ripari Luisina B. , Croci Diego O. , Sevlever Gustavo E. , Rabinovich Gabriel A.
Published: December 2021

Despite recent advances in diagnosis and treatment, glioblastoma (GBM) represents the most common and aggressive brain tumor in the adult population, urging identification of new rational therapeutic targets. Galectins, a family of glycan-binding proteins, are highly expressed in the tumor microenvironment (TME) and delineate prognosis and clinical outcome in patients with GBM. These endogenous lectins play key roles in different hallmarks of cancer by modulating tumor cell proliferation, oncogenic signaling, migration, vascularization and immunity. Additionally, they have emerged as mediators of resistance to different anticancer treatments, including chemotherapy, radiotherapy, immunotherapy, and antiangiogenic therapy. Particularly in GBM, galectins control tumor cell transformation and proliferation, reprogram tumor cell migration and invasion, promote vascularization, modulate cell death pathways, and shape the tumor-immune landscape by targeting myeloid, natural killer (NK), and CD8+ T cell compartments. Here, we discuss the role of galectins, particularly galectin-1, -3, -8, and -9, as emerging glyco-checkpoints that control different mechanisms associated with GBM progression, and discuss possible therapeutic opportunities based on inhibition of galectin-driven circuits, either alone or in combination with other treatment modalities.
Classification of Amyloidosis by Model-Assisted Mass Spectrometry-Based Proteomics
Authors: Palstrøm Nicolai Bjødstrup , Rojek Aleksandra M. , Møller Hanne E. H. , Hansen Charlotte Toftmann , Matthiesen Rune , Rasmussen Lars Melholt , Abildgaard Niels , Beck Hans Christian
Published: December 2021

Amyloidosis is a rare disease caused by the misfolding and extracellular aggregation of proteins as insoluble fibrillary deposits localized either in specific organs or systemically throughout the body. The organ targeted and the disease progression and outcome is highly dependent on the specific fibril-forming protein, and its accurate identification is essential to the choice of treatment. Mass spectrometry-based proteomics has become the method of choice for the identification of the amyloidogenic protein. Regrettably, this identification relies on manual and subjective interpretation of mass spectrometry data by an expert, which is undesirable and may bias diagnosis. To circumvent this, we developed a statistical model-assisted method for the unbiased identification of amyloid-containing biopsies and amyloidosis subtyping. Based on data from mass spectrometric analysis of amyloid-containing biopsies and corresponding controls. A Boruta method applied on a random forest classifier was applied to proteomics data obtained from the mass spectrometric analysis of 75 laser dissected Congo Red positive amyloid-containing biopsies and 78 Congo Red negative biopsies to identify novel “amyloid signature” proteins that included clusterin, fibulin-1, vitronectin complement component C9 and also three collagen proteins, as well as the well-known amyloid signature proteins apolipoprotein E, apolipoprotein A4, and serum amyloid P. A SVM learning algorithm were trained on the mass spectrometry data from the analysis of the 75 amyloid-containing biopsies and 78 amyloid-negative control biopsies. The trained algorithm performed superior in the discrimination of amyloid-containing biopsies from controls, with an accuracy of 1.0 when applied to a blinded mass spectrometry validation data set of 103 prospectively collected amyloid-containing biopsies. Moreover, our method successfully classified amyloidosis patients according to the subtype in 102 out of 103 blinded cases. Collectively, our model-assisted approach identified novel amyloid-associated proteins and demonstrated the use of mass spectrometry-based data in clinical diagnostics of disease by the unbiased and reliable model-assisted classification of amyloid deposits and of the specific amyloid subtype.
Molecular Structure of Nickel Octamethylporphyrin—Rare Experimental Evidence of a Ruffling Effect in Gas Phase
Authors: Pogonin Alexander E. , Otlyotov Arseniy A. , Minenkov Yury , Semeikin Alexander S. , Zhabanov Yuriy A. , Shlykov Sergey A. , Girichev Georgiy V.
Published: December 2021

The structure of a free nickel (II) octamethylporphyrin (NiOMP) molecule was determined for the first time through a combined gas-phase electron diffraction (GED) and mass spectrometry (MS) experiment, as well as through quantum chemical (QC) calculations. Density functional theory (DFT) calculations do not provide an unambiguous answer about the planarity or non-planar distortion of the NiOMP skeleton. The GED refinement in such cases is non-trivial. Several approaches to the inverse problem solution were used. The obtained results allow us to argue that the ruffling effect is manifested in the NiOMP molecule. The minimal critical distance between the central atom of the metal and nitrogen atoms of the coordination cavity that provokes ruffling distortion in metal porphyrins is about 1.96 Å.
Adipocyte Biology from the Perspective of In Vivo Research: Review of Key Transcription Factors
Authors: Evseeva Maria N. , Balashova Maria S. , Kulebyakin Konstantin Y. , Rubtsov Yury P.
Published: December 2021

Obesity and type 2 diabetes are both significant contributors to the contemporary pandemic of non-communicable diseases. Both disorders are interconnected and associated with the disruption of normal homeostasis in adipose tissue. Consequently, exploring adipose tissue differentiation and homeostasis is important for the treatment and prevention of metabolic disorders. The aim of this work is to review the consecutive steps in the postnatal development of adipocytes, with a special emphasis on in vivo studies. We gave particular attention to well-known transcription factors that had been thoroughly described in vitro, and showed that the in vivo research of adipogenic differentiation can lead to surprising findings.
Intermittent Hypoxic Therapy Inhibits Allogenic Bone-Graft Resorption by Inhibition of Osteoclastogenesis in a Mouse Model
Authors: Bergholt Natasja Leth , Demirel Ari , Pedersen Michael , Ding Ming , Kragstrup Tue Wenzel , Andersen Thomas , Deleuran Bent Winding , Foldager Casper Bindzus
Published: December 2021

Systemic Intermittent Hypoxic Therapy (IHT) relies on the adaptive response to hypoxic stress. We investigated allogenic bone-graft resorption in the lumbar spine in 48 mice. The mice were exposed to IHT for 1 week before surgery or 1 week after surgery and compared with controls after 1 and 4 weeks. Complete graft resorption was observed in 33–36% of the animals in the control group, but none in the preoperative IHT group. Increased bone-graft volume was demonstrated by micro-computed tomography in the preoperative IHT group after 1 week (p = 0.03) while a non-significant difference was observed after 4 weeks (p = 0.12). There were no significant differences in the postoperative IHT group. Increased concentration of immune cells was localized in the graft area, and more positive tartrate-resistant acid phosphatase (TRAP) staining was found in controls compared with IHT allogenic bone grafts. Systemic IHT resulted in a significant increase of the major osteoclast inhibitor osteoprotegerin as well as osteogenic and angiogenic regulators Tgfbr3, Fst3l, Wisp1, and Vegfd. Inflammatory cytokines and receptor activator of nuclear factor kappa-B ligand (RANKL) stimulators IL-6, IL-17a, IL-17f, and IL-23r increased after 1 and 4 weeks, and serum RANKL expression remained constant while Ccl3 and Ccl5 decreased. We conclude that the adaptive response to IHT activates numerous pathways leading to inhibition of osteoclastic activity and inhibition of allogenic bone-graft resorption.
Lipid-Induced Adaptations of the Pancreatic Beta-Cell to Glucotoxic Conditions Sustain Insulin Secretion
Authors: Oberhauser Lucie , Maechler Pierre
Published: December 2021

Over the last decades, lipotoxicity and glucotoxicity emerged as established mechanisms participating in the pathophysiology of obesity-related type 2 diabetes in general, and in the loss of β-cell function in particular. However, these terms hold various potential biological processes, and it is not clear what precisely they refer to and to what extent they might be clinically relevant. In this review, we discuss the basis and the last advances of research regarding the role of free fatty acids, their metabolic intracellular pathways, and receptor-mediated signaling related to glucose-stimulated insulin secretion, as well as lipid-induced β-cell dysfunction. We also describe the role of chronically elevated glucose, namely, glucotoxicity, which promotes failure and dedifferentiation of the β cell. Glucolipotoxicity combines deleterious effects of exposures to both high glucose and free fatty acids, supposedly provoking synergistic defects on the β cell. Nevertheless, recent studies have highlighted the glycerolipid/free fatty acid cycle as a protective pathway mediating active storage and recruitment of lipids. Finally, we discuss the putative correspondence of the loss of functional β cells in type 2 diabetes with a natural, although accelerated, aging process.
Regulation of Antimicrobial Peptide Activity via Tuning Deformation Fields by Membrane-Deforming Inclusions
Authors: Kondrashov Oleg V. , Akimov Sergey A.
Published: December 2021

Antimicrobial peptides (AMPs) are considered prospective antibiotics. Some AMPs fight bacteria via cooperative formation of pores in their plasma membranes. Most AMPs at their working concentrations can induce lysis of eukaryotic cells as well. Gramicidin A (gA) is a peptide, the transmembrane dimers of which form cation-selective channels in membranes. It is highly toxic for mammalians as being majorly hydrophobic gA incorporates and induces leakage of both bacterial and eukaryotic cell membranes. Both pore-forming AMPs and gA deform the membrane. Here we suggest a possible way to reduce the working concentrations of AMPs at the expense of application of highly-selective amplifiers of AMP activity in target membranes. The amplifiers should alter the deformation fields in the membrane in a way favoring the membrane-permeabilizing states. We developed the statistical model that allows describing the effect of membrane-deforming inclusions on the equilibrium between AMP monomers and cooperative membrane-permeabilizing structures. On the example of gA monomer-dimer equilibrium, the model predicts that amphipathic peptides and short transmembrane peptides playing the role of the membrane-deforming inclusions, even in low concentration can substantially increase the lifetime and average number of gA channels.
Exosomal MicroRNAs as Potential Biomarkers of Hepatic Injury and Kidney Disease in Glycogen Storage Disease Type Ia Patients
Authors: Resaz Roberta , Cangelosi Davide , Segalerba Daniela , Morini Martina , Uva Paolo , Bosco Maria Carla , Banderali Giuseppe , Estrella Ana , Wanner Corbinian , Weinstein David A. , Sechi Annalisa , Paci Sabrina , Melis Daniela , Di Rocco Maja , Lee Young Mok , Eva Alessandra
Published: December 2021

Glycogen storage disease type Ia (GSDIa) is an inherited metabolic disorder caused by mutations in the enzyme glucose-6-phosphatase-α (G6Pase-α). Affected individuals develop renal and liver complications, including the development of hepatocellular adenoma/carcinoma and kidney failure. The purpose of this study was to identify potential biomarkers of the evolution of the disease in GSDIa patients. To this end, we analyzed the expression of exosomal microRNAs (Exo-miRs) in the plasma exosomes of 45 patients aged 6 to 63 years. Plasma from age-matched normal individuals were used as controls. We found that the altered expression of several Exo-miRs correlates with the pathologic state of the patients and might help to monitor the progression of the disease and the development of late GSDIa-associated complications.
Extracellular Vesicles Mediate Communication between Endothelial and Vascular Smooth Muscle Cells
Authors: Fontaine Marie , Herkenne Stéphanie , Ek Olivier , Paquot Alicia , Boeckx Amandine , Paques Cécile , Nivelles Olivier , Thiry Marc , Struman Ingrid
Published: December 2021

The recruitment of pericytes and vascular smooth muscle cells (SMCs) that enwrap endothelial cells (ECs) is a crucial process for vascular maturation and stabilization. Communication between these two cell types is crucial during vascular development and in maintaining vessel homeostasis. Extracellular vesicles (EVs) have emerged as a new communication tool involving the exchange of microRNAs between cells. In the present study, we searched for microRNAs that could be transferred via EVs from ECs to SMCs and vice versa. Thanks to a microRNA profiling experiment, we found that two microRNAs are more exported in each cell type in coculture experiments: while miR-539 is more secreted by ECs, miR-582 is more present in EVs from SMCs. Functional assays revealed that both microRNAs can modulate both cell-type phenotypes. We further identified miR-539 and miR-582 targets, in agreement with their respective cell functions. The results obtained in vivo in the neovascularization model suggest that miR-539 and miR-582 might cooperate to trigger the process of blood vessel coverage by smooth muscle cells in a mature plexus. Taken together, these results are the first to highlight the role of miR-539 and miR-582 in angiogenesis and communication between ECs and SMCs.
Cloning, Functional Characterization and Response to Cadmium Stress of the Thioredoxin-like Protein 1 Gene from Phascolosoma esculenta
Authors: Meng Jiajie , Gao Xinming , Luo Shengyu , Lin Chenwen , Du Chen , Hou Congcong , Wang Jianping , Jin Shan , Tang Daojun , Zhang Chundan , Zhu Junquan
Published: December 2021

Cadmium (Cd) is a heavy metal toxicant and is widely distributed in aquatic environments. It can cause excessive production of reactive oxygen species (ROS) in the organism, which in turn leads to a series of oxidative damages. Thioredoxin (Trx), a highly conserved disulfide reductase, plays an important role in maintaining the intracellular redox homeostasis in eukaryotes and prokaryotes. Phascolosoma esculenta is an edible marine worm, an invertebrate that is extensively found on the mudflats of coastal China. To explore the molecular response of Trx in mudflat organisms under Cd stress, we identified a new Trx isoform (Trx-like protein 1 gene) from P. esculenta for the first time, designated as PeTrxl. Molecular and structural characterization, as well as multiple sequence and phylogenetic tree analysis, demonstrated that PeTrxl belongs to the Trx superfamily. PeTrxl transcripts were found to be ubiquitous in all tissues, and the highest expression level occurred in the coelomic fluid. Exposure to three sublethal concentrations of Cd resulted in the upregulation and then downregulation of PeTrxl expression levels over time in coelomic fluid of P. esculenta. The significant elevation of PeTrxl expression after 12 and 24 h of Cd exposure at 6 and 96 mg/L, respectively, might reflect its important role in the resistance to Cd stress. Recombinant PeTrxl (rPeTrxl) showed prominent dose-dependent insulin-reducing and ABTS free radical-scavenging abilities. After exposure to 96 mg/L Cd for 24 h, the ROS level increased significantly in the coelomic fluid, suggesting that Cd induced oxidative stress in P. esculenta. Furthermore, the injection of rPeTrxl during Cd exposure significantly reduced the ROS in the coelomic fluid. Our data suggest that PeTrxl has significant antioxidant capacity and can protect P. esculenta from Cd-induced oxidative stress.
The Important Role of Ion Transport System in Cervical Cancer
Authors: Chen Yih-Fung , Shen Meng-Ru
Published: December 2021

Cervical cancer is a significant gynecological cancer and causes cancer-related deaths worldwide. Human papillomavirus (HPV) is implicated in the etiology of cervical malignancy. However, much evidence indicates that HPV infection is a necessary but not sufficient cause in cervical carcinogenesis. Therefore, the cellular pathophysiology of cervical cancer is worthy of study. This review summarizes the recent findings concerning the ion transport processes involved in cell volume regulation and intracellular Ca2+ homeostasis of epithelial cells and how these transport systems are themselves regulated by the tumor microenvironment. For cell volume regulation, we focused on the volume-sensitive Cl− channels and K+-Cl− cotransporter (KCC) family, important regulators for ionic and osmotic homeostasis of epithelial cells. Regarding intracellular Ca2+ homeostasis, the Ca2+ store sensor STIM molecules and plasma membrane Ca2+ channel Orai proteins, the predominant Ca2+ entry mechanism in epithelial cells, are discussed. Furthermore, we evaluate the potential of these membrane ion transport systems as diagnostic biomarkers and pharmacological interventions and highlight the challenges.
The Plasminogen–Activator Plasmin System in Physiological and Pathophysiological Angiogenesis
Authors: Ismail Asmaa Anwar , Shaker Baraah Tariq , Bajou Khalid
Published: December 2021

Angiogenesis is a process associated with the migration and proliferation of endothelial cells (EC) to form new blood vessels. It is involved in various physiological and pathophysiological conditions and is controlled by a wide range of proangiogenic and antiangiogenic molecules. The plasminogen activator–plasmin system plays a major role in the extracellular matrix remodeling process necessary for angiogenesis. Urokinase/tissue-type plasminogen activators (uPA/tPA) convert plasminogen into the active enzyme plasmin, which in turn activates matrix metalloproteinases and degrades the extracellular matrix releasing growth factors and proangiogenic molecules such as the vascular endothelial growth factor (VEGF-A). The plasminogen activator inhibitor-1 (PAI-1) is the main inhibitor of uPA and tPA, thereby an inhibitor of pericellular proteolysis and intravascular fibrinolysis, respectively. Paradoxically, PAI-1, which is expressed by EC during angiogenesis, is elevated in several cancers and is found to promote angiogenesis by regulating plasmin-mediated proteolysis and by promoting cellular migration through vitronectin. The urokinase-type plasminogen activator receptor (uPAR) also induces EC cellular migration during angiogenesis via interacting with signaling partners. Understanding the molecular functions of the plasminogen activator plasmin system and targeting angiogenesis via blocking serine proteases or their interactions with other molecules is one of the major therapeutic strategies scientists have been attracted to in controlling tumor growth and other pathological conditions characterized by neovascularization.
NLRP3 Inflammasome Activation Controls Vascular Smooth Muscle Cells Phenotypic Switch in Atherosclerosis
Authors: Burger Fabienne , Baptista Daniela , Roth Aline , da Silva Rafaela Fernandes , Montecucco Fabrizio , Mach François , Brandt Karim J. , Miteva Kapka
Published: December 2021

(1) Background: Monocytes and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome orchestrate lipid-driven amplification of vascular inflammation promoting the disruption of the fibrous cap. The components of the NLRP3 inflammasome are expressed in macrophages and foam cells within human carotid atherosclerotic plaques and VSMCs in hypertension. Whether monocytes and NLRP3 inflammasome activation are direct triggers of VSMC phenotypic switch and plaque disruption need to be investigated. (2) Methods: The direct effect of oxLDL-activated monocytes in VSMCs co-cultured system was demonstrated via flow cytometry, qPCR, ELISA, caspase 1, and pyroptosis assay. Aortic roots of VSMCs lineage tracing mice fed normal or high cholesterol diet and human atherosclerotic plaques were used for immunofluorescence quantification of NLRP3 inflammasome activation/VSMCs phenotypic switch. (3) Results: OxLDL-activated monocytes reduced α-SMA, SM22α, Oct-4, and upregulation of KLF-4 and macrophage markers MAC2, F4/80 and CD68 expression as well as caspase 1 activation, IL-1β secretion, and pyroptosis in VSMCs. Increased caspase 1 and IL-1β in phenotypically modified VSMCs was detected in the aortic roots of VSMCs lineage tracing mice fed high cholesterol diet and in human atherosclerotic plaques from carotid artery disease patients who experienced a stroke. (4) Conclusions: Taken together, these results provide evidence that monocyte promote VSMC phenotypic switch through VSMC NLRP3 inflammasome activation with a likely detrimental role in atherosclerotic plaque stability in human atherosclerosis.
The First Line of Defense: Receptor-like Protein Kinase-Mediated Stomatal Immunity
Authors: Wang Zhe , Gou Xiaoping
Published: December 2021

Stomata regulate gas and water exchange between the plant and external atmosphere, which are vital for photosynthesis and transpiration. Stomata are also the natural entrance for pathogens invading into the apoplast. Therefore, stomata play an important role in plants against pathogens. The pattern recognition receptors (PRRs) locate in guard cells to perceive pathogen/microbe-associated molecular patterns (PAMPs) and trigger a series of plant innate immune responses, including rapid closure of stomata to limit bacterial invasion, which is termed stomatal immunity. Many PRRs involved in stomatal immunity are plasma membrane-located receptor-like protein kinases (RLKs). This review focuses on the current research progress of RLK-mediated signaling pathways involved in stomatal immunity, and discusses questions that need to be addressed in future research.
Concomitant Activation of OSM and LIF Receptor by a Dual-Specific hlOSM Variant Confers Cardioprotection after Myocardial Infarction in Mice
Authors: Lörchner Holger , Adrian-Segarra Juan M. , Waechter Christian , Wagner Roxanne , Góes Maria Elisa , Brachmann Nathalie , Sreenivasan Krishnamoorthy , Wietelmann Astrid , Günther Stefan , Doll Nicolas , Braun Thomas , Pöling Jochen
Published: December 2021

Oncostatin M (OSM) and leukemia inhibitory factor (LIF) signaling protects the heart after myocardial infarction (MI). In mice, oncostatin M receptor (OSMR) and leukemia inhibitory factor receptor (LIFR) are selectively activated by the respective cognate ligands while OSM activates both the OSMR and LIFR in humans, which prevents efficient translation of mouse data into potential clinical applications. We used an engineered human-like OSM (hlOSM) protein, capable to signal via both OSMR and LIFR, to evaluate beneficial effects on cardiomyocytes and hearts after MI in comparison to selective stimulation of either LIFR or OSMR. Cell viability assays, transcriptome and immunoblot analysis revealed increased survival of hypoxic cardiomyocytes by mLIF, mOSM and hlOSM stimulation, associated with increased activation of STAT3. Kinetic expression profiling of infarcted hearts further specified a transient increase of OSM and LIF during the early inflammatory phase of cardiac remodeling. A post-infarction delivery of hlOSM but not mOSM or mLIF within this time period combined with cardiac magnetic resonance imaging-based strain analysis uncovered a global cardioprotective effect on infarcted hearts. Our data conclusively suggest that a simultaneous and rapid activation of OSMR and LIFR after MI offers a therapeutic opportunity to preserve functional and structural integrity of the infarcted heart.
Temporal Roles of Platelet and Coagulation Pathways in Collagen- and Tissue Factor-Induced Thrombus Formation
Authors: Navarro Stefano , Stegner David , Nieswandt Bernhard , Heemskerk Johan W. M. , Kuijpers Marijke J. E.
Published: December 2021

In hemostasis and thrombosis, the complex process of thrombus formation involves different molecular pathways of platelet and coagulation activation. These pathways are considered as operating together at the same time, but this has not been investigated. The objective of our study was to elucidate the time-dependency of key pathways of thrombus and clot formation, initiated by collagen and tissue factor surfaces, where coagulation is triggered via the extrinsic route. Therefore, we adapted a microfluidics whole-blood assay with the Maastricht flow chamber to acutely block molecular pathways by pharmacological intervention at desired time points. Application of the technique revealed crucial roles of glycoprotein VI (GPVI)-induced platelet signaling via Syk kinase as well as factor VIIa-induced thrombin generation, which were confined to the first minutes of thrombus buildup. A novel anti-GPVI Fab EMF-1 was used for this purpose. In addition, platelet activation with the protease-activating receptors 1/4 (PAR1/4) and integrin αIIbβ3 appeared to be prolongedly active and extended to later stages of thrombus and clot formation. This work thereby revealed a more persistent contribution of thrombin receptor-induced platelet activation than of collagen receptor-induced platelet activation to the thrombotic process.
The Spatial Extent of Pain Is Associated with Pain Intensity, Catastrophizing and Some Measures of Central Sensitization in People with Frozen Shoulder
Authors: Balasch-Bernat Mercè , Dueñas Lirios , Aguilar-Rodríguez Marta , Falla Deborah , Schneebeli Alessandro , Navarro-Bosch Marta , Lluch Enrique , Barbero Marco
Published: December 2021

The aim of this cross-sectional study was to explore the spatial extent of pain and its association with clinical symptoms, psychological features, and pain sensitization in people with frozen shoulder (FS). Forty-eight individuals with FS completed pain drawings (PDs) and reported their clinical symptoms including pain intensity (Visual Analogue Scale) and shoulder disability (Shoulder Pain and Disability Index). Moreover, pain sensitization measurements (pressure pain thresholds, temporal summation, conditioned pain modulation, and Central Sensitization Inventory (CSI)) were assessed. Psychological features were assessed by Pain Catastrophizing Scale (PCS) and Pain Vigilance and Awareness Questionnaire. Pain frequency maps were generated, Margolis rating scale was used for pain location, and Spearman correlation coefficients were computed. The mean (SD) pain extent was 12.5% (6.7%) and the most common painful area was the anterolateral shoulder region (100%). Women presented a more widespread pain distribution compared with men. Significant positive associations were obtained between pain extent and current pain intensity (rs = 0.421, p < 0.01), PCS (rs = 0.307, p < 0.05) and CSI (rs = 0.358, p < 0.05). The anterolateral region of the shoulder was the most common painful area in people with FS. Women with FS presented more extended areas of pain; and a more widespread distribution of pain was correlated with higher levels of pain, pain catastrophizing and pain sensitization.
Deep Infiltrating Endometriosis and Adenomyosis: Implications on Pregnancy and Outcome
Authors: Gruber Teresa Mira , Ortlieb Laura , Henrich Wolfgang , Mechsner Sylvia
Published: December 2021

Endometriosis (EM), especially deep infiltrating endometriosis (DIE) and adenomyosis (AM), are known to cause pain and sterility in young women. More recently, they have also been described as risk factors for obstetric complications. While the pathophysiology is not yet completely understood, they seem to share a common origin: archimetrosis. Methods: A systematic literature review was conducted to summarize the existing evidence on DIE and AM as risk factors for obstetric complications. Results: Preterm birth, caesarean section delivery (CS) and placental abnormalities are associated with the diagnosis of DIE and AM. Women with AM seem to experience more often hypertensive pregnancy disorders, premature rupture of membranes and their children are born with lower birth weights than in the control groups. However, many of the studies tried to evaluate AM, EM and DIE as separate risk factors. Moreover, often they did not adjust for important confounders such as multiple pregnancies, parity, mode of conception and maternal age. Therefore, prospective studies with larger numbers of cases and appropriate adjustment for confounders are needed to explore the pathophysiology and to prove causality.
Fecal Calprotectin Is Increased in Stroke
Authors: Park Shin Young , Lee Sang Pyung , Kim Woo Jin
Published: December 2021

Background: While there have been major advances in unveiling the mechanisms comprising the ischemic cascade of CNS, stroke continues to be a significant burden. There is a need to extend the focus toward peripheral changes, and the brain–gut axis has recently gained much attention. Our study aimed to evaluate gut inflammation and its association with blood variables in stroke using fecal calprotectin (FC). Methods: Fecal samples were obtained from 27 stroke patients and 27 control subjects. FC was quantitatively measured using a commercial ELISA. Laboratory data on the fecal sample collection were also collected, including CBC, ESR, glucose, creatinine, total protein, albumin, transaminases, and CRP. Results: There was a significant increase in FC levels in stroke patients compared to the controls. Furthermore, FC in stroke patients was negatively correlated with the Glasgow Coma Scale. Moreover, FC in stroke patients was positively correlated with CRP and negatively correlated with lymphocyte count and albumin. Conclusions: Our findings show that increased FC is associated with consciousness and systemic response in stroke and warrants further studies to elucidate the usefulness of FC in the management of stroke.
Evolution in Real-World Therapeutic Strategies for HIV Treatment: A Retrospective Study in Southern Italy, 2014–2020
Authors: Papa Nunzia , Cammarota Simona , Citarella Anna , Atripaldi Luigi , Bernardi Francesca F. , Fogliasecca Marianna , Giugliano Nello , Trama Ugo , Spatarella Micaela
Published: December 2021

Changes in HIV treatment guidelines over the last two decades reflect the evolving challenges in this field. Our study examined treatment change patterns throughout a 7-year period in a large Italian cohort of HIV patients as well as the reasons and direction of changes. Treatment-naïve and -experienced HIV patients managed by Cotugno Hospital of Naples between 2014 and 2020 were analyzed. During the period, the proportion of single-tablet regimen treatment sharply increased for the naïve and experienced patients. Regimens containing integrase strand transfer inhibitors rapidly replaced those containing protease inhibitor and non-nucleoside reverse transcriptase inhibitors. The use of the tenofovir alafenamide fumarate/emtricitabine backbone increased rapidly after its introduction in the Italian pharmaceutical market, making up 63.7 and 54.9% of all treatments in naïve and experienced patients, respectively, in 2020. The main reason for treatment changes was optimization and/or simplification (90.6% in 2018; 85.3% in 2019; 95.5 in 2020) followed by adverse effects and virological failure. Our real-world analysis revealed that the majority of treatment-naïve and treatment-experienced patients received antiretroviral drugs listed as preferred/recommended in current recommendations. Regimen optimization and/or simplification is a leading cause of treatment modification, while virologic failure or adverse effects are less likely reasons for modification in the current treatment landscape.
Recovery Profiles of Sevoflurane and Desflurane with or without M-Entropy Guidance in Obese Patients: A Randomized Controlled Trial
Authors: Wu Yu-Ming , Su Yen-Hao , Huang Shih-Yu , Lo Po-Han , Chen Jui-Tai , Chang Hung-Chi , Yang Yun-Ling , Cherng Yih-Giun , Wu Hsiang-Ling , Tai Ying-Hsuan
Published: December 2021

Obesity increases the risk of prolonged emergence from general anesthesia due to the delayed release of anesthetic agents from body fat. This trial aimed to evaluate the effects of sevoflurane and desflurane along with anesthetic depth monitoring on emergence time from anesthesia in obese patients. Adults with a body mass index ≥ 30 kg·m−2 undergoing laparoscopic sleeve gastrectomy at a medical center were randomized into four groups: sevoflurane or desflurane anesthesia with or without M-Entropy guidance on anesthetic depth in a ratio of 1:1:1:1. In the M-Entropy guidance groups, the dosage of sevoflurane and desflurane was adjusted to achieve response and state entropy values between 40 and 60 during surgery. In the non-M-Entropy guidance groups, the dosage of anesthetics was titrated according to clinical signs. Primary outcome was time to spontaneous eye opening. A total of 80 participants were randomized. Compared to sevoflurane, desflurane anesthesia significantly reduced the time to spontaneous eye opening [mean difference (MD): −129 s; 95% confidence interval (CI): −211, −46], obeying commands (−160; −243, −77), tracheal extubation (−172; −266, −78), and leaving operating room (−148; −243, −54). M-Entropy guidance further reduced time to eye opening (MD: −142 s; 99.2% CI: −276, −8), tracheal extubation (−199; −379, −19), and leaving operating room (−190; −358, −23) in the desflurane but not the sevoflurane group. M-Entropy guidance significantly reduced the risk of agitation during emergence, i.e., risk difference: −0.275 (95% CI: −0.464, −0.086); and number needed to treat: 4. Compared to sevoflurane, using desflurane to maintain general anesthesia accelerated the return of consciousness in obese patients. M-Entropy guidance further hastened awakening in patients using desflurane and prevented emergence agitation.
Gouty Arthropathy: Review of Clinical Manifestations and Treatment, with Emphasis on Imaging
Authors: Weaver Jennifer S. , Vina Ernest R. , Munk Peter L. , Klauser Andrea S. , Elifritz Jamie M. , Taljanovic Mihra S.
Published: December 2021

Gout, a crystalline arthropathy caused by the deposition of monosodium urate crystals in the articular and periarticular soft tissues, is a frequent cause of painful arthropathy. Imaging has an important role in the initial evaluation as well as the treatment and follow up of gouty arthropathy. The imaging findings of gouty arthropathy on radiography, ultrasonography, computed tomography, dual energy computed tomography, and magnetic resonance imaging are described to include findings of the early, acute and chronic phases of gout. These findings include early monosodium urate deposits, osseous erosions, and tophi, which may involve periarticular tissues, tendons, and bursae. Treatment of gout includes non-steroidal anti-inflammatories, colchicine, glucocorticoids, interleukin-1 inhibitors, xanthine oxidase inhibitors, uricosuric drugs, and recombinant uricase. Imaging is critical in monitoring response to therapy; clinical management can be modulated based on imaging findings. This review article describes the current standard of care in imaging and treatment of gouty arthropathy.
Influence of Overhanging Bleb on Corneal Higher-Order Aberrations after Trabeculectomy
Authors: Mizuno Yu , Hirooka Kazuyuki , Kiuchi Yoshiaki
Published: December 2021

Recent advances in ocular aberrometry have revealed that ocular surgery increases ocular and corneal higher-order aberrations. This retrospective single-center study aimed to examine the effects of the overhanging bleb on corneal higher-order aberrations using a wavefront analyzer. We included 61 eyes from 50 patients with overhanging bleb after trabeculectomy with a fornix-based conjunctival flap using mitomycin C (overhanging bleb group) and 65 eyes from 54 glaucoma patients with no history of glaucoma surgery (control group). Corneal higher-order aberrations (total higher-order aberrations, coma aberrations, coma-like aberrations, spherical aberrations, and spherical-like aberrations) on a 4 mm pupil diameter were measured using the TOPCON KR-1W wavefront analyzer. Corneal coma aberrations were higher in the overhanging bleb group than in the control group (0.16 ± 0.13 μm and 0.10 ± 0.05 μm, respectively; p = 0.042). Corneal coma-like aberrations were also higher in the overhanging bleb group than in the control group (0.31 ± 0.32 μm and 0.16 ± 0.09 μm, respectively; p = 0.022). With an increasing ratio of cornea covered by the bleb to the entire cornea, all corneal higher-order aberrations increased except for corneal coma-like aberrations. Overhanging bleb after trabeculectomy with a fornix-based conjunctival flap using mitomycin C and its size influenced corneal higher-order aberrations.
The Resonance and Adaptation of Neurospora crassa Circadian and Conidiation Rhyth ms to Short Light-Dark Cycles
Authors: Ma Huan , Li Luyao , Yan Jie , Zhang Yin , Ma Xiaohong , Li Yunzhen , Yuan Yu , Yang Xiaolin , Yang Ling , Guo Jinhu
Published: December 2021

Circadian clocks control the physiological and behavioral rhythms to adapt to the environment with a period of ~24 h. However, the influences and mechanisms of the extreme light/dark cycles on the circadian clock remain unclear. We showed that, in Neurospora crassa, both the growth and the microconidia production contribute to adaptation in LD12:12 (12 h light/12 h dark, periodically). Mathematical modeling and experiments demonstrate that in short LD cycles, the expression of the core clock protein FREQUENCY was entrained to the LD cycles when LD > 3:3 while it free ran when T ≤ LD3:3. The conidial rhythmicity can resonate with a series of different LD conditions. Moreover, we demonstrate that the existence of unknown blue light photoreceptor(s) and the circadian clock might promote the conidiation rhythms that resonate with the environment. The ubiquitin E3 ligase FWD-1 and the previously described CRY-dependent oscillator system were implicated in regulating conidiation under short LD conditions. These findings shed new light on the resonance of Neurospora circadian clock and conidiation rhythms to short LD cycles, which may benefit the understandings of both the basic regulatory aspects of circadian clock and the adaptation of physiological rhythms to the extreme conditions.
Purine Auxotrophic Starvation Evokes Phenotype Similar to Stationary Phase Cells in Budding Yeast
Authors: Kokina Agnese , Tanilas Kristel , Ozolina Zane , Pleiko Karlis , Shvirksts Karlis , Vamza Ilze , Liepins Janis
Published: December 2021

Purine auxotrophy is an abundant trait among eukaryotic parasites and a typical marker for many budding yeast strains. Supplementation with an additional purine source (such as adenine) is necessary to cultivate these strains. If not supplied in adequate amounts, purine starvation sets in. We explored purine starvation effects in a model organism, a budding yeast Saccharomyces cerevisiae ade8 knockout, at the level of cellular morphology, central carbon metabolism, and global transcriptome. We observed that purine-starved cells stopped their cycle in G1/G0 state and accumulated trehalose, and the intracellular concentration of AXP decreased, but adenylate charge remained stable. Cells became tolerant to severe environmental stresses. Intracellular RNA concentration decreased, and massive downregulation of ribosomal biosynthesis genes occurred. We proved that the expression of new proteins during purine starvation is critical for cells to attain stress tolerance phenotype Msn2/4p targets are upregulated in purine-starved cells when compared to cells cultivated in purine-rich media. The overall transcriptomic response to purine starvation resembles that of stationary phase cells. Our results demonstrate that the induction of a strong stress resistance phenotype in budding yeast can be caused not only by natural starvation, but also starvation for metabolic intermediates, such as purines.
The Sanjiangyuan Nature Reserve Is Partially Effective in Mitigating Human Pressures
Authors: Tan Linyi , Guo Guancheng , Li Shicheng
Published: December 2021

Protected areas play significant roles in protecting biodiversity by mitigating human activities. As an indicator for human activities, the human footprint (HF) can be used to assess the effectiveness of protected areas. We developed a HF dataset for the Sanjiangyuan region in China after localizing the global HF model. Then we used it to assess the effectiveness of Sanjiangyuan nature reserve (SNR) in mitigating human pressures. Our results suggest that the HF value for the Sanjiangyuan region was generally low from 1995 to 2015, with a fluctuating increasing trend. The SNR is partially effective in mitigating human pressures. For 2005–2010, the HF values decreased both within and outside the reserve with more decreases for the outside. For the three functional zones of the SNR, our results show that the HF values decreased during 2005–2010 for all of them, with the largest decrease in the experimental area, and increased during 2010–2015, with the lowest increase in the core areas. The results we obtained are consistent with ecological indicator-based assessments. It is a challenge for the government to balance conservation and development in establishing Sanjiangyuan National Park.
Caveolin-1 Down-Regulation Reduces VEGF-A Secretion Induced by IGF-1 in ARPE-19 Cells
Authors: Puddu Alessandra , Sanguineti Roberta , Maggi Davide
Published: December 2021

The insulin-like growth factor 1 (IGF-1) stimulates expression and secretion of vascular endothelial growth factor-A (VEGF-A), the main actor in ocular neovascularization, by RPE cells. Activity of IGF-1 is regulated by interaction between its receptor and Caveolin-1 (Cav-1), the main component of caveolae. The aim of this study was to investigate whether modulation of Cav-1 expression affects synthesis and secretion of VEGF-A. ARPE-19 cells were transfected with small interfering RNA for Cav-1 (si-Cav-1) and with control siRNA (si-CTR) and stimulated with IGF-1. We found that down-regulation of Cav-1 did not affect activation of IGF-1R but regulated in an opposite manner the phosphorylation of Akt and Erk1/2. Moreover, we found that IGF-1 increased mRNA levels of VEGF-A in both si-CTR and in si-Cav-1 ARPE-19 cells and that Cav-1 silencing significantly reduced basal and IGF-1-stimulated VEGF-A release. Then we investigated the response of the microvascular endothelial cell line HMEC-1 to secretory products of ARPE-19 cells by evaluating wound healing closure, finding that conditioned media from si-Cav-1-ARPE-19 cells reduced endothelial cell migration rate. These data demonstrate that Cav-1 regulates secretion of VEGF-A, and that the depletion of Cav-1 reduces IGF-1 induced VEGF-A secretion in ARPE-19 cells and the migratory potential of their secretory products.
Endothelial Dysfunction in Childhood Cancer Survivors: A Narrative Review
Authors: Crocco Marco , d’Annunzio Giuseppe , La Valle Alberto , Piccolo Gianluca , Chiarenza Decimo Silvio , Bigatti Carolina , Molteni Marta , Milanaccio Claudia , Garrè Maria Luisa , Di Iorgi Natascia , Maghnie Mohamad
Published: December 2021

Assessment of endothelial dysfunction in cancer survivors may have a role in the early identification of non-communicable diseases and cardiovascular late effects. Oncological therapies may impair endothelial function. Therefore, in patients such as childhood cancer survivors who could benefit from early cardioprotective pharmacological interventions, it is essential to monitor endothelial function, even if the optimal methodology for investigating the multifaceted aspects of endothelial dysfunction is still under debate. Biochemical markers, as well as invasive and non-invasive tools with and without pharmacological stimuli have been studied. Human clinical studies that have examined lifestyle or cancer treatment protocols have yielded evidence showing the involvement of lipid and lipoprotein levels, glycemic control, blood pressure, adiposity, inflammation, and oxidative stress markers on the state of endothelial health and its role as an early indicator of cardiometabolic risk. However, with regards to pharmacological interventions, cautious interpretation of the result attained whilst monitoring the endothelial function is warranted due to methodological limitations and substantial heterogeneity of the results reported in the published studies. In this narrative review, an overview of evidence from human clinical trials examining the effects of cancer therapies on endothelial disease is provided together with a discussion of endothelial function assessment using the different non-invasive techniques available for researchers and clinicians, in recent years.
Molecular Pathogenesis in Myeloid Neoplasms with Germline Predisposition
Authors: Gao Juehua , Chen Yihua , Sukhanova Madina
Published: December 2021

Myeloid neoplasms with germline predisposition have recently been added as distinct provisional entities in the 2017 revision of the World Health Organization’s classification of tumors of hematopoietic and lymphatic tissue. Individuals with germline predisposition have increased risk of developing myeloid neoplasms—mainly acute myeloid leukemia and myelodysplastic syndrome. Although the incidence of myeloid neoplasms with germline predisposition remains poorly defined, these cases provide unique and important insights into the biology and molecular mechanisms of myeloid neoplasms. Knowledge of the regulation of the germline genes and their interactions with other genes, proteins, and the environment, the penetrance and clinical presentation of inherited mutations, and the longitudinal dynamics during the process of disease progression offer models and tools that can further our understanding of myeloid neoplasms. This knowledge will eventually translate to improved disease sub-classification, risk assessment, and development of more effective therapy. In this review, we will use examples of these disorders to illustrate the key molecular pathways of myeloid neoplasms.
Establishment of Silane/GO Multistage Hybrid Interface Layer to Improve Interfacial and Mechanical Properties of Carbon Fiber Reinforced Poly (phthalazinone ether ketone) Thermoplastic Composites
Authors: Cheng Shan , Li Nan , Pan Yuxi , Wang Bing , Hao Haoyue , Hu Fangyuan , Liu Cheng , Chen Yousi , Jian Xigao
Published: December 2021

This study focused on the faint interface bonding between carbon fiber (CF) and poly(phthalazinone ether ketone) (PPEK) thermoplastic, a multistage hybrid interface layer was constructed via the condensation reaction of N-[3-(Trimethoxysilyl)propyl]-N,N,N-trimethylammonium chloride (KHN+) and the electrostatic adsorption of graphene oxide (GO). The influence of the contents of GO (0.2 wt%, 0.4 wt%, 0.6 wt%) on the interfacial properties of composites was explored. FTIR, Raman spectra, XPS tests indicated the successful preparation of CF-KHN+-GO reinforcements. The multistage hybrid interface layer significantly increased fiber surface roughness without surface microstructure destruction. Simultaneously, polarity and wettability are remarkably improved as evidenced by the dynamic contact angle experiment. The interlaminar shear strength (ILSS) and flexural strength of the CF/PPEK composites with 0.4 wt% GO (CF-KHN+-4GO) were 74.57 and 1508 MPa, which was 25.2% and 23.5% higher than that of untreated CF/PPEK composite, respectively. Dynamic mechanical analysis proved that CF/GO/PPEK composites have excellent high-temperature mechanical properties. This study furnishes an unsophisticated and valid strategy to build an interface transition layer with a strong binding force, which would offer a new train of thought in preparing high-performing structural composites.